Endocrine disease

Endocrine disease

Classification and external resources

Major endocrine glands. (Male left, female on the right.) 1. Pineal gland 2. Pituitary gland 3.
Thyroid gland 4. Thymus 5. Adrenal gland 6. Pancreas 7. Ovary 8. Testes

Endocrine diseases are disorders of the endocrine system. The branch of medicine associated
with endocrine disorders is known as endocrinology.

Types of endocrine disease

Broadly speaking, endocrine disorders may be subdivided into three groups:

1. Endocrine gland hyposecretion (leading to hormone deficiency)

 2. Endocrine gland hypersecretion (leading to hormone excess)
3. Tumours (benign or malignant) of endocrine glands

Endocrine disorders are often quite complex, involving a mixed picture of

hyposecretion and hypersecretion because of the feedback mechanisms involved in
the endocrine system. For example, most forms of hyperthyroidism are associated
with an excess of thyroid hormone and a low level of thyroid stimulating hormone.

Diagnosis of endocrine diseases

Diagnosis of endocrine diseases may be difficult; it is often not possible to directly

assay hormone levels in the blood, making indirect measurements necessary. For
example, diabetes mellitus is diagnosed via measurements of blood glucose rather
than direct assays of plasma insulin; Cushing's syndrome is diagnosed by the
dexamethasone suppression test rather than by direct assays of serum.

List of endocrine diseases

Adrenal disorders

 Adrenal insufficiency
o Addison's disease
o Mineralocorticoid deficiency
 Diabetis

 Adrenal hormone excess

o Conn's syndrome
o Cushing's syndrome
o GRA/Glucocorticoid remediable aldosteronism
o Pheochromocytoma

 Congenital adrenal hyperplasia (adrenogenital syndrome)

 Adrenocortical carcinoma

Glucose homeostasis disorders

 Diabetes mellitus
o Type 1 Diabetes
o Type 2 Diabetes
 o Gestational Diabetes
o Mature Onset Diabetes of the Young

 Hypoglycemia
o Idiopathic hypoglycemia
o Insulinoma

 Glucagonoma

Thyroid disorders

 Goitre
 Hyperthyroidism
o Graves-Basedow disease
o Toxic multinodular goitre
 Hypothyroidism
 Thyroiditis
o Hashimoto's thyroiditis

 Thyroid cancer

Calcium homeostasis disorders and Metabolic bone disease

 Parathyroid gland disorders

o Primary hyperparathyroidism
o Secondary hyperparathyroidism
o Tertiary hyperparathyroidism
o Hypoparathyroidism
 Pseudohypoparathyroidism

 Osteoporosis
 Osteitis deformans (Paget's disease of bone)
 Rickets and osteomalacia

Pituitary gland disorders

Posterior pituitary

 Diabetes insipidus

Anterior pituitary
  Hypopituitarism (or Panhypopituitarism)

 Pituitary tumors
o Pituitary adenomas
o Prolactinoma (or Hyperprolactinemia)
o Acromegaly, gigantism
o Cushing's disease

Sex hormone disorders

 Disorders of sex development or intersex disorders

o Hermaphroditism
o Gonadal dysgenesis
o Androgen insensitivity syndromes

 Hypogonadism (Gonadotropin deficiency)

o Inherited (genetic and chromosomal) disorders
 Kallmann syndrome
 Klinefelter syndrome
 Turner syndrome
o Acquired disorders
 Ovarian failure (also known as Premature Menopause)
 Testicular failure

 Disorders of Gender
o Gender identity disorder

 Disorders of Puberty
o Delayed puberty
o Precocious puberty

 Menstrual function or fertility disorders

o Amenorrhea
o Polycystic ovary syndrome

Tumours of the endocrine glands not mentioned elsewhere

 Multiple endocrine neoplasia

o MEN type 1
o MEN type 2a
o MEN type 2b
See also separate organs

 Autoimmune polyendocrine syndromes

 Incidentaloma - an unexpected finding on diagnostic imaging, often of
endocrine glands

History

Timme's syndrome is a historical term for pluriglandular disease ( disease

involving a number of endocrine organs ) first described in 1919.[1]

Adrenal gland disorders (or diseases) are conditions that interfere with the
normal functioning of the adrenal glands.[1] They are characterized by adrenal
insufficiencies, where there are deficiencies in the availability of steroids that are
produced by the adrenal glands[2]. Adrenal Gland disorder is rather prevalent in
small animals including rabbits & guinea pigs. They may cause hyperfunction or
hypofunction, and it may be congenital or acquired. Adrenal gland disorders are
challenging to diagnose, but if left untreated, they are life threatening and can be
very deadly.

There are two parts of the adrenal glands, the adrenal cortex and the adrenal
medulla. The adrenal cortex produces cortisol, a hormone that regulates nearly
every type of organ and tissue within the body. The adrenal cortex also produces
aldosterone. It helps to maintain appropriate proportions of water and salts within
the body. When the proportions are disrupted, it results in low blood pressure.
Most patients with adrenal insufficiency may experience fatigue, poor appetites,
dizziness, weight loss, and nausea.

Contents
 1 General information
 2 Pheochromocytoma
 3 Cushing's syndrome
 4 Pituitary adenoma
 5 Hyperaldosteronism
 6 Addison's disease
 7 Adrenal gland scans
 8 Notable people with adrenal gland disorders
 9 Notes
 10 External links
General information

The adrenal glands have an effect on many functions that occur in the human body.
Adrenal glands are most known for developing a lot of female and male hormones.
These hormones are extremely necessary for one’s body due to the fact that they
are primarily responsible for providing a body with cortical, which deals with
one’s levels of stress.[3] The problem with adrenal gland disorders is that they may
cause a person’s glands to build too little of amount of hormones and it is also
possible for these disorders to cause a body’s adrenal glands to form an amount of
hormones that may be too much for anyone’s body to handle. You can be sure to
find these adrenal glands on the top of the base of each kidney. (Spontaneous
Rupture “Spontaneous Rupture of Achilles Tendon: Missed Presentation of
Cushing's Syndrome.”British Medical Journal 319.7209 (August 28, 1999): 560.
From Expanded Academic ASAP.)Each of these glands have the shape of many
tiny triangles. One of these adrenal glands takes up the space of a little less than an
inch in length and about the width of four inches at the most. Although this
disorder can be a big concern, being that it is life threatening, there are fortunately
many support groups that one is certainly able to find locally. Fortunately, many
doctors have found that the adrenal gland disorder may be treated according to the
specific disorder, such as: Cushing’s Syndrome and Pituitary Tumor. The National
Institute of Child Health and Human Development is a major branch of support
that also guides a lot of research for this disorder.[4]

Pheochromocytoma

Main article: Pheochromocytoma

Symptoms

Pheochromocytoma is a tumor of special cells that arises inside the “adrenal

glands’ chromaffin cells”.[5] These chromaffin cells may be found anywhere in the
heart and in the area around the bladder, but they are mostly found in the adrenal
glands. When adrenaline or hormones are released too much from the adrenal
gland, they cause high blood pressure.[6] Pheochromocytomas are found in a
person’s body because he has inherited these from his parents. [6] With “autosomal
dominant inheritance,” men and women are equally likely to inherit the disease. [6]
However, they are more common in women than in men. This syndrome can occur
in any age, but mostly in between the ages of 30 to 60. [5] The most common
symptoms of pheochromocytoma are hypertension or high blood pressure. [6] These
symptoms usually occur in a sudden attack. The other symptoms of the disease are
“headaches, excess sweating, racing heart, rapid breathing, anxiety, nervousness,
pain in the lower chest or upper abdomen, nausea, or heat intolerance.” [6] In
between attacks, people with the syndrome can experience weight loss or increased
sweating. The attacks occur frequently in a week and they may last up to 15
minutes.[6]

Causes

The main cause for most pheochromocytoma is not yet known. Inherited
pheochromocytoma is a 10 to 20 percent chance of causing the disease. It is from
an inherited autosomal dominant trait. According to some research patients
recently diagnosed with hypertension have pheochromocytoma. It is seen in both
sexes and usually between the age of 30 and 40.[7]

Treatments

Pheochromocytoma is a rare disease where the tumor forms in the chromaffin cells
of the body. There are many ways to treat the pheochromocytoma. One of which is
by surgery. The first step in doing so is to find out where the tumor is and then they
surgically remove it.[8] During this process one or two adrenal glands can be
removed and this is known as adrenalectomy. The lymph nodes and tissues maybe
removed if the cancer has started to spread. [9] If one does not want to do surgery
then they can do chemotherapy where drugs are used to kill the cancer cells. In this
process one can take pills or they can take it intravenously which is a bag that drips
solutions into the vein. The way this treatment works is the drugs flow through the
body killing cancer cells that are located in the body. The last method for this
treatment is radiation therapy. In this they use high energy x-rays that destroys the
cancer cells and reduces the size of the tumors. [9] Pheochromoctoma has no
methods for prevention.

Cushing's syndrome

Description

Cushing’s syndrome is the result of the excessive production of corticosteroids by

the adrenal glands. An overproduction of corticotrophin, the hormone that controls
the adrenal gland by the pituitary gland, which stimulates the adrenal glands to
produce the corticosteroids, could be of one cause. It also can be in excessive
cortisol levels in the blood which may be the result of a tumor of the pituitary
glands, adrenal glands or from tumors or cancer arising elsewhere in the body.
Cushing’s disease refers to specifically to excessive ACTH secretion by a pituitary
tumor. The cause of Cushing’s syndrome is a pituitary adenoma in over 70% of
adults and approximately 60-70% of children and adolescents. Cushing’s disease is
relatively rare, affecting ten to fifteen in every million people each year and most
commonly affected adults between the ages of 20 to 50 years. Women however,
account for over 70% of the case.

Symptoms

The symptoms and signs of Cushing’s syndrome are: change in body habitus;
weight gain in the face, above the collar bone and on the back of the neck, skin
changes with easy bruising, excess hair growth on the face, neck, chest, abdomen,
and thigh, generalized weakness and fatigue, loss of muscles, menstrual disorders
in women, decreased fertility and/or sex drive, high blood pressure, and high blood
sugar. These symptoms are brief descriptions of what can be found in patients with
Cushing’s disease and each individual may experience symptoms differently.

Causes

People can develop Cushing's syndrome by taking glucocorticoids or their body is

exposed to high levels of cortisol. Glucocorticoids are steroid hormones that are
chemically similar to the cortisol produced by our bodies. Someone can also
develop chushings syndrome if their body produces too much cortisol naturally.
Cortisol is used for many important tasks in the body. It helps to maintain blood
pressure and cardiovascular function. It breaks down glucose for energy by
balancing the effects of insulin. Its main purpose is to help the body with stress.
Depression, alcoholism, malnutrition, and panic disorders all increase levels of
cortisol. This increases the chances of getting chushings syndrome.[10]

Treatments

Treatment of Cushing’s syndrome can vary depends on the cause of cortisol

excess. People with Pituitary Adenomas can treated with several kinds of
treatments. Most preferably is to use a surgical method called transphenoidal
adenomectomy. The surgeon uses a microscope and other instrument to get to the
gland. In order to get to the gland they would either have to make an opening
below the upper lip of the patient or they would have to go through the nostril. The
success rate for this type of treatment is above 80 percent and can be use more than
one time if necessary. The level of ACTH within the patient should temporary drop
about 2 levels below normal. Patient would also be given a synthetic cortisol such
as hydrocortisone and...The end results usually are less than a year for the
treatment to take effect. For people who are not qualify for transphenoidal
adenometomy or that the treatment didn’t work, they could use radiotherapy to
treat the disease. By using radiation to treat the gland for 6 weeks, about 40 percent
to 50 percent of adults and a possible 80 percent of children improved. They also
use a drug called Miotane to decrease plasma or urine hormone levels. Other drugs
such as aminoglutethimide, metyrapone, trilostane and ketoconazole can be use as
a replacement for Miotane or to be use along with Miotane. It is up to the doctor’s
discretion because each one of these drugs has its own side effects.

People who have an Adrenal tumor as a result of Cushing syndromes can use a
procedure called laparoscopic adrenalectomy. It is only use for Adrenal tumors that
are less than 6 cm. This treatment is strongly recommended because the patient can
recover much quicker and experience less pain than other open procedures.

Ectopic ACTH syndrome can be cure by destroying all ACTH cancer tissue.
Depends on the type of cancers, surgery, chemotherapy, radiotherapy,
immunotherapy, or combination of these treatment can be use to cure the disease.

Pituitary adenoma
Symptoms

The pituitary is a “small, pea-sized gland” located at the base of the brain [11] The
pituitary adenoma disease affects hormones which regulate growth and the activity
of other glands in the body. However, with an abnormal growth or tumor in the
master gland, the pituitary adenomas do not spread to other body parts and are not
cancerous [12]. This disease is found most likely in adults than in children and
increases during adolescent years [13]. They also tend to grow slowly, but too many
hormones can cause significant problems in the body. Pituitary adenomas can
cause “disturbance of vision and growth and change in hormonal balance” [12].
Other general symptoms may be headache, infertility, fatigue, low or high blood
pressure, or growth failure . Some pituitary hormones which impact the sex
hormones can “make a woman produce breast milk even though she is not
pregnant or nursing, or cause a man to lose his sex drive or lower his sperm count”
[11]
. However, these symptoms can be the symptoms of so many other diseases.
Therefore, these tumors often go undiagnosed [11].
Causes

Pituitary adenoma is in the form of a tumor, pituitary tumor. Prolactinomas is the

most common form of a pituitary tumor. It causes amenorrhea, galactorrhea, and
infertility in females. Gigacromegaly is caused by tumors that secrete excess
growth hormones.[14]

Treatments

The small organ called pituitary adenoma helps make hormones for the growth of
the body. This is a tumor that grows in the pituitary gland. [15] There are many ways
to treat this problem one being surgery. This is the common treatment used in order
to get rid of that tumor. If the pituitary gland is accidentally damaged in the
surgery then the way to treat it is by taking pills which replaces the hormones
created. Another method for treatment is medications, which helps to shrink
tumors. The two types of medicines are bromocriptine and ocreotide.
Bromocriptine helps lower the prolactin levels and minimize the size of the tumor.
The ocreotide is used when tumors release growth hormone and when surgery is
not going to cure.[16] The last option for treatment is radiation therapy. In this
process it uses radiation to kill the tumor cells. There are three types of radiation
therapy the first which is conventional therapy. In this the radiation is intended for
the pituitary. The second is stereotactic radiosurgery. The tumor has a radiation
beam that is intended to be serious from stereotactic radiosurgery. The last one is
the proton beam radiotherapy which is a ray of protons that is directed only on the
tumor. Pituitary adenoma has no procedures or preventions for this small organ.[15]

Hyperaldosteronism
Description

In hyperaldosteronism, there is a primary and secondary condition. Primary

hyperaldosteronism are conditions in which the adrenal gland releases too much of
the hormone aldosterone. Primary hyperaldosteronism used to be considered a rare
condition, but some experts believe that it may be the cause of high blood pressure
in some patients. Most cases of primary hyperaldosteronism are caused by a
noncancerous tumor of the adrenal gland. The disease is common between the ages
of 30 and 50. In secondary hyperaldosteronism, the excess aldosterone is caused by
something outside the adrenal gland that mimics the primary condition. Secondary
hyperaldosteronism is generally related to high blood pressures, it also can be
related to: cirrhosis of the liver, heart failure and nephritic syndrome.
Symptoms

Symptoms in hyperaldosteronism includes: fatigue, headache,low serum

potassium, high blood pressure, intermittent paralysis, muscle weakness, and
numbness.

Causes

Hyperaldosteronism can be caused by adrenal cancers and hyperplasia but it is

usually caused by the invasion of adenoma. Increased cell production can increase
the bulk of an organ, which can cause hyperaldosteronism. It can also be caused by
a tumor in the adrenal gland.[17]

Addison's disease
Symptoms

Each adrenal gland in a body contains what is called a medulla. Every medulla is
protected by a tough coating, called the cortex. The medulla has nothing to do with
the cause of Addison's Disease. [3] It is primarily the cortex which is responsible for
regulating how much water is in your body and of course, the blood that flows
from one's liver. This disease usually is not noticeable until the cortex has been
completely wrecked.[3] Unfortunately, there are many negative factors that must
take place when being diagnosed with Addison's disease. This usually will contain:
major weight loss, sudden dizziness from having very low blood pressure, and
excruciating pains in your stomach muscles. It has been recorded that many people
have to also deal with a rare occasion of vomiting and nausea.[4]

Causes

Addison’s disease is caused by the failure to produce adequate levels of cortisol.

This can be caused by a disorder of the adrenal glands, autoimmune disorder. The
disorder causes the body’s immune system to gradually destroy the adrenal cortex.
[18]

Treatments

With medications, such as replacement corticosteroids, its symptoms can be

controlled. However, these drugs must be taken for life. People often receive
glucocorticoids (cortisone or hydrocortisone) and mineralocorticoids
(fludrocortisone) to control their symptoms[19]. In Addison’s disease, the adrenal
glands do not produce enough cortisol and aldersterone; therefore, the drugs
replace these missing hormones.[20] For immediate treatment, hydrocortisone, salt
water, and sugar can help in the adrenal crisis. An adrenal crisis is an extreme form
of adrenal insufficiency, therefore, hydrocortisone must be injected immediately if
one were to experience it[19].

Adrenal gland scans

For the evaluation of adrenal disorders, CT is the primary imaging method. When
characterizing the enhancement pattern of lesions on portal venous phase images,
intravenous contrast can be useful. For patients who cannot tolerate intravenous
contrast, MRI can be an alternative to CT.[21]

When too much adrenaline or noradrenaline is produced from the adrenal gland, a
tumor is suspected and therefore, an adrenal gland scan is required. One situation
where a tumor is suspected is when high blood pressure does not respond to the
medication. On the first day of the scan, a radiopharmaceutical is injected into the
patient. On the second, third, and fourth day, the camera scans the pelvis, lower
abdomen, and lower chest[22].

Notable people with adrenal gland disorders

John F. Kennedy, the 35th president of the United States was diagnosed with
Addison’s Disease while on a trip in London as a Congressman. A common
symptom of Addison’s Disease was the discoloration or bronzing of the skin.
Many observers have noticed that he had a deep tan and his skin had a green tinge.
When he was asked about his year-round tan, he answered that it was because of
“exposing a part of his anatomy that had not been burned by the sun.” This was not
proof of a natural tan, for Addison’s Disease usually consists of the bronzing of the
areas of the skin that is exposed[23]. Jane Austen, an English novelist, was thought
to have died from Addison’s Disease. Her descriptions of her illness seemed to
have fit Addison’s Disease, but a recent study has shown it is a possibility that
lymphoma, such as Hodgkin’s Disease, could have caused her death[24].

Endocrine Diseases
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articles about Endocrine Diseases causes, symptoms, diagnosis, treatment,
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Hirsutism

Hirsutism is that increased hair growth and thickening and longer in the face,
genitals, armpits, abdomen, back and four limbs; information on women with
Hirsutism causes, symptoms, diagnosis, treatment.

Pituitary dwarfism Treatment

Treatment for Pituitary dwarfism is human growth hormone replacement therapy

by intramuscular injection, anabolic hormones enhance protein synthesis, Human
chorionic gonadotropin, Thyroid tablets.

Pituitary dwarfism Symptoms and diagnosis

Symptoms of Pituitary dwarfism is growth slowed down, delay in the teeth,

ossification growth retardation; diagnosis is X-ray, reduce the serum growth
hormone levels, Insulin hypoglycemia test.

Pituitary dwarfism

Pituitary dwarfism is growth disturbance, include Primary and Secondary, causes

is anterior pituitary hypofunction lead to lack of growth hormone, or autosomal
recessive inheritance.

Pituitary apoplexy Treatment

Treatment for Pituitary apoplexy should be given hormone replacement therapy to

maintain water and electrolyte balance, hydrocortisone infusion, surgical
decompression.

Pituitary apoplexy Diagnosis

Diagnosis for pituitary apoplexy is imaging tests, such as X-ray examination, CT

scan, Cerebral angiography, MRI examination, determination of pituitary function.
Pituitary apoplexy Symptoms

Symptoms of Pituitary apoplexy and Pituitary Crisis is increased intracranial

pressure, visual impairment, blood pressure, body temperature, respiratory and
cardiac disorders, coma.

Pituitary apoplexy Causes

Pituitary apoplexy causes include Ischemic factors, blood vessel bursting and
bleeding, prolactinomas, trauma, radiation therapy, upper respiratory tract
infection, certain drugs.

Pituitary apoplexy

Pituitary apoplexy is acute neural endocrine disease due to suddenly hemorrhage,

infarction, necrosis, swelling in pituitary tumor, shows severe meningeal and
oppression surrounding tissue.

Simmonds disease Treatment

Treatment for Simmonds disease is hormone replacement therapy such as

Adrenocorticotropic hormone, Thyroid hormone, Sex hormone and gonadotropin,
and etiological treatment.

Simmonds disease Diagnosis

Diagnosis for Simmonds disease is glands and anterior pituitary function

examination, determination of adrenocortical, thyroid, gonadal, ACTH stimulation
test, TSH stimulation test.

Simmonds disease Symptoms

Symptoms of Simmonds disease is based on lack of pituitary hormones, such as
lack of gonadotropin, growth hormone, prolactin, thyroxin stimulating hormone,
adrenocorticotropic hormone and pituitary crisis.

Simmonds disease Causes

Causes of Simmonds disease is Avascular necrosis of the anterior pituitary,

Postpartum pituitary necrosis, Pituitary and hypothalamic tumors, Autoimmune
hypophysitis, Radiotherapy and chemotherapy.

Simmonds disease

Simmonds disease, anterior pituitary hypofunction, is lack secretion of pituitary

hormones, lesions of pituitary or hypothalamus involve the endocrine function in
pituitary gland.

Hypopituitarism Treatment

Treatment for Hypopituitarism include Glucocorticoid, Hydrocortisone,

prednisone, Thyroid tablets, Artificial cycle treatment, Keto acid pill Sim, Surgery
or radiotherapy, Crisis management.

Hypopituitarism Diagnosis

Diagnosis of Hypopituitarism is examine the lack of TSH and ACTH, Assessment

of thyroid function, PRL assessment, GH tests in children, Serum LH and FSH
assessment, hormone Assessment.

Hypopituitarism Symptoms

Symptoms of Hypopituitarism is based on reduction of sex hormone secretion or

thyroxine, reducted adrenocorticotropic hormone, decreased anterior pituitary.

Hypopituitarism
Hypopituitarism is reduced thyroid hormones and cause metabolism disorder,
causes of Hypopituitarism is Primary such pituitary tumor, secondary such
pituitary stalk or hypothalamus injury.

Amenorrhea Prevention

Prevention for Amenorrhea is actively cured hypomenorrhea, Make clear the cause
and locations of amenorrhea, spirit comfort and encouragement, avoid excessive
weight loss.

Amenorrhea diagnosis with examination of endocrine function

Examination of endocrine function for Amenorrhea diagnosis include Progestin

trial, Estrogen - progesterone test, Determination of pituitary gonadotropin,
Pituitary stimulation test.

Amenorrhea Treatment

Treatment for Amenorrhea include uterine expansion, separation of adhesions,

Estrogen and progesterone replacement therapy, Induced ovulation, Medication
such progesterone, B phenol.

Amenorrhea Diagnosis

Diagnosis for Amenorrhea is inquire about medical history and perform many tests
include Cervical screening, Ovarian function tests, Pituitary function tests.

Amenorrhea Causes

Causes of amenorrhea include endocrine diseases, lower reproductive tract atresia,

genital dysplasia, tuberculosis endometritis, Pituitary or hypothalamic abnormal,
gonadotropin secretion abnormal.

Secondary amenorrhea
Secondary amenorrhea is absence of menstruation more than three months in
women Menstrual period; causes is injury or endometrial adhesion, tuberculous
meningitis, premature ovarian function.

Primary Amenorrhea

Primary Amenorrhea is that have no menstrual cycle over 14 or 16 years, causes is

genital abnormalities (imperforate hymen, congenital absence of vagina or uterus)
and Endocrine disorder.

Amenorrhea

Amenorrhea is common gynecological disease, absence of menstruation, stop

menstruation after already menstrual cycle, divided into primary Amenorrhea and
secondary Amenorrhea.

Syndrome of inappropriate antidiuretic hormone secretion

Syndrome of inappropriate antidiuretic hormone secretion is excessive secretion of

endogenous antidiuretic hormone, information on SIADH causes, symptoms,
diagnosis, treatment.

Hypercalcemia Treatment

Treatment for hypercalcemia is to reduce serum calcium, include saline infusion,

expand of blood volume, increase in urinary calcium excretion.

Hypercalcemia Symptoms

Symptoms of hypercalcemia is fatigue, headache, weakness, depression,

excitability, convulsions, coma, anorexia, nausea, vomiting, abdominal pain.

Hypercalcemia Causes
Hypercalcemia is caused by primary hyperparathyroidism, malignant tumors (bone
tumor, leukemia), Secondary hyperparathyroidism, Toxicosis with vitamin D.

Endocrine Diseases
Health topics and information on Endocrine Diseases, browse comprehensive
articles about Endocrine Diseases causes, symptoms, diagnosis, treatment,
prevention from health study.

Hypercalcemia

Hypercalcemia is a condition that the concentration of serum ionized calcium

unusual increase and calcium concentration is higher than 2.75mmol / L.

Hypocalcemia Treatment

Treatment of hypocalcemia include intravenous injection of 10% diluted calcium

gluconate 10ml and take orally calcium and vitamin D.

Hypocalcemia Diagnosis

Diagnosis for Hypocalcemia include Determination of serum calcium, serum

phosphorus, phosphorus in urine, serum PTH and ECG.

Hypocalcemia Symptoms

Hypocalcemia symptoms include increased neuromuscular excitability, muscle

cramps, convulsions, easily excited, emotional instability.

Hypocalcemia Causes

Hypocalcemia causes is lack of parathyroid hormone, lack of vitamin D or

metabolic abnormalities, Chronic renal insufficiency, Acute pancreatitis.

Hypocalcemia
Hypocalcemia is a condition that Serum calcium less than 2.2mmol / L. Normal
serum calcium concentration is 2.25 ~ 2.75 mmol / L.

Hypermagnesemia Treatment

Treatment of hypermagnesemia include intravenous calcium gluconate or calcium

chloride, reduce blood magnesium, increase urine magnesium excretion,
hemodialysis.

Hypermagnesemia Diagnosis

Hypermagnesemia is diagnosed by Serum magnesium increased, volume of urine

magnesium excluded, Electrocardiogram, B-ultrasound.

Hypermagnesemia Symptoms

Symptoms of hypermagnesemia include loss of appetite, nausea, vomiting, skin

flushing, headache, dizziness and more.

Hypermagnesemia Causes

Hypermagnesemia Causes is Magnesium emission reduction from renal, shift-out

magnesium from cell, Excessive take medicine of magnesium.

Hypomagnesemia Treatment

Treatment for Hypomagnesemia is prevention of causes, supplement magnesium,

infusion magnesium salt.

Hypomagnesemia Diagnosis

Hypomagnesemia is diagnosed by Determination of serum magnesium, urinary

magnesium, intravenous magnesium load test, ECG.

Hypomagnesemia Symptoms
Symptoms of hypomagnesemia are muscle weakness, cramps, cardiac arrhythmia,
atherosclerosis, osteoporosis, bone softening.

Hypomagnesemia Causes

Hypomagnesemia is Caused by intestinal malabsorption, increase in aldosterone

secretion, kidney diseases, diabetic acidosis.

Hypomagnesemia

Hypomagnesemia is serum magnesium less than 0.75mmol / L, normal magnesium

in the plasma is 0.8. ~ 1.05mmol / L.

Hyperkalemia Treatment

Treatment for hyperkalemia include intravenous calcium gluconate, reduce serum

potassium, low potassium diet, hemodialysis.

Hyperkalemia Diagnosis

Hyperkalemia is diagnosed by Complete Blood Count, urine tests, kidney function

test, Electrocardiogram.

Hyperkalemia Symptoms

Symptoms of Hyperkalemia include arrhythmia, limbs and mouth numbness,

fatigue, muscle pain, limb pale, metabolic acidosis.

Hyperkalemia Causes

Causes of Hyperkalemia include intake for potassium too much, Excretion

reduced, potassium from intracellular move to extracellular.

Hyperkalemia
Hyperkalemia is a condition that potassium is higher than 5.5mmol / L in blood,
potassium > 7.0mmol / L is severe hyperkalemia.

Hypokalemia complications

Complications of Hypokalemia include low magnesium, low calcium, arrhythmia,

hyperkalemia, kidney diseases.

Hypokalemia Treatment

Treatment of hypokalemia include primary disease prevent, potassium supplement,

correct water and electrolyte metabolism disorder.

Hypokalemia Diagnosis

Hypokalemia is Confirm diagnosed by Blood tests (Decreased serum potassium),

Urine tests (Lower urinary potassium).

Hypokalemia Symptoms

Hypokalemia symptoms include weak, flaccid paralysis of tendon reflexes,

drowsiness, Nausea, vomiting, palpitations.

Hypokalemia Causes

Causes of Hypokalemia are Potassium intake to reduce, Potassium emits excessive,

Extracellular of potassium move to the intracellular.

Hypokalemia

Hypokalemia is a condition which the concentration of serum potassium in the

blood is less than 3.5mmol / L.

Pathophysiology of Diabetes Mellitus

Studies conducted on the pathophysiology of diabetes mellitus have suggested that
abnormal metabolism of insulin hormone is the primary cause for the development
of this complex syndrome. Even though the etiologies and triggering factors of the
three types of diabetes mellitus are different, they share nearly the same symptoms
and complications.

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What is Diabetes Mellitus

Diabetes mellitus (DM) or simply diabetes, is a chronic health condition in which

the body either fails to produce sufficient amount of insulin or responds
abnormally to insulin. Speaking about the classification of diabetes mellitus, it is of
three types, namely, Type 1 diabetes, Type 2 diabetes and Gestational diabetes.
The ultimate outcome for all three types of diabetes is high blood glucose level or
hyperglycemia. The pathophysiology of diabetes mellitus is very complex, as the
disease is characterized by different etiologies but share similar signs, symptoms
and complications.

Diabetes Mellitus and Pathophysiology

The pathophysiology of diabetes mellitus (all types) is related to the hormone
insulin, which is secreted by the beta cells of the pancreas. This hormone is
responsible for maintaining glucose level in the blood. It allows the body cells to
use glucose as a main energy source. However, in a diabetic person, due to
abnormal insulin metabolism, the body cells and tissues do not make use of
glucose from the blood, resulting in an elevated level of blood glucose or
hyperglycemia. Over a period of time, high glucose level in the bloodstream can lead
to severe complications, such as eye disorders, cardiovascular diseases, kidney
damage and nerve problems.

In Type 1 diabetes, the pancreas cannot synthesize enough amount of insulin

hormone as required by the body. The pathophysiology of Type 1 diabetes mellitus
suggests that it is an autoimmune disease, in which the body's own immune system
generates secretion of substances that attack the beta cells of the pancreas.
Consequently, the pancreas secretes little or no insulin. Type 1 diabetes is more
common among children and young adults (around 20 years). Since it is common
among young individuals and insulin hormone is used for treatment, Type 1
diabetes is also referred to as Insulin Dependent Dabetes Mellitus (IDDM) or
Juvenile Diabetes.

In case of Type 2 diabetes mellitus, there is normal production of insulin hormone but
the body cells are resistant to insulin. Since the body cells and tissues are non
responsive to insulin, glucose remains in the bloodstream. It is commonly
manifested by middle-aged adults (above 40 years). As insulin is not necessary for
treatment of Type 2 diabetes, it is known as Non-insulin Dependent Diabetes
Mellitus (NIIDM) or Adult Onset Diabetes.

Gestational diabetes, on the other hand, occurs among pregnant women. It is caused
due to fluctuations of the hormonal level during pregnancy. Usually, the blood
glucose level returns to normal after the baby is born.

As already mentioned above, the symptoms and effects of all the three forms of
diabetes are similar. The noticeable manifested symptoms include increased thirst
(polydipsia), increased urination (polyuria), increased appetite (polyphagia),
excessive fatigue, unexplained weight loss and body irritation. Regarding the
definition of diabetes mellitus, it is often described as a fasting blood glucose level
of 126 milligrams per deciliter (mg/dL) or more. As per statistics, Type 2 diabetes
is the most commonly occurring type, in comparison to the other two forms of
diabetes mellitus.

Early and correct detection of the type of diabetes is necessary to prevent severe
health effects. After diagnosis, a physician may prescribe appropriate medication
for treatment of diabetes, which could include insulin injections or oral insulin
medicines, depending upon the type of diabetes mellitus. In addition, healthy
lifestyle modifications, especially diet and exercise are recommended for the
effective management of symptoms and long-term effects. Since diabetes is a
global health issue, studies regarding the pathophysiology of diabetes mellitus are
currently in progress in order to minimize its associated health effects.

Diabetes mellitus type 2

Diabetes mellitus type 2 – formerly non-insulin-dependent diabetes mellitus
(NIDDM) or adult-onset diabetes – is a metabolic disorder that is characterized
by high blood glucose in the context of insulin resistance and relative insulin
deficiency.[2] Diabetes is often initially managed by increasing exercise and dietary
modification. As the condition progresses, medications may be needed.

Unlike type 1 diabetes, there is very little tendency toward ketoacidosis though it is
not unheard of.[3] One effect that can occur is nonketonic hyperglycemia. Long-
term complications from high blood sugar can include increased risk of heart
attacks, strokes, amputation, and kidney failure.

Signs and symptoms

The classical symptoms of diabetes are polyuria (frequent urination), polydipsia
(increased thirst), polyphagia (increased hunger), fatigue and weight loss.[4]

Cause
Type 2 diabetes is due to a combination of lifestyle and genetic factors.[5][6]
Lifestyle

A number of lifestyle factors are known to be important to the development of

type 2 diabetes. In one study, those who had high levels of physical activity, a
healthy diet, did not smoke, and consumed alcohol in moderation had an 82%
lower rate of diabetes. When a normal weight was included the rate was 89%
lower. In this study a healthy diet was defined as one high in fiber, with a high
polyunsaturated to saturated fat ratio, and a lower mean glycemic index.[7] Obesity
has been found to contribute to approximately 55% of cases of type 2 diabetes,[8]
and decreasing consumption of saturated fats and trans fatty acids while replacing
them with unsaturated fats may decrease the risk.[5] The increased rate of childhood
obesity in between the 1960s and 2000s is believed to have led to the increase in
type 2 diabetes in children and adolescents.[9]

Environmental toxins may contribute to recent increases in the rate of type 2

diabetes. A positive correlation has been found between the concentration in the
urine of bisphenol A, a constituent of some plastics, and the incidence of type 2
diabetes.[10]

Medical conditions

There are many factors which can potentially give rise to or exacerbate type 2
diabetes. These include obesity, hypertension, elevated cholesterol (combined
hyperlipidemia), and with the condition often termed metabolic syndrome (it is
also known as Syndrome X, Reavan's syndrome, or CHAOS). Other causes include
acromegaly, Cushing's syndrome, thyrotoxicosis, pheochromocytoma, chronic
pancreatitis, cancer, and drugs. Additional factors found to increase the risk of type
2 diabetes include aging,[11] high-fat diets[12] and a less active lifestyle.[13]

Subclinical Cushing's syndrome (cortisol excess) may be associated with type 1

diabetes.[14] The percentage of subclinical Cushing's syndrome in the diabetic
population is about 9%.[15] Diabetic patients with a pituitary microadenoma can
improve insulin sensitivity by removal of these microadenomas.[16]

Hypogonadism is often associated with cortisol excess, and testosterone deficiency

is also associated with type 2 diabetes, [17][18] even if the exact mechanism by which
testosterone improve insulin sensitivity is still not known.

Genetics
There is also a strong inheritable genetic connection in type 2 diabetes: having
relatives (especially first degree) with type 2 increases risks of developing type 2
diabetes very substantially. In addition, there is also a mutation to the Islet
Amyloid Polypeptide gene that results in an earlier onset, more severe, form of
diabetes.[19][20]

About 55 percent of type 2 diabetes patients are obese at diagnosis[21] —chronic

obesity leads to increased insulin resistance that can develop into type 2 diabetes,
most likely because adipose tissue (especially that in the abdomen around internal
organs) is a (recently identified) source of several chemical signals to other tissues
(hormones and cytokines).

Other research shows that type 2 diabetes causes obesity as an effect of the
changes in metabolism and other deranged cell behavior attendant on insulin
resistance.[22]

However, environmental factors (almost certainly diet and weight) play a large part
in the development of type 2 diabetes in addition to any genetic component. This
can be seen from the adoption of the type 2 diabetes epidemiological pattern in
those who have moved to a different environment as compared to the same genetic
pool who have not. Immigrants to Western developed countries, for instance, as
compared to lower incidence countries of origins.[23]

There is a stronger inheritance pattern for type 2 diabetes. Those with first-degree
relatives with type 2 diabetes have a much higher risk of developing type 2
diabetes, increasing with the number of those relatives. Concordance among
monozygotic twins is close to 100%, and about 25% of those with the disease have
a family history of diabetes. Genes significantly associated with developing type 2
diabetes, include TCF7L2, PPARG, FTO, KCNJ11, NOTCH2, WFS1, CDKAL1,
IGF2BP2, SLC30A8, JAZF1, and HHEX.[24][25] KCNJ11 (potassium inwardly
rectifying channel, subfamily J, member 11), encodes the islet ATP-sensitive
potassium channel Kir6.2, and TCF7L2 (transcription factor 7–like 2) regulates
proglucagon gene expression and thus the production of glucagon-like peptide-1.[26]
Moreover, obesity (which is an independent risk factor for type 2 diabetes) is
strongly inherited.[27]

Monogenic forms, e.g., MODY, constitute 1–5 % of all cases.[28]

Various hereditary conditions may feature diabetes, for example myotonic

dystrophy and Friedreich's ataxia. Wolfram's syndrome is an autosomal recessive
neurodegenerative disorder that first becomes evident in childhood. It consists of
diabetes insipidus, diabetes mellitus, optic atrophy, and deafness, hence the
acronym DIDMOAD.[29]

Gene expression promoted by a diet of fat and glucose as well as high levels of
inflammation related cytokines found in the obese results in cells that "produce
fewer and smaller mitochondria than is normal," and are thus prone to insulin
resistance.[30]

Pathophysiology
Insulin resistance means that body cells do not respond appropriately when insulin
is present. Unlike type 1 diabetes mellitus, insulin resistance is generally "post-
receptor", meaning it is a problem with the cells that respond to insulin rather than
a problem with the production of insulin.

This is a more complex problem than type 1, but is sometimes easier to treat,
especially in the early years when insulin is often still being produced internally.
Severe complications can result from improperly managed type 2 diabetes,
including renal failure, erectile dysfunction, blindness, slow healing wounds
(including surgical incisions), and arterial disease, including coronary artery
disease. The onset of type 2 diabetes has been most common in middle age and
later life, although it is being more frequently seen in adolescents and young adults
due to an increase in child obesity and inactivity. A type of diabetes called MODY
is increasingly seen in adolescents, but this is classified as a diabetes due to a
specific cause and not as type 2 diabetes.

Diabetes mellitus with a known etiology, such as secondary to other diseases,

known gene defects, trauma or surgery, or the effects of drugs, is more
appropriately called secondary diabetes mellitus or diabetes due to a specific cause.
Examples include diabetes mellitus such as MODY or those caused by
hemochromatosis, pancreatic insufficiencies, or certain types of medications (e.g.,
long-term steroid use).

Diagnosis
2006 WHO Diabetes criteria[31]  edit
Condition 2 hour glucose Fasting glucose
mmol/l(mg/dl) mmol/l(mg/dl)
Normal <7.8 (<140) <6.1 (<110)
 Impaired fasting glycaemia <7.8 (<140) ≥ 6.1(≥110) & <7.0(<126)
Impaired glucose tolerance ≥7.8 (≥140) <7.0 (<126)
Diabetes mellitus ≥11.1 (≥200) ≥7.0 (≥126)

The World Health Organization definition of diabetes is for a single raised glucose
reading with symptoms, otherwise raised values on two occasions, of either:[32]

 fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl)

or

 With a glucose tolerance test, two hours after the oral dose a plasma glucose
≥ 11.1 mmol/l (200 mg/dl)

Early detection

If a 2-hour postload glucose level of at least 11.1 mmol/L (≥ 200 mg/dL) is used as

the reference standard, the fasting plasma glucose > 7.0 mmol/L (126 mg/dL)
diagnoses current diabetes with[33]:

 sensitivity about 50%

 specificity greater than 95%

A random capillary blood glucose > 6.7 mmol/L (120 mg/dL) diagnoses current

diabetes with[34]:

 sensitivity = 75%
 specificity = 88%

Glycosylated hemoglobin values that are elevated (over 5%), but not in the diabetic
range (not over 7.0%) are predictive of subsequent clinical diabetes in United
States female health professionals.[35] In this study, 177 of 1061 patients with
glycosylated hemoglobin value less than 6% became diabetic within 5 years
compared to 282 of 26281 patients with a glycosylated hemoglobin value of 6.0%
or more. This equates to a glycosylated hemoglobin value of 6.0% or more having:

 sensitivity = 16.7%
 specificity = 98.9%

Screening
No major organization recommends universal screening for diabetes as there is no
evidence that such a program would improve outcomes. [36] Screening is
recommended by the United States Preventive Services Task Force in adults
without symptoms whose blood pressure is greater than 135/80 mmHg.[37] For
those whose blood pressure is less the evidence is insufficient to recommend for or
against screening.[37] The World Health Organization recommends only testing
those groups at high risk.[36]

Prevention
Onset of type 2 diabetes can be delayed or prevented through proper nutrition and
regular exercise.[38][39] Intensive lifestyle measures may reduce the risk by over half.
[6]
Evidence for the benefit of dietary changes alone however is limited. [40] In those
with impaired glucose tolerance diet and exercise and/or metformin or acarbose
may decrease the risk of developing diabetes.[41][6] Lifestyle interventions are more
effective than metformin.[6]

Management
Management of type 2 diabetes focuses on lifestyle interventions, lowering other
cardiovascular risk factors, and maintaining blood glucose levels in the normal
range.[6] Self-monitoring of blood glucose for people with newly diagnosed type 2
diabetes was recommended by the National Health Services in 2008[42] however the
benefit of self monitoring in those not using multi dose insulin is questionable.[6]

Lifestyle

Aerobic exercise is beneficial in diabetes with the greater the amount of exercise
the better the results.[43] It leads to a decrease in HbA1C, improved insulin
resistance, and a better V02 max.[43] Resistance training is also useful and the
combination of both types of exercise may be most effective.[43] A diabetic diet that
promotes weight loss is important.[44] While the best diet type to achieve this is
controversial[44] a low glycemic index diet has been found to improve blood sugar
control.[45] Culturally appropriate education may help people with type 2 diabetes
control their blood sugar levels, for up to six months at least.[46]

Medications
Metformin 500mg tablets

There are several classes of medications available. Metformin is generally

recommended first line as there is good evidence that it decreases mortality. [6]
Injections of insulin may either be added to oral medication or used alone. [6] Other
classes of medications used to treat type 2 diabetes are sulfonylureas,
nonsulfonylurea secretagogues, alpha glucosidase inhibitors, and
thiazolidinediones. [6]

Insulin

When insulin is used, it is initially usually a long acting formulation and oral
medications are continued.[6] Doses of insulin are increased to effect.[6]

The initial insulin regimen are often chosen based on the patient's blood glucose
profile.[47] Initially, adding nightly insulin to patients failing oral medications may
be best.[48] Nightly insulin combines better with metformin than with sulfonylureas.
[49]

When nightly insulin is insufficient, choices include:

 Premixed insulin with a fixed ratio of short and intermediate acting insulin;
this tends to be more effective than long acting insulin, but is associated with
increased hypoglycemia.[50][51][52] Initial total daily dosage of biphasic insulin
can be 10 units if the fasting plasma glucose values are less than 180 mg/dl
or 12 units when the fasting plasma glucose is above 180 mg/dl".[51] A guide
to titrating fixed ratio insulin is available.[47]
 Long acting insulins such as insulin glargine and insulin detemir. A meta-
analysis of randomized controlled trials by the Cochrane Collaboration
found "only a minor clinical benefit of treatment with long-acting insulin
analogues for patients with diabetes mellitus type 2". [53] More recently, a
 randomized controlled trial found that although long acting insulins were
less effective, they were associated with reduced hypoglycemic episodes.[50]

Cardiovascular risk factors

Managing other cardiovascular risk factors including hypertension, high

cholesterol, and microalbuminuria improves a persons life expectancy.[6]

Surgery

Gastric Bypass procedures are currently considered an elective procedure with no

universally accepted algorithm to decide who should have the surgery. In the
diabetic patient, certain types result in 99-100% prevention of insulin resistance
and 80-90% clinical resolution or remission of type 2 diabetes. In 1991, the NIH
(National Institutes of Health) Consensus Development Conference on
Gastrointestinal Surgery for Obesity proposed that the body mass index (BMI)
threshold to consider surgery should drop from 40 to 35 in the appropriate patient.
More recently, the American Society for Bariatric Surgery (ASBS) and the ASBS
Foundation suggested that the BMI threshold be lowered to 30 in the presence of
severe co-morbidities.[54] Debate has flourished about the role of gastric bypass
surgery in type 2 diabetics since the publication of The Swedish Obese Subjects
Study. The largest prospective series showed a large decrease in the occurrence of
type 2 diabetes in the post-gastric bypass patient at both 2 years (odds ratio was
0.14) and at 10 years (odds ratio was 0.25).[55]

A study of 20-years of Greenville (US) gastric bypass patients found that 80% of
those with type 2 diabetes before surgery no longer required insulin or oral agents
to maintain normal glucose levels. Weight loss occurred rapidly in many people in
the study who had had the surgery. The 20% who did not respond to bypass
surgery were, typically, those who were older and had had diabetes for over 20
years.[56]

Prognosis
In adults type 2 diabetes is the primary cause of blindness and kidney failure.[6]

Epidemiology
Globally in 2003 it was estimated that there were 150 million people with type 2 diabetes.[57] The
incidence varies substantially in different parts of the world, almost certainly because of
environmental and lifestyle factors, though these are not known in detail.[58] In the United States
there are 23.6 million people (7.8% of the population) with diabetes with 17.9 million being
diagnosed,[59] 90% of whom are type 2.[60] With prevalence rates doubling between 1990 and
2005, CDC has characterized the increase as an epidemic.[61] Traditionally considered a disease
of adults, type 2 diabetes is increasingly diagnosed in children in parallel to rising obesity rates
[62]
due to alterations in dietary patterns as well as in life styles during childhood.[63]

Diabetes mellitus type 1

Diabetes mellitus type 1 (Type 1 diabetes, IDDM, or, obsoletely, juvenile diabetes) is a form of
diabetes mellitus that results from autoimmune destruction of insulin-producing beta cells of the
pancreas.[2] The subsequent lack of insulin leads to increased blood and urine
glucose. The classical symptoms are polyuria (frequent urination), polydipsia
(increased thirst), polyphagia (increased hunger), and weight loss.[3]

Type 1 diabetes is fatal unless treated with insulin. Injection is the most common
method of administering insulin; insulin pumps and inhaled insulin have been
available at various times. Pancreas and islet transplants have been used to treat
type 1 diabetes; however, islet transplants are currently still at the experimental
trial stage.[4]

Most people who develop type 1 are otherwise healthy.[5] Although the cause of
type 1 diabetes is still not fully understood it is believed to be of immunological
origin.

Type 1 can be distinguished from type 2 diabetes via a C-peptide assay, which
measures endogenous insulin production.

Type 1 treatment must be continued indefinitely in all cases. Treatment need not
significantly impair normal activities, if sufficient patient training, awareness,
appropriate care, discipline in testing and dosing of insulin is taken. However,
treatment is burdensome for many people. Complications may be associated with
both low blood sugar and high blood sugar. Low blood sugar may lead to seizures
or episodes of unconsciousness and requires emergency treatment. High blood
sugar may lead to increased tiredness and can also result in long term damage to
organs.

Signs and symptoms

The classical symptoms of type 1 diabetes include: polyuria (frequent urination),
polydipsia (increased thirst), polyphagia (increased hunger), tiredness, and weight
loss.[3]
Cause
Evidence so far indicates that the development of diabetes type I is induced by
more or less a combination of genetic susceptibility, a diabetogenic trigger and
exposure to a driving antigen.[6] Many risk factors have been suggested, and there
is an ongoing research into the influence of individual factors, and whether some
may be regarded as sufficient to cause the disease by themselves or only in
addition to other risk factors.

Genetics

Type 1 diabetes is a polygenic disease, meaning many different genes contribute to

its expression. Depending on locus or combination of loci, it can be dominant,
recessive, or somewhere in between. The strongest gene, IDDM1, is located in the
MHC Class II region on chromosome 6, at staining region 6p21. Certain variants
of this gene increases the risk for decreased histocompatibility characteristic of
type 1. Such variants include DRB1 0401, DRB1 0402, DRB1 0405, DQA 0301,
DQB1 0302 and DQB1 0201, which are common in North Americans of European
ancestry and in Europeans.[7] There are also variants that appear to be protective.[7]

Environmental

Environmental factors can strongly influence expression of type 1. A study showed

that for identical twins, when one twin had type 1 diabetes, the other twin only had
type 1 30%–50% of the time. Despite having exactly the same genome, one twin
had the disease, where the other did not; this suggests that environmental factors,
in addition to genetic factors, can influence disease prevalence. [8] Other indications
of environmental influence include the presence of a 10-fold difference in
difference among Caucasians living in different areas of Europe, and a tendency to
acquire the incidence of the disease of the destination country for people who
migrate.[6]

Virus

One theory, discussed by DeLisa Fairweather & Noel R. Rose, among others, [9]
proposes that type 1 diabetes is a virally triggered autoimmune response in which
the immune system attacks virus infected cells along with the beta cells in the
pancreas. The Coxsackie virus family or Rubella is implicated, although the
evidence is inconclusive. In type 1, pancreatic beta cells in the Islets of Langerhans
are destroyed decreasing endogenous insulin production. This distinguishes
type 1's origin from type 2 DM. The type of diabetes a patient has is determined
only by the cause—fundamentally by whether the patient is insulin resistant
(type 2) or insulin deficient without insulin resistance (type 1).

This vulnerability is not shared by everyone, for not everyone infected by the
suspected organisms develops type 1 diabetes. This has suggested presence of a
genetic vulnerability[10] and there is indeed an observed inherited tendency to
develop type 1. It has been traced to particular HLA genotypes, though the
connection between them and the triggering of an auto-immune reaction is still
poorly understood.

Diet

There is a growing body of evidence that diet may play a role in the development
of type 1 diabetes, through influencing gut flora, intestinal permeability, and
immune function in the gut; wheat in particular has been shown to have a
connection to the development of type 1 diabetes, although the relationship is
poorly understood.[11]

Some researchers believe that the autoimmune response is influenced by antibodies

against cow's milk proteins.[12] No connection has been established between
autoantibodies, antibodies to cow's milk proteins, and type 1 diabetes. A subtype of
type 1 (identifiable by the presence of antibodies against beta cells) typically
develops slowly and so is often confused with type 2. In addition, a small
proportion of type 2 cases manifest a genetic form of the disease called maturity
onset diabetes of the young (MODY).[citation needed]

Vitamin D in doses of 2000 IU per day given during the first year of a child's life
has been connected in one study in Northern Finland (where intrinsic production of
Vitamin D is low due to low natural light levels) with an 80% reduction in the risk
of getting type 1 diabetes later in life. The causal connection, if any, is obscure.

Short breast-feeding period and short attendance to day care is associated with the
risk of type 1 diabetes in Czech children.[13]

Chemicals and drugs

Some chemicals and drugs preferentially destroy pancreatic cells. Pyrinuron

(Vacor, N-3-pyridylmethyl-N'-p-nitrophenyl urea), a rodenticide introduced in the
United States in 1976, selectively destroys pancreatic beta cells, resulting in type 1
diabetes after accidental or intentional ingestion. Vacor was withdrawn from the
U.S. market in 1979, but is still used in some countries. Zanosar is the trade name
for streptozotocin, an antibiotic and antineoplastic agent used in chemotherapy for
pancreatic cancer; it also kills beta cells, resulting in loss of insulin production.
Other pancreatic problems, including trauma, pancreatitis or tumors (either
malignant or benign), can also lead to loss of insulin production.

Pathophysiology
The pathophysiology in diabetes type I is basically a destruction of beta cells in the
pancreas, regardless of which risk factors or causative entities have been present.

Individual risk factors can have separate pathophysiological processes to, in turn,
cause this beta cell destruction. Still, a process that appears to be common to most
risk factors is an autoimmune response towards beta cells, involving an expansion
of autoreactive CD4+ and CD8+ T helper cells, autoantibody-producing B cells
and activation of the innate immune system.[7]

Diagnosis
See also: Glycosylated hemoglobin and Glucose tolerance test
2006 WHO Diabetes criteria[14]  
Condition 2 hour glucose Fasting glucose
mmol/l(mg/dl) mmol/l(mg/dl)
Normal <7.8 (<140) <6.1 (<110)
Impaired fasting glycaemia <7.8 (<140) ≥ 6.1(≥110) & <7.0(<126)
Impaired glucose tolerance ≥7.8 (≥140) <7.0 (<126)
Diabetes mellitus ≥11.1 (≥200) ≥7.0 (≥126)

Diabetes mellitus is characterized by recurrent or persistent

hyperglycemia, and is diagnosed by demonstrating any one of the
following:[15]
 Fasting plasma glucose level at or above 7.0 mmol/L (126 mg/dL).
 Plasma glucose at or above 11.1 mmol/L (200 mg/dL) two hours after a 75 g
oral glucose load as in a glucose tolerance test.
 Symptoms of hyperglycemia and casual plasma glucose at or above
11.1 mmol/L (200 mg/dL).
 Glycated hemoglobin (hemoglobin A1C) at or above 6.5. (This criterion was
recommended by the American Diabetes Association in 2010; it has yet to
be adopted by the WHO.)[16]
About a quarter of people with new type 1 diabetes have developed some degree of
diabetic ketoacidosis (a type of metabolic acidosis which is caused by high
concentrations of ketone bodies, formed by the breakdown of fatty acids and the
deamination of amino acids) by the time the diabetes is recognized. The diagnosis
of other types of diabetes is usually made in other ways. These include ordinary
health screening, detection of hyperglycemia during other medical investigations,
and secondary symptoms such as vision changes or unexplainable fatigue. Diabetes
is often detected when a person suffers a problem that may be caused by diabetes,
such as a heart attack, stroke, neuropathy, poor wound healing or a foot ulcer,
certain eye problems, certain fungal infections, or delivering a baby with
macrosomia or hypoglycemia.

A positive result, in the absence of unequivocal hyperglycemia, should be

confirmed by a repeat of any of the above-listed methods on a different day. Most
physicians prefer to measure a fasting glucose level because of the ease of
measurement and the considerable time commitment of formal glucose tolerance
testing, which takes two hours to complete and offers no prognostic advantage over
the fasting test.[17] According to the current definition, two fasting glucose
measurements above 126 mg/dL (7.0 mmol/L) is considered diagnostic for
diabetes mellitus.

Patients with fasting glucose levels from 100 to 125 mg/dL (5.6 to 6.9 mmol/L) are
considered to have impaired fasting glucose. Patients with plasma glucose at or
above 140 mg/dL (7.8 mmol/L), but not over 200 mg/dL (11.1 mmol/L), two hours
after a 75 g oral glucose load are considered to have impaired glucose tolerance. Of
these two pre-diabetic states, the latter in particular is a major risk factor for
progression to full-blown diabetes mellitus and cardiovascular disease.[18]

Autoantibodies

The appearance of diabetes-related autoantibodies has been shown to be able to

predict the appearance of diabetes type 1 before any hyperglycemia arises, the
main ones being islet cell autoantibodies, insulin autoantibodies, autoantibodies
targeting the 65 kDa isoform of glutamic acid decarboxylase (GAD) and
autoantibodies tergeting the phosphatase-related IA-2 molecule.[6] Per definition,
the diagnosis of diabetes type 1 can be made first at the appearance of clinical
symptoms and/or signs, but the emergence of autoantibodies may itself be termed
latent autoimmune diabetes. Not everyone with autoantibodies progress to diabetes
type 1, but the risk increases with the number of antibody types, with three to four
antibody types giving a risk of progressing to diabetes type 1 of 60%-100%. [6] The
time interval from emergence of autoantibodies to frank diabetes type 1 can be a
few months in infants and young children, but in some people it may take years - in
some cases more than 10 years.[6] Islet cell autoantibodies are detected by
conventional immunofluorescence while the rest are measured with specific
radiobinding assays.[6]

Prevention
Type 1 diabetes is not currently preventable.[19] Still, promising therapies are
emerging, and it has been suggested that, in the future, diabetes type 1 may be
prevented at the latent autoimmune stage, probably by a combination therapy of
several methods.[7]

Immunosuppressive drugs

Cyclosporine A, an immunosuppressive agent, has apparently halted destruction of

beta cells (on the basis of reduced insulin usage), but its nephrotoxicity and other
side effects make it highly inappropriate for long-term use.[7]

Anti-CD3 antibodies, including teplizimab and otelixizumab, have evidence of

preserving insulin production (as evidenced by sustained C-peptide production) in
newly diagnosed type 1 diabetes patients.[7] A probable mechanism of this effect is
preservation of regulatory T cells that suppress activation of the immune system
and thereby maintain immune system homeostasis and tolerance to self-antigens. [7]
The duration of this effect is still unknown, however.[7]

An anti-CD20 antibody, rituximab, inhibits B cells and has been shown to provoke
C-peptide responses three months after diagnosis of type 1 diabetes, but long-term
effects of this have not been reported.[7]

Dietary

Some research has suggested that breastfeeding decreased the risk in later life; [20][21]
various other nutritional risk factors are being studied, but no firm evidence has
been found.[22] Giving children 2000 IU of Vitamin D during their first year of life
is associated with reduced risk of type 1 diabetes, though the causal relationship is
obscure.[23]

Children with antibodies to beta cell proteins (i.e. at early stages of an immune
reaction to them) but no overt diabetes, and treated with vitamin B 3 (niacin), had
less than half the diabetes onset incidence in a 7-year time span as did the general
population, and an even lower incidence relative to those with antibodies as above,
but who received no vitamin B3.[24]

T helper cell shift

If a biochemical mechanism can be found that prevents the immune system from
attacking beta cells, it may be administered to prevent commencement of diabetes
type 1. Several groups are trying to achieve this by causing the activation state of
the immune system to change from type 1 T helper cell (Th1) state (“attack” by
killer T Cells) to Th2 state (development of new antibodies). This Th1-Th2 shift
occurs via a change in the type of cytokine signaling molecules being released by
T-cells. Instead of pro-inflammatory cytokines, the T-cells begin to release
cytokines that inhibit inflammation.[25] This phenomenon is commonly known as
"acquired immune tolerance".

GAD65 vaccine

Injections with a vaccine containing GAD65, an autoantigen involved in type 1

diabetes, has in clinical trials delayed the destruction of beta cells when treated
within six months of diagnosis.[7] Patients treated with the substance showed higher
levels of regulatory cytokines, thought to protect the beta cells. [26] Phase III trials
are under way in the USA [27] and in Europe.[28][29][30] Two prevention studies, where
the vaccine is given to persons who have not yet developed diabetes are underway.
[31][32][33]

Management
Further information: Diabetes management

Insulin therapy

Type 1 is treated with insulin replacement therapy—either via subcutaneous

injection or insulin pump, along with attention to dietary management, typically
including carbohydrate tracking, and careful monitoring of blood glucose levels
using glucose meters. Today the most common insulins are biosynthetic products
produced using genetic recombination techniques; formerly, cattle or pig insulins
were used, and even sometimes insulin from fish.[34] Major global suppliers include
Eli Lilly and Company, Novo Nordisk, and Sanofi-Aventis. A more recent trend,
from several suppliers, is insulin analogs which are slightly modified insulins
which have different onset of action times or duration of action times.

Untreated type 1 diabetes commonly leads to coma, often from diabetic

ketoacidosis, which is fatal if untreated. Continuous glucose monitors have been
developed and marketed which can alert patients to the presence of dangerously
high or low blood sugar levels, but technical limitations have limited the impact
these devices have had on clinical practice so far.

Driving

Treatment of diabetes focuses on lowering blood sugar or glucose (BG) to the near
normal range, approximately 80-140 mg/dl (4.4-7.8 mmol/L) [35]. The ultimate goal
of normalizing BG is to avoid long term complications that affect the nervous
system (e.g. peripheral neuropathy leading to pain and/or loss of feeling in the
extremities), and the cardiovascular system (e.g. heart attacks, vision loss). There
are two primary types of diabetes, type 1 and type 2. People with type 1 diabetes
always need to take insulin. Treatment with insulin can lead to low BG, or
hypoglycemia, i.e. BG less than 70mg/dl (3.9 mmol/L). Hypoglycemia is a
common occurrence in people with diabetes, usually the result of a mismatch in the
balance among insulin, food and physical activity.

Studies conducted in the United States[36] and Europe[37] showed that drivers with
Type 1 diabetes had twice as many collisions as their non-diabetic spouses,
demonstrating the increased risk of driving collisions in the Type 1 diabetes
population. Diabetes can compromise driving safety in several ways. First, long-
term complications of diabetes can interfere with the safe operation of a vehicle.
For example, diabetic retinopathy (loss of peripheral vision or visual acuity), or
peripheral neuropathy (loss of feeling in the feet) can impair a driver’s ability to
read street signs, control the speed of the vehicle, apply appropriate pressure to the
brakes, etc.

Second, hypoglycemia can affect a person’s thinking process, coordination, and

state of consciousness.[38][39] This disruption in brain functioning is called
neuroglycopenia. Studies have demonstrated that the effects of neuroglycopenia
impair driving ability.[40][41] A study involving people with Type 1 diabetes found
that individuals reporting two or more hypoglycemia-related driving mishaps differ
physiologically and behaviorally from their counterparts who report no such
mishaps.[42] For example, during hypoglycemia, drivers who had two or more
mishaps reported fewer warning symptoms, their driving was more impaired, and
their body released less epinephrine (a hormone that helps raise BG). Additionally,
individuals with a history of hypoglycemia-related driving mishaps appear to use
sugar at a faster rate[43] and are relatively slower at processing information. [44]
These findings indicate that although anyone with Type 1 diabetes may be at some
risk of experiencing disruptive hypoglycemia while driving, there is a subgroup of
Type 1 drivers who are more vulnerable to such events.

Given the above research findings, it is recommended that drivers with Type 1
diabetes with a history of driving mishaps should never drive when their BG is less
than 70 mg/dl. Instead, these drivers are advised to treat hypoglycemia and delay
driving until their BG is above 90 mg/dl.[45] Such drivers should also learn as much
as possible about what causes their hypoglycemia, and use this information to
avoid future hypoglycemia while driving.

Studies funded by the National Institutes of Health (NIH) have demonstrated that
face-to-face training programs designed to help individuals with Type 1 diabetes
better anticipate, detect, and prevent extreme BG can reduce the occurrence of
future hypoglycemia-related driving mishaps.[46][47][48] An internet-version of this
training has also been shown to have significant beneficial results. [49] Additional
NIH funded research to develop Internet interventions specifically to help improve
driving safety in drivers with Type 1 diabetes is currently underway: Diabetes
Driving.

Pancreas transplantation

In more extreme cases, a pancreas transplant can restore proper glucose regulation.
However, the surgery and accompanying immunosuppression required is
considered by many physicians to be more dangerous than continued insulin
replacement therapy, and is therefore generally only used together with or some
time after a kidney transplant. One reason for this is that introducing a new kidney
requires taking immunosuppressive drugs such as cyclosporine. Nevertheless this
allows the introduction of a new, functioning pancreas to a patient with diabetes
without any additional immunosuppressive therapy. However, pancreas transplants
alone can be wise in patients with extremely labile type 1 diabetes mellitus.[50]

Islet cell transplantation

Experimental replacement of beta cells (by transplant or from stem cells) is being
investigated in several research programs. Islet cell transplantation is expected to
be less invasive than a pancreas transplant which is currently the most commonly
used approach in humans.

In one variant of this procedure, islet cells are injected into the patient's liver,
where they take up residence and begin to produce insulin. The liver is expected to
be the most reasonable choice because it is more accessible than the pancreas, and
islet cells seem to produce insulin well in that environment. The patient's body,
however, will treat the new cells just as it would any other introduction of foreign
tissue, unless a method is developed to produce them from the patient's own stem
cells or there is an identical twin available who can donate stem cells. The immune
system will attack the cells as it would a bacterial infection or a skin graft. Thus,
patients now also need to undergo treatment involving immunosuppressants, which
reduce immune system activity.

Recent studies have shown that islet cell transplants have progressed to the point
that 58% of the patients in one study were insulin independent one year after islet
cell transplant.[51] Ideally, it would be best to use islet cells which will not provoke
this immune reaction. Scientists in New Zealand with Living Cell Technologies are
currently in human trials with Diabecell, placing pig islets within a protective
capsule derived of seaweed which enables insulin to flow out and nutrients to flow
in while protecting the islets from immune system attack via white blood cells.

Prognosis
Complications of poorly-managed type 1 diabetes mellitus may include
cardiovascular disease, diabetic neuropathy, diabetic retinopathy among others.
However, there is some evidence that cardiovascular disease[52] as well as
neuropathy[53] may, in fact, have an autoimmune basis as well.

Epidemiology
Type 1 diabetes causes an estimated 5%–10% of all diabetes cases[54] or 11–
22 million worldwide.[19] In 2006 it affected 440 thousand children under 14 years
of age and was the primary cause of diabetes in those less than 10 years of age. [55]
The incidence of type 1 diabetes has been increasing by about 3% per year. [55]
Rates vary widely in different countries with a low of 0.1 cases per 100,000 people
per year in China and Venezuela to a high of 37 cases per 100,000 people per year
in Finland and Sardinia.[56]

Type 1 diabetes was previously known as juvenile diabetes to distinguish it from

type 2 diabetes, which generally has a later onset; however, the majority of new-
onset type 1 diabetes is seen in adults. Scientific studies that use antibody testing
(glutamic acid decarboxylase antibodies (GADA), islet cell antibodies (ICA), and
insulinoma-associated autoantibodies (IA-2)) to distinguish between type 1 and
type 2 diabetes demonstrate that most new-onset type 1 diabetes is seen in adults.
A 2008 book, Type 1 Diabetes in Adults: Principles and Practice, says that adult-
onset type 1 autoimmune diabetes is two to three times more common than classic
childhood-onset autoimmune diabetes.[57]

Diet dos and don'ts for diabetics!

Part I: Diabetics, heed these diet tips!

Diabetes mellitus is a chronic metabolic disorder in which the body fails to convert sugars,
starches and other foods into energy.

Many of the foods you eat are normally converted into a type of sugar called glucose during
digestion. The bloodstream then carries glucose through the body. The hormone, insulin, then
turns glucose into quick energy or is stored for futher use.

In diabetic people, the body either does not make enough insulin or it cannot use the insulin
correctly. This is why too much glucose builds in the bloodstream.

There are two major types of diabetes:

1. Type 1

This is popularly known as Juvenile Onset Diabetes.

Here, the body produces little or no insulin. It occurs most often in childhood or in the teens and
could be inherited.

People with this type of diabetes need daily injections of insulin. They must balance their daily
intake of food and activites carefully with their insulin shots to stay alive.

2. Type 2
Also known as Adult Onset Diabetes, this occurs around 35 to 40 years. The more common of
the two types, it accounts for about 80 per cent of the diabetics.

Here, though the pancreas produce adequate insulin, body cells show reduced sensitivity

towards it.

Type 2 diabetes is usually triggered by obesity. The best way to fight it is by weight loss,
exercise and dietary control.

Sometimes, oral medication or insulin injections are also needed.

~ Symptoms of diabetes

Here are a few:

 Extreme thirst and hunger

 Frequent urination
 Sores or bruises that heal slowly
 Dry, itchy skin
 Unexplained weight loss
 Unusual tiredness or drowsiness
 Tingling or numbness in the hands or feet

Whether Type 1 or 2, diabetics need a balance of diet and exercise.

Here are some foods you can eat, and some foods you must avoid!

Foods you must avoid!

i. Salt

Salt is the greatest culprit for diabetics. You get enough salt from
vegetables in inorganic form, so reduce the intake of inorganic salt.

ii. Sugar

Sucrose, a table sugar, provides nothing but calories and carbohydrates.

Also, you need calcium to digest sucrose. Insufficient sucrose intake might lead to calcium
being leached off the bones.

Substitute sucrose with natural sugar, like honey, jaggery (gur), etc.

iii. Fat

Excessive fat intake is definitely not a good habit.

Try and exclude fried items from your diet totally.

But, remember, you must have a small quantity of oil to absorb fat-soluble vitamins, especially
vitamin E.

iv. For non-vegetarians

Try and stop the intake of red meat completely.

Try to go in for a vegetarian diet. If you cannot, decrease the

consumption of eggs and poultry.

You can, however, eat lean fish two to three times a week.

v. Whole milk and products

Try to switch to low fat milk and its products like yogurt (curd).

Replace high fat cheese with low fat cottage cheese.

vi. Tea and coffee

Do not have than two cups of the conventional tea or decaffeinated

coffee every day.

Try to switch to herbal teas.

vii. White flour and its products

Replace these with whole grains, wholewheat or soya breads and unpolished rice.

viii. Foods with a high glycemic index

Avoid white rice, potatoes, carrots, breads and banana -- they increase the blood-sugar levels.  

Special food for diabetics

i. Bitter gourd (karela)

This vegetable contains a high dosage of 'plant insulin'. It lowers the blood-sugar
levels effectively.

Have the juice of three to four karelas early morning on an empty stomach.

As a vegetable, too, it can be taken on a regular basis.

Powder the seeds of karela (measuring 1 teaspoon), mix with water and drink it.

ii. Fenugreek (methi)

It is the most common food used to control diabetes.

Gulp a teaspoonful of these seeds with a glass of water daily.

Soak the seeds overnight. Have the water in which the seeds were soaked.

You can make a chutney with methi seeds. You can also eat them sprouted, dried and
powdered, or mix them in wheat flour to make chapattis.

iii. Indian blackberry (jamun)

This fruit is very effective in preventing and controlling diabetes.

Powder the stone of the fruit and eat it -- it contains glucoside, which prevents the conversion of
starch into sugars.

iv. Garlic

This is used to lower blood-sugar levels.

Garlic is rich in potassium and replaces the potassium which gets

lost in urine.

It also contains zinc and sulphur, which are components of insulin.

Take about three to four flakes of freshly crushed garlic daily.

v. Onion

Because of its diuretic and digestive properties, onion works against

diabetes.

Raw onion is more useful.

vi. Flaxseed

This is the richest source of Omega 3 fatty acids.

It helps control diabetes because it maintains the sensitivity of the cell membrane,

facilitates insulin, and thereby the uptake of glucose by the cells.

vii. Fibre

Soluble fibre, found in apples, kidney beans, oatmeal, soyabean, etc,

help control diabetes.

These aid slow digestion and absorption of nutrients, resulting in a slow

and steady release of glucose.
They soak up excess bile acids found in the intestinal tract, the same acids that are converted to
blood cholesterol.

They also help empty the stomach and trigger satiety that can help Type 2 diabetics to achieve
weight loss goals.

viii. Cinnamon solution

Water extracts of cinnamon have been found to promote glucose metabolism and
reduce cholesterol.

You can boil cinnamon sticks in water and drink this water.

ix. Antioxidants

Diabetes is often associated with conditions like heart disease, diabetic retinopathy, immune
deficiency and kidney disease.

Many are caused by free radical damage. Therefore, make sure you include antioxidants,
especially vitamin C (lemons), E, selenium, zinc and chromium (Brewer's yeast), in your diet, as
they have been shown to control blood sugar levels.

Gestational diabetes
Gestational diabetes (or gestational diabetes mellitus, GDM) is a condition in
which women without previously diagnosed diabetes exhibit high blood glucose
levels during pregnancy (especially during third trimester of pregnancy).

Gestational diabetes generally has few symptoms and it is most commonly

diagnosed by screening during pregnancy. Diagnostic tests detect inappropriately
high levels of glucose in blood samples. Gestational diabetes affects 3-10% of
pregnancies, depending on the population studied.[2]

Babies born to mothers with gestational diabetes are typically at increased risk of
problems such as being large for gestational age (which may lead to delivery
complications), low blood sugar, and jaundice. Gestational diabetes is a treatable
condition and women who have adequate control of glucose levels can effectively
decrease these risks.

Women with gestational diabetes are at increased risk of developing type 2

diabetes mellitus (or, very rarely, latent autoimmune diabetes or Type 1) after
pregnancy, as well as having a higher incidence of pre-eclampsia and Caesarean
section;[3] their offspring are prone to developing childhood obesity, with type 2
diabetes later in life. Most patients are treated only with diet modification and
moderate exercise but some take anti-diabetic drugs, including insulin.[3]

Classification
Gestational diabetes is formally defined as "any degree of glucose intolerance with
onset or first recognition during pregnancy". [4] This definition acknowledges the
possibility that patients may have previously undiagnosed diabetes mellitus, or
may have developed diabetes coincidentally with pregnancy. Whether symptoms
subside after pregnancy is also irrelevant to the diagnosis.[5]

The White classification, named after Priscilla White[6] who pioneered in research
on the effect of diabetes types on perinatal outcome, is widely used to assess
maternal and fetal risk. It distinguishes between gestational diabetes (type A) and
diabetes that existed prior to pregnancy (pregestational diabetes). These two groups
are further subdivided according to their associated risks and management.[7]

There are 2 subtypes of gestational diabetes (diabetes which began during

pregnancy):

 Type A1: abnormal oral glucose tolerance test (OGTT) but normal blood
glucose levels during fasting and 2 hours after meals; diet modification is
sufficient to control glucose levels
 Type A2: abnormal OGTT compounded by abnormal glucose levels during
fasting and/or after meals; additional therapy with insulin or other
medications is required

The second group of diabetes which existed prior to pregnancy is also split up into
several subtypes.

Risk Factors
Classical risk factors for developing gestational diabetes are the following:[8]

 a previous diagnosis of gestational diabetes or prediabetes, impaired glucose

tolerance, or impaired fasting glycaemia
 a family history revealing a first degree relative with type 2 diabetes
 maternal age - a woman's risk factor increases as she gets older (especially
for women over 35 years of age)
  ethnic background (those with higher risk factors include African-
Americans, Afro-Caribbeans, Native Americans, Hispanics, Pacific
Islanders, and people originating from South Asia)
 being overweight, obese or severely obese increases the risk by a factor 2.1,
3.6 and 8.6, respectively.[9]
 a previous pregnancy which resulted in a child with a high birth weight
(>90th centile, or >4000 g (8 lbs 12.8 oz))
 previous poor obstetric history

In addition to this, statistics show a double risk of GDM in smokers.[10] Polycystic

ovarian syndrome is also a risk factor,[8] although relevant evidence remains
controversial.[11] Some studies have looked at more controversial potential risk
factors, such as short stature.[12]

About 40-60% of women with GDM have no demonstrable risk factor; for this
reason many advocate to screen all women. [13] Typically women with gestational
diabetes exhibit no symptoms (another reason for universal screening), but some
women may demonstrate increased thirst, increased urination, fatigue, nausea and
vomiting, bladder infection, yeast infections and blurred vision.

Pathophysiology

Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor
(1) on the cell membrane which in turn starts many protein activation cascades (2).
These include: translocation of Glut-4 transporter to the plasma membrane and
influx of glucose (3), glycogen synthesis (4), glycolysis (5) and fatty acid synthesis
(6).

The precise mechanisms underlying gestational diabetes remain unknown. The

hallmark of GDM is increased insulin resistance. Pregnancy hormones and other
factors are thought to interfere with the action of insulin as it binds to the insulin
receptor. The interference probably occurs at the level of the cell signaling
pathway behind the insulin receptor.[14] Since insulin promotes the entry of glucose
into most cells, insulin resistance prevents glucose from entering the cells properly.
As a result, glucose remains in the bloodstream, where glucose levels rise. More
insulin is needed to overcome this resistance; about 1.5-2.5 times more insulin is
produced than in a normal pregnancy.[14]

Insulin resistance is a normal phenomenon emerging in the second trimester of

pregnancy, which progresses thereafter to levels seen in non-pregnant patients with
type 2 diabetes. It is thought to secure glucose supply to the growing fetus. Women
with GDM have an insulin resistance they cannot compensate with increased
production in the β-cells of the pancreas. Placental hormones, and to a lesser extent
increased fat deposits during pregnancy, seem to mediate insulin resistance during
pregnancy. Cortisol and progesterone are the main culprits, but human placental
lactogen, prolactin and estradiol contribute too.[14]

It is unclear why some patients are unable to balance insulin needs and develop
GDM, however a number of explanations have been given, similar to those in type
2 diabetes: autoimmunity, single gene mutations, obesity, and other mechanisms.
[15]

Because glucose travels across the placenta (through diffusion facilitated by

GLUT3 carriers), the fetus is exposed to higher glucose levels. This leads to
increased fetal levels of insulin (insulin itself cannot cross the placenta). The
growth-stimulating effects of insulin can lead to excessive growth and a large body
(macrosomia). After birth, the high glucose environment disappears, leaving these
newborns with ongoing high insulin production and susceptibility to low blood
glucose levels (hypoglycemia).[16]

Screening
2006 WHO Diabetes criteria[17]  edit
Condition 2 hour glucose Fasting glucose
mmol/l(mg/dl) mmol/l(mg/dl)
Normal <7.8 (<140) <6.1 (<110)
Impaired fasting glycaemia <7.8 (<140) ≥ 6.1(≥110) & <7.0(<126)
Impaired glucose tolerance ≥7.8 (≥140) <7.0 (<126)
Diabetes mellitus ≥11.1 (≥200) ≥7.0 (≥126)

A number of screening and diagnostic tests have been used to look for high levels
of glucose in plasma or serum in defined circumstances. One method is a stepwise
approach where a suspicious result on a screening test is followed by diagnostic
test. Alternatively, a more involved diagnostic test can be used directly at the first
antenatal visit in high-risk patients (for example in those with polycystic ovarian
syndrome or acanthosis nigricans).[16]

Tests for gestational diabetes

Non-challenge blood glucose tests

 Fasting glucose test

 2-hour postprandial (after a meal) glucose test
 Random glucose test

Screening glucose challenge test

Oral glucose tolerance test (OGTT)

Non-challenge blood glucose tests involve measuring glucose levels in blood

samples without challenging the subject with glucose solutions. A blood glucose
level is determined when fasting, 2 hours after a meal, or simply at any random
time. In contrast, challenge tests involve drinking a glucose solution and measuring
glucose concentration thereafter in the blood; in diabetes, they tend to remain high.
The glucose solution has a very sweet taste which some women find unpleasant;
sometimes, therefore, artificial flavours are added. Some women may experience
nausea during the test, and more so with higher glucose levels.[18][19]

Pathways

There are different opinions about optimal screening and diagnostic measures, in
part due to differences in population risks, cost-effectiveness considerations, and
lack of an evidence base to support large national screening programs. [20] The most
elaborate regime entails a random blood glucose test during a booking visit, a
screening glucose challenge test around 24–28 weeks' gestation, followed by an
OGTT if the tests are outside normal limits. If there is a high suspicion, women
may be tested earlier.[5]

In the United States, most obstetricians prefer universal screening with a screening
glucose challenge test.[21] In the United Kingdom, obstetric units often rely on risk
factors and a random blood glucose test.[16][22] The American Diabetes Association
and the Society of Obstetricians and Gynaecologists of Canada recommend routine
screening unless the patient is low risk (this means the woman must be younger
than 25 years and have a body mass index less than 27, with no personal, ethnic or
family risk factors)[5][20] The Canadian Diabetes Association and the American
College of Obstetricians and Gynecologists recommend universal screening.[23][24]
The U.S. Preventive Services Task Force found that there is insufficient evidence
to recommend for or against routine screening.[25]

Non-challenge blood glucose tests

When a plasma glucose level is found to be higher than 126 mg/dl (7.0 mmol/l)

after fasting, or over 200 mg/dl (11.1 mmol/l) on any occasion, and if this is
confirmed on a subsequent day, the diagnosis of GDM is made, and no further
testing is required.[5] These tests are typically performed at the first antenatal visit.
They are patient-friendly and inexpensive, but have a lower test performance
compared to the other tests, with moderate sensitivity, low specificity and high
false positive rates.[26][27][28]

Screening glucose challenge test

The screening glucose challenge test (sometimes called the O'Sullivan test) is
performed between 24–28 weeks, and can be seen as a simplified version of the
oral glucose tolerance test (OGTT). It involves drinking a solution containing
50 grams of glucose, and measuring blood levels 1 hour later.[29]

If the cut-off point is set at 140 mg/dl (7.8 mmol/l), 80% of women with GDM will
be detected.[5] If this threshold for further testing is lowered to 130 mg/dl, 90% of
GDM cases will be detected, but there will also be more women who will be
subjected to a consequent OGTT unnecessarily.

Oral glucose tolerance test

The OGTT[30] should be done in the morning after an overnight fast of between 8
and 14 hours. During the three previous days the subject must have an unrestricted
diet (containing at least 150 g carbohydrate per day) and unlimited physical
activity. The subject should remain seated during the test and should not smoke
throughout the test.

The test involves drinking a solution containing a certain amount of glucose, and
drawing blood to measure glucose levels at the start and on set time intervals
thereafter.
The diagnostic criteria from the National Diabetes Data Group (NDDG) have been
used most often, but some centers rely on the Carpenter and Coustan criteria,
which set the cutoff for normal at lower values. Compared with the NDDG criteria,
the Carpenter and Coustan criteria lead to a diagnosis of gestational diabetes in 54
percent more pregnant women, with an increased cost and no compelling evidence
of improved perinatal outcomes.[31]

The following are the values which the American Diabetes Association considers
to be abnormal during the 100 g of glucose OGTT:

 Fasting blood glucose level ≥95 mg/dl (5.33 mmol/L)

 1 hour blood glucose level ≥180 mg/dl (10 mmol/L)
 2 hour blood glucose level ≥155 mg/dl (8.6 mmol/L)
 3 hour blood glucose level ≥140 mg/dl (7.8 mmol/L)

An alternative test uses a 75 g glucose load and measures the blood glucose levels
before and after 1 and 2 hours, using the same reference values. This test will
identify less women who are at risk, and there is only a weak concordance
(agreement rate) between this test and a 3 hour 100 g test.[32]

The glucose values used to detect gestational diabetes were first determined by
O'Sullivan and Mahan (1964) in a retrospective cohort study (using a 100 grams of
glucose OGTT) designed to detect risk of developing type 2 diabetes in the future.
The values were set using whole blood and required two values reaching or
exceeding the value to be positive.[33] Subsequent information led to alterations in
O'Sullivan's criteria. When methods for blood glucose determination changed from
the use of whole blood to venous plasma samples, the criteria for GDM were also
changed.

Urinary glucose testing

Women with GDM may have high glucose levels in their urine (glucosuria).
Although dipstick testing is widely practiced, it performs poorly, and discontinuing
routine dipstick testing has not been shown to cause underdiagnosis where
universal screening is performed.[34] Increased glomerular filtration rates during
pregnancy contribute to some 50% of women having glucose in their urine on
dipstick tests at some point during their pregnancy. The sensitivity of glucosuria
for GDM in the first 2 trimesters is only around 10% and the positive predictive
value is around 20%.[35][36]
Management

A kit with a glucose meter and diary used by a woman with gestational diabetes.

The goal of treatment is to reduce the risks of GDM for mother and child.
Scientific evidence is beginning to show that controlling glucose levels can result
in less serious fetal complications (such as macrosomia) and increased maternal
quality of life. Unfortunately, treatment of GDM is also accompanied by more
infants admitted to neonatal wards and more inductions of labour, with no proven
decrease in cesarean section rates or perinatal mortality.[37][38] These findings are
still recent and controversial.[39]

A repeat OGTT should be carried out 2–4 months after delivery, to confirm the
diabetes has disappeared. Afterwards, regular screening for type 2 diabetes is
advised.[8]

If a diabetic diet or G.I. Diet, exercise, and oral medication are inadequate to
control glucose levels, insulin therapy may become necessary.

The development of macrosomia can be evaluated during pregnancy by using

sonography. Women who use insulin, with a history of stillbirth, or with
hypertension are managed like women with overt diabetes.[13]

Lifestyle

Counselling before pregnancy (for example, about preventive folic acid

supplements) and multidisciplinary management are important for good pregnancy
outcomes.[40] Most women can manage their GDM with dietary changes and
exercise. Self monitoring of blood glucose levels can guide therapy. Some women
will need antidiabetic drugs, most commonly insulin therapy.
Any diet needs to provide sufficient calories for pregnancy, typically 2,000 - 2,500
kcal with the exclusion of simple carbohydrates.[13] The main goal of dietary
modifications is to avoid peaks in blood sugar levels. This can be done by
spreading carbohydrate intake over meals and snacks throughout the day, and
using slow-release carbohydrate sources—known as the G.I. Diet. Since insulin
resistance is highest in mornings, breakfast carbohydrates need to be restricted
more.[8]

Regular moderately intense physical exercise is advised, although there is no

consensus on the specific structure of exercise programs for GDM.[8][41]

Self monitoring can be accomplished using a handheld capillary glucose dosage

system. Compliance with these glucometer systems can be low. [42] Target ranges
advised by the Australasian Diabetes in Pregnancy Society are as follows:[8]

 fasting capillary blood glucose levels <5.5 mmol/L

 1 hour postprandial capillary blood glucose levels <8.0 mmol/L
 2 hour postprandial blood glucose levels <6.7 mmol/L

Regular blood samples can be used to determine HbA1c levels, which give an idea
of glucose control over a longer time period.[8]

Research suggests a possible benefit of breastfeeding to reduce the risk of diabetes

and related risks for both mother and child.[43]

Medication

If monitoring reveals failing control of glucose levels with these measures, or if

there is evidence of complications like excessive fetal growth, treatment with
insulin might become necessary. The most common therapeutic regime involves
premeal fast-acting insulin to blunt sharp glucose rises after meals. [8] Care needs to
be taken to avoid low blood sugar levels (hypoglycemia) due to excessive insulin
injections. Insulin therapy can be normal or very tight; more injections can result in
better control but requires more effort, and there is no consensus that it has large
benefits.[16][44][45]

There is some evidence that certain oral glycemic agents might be safe in
pregnancy, or at least, are significantly less dangerous to the developing fetus than
poorly controlled diabetes. Glyburide, a second generation sulfonylurea, has been
shown to be an effective alternative to insulin therapy. [46][47] In one study, 4% of
women needed supplemental insulin to reach blood sugar targets. [47] Metformin has
shown promising results, with its oral format being much more popular than
insulin injections.[3] Treatment of polycystic ovarian syndrome with metformin
during pregnancy has been noted to decrease GDM levels. [48] A recent randomized
controlled trial of metformin versus insulin showed that women preferred
metformin tablets to insulin injections, and that metformin is safe and equally
effective as insulin.[49] Severe neonatal hypoglycemia was less common in insulin-
treated women, but preterm delivery was more common. Almost half of patients
did not reach sufficient control with metformin alone and needed supplemental
therapy with insulin; compared to those treated with insulin alone, they required
less insulin, and they gained less weight.[49] With no long-term studies into children
of women treated with the drug, here remains a possibility of long-term
complications from metformin therapy,[3] although follow-up at the age of 18
months of children born to women with polycystic ovarian syndrome and treated
with metformin revealed no developmental abnormalities.[50]

Prognosis
Gestational diabetes generally resolves once the baby is born. Based on different
studies, the chances of developing GDM in a second pregnancy are between 30
and 84%, depending on ethnic background. A second pregnancy within 1 year of
the previous pregnancy has a high rate of recurrence.[51]

Women diagnosed with gestational diabetes have an increased risk of developing

diabetes mellitus in the future. The risk is highest in women who needed insulin
treatment, had antibodies associated with diabetes (such as antibodies against
glutamate decarboxylase, islet cell antibodies and/or insulinoma antigen-2),
women with more than two previous pregnancies, and women who were obese (in
order of importance).[52][53] Women requiring insulin to manage gestational diabetes
have a 50% risk of developing diabetes within the next five years. [33] Depending on
the population studied, the diagnostic criteria and the length of follow-up, the risk
can vary enormously.[54] The risk appears to be highest in the first 5 years, reaching
a plateau thereafter.[54] One of the longest studies followed a group of women from
Boston, Massachusetts; half of them developed diabetes after 6 years, and more
than 70% had diabetes after 28 years.[54] In a retrospective study in Navajo women,
the risk of diabetes after GDM was estimated to be 50 to 70% after 11 years. [55]
Another study found a risk of diabetes after GDM of more than 25% after 15 years.
[56]
In populations with a low risk for type 2 diabetes, in lean subjects and in
patients with auto-antibodies, there is a higher rate of women developing type 1
diabetes.[53]
Children of women with GDM have an increased risk for childhood and adult
obesity and an increased risk of glucose intolerance and type 2 diabetes later in
life.[57] This risk relates to increased maternal glucose values. [58] It is currently
unclear how much genetic susceptibility and environmental factors each contribute
to this risk, and if treatment of GDM can influence this outcome.[59]

There are scarce statistical data on the risk of other conditions in women with
GDM; in the Jerusalem Perinatal study, 410 out of 37962 patients were reported to
have GDM, and there was a tendency towards more breast and pancreatic cancer,
but more research is needed to confirm this finding.[60][61]

Complications

GDM poses a risk to mother and child. This risk is largely related to high blood
glucose levels and its consequences. The risk increases with higher blood glucose
levels.[62] Treatment resulting in better control of these levels can reduce some of
the risks of GDM considerably.[42]

The two main risks GDM imposes on the baby are growth abnormalities and
chemical imbalances after birth, which may require admission to a neonatal
intensive care unit. Infants born to mothers with GDM are at risk of being both
large for gestational age (macrosomic)[62] and small for gestational age.
Macrosomia in turn increases the risk of instrumental deliveries (e.g. forceps,
ventouse and caesarean section) or problems during vaginal delivery (such as
shoulder dystocia). Macrosomia may affect 12% of normal women compared to
20% of patients with GDM.[16] However, the evidence for each of these
complications is not equally strong; in the Hyperglycemia and Adverse Pregnancy
Outcome (HAPO) study for example, there was an increased risk for babies to be
large but not small for gestational age.[62] Research into complications for GDM is
difficult because of the many confounding factors (such as obesity). Labelling a
woman as having GDM may in itself increase the risk of having a caesarean
section.[63][64]

Neonates are also at an increased risk of low blood glucose (hypoglycemia),

jaundice, high red blood cell mass (polycythemia) and low blood calcium
(hypocalcemia) and magnesium (hypomagnesemia).[65] GDM also interferes with
maturation, causing dysmature babies prone to respiratory distress syndrome due to
incomplete lung maturation and impaired surfactant synthesis.[65]

Unlike pre-gestational diabetes, gestational diabetes has not been clearly shown to
be an independent risk factor for birth defects. Birth defects usually originate
sometime during the first trimester (before the 13th week) of pregnancy, whereas
GDM gradually develops and is least pronounced during the first trimester. Studies
have shown that the offspring of women with GDM are at a higher risk for
congenital malformations.[66][67][68] A large case-control study found that gestational
diabetes was linked with a limited group of birth defects, and that this association
was generally limited to women with a higher body mass index (≥ 25 kg/m²).[69] It
is difficult to make sure that this is not partially due to the inclusion of women with
pre-existent type 2 diabetes who were not diagnosed before pregnancy.

Because of conflicting studies, it is unclear at the moment whether women with

GDM have a higher risk of preeclampsia.[70] In the HAPO study, the risk of
preeclampsia was between 13% and 37% higher, although not all possible
confounding factors were corrected.[62]

Goitre
A goiter or goitre (Latin gutteria, struma), is a swelling in the thyroid gland,[1]
which can lead to a swelling of the neck or larynx (voice box). Goitre rarely occurs
when the thyroid gland is functioning properly.

Worldwide, over 90% cases of goitre are caused by iodine deficiency. [2]

Classification

Struma nodosa (Grad II)

Struma with autonomous adenome

Struma Grad III

They can be classified in several ways by morphology, appearance, cause and

other characteristics.

 Non-Toxic:
o Simple (struma diffuse)
o Multinodular (struma nodosa)
o Uninodular (struma uninodosa)
 Toxic:
o Diffuse (Graves)
o Toxic multinodular
 o Toxic nodule
 Special:
o Cancer
o Thyroiditides
o Inflammatory
 Various causes:
o Chronic infection
o Actinomycosis
o Amyloidosis

Other type of classification:

 Class I - palpation struma - in normal posture of the head, it cannot be seen;

it is only found by palpation.
 Class II - the struma is palpative and can be easily seen.
 Class III - the struma is very large and is retrosternal; pressure results in
compression marks.

Signs and symptoms

Goiter associated with hypothyroidism or hyperthyroidism may present with
symptoms of the underlying disorder although the symptoms are often unspecific
and hard to diagnose.

Goiter not associated with hormonal abnormalities will not cause any symptoms
aside from the presence of anterior neck mass. However, for particularly large
masses, compression of the local structures may result in difficulty in breathing or
swallowing. In those presenting with these symptoms, malignancy must be
considered.

Toxic goiters will present with symptoms of thyrotoxicosis such as palpitations,

hyperactivity, weight loss despite increased appetite, and heat intolerance.

Causes
Worldwide, the most common cause for goiter is iodine deficiency. Selenium
deficiency is also considered a contributing factor. In countries that use iodized
salt, Hashimoto's thyroiditis is the most common cause.[3]

Further causes include

  thyroid autonomy
 autoimmune conditions of the thyroid (Hashimoto thyroiditis, Morbus
Basedow)
 medications and substances such as lithium, antithyroid agents, thyocyanate
 inflammations (thyroiditis)
 cysts
 benign and malignant neoplasms
 pituitary problems
 acromegaly
 thyroid hormone insenstitvity
 sarcoidosis, amyloidosis
 hydatiform mole

Hypothyroid

 Inborn errors of thyroid hormone synthesis, causing congenital

hypothyroidism (E03.0)
 Ingestion of goitrogens, such as cassava.
 Side-effects of pharmacological therapy (E03.2)

Hyperthyroid

 Graves' disease (E05.0)

 Thyroiditis (acute or chronic) (E06)
 Thyroid cancer

Treatment
Goiter caused by suspected iodine deficiency is very frequently treated by a
combination of levothyroxine and iodine supplementation depending on thyroid
hormone levels.

Treatment may not be necessary if the goiter is small. Goiter may be related to
hyper- and hypothyroidism (especially Graves' disease) and may be reversed by
treatment. Graves' disease can be corrected with antithyroid drugs (such as
propylthiouracil and methimazole), thyroidectomy (surgical removal of the thyroid
gland), and iodine-131 (131I - a radioactive isotope of iodine that is absorbed by the
thyroid gland and destroys it). Hypothyroidism may raise the risk of goiter because
it usually increases the production of TRH and TSH. Levothyroxine, used to treat
hypothyroidism, can also be used in euthyroid patients for the treatment of goitre.
Levothyroxine suppressive therapy decreases the production of TRH and TSH and
may reduce goiter, thyroid nodules, and thyroid cancer. Blood tests are needed to
ensure that TSH is still in range and the patient has not become subclinically
hyperthyroid. If TSH levels are not carefully monitored and allowed to remain far
below the lower limits of normal (below 0.1 mIU/L or IU/mL), there is
epidemiologic evidence that levothyroxine may increase the risk of osteoporosis
and both hip and spinal fractures.[4] (Such low levels are therefore not intentionally
produced for long periods, except occasionally in the treatment of TSH-dependent
thyroid cancers.)

Thyroidectomy with 131I may be necessary in euthyroid goitrous patients who do

not respond to levothyroxine treatment, especially if the patients have difficulty
breathing or swallowing.[dubious – discuss] 131I, with or without the pre-injection of
synthetic TSH, can relieve obstruction and reduce the size of the goitre by thirty to
sixty-five percent.[citation needed] Depending on how large the goitre is and how much
of the thyroid gland must be removed or destroyed, thyroidectomy and/or 131I
treatment may destroy enough thyroid tissue as to produce hypothyroidism,
requiring life-long treatment with thyroid hormone pills

Iodine is necessary for the synthesis of the thyroid hormones thyroxine (T4) and
triiodothyronine (T3). In endemic goitre, iodine deficiency leaves the thyroid gland
unable to produce its hormones because the mature hormone molecules require
iodine atoms to be attached. When levels of thyroid hormones fall, thyrotropin-
releasing hormone (TRH) is produced by the hypothalamus. TRH then prompts the
pituitary gland to make thyrotropin or thyroid stimulating hormone (TSH), which
stimulates the thyroid gland’s production of T 4 and T3. It also causes the thyroid
gland to grow in size by increasing cell division.

Goitre is more common among women, but this includes the many types of goitre
caused by autoimmune problems, and not only those caused by simple lack of
iodine.

Some researchers [6] showed a correlation between Iodine-deficient goitre and

gastric cancer, and reported in goitrous territories a decrease of the incidence of
goitre and of stomach cancer after implementation of iodine-prophylaxis. [7] The
proposed mechanism of action is that iodide ion (I-) can function in thyroid gland
and in gastric mucosa as an antioxidant [8] reducing species that can detoxify
poisonous reactive oxygen species, such as hydrogen peroxide.