1.

Compare and contrast the pathophysiology and clinical

presentation of Type 1 and Type 2 Diabetes Mellitus
DMT1: cause not fully understood. virally triggered autoimmune
response to an infection by one of the viruses of the Coxsackie virus
family or German measles. pancreatic beta cells in the Islets of
Langerhans are destroyed or damaged sufficiently to effectively
abolish endogenous insulin production. typically characterized by
severe insulin deficiency, sudden onset of symptoms at a young age,
risk for diabetic ketoacidosis (DKA). Diabetic ketoacidosis may also be
the initial manifestation of type 1 diabetes. It usually occurs in young
patients, but a late-onset form may occur in adults. These patients
require insulin therapy for survival.
DMT2 (formerly adult-onset diabetes): MC type and accounts for over
90% of all cases of diabetes. Both genetic and environmental factors
(e.g., obesity) contribute to its development. insulin resistance, relative
insulin deficiency, and a more gradual onset of hyperglycemia.
Peripheral tissues, such as muscle, fat, and liver, are abnormally resistant
to the effects of insulin, resulting in decreased glucose uptake and
inappropriate hepatic gluconeogenesis. often is detected by screening
examinations. Insulin secretion is usually sufficient to prevent
ketoacidosis, but DKA may occur during severe illness or stress.
Peripheral neuropathy is often present when DMT2 is diagnosed and
may be the presenting feature. Less commonly, type 2 diabetes presents
with vascular complications, such as myocardial infarction, peripheral
vascular disease, or chronic kidney disease. These patients may require
insulin to control blood glucose levels.
2. Discuss the epidemiology and risk factors for Diabetes Mellitus
Type 2
incidence is increasing rapidly. occurs throughout the world, but is more
common (especially type 2) in the more developed countries.
Environmental (i.e., dietary) effect, but there is little understanding
of the mechanism(s) at present. Other 57 million people are estimated to
have pre-diabetes. CDC has termed the change an epidemic. The
National Diabetes Information Clearinghouse estimates that diabetes costs
$132 billion in the United States alone every year. About 5%10% of
diabetes cases in North America are type 1, with the rest being
type 2. The American Diabetes Association cite the 2003 assessment of
the National Center for Chronic Disease Prevention and Health Promotion
(Centers for Disease Control and Prevention) that 1 in 3 Americans born
after 2000 will develop diabetes in their lifetime. ~18.3% (8.6
million) of Americans age 60 and older have diabetes. DM
prevalence increases with age, and the numbers of older persons
with diabetes are expected to grow as the elderly population
increases in number.
About 90 to 95 percent of people with diabetes have type 2. This
form of diabetes is most often associated with older age, obesity,
family history of diabetes, previous history of gestational diabetes,
physical inactivity, and certain ethnicities. About 80 percent of

people with type 2 diabetes are overweight. increasingly being

diagnosed in children and adolescents, especially among African
American, Mexican American, and Pacific Islander youth.
OBESITY At all ages, the risk of impaired glucose tolerance (IGT) or
type 2 diabetes rises with increasing body weight. Obesity acts at
least in part by inducing resistance to insulin-mediated peripheral
glucose uptake, which is an important component of type 2 diabetes.
Reversal of obesity also decreases the risk of type 2 diabetes and, in patients
with established disease, improved glycemic control. Fat distribution In
addition to the degree of obesity, the distribution of excess adipose
tissue is another important determinant of the risk of insulin resistance and
type 2 diabetes. The degree of insulin resistance and the incidence of
type 2 diabetes are highest in those subjects with upper body or
abdominal obesity, as manifested by a waist-to-hip circumference
ratio that is >0.95 in men and >0.85 in women. Subcutaneous truncal
fat rather than intraperitoneal or retroperitoneal fat appears to be of primary
importance in this regard. This 'male' type obesity is different from the
typical 'female' type, which primarily affects the gluteal and femoral regions
and is not as likely to be associated with glucose intolerance or
cardiovascular disease. Why the pattern of fat distribution is important and
the relative roles of genetic and environmental factors in its development are
not known.
LIFESTYLE FACTORS: Exercise Physical activity of moderate intensity
reduces the incidence of new cases of type 2 diabetes, regardless of the
presence or absence of impaired glucose tolerance.
Smoking Several large prospective studies have raised the possibility that
cigarette smoking increases the risk of type 2 diabetes. Estimates
from the Physicians' Health Study suggest that in the United States, where
approximately 25 percent of people smoke, about 10 percent of the
incidence of type 2 diabetes may be attributable to smoking.
Smoking increases the blood glucose concentration after an oral
glucose challenge, may impair insulin sensitivity, linked to increased
abdominal fat distribution and greater waist-to-hip ratio.
DIETARY PATTERNS: Western versus prudent diet In a study of over
42,000 male health professionals, a western diet (characterized by high
consumption of red meat, processed meat, high fat dairy products,
sweets, and desserts) was associated with an increased risk of diabetes
independent of BMI, physical activity, age, or family history. The risk
was markedly increased among subjects who ate a western diet and
were obese (BMI 30 kg/m2 versus <25 kg m2). In contrast, men who ate a
prudent diet (characterized by higher consumption of vegetables, fruit,
fish, poultry, and whole grains) had a modest reduction in risk.
Mediterranean diet fruits, vegetables, nuts, whole grains, and
olive oil
Sugar-sweetened beverages soft drinks, have been associated
with obesity in children. It is unclear whether the described
association is due to increased caloric intake and weight gain, other
lifestyle factors (smoking, exercise, other food choices), or to

excess consumption of refined carbohydrates, such as high-fructose

corn syrup (used to sweeten beverages).
ENVIRONMENTAL EXPOSURES Chronic exposure to inorganic arsenic
in drinking water, BPA monomer used to make hard, polycarbonate
plastics, chronic exposure to organophosphate and chlorinated
pesticides
GESTATIONAL DIABETES risk for type 2 diabetes is higher in
women, defects in both insulin secretion and insulin action, the
severity of which correlate with the future risk of diabetes.
3. Describe the genetic basis for development of Diabetes both
Type 1 and Type 2.
Both type 1 and type 2 diabetes are at least partly inherited. Type 1
diabetes appears to be triggered by some (mainly viral) infections, or
less commonly, by stress or environmental exposure (such as exposure
to certain chemicals or drugs). There is a genetic element in individual
susceptibility to some of these triggers which has been traced to particular
HLA genotypes (i.e., the genetic "self" identifiers relied upon by the
immune system). However, even in those who have inherited the
susceptibility, type 1 diabetes mellitus seems to require an
environmental trigger. There is also maturity onset diabetes of the
young (MODY) which is a group of several single gene (monogenic)
disorders with strong heritability patterns which present as type 2
diabetes early in life, usually before 30 years, and sometimes in
childhood. In some cases diabetes can be brought out by some viruses like
the chicken pox.
There is a stronger inheritance pattern for type 2 diabetes. Those with
first-degree relatives with type 2 have a much higher risk of developing
type 2, 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.
KCNJ11 (potassium inwardly rectifying channel, subfamily J, member 11),
encodes the islet ATP-sensitive potassium channel Kir6.2, and TCF7L2
(transcription factor 7like 2) regulates proglucagon gene expression and
thus the production of glucagon-like peptide-1.[2] Moreover, obesity (which is
an independent risk factor for type 2 diabetes) is strongly inherited.
Monogenic forms, e.g., MODY, constitute 1-5 % of all cases.
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.
4. Diagnostic criteria for DM
8(99mg/dl is a normal plasma glucose, hypoglycemia would be lower then
50)
Random glucose >200 mg/dL with symptoms of hyperglycemia

Fasting venous plasma glucose >126 mg/dL on two or more

occasions
Oral glucose (75 g) tolerance test showing a 2-hour glucose level of
>200 mg/dL
-reserved for individuals with potential symptoms of diabetes or its complications as well as
fasting plasma glucose below 126 mg/dL.
5. Define metabolic Syndrome
cluster of the most dangerous heart attack risk factors: diabetes and
prediabetes, abdominal obesity, changes in cholesterol and high blood pressure.
For a person to be defined as having the metabolic syndrome, the new definition requires
they have central obesity ( 40 inches for men and 35 for women measured just
below the umbilicus), plus two of the following four additional factors: raised
triglycerides (TG)(>150 mg), reduced HDL (<40 in men and <50 in women),
raised BP (>135/80) or raised fasting plasma glucose level (>100mg/dl) =
increased risk of CVD, being twice as likely to die from, and three times as likely
to have a heart attack or stroke. 5-fold greater risk of developing type 2
diabetes (if not already present), a condition which is strongly associated with CVD.
6. List the complications of diabetes, including description of the two types of
diabetic retinopathy. CAD, stroke, peripheral vascular disease, DKA,
diabetic retinopathy, nephropathy, neuropathy, hypoglycemia, diabetic
venous stasis ulcers, cataracts and glaucoma, but the diseases affect on the
retina is the main threat to vision (~20yrs later). The earliest phase of the
disease is known as background diabetic retinopathy arteries in the retina
become weakened and leak, forming small, dot-like hemorrhages
swelling or edema in the retina and decreased vision.
The next stage is known as proliferative diabetic retinopathy circulation problems
cause areas of the retina to become oxygen-deprived or ischemic
neovascularization that hemorrhage easily. Blood may leak into the retina and
vitreous, causing spots or floaters, along with decreased vision. In the later phases of
the disease, continued abnormal vessel growth and scar tissue may cause serious
problems such as retinal detachment and glaucoma.
7. Signs and Symptoms of Diabetic Retinopathy using fundoscopic exam

Blurred vision (this is often linked to blood sugar levels)

Floaters and flashes
Sudden loss of vision
irreversible diabetic maculopathy. Diabetes causes leakage in small blood
vessels located around the macula, which is the center of the retina where
our vision is the sharpest. This leakage leads to focal edema and causes
damage to the retina. Over time, the leakage worsens as more vessels are
affected. Vision slowly deteriorates so that activities that require central
vision such as reading or watching TV become difficult or impossible to do.
The best treatment is laser eye surgery to seal the leaks, which usually needs to
be done several different times to be successful.

8. Describe the timeline for the development of the complications for Type 1
and Type 2 diabetes.

Macrovascular Disease:
CAD and Stroke: MI and stroke occur more frequently, at an earlier age, and with greater
severity in diabetic men and women than in nondiabetic persons. Even patients with
impaired glucose tolerance are at a greater risk for the development of atherosclerosis.
Coronary artery disease is the leading cause of mortality in people with diabetes. Because
of autonomic neuropathy, myocardial ischemia or frank infarction in diabetes may be
asymptomatic; it may present as diabetic ketoacidosis or be diagnosed incidentally by a
routine electrocardiogram. Therefore, tobacco cessation is strongly recommended and
dyslipidemia is treated aggressively. Lipid screening should occur at least annually and
more often if needed to reach goals. Aspirin should be recommended for those with
documented cardiovascular disease and considered for those diabetics over the age of 40
years who have risk factors.
Peripheral Vascular Disease: Involvement of large or medium-sized blood vessels in the
lower limbs is a common complication of diabetes. A diagnosis of arterial insufficiency is
suggested by a history of claudication. Physical examination reveals absent or weak
peripheral pulses. Noninvasive vascular testing is used to confirm the diagnosis. Patients
with peripheral vascular disease often cannot supply the increased blood flow needed to
heal foot infections, such as cellulitis and ulcerations. The inability to heal these infections
leads to osteomyelitis, gangrene, and amputations.
Microvascular Disease:
Diabetic Retinopathy: leading cause of blindness in the United States. However, with
yearly ophthalmologic examinations and preventive eye care, significant vision loss is
prevented in all but a small fraction of patients. Type 2 diabetic patients should have an
annual examination beginning after diagnosis, while type 1 diabetics should have their
initial annual exam within 3 to 5 years after onset of the disease. Less frequent
examinations (every 2 to 3 years) may be considered in those diabetics with normal eye
exams. Diabetic retinopathy has two stages: background retinopathy and proliferative
retinopathy. Background retinopathy may progress to the proliferative stage and cause
vitreous hemorrhage, retinal detachment, and vision loss. In addition to retinopathy,
cataracts and glaucoma are more prevalent in the diabetic population.
Diabetic Nephropathy: often present along with retinopathy, and occurs in
approximately one third of patients. The specific lesion of diabetic nephropathy is nodular
sclerosis (Kimmelstiel-Wilson lesion), visible on light microscopy as a rounded hyaline mass
at the center of the glomerular lobules. More common, but less specific, is diffuse
glomerulosclerosis with thickening of the glomerular basement membrane and an
increased mesangial matrix. Microalbuminuria (20 to 300 mg per 24 hours) heralds future
development of gross proteinuria and should be checked annually in all type 2 diabetics
starting at diagnosis and all type 1 diabetics who have had diabetes for 5 or more years.
Progressive nephropathy results in heavy proteinuria and the development of nephrotic
syndrome, which typically progresses to renal failure and the need for hemodialysis within
5 years.
Diabetic Neuropathy: affects both the peripheral and the autonomic nervous systems.
Distal, symmetric polyneuropathy is the most common form of diabetic peripheral
neuropathy. It usually occurs in a stocking-glove distribution with numbness, tingling,
burning, and/or pain in the feet and lower legs. Tendon reflexes and response to sensory
stimuli, particularly vibration, are decreased. Patients with peripheral neuropathy are at risk
for long-term complications of infection and amputation, especially if peripheral vascular
disease coexists. All diabetic patients should receive an annual foot examination, including

visual inspection, peripheral pulses, and sensation. The monofilament examination is

currently the best screening test to detect clinically significant neuropathy. Patient
education regarding foot care and daily monitoring for skin breakdown is essential.
Therapy of uncomfortable peripheral neuropathy involves the use of drugs such as
gabapentin, tricyclic antidepressants, and anticonvulsants. Topical agents (e.g., capsaicin)
are effective at times.
Focal peripheral neuropathies include mononeuropathies and entrapment syndromes.
Examples of focal neuropathies are femoral and cranial nerve palsies, especially the third
nerve. Carpal tunnel syndrome is an example of an entrapment syndrome and is more
common in diabetic patients.
Autonomic neuropathies can affect nearly all organs, more notably the skin, the
cardiovascular, gastrointestinal, and genitourinary systems. Diminished sweating
(anhidrosis) of the feet can result in drying, cracking, and ulcer formation. Diabetic patients
with autonomic neuropathy may present with postural hypotension (without compensatory
tachycardia). Gastroparesis presents as early satiety, vomiting after meals, and increasing
frequency of hypoglycemic episodes. Patients may also experience alternating bouts of
diarrhea and constipation (enteropathy). Bacterial overgrowth secondary to stasis may
contribute to diarrhea. Impotence, with preserved libido, is a common manifestation of
diabetic autonomic neuropathy and affects 75% of diabetic men 60 to 65 years old.
Neurogenic bladder may also occur.
Diabetic Ketoacidosis and Nonketotic Hyperosmolar Coma
Diabetic ketoacidosis and nonketotic hyperosmolar coma are potentially fatal complications
of diabetes. The distinction between ketoacidosis and nonketotic diabetic coma is not
absolute; mild ketonemia may be present in patients with a hyperosmolar state. DKA is
more common in type 1 diabetes and occurs in up to 5% of type 1 diabetes patients per
year. However, nonketotic hyperosmolar coma occurs only in type 2 diabetes and is less
common.
Hyperosmolar Hyperglycemic Nonketotic Coma (Hyperosmolar Coma)
Etiology
Hyperosmolar coma is much less common than diabetic ketoacidosis (DKA) and usually
occurs in older patients with type 2 diabetes. Conceptually, these patients usually have
enough insulin to prevent ketosis and acidosis, but not enough to prevent hyperglycemia.
Hypoglycemia
Hypoglycemia, a deficiency of glucose concentration in the blood, can occur in diabetic
(usually iatrogenic) and nondiabetic individuals. Recurrent episodes of hypoglycemia result
in a reduced ability to recognize these symptoms (hypoglycemic unawareness).
9. List guidelines for the follow up and treatment of diabetes.
Fasting Glucose
1st FG mg/dL
2nd FG, mg/dL Diagnosis
>125
>125
DM
Treat
>125
101 to 125
IFG
Treat
>125
<100
Indeterminate
125 treat as IFG;

Treatment
for DM
as IFG
Repeat; if >125 treat as DM; if 101-

<100 consider normal

101 to 125
>125
101 to 125 101 to 125
101 to 125 <100
treat as IFG;
<100 consider normal

IFG

Treat as IFG
IFG
Treat for IFG
Indeterminate
Repeat; if >125 treat as DM; if 101-125

Random Glucose
RG mg/dL FG mg/dL Diagnosis
Treatment
200
>125
DM
Treat for DM
200
101 to 125
Indeterminate
Treat as IFG
200
<100
Indeterminate
Repeat; if >125 treat as DM; if 110125 treat as
IFG; <110 consider normal
125 to 200 >125
Indeterminate
Repeat; if >125 treat as DM;
otherwise treat as
IFG
125 to 200 101 to 125
Indeterminate
Treat for IFG
125 to 200 <100
Normal
Recommend rescreening in three years
Patients classified as having impaired fasting glucose (IFG) should be counseled
vigorously on issues related to lowering their risk of macrovascular disease
(smoking cessation, use of aspirin, diet, and exercise), and should have measurements
of blood pressure and serum lipids. They should also be encouraged to modify their
lifestyle with increased exercise (ideally 150 minutes weekly) and weight reduction,
targeting a seven percent weight loss if overweight, as these measures have been shown
to significantly decrease the risk of developing type 2 diabetes. Screening for diabetes
should be repeated annually.
10.
List the classes, mechanism of action and common side effects of the
oral hyperglycemic medicines. refer to First aid
11.
List the types of insulin available and discuss their use in Type 2
Diabetes. refer to First aid

12.
Discuss recommendations for diet and exercise for patients with Type
2 Diabetes.
Diet - Diet can improve obesity, hypertension and responsiveness to insulin in Type 2 DM
patients. It is usually focused on reduction in caloric intake and weight reduction. Studies
have shown that diet alone can fix the problems of a very small percentage, 3%, of those
diagnosed with Type II diabetes. However, it should be noted that any weight reduction
generally does show to improve glycemia and tends to lead to a decrease in the

amount/dosage of medications needed. This fact could be very important when

considering the fact that many Type 2 Diabetics will go on to use insulin after oral
medications stop working and this could be delayed with diet modification.
Surgical treatment of obesity Surgical treatment of obese patients with diabetes
results in the largest degree of sustained weight loss and, in parallel, the largest
improvements in blood glucose control. In a two-year study of 60 obese patients (BMI 30 to
40), subjects randomly assigned to laparoscopic banding with conventional therapy versus
conventional therapy alone (education, lifestyle modification, pharmacologic therapy)
experienced greater weight loss (20 versus 1.4 percent) and remission rates of diabetes
(73 versus 13 percent). Despite these impressive results, concerns remain about the
rigorousness of the lifestyle modification, long-term success rates in maintaining weight
loss, and reproducibility of the results in patients with an extensive history of diabetes or
with a different surgical team. Thus, longer-term follow-up is required.
Exercise Regular exercise is also beneficial in type 2 diabetes, independent of weight
loss. It leads to improved glycemic control due to increased responsiveness to insulin; it
can also delay the progression of impaired glucose tolerance to overt diabetes. These
effects are directly due to exercise but concurrent weight reduction can play a contributory
role. However, only a fraction of patients with type 2 diabetes are able to maintain a
regular exercise regimen. In one 10-year study, for example, compliance with regular
exercise fell from 80 percent at six weeks to less than 50 percent at three months and to
less than 20 percent at one year.
Intensive lifestyle modification Intensive lifestyle intervention programs involving
weight loss, physical activity, and behavior modification are more likely to be successful in
improving long-term glycemic control than traditional diabetes support and education
programs.