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Rihab Faisal
Diabetes Mellitus
Lecture 1
Definition: According to American Diabetes Association (ADA), DM is defined
as a group of metabolic diseases characterized by hyperglycemia resulting from
defects in insulin secretion, insulin action, or both.
Classification:
Patients with any form of DM may require insulin treatment at some stage of their
disease, such use of insulin dose not, of itself, classify the patient. DM is classified
according to its etiology as follow: ()ﻟﻼطﻼع
the followings are DM diagnostic cut point criteria which were recommended by
ADA:
1. A1C ≥6.5%, or
2. FPG ≥126 mg/dl (fasting is defined as no caloric intake for at least 8 h), or
3. 2-h plasma glucose during OGTT ≥200 mg/dl, or
4. Classical symptoms of hyperglycemic crisis (diabetic ketoacidosis, DKA), a
RPG ≥200mg/dl
In the absence of unequivocal symptoms (polyuria and polydipsia), criteria 1-
3 should be confirmed by repeat testing.
INTRODUCTION
EPIDEMIOLOGY
Age: peaks of presentation occur in 2 age groups; at 5-7 year of age (correspond to
the time of increased exposure to infectious agents coincident with the beginning
of school) and at the time of puberty (correspond to the pubertal growth spurt
induced by gonadal steroids and the increased pubertal growth hormone secretion
which antagonizes insulin). Socioeconomic status: no apparent correlation. Sex:
male and females appear to be equally affected. Season: newly recognized cases
appear to occur with greater frequency in autumn and winter with fewer cases
presenting during summer months. This seasonal variation has decreased over the
past 10 years. Geographical area: generally the further from the equator, the
higher the incidence. Migration from one country to another confers the diabetic
risk of the new country within a generation.
PATHOGENESIS
1. Initiation of autoimmunity
5. Established disease
HLA Class II genes on chromosome 6 are the most strongly associated with risk of
T1DM, Some of the known associations include the HLA DR3/4-DQ2/8 genotype
(if 1 sibling has T1DM and shares the same high-risk DR3/4-DQ2/8 haplotype
with another sibling, then the risk of autoimmunity in the other sibling is 50%, and
this risk 80% when share both HLA haplotypes). Homozygous absence of aspartic
acid at position 57 of the HLA DQ b chain confers 100-fold relative risk for
developing DMT1.
*Diet: Breastfeeding may lower the risk of T1DM, either directly or by delaying
exposure to cow’s milk protein. Early introduction of cow’s milk protein and early
exposure to gluten are implicated in the development of autoimmunity. Other
dietary factors include omega-3 fatty acids, vitamin D, ascorbic acid, zinc, and
vitamin E; but the evidence is not yet conclusive.
PATHOPHYSIOLOGY
With moderate insulinopenia, glucose utilization by muscle and fat decreases and
postprandial hyperglycemia appears. At lower insulin levels, the liver produces
excessive glucose via glycogenolysis and gluconeogenesis, and fasting
hyperglycemia begins. Hyperglycemia produces an osmotic diuresis (glycosuria)
when the renal threshold is exceeded (180 mg/dl). The resulting loss of calories
and electrolytes, as well as the worsening dehydration, produces a physiologic
stress with hypersecretion of stress hormones (epinephrine, cortisol, growth
hormone, and glucagon). The combination of insulin deficiency and elevated
plasma values of the counterregulatory hormones is responsible for accelerated
lipolysis, impaired lipid synthesis and shunts the free fatty acids into ketone body
formation. The rate of formation of these ketone bodies, principally β-
hydroxybutyrate and acetoacetate, exceeds the capacity for peripheral utilization
and renal excretion. Accumulation of these ketoacids results in metabolic acidosis
(diabetic ketoacidosis [DKA]) and compensatory rapid deep breathing in an
attempt to excrete excess CO2 (Kussmaul respiration). Acetone, formed by
nonenzymatic conversion of acetoacetate, is responsible for the characteristic
fruity odor of the breath. Ketones are excreted in the urine in association with
cations and thus further increase losses of water and electrolyte. With progressive
dehydration, acidosis, hyperosmolality, and diminished cerebral oxygen
utilization, consciousness becomes impaired, and the patient ultimately becomes
comatose.
CLINICAL MANIFESTATIONS
*An insidious onset with lethargy, weakness, and weight loss is also quite
common. Calories are lost in the urine (glycosuria), triggering a compensatory
hyperphagia. If this hyperphagia does not keep pace with the glycosuria, loss of
body fat ensues, with clinical weight loss and diminished subcutaneous fat stores.
MANAGEMENT
The management of DMT1 is divided into three phases, depending on the initial
presentation:
Ketoacidosis.
Postacidotic transition (corresponds to presentations with polyuria,
polydipsia, and weight loss but without biochemical decompensation to
DKA).
Continuing phase of guidance of the child and his or her family (insulin,
nutritional intake, exercise, monitoring)
There is no one appropriate insulin regimen or meal plan, the principle is that the
diabetic care should fit wherever possible into the surrounding home, family's food
preferences and habits, school environments, and the primary child tasks of
education, socialization, growth, and maturity.
Management of DKA:
pH ≤ 7.00
Unconscious
Assess for precipitating factors and treat it (if possible): Delayed diagnosis,
infection, noncompliance, trauma.
DKA protocol
Fluid therapy:
Regarding amount, for all patients we consider the degree of dehydration as 8.5, so
deficit will be 85 cc/kg. maintenance is calculated as 100 cc/kg for first 10 kg, 50
cc for second 10 kg, and 25 cc for every kg above 20. This maintenance and
deficit should be given through 24 hr, but initially (during the first hr) patients
should receive bolus fluid as 10-20 cc/kg which can be repeated as needed. So iv
rate will be as follow:
Regarding type of fluid, bolus is 0.9 saline or RL, while the subsequent fluid is
0.45% saline, and when blood sugar < 250 add 5% dextrose ( 5% glucose in
0.45% saline).
Insulin:
Soluble insulin .05-0.1 U/kg/hr infusion started in the first hour and continue till
acidosis is resolved. But recent guidelines discourage its use in the first hour as its
use is associated with an increased risk of cerebral edema.
Potassium therapy:
Should be used after the patient has received the initial bolus fluid and when he
passed urine. The dose is 40 meq/L (10 cc/ pint), and if serum k < 3 meq/L, the
dose will be 80 meq/L (20 cc/ pint).
NaHCO3 therapy:
Bicarbonate buffers, regenerated by the distal renal tubule and by metabolism of
ketone bodies, steadily repair the acidosis once ketoacid production is controlled
by exogenous insulin. So, bicarbonate therapy is rarely necessary and may even
increase the risk of hypokalemia and cerebral edema. It indicated only when pH ≤
7.1, as severe acidosis causes depression of respiratory and cardiovascular
functions and may also be a factor in insulin resistance. At pH of 7 to 7.1, we
recommend that 40 mEq of HCO32/m2 (at pH of less than 7, 80 mEq of
HCO32/m2) should be infused over a period of 2 hours. Acid-base status should
then be reevaluated before further alkali therapy. Bicarbonate should not be given
by bolus infusion because it may precipitate cardiac arrhythmias.
During treatment of DKA, no oral intake is allowed, and we should monitor fluid
input and output, vital signs, neurologic status, blood sugar and electrolytes.
There should be a steady increase in pH, serum bicarbonate and sodium (Na
increase by approximately 1.6 mmol/L for each 100 mg/dl decline in the glucose)
and decrease in BS (not more than 100mg/dl/hr) as therapy progresses to decrease
the risk of cerebral edema. Kussmaul respirations should abate and abdominal pain
resolve. Persistent acidosis may indicate:
When DKA has resolved (total CO2 >15 mEq/L; pH >7.30; sodium stable
between 135 and 145 mEq/L; no emesis), the child can be easily transitioned to
oral intake and subcutaneous insulin ( the doses and regimens are as in
management of hyperglycemia without acidosis). The first dose of short acting
subcutaneous insulin is given with a meal, and the insulin drip is discontinued
approximately 30 min later.
More than 15 yrs ago, they used sliding scale for calculation of post DKA insulin
dose (it still be used in some hospitals in our country, although it is an old
regimen). It uses soluble insulin that had been given s.c. every 6 hours for 48 hrs
in doses according to blood sugar and as follow: ()ﻟﻼطﻼع
≤ 90mg/dl …. No insulin.
>360 mg/dl…0.4U/kg.
Then the mean is used for calculating the required insulin dose per day.