1. Diabetes Mellitus

2. Overview
A heterogeneous group of syndromes characterized by an elevation of fasting blood glucose caused by absolute or relative deficiency of insulin
Two types of DM:
Type 1 (insulin-dependent DM)
Type 2 (noninsulin dependent DM)
Prevalence of type 2 is increasing as:
Aging (increase in rate of life-age of population)
Increasing prevalence of obesity

3. Comparison between type 1 & type 2 DM

4. Type 1 Diabetes Mellitus
about 10% of diabetics (in USA)
Onset: usually during childhood
Caused by absolute deficiency of insulin caused by autoimmune attack of b-cells of the pancreas
Destruction is enhanced by environmental factors as viral infection
& a genetic element (that allows b-cells to be recognized as nonself)
(in identical twins if one sibling has type 1 DM, the other twin has only 30-50% chance of developing DM)
Rapid symptoms appear when 80-90% of the b-cells have been destroyed
Commonly complicated by DKA
treated only by insulin

6. Diagnosis of type 1 DM Clinically:
Age: during childhood or puberty (< 20 years of age)
Abrupt appearance of :
polyuria (frequent urination)
polydepsia (excessive thirst)
polyphagia (excessive hunger)
fatigue
weight loss
complicated by ketoacidosis (common, may be the cause of diagnosis)
Laboratory diagnosis:
fasting blood glucose: > or equal 126 mg/dl
100 – 125 mg/dl impaired fasting blood glucose
testing of circulating islet-cell antibodies

7. Metabolic changes of type 1 DM
1- Hyperglycemia
decreased glucose uptake by muscles & adipose tissues (by GLUT-4)
& increased hepatic gluconeogenesis
2- Ketoacidosis
(in untreated or uncontrolled cases)
in 25 – 40% of newly diagnosed type 1 DM
in stress states demanding more insulin (as during infection, illness or during surgery)
no comply with therapy (intake of meals with no insulin medication)
Biochemical causes of diabetic ketoacidosis (DKA)
no insulin increased mobilization of FFA from adipose tissues
in the liver, FFA --- b-oxidation acetyl CoA KETONE BODIES

8. Metabolic changes of type 1 DM (cont.)
3- Hypertriacylglyceridemia
Released fatty acids from adipose tissues are converted to triacylglycerol
Triacylglycerol is secreted from the liver in VLDL
Chylomicrons accumulates (low lipoprotein lipase in DM)
Increased VLDL & chylomicrons results in hypertriacylglyceridemia

10. Treatment of type 1 DM Standard treatment:
Exogenous insulin by sc injection to control hyperglycemia & ketoacidosis
Standard treatment:
by one or two injections of insulin / day
AIM: Mean blood glucose level mg/dl (normal: 110 mg/dl)
HbA1c level: 8-9 % of total Hb (normal: 6% of total HB)
HbA1c:
is proportional to average blood concentration over the previous several months
So, it provides a measure of how well treatment normalized blood glucose in diabetic over several months

11. Treatment of type 1 DM (cont.)
Intensive treatment
more closely normalize blood glucose to prevent complications of
existence of hyperglycemia for a long period
by more frequent monitoring & subsequent injection of insulin
(3 or more times / day)
AIM: Mean blood glucose levels of 150 mg/dl
HbA1c : approximately 7% of total Hb
Advantage: reduction in chances of occurrence of complications of DM:
retinopathy, nephropathy & neuropathy (about 60%)

12. Hypoglycemia in type 1 DM
is a complication of insulin treatment (in more than 90% of patients)
Common with intensive treatment regimens
Diabetics cannot depend on glucagon or epinephrine to avoid hypoglycemia ??
No glucagon (early in the disease)
No epinephrine ( with progression of the disease diabetic
autonomic neuropathy with inability to
secrete epinephrine)
So, patients with long-standing type 1 DM are particularly vulnerable to hypoglycemia

13. Contraindications of tight control
Children: risk of episodes of hypoglycemia may affect the
brain development
Elderly people: as hypoglycemia can cause strokes & heart
attacks in older people