Diabetes Mellitus

Diabetes Mellitus
Diabetes mellitus is the most common endocrine disease. It is a common,

important and interesting disease.

Definition:
Diabetes mellitus is a clinical syndrome characterized by hyperglycemia, resulting from lack of insulin action on the tissues or disordered insulin action. Acute hyperglycemia leads to the classical symptoms of polyuria and thirst, while chronic hyperlgycemia may play a role in the development of specific complications of the disease. Although hyperglycemia is the hallmark of diabetes. Other abnormalities include weight loss, ketonuria, acidosis and growth retardation in inadequately treated type 1 diabetes and abnormalities in
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circulating lipoproteins that commonly occur in type 2 diabetes. The link between many abnormalities of carbohydrate, protein and fat metabolism lies in the major hormonal regulation of insulin. 1. In type 1 diabetes, the underlying reason is clear there is diminished or absent secretion of insulin from the B-cells of the islets of Langerhans. 2. In type 2 diabetes, the basic defect is less clear. These patients almost always secrete decreased amounts of insulin following oral glucose load
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(relative insulin deficiency) and plama insulin level is decreased relative to the prevailing blood glucose. In addition the abnormalities of insulin secretion, patients with type 2 diabetes have also insulin resistance. This insulin resistance is due both to a decrease in insulin binding to its plama membrane receptor and to post-receptor defect in insulin action. Thus, both a decrease in insulin secretion and impaired insulin action contribute to the hyperglycemia in type 2 diabetes. So, the biochemical definition of diabetes mellitus is a lack
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of insulin action upon the tissues resulting in abnormalities of carbohydrate, protein and fat metabolism. A clinical syndrome resulting from chronic long-term disordered metabolism is super imposed upon the biochemical abnormality. The main feature of the syndrome are a specific microangiopathy, neuropathy and more frequent and accelerated macrovascular disease

Classification of Diabetes Mellitus

Classification of diabetes mellitus are: I. Primary diabetes mellitus

1. Type 1:
a. Autoimmune b. Idiopathic

2. Type 2:
a. Predominantly insulin resistance b. Predominantly insulin secretory defect
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II.

Secondary diabetes mellitus

There are a number of diseases which are associated with diabetes secondary diabetes. Patients with these types of diabetes may simulate patients with type 1 or type 2 diabetes depending on the primary

process involved.
1. Pancreatic diseases: pancreatitis, pancreatectomy, neoplasia and hemochrematosis.
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2.

Endocrinopathies: acromegaly, Cushings syndrome, pheochromocytoma and hyperthyroidism. Drugs or chemicals induced: corticosteroids, thiazide diuretics, thyroid hormone, Badrenego-agonists.
Gestational diabetes mellitus

3.

4.

Pathophysiology
Whatever the aetiology, hyperglycemia develops in all cases of diabetes mellitus because of an absolute (type 1) or relative (type 2) deficiency of insulin which leads to: 1. Decreased anabolism 2. Increase catabolism It should be clear that type 1 diabetes reflects a state of almost complete insulin deficiency and this can be confirmed by plasma insulin or C-peptide array). In type 2 diabetes insulin is always present and maybe increased (relative insulin deficiency) lypolysis and
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ketogenesis remain inhibited, explaining the low prevalence of ketoanaemia and ketonuria in type 2 diabetes. However, acute superimposed illness acting through increased circulating catecholamines can further reduce insulin secretion and induce acute metabolic decompression identical to an acute type 1 diabetes.

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Major consequences of insulin deficiency

1.

Hyperglycemia and glycosuria In the absence of insulin, the blood glucose concentration (normally between) 70-120mg/-) can rise to above 600 mg/. Normally, glucose is filtered by the renal glomeruli, then completely reabsorbed in the kidney tubules. However, when the filtered load exceeds the renal threshold of 180mg/, glucose appears in the urine and acts as an osmatic diuretic, leading to polyuria, dehydration and polydypsia. The renal threshold for glucose generally tends to increase with age. In severe cases, severe of all in blood
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2. Ketosis: In the absence of insulin, lipolysis is stimulated and free fatty acid levels in the blood increase. Fatty acids are normally oxidized in the mitochndria in the liver to acetyl CoA that enters the citric acid cycles to undergo further oxidation, yielding CO2 and energy. Lack of insulin causes excess acetyl CoA to accumulate in the liver (more thanthe ability of citric acid cycle to deal with), so it condenses to form ketone bodies in the circulation. High concentration of ketone bodies in the circulation also induces
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nausea, vomiting, metabolic acidosis and ultimately diabetic coma. 3. Muscle wasting: Insulin deficiency will tend to reduce all anabolic processes and facilitate catabolic processes, protein breakdown will therefore be increased and blood aminoacid levels will rise. This protein depletion (together with the enhanced fat breakdown contribute to the severe muscle wasting, weakness and loss of weight found in chronic diabetics.
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4. Attention in drawn to the additional insulin independent metabolic pathways which are activated as a result of untreated or inadequately controlled hyperglycemia. These alternative important pathways are partly responsible for the long-term vascular and neurological complications of diabetes, which form the major morbidity and mortality of this disease.

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Difference between type 1 & type 2

Type 1
1. Age of onset 2. Duration of symptoms & signs 3. Onset 4. Body weight 5. Ketonuria < 30 years Days weeks Acute Never obese Yes

Type 2
> 30 years Months-years Gradual Obese No

6. Rapid progression 7. Family history of diabetes 8. Insulin or C-peptide level 9. HLA associated

Yes No Absent, very low Yes

No Yes Normal or high No

no 10-20%
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10. Auto antibodies Yes 11.Diabetic complications at diagnosis No

Glucose measurements for diagnosis of diabetes mellitus (using venous plasma) The following three blood tests are used for diagnosis: 1. Random plasma glucose: sample taken anytime of the day 2. Fasting plasma glucose (FPG): no caloric intake for 8 hours 3. Two hours post prandial (75 gm oral glucose) plasma glucose (2h-PPPG): blood sample taken two hours after person has consumed a 75 gm glucose powder dissolved in 250 ml water.
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Interpretation: I. Diagnostic criteria of DM: a. Classic symptoms of DM + anyone of three positive tests 1. Random plasma glucose > 200 mg/dL or 2. Fasting plasma glucose > 126 mg/dL or 3. 2h-PPPG > 200 mg/dL b. Absence of classical symptoms of hyperglycemia: any abnormal test must be confirmed on a subsequent day by any one of the three tests
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II. Prediabetes: include individuals who have: a. FPG: 100-125 mg/dL (called impaired fasting glucose) b. 2h-PPPG > 140-1999 mg/dL (called impaired glucose tolerance III. Normoglycaemia: inclu individuals who have: a. FPG: < 100 mg/dL b. 2h-PPPG < 140mg/dL

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Acute complications of diabetes mellitus 1. Hypoglycaemia 2. Hyperglycemic crises:

a. Diabetic ketoacidosis b. Non-ketotic hyperomolar hyperglycaemic state (NKHH)

3. Lactic acidosis 4. Infections 5. Others:

a. Cerebrovascular strokes b. Cardiovascular strokes c. Renal failure
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Chronic complications of diabetes 1. Microvascular disease

a. Retiropathy b. nephropathy

2. Macrovascular disease
a. Coronary artery disease b. Cerebrovascular disease c. Peripheral vascular disease

3. Neuropathic
a. b. c. d. Peripheral symmetrical polyneuropathy Mononeuritis and mononeuritis multiples Diabetic amyotrophy Autonomic neuropathic
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Chronic complications of diabetes 4. Foot ulcers 5. Dermopathies 6. infections

a. Gingival b. Dermal c. vulvovaginitis

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Management of diabetesmellitus The main lines of treatment of DM are: 1. Lifestyle changes:

a. Diet b. Exercise

2. Education 3. Insulin therapy 4. Oral hypoglycaemia drugs.

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