Lecture 27 - Metabolic Disorders Diabetes)

Diabetes Mellitus Segun Mojiminiyi

DIABETES PREVALENCE MILLION DIABETICS %Chng

1995 2000 2025

WORLD

135 154 300

122

INDIA

19.4 22.9 57.2

195

MIDDLE EAST AFRICA OTHER ASIAN CNTR LATIN AMERICA CHINA SOCIALIST EUROPE

18.3 2.9 12.2 15.5 16.0 16.9

53.5 8.4 31.7 39.3 37.6 22.4

193 185 160 154 134 33

DEVELOPED (REST)

34.1 36.7 49.8

46

22.0 3.5 14.4 18.3 18.6 18.1

30-YR

What Will Be Covered in histopathology lecture… ◗ ◗ ◗

What we will talk about….. Clinical Biochemistry of Diabetes ◗ ◗ ◗ ◗ ◗

What is diabetes mellitus? Classification of diabetes mellitus Metabolic and biochemical changes in diabetes mellitus Diagnosis and monitoring of diabetes mellitus Diabetic Complications

What is diabetes mellitus?

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Disorder of carbohydrate, protein, and fat metabolism Results from defects in insulin secretion and/or insulin action

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Can represent: An absolute insulin deficiency Impaired release of insulin by the pancreatic beta cells Inadequate or defective insulin receptors Production of inactive insulin or insulin that is destroyed before it can carry out its action Clinically : Polyuria, Polydypsia, Polyphagia

Classification of diabetes mellitus

Etiological Classification I. Type 1 diabetes A. Immune mediated B. Idiopathic II. Type 2 diabetes

Etiological classification (Cont.) III. Other specific types a. Genetic defects of B cell function b. Genetic defects in Insulin action c. Diseases of the exocrine pancreas d. Endocrinopathies e. Drug or chemical –Induced f. Uncommon forms immune-mediated diabetes IV. Other genetic syndromes associated with diabetes V. Gestational diabetes mellitus

Metabolic and Biochemical Changes in Diabetes Mellitus

Excessive glucose production

Impaired glucose clearance

Hyperglycemia

Tissue injury

Normal Insulin Action Net Result: ◗ ◗ ◗

Without Insulin: ◗ ◗ ◗ ◗

Metabolic and Biochemical Changes

Mechanism • • • • • •

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Metabolic and Biochemical Changes

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Metabolic and Biochemical Changes

Mechanism • • • • • • • • • • • • •

Metabolic and Biochemical Changes

Mechanism

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Diagnosis and monitoring of diabetes mellitus

Criteria for Diagnosis of Diabetes Mellitus (American Diabetes Association) 1.

2.

3.

Symptoms of diabetes plus casual plasma glucose concentration ≥11.1 mmol/l. Casual is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia and unexplained weight loss. Or FPG ≥7.0 mmol/l. Fasting is defined as no food intake for at least 8 h. Or 2-h Post Glucose intake ≥11.1 mmol/l during an OGTT. The test should be performed as described by WHO using a glucose load containing the equivalent of 75-g anhydrous glucose dissolved in water.

Diagnostic Protocol SYMPTOMATIC

ASYMPTOMATIC PATIENTS

PATIENTS

Casual Plasma Glucose ≥ 11.1 mmol/L

Diabetes

Casual Plasma Glucose < 11.1 mmol/l

Fasting Plasma Confirm Glucose

Fasting Plasma Glucose

FPG < 6 mmol/L Normal

FPG 6 – 6.9 mmol/L Impaired Fasting Glucose

Diabetes Oral Glucose Tolerance Test

Plasma Glucose ≥ 11 mmol/Lat 2 hrs Diabetes

FPG ≥ 7.1 mmol/L (at least 2 times)

Plasma Glucose 7.8 – 11 mmol/L at 2 hrs Impaired Glucose

(no further testing)

Plasma Glucose < 8 mmol/al at 2 hrs Impaired Fasting

Monitoring Diabetes Control

• Random plasma glucose (RPG)—without regard to time of last meal • Fasting plasma glucose (FPG) —before breakfast • Postprandial plasma glucose (PPG)—2 hours after a meal • Hemoglobin A1c (A1C)— reflects mean glucose over 2– 3 months • Fructosamine/glycated serum protein—reflects mean

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Tests used for Assessment of risk factors for complications …….

Use of Urine microalbuminuria: Used for Screening for Diabetic Nephropathy ■ ■

Diabetic Complications

 Short term (Acute) Complications: (metabolic) Hypoglycemia Diabetic Ketoacidosis  Long term Complications:(Angiopathy) Microangiopathy - Retinopathy, Nephropathy, Neurophathy, dermatopathy. Macroangiopathy – Atherosclerosis.

Acute Complications of Diabetes Mellitus

Hypoglycemia Most common complication of diabetes 100% of Type 1 patients affected much less common in Type 2

Multiple causes: exercise/activity reduced food intake delayed meal

Insulin overdose alcohol use

Laboratory Findings in hyperglycaemic hyperosmolar state (HHS) and DKA Investigation

DKA

HHS

Screening For Diabetes

Screening Criteria for Diabetes Age > 45, repeat every 3 years Obesity: > 120% IBW or BMI > 27 First degree relative with DM High risk ethnic group eg Pima Indians, ?? Kuwaitis Woman with previous baby > 4 kg Hypertension, hyperlipidemia Previous Impaired Glucose Tolerance or Impaired Fasting Glucose.