DIABETES MELLITUS

PRESENTED BY , PRIYANKA GUND

TITLE1. INTRODUCTION2. DEFINITION3. SYNTHESIS , METABOLISM , ACTION OF

NORMAL INSULIN4. CLASSIFICATION5. SYMPTOMS6. PATHOPHYSIOLOGY

6. COMPLICATIONS7. DIAGNOSIS8. TEST FOR DIAGNOSIS OF DIABETES

MELLITUS

INTRODUCTION IT IS DISORDER OF ENDOCRINE

PANCREAS.

NORMAL STRUCTURE OF PANCREAS :- TOTAL WEIGHT :- 60 – 100 gm CELLS OF PANCREAS :- ISLET OF LANGERHANS ISLET POSSESS NO DUCTAL SYSTEM &

THEY DRAIN THEIR SECRETORY PRODUCT DIRECTLY

INTO THE CIRCULATION.

4 MAJOR TYPES OF CELLS

BETA CELLS [70%]

• SECRETE INSULIN.

• DEFECTIVE RESPONSE CAUSES DIABETES MELLITUS.

ALPHA CELLS [20%]

• SECRETE GLYCOGEN.

• INDUSES HYPERGYCAEMIA.

DELTA CELLS [10%]

• SECRETE SOMATOSTATIN.

• SUPPRESSES BOTH GLUCOSE & INSULIN SECRETION.

• SECRETE PANCREATIC POLYPEPTIDE.

2 MINOR TYPES OF CELLS

D1 CELLS

• SECRETE VASOACTIVE INTESTINAL PEPTIDE.

• INDUCES GLYCOGENOLYSIS & HYPERGLYCAEMIA.

ENTEROCHOMAFFIN

CELLS

• FORMATION OF SEROTONIN.

• INDUSES CARCINOID SYNDROME.

DEFINITION

AS PER WHO, “ DIABETES MELLITUS IS DEFINED AS HETEROGENOUS METABOLIC DISORDER CHARATERISED BY COMMON FEATURE OF CHRONIC HYPERGLYCAEMIA WITH DISTURBANCE OF CARBOHYDRATE PROTEIN , FAT , METABOLISM.”

ANOTHER DEFINITION, “ DIABETES MELLITUS IS A METABOLIC DISORDER CHRACTERISED BY THE PRESENCE OF HYPERGLYCAEMIA DUE TO DEFECTIVE INSULIN SECRETION , DEFECTIVE INSULIN ACTION & BOTH.”

SYNTHESIS OF INSULIN

OCCURS IN ROUGH ENDOPLASMIC RETICULUM

OF BETA CELLS IN ISLET OF LANGARHANS.

INSULUN SYNTHESIZED AS PROTEOLYSIS PREPROINSULIN PEPTIC CLAVAGE PROINSULIN INSULIN C-PEPTIDE

AT THE TIME OF SECRETION C-EPTIDE IS DETACHED

METABOLISM OF INSULIN

BINDING OF INSULIN TO RECEPTOR IS ESSENTIAL FOR ITS REMOVAL FROM CIRCULATION & DEGRADATION.

INSULIN IS DEGRADED IN LIVER &

KIDNEY BY A CELLLULAR ENZYME CALLED INSULIN DEGRADING ENZYME.

PRIMARY • JUVENILE ONCET• INSULIN DEPENDENT

SECONDARY• MATURITY ONCET• NON-INSULIN

DEPENDENT

CURRENT CLASSIFICATION BASED ON ETIOLOGY :-

1. TYPE 1 DIABETES MELLITUS2. TYPE 2 DIABETES MELLITUS3. OTHER SPECIFIC TYPE OF DIABETES

MELLLITUS4. GESTATIONAL DAIBETES MELLITUS

SINGS & SYMPTOMS INCREASED THIRST ( POLYDIPSIA ) FREQUENT URINATION ( POLYURIA ) EXTREME HUNGER ( POLYPHAGIA ) WEIGHT LOSS PRESENCE OF KETONE IN URINE FATIGUE BLURRED VISION

SLOW HEALING SORES HIGH BLOOD PRESSURE FREQUENT INFECTION

1. TYPE 1 DIABETES MELLITUS :- “ AN AUTOIMMUNE DISEASE THAT OCCURS WHEN T CELLS ATTACK & DESTORY MOST OF THE BETA CELLS IN THE PANCREAS THAT ARE NEEDED TO PRODUCE INSULIN , SO THAT THE PANCREAS MAKES TOO LITTLE INSULIN OR NO INSULIN ”.

TYPE 1 CLASSIFICATION :-

I. TYPE 1A – IMMUNE MEDIATED :-

“ IT IS CHARACTERISED BY AUTOIMMUNE DESTRUCTION OF BETA CELLS WHICH USUALLY LEADS TO INSULIN DEFICIENCY ”.

II. TYPE 2B – IDIOPATHIC :-

“ IT IS CHARACTERISED BY INSULIN DEFICIENCY WITH TENDENCY TO DEVELOP KETOSIS BUT THESE PATIENTS ARE NEGATIVE FOR AUTOIMMUNE MARKERS ”.

PATHOPHYSIOLOGY OF TYPE 1

I. GENETIC SUSCEPTIBILITY :-a. UNION IN IDENTICAL TWINS 50 %-

MUTATION OF GENE DUE TO INSULIN DEFICIENCYBETA CELLS MAY HAVE TO WORK HARDER TO PRODUCE

INSULIN STRESS ON BETA CELL INCREASES

STIMULATES AUTOIMMUNE PROCESS INCREASES BETA CELL STRESS

II. AUTOIMMUNE FACTOR :-a. INSULITIS – OCCURRENCE OF LYMPHOCYTIC INFILTRATE IN & AROUND THE PANCREATIC ISLET .

b. DESTRUCTION OF BETA CELL –

GENERALLY INFLAMMATION PLAY VITAL ROLE IN BETA CELL DESTRUCTION . BUT PRECISE FACTOR ARE NOT KNOWN .

A PROTIEN BASED ENZYME FOUND IN BETA CELL PRODUCES SPECIFIC LIPIDS THAT CAUSE INFLAMMATION & LEAD TO DEATH OF BETA CELLS

III. ENVIRONMENTAL FACTOR :-a. VIRAL INFECTION b. EXPERIMENTAL INDUCTION WITH

CHEMICALc. GEOGRAPHIC

2. TYPE 2 DIABETES MELLITUS :-

“THE BASIC METABOLIC DEFECT IN TYPE 2DM IS EITHER DELAYED INSULIN SECRETION RELATIVE TO GLUCOSE LOAD OR THE PERIPHERAL TISSUES ARE UNABLE TO RESPOND TO INSULIN ”.

PATHOPHYSIOLOGY OF TYPE 2

I. GENETIC FFACTOR :-a. GENETIC COMPONENT HAS A STRONGER

BASIS FOR TYPE 2DM THAN TYPE 1DM .

b. UNION IN IDENTICAL TWINS 80% - PERSONS WITH ONE PARENT HAVING TYPE 2DM IS AT AN INCREASED RISK OF GETTING DIABETICS .

II. CONSTITUTIONAL FACTORS :- a. OBESITY

STRESS THE MEMBRANOUS NETWORK INSIDE THE CELL

WEAKEN THE INSULIN RECEPTOR INCREASES BLOOD SUGER LEVEL

b. HYPERTENSION :-

OCCURS BECAUSE OF A NARROWING IN THE ARTERIES CAUSED BY CONTINUED & CONSISTENTLY HIGH BLOOD GLUCOSE LEVEL .

III. INSULIN RESISTANCE :-a. LACK OF RESPONSIVENESS OF

PERIPHERAL TISSUE TO INSULIN SPECIALLY SKELETAL MUCSLE & LIVER .

IV. IMPAIRED INSULIN SECRETION :-a. IN CASE OF TYPE 2DM HAVE MILD

DEFICIENCY OF INSULIN BUT NOT ITS TOTAL ABSENCE .

IV. INCREASED HEPATIC GLUCOSE SYNTHESIS :-a. TYPE 2DM PART OF INSULIN RESISTANCE

BY PERIPHERAL TISSUE & LIVER .b. INSULIN SUPRESS GLYCONEOGENESIS DUE TO GF , CF , IR GLYCONEOGENESIS IN LIVER IS NOT SUPRESSED INCREASES HEPATIC SYNTHESIS OF GLUCOSE HYPERGLYCAEMIA

3. OTHER SPECIFIC TYPES OF DIABETES MELLITUS :-

I. GENETIC DEFECT OF BETA CELLII. GENETIC DEFECT IN INSULIN ACTIONIII. DISEASE OF EXOCRINE PANCREASEIV. DRUG OR CHEMICAL INDUSEDV. INFECTIN

4. GESTATIONAL DIABETES MELLITUS :- “ IT IS DEFINED AS ANY DEGREE OF GLUCOSE INTOLERANCE WITH ONSET OR FIRST RECOGNITION DURING PREGNANCY ”. DURING PREGNANCY THE PLACENTA PRODUCES HIGH LEVELS OF VARIOUS OTHER HORMONS. ALMOST ALL OF THEM IMPAIR THE ACTION OF INSULIN IN CELLS & RAISING BLOOD SUGER.

COMPLICATIONS 2 MAJOR GROUPS :-

I. ACUTE METABOLIC COMPLICATIONS :-

DIABETIC KETOACIDOSIS HYPEROSMOLAR NONKETOTIC COMA HYPOGLYCAEMIA

II. LATE SYSTEMIC COMPLICATIONS :-

ATHEROSCLEROSIS DIABETIC MICROANGIOPATHY DIABETIC NEUROPATHY DIABETIC RETINOPATHY

KETOACIDOSIS :- SEVERE LACK INSULIN

LIPOLYSIS IN ADIPOSE TISSUE RELEASE OF FREE FATTY ACID IN PLASMA OXIDATION IN LIVER KETOACIDOSIS

HYPEROSMOLAR HYPERGLYCAEMIC NONKETOTIC COMA :-

INSULIN DEFICIENCY HYPERGLYCAEMIA GLYCOSURIA DECRESED ANABOLISM OSMOTIC DIURESIS DEHYDRATION & LOSS OF ELECTROLYSIS DIABETIC COMA

ATHEROSCLEROSIS :-

INSULIN DEFICIENCY

INCREASES BLOOD GLUCOSE

MORE IN SYNTHESIS

FAT DEPOSITION IN LARGE VESSELS

EVIDENCE OF THROMBOTIC STATE

ATHEROSCLEROSIS

ILL EFFECT :-i. CORONARY ARTERY DISEASE ii. SILENT MYOCARDIA INFARCTIONiii. GANGRENE OF TOE & FEET

MICROANGIOPATHY :-CHARACTERISED BY BASEMENT MEMBRANE THICKING OF SMALL BLOOD VESSELS

HYPERGLYCAEMIA INCREASED GLYCOSYLATION OF Hb INCREASES BASEMENT MEMBRANE OF VESSELS

NEPHROPATHY :-

HYPERGLYCAEMIA GLOMERULAR HYPERTENSION

RENAL HYPERPERFUSION

DEPOSITION OF PROTEIN

GLOMERULOSCLEROSIS

RENAL FAILUER

NEUROPATHY :- HYPERGLYCAEMIA TRYGLYCERIDES SUGER AUTOXIDATION POLYOL PATHWAY

OXIDATIVE STRESS ENDOTHELIAL DYSFUNCTION DECREASES CAPILLARY FLOW NERVE DYSFUNCTION NERVE REGENERATION

RETINOPATHY :-DIABETES AFFECT ON BLOOD VESSELS IN RATINA THE TISSUE WHICH LINES THE INNER EYE .

CAUSES PERMENANT RETINAL BLOOD VESSEL CHANGES LIKE OBSTRUCTION TO INNER FLOW OF BLOOD , LEAKAGE & ABNORMAL GROWTH .

2 STAGES :-I. NON – PROLIFERATIVE :- FAT & PROTEIN FLUID LEAKAGE DEPOSITED IN RATINA .

II. PROLIFERATIVE :- ABNORMAL GROWTH OF BLOOD VESSELS & TISSUE AROUND THE VESSELS IN RATINA .

DIAGNOSIS

A1C ( PERCENT )

FASTING PLASMA GLUCOSE ( Mg/dL )

ORAL GLUCOSE TOLERANCE TEST ( Mg/dL )

DIABETES 6.5 OR ABOVE

126 OR ABOVE

200 OR ABOVE

PREDIABETES 5.7 TO 6.4 100 OR 125 140 TO 199

NORMAL ABOUT 5 99 OR BELOW 139 OR BELOW

TEST FOR DIAGNOSIS URINE TEST SINGLE BLOOD SUGER ESTIMATION SCREENING BY FASTING GLUCOSE

TEST ORAL GLUCOSE TOLEANCE TEST

BIBLIOGRAPHY

BOOK NAME AUTHER NAME EDITION

TEXT BOOK OF PATHOLOGY

HARSH MOHAN 7th EDITION

MEDICAL PHYSIOLOGY

S.MANJUNATH 4th EDITION

MEDICAL PHYSIOLOGY

K.SHAMBHULIGAM

4th EDITION

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