Facts about Type II Diabetes Mellitus Diabetes was

Facts about Type II Diabetes Mellitus

“ Diabetes was long thought to be a kidney disease” (Greek & Arabic Methodology).

“ Thomas Willis (1621 - 1679), discovered the sweetness of urine, hence, the name Diabetes Mellitus arised”

“Mathew Dobson (1776), identified glycosuria”.

“Claude Bernard and Von Mering (1889), discovered in the same year that pancreatectomy causes diabetes”

“Fredrick Banting (1921), successfully, extracted insulin, gaining the Nobel prize for this great discovery”.

“Leonard Thompson (14 year old boy) & Elizabeth Hughes (aged 14 years), were the first patients to be treated with insulin in 1922.

Dear Mom, . . I look entirely different gaining every hour strength & weight. . it is truly miraculous. . I wish you could see the expression on there faces, they are so astounded in my unheard of progress. . Leonard, April, 1922

METABOLISM + It includes all the biochemical reactions that start in the cell after the absorption of food stuff. + Metabolism may be: t Anabolism: building up, needs energy. u Catabolism: breaking down, gives energy.

Important Terminology In Carbohydrate Metabolism Glycolysis: Glucose breakdown & utilization that occurs in cells. Glycogenolysis: The breakdown of glycogen to glucose.

Glycogenesis: Glycogen formation that occurs in liver & muscles for storage of carbohydrates (as glycogen). Gluconeogenesis: Formation of glucose from fatty acids & amino acids (new glucose formation).

CARBOHYDRATES í Organic substance composed of carbon, hydrogen & oxygen. í CHO are the first source of energy for the organism.

CLASSIFICATION OF CHO Simple sugar Complex sugar *Rapidly-absorbed CHO * Slowly-absorbed CHO. *Monosaccharides directly * Disaccharides to polysaccharides need to be broken down to be absorbed as simple sugar. absorbed. *Glucose - Fructose Galactose. * Starch - Maltose.

Fate of Absorbed Glucose G Glycogenesis Glycolysis Muscle Cells 50 % Glycogenesis Liver Cells 30 % Glycolysis Lipogenesis Glycolysis Fat Cells 5 %

Regulation of Blood Glucose Hormonal Regulation o Organic Regulation o

Hormonal Regulation Blood Glucose Level < 110 mg/L Insulin Hypoglycemic Hormone Glucagon Growth Hormone Adrenaline Cortisol Counterregulatory Hormones

Insulin The only Hypoglycemic Hormone + It is secreted by ß- cells of the islets of Langerhans of the pancreas. + Daily 20 - 50 units are secreted. +

Insulin Synthesis Pre. Pro Insulin Split at position 61/62 Insulin Pro Insulin C peptide

INSULIN SECRETION Glu t 2 e cos lu G od Blo GLUCOSE GK G-6 -P PK PYRUVATES K+ _ + _+ INSULIN ATP _+ DEPOLARIZATION Ca 2+

Insulin Secretion Curve Biphasic insulin response to a constant glucose stimulation (IVGTT - hyperglycemic Clamp) Insulin rate Basal Time (min) 4 60

Insulin secretion pattern Early Peako Late Phaseo

Insulin Secretion Pattern Early peak: o rapid. . Prestored insulin to prevent the marked increase of the blood glucose level. Late phase: o slow. . Newly fabricated insulin to normalise the blood glucose level.

Insulin Controls Blood Glucose metabolism by: Uptake Utilization

Insulin: Uptake of glucose Stimulates glucose transporters to move to the cell surface. The process is passive in the kidney, n liver and brain. Active in the other tissues. n o

Insulin: Glucose utilisation Oxidation o Storage o Liver & Muscles Adipocytes glycogen n lipids n

Glucose Oxidation (Glycolysis) Glucose Insulin T+ Glucose GK G-6 -P PK -0 Pyruvates 2 GK: PDH: T: Glucokinase Pyruvate Kinase Pyruvate Dehydrogenase Insulin-dependent Transporter PDH Kreb’s Cycle 36 ATP + CO 2 + H 2 O Lactic Acid +2 ATP

How is Glucose Used in the Liver? Glucose Insulin TGlucose GK G-6 -P GS Glycogen PK Pyruvates ATP GS: T-: Glycogen Synthase Non-insulin Dependent Transporter

How is Glucose Used in the Muscle Cells? Glucose Insulin TGlucose HK G-6 -P GS PK Glycogen Pyruvates ATP HK = Hexokinase

How is Glucose Used in the Adipocytes? Glucose Insulin T+ Glucose GK G-6 -P PK Pyruvates PDH ATP GPDH Glycerol 3 P + 3 Fatty Acids Triglycerides

I What Happens Between Meals? glycogenolysis Lipolysis Glucose Gluconeogenesis Fatty Acids + Glycerol I glycogenolysis Glucose Gluconeogenesis I energy

Organic regulation of the blood glucose I- Liver: Blood glucose glycogenolysis gluconeogenesis glycolysis HGP

Organic regulation of the blood glucose II. Kidney Normally no glucosuria o Above renal thresholdglucosuria o (1. 8 g / L)

Definition + Diabetes Mellitus is a group of Metabolic Diseases characterized by Hyperglycemia resulting from defects in insulin secretion, insulin action, or both. American Diabetes Association

Diabetes Estimates and Projection

Classification of Diabetes Mellitus Primary Diabetes o Type 1 insulin dependent n diabetes Type 2 non insulin dependent diabetes n

Classification of Diabetes Mellitus Secondary Diabetes o Gestational diabetes n Malnutrition related diabetes n Diabetes resulting from: n Pancreatic disease Hormonal diseases Drug/chemical induced Genetic syndromes p p

New Criteria: Diagnosis of D. Mellitus American Diabetes Association

Diabetes: Clinical Features Symptoms: o Polyuria Polydypsia=thrit Polyphagia=appetite Asthenia & Loss of weight n n Signs: o No specific signs may be signs of complications

Key Organs of Diabetes Pancreas insulin secretion disorder Liver Muscle in hepatic glucose production in glucose storage Hyperglycemia

Peripheral Abnormalities Liver Fat tissues Gluconeogenesis Glycogenosis Glycolysis Gluconeogenesis Muscles Lipogenesis Lipolysis Glycogenesis FFA Glucose production Glucose Storage Hyperglycaemia

Pathogenesis of diabetes: metabolic features Genetic predisposition Insulin resistance Defective insulin secretion Hyperglycemia

Impaired Insulin Secretion

Causes of Impaired Insulin Secretion Decrease in number of Beta cells by o 40 -50 % {In Insulin resistance states, the number is either normal or increased}

Causes of Impaired Insulin Secretion Amyloid deposits Amylin : amyloid material secreted by B cells Interferes with the recognition of the glucose signal

Causes of Impaired Insulin Secretion Reduced activity of the glucokinaseo ATP production reduced inside B cellsn Closure of K channel decreasesn Entry of Calcium reduced n release of Insulin reducedn

Insulin Resistance

Types of Insulin Resistance o. Receptor defect o Post Receptor defect

Types of Insulin Resistance o. Receptor defect n. Decrease in the affinity n. Decrease in number (rare)

Types of Insulin Resistance o. Post receptor defect Glucose Transporter Intra cellular utilization Enzymatic activity

Gluco-toxicity Insulin secretion disorder Chronic hyperglycemia Insulin resistance

Vascular complications o Microvascular complications o Macrovascular complications

Microvascular complications o Retinopathy o Nephropathy o Neuropathy

Macrovascular complications o CHD o CVD o PAD 10 years accelerated

o. Thank You