Diabetes Mellitus and metabolic syndrome

Metabolic syndrome

Insulin Resistance Syndrome

Glucose Intolerance

Dyslipidemia Hypertension

Endothelial dysfunction Macrovascular disease

Dysfibrinolysis

Metabolic syndrome• Identified insulin resistance subjects• Identified high risk for develop T2 DM• Identified high risk for CVD

IDF(2005) criteria• Abdominal obesity (Ethnic specific)– Waist >102 cm (men), >88 cm (women)– Waist >90 cm (m), >80 cm (w) Asian

• Hypertriglyceridemia > 150 mg/dl• HDL <40 mg/dl (men); < 50 mg/dl (women)• Hypertension 130/85 mmHg≥• Fasting hyperglycemia (serum) 100 mg/dl≥

“Plus 2 of the following”

Pre-diabetic stages• Impaired glucose tolerance

– 2 hrs OGTT: 140<IGT<200• Impaired fasting glucose

– Fasting plasma: 100<IFG<126

Diabetes Mellitus

Symtoms• Asymtomatic(~50%)• Polyurea• Acute complication ex DKA, Focal

seizure, Coma.• Chronic complication

Diagnosis• Symptoms + Plasma glucose>=200 mg%• Fasting plasma glucose>=126 mg%• 75 gm OGTT

– 2 hr plasma glucose > =200 mg%

Diagnosis• Repeat 1 time after abnormal of the first

test.• Except, in case of hyperglycemia with

acute diabetic complication

Diabetes classification• Primary diabetes

– Type 1 diabetes– Type 2 diabetes

• Secondary diabetes

Diabetes classification• Secondary diabetes

– Pancreatic Diabetes– Endocrine disorder ex Hyperthyroidism

,Cushing’s syndrom, Primary hyperaldosteronism, Acromegary, Pheochromocytoma, Glucagonnoma.

Diabetes classification• Secondary diabetes

– Drug ex Glucocorticoid, B-adrenergic blocked, thiazide diuretic

– Other ex genetic syndrome, Insulin antibody

Type 1 diabetes• Acute onset• Ketoacidosis pone• Thin• Young age• Need insulin treatment

Type 2 diabetes• Slow onset• Ketoacidosis resistance• Norma weight or obese• Middle to old age• Response to oral hypoglycemic agent

Pathogenesis• Type 1 diabetes• Type 2 diabetes

Pathogenesis of type 1 DM

Pathogenesis of type 1 DM

Islet cell auto antibody

Pathogenesis of type 1 DM

Islet cell auto antibody

Destruction of Islet cell

Pathogenesis of type 1 DM

Islet cell auto antibody

Destruction of Islet cell

Insulin deficiency

Pathogenesis of type 1 DM

Islet cell auto antibody

Destruction of Islet cell

Insulin deficiency

Host Factor

Pathogenesis of type 1 DM

Islet cell auto antibody

Destruction of Islet cell

Insulin deficiency

Host Factor Precipitating Factor

Pathogenesis of type 2 DM

Insulin resistance is an etiology of type 2 DM

Insulin Resistance• A core defect in type 2 diabetes – 92% of

patients with type 2 diabetes have insulin resistance

• Definition: Impaired response to the physiological effects of insulin, including those on glucose, lipid, protein metabolism and vascular endothelial functionHaffner SM, et al. Diabetes Care, 1999

Consensus Development Conference of the American Diabetes Association, Diabetes Care, 1997

Emerging Strategies Emerging Strategies

• Insulin acts like a key

• Sugar get into cell

• Lower blood sugar to normal

                                      

NormalIGTDM

Insulin secretion

Insulin resistance

NormalIGTDM

Insulin secretion

Insulin resistance

Insulin secretion

Insulin resistance

NormalIGTDM

Insulin secretion

Insulin resistance

NormalIGTDM

Diabetic complication• Acute diabetic complication• Chronic diabetic complication

Acute complication• Diabetic Ketoacidosis (DKA)• Hyperosmolar non-ketotic coma (HNKC)• Focal hyperglycemic seizure

Diabetic Ketoacidosis• Severe hyperglycemia (plasma glucose

>300 mg%)• Ketoacidosis

– Wide anion gap metabolic acidosis– Positive serum ketone

Hyperosmolar non-ketotic coma• Very severe hyperglycemia( plasma

glucose> 600 mg%)• Neurological change• Severe hyperosmolarity (serum

osmole>320mOsm/l)• No ketoacidosis

Focal hyperglycemic seizure• Severe hyperglycemia( plasma glucose>

300 mg%)• Seizure mostly focal seizure• Mild Hyperosmolarity (serum osmole

290-310mOsm/l)• No ketoacidosis

Chronic complication• Macrovascular complication• Microvascular complication

– Diabetic retinopathy– Diabetic nephropathy

• Diabetic neuropathy

National Diabetes Data Group. Diabetes in America. 2nd ed. NIH;1995.

Atherosclerosis in Diabetes

• ~80% of all diabetic mortality– 75% from coronary atherosclerosis– 25% from cerebral or peripheral

vascular disease• >75% of all hospitalizations for diabetic

complications

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Framingham Study: DM and CHD Mortality

20-Year Follow-up1717

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DMDM

Non-DMNon-DM

MRFIT – CV mortality increases withnumber of risk factors

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DiabetesNondiabetes

MRFIT: Multiple Risk Factor Intervention Trial

Thrombosis

PAI-1

Fibrinogen

C-reactiveprotein

FFADyslipidaemiaVLDL ( triglycerides)

HDL

Obesity

TNF-α

Lipaemia

Advanced glycation

end products

Geneticpredisposition

Hypertension

Hyper-insulinaemia

Pancreas

Liver

Adipo-cytes

Skeletal muscles

Glycatedprotein

Hyperglycaemia

Insulin resistance FFA

Libby P, et al. Circulation 2002;106:2760–63.FFA: free fatty acid; HDL: high-density lipoprotein, PAI: plasminogen activator inhibitor, TNF: tumour necrosis factor, VLDL: very low-density lipoprotein

Multiple mechanisms of vascular damage associated with dysglycaemia

Diabetic retinopathy• Most common cause of blindness in

developed country• Recommended to screen by fundoscopic

exam every year.• Improve glycemic and hypertensive control

are the best method to prevent DR

Diabetic retinopathy• Classification

– Non-proliferative DR– Proliferative DR– Proliferative DR with vitreous

Hemorrage or retinal detachment

Screening• Annual test for

– Type 1: duration more than 5 years– Type 2: ALL– Plan for or during pregnancy

Diabetic nephropathy• Most common cause of ESRD in developed

country• Recommended to screen urine for

microalbumin every year• Improve glycemic and hypertension

control are the best method to prevent DN

Diabetic nephropathy• Classification

– Microalbuminuria (30-300mg/day)– Macroalbuminuria( > 300 mg/day)– Renal insufficiency (serum Cr >2 mg/dl)– ESRD

Screening• Annual test for

– Type 1: duration more than 5 years– Type 2: ALL– Plan for or during pregnancy

Diabetic neuropathy• Discomfort and lead to serious

compliaction such as amputation.• Recommended to screening by test pinpick

and vibration sensation very year. However, those tests are not early diagnostic test.

Diabetic neuropathy• Distal Symmetrical Polyneuropathy• Autonomic neuropathy: postural

hypotension, neurogenic bladder, gastroparesis, diarrhea, impotent.

• Focal and multifocal neuropathy

Management• Diet control• Diabetic education• Drug

– Oral hypoglycemic agents– Insulin

Follow up• Glycemic control

– FPG– Glycosylated protein

• Fructosamine: 2-3 weeks• Hb a1c:2-3 months

Follow up• Chronic complication screening

– Urine microalbuminemia– Fundoscope– Sensation test– Lipid– EKG