המנגנונים הקשורים בהתפתחות הסוכרת: ממחקר ליישום בבריאות האדם. אהוד זיו, היח' לסוכרת, הדסה עין כרם.

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Presentation transcript:

המנגנונים הקשורים בהתפתחות הסוכרת: ממחקר ליישום בבריאות האדם. אהוד זיו, היח' לסוכרת, הדסה עין כרם.

סוכרת המשותף לכל סוגי הסוכרת: היפרגליקמיה כרונית.

שני סוגי הסוכרת הנפוצים ביותר: Type 1 diabetes mellitus (IDDM - Insulin Dependent Diabetes Mellitus) (Juvenile diabetes) Type 2 diabetes mellitus (NIDDM - Non-Insulin Dependent Diabetes Mellitus) (Adult onset diabetes)

Normal physiology of glucose homeostasis hepatic glucose production and storage of glycogen Insulin-stimulated glucose uptake Regulation of lipolysis Adipose tissue Carbohydrate Blood Glucose Digestive enzymes Gut Pancreas Muscle Liver Insulin

HOMA=homeostasis model assessment. UKPDS Group. Diabetes 1995;44:1249―58. Adapted from Holman RR. Diabetes Res Clin Pract 1998;40(suppl 1):S21 ― 5. Decline of  -cell function determines the progressive nature of T2DM  -cell function (% of normal by HOMA) Time (years) ― 10 ―8―8―6―6―4―4―2―20246 Time of diagnosis ? Pancreatic function = 50% of normal

Excessive hepatic glucose production is the main cause of fasting hyperglycaemia Adapted from DeFronzo R. Diabetes 1988;37:667  87. Fasting plasma glucose (mmol/l) Fasting plasma glucose (mg/dl) r=0.847 p<0.001 Hepatic glucose production (mg/kg.min) Normal (n=73) T2DM (n=77) Normal range

Insulin resistance Adipose tissue Carbohydrate Blood Glucose Digestive enzymes Gut Pancreas Muscle Liver Insulin Excess glucose production Decreased insulin-dependent glucose uptake Excessive fat breakdown leading to increase in free fatty acids Compensatory increase in insulin secretion

תנגודת לאינסולין - Insulin resistance תגובת חסר של הרקמות לאינסולין. אי סבילות לאינסולין. אפקט ביולוגי מוקטן לאינסולין אנדוגני (ממקור פנים-גופי) או ממקור חיצוני.

The natural history of insulin resistance, progressing from impaired glucose tolerance to overt type 2 diabetes.

Fig. 1: Numbers of people with diabetes (in millions) for 2000 and 2010 (top and middle values, respectively), and the percentage increase. Zimmet et al, Nature, 414: , 2001.