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Abstract Non-insulin dependent diabetes mellitus (NIDDM) or Type 2 .diabetes is a common metabolic disorder with considerable morbidity and mortality, where obesity constitutes the major predisposing risk factor which is determined by both environmental and genetic factors. Obesity is strongly associated with NIDDM although the nature of the association is not clearly understood. Genetic screening programs to detect individuals at risk may help in prevention and or avoidance of diseases, therefore, analytic stratigies for performing genome screening for NIDDM susceptibility genes need .to be addressed. The aim of this work was to study genes predisposition to diabetes mellitus among families of non-insulin dependent diabetic patients in a trial to find the genes responsible for causation of type 2 diabetes mellitus. Twenty five subjects with non-insulin dependent diabetes mellitus were selected with his or her partner free from diabetes and had offsprings. The subjects and their partners and their offsprings collecively were one hundred and four individuals, to all of them, full medical history, full clinical examination, plain x-ray chest & heart, resting E.C.G’H abdominal ultrasonography and fundus examination were done. The following investigations were done: stool & urine analysis, full blood picture, fasting and postprandial blood glucose level, serum insulin -<A 226 It#- SUMMARY level, liver and kidney functions, serum sodium and potassium, lipidogram which include total lipids, cholesterol, triglyceride and screening of three genes: Obesity gene, Hepatocyte Nuclear Factor-4 a gene and Glycogen Synthase gene which represents a predispose genes for diabetes mellitus. Oral glucose tolerance test was done to the susceptible offsprings who had one or more genes predispose to diabetes mellitus. The results of this work showed that: • The prevalence of diabetes among the studied families was more in middle age (P < 0.05). • There was no sex predominance of diabetes (P > 0.05). • The disease was more in families with past history of diabetes (P<0.05). • Diabetics had Increase in their body mass index when compared with non-diabetics (P < 0.05). • Diabetics had increase in the mean of systolic & diastolic blood pressure, serum insulin level, serum uric acid level, serum cholesterol & serum triglyceride levels when compared with non-diabetics (P<O.O 1 & P < 0.05). • The presence of bp < 125 in marker D78680 and bp < 153 in marker D78514 of the OB gene denoting us that the individuals is lean since these bps were statistically highly significance in lean when compared with obese (P < 0.01) and were statistically significance in lean diabetics when compared with obese diabetics (P < 0.05). • The presence of bp > 129 in marker D78680 and bp > 155 in marker D7S514 of the OB gene denoting us that the individuals is obese since these bps were statistically highly significance in obese .q.227 IDe SUMMARY when compared with lean (P < 0.01) and were statistically significance in obese diabetics when compared with lean diabetics (P < 0.05). • The presence of allele A 1 of the glycogen synthase was statistically significance in lean and in non-diabetics when compared with obese and diabetics (P < 0.05). • The presence of allele A2 of the glycogen synthase was statistically significance in obese and in diabetics when compared with lean and non-diabetics (P < 0.05). • There was mutation in exon 8 and in exon 4 of the Hepatocyte Nuclear Factor 4-0. gene where mutation of exon 8 was statistically significance in diabetics when compared with non-diabetics (P < 0.05) and in obese diabetics when compared with lean diabetics (P<0.05), while mutation of exon 4 was statistically significance in obese diabetics when compared with obese-non diabetics (P<O.05). • Mutation in exon 4 of the HNF-4o. gene occur in MODY mothers and in their first offspring who had impaired oral glucose tolerance test. So, the first offspring of the family with diabetes is a risk individual for susceptibility of developing diabetes mellitus in the future. • The presence of: a- bp > 129 in marker D7S680. b- A2 allel of the GYS 1 gene. c- Mutation of exon 4 or exon 8 of the HNF-40. gene, denote that the offsprings predispose to obesity and diabetes. |