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Summary and conclusionSummaryThe early phase of insulin secretion promotes peripheral utilization of the prandial nutrient load,suppresses hepatic glucose production and limits postprandial glucose elevation(Melissa,2004).Convergent data suggest that early phase insulin secretion has a pivotal role in moving the metabolism from the fasting to the prandial state (Pierre,2004).With evidence now suggesting that β-cell dysfunction is an early and important underlying cause of type 2 diabetes, restoring the physiological pattern of insulin secretion could be a major treatment objective (Efendic,2004).The availability of restoring prandial glucose regulation with oral therapy has established itself as an antidiabetic agent that is highly effective when used in flexible mealtime regimens (Gerber, 2002).This work aimed to study the early phase insulin secretion in subjects at risk of type 2 DM and those with recently diagnosed type 2 DM and the effect of some oral hypoglycemic medications (metformin, repaglinide and glipizide) on the early phase insulin secretion in diabetic group.This study included 50 subjects,10 subjects have +ve family history of type 2DM, 10 obese non diabetics,20 recently diagnosed type 2 diabetics(7 were treated with metformin, 6 with repaglinide and 7 with glipizide) and 10 lean subjects served as controls.*** The results showed:The early phase insulin secretion (Insulinogenic Index) was significantly lower in diabetic groups and at risk groups compared to the control group.After 24 months,despite life style modification has been adviced,no improvement could be achieved in the at risk groups,moreover the early phase secretions showed a significant decrease compared to baseline study.On the other hand a significant improvement was seen in diabetic patients treated with either repaglinide or glipizide compared to baseline,while metformin showed a non beneficial effect on early phase insulin secretion.A significant increase in fasting plasma insulin and insulin resistance (expressed by HOMA-IR) in the risky group as reflected by increasing delta of change after 24 months,despite standard life style modification.Significant improvement in insulin resistance was found with glipizide and metformin then repaglinide,as reflected by decreasing delta of change in comparison with the other groups(P<0.001).Deterioration in all glycemic parameters specially the post prandial plasma glucose was seen in the risky groups as reflected by increasing delta of change after 24 months in comparison with other groups.This deterioration was significantly correlated with the decreased early phase insulin secretion in these groups.Patients treated with either metformin or repaglinide showed a significant improvement in both Hb A1c and post prandial plasma glucose by the 24th month,however glipizide had a significant beneficial effect on improving fasting plasma glucose compared to both metformin and repaglinide.Significant deterioration in some lipid parameters (Total cholesterol and TG) after 24 months was seen in the at risk groups as reflected by delta of change in comparison to other groups,with significant negative correlation between the delta of change of total cholesterol and TG and the delta of change of the early insulin secretion in all groups.Repaglinide showed the most favourable effect on lipids by reducing the total cholesterol and LDL and by by improving HDL ( p<0.05 for both parameters).But metformin showed the most beneficial reducing effect on TG in comparison with the baseline values (P<0.05).Maximum weight reduction was achieved with metformin while glipizide showed modest weight gain.***ConclusionDiminution of first phase insulin release is detected in individuals at risk of developing type 2DM and progressive reduction in this phase are present in them even without overt hyperglycemia.Standard diet and exercise program in subjects at risk of developing type 2 diabetes are not beneficial to delay or prevent the progression to type 2 DM.Enhancement of the early phase insulin secretion in recently discovered type 2DM is achieved with repaglinide and glipizide and this enhancement was asociated with significant improvement in glycemic control,insulin resistance and lipid control.*** RecommendationsØ First phase insulin secretion should be assessed in all subjects at risk of developing type 2 DM and restoration of the physiological pattern of insulin secretion by strict life style modification (diet and exercise) or even pharmacotherapy could be a major treatment objective for these subjects.Ø Long term prospective study on large number of subjects is needed to evaluate the long-term effect of different classes of drugs,as a monotherapy or combination therapy,on early insulin secretion in diabetic patients .
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