INSULIN SECRETION IN NON-OBESE NIGERIANS (effect of glucose, sulphonylureas and weight reduction

Abstract

Protein calorie malnutrition in man and experimental animals produces striking changes in the pancreas; and clinically, protein deficiency has been shown to diminish exocrine pancreatic secretions in addition to the histological changes in the pancreas. The effects of this in childhood and the subsequent effects in adulthood are not clear but certain observations made on carbohydrate tolerance and metabolism in adult Africans are relevant. These raised a number of questions which have been investigated in this thesis by the administration of sulphonylurea drugs of different potency to study their relative insulinogenic effects, their particular stimulatory effects given orally and intravenously, with and without glucose; and the effect of obesity on insulin secretion. 45 normal adult individuals were studied with oral sulphonylureas, 52 with intravenous sulphonylurea and 23 were in the obese group. The insulinogenic response of the obese group to glucose was studied in a cross-over clinical trial of fenfluramine and placebo before and after weight reduction. The study confirm that notwithstanding certain known differences in blood glucose and insulin levels in normal Nigerians, the responses to oral sulphonylureas are similar to those in non-African subjects. However, the Ngerians fell into the group of slow absorbers of sulphonylureas. The oral hypoglycaemic sulphonylureas increased insulin secretion through the normal physiological stimulus of glucose and in addition had possible extrapancreatic effects associated with a lowering of blood glucose without a rise in serum insulin. The study tends to confirm the extrapancreatic effect of sulphonylureas, in particular in normal subjects given the short-acting preparations acutely and at doses that are also therapeutic. Glutril gave an earlier but non-persistent hypoglycaemic effect whilst Daonil a more prolonged hypoglycaemic effect. No adverse effects, in particular, clinical hypoglycaemia were however observed in spite of the marked lowering of blood glucose. Although Nigerian subjects studied responded promptly and adequately to a standard intravenous tolbutamide test, a delay in return of blood sugar to fasting level was characteristic. An early return of the serum insulin to fasting level was observed and this was most likely due to a lower peak insulin level. Where a relatively better insulin response occurred, the return to fasting level occurred later. The combined effect of intravenous tolbutamide and oral glucose given simultaneously at 0 hour compared to the combined administration of tolbutamide and glucose, intravenously at 0 hour showed that in spite of the initial massive glycaemic stimulus in the latter group, overall insulin production over the period of 240 minutes judged by the total area of the curves is greater in the former. Peak insulin secretion at 15 minutes was greater where intravenous tolbutamide was combined with oral or intravenous glucose than when given alone. This different appears to be the summed effect of glucose and tolbutamide. The administration of intravenous glucose at 120 minutes following intravenous tolbutamide at 0 hour produced no Increase in serum insulin at 180 minutes in contrast to when glucose was given orally at 120 minutes; thus indicating that the insulinogenic effect of the intravenou glucose was short lived. The serum insulin concentration at 30 minutes following intravenous tolbutamide was 200 percent of the basal level and 130 percent following intravenous glucose -a relationship which is the reverse of the finding in a study of non-Africans by Yalow et al. (1960). Since the observations made from the insulin response to intravenous tolbutamide in the Nigerians did not show much disparity from studies elsewhere, this response to intravenous glucose is to be considered inadequate. In the obese, eighteen (82%) of the twenty-two subjects with complete insulin and glucose results had impaired carbohydrate tolerance initially and nineteen (86%) had abnormal insulin responses to oral glucose load. Sixteen subjects (73%) had both an abnormal glucose tolerance and insulin response, whilst three had only an abnormal glucose tolerance. Thus of the twenty two subjects, only one was free of any abnormality in both the glucose tolerance and the insulin response. These observations suggest a high incidence of asymptomatic or subclinical diabetes, and support the generally accepted concept of impairment in carbohydrate metabolism in the obese. In spite of the high incidence of abnormality in insulin response to oral glucose, and the significant weight educing effect of fenfluramine, in none of the subjects was there a significant difference in the insulin responses to glucose load during either fenflaramine or placebo drug therapy. Since weight reduction was achieved without the restriction of dietary intake, the known high carbohydrate intake of Nigerians might be suggested as one of the common factors responsible for the pattern of insulin response of the obese as well as the non-obese.