[Insulin resistance and insulin secretion in type II non-obese diabetics].

BACKGROUND

Glucose tolerance depends essentially on insulin secretion and its action in target tissues. Diabetes mellitus type II (insulin-nondependent diabetes) is a disease conditioned by a dysbalance between insulin secretion and effect; it has not been decided whether the cause is insulin resistance or impaired insulin secretion, although a defect of insulin secretion for the manifestation of the disease is generally accepted. The purpose of the submitted study was to assess to what extent insulin secretion and its effect after an oral glucose load and a hyperglycaemic clamp is affected in different groups of non-obese patients with diabetes type II.

METHODS AND RESULTS

The authors examined 21 men with diabetes type II (age 41 +/- 2.6 years, BMI 26.2 +/- 3.2, HbA1,c 9.4 +/- 2.9%) in the course of one year after detection of the disease, treated by diet alone. The second group was formed by 20 patients with diabetes type II (age 46.1 +/- 3.6 years, BMI 26.0 +/- 2.1, HbA1,c 6.94 +/- 1.6%) who suffered from diabetes for 5-10 years and who were treated by diet alone. The third group was formed by 32 diabetics type II (age 51.8 +/- 6.1 years, BMI 26.7 +/- 2.2, HbA1,c 8.7 1.2% +/-) who suffered from diabetes for 5-10 years and were treated with oral antidiabetics. The control group was formed by 42 healthy men matched for body weight and age (age 39.9 years, BMI 25.3, blood sugar level 4.8 mmol/l). Although the diabetic groups did not differ in the fasting blood sugar level (8.0-8.29-8.2 mmol/l), the glycosylated haemoglobin HbA1,c level is lowest in the group of diabetics treated by diet alone, similarly as the rise of the blood sugar level 120 mins, following oral administration of 75 g of glucose (10.3 mmol/l, as compared with 16.2 mmol/l and 15.5 mmol/l in the other groups). The authors found in all groups of diabetic patients, as compared with controls, a comparable drop of the insulin effect evaluated as the metabolic glucose clearance during an hyperinsulinaemic euglycaemic (5 mmol/l) or isoglycaemic (fasting blood sugar level) clamp, the insulin level being 75 microU/ml (controls 10.9 +/- 3.3 ml/kg.min., first group 5.35 +/- 2.7 ml/kg.min., second group 5.47 +/- 2.35 ml/kg.min., third group 5.38 +/- 2.1 ml/kg.min. The differences, as compared with controls, were significant in all groups, p < 0.01). At an insulin level of 1500 microU/ml the results are similar (controls 17.4 +/- 3.8 ml/kg.min., as compared with 13.3 +/- 3.3 in the first group, 13.3 +/- 3.0 in the second group and 12.5 +/- 3.0 ml/kg.min. in the third group: statistical significance in all three groups, as compared with controls, is p < 0.05). The authors did not reveal any differences in the specific insulin bond to insulin receptors of erythrocytes. The total glucose consumption during an isoglycaemic clamp in diabetics and a euglycaemic clamp in controls did not differ. In all diabetic groups, as compared with controls, higher C peptide values and insulin values (IRI) were found on fasting and a slower rise and longer persistence of higher levels after oral glucose administration, although an inadequate secretory response during the hyperglycaemic clamp in diabetics is apparent. Hyperinsulinism was significantly higher in the second group. The number of insulin receptors on erythrocytes, the affinity for insulin, regardless whether the receptors were free or occupied, did not differ significantly between groups.

CONCLUSIONS

All investigated groups of type II diabetics had a comparable degree of insulin resistance which did not depend on the duration of diabetes, its compensation or the type of treatment. Although impaired insulin action was proved, the total glucose utilization in relation to hyperglycaemia is not reduced. The differences in the degree of glucose intolerance in the investigated groups of diabetics type II depend on the degree of impairment of insulin secretion.