IS BETA CELL DYSFUNCTION RESPONSIBLE FOR FLAT GLUCOSE TOLERANCE CURVE IN PRIMARY HYPOTHYROIDISM? (A HYPOTHESIS)

An intimate relationship between thyroid hormones and carbohydrate metabolism has long been recognised and oral glucose load produces flat glucose tolerance curve in patients with primary hypothyroidism. Although delayed glucose absorption was proposed to explain flat glucose tolerance curve exact mechanism remains to be elucidated. Hence this study was undertaken to assess glucose and insulin response to OGTT and IVGTT in 25 freshly detected cases of hypothyroidism and 25 healthy control. The cases were matched for sex, age, BMI, and waist hip ratio with controls. Cases and controls with past or family history of obesity, diabetes mellitus, or hypertension were excluded from study. The biochemical profile of the cases and controls was also comparable except for haemoglobin (11.2±0.31 vs 12.9±0.22 gm/dl)(p=0.0004). Serum cholesterol and triglyceride levels were higher in the cases but difference was not statistically significant Fasting plasma glucose level was significantly lower in hypothyroid patients (78±2.2 vs88±4.4 mg/dl, p=0.049). The oral glucose tolerance curve was flat with plasma glucose levels significantly lower at 30 minutes. The insulin levels during OGTT were found to be higher in the cases at all stages. There was loss of first phase insulin response to the glucose load during the IVGTT, which was blunted at all stages and the difference was statistically significant at 0 and 3 minutes. Loss of first phase insulin response to IV glucose suggests that there is evidence of beta-cell dysfunction. Patients with hypothyroidism were more insulin sensitive than control and insulin secretion was comparable with controls. Therefore flat glucose tolerance curve can be explained by absence of insulin priming effect leading to decreased glucose absorption followed by increased glucose disposal because of higher insulin levels following OGTT and increased glucose disposal caused by increased insulin sensitivity.