R. Niththyananthan

The relationship of insulin insensitivity to menstrual pattern in women with hyperandrogenism and polycystic ovaries

OBJECTIVE Insulin insensitivity is a recognized feature of polycystic ovary syndrome (PCOS) but previous studies have suggested that circulating insulin concentrations are normal in hyperandrogenaemic women with regular cycles. The aim of this study was to examine the relationship between insulin sensitivity and menstrual pattern in women with PCO.

Dyslipidaemia is associated with insulin resistance in women with polycystic ovaries

OBJECTIVE Polycystic ovary syndrome (PCOS) is characterized by hyperinsulinaemia and insulin resistance. Previous reports of lipid abnormalities in the syndrome have produced conflicting results which may, in part, be related to the lack of appropriate controls for the obese women with PCOS. Only one study has related lipid levels to insulin sensitivity. The objective of this study was to assess lipids and lipoproteins in women with PCOS, to compare the results with weight matched controls, and to relate the findings to indices of insulin secretion and action, and to menstrual history.

Validation of the low dose short insulin tolerance test for evaluation of insulin sensitivity.

OBJECTIVES The assessment of insulin sensitivity requires an accurate and reproducible technique. The short insulin tolerance test is a simple and rapid method for screening large numbers of subjects when the fasting glucose level is normal. Conventionally, an insulin dose of 0·1 units/kg is used, but this may result in symptomatic hypoglycaemia in healthy thin subjects who are insulin sensitive. In order to overcome this problem we have employed a lower dose of insulin and have studied the reproducibility of this modified technique comparing it with the euglycaemic hyperinsulinaemic clamp.

Effect of glucocorticoid replacement therapy on glucose tolerance and intermediary metabolites in hypopituitary adults

BACKGROUND AND OBJECTIVES Excess Impaired glucose tolerance and diabetes mellitus have been reported in hypopituitary adults on conventional replacement therapy Including glucocorticoids. We investigated the effect of the glucocorticoid component on glucose tolerance and intermediary metabolites in hypopituitary adults.

Overnight metabolic fuel deficiency in patients treated conventionally for hypopituitarism

BACKGROUND Hormone replacement in hypopituitary adults attempts to reproduce normal physiology. Conventional regimens fail to mimic normal hormone profiles over 24 hours.

Insulin resistance with respect to lipolysis in non-diabetic relatives of European patients with type 2 diabetes

Type 2 diabetes is characterized by resistance to insulin action of glucose metabolism and lipolysis. First‐degree relatives of diabetic patients are at increased risk of developing diabetes themselves and early metabolic abnormalities in these relatives may represent primary defects in the pathogenesis of diabetes. Our previous work has demonstrated impaired suppression of lipolysis after an oral glucose load in glucose‐tolerant relatives of Asian origin, but not in European relatives. To investigate whether a more subtle defect exists in the European population we studied 8 first‐degree relatives of European patients and 9 matched control subjects. All had normal glucose tolerance. Glycerol and glucose turnovers were measured using a primed constant infusion of the stable isotopic tracers [1, 1, 1, 2, 32H5] glycerol and [6, 62H] glucose, basally and in response to a very low dose insulin infusion (0.005 units kg‐1 h‐1). The relatives had higher basal insulin concentrations (median (range): 49 (30 to 113) vs 28 (18 to 66) pmol 1‐1, p < 0.05) compared to controls, but basal glycerol and glucose turnovers and plasma concentrations of glycerol, glucose, and non‐esterifed fatty acids (NEFA) were similar. Following insulin, the suppression of glycerol appearance in the circulation measured isotopically was significantly less complete in the relatives compared with controls (mean change ± SEM: + 0.06 ± 0.21 vs ‐0.51 ± 0.16 μmol kg‐1 min‐1, p < 0.05). Plasma glycerol concentration decreased to a similar extent in relatives and controls, as did glucose and NEFA levels (mean change ± SEM: glycerol ‐12 ± 3 vs ‐8 ± 4 μmol 1‐1; glucose ‐0.37 ± 0.06 vs ‐0.30 ± 0.10 mmol.l‐1; NEFA ‐152 ± 48 vs ‐130 ± 32 μmol.1‐1). The change in glucose turnover was not different in relatives and controls (change ‐0.10 ± 0.03 vs ‐0.07 ± 0.06 mg kg‐1 min‐1). We conclude that glucose‐tolerant relatives of European origin exhibit subtle defects in insulin sensitivity with respect to lipolysis.

Insulin sensitivity in non-diabetic relatives of patients with non-insulin-dependent diabetes from two ethnic groups

OBJECTIVE Non‐insulin‐dependent diabetes is a heterogeneous disorder, the basis of which may differ in different ethnic groups. In order to investigate early metabolic abnormalities occurring during the development of the condition we assessed insulin secretion and insulin action in subjects predisposed to the later development of non‐insulin‐dependent diabetes from two different ethnic groups.

Increased secretion of 32,33 split proinsulin after intravenous glucose in glucose‐tolerant first‐degree relatives of patients with non‐insulin dependent diabetes of European, but not Asian, origin

OBJECTIVE The aetiology of non‐Insulin dependent diabetes Is unknown, but defective insulin Secretion is a feature. The disease also has a strong genetic basis and first‐degree relatives of patients have an increased risk of future diabetes. To investigate whether β‐cell dysfunction is an early feature of the disease, we studied insulin secretion In healthy first‐degree relatives of patients with non‐insulin dependent diabetes.

Fetal Proinsulin and Birth Weight

In both diabetic and non‐diabetic pregnancies fetal insulin is an important anabolic hormone. Fetal hyperinsulinaemia is associated with accelerated fetal growth and increased birth weight. Insulin and C‐peptide concentrations in both umbilical cord and amniotic fluid reflect fetal β‐cell secretion and are correlated with birth weight. In the present study umbilical venous proinsulin and insulin concentrations were measured in 54 term infants born to women with and without mild disturbances of glucose tolerance. Umbilical venous cord proinsulin, assayed using a highly specific immunoradiometric assay, was independently correlated with infant birth weight (Rho = 0.53, p ± 0.0001) and birth percentile (Rho = 0.65, p ± 0.0001). The correlation between birth weight and birth percentile weight with umbilical venous insulin, measured using a non‐specific insulin assay, was lost following correction for the influence of proinsulin. Umbilical venous cord proinsulin appears to be a good indicator of fetal β‐cell activity, and in this study, a superior marker to insulin assayed using a non‐specific insulin radioimmunoassay. The longer half‐life of proinsulin compared with insulin may contribute to proinsulin being a more robust marker of overall fetal β‐cell activity than insulin.

Reduced postprandial energy expenditure in women predisposed to type 2 diabetes.

Type 2 (non‐insulin dependent) diabetes is so common that it has been hypothesized that in the course of evolution the predisposition to it may have conferred some advantage, before or during the reproductive years. It is frequently preceded by gestational diabetes. In order to test the basis for the hypothetical advantage, energy expenditure was investigated in 10 women with documented transient diabetes in a previous pregnancy. They were studied early in a subsequent pregnancy while glucose tolerance was still normal and 9 were re‐studied after pregnancy. Their results were compared with normal matched controls. During pregnancy, resting energy expenditure was similar in the study group and controls (6.58 (5.77–7.55) median (range) vs 6.91 (6.56–7.36) MJ day‐1, respectively). However, the energy response to a mixed meal (42 kJ kg‐1 lean body mass) was decreased in the study group (45 (33–68) vs 76 (50–89) kJ, p<0.05). After pregnancy resting energy expenditure was again similar in the two groups, but the decrease in postprandial thermogenesis persisted (78 (59–84) vs 92 (79–105) kJ, p<0.05). The patients were resistant to exogenous insulin, 0.05 U kg‐1 intravenously (slope of the plasma glucose decline in the 15 min after insulin; during pregnancy patients 52 (37–92) vs controls 111 (104–121) μmol l‐1 min‐1, p<0.01; after pregnancy 130 (88–156) vs controls 186 (152–221) μmol l‐1 min‐1, p<0.01). The postprandial energy saving in these women could constitute an evolutionary advantage. Insulin resistance may be the mechanism for limiting postprandial thermogenesis.