Background The role of adiponectin, tumour necrosis factor α (TNFα), leptin and C-reactive protein in the insulin resistance of pregnancy is not clear. We measured their levels in women with gestational diabetes (GDM) and in controls, during and after pregnancy, and related them to insulin secretion and action.

20 normoglycemic first degree relatives of non-insulin-dependent diabetes mellitus (NIDDM) patients were compared with 20 matched subjects without any family history of diabetes using the intravenous glucose tolerance test with minimal model analysis of glucose disappearance and insulin kinetics. Intravenous glucose tolerance index (Kg) was similar in both groups (1.60±0.14 vs 1.59±0.18, x 10-2 minm-, NS). However, insulin sensitivity (Si) was reduced (3.49±0.43 vs 4.80±0.61, x 10-4 mind per mU/liter, P = 0.05), whereas glucose effectiveness (Sg) was increased (1.93±0.14 vs 1.52±0.16, X 10-2 min-, P < 0.05) in the relatives. Despite insulin resistance neither fasting plasma insulin concentration (7.63±0.48 vs 6.88±0.45, mU/liter, NS) nor first phase insulin responsiveness (Phil) (3.56±0.53 vs 4.13±0.62, mU/liter min' per mg/dl, NS) were increased in the relatives. Phil was reduced for the degree of insulin resistance in the relatives so that the Phil x Si index was lower in the relatives (11.5±2.2 vs 16.7±2.0, x 10-4 min 2 per mg/dl, P < 0.05). Importantly, glucose effectiveness correlated with Kg and with basal glucose oxidation but not with total glucose transporter 4 (GLUT4) content in a basal muscle biopsy. In conclusion we confirm the presence of insulin resistance in first degree relatives of NIDDM patients. However, insulin secretion was altered and reduced for the degree of insulin resistance in the relatives, whereas glucose effectiveness was increased. We hypothesize that increased glucose effectiveness maintains glucose tolerance

Fourteen GH-deficient (GHD) adults were compared with 12 age-, sex-, and body mass index-matched control subjects using a baseline tritiated glucose equilibration period and euglycemic-hyperinsulinemic (approximately 55 mU/L) clamp in conjunction with paired muscle biopsies for measurement of glycogen synthase fractional velocity (FV0.1). Despite similar basal rates of total glucose disposal (Rd), there was a 64% reduction in the insulin-stimulated rise (delta) in Rd in the GHD adults compared to that in controls [16.6 +/- 2.8 vs. 44.7 +/- 6.0 mumol/kg fat free mass (FFM)/min; P < 0.001], which was mainly due to a decreased glucose storage (GS) rate (delta GS, 12.6 +/- 2.9 vs. 39.5 +/- 7.5 mumol/kg FFM/min; P < 0.01). Furthermore, the insulin sensitivity indexes of Rd (0.39 +/- 0.07 vs. 0.85 +/- 0.11; P < 0.05) and GS (0.25 +/- 0.07 vs. 0.72 +/- 0.13 mumol/kg FFM/min per mU/L; P < 0.02) were reduced in GHD adults compared to the control values. The insulin sensitivity of the glycolytic pathway was also reduced by approximately 50% in GHD adults (P = 0.07 vs. controls). Insulin-stimulated FV0.1 was decreased in GHD adults (0.31 +/- 0.02 vs. 0.47 +/- 0.03; P < 0.005) despite similar basal FV0.1. Using multiple and stepwise regression analysis, duration of GH deficiency, fasting triglycerides and fasting insulin accounted for 67% of the variance in the insulin sensitivity index of Rd. In conclusion, the severe insulin resistance in GHD adults is mainly due to the inhibition of the GS pathway and glycogen synthase activity in peripheral tissues, which is related to the duration of GH deficiency, fasting triglycerides, and fasting insulin.

Both insulin secretion and insulin sensitivity are important in the development of diabetes but current methods used for their measurements are complex and cannot be used for epidemiological surveys. This study describes a simplified approach for the estimation of first phase insulin release and insulin sensitivity from a standard 40-min intravenous glucose tolerance test (IVGTT), and compares these parameter estimations with the sophisticated minimal model analysis of a frequently sampled 3-h IVGTT and the euglycaemic clamp technique. For the simplified IVGTT, first phase insulin release was measured as the insulin area above basal post glucose load unit-1 incremental change (i.e. peak rise) in plasma glucose over 0-10 min, and insulin sensitivity as a rate of glucose disappearance (Kg) unit-1 insulin increase above basal from 0-40 min post-glucose load in 18 subjects who were studied twice, either basally or in a perturbed pathophysiological state (i.e. pre- and post-ultramarathon race, n = 5; pre- and post-20 h pulsatile hyperinsulinaemia, n = 8; pre- and post-thyrotoxic state, n = 5). A further 12 subjects were compared by IVGTT, and glucose clamp. In addition, seven dogs were studied three times by IVGTT during normal saline infusion and after short-term (1/2 hour) or long-term (72 hour) adrenaline infusions. First phase insulin release and insulin sensitivity estimated from the simplified IVGTT as calculated by the two methods correlated closely (rs = 0.89 and rs = 0.87, respectively), although less precisely in markedly insulin-resistant subjects and the slopes and y intercepts of the linear regression lines were similar in the basal and perturbed states.(ABSTRACT TRUNCATED AT 250 WORDS)

Cirrhosis of the liver is frequently associated with carbohydrate intolerance but it is unknown whether this intolerance is due to increased hepatic glucose production (HGP), decreased glucose utilization, or both. HGP and the MCR of glucose [(MCR)G] were measured at steady state, basally and during an infusion of insulin (25 mU/kg x h) and glucose (11 mumol/kg x min), in 11 cirrhotics and 8 controls using the technique of a primed constant infusion of [3H]3-glucose. HGP was also estimated at nonsteady state during an infusion of glucagon (8 ng/kg x min). Basal HGP was significantly lower in cirrhotics compared to controls (10.2 +/- 0.6 vs. 13.2 +/- 0.6 mumol/kg x min; P < 0.0025). During the insulin/glucose infusion, HGP was suppressed to the same degree in both groups [in controls by 83% (13.2 +/- 0.6 to 2.2 +/- 0.8 mumol/kg x min) and in cirrhotics by 87% (10.2 +/- 0.6 to 1.3 +/- 0.4 mumol/kg x min)]. After the glucagon infusion, HGP rose by a similar degree in cirrhotics and controls. In contrast, basal (MCR)G was significantly lower in the nondiabetic cirrhotics (2.1 +/- .02 ml/kg x min; P < 0.005) and diabetic cirrhotics (1.2 +/- 0.2 ml/kg x min; P < 0.0005) compared to that in the control subjects (2.8 +/- 0.2 ml/kg x min). Moreover, there was a highly significant (P < 0.001) negative correlation between basal (MCR)G and the fasting glucose level (r = 0.82), and the degree of glucose intolerance as expressed by the 2-h glucose level determined by the oral glucose tolerance test (r = 0.87). It is concluded that the glucose intolerance of cirrhosis is due to a defect in peripheral glucose utilization.