A b b re v i a t i o n s : AUC, area under the curve; 1st PH, first-phase insulin release; Gluc, plasma glucose concentration during the OGTT; HOMA, homeostasis model assessment; IGT, impaired glucose tolerance; Ins, plasma insulin concentration during the OGTT; IR, insulin resistance index; ISI, insulin sensitivity index; ISI(comp), composite insulin sensitivity index; MCR, metabolic clearance rate; NGT, normal glucose tolerance; OGTT, oral glucose tolerance test; 2nd PH, second-phase insulin release; Secr, insulin release index; SI, sensitivity index; S y x , residual error of re g ression; WHR, waist-to-hip ratio.A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Use of the Oral Glucose Tolerance Test to Assess Insulin Release and Insulin S e n s i t i v ity O R I G I N A L A R T I C L E O B J E C T I V E -The oral glucose tolerance test (OGTT) has often been used to evaluate a p p a rent insulin release and insulin resistance in various clinical settings. However, because insulin sensitivity and insulin release are interdependent, to what extent they can be pre d i c t e d f rom an OGTT is unclear.RESEARCH DESIGN AND METHODS -We studied insulin sensitivity using the euglycemic-hyperinsulinemic clamp and insulin release using the hyperglycemic clamp in 104 nondiabetic volunteers who had also undergone an OGTT. Demographic parameters (BMI, waist-to-hip ratio, age) and plasma glucose and insulin values from the OGTT were subjected to multiple linear re g ression to predict the metabolic clearance rate (MCR) of glucose, the insulin sensitivity index (ISI), and first-phase (1st PH) and second-phase (2nd PH) insulin release as measured with the respective clamps. R E S U LT S -The equations predicting MCR and ISI contained BMI, insulin (120 min), and glucose (90 min) and were highly correlated with the measured MCR (r = 0.80, P 0 . 0 0 0 0 5 ) and ISI (r = 0.79, P 0.00005). The equations predicting 1st PH and 2nd PH contained insulin (0 and 30 min) and glucose (30 min) and were also highly correlated with the measured 1st PH (r = 0.78, P 0.00005) and 2nd PH (r = 0.79, P 0.00005). The parameters predicted by our equations correlated better with the measured parameters than homeostasis model assessment for secretion and resistance, the 30-min insulin/ 30-min glucose ratio for secretion and insulin (120 min) for insulin resistance taken from the OGTT. C O N C L U S I O N S E p i d e m i o l o g y / H e a l t h S e r v i c e s / P s y c h o s o c i a l R e s e a r c h 296DIABETES CARE, VOLUME 23, NUMBER 3, MARCH 2000Insulin release and insulin sensitivity 0.5 kg/m 2 (19.7-45.8), and waist-to-hip ratio (WHR) 0.84 ± 0.10 (0.67-1.03); 65 had normal glucose tolerance (NGT), and the remainder had impaired glucose tolerance (IGT) according to the World Health O rganization criteria (1). Within 2 months, all subjects underwent a 75-g OGTT, a h y p e rglycemic clamp study in which the a rterialized venous plasma glucose concentration was increas...

Insulin resistance plays an important role in the pathogenesis of type 2 diabetes; however, the multiple mechanisms causing insulin resistance are not yet fully understood. The aim of this study was to explore the possible contribution of intramyocellular lipid content in the pathogenesis of skeletal muscle insulin resistance. We compared insulin-resistant and insulin-sensitive subjects. To meet stringent matching criteria for other known confounders of insulin resistance, these individuals were selected from an extensively metabolically characterized group of 280 first-degree relatives of type 2 diabetic subjects. Some 13 lean insulin-resistant and 13 lean insulin-sensitive subjects were matched for sex, age, BMI, percent body fat, physical fitness, and waist-to-hip ratio. Insulin sensitivity was determined by the hyperinsulinemic-euglycemic clamp method (for insulin-resistant subjects, glucose metabolic clearance rate [MCR] was 5.77+/-0.28 ml x kg(-1) x min(-1) [mean +/- SE]; for insulin-sensitive subjects, MCR was 10.15+/-0.7 ml x kg(-1) x min(-1); P<0.002). Proton magnetic resonance spectroscopy (MRS) was used to measure intramyocellular lipid content (IMCL) in both groups. MRS studies demonstrated that in soleus muscle, IMCL was increased by 84% (11.8+/-1.6 vs. 6.4+/-0.59 arbitrary units; P = 0.008 ), and in tibialis anterior muscle, IMCL was increased by 57% (3.26+/-0.36 vs. 2.08+/-0.3 arbitrary units; P = 0.017) in the insulin-resistant offspring, whereas the extramyocellular lipid content and total muscle lipid content were not statistically different between the two groups. These data demonstrate that in these well-matched groups of lean subjects, IMCL is increased in insulin-resistant offspring of type 2 diabetic subjects when compared with an insulin-sensitive group matched for age, BMI, body fat distribution, percent body fat, and degree of physical fitness. These results indicate that increased IMCL represents an early abnormality in the pathogenesis of insulin resistance and suggest that increased IMCL may contribute to the defective glucose uptake in skeletal muscle in insulin-resistant subjects.

The adipocyte-derived hormone adiponectin seems to protect from insulin resistance, a key factor in the pathogenesis of type 2 diabetes. Genome-wide scans have mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome to chromosome 3q27, where the adiponectin gene is located. A common silent T-G exchange in nucleotide 94 (exon 2) of the adiponectin gene has been associated with increased circulating adiponectin levels. Metabolic abnormalities associated with the G allele have not been reported. We therefore assessed whether this polymorphism alters insulin sensitivity and/or measures of obesity using the Tü bingen Family Study database (prevalence of the G allele, 28%). In 371 nondiabetic individuals, we found a significantly greater BMI in GG ؉ GT (25.5 ؎ 0.7 kg/m 2 ) compared with TT (24.1 ؎ 0.3 kg/m 2 ; P ‫؍‬ 0.02). Insulin sensitivity (determined by euglycemic clamp, n ‫؍‬ 209) was significantly lower in GG ؉ GT (0.089 ؎ 0.007 units) compared with TT (0.112 ؎ 0.005 units; P ‫؍‬ 0.02). This difference disappeared completely on adjustment for BMI. Because our population contains a relatively high proportion of first-degree relatives of patients with type 2 diabetes, we stratified by family history (FHD). Much to our surprise, the genotype differences in BMI and insulin sensitivity in the whole population were attributable entirely to differences in the subgroup without FHD, whereas in the subgroup with FHD, the G allele had absolutely no effect. Moreover, individuals without FHD had a significantly lower BMI than individuals with FHD (25.2 ؎ 0.4 vs. 26.2 ؎ 0.5 kg/m 2 ; P ‫؍‬ 0.01), which was not the case for the GG ؉ GT subgroup without FHD (27.0 ؎ 0.9 kg/m 2 ; NS). This suggests that in individuals without familial predisposition for type 2 diabetes, the adiponectin polymorphism may mildly increase the obesity risk (and secondarily insulin resistance). In contrast, in individuals who are already burdened by other genetic factors, this small effect may be very hard to detect. Diabetes 51:37-41, 2002

No abstract

No abstract