Peripheral and hepatic insulin sensitivity in subjects with impaired glucose tolerance

Abstract

Recent evidence suggests that the postprandial hyperglycaemia in impaired glucose tolerance is primarily due to impaired suppression of basal hepatic glucose output. This in turn appears to be secondary to decreased first phase insulin secretion, although decreased hepatic insulin sensitivity, which is a feature of non-insulin-dependent diabetes mellitus, might also play a role. Eight mildly overweight subjects with impaired glucose tolerance and eight closely matched control subjects with normal glucose tolerance underwent an intravenous glucose tolerance test to assess first phase insulin secretion. Insulin sensitivity was examined by a 150-min hyperinsulinaemic-euglycaemic clamp. Somatostatin was infused from 150 min to suppress endogenous insulin secretion, and glucagon and insulin were replaced by constant infusion. Glucose with added dideuterated glucose (labelled infusion technique) was infused to maintain euglycaemia. First phase insulin secretion (delta 0-10 min insulin area divided by delta 0-10 min glucose area) was significantly decreased in the subjects with impaired glucose tolerance (median [range]: 1.2 [0.2-19.4] vs 9.1 [2.6-14.5] mU.mmol-1; p < 0.01). During the clamp, circulating insulin (93 +/- 8 [mean +/- SEM] and 81 +/- 10 mU.l-1) and glucagon (54 +/- 4 and 44 +/- 6 ng.l-1) levels were comparable. Total glucose disposal was decreased in subjects with impaired glucose tolerance (2.78 +/- 0.27 vs 4.47 +/- 0.53 mg.kg-1.min-1; p< 0.02), and was primarily due to decreased non-oxidative glucose disposal. However, hepatic glucose output rates were comparable during the clamp (0.38 +/- 0.10 and 0.30 +/- 0.18 mg.kg-1.min-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Disturbances in β-Cell Function in Impaired Fasting Glycemia

“…This has also been found in previous reports from our group and from others (2)(3)(4)(5)(6)(7)(8)(15)(16)(17). At the same time, these subjects were obese and showed a diminished tissue insulin sensitivity compared with control subjects (NFG/NGT), as previously reported from studies in other IGT subjects (18). However, since ANOVA showed that the difference in tissue insulin sensitivity disappeared when gender, age, BMI, and WHR were used, it follows that the Data are mean Ϯ SEM, expressed as percentage of expected.…”

Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance

“…Furthermore, we have previously shown that EGP during glucose loading is proportional to fasting EGP, both in non-diabetic and Type 2 diabetic subjects [41,42]. These findings stand in contrast to the conclusion reached by another study [5], in which IGT subjects had normal hepatic sensitivity to insulin. This conclusion, however, was based on the finding of similarly suppressed EGP during a euglycaemic clamp using exogenous insulin infusion rates (equivalent to those used in this study) which are maximally suppressive for EGP and, therefore, cannot detect differences in EGP.…”

“…In studies using graded glucose infusions and the C-peptide deconvolution technique to reconstruct insulin secretory rates, one study [14] documented a slower rise in insulin secretion as a function of rising plasma glucose concentrations in IGT subjects in comparison with subjects with normal gluImpaired glucose tolerance (IGT) is a condition of high risk for the development of Type 2 diabetes. Early physiological studies consistently showed that IGT is an insulin-resistant state [1,2,3,4,5] and documented the presence of impaired insulin response to intravenous glucose [6,7,8,9,10,11]. The general cose tolerance.…”

Early disturbances in insulin secretion in the development of type 2 diabetes mellitus

“…Various studies have shown that many of these subjects are overweight, and that they are moderately insulin-resistant (Reaven et al, 1989;Berrish et al, 1995). Early studies have already demonstrated increased plasma insulin levels after an OGTT in IGT subjects (Reaven et al, 1989).…”

“…Various studies have addressed the acute insulin release seen after ivGTT, which have shown decreased (Davies et al, 1994;Ahren and Pacini, 1997) normal (Berrish et al, 1995), increased (Walker et al, 1997) or disturbed first phase release (Lillioja et al, 1988;Byrne et al, 1996). Again, matching for obesity (and age) is important for the interpretation of these results (Kahn et al, 2001).…”