Glucose Effectiveness in Two Subtypes Within Impaired Glucose Tolerance: A Minimal Model Analysis

Abstract

To clarify the event that is involved in the pathogenesis of impaired glucose tolerance (IGT), we studied 15 individuals with IGT and 15 subjects with normal tolerance using the minimal model approach. Our IGT subjects were characterized by normal insulin secretory responses to oral glucose and mild impairments in insulin sensitivity (SI) and glucose effectiveness (SG) at basal and zero insulin. Next, we classified our IGT subjects into two subpopulations: one with normal insulin sensitivity (SI: 0.92 +/- 0.11 x 10(-4) min-1.pmol/l-1 and the other with insulin resistance (SI:0.31 +/- 0.06 x 10(-4)min-1.pmol/l-1, P < 0.05). The populations did not differ with respect to body mass index and fasting plasma glucose level. Basal plasma insulin level was higher in the insulin-resistant group (84.8 +/- 23.3 pmol/l) than in the insulin-sensitive group (48.7 +/- 6.8 pmol/l), but the difference was not statistically significant. The absolute insulin secretory responses to oral glucose were significantly higher in the resistant group (83,205 +/- 17,787 pmol/l x min) than in the sensitive group (24,727 +/- 3,591 pmol/l x min, P < 0.01), whose absolute responses were similar to those of normal control subjects (24,576 +/- 2,767 pmol/l x min). No significant difference was observed in SG between the resistant (0.016 +/- 0.002 min-1) and sensitive (0.013 +/- 0.002 min-1, P > 0.05) type of IGT, but SG was significantly type of IGT, but SG was significantly decreased in both groups compared with normal control subjects (0.023 +/- 0.002 min-1, P < 0.05-0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

β‐cell deterioration – prospects for reversal or prevention

“…Furthermore, in studies where S I and AIRg have been measured in subjects with impaired glucose tolerance (IGT) and type 2 diabetes, S I × AIRg is reduced (Fig. 1) [15–39]. In studies performed in subjects with IGT, the product of the mean values of S I and AIRg was between the 1st and the 28th percentile, as originally defined by Kahn et al.…”

Glucose effectiveness: Lessons from studies on insulin‐independent glucose clearance in mice

“…Therefore, different ethnic groups might show differences in the impact on type 2 diabetes by S G . However, in impaired glucose tolerance, S G was found to be lower than in controls in Japanese people 43 , but not reduced in white people 20 or in African Americans 41 . These differences are of interest on the background that type 2 diabetes in Asian people is primarily characterized by impaired insulin secretion rather than an interplay between insulin resistance and failed islet compensation 44 .…”

“…These differences are of interest on the background that type 2 diabetes in Asian people is primarily characterized by impaired insulin secretion rather than an interplay between insulin resistance and failed islet compensation 44 . The finding of reduced S G in individuals with impaired glucose tolerance among Japanese individuals 43 would suggest that reduced glucose effectiveness contributes to diabetes development in these patients, and this is supported by the results of a study showing reduced S G in the offspring of Japanese patients with type 2 diabetes even at normal glucose tolerance 45 . However, to study whether the contribution by S G to the development of type 2 diabetes is different in ethnic groups, direct comparisons need to be carried out in individual studies.…”

Is the concept of ‘cardiometabolic risk’ more useful than ‘metabolic syndrome’?

“…Of particular interest is that, as suggested by one of us (YS) [7], Type 2 diabetes in the Japanese population is very different from that of Caucasians, in that the former is predominantly associated with insulin deficiency while the latter is mostly associated with insulin resistance [8,9]. The significance of insulin deficiency in the development of Japanese Type 2 diabetes is supported by our previous reports [8,10,11] using techniques such as the minimal model approach [12]. In this context, the term ‘cardiometabolic risk’ is as confusing as the ‘metabolic syndrome’ in clarifying the pathogenesis of diabetes mellitus particularly in Asian populations.…”