Pathogenic Factors Responsible for Glucose Intolerance in Patients With NIDDM

Abstract

To define the pathogenic factors responsible for glucose intolerance in NIDDM, we estimated insulin secretory capacity, SI, and SG in 11 healthy, nondiabetic subjects and 9 NIDDM patients who had no SI impairment. All subjects studied were nonobese and normotensive. Each underwent a 75-g OGTT and a modified FSIGT: glucose was administered (300 mg/kg body weight), and insulin was infused (20 mU/kg over 5 min) from 20 to 25 min after the administration of glucose. SI and SG were estimated by Bergman's minimal-model method. The insulin response to oral glucose was significantly lower in NIDDM patients than in normal control subjects. First-phase insulin secretion expressed as the integrated area of plasma insulin above the basal level during the first 20 min was much smaller in NIDDM subjects (214 +/- 112 pM.min) than in control subjects (4643 +/- 885 pM.min, P < 0.01). SI was not statistically different in normal control subjects (1.27 +/- 0.18 x 10(-4) min-1.pM-1) versus diabetic patients (1.62 +/- 0.33 x 10(-4) min-1.pM-1). However, SG was significantly lower in diabetic subjects (1.11 +/- 0.17 x 10(-2) min-1) than in control subjects (2.35 +/- 0.26 x 10(-2) min-1, P < 0.01). These results suggest that impaired insulin secretion and decreased SG are the factors responsible for glucose intolerance of Japanese NIDDM patients with normal insulin sensitivity. Because SI and SG are the factors responsible for glucose intolerance of NIDDM patients with insulin resistance, it is conceivable that decreased SG is common in NIDDM patients regardless of their SI index.

Increase in Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) Had a Strong Impact on the Development of Type 2 Diabetes in Japanese Individuals with Impaired Insulin Secretion: The Saku Study

“…Insulin secretion in Japanese individuals is reported to be less than half that of whites [16], [17], and most Japanese patients with type 2 diabetes do not have IR [18]. Additionally, studies in Sweden and those conducted in Pima Native Americans have shown that the acute insulin secretory response to intravenous glucose is an independent predictor of the development of diabetes [19]–[22].…”

SG, SI, and EGP of exercise-trained middle-aged men estimated by a two-compartment labeled minimal model

“…Using a minimal model, Welch et al (50) showed that S G as well as S I decreased in type 2 diabetes mellitus. Moreover, our previous reports (11,42,43) demonstrated that S G decreased in Japanese type 2 diabetic patients as well as in subjects with impaired glucose tolerance and type 2 diabetic offspring. Furthermore, an epidemiological study reported that a reduced S I and reduced S G are both strong predictors of type 2 diabetes mellitus (26).…”

Leptin:Adiponectin Ratio and Metabolic Syndrome in the General Japanese Population

“…The ratio of adiponectin and leptin has also been reported to be associated with insulin resistance, which is considered to be one of the pathophysiological conditions underlying MetS [8, 9]. However, for instance, diabetes mellitus, a component of MetS, is not always caused by insulin resistance in Japanese people [10]. Furthermore, these earlier studies have not explored the association between L:A and MetS with regard to the determination of a potential cut-off level of L:A for detecting MetS and have not fully examined the L:A in the general community-dwelling population of Japan.…”