Pathogenic Factors Responsible for Glucose Intolerance in Patients With NIDDM

To define the pathogenic factors responsible for glucose intolerance in NIDDM, we estimated insulin secretory capacity, S_I, and S_G in 11 healthy, nondiabetic subjects and 9 NIDDM patients who had no S_I 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. S_I and S_G 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). S, was not statistically different in normal control subjects (1.27 ± 0.18 × 10⁻⁴ min⁻¹ · pM⁻¹) versus diabetic patients (1.62 ± 0.33 × 10⁻⁴ min⁻¹ · pM⁻¹). However, S_G was significantly lower in diabetic subjects (1.11 ± 0.17 × 10⁻² min⁻¹) than in control subjects (2.35 ± 0.26 × 10⁻² min⁻¹ P < 0.01). These results suggest that impaired insulin secretion and decreased S_G are the factors responsible for glucose intolerance of Japanese NIDDM patients with normal insulin sensitivity. Because S_I and S_G are the factors responsible for glucose intolerance of NIDDM patients with insulin resistance, it is conceivable that decreased S_G is common in NIDDM patients regardless of their S_I index.