[Evaluation of islet beta cell function in subjects with normal glucose tolerance, impaired glucose regulation, and type 2 diabetes mellitus]

Abstract

Objective: To investigate the function of islet beta cells in subjects with normal glucose tolerance (NGT), impaired glucose regulation (IGR), and type 2 diabetes mellitus (T2DM). Different indexes of insulin secretion, including DeltaI30/DeltaG30, AIR or HOMAbeta, were compared.

Methods: 178 subjects without overt diabetes were classified into three groups according to the results of 75 g oral glucose tolerance test (OGTT): NGT group (n = 68), IGR group (n = 75), and T2DM group (n = 35). Intravenous glucose tolerance test (IVGTT) was carried out 1 approximately 3 days later in all participants, with measurement of plasma insulin. The ratio of insulin-to-glucose levels increment during the first 30 min of OGTT (DeltaI30/DeltaG30) and the acute insulin response (AIR) in IVGTT were used as indexes of early insulin secretion. Homeostasis model assessment of insulin secretion (HOMAbeta) was another indicator of insulin secretion. The fasting plasma proinsulin level (FPI) was measured and the ratio fasting proinsulin to fasting insulin (PI/I) was calculated. HOMA insulin resistance index (HOMA IR) was used to assess the insulin resistance.

Results: The DeltaI30/DeltaG30 and AIR of the IGR group, adjusted by age, sex, and BMI, were both significantly lower than those of the NGT group. But the HOMAbeta of the IGR group was only slightly lower than that of the NGT group. Compared with the NGT subjects, the T2DM patients had a very severe islet beta cell dysfunction (84% decrease in AIR, 70% decrease in DeltaI30/DeltaG30 and 62% decrease in HOMA beta). When the DeltaI30/DeltaG30 was adjusted by HOMR IR, the extent of impairment in early insulin response was similar to that of AIR (87% versus 84% lower than that of the NGT group). The FPI and ratio of proinsulin to insulin were higher in the T2DM subjects compared with the NGT subjects (24.4 pmol/L +/- 18.0 pmol/L vs 10.9 pmol/L +/- 6.7 pmol/L; and 14.7% +/- 10.5% vs. 10.0% +/- 6.5%, both P < 0.05). There was a significantly positive correlation between DeltaI30/DeltaG30 and AIR (r = 0.75, P < 0.001).

Conclusion: In the stage of IGR, an evident deficit in phasic insulin secretion after glucose load and a decreasing HOMAbeta are exhibited. In addition to this, qualitative decrease of insulin secretion appears in the DM stage. AIR is a reliable index of isletbeta cell function. DeltaI30/DeltaG30 is an alternative one in the subjects with NGT and IGR. But it should be adjusted by IR in diabetic patients.