Disproportionately Elevated Proinsulin Levels as an Early Indicator of β-Cell Dysfunction in Nondiabetic Offspring of Chinese Diabetic Patients.

Ming Li,Dan Feng,Juming Lu,Kui Zhang,Shan Gao

doi:10.1155/2016/4740678

Abstract

Objective. To study the characteristics of β-cell dysfunction and insulin resistance (IR) in the first-degree relatives (FDRs) of T2DM in Chinese population and to examine the usefulness of proinsulin (PI) for evaluating β-cell dysfunction. Methods. 229 subjects of nondiabetic FDRs, 71 newly diagnosed T2DM, and 114 with normal glucose tolerance (NGT) but not FDRs (NGT-non-FDRs) were verified by a 2-hour oral glucose tolerance test. Specific insulin (SI) and PI were measured by highly sensitive ELISA. Results. Compared to NGT-non-FDRs, NGT-FDRs showed higher levels of fasting and 2-hour PI, fasting PI-to-SI ratio (FPI/SI), and HOMA-IR (p < 0.01). Meanwhile, fasting PI, FPI/SI, and HOMA-IR were increased steadily from NGT-FDRs to prediabetes-FDRs and were highest in T2DM group (p < 0.001), whereas a significant decrease in HOMA-B could be observed only in T2DM group. Moreover, a progressive deterioration of β-cell function in NGT-FDRs, prediabetes-FDRs, and T2DM could be identified by FPI/SI even after adjusting for HOMA-IR: relative to non-FDRs controls, mean FPI/SI levels were increased 1.5, 2.0, and 4.7-fold, respectively (all p < 0.01). Conclusions. β-cell dysfunction as assessed by disproportionate secretion of proinsulin and IR by HOMA (using specific insulin assay) already exist in FDRs of T2DM even with normal glucose status. Compared with HOMA-B, FPI/SI could detect β-cell failure in earlier stage of diabetes development.

Highlights

Insulin resistance (IR) and β-cell dysfunction play the major pathophysiologic roles in type 2 diabetes mellitus (T2DM) [1]
Glucose tolerance status was defined according to the American Diabetes Association [20]; a subject was classified as having prediabetes including the following: impaired fasting glucose (IFG): FBG ≥ 5.6 mmol/L to 7.0 mmol/L; impaired glucose tolerance (IGT): 2 h BG 7.8 mmol/L to 11.1 mmol/L
The major finding is that, even evaluated by the simple indices based solely on fasting status, both IR as determined by HOMAIR and β-cell dysfunction by increased fasting proinsulin (FPI)/Specific insulin (SI) ratio appear to exist in the first-degree relatives (FDRs) of T2DM when glucose tolerance was still in normal status

Summary

Introduction

Insulin resistance (IR) and β-cell dysfunction play the major pathophysiologic roles in type 2 diabetes mellitus (T2DM) [1]. Assessment of IR and β-cell dysfunction is essential to predict diabetes onset and progression and to improve prevention and therapeutic strategies [2]. With the availability of specific method to measure proinsulin, it has been shown that the disproportionate secretion of proinsulin, the precursor of insulin, can be a specific indicator of IR and a hallmark of β-cell dysfunction [11, 12]; circulation proinsulin levels as well as proinsulin-to-insulin ratios have become the valuable measures to assess the impact of therapeutic interventions on the improvement of islet insulin-secreting function [13,14,15] and were somewhat better than HOMA indices.

Methods

Results

Conclusion