Dynamic assessment of insulin secretion and insulin resistance in Asians with prediabetes

Abstract

Aims/hypothesis: Prediabetes and type 2 diabetes are highly prevalent in Asia. Understanding the pathophysiology of abnormal glucose homeostasis in Asians will have important implications for reducing disease burden, but there have been conflicting reports on the relative contributions of insulin secretion and action in disease progression. In this study, we aimed to assess the contribution of β-cell dysfunction and insulin resistance in the Asian prediabetes phenotype. Methods: We recruited 1679 Asians with prediabetes (n = 659) or normoglycemia (n = 1020) from a multiethnic population in Singapore. Participants underwent an oral glucose tolerance test, an intravenous glucose challenge, and a hyperinsulinemic-euglycemic clamp procedure to determine glucose tolerance, β-cell responsivity, insulin secretion, insulin clearance and insulin sensitivity. Results: Participants with prediabetes had significantly higher glucose concentrations in the fasting state and after glucose ingestion than did normoglycemic participants. Insulin sensitivity (M/I ratio) was ~15% lower, acute insulin response (AIR) to intravenous glucose and β-cell responsivity to oral glucose were ~35% lower, but total insulin secretion rate in the fasting state and after glucose ingestion was ~10% greater in prediabetic than in normoglycemic participants. The decrease in β-cell function with worsening glucose homeostasis in Asians with prediabetes was associated with progressively greater defects in AIR rather than M/I. However, analysis using static surrogate measures (HOMA indices) of insulin resistance and β-cell function revealed a different pattern. Conclusions: Lower AIR to intravenous glucose and β-cell responsivity to oral glucose, on a background of mild insulin resistance, are the major contributors to the dysregulation of glucose homeostasis in Asians with prediabetes.

CLSTN3 gene variant associates with obesity risk and contributes to dysfunction in white adipose tissue

“…In particular, compared to GG genotype carriers, AA genotype carriers exhibited a higher BMI (mean, 24.28 kg/m 2 vs 24.74 kg/m 2 ) and body fat (mean, 28.4% vs. 29.4%) ( Figure 2 A,B). Since individuals with modest BMIs in the SHOS cohort had the compensatory ability of insulin action under glucose challenge, there was no significant difference in glucose metabolism between two groups ( Table S1 ) [ 34 ].

Figure 2 Association of SNP rs7296261 in the CLSTN3 locus with human obesity risk.

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Long‐Term High‐Fat Diet Decreases Renal Insulin‐Degrading Enzyme Expression and Function by Inhibiting the PPARγ Pathway

“…[42] Increased insulin secretion is well documented in insulin resistance. [43,44] However, the role of insulin clearance in the pathogenesis of HFD-induced insulin resistance and related obesity remains still unclear.…”

Identifying Glucose Metabolism Status in Nondiabetic Japanese Adults Using Machine Learning Model with Simple Questionnaire

“…Each category had distinctly different insulin sensitivity and secretory characteristics [21]. However, prediabetes presents overlapping pathophysiology of impaired insulin sensitivity and secretion [25,26]. Although screening tools for prediabetes have been developed [14,[16][17][18][19][20], this is the first study to develop a model to identify the glucose metabolism status of individuals without diabetes.…”