Insulin sensitivity variations in apparently healthy Arab male subjects: correlation with insulin and C peptide

Abstract

Introduction: Decreased insulin sensitivity occurs early in type 2 diabetes (T2D). T2D is highly prevalent in the Middle East and North Africa regions. This study assessed the variations in insulin sensitivity in normal apparently healthy subjects and the levels of adiponectin, adipsin and inflammatory markers.

Research design and methods: A total of 60 participants (aged 18-45, body mass index <28) with a normal oral glucose tolerance test (OGTT) completed hyperinsulinemic-euglycemic clamp (40 mU/m²/min) and body composition test by dual-energy X-ray absorptiometry scan. Blood samples were assayed for glucose, insulin, C peptide, inflammatory markers, oxidative stress markers, adiponectin and adipsin.

Results: The subjects showed wide variations in the whole-body glucose disposal rate (M value) from 2 to 20 mg/kg/min and were divided into three groups: most responsive (M>12 mg/kg/min, n=17), least responsive (M≤6 mg/kg/min, n=14) and intermediate responsive (M=6.1-12 mg/kg/min, n=29). Insulin and C peptide responses to OGTT were highest among the least insulin sensitive group. Triglycerides, cholesterol, alanine transaminase (ALT) and albumin levels were higher in the least responsive group compared with the other groups. Among the inflammatory markers, C reactive protein (CRP) was highest in the least sensitivity group compared with the other groups; however, there were no differences in the level of soluble receptor for advanced glycation end products and Tumor Necrosis Factor Receptor Superfamily 1B (TNFRS1B). Plasma levels of insulin sensitivity markers, adiponectin and adipsin, and oxidative stress markers, oxidized low-density lipoprotein, total antioxidant capacity and glutathione peroxidase 1, were similar between the groups.

Conclusions: A wide range in insulin sensitivity and significant differences in triglycerides, cholesterol, ALT and CRP concentrations were observed despite the fact that the study subjects were homogenous in terms of age, gender and ethnic background, and all had normal screening comprehensive chemistry and normal glucose response to OGTT. The striking differences in insulin sensitivity reflect differences in genetic predisposition and/or environmental exposure. The low insulin sensitivity status associated with increased insulin level may represent an early stage of metabolic abnormality.

Keywords: diabetes mellitus; glucose tolerance test; hyperinsulinism; insulin resistance; type 2.

Figure 1

Study participants’ recruitment criteria. OGTT, oral glucose tolerance test.

Figure 2

(A) Individual M values across the 60 individuals, arranged by increasing order. (B) Mean±SEM of M values grouped into three groups: least sensitive (M≤6), intermediate sensitive (M=6.1–12) and most sensitive (M>12). One-way analysis of variance followed by Bonferroni statistical test was performed for multiple comparisons. *P<0.001 versus the least sensitive group. (C) Insulin concentrations during the clamp procedure and (D) AUC for insulin concentrations during the clamp procedure. AUC, area under the curve; Ins, insulin; M value, whole-body glucose disposal rate.

Figure 3

(A) Plasma concentrations of glucose (mmol/L), insulin (mIU/L) and C peptide (nmol/L) during 75 g OGTT. White square: most sensitive group (M>12); gray diamond: intermediate sensitive group (M=6.1–12); and black circle, least sensitive group (M≤6). (B) AUCs for the glucose, insulin and C peptide responses during OGTT were calculated using the trapezoid method. One-way analysis of variance followed by Bonferroni statistical test was performed for multiple comparisons. *P<0.01 versus M≤6. (C and D) Correlation between M values and the AUC of insulin (C) and C peptide (D) responses to OGTT. AUC, area under the curve; C pep, C peptide; Ins, insulin; M value, whole-body glucose disposal rate; OGTT, oral glucose tolerance test.