Beta-cell failure rather than insulin resistance is the major cause of abnormal glucose tolerance in Africans: insight from the Africans in America study

Abstract

Introduction: Uncertainties exist on whether the main determinant of abnormal glucose tolerance (Abnl-GT) in Africans is β-cell failure or insulin resistance (IR). Therefore, we determined the prevalence, phenotype and characteristics of Abnl-GT due to β-cell failure versus IR in 486 African-born blacks (male: 64%, age: 38±10 years (mean±SD)) living in America.

Research design and methods: Oral glucose tolerance test were performed. Abnl-GT is a term which includes both diabetes and prediabetes and was defined as fasting plasma glucose (FPG) ≥5.6 mmol/L and/or 2-hour glucose ≥7.8 mmol/L. IR was defined by the lowest quartile of the Matsuda Index (≤2.98) and retested using the upper quartile of homeostatic model assessment of insulin resistance (HOMA-IR) (≥2.07). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell failure was defined as Abnl-GT without IR. Beta-cell compensation was assessed by the Disposition Index (DI). Fasting lipids were measured. Visceral adipose tissue (VAT) volume was obtained with abdominal CT scan.

Results: The prevalence of Abnl-GT was 37% (182/486). For participants with Abnl-GT, IR occurred in 38% (69/182) and β-cell failure in 62% (113/182). Compared with Africans with Abnl-GT-IR, Africans with Abnl-GT-β-cell failure had lower body mass index (BMI) (30.8±4.3 vs 27.4±4.0 kg/m²), a lower prevalence of obesity (52% vs 19%), less VAT (163±72 vs 107±63 cm²), lower triglyceride (1.21±0.60 vs 0.85±0.42 mmol/L) and lower FPG (5.9±1.4 vs 5.3±0.6 mmol/L) and 2-hour glucose concentrations (10.0±3.1 vs 9.0±1.9 mmol/L) (all p<0.001) and higher DI, high-density lipoprotein (HDL), low-density lipoprotein particle size and HDL particle size (all p<0.01). Analyses with Matsuda Index and HOMA-IR yielded similar results. Potential confounders such as income, education, alcohol and fiber intake did not differ by group.

Conclusions: Beta-cell failure occurred in two-thirds of participants with Abnl-GT and may be a more frequent determinant of Abnl-GT in Africans than IR. As BMI category, degree of glycemia and lipid profile appeared more favorable when Abnl-GT was due to β-cell failure rather than IR, the clinical course and optimal interventions may differ.

Trial registration number: NCT00001853.

Keywords: developing countries; diabetes mellitus; diagnosis; prediabetic state; type 2.

Figure 1

Phenotype and glucometabolic parameters by glucose tolerance group. (A) Body mass index (BMI), (B) waist circumference, (C) visceral adipose tissue (VAT), (D) Matsuda Index, (E) Insulin Secretion Index, (F) Disposition Index. In each panel, the four bars in sequence represent: normal glucose tolerant-reference (NGT-Ref), NGT-insulin resistant (NGT-IR), abnormal glucose tolerance-insulin resistant (Abnl-GT-IR), Abnl-GT-β-cell failure. Raw data are presented as mean±SE. Asterisks are for differences adjusted for age and are in comparison to NGT-reference. *p≤0.05, **p≤0.01, ***p≤0.001. Hashtags are for differences between the two groups with Abnl-GT. ^#p≤0.05, ^##p≤0.01, ^###p≤0.001. The blue dash line in panel A demarcates the BMI threshold for obesity (BMI ≥30 kg/m²). The red dash line in panel D demarcates insulin resistance (Matsuda Index ≤2.98).

Figure 2

Lipid parameters by glucose tolerance group. (A) Triglyceride, (B) high-density lipoprotein (HDL), (C) low-density lipoprotein (LDL)-size, (D) HDL-size. In each panel, the four bars in sequence represent: normal glucose tolerant-reference (NGT-Ref), NGT-insulin resistant (NGT-IR), abnormal glucose tolerance-insulin resistant (Abnl-GT-IR), Abnl-GT-β-cell failure. Raw data are presented as mean±SE. Asterisks are for differences adjusted for age and are in comparison to NGT-reference. *p≤0.05, **p≤0.01, ***p≤0.001. Hashtags are for differences between the two groups with Abnl-GT. #p≤0.05, ##p≤0.01, ###p≤0.001.

Figure 3

Glucose concentrations and diabetes prevalence in the abnormal glucose tolerance-insulin resistant (Abnl-GT-IR) and Abnl-GT-β-cell failure groups. (A) Glucose concentrations at each timepoint during the oral glucose tolerance test. (B) Prevalence of diabetes and prediabetes in each group. *p≤0.05, **p≤0.01, ***p≤0.001.