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

IntroductionUncertainties 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 methodsOral 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.ResultsThe 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.ConclusionsBeta-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 numberNCT00001853.

The Cardiometabolic Health of African Immigrants in High-Income Countries: A Systematic Review

“…While the pathogenesis of diabetes in SSA is poorly understood, some studies have shown that the phenotype of diabetes in Africa is distinct, with most Africans developing diabetes at a younger age (<50 years), at a relatively leaner body size (normal BMI), and with betacell secretory dysfunction [69]. Ishimwe and colleagues have shown that beta-cell failure rather than insulin resistance may be the underlying cause of abnormal glucose tolerance among African immigrants [70]. Since obesity and smoking are associated with beta-cell dysfunction, [71] interventions targeting these risk factors, which are more prevalent in HICs, may prevent CMD among African immigrants [61].…”

Sleep and Economic Status Are Linked to Daily Life Stress in African-Born Blacks Living in America

“…The Africans in America cohort was established to assess both the well-being and cardiometabolic health of African-born Blacks living in the United States [ 23 , 25 , 26 , 27 , 28 ]. The recruitment methods included announcements on the NIH website, flyers, presentations at community events (in-person and virtual) and previous participant referrals.…”

Assessing Insulin Sensitivity and Postprandial Triglyceridemic Response Phenotypes With a Mixed Macronutrient Tolerance Test

“…While the glucose to insulin ratio provides potentially useful indication of insulin sensitivity in the absence of diabetes, this measure loses utility with elevated fasting glucose ( 5 ). Clinically relevant models validated against the gold standard euglycemic clamp include those assessing basal glucose and insulin homeostasis [e.g., the homeostasis model of insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)], and those incorporating the postprandial response to a glucose challenge [e.g., Matsuda insulin sensitivity index (ISI Matsuda ), beta-cell disposition index], probing a glucose challenge response provides opportunities to assess pancreatic function and peripheral glucose disposal ( 6 , 7 ). However, mixed macronutrient tolerance tests (MMTTs) are gaining popularity as they allow for a broader probe of the nutritional phenotype, including evaluations of metabolic flexibility (i.e., fuel switching), insulin sensitivity, and lipid tolerance ( 8 – 14 ).…”