The Africans in America study demonstrates that subclinical cardiovascular risk differs by etiology of abnormal glucose tolerance

Abstract

Abnormal-glucose tolerance (Abnl-GT) is due to an imbalance between β-cell function and insulin resistance (IR) and is a major risk factor in cardiovascular disease (CVD). In sub-Saharan Africa, β-cell failure is emerging as an important cause of Abnl-GT (Abnl-GT-β-cell-failure). Visceral adipose tissue (VAT) volume and hyperlipidemia are major contributors to CVD risk when Abnl-GT is due to IR (Abnl-GT-IR). Yet, the CVD profile associated with Abnl-GT-β-cell failure is unknown. Therefore, our goals in 450 African-born Blacks (Male: 65%; Age: 39 ± 10 years; BMI 28 ± 5 kg/m²), living in America were to: (1) determine Abnl-GT prevalence and etiology; (2) assess by Abnl-GT etiology, associations between four understudied subclinical CVD risk factors in Africans: (a) subclinical myocardial damage (high-sensitivity troponin T (hs-cTnT)); (b) neurohormonal regulation (N-terminal pro-Brain-natriuretic peptide (NT-proBNP)); (c) coagulability (fibrinogen); (d) inflammation (high-sensitivity C-reactive protein (hsCRP)), as well as HbA_1c, Cholesterol/HDL ratio and VAT. Glucose tolerance status was determined by the OGTT. IR was defined by the threshold at the lowest quartile for the Matsuda Index (≤ 2.97). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell-failure was defined as Abnl-GT without IR. VAT was assessed by CT-scan. For both the Abnl-GT-β-cell-failure and Abnl-GT-IR groups, four multiple regression models were performed for hs-cTnT; NT-proBNP; fibrinogen and hsCRP, as dependent variables, with the remaining three biomarkers and HbA_1c, Cholesterol/HDL and VAT as independent variables. Abnl-GT occurred in 38% (170/450). In the Abnl-GT group, β-cell failure occurred in 58% (98/170) and IR in 42% (72/170). VAT and Cholesterol/HDL were significantly lower in Abnl-GT-β-cell-failure group vs the Abnl-GT-IR group (both P < 0.001). In the Abnl-GT-β-cell-failure group: significant associations existed between hscTnT, fibrinogen, hs-CRP, and HbA_1c (all P < 0.05), and none with Cholesterol/HDL or VAT. In Abnl-GT-IR: hs-cTnT, fibrinogen and hsCRP significantly associated with Cholesterol/HDL (all P < 0.05) and NT-proBNP inversely related to fibrinogen, hsCRP, HbA_1c, Cholesterol/HDL, and VAT (all P < 0.05). The subclinical CVD risk profile differed between Abnl-GT-β-cell failure and Abnl-GT-IR. In Abnl-GT-β-cell failure subclinical CVD risk involved subclinical-myocardial damage, hypercoagulability and increased inflammation, but not hyperlipidemia or visceral adiposity. For Abnl-GT-IR, subclinical CVD risk related to subclinical myocardial damage, neurohormonal dysregulation, inflammation associated with hyperlipidemia and visceral adiposity. ClinicalTrials.gov Identifier: NCT00001853.