Comparative Study of Glucose Homeostasis, Lipids and Lipoproteins, HDL Functionality, and Cardiometabolic Parameters in Modestly Severely Obese African Americans and White Americans With Prediabetes: Implications for the Metabolic Paradoxes

Abstract

OBJECTIVETo determine whether modestly severe obesity modifies glucose homeostasis, levels of cardiometabolic markers, and HDL function in African Americans (AAs) and white Americans (WAs) with prediabetes.RESEARCH DESIGN AND METHODSWe studied 145 subjects with prediabetes (N = 61 WAs, N = 84 AAs, mean age 46.5 ± 11.2 years, mean BMI 37.8 ± 6.3 kg/m2). We measured fasting levels of lipids, lipoproteins, and an inflammatory marker (C-reactive protein [CRP]); HDL functionality (i.e., levels of paraoxonase 1 [PON1]); and levels of oxidized LDL, adiponectin, and interleukin-6 (IL-6). We measured serum levels of glucose, insulin, and C-peptide during an oral glucose tolerance test. Values for insulin sensitivity index (Si), glucose effectiveness index (Sg), glucose effectiveness at zero insulin (GEZI), and acute insulin response to glucose (AIRg) were derived using a frequently sampled intravenous glucose tolerance test (using MINMOD software).RESULTSMean levels of fasting and incremental serum glucose, insulin, and C-peptide tended to be higher in WAs versus AAs. The mean Si was not different in WAs versus AAs (2.6 ± 2.3 vs. 2.9 ± 3.0 × 10−4 × min−1 [μU/mL]−1). Mean values for AIRg and disposition index as well as Sg and GEZI were lower in WAs than AAs. WAs had higher serum triglyceride levels than AAs (116.1 ± 55.5 vs. 82.7 ± 44.2 mg/dL, P = 0.0002). Mean levels of apolipoprotein (apo) A1, HDL cholesterol, PON1, oxidized LDL, CRP, adiponectin, and IL-6 were not significantly different in obese AAs versus WAs with prediabetes.CONCLUSIONSModestly severe obesity attenuated the ethnic differences in Si, but not in Sg and triglyceride levels in WAs and AAs with prediabetes. Despite the lower Si and PON1 values, AAs preserved paradoxical relationships between the Si and HDL/apoA1/triglyceride ratios. We conclude that modestly severe obesity has differential effects on the pathogenic mechanisms underlying glucose homeostasis and atherogenesis in obese AAs and WAs with prediabetes.

Association between ethnicity and obesity with high-density lipoprotein (HDL) function and subclass distribution

“…Low serum PON activity levels have been associated with an increased risk for major adverse cardiovascular events (MACE), including myocardial infarction and stroke in an American study [ 29 ]. The novel finding of higher PON activity levels in black women compared to white women, independent of protein expression levels is in contrast to other studies in the USA that found that African Americans had lower or similar PON activity levels than their white counterparts, despite similar HDL-C concentrations [ 30 , 31 ].…”

Effect of body mass index on diabetogenesis factors at a fixed fasting plasma glucose level

“…reported that GE deteriorates as body mass index (BMI) increases in nondiabetic individuals, whereas Healy et al . reported contrasting findings [ 13 , 14 ].…”

Clinical and Histologic Characterization of Nonalcoholic Steatohepatitis in African American Patients

“…2). Similarly, in the study by Healy et al (20), modestly severe obesity attenuated the ethnic differences in insulin sensitivity. Of note, when African American and Caucasian patients were matched for adiposity, insulin sensitivity was also similar between ethnic groups (19).…”

“…Genetic variations of apoCI, apoCIII, and apoE have also been reported in African American subjects with different frequencies than in Caucasian subjects (27,28). Also, previous studies have found that paraoxonase-1 (PON1) is lower in African Americans compared with Caucasians, suggesting potential HDL-C dysfunction in this ethnic group (20).…”