Elsevier

Metabolism

Volume 59, Issue 9, September 2010, Pages 1358-1364
Metabolism

The contribution of race and diabetes status to metabolic flexibility in humans

https://doi.org/10.1016/j.metabol.2009.12.020Get rights and content

Abstract

Factors controlling metabolic flexibility (MF), the ability of the body to switch from fat to carbohydrate oxidation in response to feeding or with insulin administration, are being actively investigated. We sought to determine the effects of race (African American vs Caucasian) and diabetes status (nondiabetic vs type 2 diabetes mellitus individuals) on MF to glucose in humans. Respiratory quotient (RQ) and macronutrient substrate utilization were evaluated by indirect calorimetry during baseline (fasting) and hyperinsulinemic-euglycemic clamp (insulin infusion of 120 mU·m−2·min−1); ΔRQ (MF) = clamp RQ − fasting RQ. The study included 168 human subjects of different races (55 African Americans, 113 Caucasians), sex (73 men, 95 women), ages (18-73 years), body mass index (19.3-47.7 kg/m2), and diabetes status (89 nondiabetic, 79 type 2 diabetes mellitus subjects). Metabolic flexibility was negatively correlated (P < .01) with age (r = − 0.41), fasting RQ (r = −0.22), fasting glucose (r = −0.55), insulin (r = −0.40), and triglyceride (r = −0.44) concentrations; whereas a positive association was observed with insulin sensitivity (r = 0.69, P < .0001). Insulin sensitivity, fasting RQ, triglyceride concentrations, diabetes status, and race accounted for 71% of the variability in MF with insulin sensitivity being the main determinant factor (model R2 = 0.48, P < .0001). After controlling for the significant predictors, MF was higher in African Americans vs Caucasians (mean ± SEM 0.080 ± 0.004 vs 0.069 ± 0.002, P = .008) and in nondiabetic vs type 2 diabetes mellitus subjects (P = .003). This study confirms that insulin sensitivity is the major contributor to MF in humans, but provides the novel findings that African Americans have significantly greater MF than Caucasians even after adjusting for insulin sensitivity and diabetes status.

Introduction

Metabolic flexibility (MF) is characterized by increased fat oxidation in skeletal muscle during fasting conditions and the ability to switch from fat to carbohydrate oxidation in response to a meal or insulin [1]. Factors that control MF are felt to reside at the mitochondrial level, as prior research suggests that insulin resistance and metabolic inflexibility are potentially caused by mitochondrial impairments in obesity and type 2 diabetes mellitus [2], [3]. Previous research suggested that lean individuals had greater MF than obese individuals [4]. Specifically, lean individuals were able to successfully switch from primarily oxidizing fat during the fasting state (lower respiratory quotient [RQ]) to glucose during the insulin-stimulated state (higher RQ). In addition, there were reports of reduced MF in nondiabetic individuals with a family history of type 2 diabetes mellitus [5] and individuals with type 2 diabetes mellitus [6] when compared with nondiabetic individuals without a family history of type 2 diabetes mellitus and nondiabetic obese individuals. The reduced MF that was observed in the individuals with type 2 diabetes mellitus was mainly explained by the glucose disposal rate [6]. Galgani and colleagues [7] suggested that the glucose disposal rate, baseline fasting RQ, and steady-state plasma free fatty acid concentrations were important contributing factors to MF. Although the effects of body mass index (BMI) and diabetes status on MF have been observed, the contribution of race to MF has been less explored.

African Americans have a higher prevalence of obesity [8] and type 2 diabetes mellitus [9] than Caucasians. The reasons for this disparity are not precisely known, but some possible explanations may be that African Americans have lower skeletal muscle fatty acid oxidation [10], resting metabolic rate [11], insulin sensitivity [12], and higher 24-hour RQ [13]. To our knowledge, only one study [14] has reported results on race and MF. Specifically, Berk et al [14] observed that obese African American women were not able to efficiently switch between fat oxidation during the fasting state and carbohydrate oxidation during a fed and insulin-stimulated state, suggestive of reduced MF in this African American population. This study was restricted to a small group of premenopausal, nondiabetic, obese, and healthy women. Whether these effects are considered to be applicable to the general population encompassing a wide range of phenotypes and levels of glycemia are unknown. Thus, we sought to determine the effect of race and diabetes status on MF in a larger cohort of African Americans and Caucasians consisting of both sexes, a wide range for BMI and insulin sensitivity, and diabetes status (nondiabetic vs type 2 diabetes mellitus individuals).

Section snippets

Subjects

The study population comprised 168 individuals (55 African Americans, 113 Caucasians) with a wide range of characteristics. The characteristics included the following: (1) sex (73 men, 95 women), (2) ages (18-73 years), (3) BMI (19.3-47.7 kg/m2), and (4) diabetes status (89 nondiabetic, 79 type 2 diabetes mellitus individuals). If the subject had a history of type 2 diabetes mellitus, he/she was required to be on dietary therapy only, that is, drug naïve, with a fasting plasma glucose between

Subject characteristics

Table 1 lists the metabolic and physiologic parameters for the entire cohort. None of the parameters for the women were significant except that the nondiabetic African Americans had lower triglyceride levels than the Caucasians. The nondiabetic men who were African American had lower triglyceride, cholesterol, and low-density lipoprotein levels and higher insulin sensitivity when compared with the Caucasians. In addition, the African American men with type 2 diabetes mellitus had a higher

Discussion

In this study, we confirmed that insulin sensitivity was the main predictor of whole-body MF to glucose as previously reported [6]. In addition, metabolic factors such as fasting RQ and fasting triglyceride concentrations contributed to MF. Although the contribution was small, diabetes status and race were also significant determinant factors. Specifically, our data suggest that in response to an insulin/glucose infusion, MF was higher in African Americans and nondiabetic individuals as opposed

Acknowledgment

The authors would like to express their appreciation to the participants and the PBRC inpatient and outpatient unit staff who made it possible to complete this research project.

This study was supported in part by National Institute of Health Grants RO1 DK060126, T32 AT004094, and by a Nutrition Obesity Research Center Grant 1P30 DK072476 entitled “Nutritional Programming: Environmental and Molecular Interactions” sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases.

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