Comprehensive assessment of insulin resistance in non-obese Asian Indian and Chinese men

Abstract

Aims/introduction: Indian individuals are more insulin resistant (IR) than Chinese individuals, even among those with a non-obese body mass index (BMI). However, BMI often underestimates body fat in Indian individuals, and it remains unclear whether Indians would remain more IR than Chinese individuals when both BMI and body fat are equally matched.

Materials and methods: Using the hyperinsulinemic-euglycemic clamp with stable-isotope infusion, we comprehensively assessed IR between 13 non-obese Indian men with 13 Chinese men matched for age, BMI and body fat. We further compared the differences in insulin metabolic clearance rate (MCR) between the two groups and its relationship with various metabolic parameters. The response of lipid and amino acid metabolism to insulin stimulation was also evaluated using metabolomic profiling.

Results: The rates of endogenous glucose production during fasting were similar, and endogenous glucose production was completely suppressed during insulin clamp for both ethnic groups. Glucose disappearance during insulin clamp was also similar between the two groups, even after accounting for differences in insulin concentration. Metabolomic profiles of amino acids and various acylcarnitines were similar during both fasting and insulin clamp. However, plasma insulin during clamp was significantly higher in Indian men, indicating that insulin MCR was lower. Insulin MCR correlated significantly with total adiposity and skeletal muscle insulin sensitivity.

Conclusion: When equally matched for body fat, non-obese Indian men had similar skeletal muscle insulin sensitivity and endogenous glucose production to Chinese men. The effects of insulin on lipid and amino acid metabolism were also similar. Low insulin MCR is associated with greater adiposity and lower skeletal muscle insulin sensitivity.

Keywords: Endogenous glucose production; Non-obese Asian Indian; Skeletal muscle insulin sensitivity.

Figure 1

Endogenous glucose production in Chinese and Indian men during fasting and insulin clamp steady‐state. Rates of endogneous glucose production (EGP) in Chinese and Indian men were measured and compared during fasting and insulin clamp steady‐state. No significant between‐group differences in EGP were detected in the fasted state, but EGP was completely and equally suppressed in response to insulin infusion. FFM, fat free mass.

Figure 2

Respiratory quotient, plasma pyruvate and 3‐hydroxy‐butylrate in Indian and Chinese men during the fasted and insulin clamp steady‐state. (a) Respiratory quotient, (b) plasma pyruvate and (c) 3‐hydroxy‐butylrate (4‐OH) were measured in Chinese and Indian men in the fasted and insulin clamp steady‐state. All measured parameters responded significantly to insulin stimulation, but no significant interethnic differences were detected. Data presented as mean ± standard deviation.

Figure 3

Plasma amino acids in Indian and Chinese men at the fasting and during insulin clamp steady‐state. (a) Essential and (b) non‐essential amino acids in Indian and Chinese men measured after an overnight fast and during insulin clamp steady state. All amino acids decreased significantly in response to insulin infusion. No significant interethnic differences were found in either the fasting or insulin‐stimulated state. *P < 0.05 of fasting vs insulin clamp.

Figure 4

Acylcarnitine profiling in Indian and Chinese men during the fasting and insulin clamp steady‐state. (a) Plasma measurements of long, (b) intermediate, (c) short and (d) acetyl carnitines in the fasted and insulin clamp steady‐state. Insulin stimulation resulted in a statistically significant decrease in various acylcarnitines, but neither the fasting nor insulin clamp steady‐state values were different between ethnic groups. The acyl chain length, C, is denoted by the corresponding acyl chain length with C2 (acetyl carnitine), short‐chain (C3–C5), intermediate chain (C6–C12), long‐chain (C14–C18). *P < 0.05 of fasting vs insulin clamp. Data presented as mean ± standard deviation.