Abstract
BackgroundInsulin resistance and type 2 diabetes are more prevalent in people of South Asian ethnicity than in people of Western European origin. To investigate the source of these differences, we compared insulin sensitivity, insulin secretion, glucose and lipid metabolism in South Asian and Nordic subjects with type 2 diabetes.MethodsForty-three Nordic and 19 South Asian subjects with type 2 diabetes were examined with intra-venous glucose tolerance test, euglycemic clamp including measurement of endogenous glucose production, indirect calorimetry measuring glucose and lipid oxidation, and dual x-ray absorptiometry measuring body composition.ResultsDespite younger mean ± SD age (49.7±9.4 vs 58.3±8.3 years, p = 0.001), subjects of South Asian ethnicity had the same diabetes duration (9.3±5.5 vs 9.6±7.0 years, p = 0.86), significantly higher median [inter-quartile range] HbA1c (8.5 [1.6] vs 7.3 [1.6] %, p = 0.024) and lower BMI (28.7±4.0 vs 33.2±4.7 kg/m2, p<0.001). The South Asian group exhibited significantly higher basal endogenous glucose production (19.1 [9.1] vs 14.4 [6.8] µmol/kgFFM⋅min, p = 0.003). There were no significant differences between the groups in total glucose disposal (39.1±20.4 vs 39.2±17.6 µmol/kgFFM⋅min, p = 0.99) or first phase insulin secretion (AUC0–8 min: 220 [302] vs 124 [275] pM, p = 0.35). In South Asian subjects there was a tendency towards positive correlations between endogenous glucose production and resting and clamp energy expenditure.ConclusionsSubjects of South Asian ethnicity with type 2 diabetes, despite being younger and leaner, had higher basal endogenous glucose production, indicating higher hepatic insulin resistance, and a trend towards higher use of carbohydrates as fasting energy substrate compared to Nordic subjects. These findings may contribute to the understanding of the observed differences in prevalence of type 2 diabetes between the ethnic groups.
Highlights
The prevalence of type 2 diabetes (T2D) varies between different ethnic groups, and is known to be high in South Asians (SA) in their countries of origin, in urban areas, and after migration to Western countries [1]
This difference remained significant after adjustment for possible confounders, including sex, age, height, weight, BMI, %TBF, fat free body mass (FFM), HbA1c, fasting C-peptide, or fasting plasma glucose
We have demonstrated higher basal endogenous glucose production (EGP) in SA patients with established T2D
Summary
The prevalence of type 2 diabetes (T2D) varies between different ethnic groups, and is known to be high in South Asians (SA) in their countries of origin, in urban areas, and after migration to Western countries [1]. The metabolic inflexibility theory proposes that the normal switch in energy substrate between high lipid oxidation in the fasting state and high glucose oxidation in the post-prandial state is impaired in T2D. This results in accumulation of intramuscular lipids and increased plasma glucose values [3]. A third suggested mechanism involves the theory that SA have lower resting energy expenditure (REE) than Western Europeans, and are more prone to obesity and insulin resistance This theory is disputed, where some argue that the lower REE is due to differences in body composition and not ethnicity [4,5]. To investigate the source of these differences, we compared insulin sensitivity, insulin secretion, glucose and lipid metabolism in South Asian and Nordic subjects with type 2 diabetes
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