Abstract
BackgroundThe rise in prevalence rates of Type 2 Diabetes among Indians is well recognized. The research focus has been primarily to understand the changes in insulin sensitivity and beta cell dysfunction among Indians with Type 2 Diabetes. However, no data are available on the role of peripheral tissue, in particular intramyocellular lipid (IMCL) content and its impact on glucose homeostasis among Indians with prediabetes.Methods28 male subjects (20–40 year) were studied. 13 with prediabetes (BMI ranging from 25.4 ± 2.9 kg/m2) and 15 controls (BMI ranging from 24.6 ± 2.8 kg/m2) were recruited. Body composition by dual energy X-ray absorptiometry (DXA), insulin sensitivity, insulin secretion rates were derived using the minimal model of C-peptide secretion and kinetics rates and skeletal muscle strength of the lower limb (quadriceps) was assessed using Isokinetic dynamometry. From muscle biopsy samples of the vastus lateralis, IMCL fat content (Oil red O staining) was determined.ResultsThe prediabetes group were older compared to controls (P < 0.01), but had similar BMI. The muscle to fat ratio, plasma Insulin, C peptide, HOMA-IR and HOMA % B were also comparable between the groups. IMCL fat content (%) was significantly higher in the prediabetes group compared to controls (7.0 ± 0.7% vs. 2.0 ± 0.3%, P < 0.01). This difference persisted even after controlling for age. Overall the IMCL fat content (%) was positively and significantly associated with HbA1c (r = 0.76, P < 0.01). HOMA-IR was significantly correlated with central (android, trunk) adiposity (kg) (r = 0.71, P < 0.01) but not with IMCL (%).ConclusionsThis is the first direct evidence of existence of significantly higher lipid levels within skeletal muscle cells among normal and overweight young Indians with prediabetes. However, there was no association between IMCL and HOMA-IR among the prediabetes group.
Highlights
Asian Indians are said to have a greater propensity for a phenotype characterized by an excessive accumulation of fat, even with a normal body mass index (BMI), which has been termed “metabolically obese” [1, 2]
The prediabetes group was older than the controls (P < 0.01), but otherwise, the groups were comparable in terms of their level of physical activity, lipid profile basal glucose, insulin and C-Peptide levels
The average intramyocellular lipid (IMCL) (%) was significantly higher in the prediabetes group compared to controls (7.0 ± 0.7% vs. 2.0 ± 0.3%, P < 0.001)
Summary
Asian Indians are said to have a greater propensity for a phenotype characterized by an excessive accumulation of fat, even with a normal body mass index (BMI) (kg/m2), which has been termed “metabolically obese” [1, 2]. The role of ectopic fat, an excess of adipose tissue in locations that are not classically associated with adipose tissue storage has not been explored among the Indian population, in particular in regard to lipid accumulation within skeletal muscle fibers (intramyocellular lipid content, IMCL). Free fatty acids shift to ectopic sites or non-adipose tissue such as the heart, skeletal muscle, as well as the vasculature, once the storage capacity of subcutaneous adipose tissue is exhausted [7]. Since this fat storage in non-adipose tissue is independent of more generalized adiposity, it is difficult to establish robust associations with insulin resistance [8]. From muscle biopsy samples of the vastus lateralis, IMCL fat content (Oil red O staining) was determined
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