Metabolic implications of hepatic, pancreatic and abdominal adipose tissue depots in Asian Indians across normoglycaemia, prediabetes and type 2 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to evaluate hepatic, pancreatic and abdominal fat depots across glycaemic categories in Asian Indians with matched BMI, and to identify predictors of dysglycaemia.

METHODS

In this cross-sectional study, 45 adults (15 each with normoglycaemia or living with prediabetes and newly diagnosed type 2 diabetes) were matched for BMI. Fat fractions in the liver and pancreas were quantified on the basis of the proton density fat fraction (PDFF) measured using multi-echo chemical-shift-encoded MRI (CSE-MRI). We quantified the cross-sectional area of following abdominal fat compartments by MRI: subcutaneous adipose tissue (SCAT) (anterior, posterior, superficial, deep), intra-abdominal adipose tissue (IAAT), intra-peritoneal adipose tissue, retroperitoneal adipose tissue etc. Total body fat (%) and total fat mass (g) were measured using dual-energy x-ray absorptiometry (DEXA). Insulin sensitivity and beta cell function were derived from HOMA indices.

RESULTS

The hepatic fat fraction (HFF) was nearly twofold higher in the prediabetes group (10.78 ± 6.50%) and the type 2 diabetes group (10.35 ± 9.95%) compared with the normoglycaemia group (5.34 ± 4.69%), with significant differences for both comparisons (p=0.009 and p=0.026, respectively). The fat fractions in the pancreas were similarly elevated in individuals living with prediabetes (5.83 ± 4.73%) and type 2 diabetes (5.35 ± 4.75%) compared with the normoglycaemic group (2.97 ± 3.56%, p<0.05). IAAT, superficial SCAT, posterior SCAT and retroperitoneal adipose tissue were significantly higher in individuals living with prediabetes and those with type 2 diabetes than in the normoglycaemic group (p<0.05). Superficial SCAT and posterior SCAT were also significantly higher in individuals living with prediabetes compared to those with type 2 diabetes (p<0.05). After adjustment for age and BMI, only fat fractions in the liver remained an independent predictor of dysglycaemia (OR 1.11 per 1% increase; p=0.023). Each 1% increase in the fat fraction in the liver increased odds of prediabetes by 16% and those of overall dysglycaemia by 11%. HOMA-β was preserved or elevated in individuals living with prediabetes but decreased in those with type 2 diabetes.

CONCLUSIONS/INTERPRETATION: Asian Indians living with prediabetes or type 2 diabetes at a modestly increased BMI of approximately 25 kg/m2 exhibit marked ectopic fat. The fat fraction in the liver independently predicted dysglycaemia. These findings highlight the need for early and aggressive interventions at the stage of normoglycaemia and prediabetes to avert beta cell decline and diabetes progression in Asian Indians.

TRIAL REGISTRATION: Clinical Trials Registry of India (CTRI/2023/06/054228).