Pancreatic fat in type 2 diabetes:Causal or coincidental?

Type 2 diabetes(T2D)is a multifactorial metabolic disorder affecting more than 450 million people across the globe.With the increasing prevalence of T2D and obesity,the role of fat accumulation at sites other than subcutaneous adipose tissue has received significant attention in the pathophysiology of T2D.Over the past decade and a half,a pressing concern has emerged on investigating the association of pancreatic fat accumulation or pancreatic steatosis with the development of disease.While a few reports have suggested a possible association between pancreatic fat and T2D and/or impaired glucose metabolism,a few reports suggest a lack of such association.Pancreatic fat has also been linked with genetic risk of developing T2D,prediabetes,reduced insulin secretion,and beta cell dysfunction albeit some confounding factors such as age and ethnicity may affect the outcome.With the technological advancements in clinical imaging and progress in assessment of pancreatic beta cell function,our understanding of the role of pancreatic fat in causing insulin resistance and development of various etiologies of T2D has significantly improved.This review summarizes various findings on the possible association of pancreatic fat accumulation with the pathophysiology of T2D.

The impact of codon 54 variation in intestinal fatty acid binding protein gene on the pathogenesis of diabetes mellitus in Chinese

Objective To investigate whether or not the intestinal fatty acid binding protein gene (FABP2) Ala54Thr variation is related to non insulin dependent diabetes mellitus (NIDDM), obesity, dyslipidemia and glucose stimulated insulin secretion (GSIS) in Chinese.Methods The FABP2 Ala54Thr variation was detected by PCR/HhaI digestion in 231 Chinese subjects (116 with normal glucose tolerance (NGT), 54 with impaired glucose tolerance (IGT) and 61 with NIDDM). Plasma glucose, insulin and C peptide levels before and after 75 g glucose load as well as fasting lipid profile were determined.Results (1) The Ala54 and Thr54 allele frequencies in Chinese were 0.71 and 0.29 respectively; (2) The FABP2 Ala54Thr variation was neither associated with fasting and post challenged plasma glucose levels nor with NIDDM; (3) This variation was neither associated with fasting lipid profile nor with obesity; (4) The IGT subjects with genotype Thr54(+) (Thr54 homozygotes and heterozygotes) had lower fasting, 2 hour and total C peptide levels and smaller AUC representing lesser C peptide secretion after glucose challenge than those with genotype Thr54( ) (Ala54 homozygotes) (P= 0.04 , 0.03, 0.01 and 0.01 respectively). The serum insulin levels changed in the same tendency.Conclusions The glucose stimulated insulin secretion (GSIS) reserve of islet beta cells is more limited in subjects with FABP2 Thr54(+) genotype than in those with FABP2 Thr54(-) genotype. It suggests that FABP2 codon 54 variation might contribute to the insufficient insulin secretion in the development of NIDDM in Chinese.