Association of Genetic Non-alcoholic Fatty Liver Disease with Insulin Resistance-Are we Different?

INTRODUCTION: Metabolic risk factors such as obesity, insulin resistance, type 2 diabetes mellitus and dyslipidemia are associated with non-alcoholic fatty liver disease (NAFLD). In the development and progression of NAFLD genetic mutations also play a significant role. NAFLD associated with the rs 738409 polymorphism of patatin-like phospholipase domain containing 3 gene (PNPLA3) G allele does not feature the typical metabolic abnormalities of NAFLD, including insulin resistance. In the light of rising epidemic of metaobesity in our population this study aimed to evaluate the relation of PNPLA3 polymorphism with insulin resistance. METHODS: In this case control hospital based study, 100 patients of NAFLD were recruited based on ultrasound findings of hepatic steatosis. Healthy subjects age and gender matched(n = 100) from the institute who volunteered to be part of the study were recruited as controls based on the sole criteria of the absence of fatty liver on ultrasonography and normal alanine and aspartate transaminases (ALT and AST) levels. Anthropometry, biochemical profiles and insulin resistance by homeostatic model assessment of insulin resistance (HOMA-IR) were assessed. RESULTS: A higher frequency of CG and GG genotypes of rs738409 polymorphism of PNPLA3 was observed in patients with NAFLD than controls. These patients with G allele had increased ALT, dyslipidemia and insulin resistance. The polymorphism had positive correlation with severity of hepatic steatosis. CONCLUSION: The presence of the PNPLA3 G allele is associated with a risk of NAFLD. Our study shows that subjects with variant PNPLA3 are not only at increased risk for the development and progression of NAFLD, but also have increased insulin resistance.

Evaluation of neutrophil gelatinase-associated lipocalin and cystatin C as early markers of diabetic nephropathy.

INTRODUCTION: Diabetes mellitus (DM) is a major cause of concern because of its increasing prevalence rate and related microvascular as well as macrovascular complications, including kidney disease. Microalbuminuria has been accepted as the earliest marker for diabetic nephropathy; however, a large proportion of renal impairment occurs in nonalbuminuric state. We planned to investigate the serum and urinary levels of the tubular damage markers (neutrophil gelatinase-associated lipocalin [NGAL] and cystatin C [Cys C]) in patients of type 2 diabetes to detect early kidney injury. MATERIALS AND METHODS: This cross-sectional hospital-based study included 180 patients with type 2 DM according to the American Diabetes Association criteria. Serum NGAL (S.NGAL) and urine NGAL (U.NGAL) and Cys C were measured in all study participants and investigated for correlation with microalbuminuria. RESULTS: Our results showed that U.NGAL and S.NGAL levels were significantly high in patients with microalbuminuria as compared to normoalbuminuric controls. Serum Cys C was also higher in microalbuminuric patients than who had normoalbuminuria. A positive correlation of urinary albumin excretion with S.NGAL and U.NGAL was noted. U.NGAL also showed positive correlation with duration of diabetes, glycated hemoglobin, and dyslipidemia. Receiver operating characteristic curve analysis showed that the area under the curve for U.NGAL and S.NGAL were 1 and 0.8, respectively, which indicates that they are sensitive markers for early renal damage. CONCLUSION: Urinary biomarkers were significantly elevated in normoalbuminuric type 2 diabetic patients compared with nondiabetic controls and could be used as markers of nephropathy at a very early stage even before the development of microalbuminuria, the current gold standard for early diagnosis. Despite the promise of these new biomarkers, further large, multicenter prospective studies are still needed.