Elevations in markers of liver injury and risk of type 2 diabetes - The insulin resistance atherosclerosis study
ABSTRACT A limited number of studies have reported associations of markers of liver injury, including elevated concentrations of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), with prospective risk of type 2 diabetes. However, only one study has adjusted for a detailed measure of insulin sensitivity (insulin sensitivity index [S(i)]), which is important given associations of obesity and S(i) with nonalcoholic fatty liver disease (NAFLD). Our objective was to investigate the associations of elevated AST and ALT with incident type 2 diabetes among 906 participants in the Insulin Resistance Atherosclerosis Study who were nondiabetic at baseline. S(i) and acute insulin response (AIR) were measured directly from the frequently sampled intravenous glucose tolerance test among black, Hispanic, and non-Hispanic white participants aged 40-69 years. After 5.2 years, 148 individuals had developed type 2 diabetes. Baseline AST and ALT were positively correlated with fasting insulin (r = 0.22 and r = 0.35, respectively), waist circumference (r = 0.18 and r = 0.34), and fasting glucose (r = 0.13 and r = 0.29) and inversely with S(i) (r = -0.18 and r = -0.30; all P < 0.0001). In separate logistic regression models adjusting for age, sex, ethnicity, clinical center, and alcohol consumption, participants in the highest quartiles (Q4) of AST and ALT were at significantly increased risk of incident type 2 diabetes compared with those in the lowest three quartiles (Q1-Q3): AST: odds ratio (OR) 1.73 (95% CI 1.17-2.57); ALT: OR 2.32 (1.36-3.75). After further adjustment for smoking, waist circumference, triglyceride, HDL, impaired glucose tolerance, S(i), and AIR, both AST and ALT remained significantly associated with incident type 2 diabetes: AST, Q4 vs. Q1-Q3: OR 1.98 (1.23-3.17); ALT, Q4 vs. Q1-Q3: OR 2.00 (1.22-3.28). There were no interactions of sex, ethnicity, obesity, impaired glucose tolerance, or S(i) with AST or ALT in the prediction of type 2 diabetes. When entered into the same model with adjustment for demographic variables, both C-reactive protein and ALT independently predicted type 2 diabetes. In addition, AST and ALT were positively associated with incident type 2 diabetes after excluding former and moderate to heavy drinkers. In conclusion, AST and ALT independently predict type 2 diabetes. Baseline elevations of these markers may reflect NAFLD or related pathologies.
SourceAvailable from: Setor KunutsorFrontiers in Endocrinology 11/2014; 5:189. DOI:10.3389/fendo.2014.00189
Article: Prediabetes and associated disorders[Show abstract] [Hide abstract]
ABSTRACT: Prediabetes represents an elevation of plasma glucose above the normal range but below that of clinical diabetes. Prediabetes includes individuals with IFG, IGT, IFG with IGT and elevated HbA1c levels. Insulin resistance and β-cell dysfunction are characteristic of this disorder. The diagnosis of prediabetesis is vital as both IFG and IGT are indeed well-known risk factors for type 2 diabetes with a greater risk in the presence of combined IFG and IGT. Furthermore, as will be illustrated in this review, prediabetes is associated with associated disorders typically only considered in with established diabetes. These include cardiovascular disease, periodontal disease, cognitive dysfunction, microvascular disease, blood pressure abnormalities, obstructive sleep apnea, low testosterone, metabolic syndrome, various biomarkers, fatty liver disease, and cancer. As the vast majority of individuals with prediabetes are unaware of their diagnosis, it is therefore vital that the associated conditions are identified, particularly in the presence of mild hyperglycemia, so they may benefit from early intervention.Endocrine 10/2014; 48(2). DOI:10.1007/s12020-014-0436-2 · 3.53 Impact Factor
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ABSTRACT: To determine the ability of the proposed diagnostic value of a 1-h OGTT glucose ≥155mg/dL to identify individuals with non-alcoholic fatty liver disease (NAFLD) diagnosed by ultrasonography in a cohort of adult white individuals. The study group comprised 710 white individuals participating to the CATAnzaro MEtabolic RIsk factors (CATAMERI) Study, a cross-sectional study assessing cardio-metabolic risk factors in individuals carrying at least one risk factor including dysglycemia, overweight/obesity, hypertension, dyslipidemia. a 75 g oral Oral Glucose Tolerance Test (OGTT) was performed with 0, 30, 60, 90 and 120 min sampling for plasma glucose and insulin measurements. Cardio-metabolic risk factors including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT) were assessed in the whole cohort. Of the 710 participants examined, 295 had normal glucose tolerance (NGT) with 1-hour post-load plasma glucose <155 mg/dL (NGT 1h-low), 109 individuals had NGT 1h-high, 104 had isolated impaired fasting glucose (IFG), and 202 had impaired glucose tolerance (IGT). As compared with NGT 1h-low, NGT 1h-high and IGT subjects exhibited significantly higher body mass index (BMI), triglycerides, high sensitivity C reactive protein, ALT, GGT, and hepatic insulin resistance (IR), assessed by the liver IR index, as well as lower high density lipoprotein, and insulin-like growth factor-1 (IGF-1) levels. In a logistic regression analysis adjusted for age, gender, and BMI, NGT 1h-high participants had a 1.5-fold increased risk of having NAFLD and an even increased risk was observed in subjects with IGT (1.8-fold), but not in the isolated IFG group (1.01-fold). These data suggest that the value of a 1-hour OGTT glucose ≥155 mg/dL may be helpful to identify a subset of NGT individuals at risk for NAFLD.04/2014; 2(1):e000016. DOI:10.1136/bmjdrc-2014-000016