Non-alcoholic fatty liver disease and risk of type 2 diabetes

Non-alcoholic fatty liver disease (NAFLD) covers a spectrum of liver disease from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. NAFLD is commonly associated with features of the metabolic/insulin resistance syndrome ('Metabolic/Obese NAFLD') and may therefore predict type 2 diabetes (T2DM). For this review, we searched for prospective studies examining whether NAFLD predicts T2DM, and if so, whether this occurs independently of factors such as age and obesity. These studies included NAFLD diagnosed by ultrasonography (n = 6) or liver enzymes (n = 14). All ultrasonography studies found NAFLD to predict the risk of T2DM independently of age, and in 4 out of 6 studies NAFLD was also a predictor independently of BMI. NAFLD was a predictor of T2DM in all 14 studies where NAFLD was diagnosed by liver enzymes. In 12 of these studies, ALT or AST or GGT were significant predictors of T2DM risk, independently of age and BMI. NAFLD, however, is heterogeneous and may also be caused by common genetic variants. The I148M variant in PNPLA3 and the E167K variant in TM6SF2 are both associated with increased liver fat content, but not features of the metabolic/insulin resistance syndrome. These genetic forms of NAFLD predict NASH and cirrhosis but not T2DM. Taken together these data imply that 'Metabolic/Obese NAFLD' predicts T2DM independently of age and obesity and support the role of hepatic insulin resistance in the pathogenesis of this disease. (C) 2016 Elsevier Ltd. All rights reserved.Peer reviewe

Hypoglycaemia in Type 2 diabetes

The primary cause of hypoglycaemia in Type 2 diabetes is diabetes medication—in particular, those which raise insulin levels independently of blood glucose, such as sulphonylureas (SUs) and exogenous insulin. The risk of hypoglycaemia is increased in older patients, those with longer diabetes duration, lesser insulin reserve and perhaps in the drive for strict glycaemic control. Differing definitions, data collection methods, drug type/regimen and patient populations make comparing rates of hypoglycaemia difficult. It is clear that patients taking insulin have the highest rates of self-reported severe hypoglycaemia (25% in patients who have been taking insulin for > 5 years). SUs are associated with significantly lower rates of severe hypoglycaemia. However, large numbers of patients take SUs in the UK, and it is estimated that each year > 5000 patients will experience a severe event caused by their SU therapy which will require emergency intervention. Hypoglycaemia has substantial clinical impact, in terms of mortality, morbidity and quality of life. The cost implications of severe episodes—both direct hospital costs and indirect costs—are considerable: it is estimated that each hospital admission for severe hypoglycaemia costs around £1000. Hypoglycaemia and fear of hypoglycaemia limit the ability of current diabetes medications to achieve and maintain optimal levels of glycaemic control. Newer therapies, which focus on the incretin axis, may carry a lower risk of hypoglycaemia. Their use, and more prudent use of older therapies with low risk of hypoglycaemia, may help patients achieve improved glucose control for longer, and reduce the risk of diabetic complications

Comparison of insulin glargine and liraglutide added to oral agents in patients with poorly controlled type 2 diabetes

Peer reviewe

Relationship between protein O -linked glycosylation and insulin-stimulated glucose transport in rat skeletal muscle following calorie restriction or exposure to O -(2-acetamido-2-deoxy-d-glucopyranosylidene)amino- N -phenylcarbamate

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/65566/1/j.1365-201X.2004.01403.x.pd

Variation at the NFATC2 Locus Increases the Risk of Thiazolidinedione-Induced Edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) Study

Objective: Thiazolidinediones are used to treat type 2 diabetes. Their use has been associated with peripheral edema and congestive heart failure - outcomes that may have a genetic etiology. Research Design and Methods: We genotyped 4,197 participants of the multiethnic DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication) trial with a 50k single nucleotide polymorphisms (SNP) array, which captures ∼2000 cardiovascular, inflammatory, and metabolic genes. We tested 32,088 SNPs for an association with edema among Europeans who received rosiglitazone (n = 965). Results: One SNP, rs6123045, in NFATC2 was significantly associated with edema (odds ratio 1.89 [95% CI 1.47-2.42]; P = 5.32 × 10-7, corrected P = 0.017). Homozygous individuals had the highest edema rate (hazard ratio 2.89, P = 4.22 × 10-4) when compared with individuals homozygous for the protective allele, with heterozygous individuals having an intermediate risk. The interaction between the SNP and rosiglitazone for edema was significant (P = 7.68 × 10-3). Six SNPs in NFATC2 were significant in both Europeans and Latin Americans (P < 0.05). Conclusions: Genetic variation at the NFATC2 locus contributes to edema among individuals who receive rosiglitazone

DURAbility of Basal Versus Lispro Mix 75/25 Insulin Efficacy (DURABLE) Trial 24-Week Results: Safety and efficacy of insulin lispro mix 75/25 versus insulin glargine added to oral antihyperglycemic drugs in patients with type 2 diabetes

OBJECTIVE - To compare the ability of two starter insulin regimens to achieve glycemic control in a large, ethnically diverse population with type 2 diabetes. RESEARCH DESIGN AND METHODS - During the initiation phase of the DURABLE trial, patients were randomized to a twice-daily lispro mix 75/25 (LM75/25; 75% lispro protamine suspension, 25% lispro) (n = 1,045) or daily glargine (GL) (n = 1,046) with continuation of prestudy oral antihyperglycemic drugs. RESULTS - Baseline A1C was similar (LM75/25: 9.1 +/- 1.3%; GL: 9.0 +/- 1.2%; P = 0.414). At 24 weeks, LM75/25 patients had tower A1C than GL patients (7.2 +/- 1.1. vs. 7.3 +/- 1.1%, P = 0.005), greater A1C reduction (-1.8 +/- 1.3 vs. -1.7 +/- 1.3%, P = 0.005), and higher percentage reaching A1C target CONCLUSIONS - Compared With GL, LM75/25 resulted in slightly lower A1C at 24 weeks and a moderately higher percentage reaching A1C targe