1,721,235 research outputs found
Albiglutide for the treatment of type 2 diabetes mellitus
No full textThe glucagon-like peptide 1 (GLP-1) receptor agonists are a new class of antidiabetic drugs that provide the benefits of decreasing HbA1c and plasma glucose concentrations, stimulating insulin secretion with a very low risk of hypoglycemia, and promoting weight loss. With the exception of once-weekly exenatide, currently available GLP-1 receptor agonists are administered once or twice daily by injection. Albiglutide is a new GLP-1 receptor agonist recently approved in the U.S. (TanzeumTM) and European Union (Eperzan®) for the treatment of patients with type 2 diabetes with a dosage of 30 mg once weekly, which may be increased to 50 mg if the glycemic response is inadequate. Clinical trials showed that albiglutide once weekly delayed gastric emptying, mildly decreased body weight and had similar efficacy in the reduction of HbA1c as comparators, but it failed to demonstrate noninferiority to liraglutide. Albiglutide exhibits an acceptable safety profile, although it is associated with more frequent gastrointestinal complaints (e.g., nausea, diarrhea, vomiting) and injection-site reactions. Immunogenicity (i.e., testing positive for antidrug antibody) was observed in 5.5% of subjects but it was not associated with increased adverse events. Long-term studies are needed to fully assess potential adverse events
Decreased whole body lipolysis as a mechanism of the lipid-lowering effect of pioglitazone in type 2 diabetic patients
No full textGastaldelli A, Casolaro A, Ciociaro D, Frascerra S, Nannipieri M, Buzzigoli E, Ferrannini E. Decreased whole body lipolysis as a mechanism of the lipid-lowering effect of pioglitazone in type 2 diabetic patients. Am J Physiol Endocrinol Metab 297: E225-E230, 2009. First published May 5, 2009; doi: 10.1152/ajpendo.90960.2008.-Pioglitazone has been shown to reduce fasting triglyceride levels. The mechanisms of this effect have not been fully elucidated, but decreased lipolysis may contribute to blunt the hypertriglyceridemic response to a meal. To test this hypothesis, we studied 27 type 2 diabetes mellitus (T2DM) patients and 7 sex-, age-, and body mass index-matched nondiabetic controls. Patients were randomized to pioglitazone (45 mg/day) or placebo for 16 wk. Whole body lipolysis was measured [as the [(2)H(5)] glycerol rate of appearance (R(a))] in the fasting state and for 6 h following a mixed meal. Compared with controls, T2DM had higher postprandial profiles of plasma triglycerides, free fatty acid (FFA), and beta-hydroxybutyrate, and a decreased suppression of glycerol R(a) (P < 0.04) despite higher insulin levels [268 (156) vs. 190 (123) pmol/l, median (interquartile range)]. Following pioglitazone, triglycerides and FFA were reduced (P = 0.05 and P < 0.04, respectively), and glycerol R(a) was more suppressed [-40 (137) vs. +7 (202) mu mol/min of placebo, P < 0.05] despite a greater fall in insulin [-85 (176) vs. -20 (58) pmol/l, P = 0.05]. We conclude that, in well-controlled T2DM patients, whole body lipolysis is insulin resistant, and pioglitazone improves the insulin sensitivity of lipolysis
Improved tolerance to sequential glucose loading (Staub-Traugott effect): size and mechanisms
No full textBonuccelli S, Muscelli E, Gastaldelli A, Barsotti E, Astiarraga BD, Holst JJ, Mari A, Ferrannini E. Improved tolerance to sequential glucose loading (Staub-Traugott effect): size and mechanisms. Am J Physiol Endocrinol Metab 297: E532-E537, 2009. First published June 16, 2009; doi:10.1152/ajpendo.00127.2009. - Improved glucose tolerance to sequential glucose loading (Staub-Traugott effect) is an important determinant of day-to-day glycemic exposure. Its mechanisms have not been clearly established. We recruited 17 healthy volunteers to receive two sequential oral glucose tolerance tests (OGTTs), at time 0 min and 180 min (Study I). The protocol was repeated on a separate day (Study II) except that plasma glucose was clamped at 8.3 mmol/l between 60 and 180 min. beta-Cell function was analyzed by mathematical modeling of C-peptide concentrations. In a subgroup, glucose kinetics were measured by a triple-tracer technique (infusion of [6,6-(2)H(2)] glucose and labeling of the 2 glucose loads with [1-(2)H] glucose and [U-(13)C] glucose). In both Studies I and II, the plasma glucose response to the second OGTT equaled 84 +/- 2% (P = 0.003) of the response to the first OGTT. Absolute insulin secretion was lower (37.8 +/- 4.3 vs. 42.8 +/- 5.1 nmol/m(2), P = 0.02), but glucose potentiation (i. e., higher secretion at the same glycemia) was stronger (1.08 +/- 0.02 vs. 0.92 +/- 0.02-fold, P = 0.006), the increment being higher in Study II (+36 +/- 5%) than Study I (+19 +/- 6%, P < 0.05). In pooled data, a higher glucose area during the first OGTT was associated with a higher potentiation during the second OGTT (rho = 0.60, P = 0.002). Neither insulin clearance nor glucose clearance differed between loads, and appearance of glucose over 3 h totalled 60 +/- 6 g for the first load and 52 +/- 5 g for the second load (P = not significant). Fasting endogenous glucose production [13.3 +/- 0.6 mu mol.min(-1).kg fat-free mass (FFM)(-1)] averaged 6.0 +/- 3.8 mu mol.min(-1).kg FFM(-1) between 0 and 180 min and 1.7 +/- 2.6 between 180 and 360 min (P < 0.03). Glucose potentiation and stronger suppression of endogenous glucose release are the main mechanisms underlying the Staub-Traugott effect
Fatty liver, cardiometabolic disease and mortality
No full textPurpose of review We discuss the findings of the most recent metanalyses on the association between nonalcoholic fatty liver disease (NAFLD), cardiometabolic disease and mortality. Recent findings Recent metanalyses have shown that NAFLD is associated with incident type 2 diabetes mellitus (T2DM) and incident cardiovascular disease (CVD). Nonalcoholic steatohepatitis, which can be diagnosed by liver biopsy only in tertiary care centers, is often associated with liver fibrosis, which has been shown by metanalyses to increase both cardiovascular and liver-related mortality. Hyperlipidemia, lipotoxicity and impaired insulin secretion are among the possible mechanisms underlying the association of NAFLD with T2DM and CVD. Metanalyses of the association between NAFLD and mortality in the general population, where risk stratification cannot be performed on the basis of liver biopsy, have given contradictory results. To establish conclusively whether NAFLD adds to known prognostic factors of death in the general population will require a shared operational definition of NAFLD, purposefully designed cohort studies, and the use of clinically relevant measures of effect size
Editorial: Mechanisms for the Alteration in the Crosstalk Among Insulin-Sensitive Tissues
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[Bariatric surgery as a treatment of type 2 diabetes]. FT La chirurgia bariatrica come trattamento del diabete di tipo 2.
No full textObesity has reached epidemic proportions, predisposing to the development of type 2 diabetes and cardiovascular diseases. Weight loss is a major objective, although often difficult to achieve with medical treatments. Bariatric surgery has proven its efficacy in obtaining marked and sustained weight loss, and is also associated with a significant improvement in insulin resistance, beta cell function, lipidmetabolism, blood pressure and even diabetes remission.We examined the long termeffect of Roux-en-Y gastric bypass (RYGB, a predominantly restrictive procedure) in a patient with uncontrolled type 2 diabetes. One year after surgery, the patient had lost 30% of initial weight with a significant improvement in blood pressure, withdrawal of cholesterollowering therapy, complete remission of diabetes
Insulin resistance, adipose depots and gut: Interactions and pathological implications
No full textThis review article focuses on the many metabolic actions of insulin at the level of muscle, liver and adipose tissue. In terms of pathogenetic mechanisms, the condition of insulin resistance is complex, as multiple genetic and environmental factors, among which an increasingly sedentary lifestyle associated with high-fat diet, mutually interact according to variable patterns in time in any given individual. It is well recognized that obesity (in particular abdominal obesity) favours the development of insulin resistance. Here we evaluate the impact of obesity and ectopic fat accumulation (visceral and hepatic) on insulin resistance at the level of different target organs, i.e., muscle, liver and adipose tissue. The roles of the gut and the liver, in particular of bile acids and gut microflora, are also discussed as possible determinants of energy balance and glucose metabolis
Insulin resistance, adipose depots and gut: Interactions and pathological implications
No full textThis review article focuses on the many metabolic actions of insulin at the level of muscle, liver and adipose tissue. In terms of pathogenetic mechanisms, the condition of insulin resistance is complex, as multiple genetic and environmental factors, among which an increasingly sedentary lifestyle associated with high-fat diet, mutually interact according to variable patterns in time in any given individual. It is well recognized that obesity (in particular abdominal obesity) favours the development of insulin resistance. Here we evaluate the impact of obesity and ectopic fat accumulation (visceral and hepatic) on insulin resistance at the level of different target organs, i.e., muscle, liver and adipose tissue. The roles of the gut and the liver, in particular of bile acids and gut microflora, are also discussed as possible determinants of energy balance and glucose metabolism. (C) 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved
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