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DPP-4 inhibitors and cardiovascular disease in type 2 diabetes mellitus. Expectations, observations and perspectives
No full textAims: Cardiovascular disease (CVD) is the greatest burden of type 2 diabetes mellitus (T2DM) in terms of morbility, mortality and costs for individuals and societies. Therefore, its prevention is a major goal in diabetes care. Optimal treatment of hyperglycemia is certainly instrumental to CVD prevention. Optimal treatment means both establishing the most appropriate glycemic target for the given individual and selecting the medication(s) with the most favourable benefit/safety ratio. CVD safety, if not a clear CVD benefit, is certainly required for all antidiabetic agents.Dipeptidyl-peptidase-4 (DPP-4) inhibitors are among the classes of antidiabetic agents most recently made available for diabetes care. A major question to be addressed is the effect of these compounds on CVD. Expectations were high for their mechanism of action, which targets also post-prandial glucose and minimize hypoglycemia risk, thereby providing a sort of global glucose control, and for some potentially beneficial extra-glycemic effects. This article reviews the existing literature on this issue.Data synthesis: Data published so far document that DPP-4 inhibitors have a wide spectrum of glycemic and extra-glycemic effects potentially reducing the risk of CVD as well as favourable effects on intermediate or surrogate CVD endpoints. These data heralded a better CVD outcome. Accordingly, pooling CVD safety data from phase 3 and 4 studies conducted with DPP-4 inhibitors suggested that their use might translate into a better CVD outcome. Data from three CVD outcome RCTs with alogliptin, saxagliptin and sitagliptin documented no harm but did not show any benefit on major CVD events. A modest but significant increased risk of hospitalization for heart failure was observed with saxagliptin and with alogliptin (only in subjects with no history of heart failure before randomization) but not with sitagliptin. A study currently in progress with linagliptin will provide further insights in the issue of CVD safety and benefit.Conclusions: It should be considered that most alternative oral antidiabetic agents generally do not possess a better CVD risk profile than DPP-4 inhibitors and that some of them, indeed, should be used with caution because of potentially adverse effects on heart and vasculature. Overall, the selection of antidiabetic agent(s) with the most favourable CVD profile is mandatory but still challenging in diabetes care. (C) 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved
The white blood cell count:its relatioship to plasma insulin and other cardiovascular risk factors in healthy male
No full textGlucose and insulin suppression of plasma free fatty acids in obese subjects with normal glucose tolerance or mild, newly diagnosed type 2 (non-insulin-dependent) diabetes
No full textThe in vivo suppressive effect of glucose and insulin on plasma free fatty acid concentrations was investigated in obese subjects with (n = 6) and without (n = 6) Type 2 (non-insulin-dependent) diabetes mellitus during a 4h-hyperglycemic glucose clamp (about 11.2 mmol/l). Somatostatin was infused (250 micrograms/h) during the third h of glucose clamp to inhibit glucose-stimulated insulin secretion. Plasma insulin values were similar in the two groups at fasting and all throughout the study (F = 0.04; p = NS, two way analysis of variance), while the amount of glucose metabolized during the clamp was lower in diabetic subjects. Plasma free fatty acid concentrations, which were similar in the two groups at fasting, decreased during hyperglycemia and glucose-induced hyperinsulinemia (0-120 min; 180-240 min), and rose during hyperglycemia and somatostatin-inhibited insulin secretion (120-180 min). However, plasma free fatty acid concentrations were significantly higher in diabetic subjects all along the study period both in absolute terms (F = 11.4; p less than 0.0001) and when individual data were recalculated as percent of fasting value (F = 13.3; p less than 0.0001). Our data suggest that suppressibility of fasting plasma free fatty acids is lower in obese Type 2 diabetes in comparison with obese non-diabetic subjects
Hyperuricaemia: relationships to body fat distribution and other components of the insulin resistance syndrome in 38-year-old healthy men and women
No full textThe aim of this work was to evaluate whether hyperuricaemia correlates with the cluster of metabolic and haemodynamic disorders closely associated with insulin resistance syndrome (IRS) in young apparently healthy individuals also, and, if so, whether hyperinsulinaemia itself or some other component of this syndrome, are independently associated with hyperuricaemia. The subjects were a random population sample of 181 (M = 94/F = 87) 38-year-old apparently healthy subjects, non-diabetic, without a history of gout. Obesity (overall and regional), serum lipid profile, uric acid, fasting glucose and insulin, 2 h insulin after glucose-load (only in men), blood pressure and main behavioural variables were measured. As expected, most parameters were statistically different between men and women. In particular, serum uric acid levels were significantly higher in the male group than in female group (348 +/- 59 mumol l-1 vs 277 +/- 59 mumol l-1, P < 0.0001). After adjustment for sex, in pooled individuals, serum uric acid concentration showed positive associations with BMI (r = 0.21; P < 0.001), waist/hip girth (WHR; r = 0.45; P < 0.0001), waist/thigh girth (WTR; r = 0.35; P < 0.0001) and subscapula/triceps skinfold ratios (STR; r = 0.30; P < 0.001). Furthermore, serum uric acid was also positively correlated with fasting insulin (r = 0.23; P < 0.001), serum triglycerides (r = 0.34; P < 0.0001), LDL cholesterol (r = 0.16; P = < 0.01), diastolic blood pressure (r = 0.26; P < 0.001), and negatively with HDL/total cholesterol ratio (r = 0.28; P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS
Serum 25-hydroxyvitamin D3 concentrations and carotid artery intima-media thickness among type 2 diabetic patients
No full textStudio comparativo dell'attività di alcuni enzimi del metabolismo glucidico nelle cellule mononucleate circolanti e nel tessuto adiposo.
No full textEnzymatic activities related to intermediary metabolism of glucose in circulating mononuclear cells from obese humans: relationship to enzyme activity in adipose tissue
No full textIn order to assess whether enzyme activities of glucose metabolism measured in mononuclear blood cells reflect those in a typical insulin target tissue, we studied hexokinase, 6-phosphofructokinase, glucose-6-phosphate dehydrogenase, and 6-phosphogluconate dehydrogenase activities in lymphomonocytes and in hypogastric adipose tissue from 15 nondiabetic obese women. Statistically significant relationships were found in the activities of hexokinase (r = 0.53, p less than 0.05), 6-phosphofructokinase (r = 0.85, p less than 0.01), and 6-phosphogluconate dehydrogenase (r = 0.72, p less than 0.01) between the two tissues. These results suggest that mononuclear blood cells may be suitable as a model for studying cytosolic key enzymes involved in the glucose metabolism of humans
Differences in glucose metabolic enzyme activities in human adipose tissue from abdominal and gluteal regions
No full textIn order to verify whether intersite differences exist in glucose metabolism of subcutaneous human adipose tissue, basal and insulin-stimulated 14C-1-glucose incorporation into triglycerides and the activities of some enzymes of glucose disposal were tested in abdominal and gluteal adipose tissue of 31 nondiabetic obese otherwise healthy women during isocaloric diet and after 2 weeks of very-low-calorie-protein-sparing modified diet. Basal 14C-1-glucose incorporation into triglycerides was quite similar in the adipose tissue of the two sites, and it was not influenced by dietary restriction. Insulin stimulated this metabolic activity to the same extent in both sites during isocaloric diet; after hypocaloric diet this effect of insulin was slightly decreased in adipose tissue of the abdominal site and completely abolished in the gluteal site. No enzymatic activity was different between the examined subcutaneous regions during the isocaloric diet; after very-low-calorie intake, hexokinase activity decreased in both sites, once again more markedly in the gluteal one; glucose-6-P-dehydrogenase activity decreased in the adipose tissue of the gluteal region only. These data suggest that glucose metabolism of the adipose tissue of the gluteal region is particularly decreased by severe calorie restriction. Therefore, since lipolysis does not occur at a higher rate in gluteal adipose tissue during calorie restriction, this tissue seems to undergo a resting metabolic phase during hypocaloric diet
Estimates of in vivo insulin action in man: comparison of insulin tolerance tests with euglycemic and hyperglycemic glucose clamp studies
No full textWe compared estimates of in vivo insulin action derived from insulin tolerance tests (ITT) and euglycemic and hyperglycemic glucose clamp studies in 17 normal subjects and 19 patients with various diseases characterized by insulin resistance. Fifteen subjects underwent an ITT and a euglycemic clamp study, 17 subjects underwent an ITT and a hyperglycemic clamp study, and 4 subjects underwent all 3 tests. The ITT consisted of a bolus iv injection of regular insulin (0.1 U/kg BW). The plasma glucose disappearance rate during the 3- to 15-min period following the insulin injection was taken as a measure of insulin action. In both euglycemic and hyperglycemic clamp studies, which were carried out with standard techniques, the ratio between the amount of glucose infused to maintain glycemia at the desired level and the mean plasma insulin concentration from 60-120 min (M) (euglycemic clamp studies) or 20-120 min (I) (hyperglycemic clamp studies) was used as a measure of insulin action. A close correlation was found between plasma glucose disappearance rate and the M/I ratio during either the euglycemic (r = 0.811; P less than 0.001) or the hyperglycemic (r = 0.826; P less than 0.001) clamp studies. These results suggest that the 15-min ITT is suitable as a simple and rapid estimation of in vivo insulin action when glucose clamp studies are not feasible, as in large series of subjects or serial studies
Normale effetto inibitorio della somatostatina sulla secrezione della cellula B pancreatica nell'obesità umana
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