Pramlintide, the synthetic analogue of amylin: physiology, pathophysiology, and effects on glycemic control, body weight, and selected biomarkers of vascular risk

Pramlintide is a synthetic version of the naturally occurring pancreatic peptide called amylin. Amylin and pramlintide have similar effects on lowering postprandial glucose, lowering postprandial glucagon and delaying gastric emptying. Pramlintide use in type 1 and insulin requiring type 2 diabetes mellitus (DM) is associated with modest reductions in HbA1c often accompanied by weight loss. Limited data show a neutral effect on blood pressure. Small studies suggest small reductions in LDL-cholesterol in type 2 DM and modest reductions in triglycerides in type 1 DM. Markers of oxidation are also reduced in conjunction with reductions in postprandial glucose. Nausea is the most common side effect. These data indicate that pramlintide has a role in glycemic control of both type 1 and type 2 DM. Pramlintide use is associated with favorable effects on weight, lipids and other biomarkers for atherosclerotic disease

Baseline Factors Associated With Glycemic Control and Weight Loss When Exenatide Twice Daily Is Added to Optimized Insulin Glargine in Patients With Type 2 Diabetes

OBJECTIVETo determine variables associated with glycemic and body weight responses when adding exenatide to basal insulin–treated type 2 diabetes.RESEARCH DESIGN AND METHODSExploratory subgroup analyses based on baseline A1C, disease duration, and BMI of a 30-week study comparing exenatide twice daily to placebo, added to optimized insulin glargine (intent-to-treat analysis: 137 exenatide; 122 placebo).RESULTSExenatide participants had greater A1C reductions compared with optimized insulin glargine alone, irrespective of baseline A1C (P < 0.001). Exenatide participants with longer diabetes duration and those with lower BMI had greater A1C reductions (P < 0.01). Exenatide participants lost more weight, regardless of baseline A1C or BMI (P < 0.05). Exenatide participants with longer diabetes duration lost the most weight (P < 0.001).CONCLUSIONSExenatide added to optimized basal insulin was associated with improved glycemic control and weight loss, irrespective of baseline A1C, diabetes duration, and BMI. Changes were evident in modestly obese patients and in those with longer diabetes duration

The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study

Objective To determine whether there is a link between hypoglycaemia and mortality among participants in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial

Revascularization for coronary artery disease in diabetes mellitus: Angioplasty, stents and coronary artery bypass grafting

Author Manuscript: 2011 April 14Patients with diabetes mellitus (DM) are prone to a diffuse and rapidly progressive form of atherosclerosis, which increases their likelihood of requiring revascularization. However, the unique pathophysiology of atherosclerosis in patients with DM modifies the response to arterial injury, with profound clinical consequences for patients undergoing percutaneous coronary intervention (PCI). Multiple studies have shown that DM is a strong risk factor for restenosis following successful balloon angioplasty or coronary stenting, with greater need for repeat revascularization and inferior clinical outcomes. Early data suggest that drug eluting stents reduce restenosis rates and the need for repeat revascularization irrespective of the diabetic state and with no significant reduction in hard clinical endpoints such as myocardial infarction and mortality. For many patients with 1- or 2-vessel coronary artery disease, there is little prognostic benefit from any intervention over optimal medical therapy. PCI with drug-eluting or bare metal stents is appropriate for patients who remain symptomatic with medical therapy. However, selection of the optimal myocardial revascularization strategy for patients with DM and multivessel coronary artery disease is crucial. Randomized trials comparing multivessel PCI with balloon angioplasty or bare metal stents to coronary artery bypass grafting (CABG) consistently demonstrated the superiority of CABG in patients with treated DM. In the setting of diabetes CABG had greater survival, fewer recurrent infarctions or need for re-intervention. Limited data suggests that CABG is superior to multivessel PCI even when drug-eluting stents are used. Several ongoing randomized trials are evaluating the long-term comparative efficacy of PCI with drug-eluting stents and CABG in patients with DM. Only further study will continue to unravel the mechanisms at play and optimal therapy in the face of the profoundly virulent atherosclerotic potential that accompanies diabetes mellitus.National Institutes of Health (U.S.) (GM 49039

Ramipril and the development of diabetes

La Convención de las Naciones Unidas sobre la Utilización de las Comunicaciones Electrónicas en los Contratos Internacionales es el primer tratado suscrito con el objetivo de facilitar el uso transfronterizo de las comunicaciones electrónicas en las relaciones comerciales. Este artículo describe los objetivos de la política detrás de la preparación de dicho instrumento, su ámbito de aplicación y sus principales disposiciones sustantivas. Se hace referencia específica a la interacción de esa Convención con otros tratados ya adoptados por Colombia y otros Estados, como la Convención sobre el Reconocimiento y Ejecución de las Sentencias Arbitrales Extranjeras (la “Convención de Nueva York”) y la Convención de las Naciones Unidas sobre Contratos de Compraventa Internacional de Mercaderías (cisg). Por último, el artículo analiza los patrones en la adopción de la Convención en la última década y concluye que Colombia debería considerar la posibilidad de ratificar la Convención, que ha firmado en 2007, para fortalecer su economía digital mediante la modernización de la legislación vigente sobre el comercio electrónico

Ramipril and the development of diabetes

Ramipril and the development of diabetes. Yusuf S, Gerstein H, Hoogwerf B, Pogue J, Bosch J, Wolffenbuttel BH, Zinman B; HOPE Study Investigators. Canadian Cardiovascular Collaboration Project Office, Hamilton General Hospital, 237 Barton St East, Hamilton, Ontario, Canada L8L 2X2. [email protected] CONTEXT: Type 2 diabetes is a growing clinical and public health problem. Preventive efforts related to lifestyle modification are not always successful; therefore, alternative prevention strategies need to be studied. OBJECTIVE: To investigate the effectiveness of ramipril, an angiotensin-converting enzyme inhibitor, in preventing diabetes among high-risk persons. DESIGN, SETTING, AND PARTICIPANTS: The randomized, controlled Heart Outcomes Prevention Evaluation trial of 5720 patients older than 55 years without known diabetes but with vascular disease who were followed up for a mean of 4.5 years. The study included 267 hospitals in 19 countries and was conducted between 1994 and 1999. INTERVENTION: Patients were randomly assigned to receive ramipril, up to 10 mg/d (n = 2837), or placebo (n = 2883). MAIN OUTCOME MEASURE: Diagnosis of diabetes determined from self-report at follow-up visits every 6 months, compared between the 2 groups. RESULTS: One hundred and two individuals (3.6%) in the ramipril group developed diabetes compared with 155 (5.4%) in the placebo group (relative risk [RR], 0.66; 95% confidence interval [CI], 0.51-0.85, P<.001). Similar results were noted when different diagnostic criteria were used; in the ramipril group, the RR for diagnosis of diabetes and hemoglobin A(1c) greater than 110% was 0.60 (95% CI, 0.43-0.85), for initiation of glucose-lowering therapy, 0.56 (95% CI, 0.41-0.77), and for both, 0.51 (95% CI, 0.34-0.76). These effects were also consistently seen in several subgroups examined. CONCLUSIONS: Ramipril is associated with lower rates of new diagnosis of diabetes in high-risk individuals. Because these results have important clinical and public health implications, this hypothesis requires prospective confirmatio