Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

Women with IBD had a higher rate of voluntary childlessness and fewer children than the general population. These observations are likely attributable to a higher educational achievement and to racial background of the patients rather than to IBD-related reasons. Although contraception use in patients with IBD was lower that in the general population, use was higher after the diagnosis of IBD than before the diagnosis. Contraceptive choices and adoption rates were similar to the general population. Women with CD were more affected by miscarriages after diagnosis with IBD than those with UC.

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Aims/Introduction: To compare safety and efficacy of the extended-release formulation exenatide once weekly (EQW) vs exenatide twice daily (EBID) for 26 weeks in type 2 diabetes patients from China, India, Japan, South Korea and Taiwan. Materials and Methods: A randomized, comparator-controlled, open-label study included 681 patients with type 2 diabetes inadequately controlled (hemoglobin A1c [HbA 1c ] ! 7 and 11%) with oral antihyperglycemic medications (OAMs). Patients added 2 mg EQW or 10 lg EBID to current OAMs. Safety was re-evaluated 10 weeks after last treatment. Results: EQW was superior to EBID on HbA 1c measures at week 26 (Least-squares mean treatment difference: À0.31% [95% confidence interval À0.49, À0.14%]). More EQW-treated patients achieved target HbA 1c 7.0% (P = 0.003), 6.5% (P < 0.001), or 6.0% (P = 0.003). Fasting serum glucose reductions were greater among EQW-treated patients (P < 0.001). Blood glucose profiles improved in both treatment groups (P < 0.001). Weight loss occurred with both treatments, but was greater with EBID. Adverse events ( ! 10%, either group) were nausea, injection-site induration, dyslipidemia and vomiting. Injection-site induration was more frequent with EQW, whereas nausea, vomiting and hypoglycemia were less frequent. One episode each of major hypoglycemia (EBID) and pancreatitis (EQW) were reported. Conclusion: In this population, EQW and EBID showed efficacious glucose and weight control; safety and tolerability were consistent with observations in non-Asian patients. This trial was registered with ClinicalTrials.gov (no. NCT00917267). (J Diabetes Invest,

Aims We investigated the prevalence and risk factors for developing erectile dysfunction (ED) in 1312 Korean men with diabetes in a multicentre study. MethodsWe used the modified International Index for Erectile Function-5 criteria to identify mild, moderate and complete ED. A standardized face-toface questionnaire was used by trained interviewers, and validated against telephone interviews. We recorded the duration of diabetes, level of glycaemic control, vital signs, complications, exercise and alcohol and smoking habits, and diabetes treatments used. ResultsThe mean age and median duration of diabetes were 53.8 ± 6.65 and 6 years (range 1-43), respectively. The mean HbA 1c and fasting glucose levels were 7.9 ± 1.65% and 8.6 ± 2.82 mmol/l, respectively. The overall prevalences of mild, moderate, complete ED and all ED (mild-to-complete) were 20.1, 19.5, 25.8 and 65.4%, respectively. ED was more common with age, reaching 79.3% in men aged > 60 years. Subjects aged > 60 years and with a duration of diabetes > 10 years were at greatest risk for all ED (OR = 10.4, 95% CI 5.8-18.5, P < 0.001) and complete ED (OR = 13.2, 95% CI 7.3-23.9, P < 0.001) when compared with the reference group (age 40-50 years with duration < 6 years). Age, duration of diabetes, HbA 1c , insulin use, neuropathy and macrovascular complications were positively associated with ED, but alcohol consumption and exercise habits were negatively associated. ConclusionsThe prevalence of complete ED was approximately six times higher than in the general population.

OBJECTIVE -The aim of this study was to examine the effects of rosiglitazone on adiponectin and plasma glucose levels in relation with common adiponectin gene (ACDC) polymorphisms.RESEARCH DESIGN AND METHODS -A total of 166 patients with type 2 diabetes were treated with rosiglitazone (4 mg/day) for 12 weeks without changing any of their previous medications. In all, single nucleotide polymorphism (SNP)45 and SNP276 of ACDC were examined.RESULTS -Regarding SNP45, there was a smaller reduction in the fasting plasma glucose (FPG) level and the HbA 1c value in the carriers of the GG genotype than in the carriers of the other genotypes (P ϭ 0.031 and 0.013, respectively). There was a smaller increase in the serum adiponectin concentration for the GG genotype than for the other genotypes (P ϭ 0.003). Regarding SNP276, there was less reduction in the FPG level for the GG genotype than for the other genotypes (P ϭ 0.001). In the haplotype analysis, the reductions in the FPG and HbA 1c levels were smaller for the GG homozygote haplotype than for the other haplotypes (P ϭ 0.001 and 0.001, respectively). The increase in the plasma adiponectin concentration for the GG homozygote haplotype was smaller than that of the other haplotypes (P ϭ 0.003).CONCLUSIONS -These data suggest that genetic variations in the adiponectin gene can affect the rosiglitazone treatment response of the circulating adiponectin level and blood glucose control in type 2 diabetic patients. Diabetes Care 28:1139 -1144, 2005A diponectin is a circulating protein secreted by adipocytes and is associated with the development of insulin resistance and atherosclerosis (1,2). Serum adiponectin concentrations are lower in patients with type 2 diabetes, obesity, and coronary heart disease than in healthy subjects (3,4). This molecule is known to be a potent insulin sensitizer. Thiazolidinediones lower the blood glucose level primarily by activating the peroxisome proliferator-activated receptor (PPAR)-␥, which then improves insulin sensitivity (5). The synthetic PPAR-␥ agonist, rosiglitazone, is reported to increase the serum adiponectin level in type 2 diabetes (6).Adiponectin is encoded by ACDC, which is located on chromosome 3q27 (7,8). Studies of ACDC mutations have revealed 16 single nucleotide polymorphisms (SNPs) (9). Among them Ϫ11377, ϩ45, and ϩ276 have been reported to be associated with type 2 diabetes, circulating adiponectin levels, and insulin resistance in a Japanese population (10,11). However, previous studies on the association between ACDC SNPs, type 2 diabetes, and adiponectin levels have shown that the specific SNPs associated with this process differ according to both the study and the ethnic population. The aim of this study was to examine the association between SNPs in ACDC and the response to rosiglitazone. In addition, this study also investigated the PPAR responsive element (PPRE) polymorphism in the ACDC promoter. RESEARCH DESIGN ANDMETHODS -A total of 166 patients were treated with rosiglitazone (4 mg/ day) during a 12-week treatme...

Pancreatic b cells adapt to pregnancy-induced insulin resistance by unclear mechanisms. This study sought to identify genes involved in b cell adaptation during pregnancy. To examine changes in global RNA expression during pregnancy, murine islets were isolated at a time point of increased b cell proliferation (E13 . 5), and RNA levels were determined by two different assays (global gene expression array and G-protein-coupled receptor (GPCR) array). Follow-up studies confirmed the findings for select genes. Differential expression of 110 genes was identified and follow-up studies confirmed the changes in select genes at both the RNA and protein level. Surfactant protein D (SP-D) mRNA and protein levels exhibited large increases, which were confirmed in murine islets. Cytokine-induced expression of SP-D in islets was also demonstrated, suggesting a possible role as an anti-inflammatory molecule. Complementing these studies, an expression array was performed to define pregnancy-induced changes in expression of GPCRs that are known to impact islet cell function and proliferation. This assay, the results of which were confirmed using realtime reverse transcription-PCR assays, demonstrated that free fatty acid receptor 2 and cholecystokinin receptor A mRNA levels were increased at E13 . 5. This study has identified multiple novel targets that may be important for the adaptation of islets to pregnancy.

Telehealthcare was as effective as conventional care at improving glycemia in patients with type 2 diabetes without serious adverse effects.