SGLT2 inhibition increases serum copeptin in young adults with type 1 diabetes

AimsCopeptin, a surrogate of vasopressin, is elevated in type 1 diabetes (T1D) and predicts kidney disease and cardiovascular mortality. Given the cardiorenal protective effects of SGLT2 inhibition (SGLT2i), our aim was to examine: 1) the relationship between serum copeptin, metabolic, renal and systemic hemodynamic parameters in adults with T1D; and 2) serum copeptin after SGLT2i with empagliflozin.Materials and methodsIn this post-hoc, exploratory analysis, serum copeptin, glomerular filtration rate (GFR_Inulin), effective renal plasma flow (ERPF_PAH), plasma renin angiotensin aldosterone system markers, HbA_1c, 24-hour urine volume and sodium excretion were measured in 40 participants with T1D (24.3 ± 5.1 years) during eu- and hyperglycaemia before and after 8 weeks of 25 mg of daily empagliflozin.ResultsHigher baseline copeptin correlated with higher HbA_1c, lower 24-hour urine volume and sodium excretion, after correcting for age, sex, systolic blood pressure, and HbA_1c. Copeptin concentrations increased in response to empagliflozin under euglycaemia (4.1 ± 2.1 to 5.1 ± 2.8 pmol/L, P = 0.0053) and hyperglycaemia (3.3 ± 1.4 to 5.6 ± 2.8 pmol/L, P < 0.0001). The rise in copeptin in response to empagliflozin correlated with change in 24-hour urine volume, but was independent of changes in fractional excretion of sodium and haematocrit.ConclusionsElevated serum copeptin was associated with worse glycaemic control and lower diuresis and natriuresis. SGLT2i increased serum copeptin in adults with T1D, and the rise correlated with change in diuresis, but not natriuresis and hemo-concentration. Further work is required to evaluate the clinical implications of elevated copeptin with SGLT2i, including whether it is simply a marker of diuresis or may contribute to cardiorenal disease long-term.     

Efficacy,safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are recommended for glycaemic management in patients with type 2 diabetes (T2D). Oral semaglutide, the first oral GLP-1RA, has recently been approved for clinical use, based on the results of the randomized, Phase 3a Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) clinical trials. The PIONEER programme tested oral semaglutide in patients with T2D of duration ranging from 3.5 to 15 years, from monotherapy through to insulin add-on, in global populations and two trials dedicated to Japanese patients. Outcomes (glycated haemoglobin [HbA1c] and body weight reduction, plus other relevant efficacy and safety endpoints) were tested against both placebo and active standard-of-care medications. A separate trial evaluated the cardiovascular safety of oral semaglutide in patients with T2D at high cardiovascular risk. Over periods of treatment up to 78 weeks, oral semaglutide 7 and 14 mg once daily reduced HbA1c and body weight across the spectrum of T2D, and improved other diabetes-related endpoints, such as fasting plasma glucose. Oral semaglutide provided significantly better efficacy than placebo and commonly used glucose-lowering medications from the dipeptidyl peptidase-4 inhibitor (sitagliptin) and sodium-glucose co-transporter-2 inhibitor (empagliflozin) classes, as well as the subcutaneous GLP-1RAs liraglutide and dulaglutide. Oral semaglutide was well tolerated in line with the known safety profile of GLP-1RAs, with transient gastrointestinal events being the most common side effects reported. Cardiovascular safety was demonstrated for oral semaglutide in patients with cardiovascular disease or high cardiovascular risk. The results of the PIONEER programme suggest that oral semaglutide is efficacious and well tolerated for glycaemic control of T2D. The availability of oral semaglutide may help to broaden treatment choice and facilitate adoption of earlier GLP-1RA treatment in the paradigm of T2D management.     

Design,synthesis, and evaluation of a series of novel phenylpropanoic acid derivatives agonists for the FFA1

Free fatty acid 1 (FFA1/GPR40) has attracted extensive attention as a novel target for the treatment of type 2 diabetes for its role in the enhancement of insulin secretion with glucose dependency. Aiming to develop novel potent FFA1 agonists, a new series of phenylpropionic acid derivatives were designed and synthesized on the basis of the modification of chemical cement of TAK‐875, AMG‐837, and LY2881835. Among them, most promising compounds 7 , 14 , and 15 were obtained with EC₅₀ values of 82, 79, and 88 nM, exhibiting a powerful agonistic activity compared to TAK‐875 (95.1 nM). During Oral glucose tolerance test in normal mice, compound 7 , 14 , and 15 had significant glucose‐lowering effect at the dose of 50 mg/kg. Furthermore, compound 15 (50 mg/kg) also significantly improved in glucose tolerance in type 2 diabetic mice. Herein, we reported the discovery and optimization of a series of potent FFA1 agonists. The discovery supported further exploration surrounding this scaffold.     

电话随访对妊娠期糖尿病孕妇遵医行为及妊娠结局的影响

目的探讨电话随访对妊娠期糖尿病(GDM)孕妇遵医行为及妊娠结局的影响。方法选择2013年10月~2014年10月在我院就诊的100例GDM孕妇,随机分为研究组和对照组,各50例。对照组采用常规护理。研究组在常规护理的基础上采用电话随访指导。比较两组遵医行为及各项临床参数和妊娠并发症。结果研究组遵医行为明显优于对照组;增重、空腹血糖、餐后2h血糖、糖化血红蛋白均控制在正常范围;妊娠期高血压、早产、巨大儿、羊水过多等妊娠并发症发生率均低于对照组,两组比较有显著性差异(P0.05)。结论电话随访能帮助GDM孕妇提高遵医行为,较好地控制血糖,从而有效降低GDM孕妇并发症的发生。     

动吃两平衡换算工具对2型糖尿病患者教育效果的影响

目的探讨动吃两平衡换算工具对2型糖尿病患者教育效果的影响。方法将我院辖区内的128例2型糖尿病患者,按随机数字表法分为观察组65例和对照组63例。两组均进行糖尿病健康教育,观察组采用动吃两平衡换算工具加以指导。对照组采用常规方式进行健康教育。3个月后,观察两组各项指标及其教育依从性。结果干预后两组生化指标比较,观察组明显优于对照组,有显著性差异(P0.05),观察组依从性(除戒烟戒酒外)明显高于对照组,有显著性差异(P0.05)。结论采用动吃两平衡换算工具进行糖尿病健康教育指导,有利于糖尿病患者进行自我管理。     

Effect of new criteria on the diagnosis of gestational diabetes in women submitted to gastric bypass

BackgroundBariatric surgery has been shown to improve many obesity related co-morbidities, including gestational diabetes mellitus (GDM). Recently, new diagnostic criteria for GDM following the International Association of Diabetes and Pregnancy Study Group recommendations were implemented. The objective of this study was to compare the use of 2 different GDM criteria in diagnostic and pregnancy outcome after Roux-en-Y gastric bypass (RYGB).MethodsPregnant women who had previously undergone RYGB (n = 30) were screened for GDM with Carpenter and Coustan (C&C) criteria (n = 18) or the new diagnostic criteria (n = 12).ResultsNone of the patients screened using C&C criteria where diagnosed with GDM, while 50% of the patients screened with the new criteria had GDM. Among women that underwent oral glucose tolerance tests (OGTT) (n = 19) as required for the new diagnostic criteria, 57.9% developed reactive hypoglycemia. All women diagnosed with GDM had excellent metabolic control during pregnancy and comparing the outcome of these pregnancies and those of women without GDM, there were no significant differences regarding the age at time of surgery or at pregnancy, body mass index before surgery and pregnancy, parity, previous history of GDM, time from surgery to conception, weight lost until pregnancy, weight gain during pregnancy, gestational age at delivery, and birth weight adjusted for gestational age.ConclusionNew GDM diagnostic criteria in post-RYGB pregnant women increased the prevalence of GDM diagnostic without changing pregnancy outcomes. In addition, OGTTs were associated with a high rate of reactive hypoglycemia. These data suggest that alternative GDM diagnostic criteria are needed for these postbariatric patients.