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OBJECTIVE We examined the impact of acarbose, an α-glucosidase inhibitor, on incident diabetes and regression to normoglycemia in 6,522 Acarbose Cardiovascular Evaluation (ACE) trial participants in China who had impaired glucose tolerance (IGT) and coronary heart disease (CHD). RESEARCH DESIGN AND METHODS Participants were randomly assigned to acarbose or placebo and followed with four monthly fasting plasma glucose (FPG) tests and annual oral glucose tolerance tests. Incident diabetes was defined as two successive diagnostic FPG levels ≥7 mmol/L or 2-h plasma glucose (PG) levels ≥11.1 mmol/L while taking study medication or a masked adjudicated confirmation of this diagnosis. Regression to normoglycemia was defined as FPG RESULTS Incident diabetes was less frequent with acarbose compared with placebo (3.2 and 3.8 per 100 person-years, respectively; rate ratio 0.82 [95% CI 0.71, 0.94], P = 0.005), with no evidence of differential effects within the predefined subgroups after accounting for multiple testing. Regression to normoglycemia occurred more frequently in those randomized to acarbose compared with placebo (16.3 and 14.1 per 100 person-years, respectively; 1.16 [1.08, 1.25], P < 0.0001). This effect was greater in participants not taking an ACEi or ARB (1.36 [1.21, 1.53], Pinteraction = 0.0006). The likelihood of remaining in normoglycemic regression did not differ between the acarbose and placebo groups (P = 0.41). CONCLUSIONS Acarbose reduced the incidence of diabetes and promoted regression to normoglycemia in Chinese people with IGT and CHD.

Robust diabetes risk estimates in Asian patients with impaired glucose tolerance (IGT) and coronary heart disease (CHD) are lacking. We developed a Chinese type 2 diabetes risk calculator using Acarbose Cardiovascular Evaluation (ACE) trial data.There were 3105 placebo-treated ACE participants with requisite data for model development. Clinically relevant variables, and those showing nominal univariate association with new-onset diabetes (P .10), were entered into BASIC (clinical variables only), EXTENDED (clinical variables plus routinely available laboratory results), and FULL (all candidate variables) logistic regression models. External validation was performed using the Luzhou prospective cohort of 1088 Chinese patients with IGT.Over median 5.0 years, 493 (15.9%) ACE participants developed diabetes. Lower age, higher body mass index, and use of corticosteroids or thiazide diuretics were associated with higher diabetes risk. C-statistics for the BASIC (using these variables), EXTENDED (adding male sex, fasting plasma glucose, 2-hour glucose, and HbA1c), and FULL models were 0.610, 0.757, and 0.761 respectively. The EXTENDED model predicted a lower 13.9% 5-year diabetes risk in the Luzhou cohort than observed (35.2%, 95% confidence interval 31.3%-39.5%, C-statistic 0.643).A risk prediction model using routinely available clinical variables can be used to estimate diabetes risk in Chinese people with CHD and IGT.目的: 对亚洲冠心病合并糖耐量受损人群, 目前还缺乏可靠的糖尿病风险估算。因此我们利用阿卡波糖心血管评估(ACE)试验数据, 建立了一个中国糖尿病风险计算工具。 方法: 建模人群为ACE研究安慰剂组并有建模所需的完整数据的受试者, 共有3105名。临床相关变量和单因素分析中与新发糖尿病有显著相关的变量(P0.10)作为候选变量, 用于建立基础模型(仅有临床变量)、扩展模型(临床变量加上常用的实验室指标)和完全模型(所有候选变量)。利用四川泸州前瞻性队列中的1088例IGT受试者进行模型外部验证。 结果: 在5.0年的中位随访中, 共有493名(15.9%)ACE受试者进展为糖尿病。较低的年龄、较高的体重指数、使用皮质类固醇或噻嗪类利尿剂均与较高的糖尿病风险相关。基础模型(使用以上变量)、扩展模型(加上男性、空腹血糖、2小时血糖和HbA1c)和完整模型的C统计量分别为0.610、0.757和0.761。扩展模型预测泸州队列5年糖尿病风险为13.9%, 比实际观察低[35.2% (95%CI 31.3%-39.5%), C统计量:0.643]。 结论: 使用常规临床变量的风险预测模型可用于估计中国成人冠心病合并糖耐量受损人群的糖尿病风险。.

Background: Pharmacotherapy provides an option for overweight and obese adults to reduce their body weight if lifestyle modification fails. This systematic review summarises latest and likely practice-changing evidence for the benefits and harms of weight-lowering drugs. Methods: The network meta-analysis included searches of PubMed, Embase, and Cochrane Library (CENTRAL) for randomised controlled trials of weight-lowering drugs in overweight and obese adults. We performed a frequentist random-effect network meta-analysis to summarise the evidence and applied GRADE frameworks to rate the certainty of the evidence, calculate the absolute effects, categorise interventions and present the findings. Findings: The 143 eligible trials enrolled 49 810 participants. Except for levocarnitine, all drugs lowered body weight compared with lifestyle modification alone; all subsequent numbers refer to comparisons with lifestyle modification alone. High to moderate certainty evidence established phentermine/topiramate (odds ratio [OR] of ≥5% weight reduction: 8·00, 95% confidence interval [CI]: 5·19 to 12·34; mean difference [MD] of percent body weight change: −7·97%, 95%CI: −9·28 to −6·66%) and glucagon-like peptide-1 (GLP-1) receptor agonists (OR: 6·20, 95% CI: 4·88 to 7·89; MD: −5·75%, 95%CI: −6·30 to −5·20%) were among the most effective in lowering weight. Naltrexone/bupropion (OR: 2·68, 95% CI: 2·06 to 3·49), phentermine/topiramate (OR, 2·36, 95% CI: 1·60 to 3·46), GLP-1 receptor agonists (OR: 2·16, 95% CI: 1·68 to 2·78), and orlistat (OR: 1·68, 95% CI: 1·38 to 2·05) increase any adverse event leading to drug discontinuation. In a post hoc analysis, semaglutide, one of the GLP-1 receptor agonists, demonstrated for both likelihood of ≥5% weight loss (OR: 9·81, 95% CI: 7·06 to 13·63) and percent body weight change (MD: −11.41%, 95%CI: −12.54 to −10.27%) and substantially larger than any other drugs with an increased risk of adverse events leading to discontinuation (OR: 1·98; 95% CI: 1·33 to 2·96). Interpretation: In overweight and obese adults, phentermine/topiramate and GLP-1 receptor agonists proved the best drugs in reducing weight; of the GLP-1 agonists, semaglutide may be the most effective. Funding: 1.3.5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (grant numbers ZYGD18022 and 2020HXF011). Declaration of Interest: We declare no competing interests.

OBJECTIVES To evaluate the performance and cost-effectiveness of existing diabetes risk scores (DRSs) to screen for undiagnosed diabetes mellitus (UDM) and prediabetes (PD) in a community-based southwestern Chinese population. METHODS Participants in TIDE-Chengdu survey with requisite data and without known diabetes were included. Five Chinese-derived DRSs and six non-Chinese-derived DRSs were included for evaluation. Their performance in detecting UDM and UMD or PD (UDM/PD) was assessed using the C-statistic. The cost-effectiveness of the optimal DRS was compared with that of capillary fasting blood glucose (CFBG). RESULTS Of the 1,692 TIDE-Chengdu survey participants included, 177 (10.5%) had UDM and 339 (20.0%) had PD. The rural participants (N = 737) were more likely to have UDM (13.4% vs. 8.2%) and PD (24.8% vs. 16.3%) than their urban counterparts (N = 955) (P

Patients with type 2 diabetes (T2D) have a higher risk of heart failure (HF) than healthy people, and the prognosis of patients with diabetes and current or previous HF is worse than that of patients with only diabetes. We reviewed the HF outcomes in recently published cardiovascular outcome trials (CVOTs) of three new classes of anti-diabetic agents, namely, dipeptidyl peptidase-4 inhibitors (DPP-4is), glucagon-like-peptide 1 receptor agonists (GLP-1RAs), and sodium glucose cotransporter-2 inhibitors (SGLT-2is) or SGLT-2 and SGLT-1 dual inhibitors and divided the patients into two groups based on the history of HF (with or without) and analyzed their risks of HHF based on the receipt of the aforementioned anti-diabetes drug types. Since the follow-up period differed among the trials, we expressed the rate of HHF as events/1,000 person-years to describe the HF outcome. At last we pooled the data and analyzed their different effects and mechanisms on heart failure outcomes. Although DPP-4is did not increase the risk of HHF in T2D patients with a history of HF, they were associated with a significantly higher risk of HHF among patients without history of HF. Some GLP-1RAs reduced the risk of macrovascular events, but none of these drugs reduced the risk of HHF in patients with T2D irrespective of their HF history. It was not clarified whether SGLT-1/2is can improve the prognosis of macrovascular events in patients with T2D, but these drugs reduced the risk of HHF regardless of patients’ histories of HF. This information may be useful or referential for the “precise” selection of hyperglycemic medications. Further researches still needed to clarify the mechanisms of these anti-diabetic medications.

Background: Acarbose and dipeptidyl peptidase-4 inhibitors (DPP-4is) have several similarities regarding their efficacy. Assessing the hypoglycemic and weight-loss effects, as well as the tolerability between them at their optimal dosages, could provide a better management of adult type 2 diabetics.Methods: We performed a systematic review and network meta-analysis (NMA) on randomized controlled trials that were identified from the databases of EMBASE, MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, Conference Proceedings Citation Index, ClinicalTrials.gov, China National Knowledge Infrastructure, Wan Fang, and SinoMed. The trials with 300 mg/day of acarbose or the recommended doses of DPP-4is were the most optimal for our NMA. The mean differences (MD) and relative risk (RR) derived from eligible studies were used.Results: Among the 15,411 obtained potential studies, 13 pair-wise trials and 48 monotherapy studies were included in the meta-analysis and NMA, respectively. DPP-4is had a greater glucose-lowering effect, but a weaker weight-loss effect than acarbose in pair-wise meta-analysis (p < 0.05). However, NMA with 11,877 participants showed that, at their optimal doses, acarbose and DPP-4is had similar glucose-lowering effects on the 2-h postprandial glucose (MD 0.96 mmol/L, 95% credible interval −0.56 to 2.54), HbA1c (0.05%, −0.25 to 0.33), fasting plasma glucose reductions (−0.27 mmol/L, −0.76 to 0.24), and HbA1c < 7.0% target goal achievement (RR 1.33, 0.51 to 3.64). Acarbose was superior to DPP-4is regarding weight loss (MD −1.23 kg, −2.08 to −0.33). Acarbose had more withdrawal, gastrointestinal, and overall adverse events than DPP-4is (p < 0.05), but the differences disappeared after longer treatment (p > 0.05).Conclusions: Acarbose and DPP-4is have similar glucose-lowering effects, but the weight-loss effects of acarbose are superior. Therefore, in the use of the most optimal dosages, overweight/obese type 2 diabetics might benefit more from a treatment with acarbose than DPP-4is.

Background Preventing type 2 diabetes is a major challenge in China, which has the world's largest population with impaired glucose tolerance (IGT). Given that no validated diabetes risk-prediction tools exist for Chinese people with IGT to inform decision making when considering primary diabetes prevention measures, we evaluated the performance of published Asian-derived type 2 diabetes risk-prediction models in Chinese people with IGT. Methods To identify Asian-derived type 2 diabetes risk-prediction models we did a systematic MEDLINE and Embase literature search for publications from inception until July 13, 2019. The publications identified were divided into basic (clinical variables only) and extended (plus laboratory variables) models. Validation was done in two prospective Chinese IGT cohorts: the Acarbose Cardiovascular Evaluation (ACE) trial of participants with IGT and coronary heart disease treated with placebo (n=3241), and the Luzhou survey cohort with IGT in which 96% did not have coronary heart disease (n=1155). Model performance was assessed in terms of discrimination (C-statistic) and calibration (Hosmer-Lemeshow test and calibration plot). Findings We identified 36 Asian-derived models (13 basic and 23 extended). In the ACE trial type 2 diabetes developed over a median of 5 years (IQR 3·4–6·0) with a follow-up for 15·7% of participants and in the Luzhou cohorts the disease developed over 3 years (3·0–3·0) with a follow-up for 20·7%. Basic models showed poor discrimination in these populations (C-statistic 0·53–0·59 for the ACE trial participants and 0·52–0·58 for the Luzhou cohorts). Extended models showed poor-to-acceptable discrimination (C-statistic 0·56–0·73 for the ACE trial participants and 0·51–0·66 for the Luzhou cohorts). Most extended models overestimated diabetes risk in the ACE cohort and underestimated risk in the Luzhou cohort, whereas all basic models underestimated diabetes risk in both populations. Basic and extended models showed poor calibration, although performance was improved by recalibration. The navigator model showed the best discrimination in both populations but had poor calibration. Interpretation In Chinese people with IGT (with or without coronary heart disease), Asian-derived basic models to predict type 2 diabetes did not exhibit good discrimination or calibration. Several extended models performed better, but a robust Chinese diabetes risk-prediction tool remains a major unmet need. Funding None.

GW501516-activated peroxisome proliferator-activated receptor (PPAR) β/δ and G-protein-coupled receptor (GPR) 40 were shown to protect pancreatic β cells against lipoapoptosis. Therefore, this study aimed to investigate whether activated PPARβ/δ could protect type 2 diabetic rats from lipoapoptosis through regulation of GPR40 and to compare the protective effects of activated PPARβ/δ and PPARγ. We made an animal model of type 2 diabetic lipoapoptosis by feeding spontaneously type 2 diabetic Goto-Kakizaki (GK) rats with a high-fat diet (HFD) to evaluate the effects of PPARβ/δ on islet β cell apoptosis. And, treated INS-1 cells with 0.5 mM palmitate (PAM) in the absence/presence of GW501516 (a specific agonist of PPAR β/δ) and with/without transfection of GPR40 siRNA to explore the underlying molecular mechanism. HFD aggravated GK rats' poorer INSR30, lower mass, greater apoptosis of β cells, lower mass, and lower expression of GPR40, which were similarly improved by GW501516 at 3 or 6 mg/kg day and pioglitazone. Compared with pioglitazone, GW501516 caused more weight loss and had no effect on insulin resistance. GW501516 protected INS-1 cells from PAM-induced apoptosis by upregulating GPR40 and activating Akt/Bcl-2/caspase-3. Activated extracellular regulated protein kinases (ERK) was relevant to the lipoapoptosis in INS-1 cells, but was not involved in the antilipoapoptotic effect of GW501516. These results showed that the PPARβ/δ agonist GW501516 protected β cells from lipoapoptosis and improved β cell mass by upregulating GPR40 and activating the Akt/Bcl-2/caspase-3 pathway, but not the ERK-signaling pathway.

We aim to conduct a meta-analysis, by stratifying diabetic patients with or without clinical cardiovascular diseases (CVD), to explore whether there are different cardiovascular effects of dipeptidyl peptidase-4 inhibitors (DPP-4is) on these two different classes of diabetic patients.We searchedMedline,Embase, theCochrane Libraryand ClinicalTrials.gov for relevant randomized controlled trials (RCTs). The included trials are divided into CVD (+) trials (subjects with established CVD), and CVD (-) trials (subjects with no CVD). We use all-cause mortality and cardiovascular outcomes as primary endpoints.(1) Three CVD (+) trials were included and 36,895 subjects were enrolled with a mean follow-up duration of 127.1 weeks. The pooled results showed that DPP-4is treatment, compared with the placebo, did not significantly affect all-cause mortality (RR, 1.03; 95% CI, 0.95 to 1.11), cardiovascular death (1.01, 0.91 to 1.12), myocardial infarction (0.98, 0.88 to 1.08) or stroke (1.02, 0.88 to 1.18) in diabetic patients with coexisting CVD history; however, it significantly increased the risk of heart failure (1.14, 1.01 to 1.27) in this population. 2) Thirty-five CVD (-) trials were included, and 29,600 patients were enrolled with a mean follow-up duration of 77.8 weeks. The analysis comparing DPP-4is with the placebo control showed that DPP-4is treatment did not significantly affect the risk of all-cause mortality or cardiovascular outcomes in diabetic patients free of CVD history. However, when compared with the active control, the pooling data showed that DPP-4is had a significant reduction on the risk of stroke (0.58, 0.34 to 0.99) but did not significantly affect the risk of all-cause mortality and other cardiovascular outcomes.DPP-4is may have no cardiovascular protective effects in diabetic patients with coexisting CVD, while there is a lack of definitive evidence supporting the cardiovascular benefits of DPP-4is treatment among diabetic patients free of CVD history.

Rationale: Pheochromocytomas are rare catecholamine-secreting tumors arising from adrenomedullary chromaffin cells, usually causing hypertension, palpitation and headache. However, pheochromocytoma crisis, on the contrary, might present with hypotension, multiple organ dysfunction or even mimicking other diseases, leaving physician with diagnostic difficulties. In this study, we present a case featured hypotension, shock and multiple organ dysfunction syndrome on admission, which nearly lead us to miss the diagnosis of pheochromocytoma. Patient concerns: A 14-year-old female student presented with cough, hemoptysis and dyspnea for one week was reported. Diagnoses: The laboratory test showed significantly increase in plasma norepinephrine and 24-hour urine norepinephrine, the enhanced CT of bilateral adrenal gland showed two round-like masses (left: 4 × 5 × 3 cm; right: 6 × 4 × 3 cm) with soft tissue density in each adrenal gland. The post-surgical pathology confirmed the diagnosis of pheochromocytoma. Interventions: The resection of bilateral adrenal tumors was conducted after the preoperative medical treatment of phenoxybenzamine for two weeks. Outcomes: The patient underwent follow-up for a year and a half and showed no signs of recurrence. Lessons: The diagnosis and treatment process of the patient in this study indicates us that when we meet a patient with hypotension and multiple organ dysfunctions in a relatively short time, the suspicion of pheochromocytoma should not be missed.