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Background: This study investigated the association between birth weight and diabetes in a Chinese population, and the effects of body mass index (BMI) and lifestyle factors in later life on this association. Methods: Data from 49 118 participants aged ≥40 years with recalled birth weight from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study, a nationwide population‐based cohort, were used. Diabetes diagnosis was based on oral glucose tolerance tests and HbA1c measurements. Logistic regression models were used to evaluate the association of birth weight and risk of diabetes in later life. Results: Increased risk of diabetes was associated with lower or higher birth weight. Compared with individuals with a birth weight of 2500 to 3499 g, the odds ratios (ORs) and 95% confidence intervals (CIs) of diabetes for individuals with a birth weight of <2500, between 3500 and 3999, and ≥4000 g were 1.28 (1.11‐1.47), 1.11 (1.04‐1.19), and 1.20 (1.07‐1.34), respectively. Significant associations were prominent in participants with a current BMI ≥24 kg/m2, but not detected in those with a normal BMI (OR 1.20 [95% CI 0.96‐1.49], 1.11 [95% CI 0.98‐1.25], and 1.10 [95% CI 0.89‐1.37], respectively). Moreover, there was no increased risk of diabetes in individuals with a low birth weight but with healthy dietary habits (OR 0.94; 95% CI 0.68‐1.29) or ideal physical activity (OR 1.41; 95% CI 0.97‐2.04). Conclusions: A U‐shaped association was observed between birth weight and the risk of diabetes. Healthy lifestyles (healthy dietary habits or ideal physical activity) may eliminate the negative effects of low birth weight in the development of diabetes, but not the effect of high birth weight. [ABSTRACT FROM AUTHOR]

We performed a meta‐analysis of randomized controlled trials (RCTs) to compare the long‐term glycaemic durability of dipeptidyl‐peptidase 4 (DPP‐4) inhibitors vs that of sulphonylureas (SUs) in patients with type 2 diabetes mellitus (T2DM), in terms of the changes in glycated haemoglobin (HbA1c) levels from an intermediate time point (26 or 52 weeks) to 104 weeks of treatment. The Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library) databases were searched for relevant RCTs. Eight RCTs were included. Compared with SUs, DPP‐4 inhibitors were associated with significantly smaller increases in the HbA1c level from 24 to 28 weeks to 104 weeks (mean difference [MD]: −0.16%, 95% confidence interval [CI]: −0.21 to −0.11; P < .001) and from 52 weeks to 104 weeks (MD −0.06%, 95% CI −0.10 to −0.02; P = .001). No significant heterogeneities were detected among the included comparisons (I2 = 0%). These results suggest that long‐term treatment with DPP‐4 inhibitors confers better durability of glycaemic response than treatment with SUs in patients with T2DM, which may indicate that DPP‐4 inhibitors better preserve islet β‐cell function compared with SUs. [ABSTRACT FROM AUTHOR]

Abstract: Background: Limited information exists regarding the efficacy of pregabalin in Chinese patients with painful diabetic peripheral neuropathy (pDPN). Methods: An 11‐week double‐blind placebo‐controlled trial was performed in Chinese pDPN patients randomized (1 : 1) to 300 mg/day pregabalin or placebo. The primary outcome was change from baseline to endpoint in mean pain score (MPS; 0, no pain; 10, worst possible pain; using the mean of the last seven daily pain scores). Secondary outcomes included weekly MPS and responder status (MPS reduced by ≥30% or ≥50% vs baseline). Subgroup analysis assessed patients with severe (≥7) baseline MPS. Adverse events (AEs) were reported. Results: In all, 620 patients were randomized (pregabalin, n = 313; placebo, n = 307). Improvement in MPS with pregabalin versus placebo was not significant (P = 0.0559). Post hoc sensitivity analyses, excluding one patient/site due to Good Clinical Practice (GCP) non‐compliance, showed pregabalin significantly improved MPS when excluding the patient (P = 0.0448) or site (P = 0.0142). Pregabalin significantly improved weekly MPS (P = 0.0164) and ≥50% responders at endpoint (P = 0.0384). Improvement in proportion of ≥30% responders, impression of change, pain intensity, and sleep did not differ significantly between the treatment groups. In the severe pDPN subpopulation, pregabalin significantly improved MPS versus placebo (P = 0.0040). The most commonly reported AE was dizziness (9.6% vs 3.9% with placebo). Conclusions: Pregabalin did not significantly improve the primary measure of pain in the trial. Significant reductions in MPS were observed when excluding the GCP non‐compliant patient/site and in the severe pDPN subpopulation. Pregabalin was well tolerated in Chinese pDPN patients. [ABSTRACT FROM AUTHOR]

Aim: To assess efficacy/safety of initial linagliptin/metformin single-pill combination (SPC) therapies versus individual drug components over 24weeks in treatment-naïve Asian patients with type 2 diabetes mellitus and insufficient glycemic control.Methods: Patients (initial glycated hemoglobin [HbA1c] ⩾7.5% to <11.0% [58-97mmol/mol]; main group) were randomized to: linagliptin 5mg once daily (qd); metformin 500mg twice daily (bid); metformin 1000mg bid; linagliptin 2.5mg/metformin 500mg bid; or linagliptin 2.5mg/metformin 1000mg bid. Patients with severe hyperglycemia (HbA1c ⩾11.0% [97mmol/mol]) received linagliptin 2.5mg/metformin 1000mg bid or linagliptin 5mg qd (switched at week 12 from linagliptin to SPC if HbA1c >8.0% [64mmol/mol]). The main group primary endpoint was HbA1c change from baseline to week 24.Results: At week 24, adjusted mean change from baseline in HbA1c (main group, n=733) was: linagliptin 5mg qd, -1.3%; metformin 500mg bid, -1.6%; metformin 1000mg bid, -2.1%; linagliptin 2.5mg/metformin 500mg bid, -2.2%; linagliptin 2.5mg/metformin 1000mg bid, -2.3%. The first test of primary HbA1c analysis (linagliptin 2.5mg/metformin 1000mg bid vs. metformin 1000mg bid) was borderline non-significant; however, SPCs produced significantly greater reductions in HbA1c from baseline versus respective monotherapies in all but one pre-defined sensitivity analysis. In the severe hyperglycemia group (n=143), linagliptin 2.5mg/metformin 1000mg bid produced a superior HbA1c reduction (-4.7%) versus linagliptin 5mg qd (-3.5%) after 12weeks. Hypoglycemic adverse events were low across groups.Conclusions: Initial linagliptin/metformin SPC significantly improved glycemic control in this population. [ABSTRACT FROM AUTHOR]

Backgrounds: As patients attending hospitals of different grades in China may receive different medical care, we investigated the clinical efficacy and safety of routine insulin therapy in patients with type 2 diabetes who were treated at grade 2 and grade 3 (highest grade) hospitals in China.Methods: 2683 patients with type 2 diabetes were enrolled in a multicenter, nonrandomized, open-label, noninterventional, 12-week clinical trial performed at 62 Chinese hospitals. Patients were divided into two groups according to the hospitals' grading. Data were analyzed for efficacy (changes and normalization of glycated hemoglobin [HbA1c] and changes in fasting plasma glucose and 2-h postprandial blood glucose [PBG] levels from baseline to the final visit) and for safety (hypoglycemia).Results: After 12 weeks of routine human insulin (SciLin) therapy, decreases in mean HbA1c and PBG levels were significantly greater in patients treated at second-grade hospitals (all P < 0.001 vs. third-grade hospitals), and the HbA1c success rate (<7%) was significantly higher (46.94% vs. 38.85%; P = 0.0002). However, patients treated at second-grade hospitals had more weight gain (0.29 kg vs. 0.04 kg; P < 0.0001) and a higher incidence of total hypoglycemic events (21.82% vs. 16.79%; P = 0.0002).Conclusions: Routine insulin treatment of patients with type 2 diabetes in China demonstrates acceptable safety and effectiveness, improving blood glucose control with a low incidence of severe hypoglycemia. Patients treated at second-grade hospitals had a greater HbA1c success rate than those treated at third-grade hospitals, but with more weight gain and more hypoglycemic events. [ABSTRACT FROM AUTHOR]

Objective: To estimate the long-term cost-effectiveness of dapagliflozin versus acarbose as monotherapy in treatment-naïve patients with type 2 diabetes mellitus (T2DM) in China. Methods: The Cardiff Diabetes Model, an economic model designed to evaluate the cost-effectiveness of comparator therapies in diabetes was used to simulate disease progression and estimate the long-term effect of treatments on patients. Systematic literature reviews, hospital surveys, meta-analysis and indirect treatment comparison were conducted to obtain model-required patient profiles, clinical data and costs. Health insurance costs (2015¥) were estimated over 40 years from a healthcare payer perspective. Univariate and probabilistic sensitivity analyses were performed. Results: The model predicted that dapagliflozin had lower incidences of cardiovascular events, hypoglycemia and mortality events, was associated with a mean incremental benefit of 0.25 quality-adjusted life-years (QALYs) and with a lower cost of ¥8,439 compared with acarbose. This resulted in a cost saving of ¥33,786 per QALY gained with dapagliflozin. Sensitivity analyses determined that the results are robust. Conclusion: Dapagliflozin is dominant compared with acarbose as monotherapy for Chinese T2DM patients, with a little QALY gain and lower costs. Dapagliflozin offers a well-tolerated and cost-effective alternative medication for treatment-naive patients in China, and may have a direct impact in reducing the disease burden of T2DM. [ABSTRACT FROM AUTHOR]

We recruited a group of 6713 consecutive Chinese patients with T2D but normal renal and liver function who were admitted to one of 81 top tertiary care hospitals in China. Mild hypoglycaemia was defined as having symptomatic hypoglycaemia in one month before hospitalization. Severe hypoglycaemia was defined as having hypoglycaemia that needed assistance from other people in three months before hospitalization. Prior cardiovascular disease (CVD) was defined as having coronary heart disease, stroke, or peripheral arterial disease. Of 6713 patients, 80 and 304 had severe and mild hypoglycaemia episodes, respectively, and 561 had CVD. Patients with severe and mild hypoglycaemia episodes were more likely to have prior CVD (32.5% versus 16.5% versus 7.7%, P < 0.0001). Both mild and severe hypoglycaemia were associated with increased risk of CVD (adjusted odds ratios (ORs): 2.64, 95% CI: 1.85-3.76 for mild hypoglycaemia; 6.59, 95% CI: 3.79-11.45 for sever hypoglycaemia) than those patients free of hypoglycaemia. Further adjustment for lipid profile did not change these two ORs. In the same way, the ORs of lipid profile for CVD were similar before and after adjustment for hypoglycaemia. We concluded that hypoglycaemia and lipid profile were independently associated with increased risk of CVD. [ABSTRACT FROM AUTHOR]

The article offers information on the guidelines for insulin pump therapy guidelines in China that was released in July 2010. It states that the said therapy refers to the administration of insulin via continuous subcutaneous infusion to stimulate physiological insulin secretion to control hyperglycemia. It mentions that the use of insulin pump can improve patient's quality of life in terms of treatment compliance as well as the ability to control blood glucose level.

Premixed insulin is the most commonly used insulin in China. This trial compared the efficacy and safety of once-daily insulin glargine 100 U/mL (Gla-100) + oral antihyperglycemic drugs (OADs) and twice-daily insulin aspart 70/30 (Asp 30) + OAD in T2D patients. Chinese adults with T2D receiving stable doses of metformin and 1-2 OADs with HbA1c 7.5%-11.0% were enrolled and entered a 7-10 day SIT period in which they were treated with basal-bolus to achieve a fasting blood glucose (FBG) <7 mmol/L and 2-hour postprandial glucose (2hPG) <10 mmol/L. Patients were then randomized 1:1 to receive Gla-100 + OADs (n=192) or Asp 30 + OAD (n=192) for 24 weeks. Baseline characteristics were balanced across groups. Mean (SD) age was 54.2 (8.8) years, BMI was 26.0 (3.1) kg/m2, and duration of diabetes was 6.8 (3.0) years. At week 24, the least square mean (SE) change from baseline in HbA1c was -1.72% (0.07) and -1.70% (0.07) in the Gla-100 and Asp 30 groups, respectively (Table); group difference (-0.01%; 95% CI -0.20, 0.17) met the pre-specified non-inferiority criteria (upper bound 95% CI <0.4%). All hypoglycemia events were significantly lower in the Gla-100 group. In conclusion, compared with Asp 30 + OAD, Gla-100 + OAD showed similar efficacy but lower hypoglycemia risk in Chinese T2D patients. Disclosure: Y. Mu: Speaker's Bureau; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi-Aventis. J. Liu: Employee; Self; Sanofi China. X. Zhang: None. N. Cui: Employee; Self; Sanofi China. H. Yin: None. L. Guo: Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., BD, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Sanofi China. H. Wan: None. J. Wang: None. B. Xu: None. G. Wang: None. C. Jiang: None. L. Liang: None. W. Feng: Employee; Self; Sanofi China. Funding: Sanofi China (NCT03359837) [ABSTRACT FROM AUTHOR]

To titrate basal and bolus insulin sequentially or simultaneously during SIT remains controversial. Here we report an easy titration order verified in a 7-10 day SIT period. Insulin naïve Chinese T2D adults receiving stable doses of metformin and 1-2 oral antihyperglycemic drugs with HbA1c 7.5%-11.0% were treated with once-daily insulin glargine 100 U/mL (Gla-100) and thrice-daily insulin glulisine (Glu) for 7-10 days titrated to achieve a fasting blood glucose (FBG) <7 mmol/L and 2-hour postprandial glucose (2hPG) <10 mmol/L. Gla-100 was titrated first until FBG achieved 4.4-6.1 mmol/L, then Glu was titrated to achieve pre-meal blood glucose 4.4-6.1 mmol/L. Of 466 patients screened, 397 entered the SIT period; 391 (98.5%) completed. Baseline mean (SD) age was 54.2 (8.8) years, duration of disease was 6.8 (3.0) years, BMI was 26.0 (3.2) kg/m2, HbA1c was 9.1% (1.1), and FBG was 10.7 (2.5) mmol/L; 59.2% were male. Overall, 94.4% of patients achieved the predefined target at the end of the SIT period (Table). The mean time to first achieving 2hPG target was less than the time to first achieving FBG target, implying that titrating basal insulin first could minimize Glu dose increases and potential hypoglycemia risk. In conclusion, when starting basal-bolus regimen in SIT, basal-first titration order was effective, fast to target and well tolerated in Chinese T2D patients. Disclosure: L. Guo: Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., BD, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Sanofi China. J. Liu: Employee; Self; Sanofi China. X. Zhang: None. N. Cui: Employee; Self; Sanofi China. H. Yin: None. Y. Mu: Speaker's Bureau; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi-Aventis. H. Wan: None. J. Wang: None. B. Xu: None. G. Wang: None. C. Jiang: None. L. Liang: None. W. Feng: Employee; Self; Sanofi China. Funding: Sanofi China (NCT03359837) [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions To compare the efficacy and safety of a fixed‐ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin, insulin degludec plus insulin aspart (IDegAsp), in Chinese people with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drug(s) (OADs).In Soli‐D, a 24‐week, multicentre, open‐label, study, insulin‐naïve adults were randomized 1:1 to once‐daily injections of iGlarLixi (n = 291) or IDegAsp (n = 291), with continued metformin ± sodium‐glucose co‐transporter‐2 inhibitors. The primary endpoint was non‐inferiority in HbA1c change from baseline to week 24. Key secondary endpoints included superiority in HbA1c change and body weight (BW) change at week 24. Hypoglycaemia rates were also assessed.At week 24, iGlarLixi showed non‐inferiority and superiority over IDegAsp in HbA1c reduction (least squares [LS] mean difference: −0.20 [95% confidence interval {CI}: –0.33, −0.07]; P < .001 for non‐inferiority; [97.5% CI: –0.35, −0.05]; P = .003 for superiority). iGlarLixi decreased BW and IDegAsp increased BW from baseline to week 24, with a statistically significant LS mean difference of −1.49 kg in favour of iGlarLixi (97.5% CI: –2.32, −0.66; P < .001). Event rates (per person‐year) for American Diabetes Association (ADA) Level 1, 2 or 3 hypoglycaemia were lower for iGlarLixi (1.90) versus IDegAsp (2.72) (relative risk: 0.71; 95% CI: 0.52, 0.98). No ADA Level 3 hypoglycaemia or unexpected safety findings were reported.In Chinese people with T2D suboptimally controlled with OADs, once‐daily iGlarLixi provided better glycaemic control with BW benefit and lower hypoglycaemia event rates versus IDegAsp. [ABSTRACT FROM AUTHOR]

Objective: Several studies have demonstrated a significant association between the presence of the ear lobe crease (ELC) and cardiovascular disease. Advanced glycation end‐products (AGEs) can affect the structures and functions of proteins and contribute to the development of diabetic complications. However, few studies have reported the relationship between AGEs and ELC. The purpose of this study was to investigate the correlation of skin autofluorescence (SAF)‐AGEage (SAF‐AGEs × age/100) with ELC. Methods: This cross‐sectional study enrolled 6500 eligible participants from two communities in Beijing. Skin autofluorescence (SAF) was used to measure skin AGEs (SAF‐AGEs). SAF‐AGEage was defined as AGEs × age/100. Binary logistic regression analysis and linear regression analysis nested in logistic models were applied to test outcomes. Results: The overall prevalence of ELC with an average age of 62.7 years participants was 57.1% (n = 3714). Age, fasting blood glucose, systolic blood pressure, and lipoprotein cholesterol were all greater in participants with ELC. ELC‐positive participants had higher prevalence of coronary heart disease. Logistic analysis showed a significantly positive relationship between quartiles of SAF‐AGEage and ELC (odds ratio [OR] 1.526, 95% CI 1.324–1.759; OR 2.072, CI 1.791–2.396; and OR 2.983, CI 2.551–3.489) for the multivariate‐adjusted models, respectively. Stratified research revealed that those with a history of diabetes, hypertension, or coronary heart disease experienced the connection between SAF‐AGEage and ELC. Conclusion: ELC is associated with coronary heart disease, and the SAF‐AGE has a potential role in ELC development in elder people. [ABSTRACT FROM AUTHOR]

Our previous single-center, randomized, double-blinded, placebo-controlled phase 2 study evaluated the safety and effectiveness of human umbilical cord mesenchymal stromal cell (UC-MSC) transfusion for treating patients with type 2 diabetes mellitus (T2DM). Indeed, this potential treatment strategy was able to reduce insulin use by half in a considerable number of patients. However, many other patients' responses to UC-MSC transfusion were insignificant. The selection of patients who might benefit from UC-MSC treatment is crucial from a clinical standpoint. In this post hoc analysis, 37 patients who received UC-MSC transfusions were divided into two groups based on whether their glycated hemoglobin (hemoglobin A1c, or HbA1c) level was less than 7% after receiving UC-MSC treatment. The baseline differences between the two groups were summarized, and potential factors influencing efficacy of UC-MSCs for T2DM were analyzed by univariate and multivariate logistic regression. The correlations between the relevant hormone levels and the treatment effect were further analyzed. At the 9-week follow-up, 59.5% of patients achieved their targeted HbA1c level. Male patients with lower baseline HbA1c and greater C-peptide area under the curve (AUCC-pep) values responded favorably to UC-MSC transfusion, according to multivariate analysis. The effectiveness of UC-MSCs transfusion was predicted by AUCC-pep (cutoff value: 14.22 ng/h/mL). Further investigation revealed that AUCC-pep was increased in male patients with greater baseline testosterone levels. Male patients with T2DM with greater AUCC-pep may be more likely to respond clinically to UC-MSC therapy, and further large-scale multi-ethnic clinical studies should be performed to confirm the conclusion. [ABSTRACT FROM AUTHOR]

Objective: The sneaky onset and dismal prognosis of chronic kidney disease (CKD) make it an important public health issue. Obesity-related kidney illness has garnered more attention in recent times. Establishing and validating a risk prediction model for chronic renal illness in overweight or obese adults was the goal of this investigation. Methods: Data from the China Health and Retirement Longitudinal Study were used for analysis. The definition of CKD was reduced renal function (eGFR < 60 mL/min/1.73 m²), while overweight and obesity were characterized through a body mass index exceeding 24 kg/m². The dataset was divided into derivation and validation cohorts using a 7:3 ratio. With respect to the derivation cohort, we constructed a prediction model using LASSO analysis and multivariate logistic regression. The model's performance was evaluated using Hosmer-Lemeshow tests, calibration curves, decision curve analysis, and receiver operating characteristic (ROC) curves. The validation cohort's model was subjected to additional assessment. Results: The study was based on survey data from 2011 to 2015 and comprised 3246 individuals who were overweight or obese, with 2274 being part of the derivation cohort and 972 being part of the validation cohort. The research constructed a prediction model that included age, sex, fasting blood glucose, glycated hemoglobin, triglyceride, hypertension, and BMI. The validation cohort's area under the ROC curve was 0.812 (95% CI = 0.763, 0.859) while the derivation cohort's was 0.789 (95% CI = 0.754, 0.831). Hosmer-Lemeshow tests were utilized to evaluate the model's accuracy in the validation and derivation cohorts (P = 0.681 and 0.547, respectively). The calibration curve showed a high level of consistency between the actual observations and the projected outcomes. According to decision curve analysis, the model offered significant net advantages. Conclusions: The forecasting model established in this research has predictive value for CKD in patients with overweight or obesity. These findings could help doctors conduct early detection and intervention in clinical practice and further improve patient prognosis. [ABSTRACT FROM AUTHOR]

Aim: To investigate the efficacy and safety of beinaglutide as an adjunct to lifestyle intervention among non‐diabetic Chinese individuals with overweight or obesity. Methods: This multicentre, randomized, double‐blind, placebo‐controlled trial (ChiCTR1900023428) included 427 Chinese adults with a body mass index of 28 kg/m2 or higher (obesity) or 24‐27.9 kg/m2 (overweight) with weight‐related complications. Patients were randomized in a 2:1 ratio to receive 0.2 mg of beinaglutide (subcutaneous) thrice daily or placebo for 16 weeks. Co‐primary endpoints were body weight change and the proportion of patients with a weight reduction of 5% or more. Results: Mean body weight change from baseline to week 16 was −6.0% and −2.4% in the beinaglutide (n = 282) and placebo (n = 138) groups, respectively; the mixed model repeated measures difference was −3.6% (95% confidence interval: −4.6% to −2.6%; P <.0001). At week 16, more beinaglutide‐treated patients achieved a weight reduction of 5% or more (58.2% vs. 25.4% [placebo], odds ratio: 4.4; P <.0001) and of 10% or more (21.3% vs. 5.1% [placebo], odds ratio: 5.5; P <.0001). Beinaglutide also resulted in greater waist circumference reduction (difference: −1.81 cm; P <.01). The weight regain rate 12 weeks after beinaglutide treatment was 0.78%. Nausea (transient and mild‐to‐moderate) was the most common adverse event in the beinaglutide group (49.3% vs. 7.1% [placebo]). More patients receiving beinaglutide discontinued treatment because of adverse events (5.9% vs. 0.7% [placebo]). Pancreatitis or an increased resting heart rate was not observed in the beinaglutide group. Conclusion: Beinaglutide combined with lifestyle intervention resulted in significant and clinically meaningful weight reduction with good tolerance in non‐diabetic Chinese individuals with overweight or obesity. [ABSTRACT FROM AUTHOR]

Aim: To investigate whether the cardiorenal benefits of the sodium‐glucose co‐transporter‐2 inhibitor empagliflozin are affected by body mass index (BMI) in type 2 diabetes patients with established cardiovascular (CV) disease, including Asians. Methods: In this exploratory analysis of the EMPA‐REG OUTCOME trial, we used Cox regression to evaluate the effects of empagliflozin on all‐cause mortality, hospitalization for heart failure (HHF) or CV death, and incident or worsening nephropathy by baseline BMI category. Results: Of the 7020 participants (1517 Asians [21.6%]), 934 (13.3%), 2465 (35.1%) and 3621 (51.6%) had a BMI of less than 25, 25 to less than 30, and 30 kg/m2 or higher, respectively. Overall, hazard ratios for empagliflozin versus placebo for all‐cause mortality, HHF or CV death, and incident or worsening nephropathy were 0.68 (95% CI 0.57, 0.82), 0.66 (0.55, 0.79) and 0.61 (0.53, 0.70), respectively, and were consistent across BMI categories (P values for interaction between treatment and BMI were.6772,.3087 and.6265, respectively). Results were similar in Asians using these BMI categories and categories of less than 24, 24 to less than 28, and 28 kg/m2 or higher. Conclusion: Empagliflozin reduced cardiorenal and mortality risk regardless of BMI at baseline, including in Asians with a lower BMI. [ABSTRACT FROM AUTHOR]

Background: Triglyceride glucose index (TyG index) was related with both type 2 diabetes (T2DM) and hypertension (HTN). Prospective studies linking the TyG index to the incidence of T2DM and HTN comorbidity remain unclear. This study aimed to to explore the longitudinal association between TyG and new-onset T2DM with HTN. Methods: 4,434 subjects (1249 males and 3185 females) without initial T2DM and HTN were followed up for 7 years. This study was conducted from November 2011 to August 2018 in the Gucheng, Laoshan and Jinding communities of Beijing. The incidence of T2DM with HTN during the 7-year follow-up was identified as the endpoint. The TyG index was divided into four quartiles: the < 25% level, the 25–50% level, the 50–75% level and the ≥ 75% level. The relationships between the TyG index and T2DM with HTN were evaluated by Cox proportional hazards regression models. Results: During 7 years, the augmented trend of T2DM with HTN was observed in the participants. After adjusting for all confounding factors, compared with those in the lowest quartile of TyG index, the population in the highest quartile of TyG index had a higher risk of T2DM with HTN (hazard ratio (HR), 2.878; 95% confidence intervals (95% CI), 1.230–6.731, P = 0.015), however, the association remained significant only in the female population (HR 2.753, 95% CI, 1.061–7.139, p = 0.037). The TyG had superior predictive ability of increased risk of T2DM with HTN for the populations of older age (≥ 65 years) (HR 2.694, 95% CI 1.212–5.989, p = 0.015), higher eGFR (≥ 90 mL/(min·1.73 m2)) (HR 2.603, 95% CI 1.164–5.818, p = 0.020) or obesity (BMI ≥ 28 kg/m2) (HR 2.547, 95% CI 1.001–6.478, p = 0.020). Conclusion: A population with a higher TyG index level was more likely to have an enhanced incidence of T2DM and HTN comorbidity. TyG index could have the significance of clinical in early protection against T2DM with HTN. [ABSTRACT FROM AUTHOR]

Background: The association between weight change during early adulthood and cardiometabolic diseases remains uncertain in Chinese population. Whether the association varies with comprehensive cardiovascular health (CVH) in midlife assessed by "Life's Essential 8" has not been characterized. We aim to examine the associations of early adulthood weight change and midlife "Life's Essential 8" CVH status with cardiometabolic outcomes in a Chinese cohort. Methods: The study participants were from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study. This analysis included 72,610 middle-aged and older participants followed for a median of 3.6 years. At baseline, the participants recalled body weight at age 20 and 40 years, and we calculated change in weight and BMI between 20 and 40 years of age. Health behaviors information in "Life's Essential 8" was collected by questionnaire, and health factors were measured in the study center. During follow-up, we ascertained incident cardiovascular events based on medical records, and diagnosed incident diabetes according to the American Diabetes Association 2010 criteria. Results: 72,610 study participants were included with a mean age of 56.0 ± 8.8 years and 29% of them were males. Weight gain of more than 10 kg between 20 and 40 years of age was associated with 22% increased risk of incident cardiovascular events (HR: 1.22; 95%CI: 1.04–1.43) and 38% increased risk of diabetes (HR: 1.38; 95%CI: 1.25–1.53) compared to stable weight. Besides, the association of weight gain more than 10 kg in early adulthood with cardiometabolic risk was even stronger in those with low CVH score in midlife (HR: 2.44; 95%CI: 2.01–2.97 for incident cardiovascular events; HR: 2.20; 95%CI: 1.90–2.55 for incident diabetes) or with few ideal cardiovascular health metrics in midlife. Conclusions: Our study indicated that weight gain in early adulthood was associated with significantly increased risk of cardiometabolic diseases. And the association could be stronger in those with poor CVH profiles in midlife. These findings confirmed the significance of weight management during early adulthood and suggested that individuals who experienced substantial weight gain in early life should be encouraged to maintain good CVH status in Chinese population. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the prevalence of overweight/obesity and associated complications from a large, cross‐sectional, nationwide database in China. Materials and Methods: Data were obtained from 519 Meinian health check‐up centres across 243 cities. Eligible participants were aged ≥18 years, with a routine check‐up in 2019 (N = 21 771 683) and complete height, weight, sex and region data. The unadjusted prevalence rates of overweight/obesity were calculated by age, sex and region. In addition, the nationwide prevalence rates of overweight and obesity were standardized according to the 2010 China census by age group and sex. The prevalence of obesity‐related complications by body mass index (BMI) groups was calculated using logistic regression. Results: There were 15 770 094 eligible participants (median age 40 years; mean BMI 24.1 kg/m2; 52.8% male). By Chinese BMI classification, 34.8% were overweight and 14.1% were obese. Overweight and obesity were more prevalent in male than female participants (standardized: overweight 40.2% vs. 27.4%; obesity 17.6% vs. 9.6%, respectively). The prevalence of assessed complications was higher in participants with overweight/obesity versus those with normal BMI (P < 0.001 for trends). The most prevalent complications in participants with overweight/obesity were fatty liver disease, prediabetes, dyslipidaemia and hypertension. The number of complications increased with higher BMI. Conclusions: Overweight/obesity and related complications are highly prevalent in this population. These data may better inform management and prevention public health strategies in China. [ABSTRACT FROM AUTHOR]

Background: While evidence supports glycemic control benefits for individuals with type 1 diabetes mellitus (T1DM) using hybrid closed-loop (HCL) systems, HCL automated insulin delivery therapy in China has not been assessed. This study evaluated safety events and effectiveness during HCL system use by Chinese adolescents and adults with T1DM. Methods: Sixty-two participants (n = 12 adolescents with a mean ± standard deviation [SD] of 15.5 ± 1.1 years and n = 50 adults [mean ± SD of 37.6 ± 11.1 years]) with T1DM and baseline A1C of 7.1% ± 1.0% underwent a run-in period (∼2 weeks) using open-loop Manual Mode (sensor-augmented pump) insulin delivery with the MiniMed™ 770G system with the Guardian™ Sensor (3) glucose sensor, followed by a study period (4 weeks) with HCL Auto Mode enabled. Analyses compared continuous glucose monitoring data and insulin delivered during the run-in versus study period (Wilcoxon signed-rank test or t-test). Safety events included rates of severe hypoglycemia and diabetic ketoacidosis (DKA). Results: Compared to baseline run-in, overall Auto Mode use increased time in range (TIR, 70–180 mg/dL) from 75.3% to 80.9% (P < 0.001) and reduced time below range (TBR, <70 mg/dL) from 4.7% to 2.2% (P < 0.001). Subgroup analysis demonstrated that participants (n = 29) with baseline A1C <7.0% had TBR that reduced from 5.6% to 2.0%, while participants (n = 21) with baseline A1C ≥7.5% had time above range (TAR, >180 mg/dL) that reduced from 31.6% to 20.8%. Auto Mode use also increased the percentage achieving combined recommendations for time at sensor glucose ranges (i.e., TIR of >70%, TBR of <4% and TAR of <25%) from 24.2% at baseline to 77.4% at study end. Total daily insulin dose reduced from 42.8 ± 19.8 to 40.7 ± 18.9 U (P = 0.013). There were no severe hypoglycemic, DKA, or serious adverse events. Conclusions: Chinese adolescents and adults, some of whom met target A1C at baseline, safely achieved significantly improved glycemia with 1 month of MiniMed 770G system use when compared to open-loop insulin delivery. ClinicalTrials.gov ID: NCT04663295. [ABSTRACT FROM AUTHOR]

Key Points: Question: How does once-weekly insulin icodec compare with once-daily insulin degludec in glucose-lowering efficacy (hemoglobin A1c [HbA1c]) in people with insulin-naive type 2 diabetes? Findings: In this randomized, double-masked, double-dummy trial that enrolled 588 people with type 2 diabetes, estimated mean HbA1c change from baseline to week 26 was noninferior with insulin icodec (−1.6 percentage points) compared with insulin degludec (−1.4 percentage points), with confirmed statistical superiority (estimated treatment difference, −0.2 percentage points). Meaning: The results demonstrate the efficacy of once-weekly insulin icodec treatment in people with insulin-naive type 2 diabetes. Importance: Once-weekly insulin icodec could provide a simpler dosing alternative to daily basal insulin in people with type 2 diabetes. Objective: To evaluate the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes. Design, Setting, and Participants: Randomized, double-masked, noninferiority, treat-to-target, phase 3a trial conducted from March 2021 to June 2022 at 92 sites in 11 countries in adults with type 2 diabetes treated with any noninsulin glucose-lowering agents with hemoglobin A1c (HbA1c) of 7%-11% (53-97 mmol/mol). Interventions: Participants were randomly assigned in a 1:1 ratio to receive either once-weekly icodec and once-daily placebo (icodec group; n = 294) or once-daily degludec and once-weekly placebo (degludec group; n = 294). Main Outcomes and Measures: The primary end point was change in HbA1c from baseline to week 26 (noninferiority margin, 0.3% percentage points). Secondary end points included change in fasting plasma glucose from baseline to week 26, mean weekly insulin dose during the last 2 weeks of treatment, body weight change from baseline to week 26, and number of level 2 (clinically significant; glucose level <54 mg/dL) and level 3 (severe; requiring external assistance for recovery) hypoglycemic episodes. Results: Among 588 randomized participants (mean [SD] age, 58 [10] years; 219 [37%] women), 564 (96%) completed the trial. Mean HbA1c level decreased from 8.6% (observed) to 7.0% (estimated) at 26 weeks in the icodec group and from 8.5% (observed) to 7.2% (estimated) in the degludec group (estimated treatment difference [ETD], −0.2 [95% CI, −0.3 to −0.1] percentage points), confirming noninferiority (P <.001) and superiority (P =.002). There were no significant differences between the icodec and degludec groups for fasting plasma glucose change from baseline to week 26 (ETD, 0 [95% CI, −6 to 5] mg/dL; P =.90), mean weekly insulin dose during the last 2 weeks of treatment, or body weight change from baseline to week 26 (2.8 kg vs 2.3 kg; ETD, 0.46 [95% CI, −0.19 to 1.10] kg; P =.17). Combined level 2 or 3 hypoglycemia rates were numerically higher in the icodec group than the degludec group from week 0 to 31 (0.31 vs 0.15 events per patient-year exposure; P =.11) and statistically higher in the icodec group from week 0 to 26 (0.35 vs 0.12 events per patient-year exposure; P =.01). Conclusions and Relevance: Among people with insulin-naive type 2 diabetes, once-weekly icodec demonstrated superior HbA1c reduction to once-daily degludec after 26 weeks of treatment, with no difference in weight change and a higher rate of combined level 2 or 3 hypoglycemic events in the context of less than 1 event per patient-year exposure in both groups. Trial Registration: ClinicalTrials.gov Identifier: NCT04795531 This randomized clinical trial examines the efficacy and safety of once-weekly icodec vs once-daily insulin degludec in people with insulin-naive type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short‐term intensive insulin therapy (SIIT) during study run‐in (prior to randomization) using a basal‐first insulin titration method. Materials and methods: This was exclusively an exploratory analysis of the 7‐ to 10‐day run‐in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once‐daily insulin glargine and three‐times‐daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre‐meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2‐hour postprandial blood glucose (PBG) targets. Results: Overall, 397 entered the run‐in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2‐hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2‐hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2‐hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia. Conclusions: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia. [ABSTRACT FROM AUTHOR]

Background: The association between remnant cholesterol (RC) and diabetes remains unclear because of limited study and data. This study attempted to explore the association between RC and diabetes in a large sample, multicenter general population. Methods: The current study included 36 684 participants from eight provinces across China. Subjects were quartered according to the RC quartile. Logistic regression analysis was used to evaluate the association between RC and diabetes. Results: After adjusting for potential confounding factors, RC was still significantly associated with diabetes (Q4: odds ratio [OR]:1.147, 95% confidence interval [CI]: 1.049–1.254, p =.003). In addition, RC and diabetes were still significantly associated when triglycerides (TG) were <1.7 mmol/L (Q4: OR: 1.155, 95% CI: 1.005–1.327, p =.042), low‐density lipoprotein cholesterol (LDL‐C) <3.4 mmol/L (Q4: OR: 1.130, 95% CI: 1.011–1.264, p =.032), or HDL‐C (high‐density lipoprotein cholesterol) ≥1.0 mmol/L (Q4: OR: 1.116, 95% CI: 1.007–1.237, p =.037). In the stratification analysis, elevated RC was significantly associated with diabetes in subjects with systolic blood pressure (SBP) <140 mm Hg and diastolic blood pressure (DBP) <90 mm Hg, 60 ≤ estimated glomerular filtration rate (eGFR) ≤90 ml/min per 1.73 m2, younger than 55 years old and female. Conclusion: In the Chinese community, RC is significantly correlated with diabetes, even when TG, LDL‐C, or HDL‐C were controlled within the appropriate range recommended by the guidelines. [ABSTRACT FROM AUTHOR]

Background: The association between the Chinese Visceral Adiposity Index (CVAI) and urinary albumin to creatinine ratio (UACR) has not been illustrated. The current study aimed to investigate the association between CVAI and UACR and to compare the discriminative power of CVAI, triglyceride, body mass index (BMI), waist circumference (WC), and waist‐to‐hip ratio (WHR) with UACR in the Chinese community population. Methods: This study included 34 732 participants from the REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study. Binary logistic regression analyses were performed to detect the association between CVAI, triglyceride, BMI, WC, WHR and UACR. Results: Binary logistic regression analysis showed that, after adjusting for potential confounders, in women, CVAI (odds ratio [OR]:1.16, 95% confidence interval [CI]: 1.01–1.34) and triglyceride (OR: 1.18, 95% CI: 1.04–1.33) were associated with UACR, whereas BMI, WC, and WHR were not associated with UACR; in men, CVAI (OR: 1.24, 95% CI: 1.02–1.50), WC (OR: 1.21, 95% CI 1.00–1.48), and triglycerides (OR: 1.18, 95% CI 0.97–1.44) were associated with UACR, whereas BMI and WHR were not associated with UACR. Stratified analysis showed that the correlation between CVAI and UACR was stronger in the population with 5.6 ≤ fasting blood glucose (FBG) <7.0 or 7.8 ≤ post‐load blood glucose (PBG) <11.1 mmol/L, FBG ≥7.0 or PBG ≥11.1, systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg. Conclusions: In the Chinese general population, CVAI and UACR were significantly associated in both genders. At higher CVAI levels, the population with prediabetes, diabetes, and hypertension has a more significant association between CVAI and UACR. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy and safety of basal insulin glargine 100 units/ml (Gla) + 2‐3 oral antihyperglycaemic drugs (OADs) with twice‐daily premixed insulin aspart 70/30 (Asp30) + metformin (MET) after short‐term intensive insulin therapy in adults with type 2 diabetes in China. Materials and Methods: This open‐label trial enrolled insulin‐naïve adults with type 2 diabetes and an HbA1c of 7.5%‐11.0% (58‐97 mmol/mol) despite treatment with 2‐3 OADs. All participants stopped previous OADs except MET, then received short‐term intensive insulin therapy during the run‐in period, when those with a fasting plasma glucose of less than 7.0 mmol/L and 2‐hour postprandial glucose of less than 10.0 mmol/L were randomized to Gla + MET + a dipeptidyl peptidase‐4 inhibitor or twice‐daily Asp30 + MET. If HbA1c was more than 7.0% (>53 mmol/mol) at week 12, participants in the Gla group were added repaglinide or acarbose, at the physician's discretion, and participants in the Asp30 group continued to titrate insulin dose. The change in HbA1c from baseline to week 24 was assessed in the per protocol (PP) population (primary endpoint). Results: There were 384 enrollees (192 each to Gla and Asp30); 367 were included in the PP analysis. The threshold for non‐inferiority of Gla + OADs versus Asp30 + MET was met, with a least squares mean change from baseline in HbA1c of –1.72% and –1.70% (–42.2 and –42.1 mmol/mol), respectively (estimated difference –0.01%; 95% CI –0.20%, 0.17% [–0.1 mmol/mol; 95% CI –2.2, 1.9]). Achievement of HbA1c less than 7.0% (<53 mmol/mol) was comparable between the groups (60% vs. 57%). The proportion of participants with any (24% vs. 38%; P =.003), symptomatic (19% vs. 31%; P =.007) or confirmed hypoglycaemia (18% vs. 33%; P <.001) was lower in the Gla + OADs group. Conclusions: Compared with Asp30 + MET, Gla + 2‐3 OADs showed similar efficacy but a lower hypoglycaemia risk in Chinese individuals with type 2 diabetes who had undergone short‐term intensive insulin therapy. [ABSTRACT FROM AUTHOR]

Background: Advanced glycation end products (AGEs) that abnormally accumulate in diabetic patients have been reported to damage bone health. We aimed to investigate the association between skin autofluorescence (SAF)‐AGEage (SAF − AGEs × age/100) and low bone density (LBD)/osteoporosis or major osteoporotic fractures (MOFs) in patients with type 2 diabetes mellitus (T2DM). Methods: This study was nested in the prospective REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals) study and included 1214 eligible participants. SAF was used to measure skin AGEs (SAF‐AGEs). Fracture events were determined by an in‐person clinical follow‐up. Binary logistic regression analysis, linear regression analysis, and a restricted cubic spline nested in logistic models were used to test outcomes. Results: The overall prevalence of LBD/osteoporosis in middle‐aged or elderly T2DM patients was 35.7% (n = 434), and the overall incidence of MOFs was 10.5% (n = 116). Logistic analysis showed a significantly positive relationship between quartiles of SAF‐AGEage and the risk of LBD/osteoporosis (odds ratio [OR] 2.02, 95% CI 1.34–3.03; OR 3.63, CI 2.44–5.39; and OR 6.51, CI 4.34–9.78) for the multivariate‐adjusted models, respectively. SAF‐AGEage was associated with MOFs with a multivariate‐adjusted OR of 1.02 (CI 0.52–2.02), 2.42 (CI 1.32–4.46), and 2.70 (CI 1.48–4.91), respectively. Stratified analyses showed that SAF‐AGEage was significantly associated with MOFs only in females, nonsmokers, nondrinkers, individuals with lower body mass index, and those without LBD/osteoporosis. Linear regression analyses showed that higher SAF‐AGEs were associated with a higher level of serum N‐terminal propeptide of type I procollagen (s‐PINP) and serum carboxy‐terminal cross‐linking peptide of type I collagen (s‐CTX), with a multivariate‐adjusted OR of 1.02 (CI 0.24–1.80) and 6.30 (CI 1.77–10.83), respectively. Conclusions: In conclusion, SAF‐AGEage was positively associated with the prevalence of LBD/osteoporosis or MOFs in patients with T2DM. A positive association between SAF‐AGEs and the level of s‐PINP and s‐CTX was found. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) exert anti-diabetic effects and improve long-term complications via secretory effects that regulate macrophage polarisation and attenuate inflammation. Enhancing the efficacy of MSCs needs to be explored further. The in vitro culture microenvironment influences the secretory profile of MSCs. Therefore, we hypothesised that a diabetic microenvironment would promote the secretion of cytokines responsible for macrophage polarisation, further attenuating systemic inflammation and enhancing the effects of MSCs on type 2 diabetes (T2D) and long-term diabetic complications. Methods: Preconditioned adipose-derived mesenchymal stem cells (pre-ADSCs) were obtained after co-cultivating ADSCs in a diabetic metabolic environment (including high sugar, advanced glycation end-product, and lipopolysaccharides). The regulatory effects of pre-ADSCs on macrophages were observed in vitro. A T2D rat model was induced with a high-fat diet for 32 weeks combined with an intraperitoneal injection of streptozotocin. Sprague–Dawley (SD) rats were divided into four groups: normal group, diabetes without treatment group (PBS), ADSC treatment group, and pre-ADSC treatment group. ADSCs and pre-ADSCs were intravenously administered weekly to SD rats for 6 months, and then glucose homeostasis and long-term diabetic complications were evaluated in each group. Results: The secretion of cytokines related to M2 macrophage polarisation (IL-6, MCP-1, etc.) was increased in the pre-ADSC group in the in vitro model. Pre-ADSC treatment significantly maintained blood glucose homeostasis, reduced insulin resistance, promoted islet regeneration, and ameliorated the complications related to diabetes in rats (chronic kidney disease, non-alcoholic steatohepatitis, lung fibrosis, and cataract) compared to the ADSC group (P < 0.05). Additionally, the number of anti-inflammatory M2 macrophage phenotypes was enhanced in tissues following pre-ADSC injections. Moreover, the expression of pro-inflammatory genes (iNOS, TNF-α, IL-1β) was reduced whereas that of anti-inflammatory genes (Arg1, CD206, and Il-10) was increased after cultivation with pre-ADSCs. Conclusion: Diabetic microenvironment-preconditioned ADSCs effectively strengthen the capacity against inflammation and modulate the progress of long-term T2D complications. [ABSTRACT FROM AUTHOR]

Background: The coexistence of primary hyperparathyroidism (PHPT) and giant toxic nodular goiter is very rare. Moreover, PHPT could be easily overlooked because hyperthyroidism may also lead to hypercalcemia. A 99mTc-MIBI scan of the parathyroid glands is often negative when they are concomitant. Case presentation: Here, we report a rare case of the coexistence of giant toxic nodular goiter and PHPT that had been ignored for many years but was successfully treated with an ultrasound-guided parathyroid adenoma microwave ablation (MWA). Conclusion: Reoperation for PHPT carries an increased risk of cure failure and complications. Thermal ablation has been proven effective in inactivating hyperfunctioning parathyroid lesions and in normalizing both serum parathyroid hormone (PTH) and calcium. [ABSTRACT FROM AUTHOR]

Background: Urinary albumin‐creatinine ratio (UACR) is a sensitive marker of kidney injury. This study analyzed the prevalence of different metabolic phenotypes and investigated their relationship with UACR in Chinese community adults. Methods: This study involved 33 303 participants over 40 years old from seven centers across China. They were stratified into six groups according to their body mass index (BMI) and metabolic status: metabolically healthy normal weight (MHNW), metabolically healthy overweight (MHOW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), metabolically unhealthy overweight (MUOW), and metabolically unhealthy obesity (MUO). Increased albuminuria was defined as a UACR ≥30 mg/g. Results: The percentages of MHNW, MHOW, MHO, MUNW, MUOW, and MUO were 27.6%, 15.9%, 4.1%, 19.8%, 22.5%, and 9.6%, respectively. Multiple logistic regression analysis showed that the MHO group (odds ratio [OR] 1.205; 95% CI, 1.081‐1.343), MUNW group (OR 1.232; 95% CI, 1.021‐1.486), MUOW group (OR 1.447; 95% CI, 1.303‐1.607), and MUO group (OR 1.912; 95% CI, 1.680‐2.176) were at higher risk of increased albuminuria compared to the MHNW group. Subgroup analysis indicated that the risk of increased albuminuria was further elevated among regular smokers in men aged 40 to 55 years old with abdominal obesity. Conclusions: Among Chinese community adults, increased albuminuria was associated with increased BMI whether metabolism was normal or not, and those with abnormal metabolism were at greater risk of increased albuminuria than those with normal metabolism. These findings suggest that overweight or obesity or metabolic abnormalities are risk factors for chronic kidney disease. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether the association between insulin resistance and cardiovascular disease (CVD) differs by glucose tolerance status.Research Design and Methods: We analyzed a nationwide sample of 111,576 adults without CVD at baseline, using data from the China Cardiometabolic Disease and Cancer Cohort Study. Insulin resistance was estimated by sex-specific HOMA of insulin resistance (HOMA-IR) quartiles for participants with normal glucose tolerance, prediabetes, or diabetes, separately, and by 1 SD of HOMA-IR for the overall study participants. We used Cox proportional hazards models to examine the association between insulin resistance and incident CVD according to glucose tolerance status and evaluate the CVD risk associated with the combined categories of insulin resistance and obesity in prediabetes and diabetes, as compared with normal glucose tolerance. Models were adjusted for age, sex, education attainment, alcohol drinking, smoking, physical activity, and diet quality.Results: In participants with normal glucose tolerance, prediabetes, and diabetes defined by three glucose parameters, multivariable-adjusted hazard ratios (95% CIs) for incident CVD associated with the highest versus the lowest quartile of HOMA-IR were 1.03 (0.82-1.30), 1.23 (1.07-1.42), and 1.61 (1.30-2.00), respectively; the corresponding values for CVD per 1-SD increase in HOMA-IR were 1.04 (0.92-1.18), 1.12 (1.06-1.18), and 1.15 (1.09-1.21), respectively (P for interaction = 0.011). Compared with participants with normal glucose tolerance, in participants with prediabetes, the combination of the highest HOMA-IR quartile and obesity showed 17% (95% CI 2-34%) higher risk of CVD, while the combination of the lowest two HOMA-IR quartiles and nonobesity showed 15-17% lower risk of CVD. In participants with diabetes, the upper two HOMA-IR quartiles exhibited 44-77% higher risk of CVD, regardless of obesity status. Consistent findings were observed for glucose tolerance status defined by different combinations of glycemic parameters.Conclusions: Glucose intolerance status exacerbated the association between insulin resistance and CVD risk. Compared with adults with normal glucose tolerance, adults with prediabetes who were both insulin resistant and obese exhibited higher risks of CVD, while in adults with diabetes, the CVD risk related to insulin resistance remained, regardless of obesity. [ABSTRACT FROM AUTHOR]

Background. To identify novel clinical phenotypic signatures of congenital nephrogenic diabetes insipidus (CNDI). Methods. A Chinese family with CNDI was recruited for participation in this study. The proband and one of his uncles suffered from polydipsia and polyuria since infancy. The results of clinical testing indicated the diagnosis of CNDI. 10 family members had similar symptoms but did not seek medical advice. Genetic testing of mutations in the coding region of the aquaporin 2 (AQP2) gene and the arginine vasopressin receptor 2 (AVPR2) gene were carried out in 11 family members. Somatic DNA from 5 female family members was used to test for methylation of polymorphic CAG repeats in the human androgen receptor (AR) gene, as an index for X-chromosome inactivation pattern (XCIP). Results. AQP2 gene mutations were not found in any family members, but a novel missense mutation (814th base A>G) in exon 2 of the AVPR2 gene was identified in 10 individuals. This mutation leads to a Met 272 Val (GAT-GGT) amino acid substitution. Skewed X-chromosome inactivation patterns of the normal X allele were observed in 4 females with the AVPR2 gene mutation and symptoms of diabetes insipidus, but not in an asymptomatic female with the AVPR2 gene mutation. Conclusions. Met 272 Val mutation of the AVPR2 gene was identified as a novel genetic risk factor for CDNI. The clinical NDI phenotype of female carriers with heterozygous AVPR2 mutation may be caused by X-chromosome inactivation induced by dominant methylation of the normal allele of AVPR2 gene. [ABSTRACT FROM AUTHOR]

Aims/Introduction: The Metabolic Score for Insulin Resistance (METS‐IR) is a novel non‐insulin‐based metabolic index used as a substitution marker of insulin resistance. However, whether METS‐IR is associated with the urinary albumin‐to‐creatinine ratio (UACR) is not well known. Therefore, we explored the associations between METS‐IR and UACR, and compared the discriminative ability of METS‐IR and its components for elevated UACR. Materials and Methods: This study included 37,290 participants. METS‐IR was calculated as follows: (Ln[2 × fasting blood glucose + fasting triglyceride level] × body mass index) / (Ln [high‐density lipoprotein cholesterol]). Participants were divided into four groups on the basis of METS‐IR: <25%, 25–49%, 50–74% and ≥75%. Logistic regression analyses were carried out to determine the associations between METS‐IR versus its components (fasting blood glucose, triglyceride level, body mass index and high‐density lipoprotein cholesterol) with UACR. Results: Participants with the highest quartile METS‐IR presented a more significant trend toward elevated UACR than toward its components (odds ratio 1.260, 95% confidence interval 1.152–1.378, P < 0.001 in all participants; odds ratio 1.321, 95% confidence interval 1.104–1.579, P = 0.002 in men; odds ratio 1.201, 95% confidence interval 1.083–1.330, P < 0.001 in women). There were significant associations between METS‐IR and UACR in younger participants (aged <65 years for women and aged 55–64 years for men). Increased METS‐IR was significantly associated with UACR in men with fasting blood glucose ≥5.6 or postprandial blood glucose ≥7.8 mmol/L and systolic blood pressure ≥120 or diastolic blood pressure ≥80 mmHg. The relationships were significant in women with diabetes and hypertension. Conclusions: Increased METS‐IR was significantly associated with elevated UACR, its discriminative power for elevated UACR was superior to that of its components. [ABSTRACT FROM AUTHOR]

Background: Studies have demonstrated the relationship between the fatty liver index (FLI) and metabolism, while few research reported its relationship with hyperuricemia (HUA). This study aimed to predict HUA by determining the relationship between the baseline FLI and HUA events and by validating the FLI–HUA correlation through follow-up. Methods: This study was a community-based cohort study involving 8851 adults in China. We performed anthropometric assessments and analyzed baseline and follow-up blood samples. HUA was defined as a uric acid level of > 420 µmol/L (7 mg/dL). Results: Patients with HUA had a higher prevalence of diabetes mellitus, lipid metabolism disorders, and hypertension and higher FLI values than those with normal uric acid levels (P < 0.001). Serum uric acid was positively correlated with the FLI (r = 0.41, P < 0.001); the diagnostic cut-off value of FLI for the diagnosis of HUA was 27.15, with a specificity of 70.9% and sensitivity of 79.6%. FLI was an independent risk factor for HUA, with a 1.72-, 2.74-, and 4.80-fold increase in the risk of developing HUA with increasing FLI quartile levels compared with the FLI at quartile level 1 (P < 0.001). After a mean follow-up of 4 years, as the FLI values increased compared with the FLI at quartile level 1, the risk of new-onset HUA increased by 3.10-, 4.89-, and 6.97-fold (P < 0.001). Conclusion: There is a higher incidence of metabolic abnormalities in HUA populations, and FLI is an independent factor that may contribute to HUA development. Therefore, FLI is a potential tool to predict the risk of developing HUA. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to clarify the association of soy intake with cardiovascular disease (CVD) and all-cause mortality. Methods: We conducted a prospective cohort study in a Chinese population composed of 97,930 participants aged ≥ 40 years old without CVD at baseline in 2011. Habitual soy intake over a period of 12 months was evaluated using a food frequency questionnaire. All participants were classified into four groups based on their soy food consumption levels: < 15, 15–29, 30–59, and ≥ 60 g/day, with the lowest category as the reference group. Follow-up was conducted between 2014 and 2016 to assess CVD incidence and all-cause mortality since baseline, which was collected from the local mortality and disease registers of the National Disease Surveillance Point System and National Health Insurance System. The Cox proportional hazards regression models were used to analyze the relationship of soy intake with later CVD events and all-cause mortality. Results: During 350,604 person-years of follow-up (median [interquartile range]: 3.16 [2.98, 4.77] years), 2523 total CVD events and 1473 all-cause mortalities were documented. After controlling for covariates, the hazard ratios (95% confidence intervals) for total CVD events across increasing soy intake levels were 1.03 (0.93–1.14); 0.96 (0.86–1.07); and 0.86 (0.75–0.98; p for trend = 0.0434), while those for all-cause mortality were 0.88 (0.77–1.02); 0.86 (0.74–1.00); and 0.83 (0.69–0.99; p for trend = 0.0084). Conclusion: High soy intake was associated with a reduced risk of total CVD events and all-cause mortality among a Chinese population. [ABSTRACT FROM AUTHOR]

Background: Previous research has demonstrated that the spleen plays an important role in mesenchymal stem cell (MSC)-mediated alleviation of acute inflammation, as MSC infusion increases the spleen-derived anti-inflammatory cytokine interleukin 10 (IL-10) levels. However, studies on splenic involvement in MSC-induced protection against chronic inflammatory diseases are limited. Obesity is characterized by chronic low-grade inflammation, a key driver of insulin resistance. This study aims to evaluate the effects of MSCs on obesity-related insulin resistance and explore the underlying mechanism, particularly regarding splenic involvement. Methods: We induced obesity in mice by feeding them high-fat diets for 20 weeks. Human umbilical cord-derived MSCs (UC-MSCs) were systemically infused into the obese mice once per week for 6 weeks. Systemic glucose metabolic homeostasis and insulin sensitivity in epididymal adipose tissue (EAT) were evaluated. Then, we conducted in vivo blockade of IL-10 during UC-MSC infusion by intraperitoneally administrating an IL-10-neutralizing antibody twice per week. We also investigated the therapeutic effects of UC-MSCs on obese mice after removal of the spleen by splenectomy. Results: UC-MSC infusions improved systemic metabolic homeostasis and alleviated insulin resistance in EAT but elicited no change in weight. Despite rare engraftment of UC-MSCs in EAT, UC-MSC infusions attenuated insulin resistance in EAT by polarizing macrophages into the M2 phenotype, coupled with elevated serum IL-10 levels. In vivo blockade of IL-10 blunted the effects of UC-MSCs on obese mice. Furthermore, UC-MSCs overwhelmingly homed to the spleen, and the ability of UC-MSCs to elevate serum IL-10 levels and alleviate insulin resistance was impaired in the absence of the spleen. Further in vivo and in vitro studies revealed that UC-MSCs promoted the capacity of regulatory T cells (Treg cells) to produce IL-10 in the spleen. Conclusions: Our results demonstrated that UC-MSCs elevated serum IL-10 levels and subsequently promoted macrophage polarization, leading to alleviation of insulin resistance in EAT. The underlying mechanism was that UC-MSCs improved the capacity of Treg cells to produce IL-10 in the spleen. Our findings indicated that the spleen played a critical role in amplifying MSC-mediated immunomodulatory effects, which may contribute to maximizing MSC efficacy in clinical applications in the future. [ABSTRACT FROM AUTHOR]

Interferon (IFN) is a broad-spectrum antiviral agent that activates cell surface receptors and causes cells to produce antiviral proteins, inhibiting viral replication. Interferon use has long been associated with diabetes. The PubMed database was searched for articles related to diabetes and interferon from March 30, 2020. Patients were divided into type 1 diabetes group and type 2 diabetes group. We reviewed the relevant literature to compare interferon-associated T1D and interferon-associated T2D differences. Interferon treatment shortened the incubation period of T2D and changed the original T2D to T1D. The onset of interferon-associated T1D required longer periods of IFN treatment than interferon-associated T2D, and the interferon-associated T1D group had higher GADA positive rates, lower BMI, lower fasting blood glucose, and greater insulin dependence (p<0.05). More patients in the T1D group were positive for HLA-DRB1*04, DRB1*03, DRB1*09, DRB1*14, HLA-DQB1*04, HLA-DQB1*02, HLA-DQB1*03, and HLA-DQB1*05. The combined detection of GAD antibodies and HLA alleles may be an effective method to predict the incidence of T1D after IFN treatment. [ABSTRACT FROM AUTHOR]

Infusion of mesenchymal stem cells (MSCs) induces polarization of M2 macrophages in adipose tissue of type 2 diabetes (T2D) mice. Studies have shown that M2 macrophages were divided into four sub-phenotypes (M2a, M2b, M2c and M2d) with different functions, and manuscripts have also confirmed that macrophages co-cultured with MSCs were not matched with known four phenotype macrophages. Therefore, our study explored the phenotype and related gene expressions of macrophages in the adipose tissue of T2D mice with/without MSCs infusion. We induced a T2D mouse model by using high-fat diets and streptozotocin (STZ) injection. The mice were divided into three groups: the control group, the T2D group, and the MSCs group. MSCs were systemically injected once a week for 6 weeks. The phenotype of macrophages in adipose tissue was detected via flow cytometric analysis. We also investigated the gene expression of macrophages in different groups via SMART-RNA-sequencing and quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR). The present study found that the macrophages of adipose tissue in the MSCs group were polarized to the M2 phenotype mixed with four sub-phenotypes. Besides, M2a and M2c held a dominant position, while M2b and M2d (tumor-associated macrophages, TAMs) exhibited a decreasing trend after infusion of MSCs. Moreover, the MSCs group did not appear to express higher levels of tumor-associated, inflammation-associated, or fibrosis-associated genes in comparison to the T2D group. The present results unveiled that the macrophage phenotype was inclined to be present in a hybridity state of four M2 sub-phenotypes and the genes related to tumor-promoting, pro-inflammation and pro-fibrosis were not increased after MSCs injection. [ABSTRACT FROM AUTHOR]

Background: Whether smoking modifies the associations of diabetes and risk factor management with subsequent risk of cardiovascular disease (CVD), and whether the smoking related CVD risk differs among people with and without diabetes are unclear. This study aimed to examine the associations and interactions of smoking, diabetes, and risk factor management in relation to incident CVD. Methods: This nationwide, population-based, prospective cohort study of 20 communities from various geographic regions recruited adults aged 40 years or older during 2011–2012. The follow-up survey was conducted between 2014 and 2016. This study included 126,181 participants who were free from CVD at baseline. Results: Study participants included 19,397 current smokers (15.4%), 6,049 former smokers (4.8%), and 100,735 never smokers (79.8%). Mean (SD) age ranged from 55.8 (8.6) years to 60.7 (9.1) years. Compared with never smokers, heavy smokers exhibited a greater risk of CVD events among participants with diabetes (multivariable-adjusted hazard ratio [HR], 1.45; 95% CI, 1.17–1.78) than among participants without diabetes (HR, 1.20; 95% CI, 1.01–1.42; P for interaction = 0.006). Compared with participants without diabetes, participants with diabetes who were never smokers and had 5 or more controlled risk factors showed no significantly excess CVD risk (HR, 0.93; 95% CI, 0.71–1.22), but the cardiovascular benefits from risk factor management were counteracted among participants with diabetes who were current smokers (HR, 1.28; 95% CI, 0.77–2.14) or former smokers (HR, 1.22; 95% CI, 0.66–2.28). Conclusions: Smoking and diabetes interacted with each other in relation to increased risk of CVD events, and the beneficial effect of risk factor management on CVD risk among participants with diabetes was attenuated by current or former smoking. [ABSTRACT FROM AUTHOR]

Background: Patients with normoalbuminuria and a reduced estimated glomerular filtration rate (eGFR) account for a considerable proportion of type 2 diabetes patients. The aim of this research was to investigate the epidemiological and clinical characteristics of normoalbuminuric kidney disease in a Chinese population. Methods: We included 8131 diabetic patients from a multicenter prospective study in China. Based on eGFR and urinary albumin‐to‐creatinine ratio (UACR), participants were stratified into four groups—normal albuminuria, albuminuria, normoalbuminuria with eGFR < 60 mL/min/1.73 m2, and albuminuria with eGFR < 60 mL/min/1.73 m2. Clinical parameters and characteristics of patients with normoalbuminuria and eGFR < 60 mL/min/1.73 m2 were retrospectively analyzed. Results: A total of 1060 out of 8131 individuals with diabetes had decreased eGFR (<60 mL/min/1.73 m2). Normoalbuminuria accounted for 63.3% of participants with eGFR < 60 mL/min/1.73 m2, and microalbuminuria and macroalbuminuria accounted for 30.1% and 6.3%, respectively. Patients with normoalbuminuria and reduced eGFR were more frequently male, older, and had higher levels of triglycerides than patients with normal albuminuria and eGFR. We also detected a correlation between lower extremity arterial disease, newly diagnosed diabetes, and normoalbuminuria‐reduced eGFR. Compared with participants with both albuminuria and eGFR decline, those with normoalbuminuria had better metabolic indicators, including systolic blood pressure and glycosylated hemoglobin, and shorter diabetes duration. Even in the normal range, UACR has a significant correlation with the risk of eGFR insufficiency. Conclusions: Normoalbuminuric renal insufficiency, characterized by male sex, older age, a higher level of triglyceride levels, and a higher risk of lower extremity arterial disease, accounted for a dominant proportion of diabetic patients with eGFR decline. [ABSTRACT FROM AUTHOR]

Aim: To assess the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin degludec (degludec) in Chinese people with type 2 diabetes (T2D) treated with basal insulin. Materials and Methods: In DUAL II China, a randomized, double‐blinded, multicentre, treat‐to‐target trial, Chinese adults with T2D and HbA1c of 7.5% or more on basal insulin and metformin, with or without other oral antidiabetic drugs (OADs), were randomized 2:1 to 26 weeks of treatment with either IDegLira (max. dose 50 U degludec/1.8 mg liraglutide) or degludec (max. 50 U/day), respectively, combined with metformin. At 26 weeks, superiority of IDegLira over degludec was assessed for change in HbA1c (primary endpoint), and body weight and number of severe or blood glucose (BG)‐confirmed hypoglycaemic episodes (confirmatory secondary endpoints). Results: Overall, 453 participants were randomized to IDegLira (n = 302) or degludec (n = 151). Superiority was confirmed for IDegLira over degludec in HbA1c change (−1.9% vs. −1.0%, respectively, estimated treatment difference [ETD] [95% confidence interval]: −0.92% [−1.09; −0.75], P <.0001), body weight change (−0.7 vs. +0.4 kg, respectively, ETD [95% CI]: −1.08 kg [−1.63; −0.52], P =.0002) and severe or BG‐confirmed hypoglycaemia (estimated rate ratio [95% CI]: 0.53 [0.30; 0.94], P =.0297). The odds of achieving HbA1c less than 7.0% without hypoglycaemia and/or weight gain were greater with IDegLira than degludec (P <.0001 for all). Daily insulin dose at 26 weeks was lower for IDegLira (34.3 U) than degludec (37.4 U) (P =.0014). No unexpected safety signals were observed. Conclusions: IDegLira may be an efficacious and well‐tolerated treatment intensification option for Chinese people with T2D uncontrolled on basal insulin and OADs. [ABSTRACT FROM AUTHOR]

Aims: The aims of this study were to evaluate the associations of metabolic abnormalities with incident diabetic kidney disease (DKD) and to explore whether dyslipidaemia, particularly high fasting triglyceride (TG), was associated with the development of DKD. Methods: In total, 11 142 patients with new‐onset type 2 diabetes with baseline estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m2 were followed up during 2011‐2016. Incident DKD was defined as eGFR <60 mL/min/1.73 m2 at follow‐up. Multiple logistic regression analysis was conducted to explore the relationship of metabolic abnormalities at baseline and at follow‐up with risks of DKD. High TG was defined by TG ≥1.70 mmol/L. Low high‐density lipoprotein cholesterol (HDL‐c) was defined by HDL‐c <1.0 mmol/L for men or <1.3 mmol/L for women. Results: Participants who developed DKD had higher levels of waist circumference and systolic blood pressure, and lower levels of HDL‐c at both baseline and follow‐up visits. The DKD group also had higher levels of post‐load plasma glucose and TG at follow‐up. Multivariate logistic regression analysis revealed that both high TG at baseline [odds ratio (OR) = 1.37, p =.012) and high TG at follow‐up (OR = 1.71, p <.001) were significantly associated with increased risks of DKD. Patients with high TG levels at both baseline and follow‐up had higher risk of DKD compared with constantly normal TG (OR = 1.65, p <.001) after adjustment for covariates. Conclusions: In a large population of patients with new‐onset type 2 diabetes, a high TG level was an independent risk factor for the development of DKD. Tight TG control might delay the occurrence of DKD. [ABSTRACT FROM AUTHOR]

Objective: To explore the association between metabolic syndrome (MetS) and its component and thyroid volume in Chinese adolescents, and to compare the detection rate of MetS under the three different diagnostic criteria. Methods: A total of 1097 school students (610 males and 487 females, ages 12–15 years) were enrolled. All the participants underwent physical examination, biochemical test, and thyroid gland ultrasonography. The thyroid volume of normal, overweight and obese group was compared. We also analyzed the association between the number of MetS components and thyroid volume. Linear and multiple linear regression were applied to explore the association between metabolic parameters and thyroid volume. Results: The thyroid volume of the males in overweight (t = 3.784, P < 0.001) and obese group (t = 5.068, P < 0.001) was significantly larger than that in normal group; the thyroid volume of the females in overweight group (t = 4.627,P < 0.001) was significantly larger than that of normal group. As the number of MetS components increased, the thyroid volume also increased significantly (F = 10.64, P < 0.01). Height, weight, body mass index (BMI), waist circumference, hip circumference, systolic blood pressure, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), uric acid and triglyceride were all positively associated with thyroid volume in the adolescents (P all < 0.001). Meanwhile, there was a negative association between high-density lipoprotein cholesterol (HDL-C) and thyroid volume (P < 0.001). According to multiple linear regression, waist circumference (β = 0.029, 95 %CI: 0.015 ~ 0.042; P < 0.01) and waist height ratio (β = 3.317, 95 %CI: 1.661 ~ 4.973; P < 0.01) were predict factors of thyroid volume. No statistical difference was found in the detection rates of metabolic syndrome under the three diagnostic criteria. Conclusions: Overweight, obesity and metabolic syndrome was associated with adolescent thyroid volume. Central obesity may be an independent risk factor for thyroid enlargement in adolescents. [ABSTRACT FROM AUTHOR]

Background: Data are limited with regard to the association between low‐grade albuminuria (below the threshold of microalbuminuria) and high cardiovascular risk in normoalbuminuric Chinese adults free of cardiovascular disease (CVD). Methods: A total of 32 650 participants aged over 40 years from seven regional centers in China were included in this study. The single‐void first morning urine sample was collected to measure the urinary albumin to creatinine ratio (UACR) and the data were divided into sex‐specific quartiles. The Framingham Risk Score (FRS) was used to identify participants at high risk of developing coronary heart disease (CHD) over the next 10 years and the association between low‐grade albuminuria and high 10‐year Framingham risk for CHD (FRS ≥20%) was investigated. Results: Among males and females, the prevalence of cardiometabolic risk factors (diabetes, hypertension, and dyslipidemia) increased markedly with the elevation of UACR quartiles. Logistic regression analysis showed that the odds ratios (ORs) for high 10‐year risk of CHD increased significantly from the second quartile in males (UACR: 4.78 ~ 7.53 mg/g, OR = 1.21, 95% confidence interval [CI]: 1.05‐1.40) and the third quartile in females (UACR: 9.13 ~ 15.04 mg/g, OR = 3.07, 95% CI: 1.75‐5.40). Stratified analysis showed that in males, the association was especially pronounced in elderly, overweight/obese participants and those without diabetes and hypertension whereas in females, the association was especially pronounced in elderly, overweight/obese participants and those without diabetes and with hypertension. Conclusions: Low‐grade albuminuria was significantly associated with high 10‐year cardiovascular risk among CVD‐free and normoalbuminuric Chinese adults. [ABSTRACT FROM AUTHOR]

Background: Several studies have suggested that nonalcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD). The excretion of low‐level albuminuria (LLA) elevates as the prevalence of CVD increases. However, few studies have explored the association between NAFLD and LLA. Methods: This cross‐sectional study included 31 147 Chinese adults (7664 men and 23 483 women). The "normal" level of albuminuria as determined by the urinary albumin to creatinine ratio (UACR) was below 30 mg/g. LLA was defined as a higher level within the "normal" albuminuria range (5.54 mg/g < LLA≤29.9 mg/g). The participants with NAFLD were defined as having a fatty liver index (FLI) ≥ 60. The FLI was calculated using the Bedogni equation. Results: A positive association was found between UACR and FLI through multivariate linear regression analyses (nonstandardized β ± SE:.047 ± 0.004, P <.001). The logistic regression analyses revealed that NAFLD had adjusted odds ratios (ORs) showing a significant relationship with LLA in models 1 to 4 (all subjects: OR, 1.207; 95% CI, 1.098‐1.326; women: OR, 1.43; 95% CI, 1.26‐1.63; all P <.001); however, we did not find significant adjusted ORs among the men. In the stratified analyses, the relationship between NAFLD and LLA was significant among postmenopausal women with a body mass index ≥24 but <28 kg/m2, fasting plasma glucose ≥5.6 but <7.0 mmol/L, or postprandial plasma glucose ≥7.8 but <11.1 mmol/L and those aged below 60 years without moderate‐intensity exercise. Conclusions: A noteworthy association between NAFLD and LLA was found among postmenopausal women who had borderline blood glucose values, were overweight, and did not engage in moderate‐intensity physical activity. [ABSTRACT FROM AUTHOR]

The authors aimed to observe β-cell dedifferentiation in type 2 diabetes mellitus (T2DM) and investigate the reversal effect of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on early- and late-stage β-cell dedifferentiation. In high-fat diet (HFD)/streptozotocin (STZ)-induced T2DM mice, the authors examined the predominant role of β-cell dedifferentiation over apoptosis in the development of T2DM and observed the reversion of β-cell dedifferentiation by UC-MSCs. Next, the authors used db/db mice to observe the progress of β-cell dedifferentiation from early to late stage, after which UC-MSC infusions of the same amount were performed in the early and late stages of dedifferentiation. Improvement in metabolic indices and restoration of β-cell dedifferentiation markers were examined. In HFD/STZ-induced T2DM mice, the proportion of β-cell dedifferentiation was much greater than that of apoptosis, demonstrating that β-cell dedifferentiation was the predominant contributor to T2DM. UC-MSC infusions significantly improved glucose homeostasis and reversed β-cell dedifferentiation. In db/db mice, UC-MSC infusions in the early stage significantly improved glucose homeostasis and reversed β-cell dedifferentiation. In the late stage, UC-MSC infusions mildly improved glucose homeostasis and partially reversed β-cell dedifferentiation. Combining with other studies, the authors found that the reversal effect of UC-MSCs on β-cell dedifferentiation relied on the simultaneous relief of glucose and lipid metabolic disorders. UC-MSC therapy is a promising strategy for reversing β-cell dedifferentiation in T2DM, and the reversal effect is greater in the early stage than in the late stage of β-cell dedifferentiation. [ABSTRACT FROM AUTHOR]

This study was designed to assess whether the combination of the glucagon-like peptide-1 (GLP-1) analog exendin-4 (Ex4) and bone marrow-derived mesenchymal stem cell (BM-MSC) could enhance β-cell action in streptozotocin (STZ)-induced diabetic rats. Forty male Sprague–Dawley rats were randomly assigned to five groups: the normal control group (Normal), diabetes mellitus (DM) group, MSC-treated group (MSC), Ex4-treated group (Ex4), and MSC plus Ex4-treated group (MSC+Ex4). Body weight, blood glucose level, intraperitoneal glucose tolerance test, and in vitro glucose-stimulated insulin secretion were used to assess the treatment efficacy. The expression level of insulin, glucagon, pancreatic duodenal homeobox-1 (PDX-1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA), glucagon-like peptide-1 receptor (GLP-1R), and forkhead transcription factor 1 (FoxO1) was estimated by immunofluorescence analysis. Proliferation was assessed by Ki67 staining, and apoptosis was determined by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining in β-cells. Glucose-induced insulin secretion in the MSC+Ex4 group was significantly increased compared to that in the MSC group in vitro and in vivo. Compared to that of the other groups, the number of insulin-immunopositive cells was increased in both the MSC and MSC+Ex4 groups. However, β-cell proliferation and apoptosis in the MSC group and MSC+Ex4 group were not significantly different. Importantly, the expression level of PDX-1, MafA, FoxO1, and GLP-1R in β-cells in the MSC+Ex4 group was significantly higher than those in the MSC group. The numbers of insulin+ glucagon+ double positive cells and glucagon+ GLP-1+ double positive cells were significantly increased after MSC treatment and MSC+Ex4 combined treatment, suggesting the enhanced function of newly formed islet β-cells. Our findings showed that the combination of MSC and Ex4 enhanced the function of newly formed β-cells in STZ-induced diabetic rats by acting on multiple insulin transcription factors. Thus, combined MSC and Ex4 therapy provides a feasible approach for future diabetes treatments. [ABSTRACT FROM AUTHOR]

Background. Previous studies have shown that the ratio of triglyceride to high-density lipoprotein cholesterol level (TG/HDL-C) is a risk factor for type 2 diabetes mellitus (T2DM). The aim of this study was to investigate the nonlinear relationship between TG/HDL-C and the incidence of T2DM in a Chinese population. Methods. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the incidence of T2DM among 7,791 participants from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) cohort study at baseline. Results. After adjusting for age, sex, body mass index, smoking status, alcohol intake, low-density lipoprotein cholesterol level, strenuous activity, education level, family histories of T2DM and tumors, and the presence of hypertension, tumor, stroke, and coronary heart disease, we showed that TG/HDL-C was positively associated with the incidence of T2DM at the 4-year follow-up (OR = 1.49 , 95 % CI = 1.26 – 1.78). TG/HDL-C and incidence of T2DM showed a nonlinear relationship; the inflection point of TG/HDL-C was 1.50. The ORs (95% CI) on the left and right sides of the inflection point were 2.50 (1.70–3.67) and 0.96 (0.67–1.37), respectively. After adjusting for age, sex, and body mass index (BMI) in the linear relationship, the OR of the incidence of T2DM was 1.60 (95 % CI = 1.37 – 1.87). When the TG/HDL-C was less than 1.50 or greater than 1.76, the ORs (95% CI) were 2.41 (1.82–3.18) or 0.81 (0.53–1.25), respectively. Subgroup analysis showed no relationships of T2DM incidence with sex, BMI, family history of T2DM, or TG/HDL-C. Conclusion. TG/HDL-C is positively associated with diabetes risk. In our study, with each increasing quintile, the risk of T2DM after 4 years was 1.60 or 1.49 depending on the variables adjusted. In addition, our cohort study showed a nonlinear relationship between TG/HDL-C and T2DM incidence, with an inflection point of 1.76 or 1.50, depending on the variables adjusted. When the TG/HDL was less than 1.50, the ORs (95% CI) were 2.41 (1.82–3.18) and 2.50 (1.70–3.67). When the TG/HDL-C was greater than 1.76 or 1.50, there was no significant difference in the change in OR. [ABSTRACT FROM AUTHOR]

Introduction: Although diabetes is associated with hypertension, whether high blood glucose levels promote hypertension remains controversial. In this study we compared the predictive power of fasting plasma glucose (FPG), 2-h postprandial blood glucose (2hPG), and glycated hemoglobin (HbA1c) for the development of hypertension. Methods: This study was a substudy of the REACTION study, an ongoing longitudinal cohort study investigating the relationship of prediabetes and type 2 diabetes with the risk of cancer in an urban Northern Chinese population in Beijing. Logistic regression analysis was used to calculate odds ratios (ORs) after adjustment for risk factors for hypertension, including age, sex, body mass index, and triglycerides. Results: Among the 3437 participants, 497 developed hypertension during the 4-year follow-up. The logistic regression analysis showed that elevated FPG and 2hPG levels (FPG: OR 1.529; 95% confidence interval [CI] 1.348–1.735; 2hPG: OR 1.144; 95% CI 1.100–1.191), but not HbA1c, were independent risk factors for the development of hypertension. In the highest quartile of FPG and 2hPG levels, the multivariable-corrected ORs were 2.115 (95% CI 1.612–2.777) and 2.346 (95% CI 1.787–3.080), respectively, compared with the lowest quartile. The adjusted models showed no significant correlations between quartile HbA1c levels and the development of hypertension. Conclusion: Higher FPG and 2hPG levels, but not HbA1c levels, are independent risk factors for developing hypertension in an urban Northern Chinese population. Trial Registration: ClinicalTrials.gov NCT01206869. [ABSTRACT FROM AUTHOR]