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/m ² ; 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.

OBJECTIVE Uncertainty remains regarding the predictive value of various glycemic measures as they relate to the risk of diabetes and its complications. Using the cutoffs recommended by the American Diabetes Association’s 2010 criteria, we determined the associations of fasting plasma glucose (FPG), 2-h postload glucose (2h-PG), and HbA_1c with the outcomes. RESEARCH DESIGN AND METHODS Baseline medical history, FPG, 2h-PG, and HbA_1c were obtained from a population-based cohort of 193,846 adults aged ≥40 years in China during 2011–2012. A follow-up visit was conducted during 2014–2016 in order to assess incident diabetes, cardiovascular disease (CVD), cancer, and mortality. RESULTS We documented 8,063 cases of diabetes, 3,014 CVD-related events, 1,624 cases of cancer, and 2,409 deaths during up to 5 years of follow-up. Multivariable-adjusted risk ratios (95% CIs) of diabetes associated with prediabetes based on FPG of 100–125 mg/dL, 2h-PG of 140–199 mg/dL, or HbA_1c of 5.7–6.4% (39–47 mmol/mol) were 1.60 (1.43–1.79), 2.72 (2.43–3.04), and 1.49 (1.36–1.62), respectively. Restricted cubic spline analyses suggested J-shaped associations of FPG, 2h-PG, and HbA_1c levels with CVD, cancer, and mortality. Multivariable-adjusted hazard ratios (95% CIs) associated with untreated diabetes based on FPG ≥126 mg/dL, 2h-PG ≥200 mg/dL, or HbA_1c ≥6.5% (48 mmol/mol) were 1.18 (1.05–1.33), 1.31 (1.18–1.45), and 1.20 (1.07–1.34) for CVD; 1.10 (0.92–1.32), 1.44 (1.25–1.67), and 1.08 (0.92–1.28) for cancer; and 1.37 (1.20–1.57), 1.57 (1.41–1.76), and 1.33 (1.17–1.52) for mortality, respectively. 2h-PG remained significantly associated with outcomes in models including FPG and HbA_1c as spline terms. Furthermore, 2h-PG significantly improved the ability of the C statistic to predict diabetes, CVD, and mortality. CONCLUSIONS 2h-PG remains independently predictive of outcomes in models including FPG and HbA_1c. Therefore, in addition to FPG and HbA_1c, routine testing of 2h-PG should be considered in order to better assess the risks of outcomes.

Insulin resistance, a major characteristic of type 2 diabetes (T2D), is closely associated with adipose tissue macrophages (ATMs) that induce chronic low-grade inflammation. Recently, mesenchymal stem cells (MSCs) have been identified in alleviation of insulin resistance. However, the underlying mechanism still remains elusive. Thus, we aimed to investigate whether the effect of MSCs on insulin resistance was related to macrophages phenotypes in adipose tissues of T2D rats. In this study, human umbilical cord-derived MSCs (UC-MSCs) infusion produced significantly anti-diabetic effects and promoted insulin sensitivity in T2D rats that were induced by a high-fat diet combined with streptozotocin and directed ATMs into an alternatively activated phenotype (M2, anti-inflammatory). In vitro, MSC-induced M2 macrophages alleviated insulin resistance caused by classically activated macrophages (M1, pro-inflammatory). Further analysis showed that M1 stimulated UC-MSCs to increase expression of interleukin (IL)-6, a molecule which upregulated IL4R expression, promoted phosphorylation of STAT6 in macrophages, and eventually polarized macrophages into M2 phenotype. Moreover, the UC-MSCs effect on macrophages was largely abrogated by small interfering RNA (siRNA) knockdown of IL-6. Together, our results indicate that UC-MSCs can alleviate insulin resistance in part via production of IL-6 that elicits M2 polarization. Additionally, human obesity and insulin resistance were associated with increased pro-inflammatory ATMs infiltration. Thus, MSCs may be a new treatment for obesity-related insulin resistance and T2D concerning macrophage polarized effects.

Background: Long-term diabetes-associated complications are the major causes of morbidity and mortality in individuals with diabetes. These diabetic complications are closely linked to immune system activation along with chronic, non-resolving inflammation, but therapies to directly reverse these complications are still not available. Our previous study demonstrated that mesenchymal stem cells (MSCs) attenuated chronic inflammation in type 2 diabetes mellitus (T2DM), resulting in improved insulin sensitivity and islet function. Therefore, we speculated that MSCs might exert anti-inflammatory effects and promote the reversal of diabetes-induced kidney, liver, lung, heart, and lens diseases in T2DM rats. Methods: We induced a long-term T2DM complication rat model by using a combination of a low dose of streptozotocin (STZ) with a high-fat diet (HFD) for 32 weeks. Adipose-derived mesenchymal stem cells (ADSCs) were systemically administered once a week for 24 weeks. Then, we investigated the role of ADSCs in modulating the progress of long-term diabetic complications. Results: Multiple infusions of ADSCs attenuated chronic kidney disease (CKD), nonalcoholic steatohepatitis (NASH), lung fibrosis, and cataracts; improved cardiac function; and lowered serum lipid levels in T2DM rats. Moreover, the levels of inflammatory cytokines in the serum of each animal group revealed that ADSC infusions were able to not only inhibit pro-inflammatory cytokines IL-6, IL-1β, and TNF-α expression but also increase anti-inflammatory cytokine IL-10 systematically. Additionally, MSCs reduced the number of iNOS(+) M1 macrophages and restored the number of CD163(+) M2 macrophages. Conclusions: Multiple intravenous infusions of ADSCs produced significant protective effects against long-term T2DM complications by alleviating inflammation and promoting tissue repair. The present study suggests ADSCs may be a novel, alternative cell therapy for long-term diabetic complications.

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 A_1c (HbA_1c) 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 HbA_1c 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 HbA_1c 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 HbA_1c 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