Qiuhe Ji

Prevalence of Diabetes among Men and Women in China

BACKGROUND Because of the rapid change in lifestyle in China, there is concern that diabetes may become epidemic. We conducted a national study from June 2007 through May 2008 to estimate the prevalence of diabetes among Chinese adults. METHODS A nationally representative sample of 46,239 adults, 20 years of age or older, from 14 provinces and municipalities participated in the study. After an overnight fast, participants underwent an oral glucose-tolerance test, and fasting and 2-hour glucose levels were measured to identify undiagnosed diabetes and prediabetes (i.e., impaired fasting glucose or impaired glucose tolerance). Previously diagnosed diabetes was determined on the basis of self-report. RESULTS The age-standardized prevalences of total diabetes (which included both previously diagnosed diabetes and previously undiagnosed diabetes) and prediabetes were 9.7% (10.6% among men and 8.8% among women) and 15.5% (16.1% among men and 14.9% among women), respectively, accounting for 92.4 million adults with diabetes (50.2 million men and 42.2 million women) and 148.2 million adults with prediabetes (76.1 million men and 72.1 million women). The prevalence of diabetes increased with increasing age (3.2%, 11.5%, and 20.4% among persons who were 20 to 39, 40 to 59, and > or = 60 years of age, respectively) and with increasing weight (4.5%, 7.6%, 12.8%, and 18.5% among persons with a body-mass index [the weight in kilograms divided by the square of the height in meters] of < 18.5, 18.5 to 24.9, 25.0 to 29.9, and > or = 30.0, respectively). The prevalence of diabetes was higher among urban residents than among rural residents (11.4% vs. 8.2%). The prevalence of isolated impaired glucose tolerance was higher than that of isolated impaired fasting glucose (11.0% vs. 3.2% among men and 10.9% vs. 2.2% among women). CONCLUSIONS These results indicate that diabetes has become a major public health problem in China and that strategies aimed at the prevention and treatment of diabetes are needed.

Impact of waist circumference and body mass index on risk of cardiometabolic disorder and cardiovascular disease in Chinese adults: a national diabetes and metabolic disorders survey.

Background We updated the prevalence of obesity and evaluated the clinical utility of separate and combined waist circumference (WC) or body mass index (BMI) category increments in identifying cardiometabolic disorder (CMD) and cardiovascular disease (CVD) risk in Chinese adults. Methods and Findings 46,024 participants aged ≥20 years, a nationally representative sample surveyed in 2007–2008, were included in this analysis. Taking the cutoffs recommended by the Chinese Joint Committee for Developing Chinese Guidelines (JCDCG) and the Working Group on Obesity in China (WGOC) into account, the participants were divided into four WC and four BMI groups in 0.5-SD increments around the mean, and 16 cross-tabulated combination groups of WC and BMI. 27.1%, 31.4%, and 12.2% of Chinese adults are centrally obese, overweight, or obese according to JCDCG and WGOC criteria. After adjustment for confounders, after a 1-SD increment, WC is associated with a 1.7-fold or 2.2-fold greater risk of having DM or DM plus dyslipidemia than BMI, while BMI was associated with a 2.3-fold or 1.7-fold higher hypertension or hypertension plus dyslipidemia risk than WC. The combination of WC and BMI categories had stronger association with CMD risk, i.e., the adjusted ORs (95% CI) of having DM, hypertension, and dyslipidemia for the combined and separate highest WC and BMI categories were 2.19 (1.96–2.44) vs 1.88 (1.67–2.12) and 1.12 (0.99–1.26); 5.70 (5.24–6.19) vs 1.51 (1.39–1.65) and 1.69 (1.57–1.82); and 3.73 (3.42–4.07) vs 2.16 (1.98–2.35) and 1.33 (1.25–1.40), respectively. The combination of WC and BMI categories was more likely to identify individuals with lower WC and lower BMI at CVD risk, even after the effects of CMD were controlled (all P<0.05). Conclusion Central obesity, overweight, and obesity are epidemic in Chinese adults. The combination of WC and BMI measures is superior to the separate indices in identifying CMD and CVD risk.

Serum Lipids and Lipoproteins in Chinese Men and Women

Background— Because of rapid change in lifestyle risk factors, cardiovascular disease has become the leading cause of death in China. We sought to estimate the national levels of serum lipids and lipoproteins among the Chinese adult population. Methods and Results— We conducted a cross-sectional study in a nationally representative sample of 46 239 adults aged ≥20 years. Fasting serum total, high-density lipoprotein, and low-density lipoprotein cholesterol and triglycerides were measured by standard methods. The age-standardized estimates of total, high-density lipoprotein, and low-density lipoprotein cholesterol and triglycerides were 4.72 (95% confidence interval, 4.70–4.73), 1.30 (1.29–1.30), 2.68 (2.67–2.70), and 1.57 (1.55–1.58) mmol/L, respectively, in the Chinese adult population. In addition, 22.5% (21.8–23.3%) or 220.4 million (212.1–228.8) Chinese adults had borderline high total cholesterol (5.18–6.21 mmol/L), and 9.0% (8.5–9.5%) or 88.1 million (83.4–92.8) had high total cholesterol (≥6.22 mmol/L). The population estimates for borderline high (3.37–4.13 mmol/L), high (4.14–4.91 mmol/L), and very high (≥4.92 mmol/L) low-density lipoprotein cholesterol were 13.9% (13.3–14.5%) or 133.5 million (127.0–140.1), 3.5% (3.3–3.8%) or 33.8 million (31.2–36.5), and 3.0% (2.8–3.3%) or 29.0 million (26.3–31.8) persons, respectively. In addition, 22.3% (21.6–23.1%) or 214.9 million (207.0–222.8) persons had low high-density lipoprotein cholesterol (<1.04 mmol/L). The awareness, treatment, and control of borderline high or high total cholesterol were 11.0%, 5.1%, and 2.8%, respectively, in the Chinese adult population. Conclusions— Serum total and low-density lipoprotein cholesterol levels were high and increasing in the Chinese population. Without effective intervention, atherosclerotic cardiovascular diseases may soar in the near future in China.

Acarbose compared with metformin as initial therapy in patients with newly diagnosed type 2 diabetes: an open-label, non-inferiority randomised trial

BACKGROUND Metformin is the only first-line oral hypoglycaemic drug for type 2 diabetes recommended by international guidelines with proven efficacy, safety, and cost-effectiveness. However, little information exists about its use in Asian populations. We aimed to ascertain the effectiveness of the α-glucosidase inhibitor acarbose, extensively adopted in China, compared with metformin as the alternative initial therapy for newly diagnosed type 2 diabetes. METHODS In this 48-week, randomised, open-label, non-inferiority trial, patients who were newly diagnosed with type 2 diabetes, with a mean HbA1c of 7·5%, were enrolled from 11 sites in China. After a 4-week lifestyle modification run-in, patients were assigned to 24 weeks of monotherapy with metformin or acarbose as the initial treatment, followed by a 24-week therapy phase during which add-on therapy was used if prespecified glucose targets were not achieved. Primary endpoints were to establish whether acarbose was non-inferior to metformin in HbA1c reduction at week 24 and week 48 timepoints. The non-inferiority margin was 0·3%, with an expected null difference in the change from baseline to week 48 in HbA1c. Analysis was done on a modified intention-to-treat population. This study was registered with Chinese Clinical Trial Registry, number ChiCTR-TRC-08000231. FINDINGS Of the 788 patients randomly assigned to treatment groups, 784 patients started the intended study drug. HbA1c reduction at week 24 was -1·17% in the acarbose group and -1·19% in the metformin group. At week 48, the HbA1c reduction was -1·11% (acarbose) and -1·12% (metformin) with difference 0·01% (95% CI -0·12 to 0·14, p=0·8999). Six (2%) patients in the acarbose group and seven (2%) patients in the metformin group had serious adverse events, and two (1%) and four (1%) had hypoglycaemic episodes. INTERPRETATION This study provides evidence that acarbose is similar to metformin in efficacy, and is therefore a viable choice for initial therapy in Chinese patients newly diagnosed with type 2 diabetes. FUNDING Bayer Healthcare (China) and Double Crane Phama.

Glycemic control among patients in China with type 2 diabetes mellitus receiving oral drugs or injectables

BackgroundThe prevalence of type 2 diabetes mellitus (T2DM) is increasing rapidly among Chinese adults, and limited data are available on T2DM management and the status of glycemic control in China. We assessed the efficacy of oral antidiabetes drugs (OADs), glucagon-like peptide-1 (GLP-1) receptor agonists, and insulin for treatment of T2DM across multiple regions in China.MethodsThis was a multicenter, cross-sectional survey of outpatients conducted in 606 hospitals across China. Data from all the patients were collected between April and June, 2011.ResultsA total of 238,639 patients were included in the survey. Eligible patients were treated with either OADs alone (n=157,212 [65.88%]), OADs plus insulin (n=80,973 [33.93%]), or OADs plus GLP-1 receptor agonists (n=454 [0.19%]). The OAD monotherapy, OAD + insulin, and OAD + GLP-1 receptor agonist groups had mean glycosylated hemoglobin (HbA1c) levels (±SD) of 7.67% (±1.58%), 8.21% (±1.91%), and 7.80% (±1.76%), respectively. Among those three groups, 34.63%, 26.21%, and 36.12% met the goal of HbA1c <7.0%, respectively. Mean HbA1c and achievement of A1c <7.0% was related to the duration of T2DM.ConclusionsLess than one third of the patients had achieved the goal of HbA1c <7.0%. Glycemic control decreased and insulin use increased with the duration of diabetes.

Standards of care for type 2 diabetes in China

Department of Endocrinology and Metabolism, Guangdong Provincial Key Laboratory of Diabetology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China Department of Endocrinology, Peking University People’s Hospital, Beijing, China Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China Department of Endocrinology, Chinese People’s Liberation Army General Hospital, Beijing, China Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, National Clinical Research Center for Metabolic Diseases, The Second Xiangya Hospital and the Diabetes Center, Central South University, Changsha, China Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, China Department of Endocrinology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China Tianjin Metabolic Diseases Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China Department of Endocrinology, Qilu Hospital of Shandong University, Ji’nan, China Department of Endocrinology, Beijing Hospital, Beijing, China Department of Endocrinology, Peking University First Hospital, Beijing, China Department of Endocrinology, Xijing Hospital, Fourth Military Medical University, Xi’an, China Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China Department of Endocrinology, Rui Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrinology, Gansu Provincial Hospital, Lanzhou, China Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu, China Department of Endocrinology, The First Hospital of China Medical University, Shenyang, China Department of Endocrinology, Affiliated Hospital of Guiyang Medical University, Guiyang, China Department of Endocrinology, Hebei General Hospital, Shijiazhuang, China Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China Department of Endocrinology, Heilongjiang Provincial Hospital, Harbin, China Department of Endocrinology, China Japan Friendship Hospital, Beijing, China

Medical care and payment for diabetes in China: enormous threat and great opportunity.

Background The Diabetes Impact Study followed up a large national population-based screening study to estimate the use of and expenditures for medical care caused by diabetes in China and to ascertain the use and cost of essential basic medicines and care. Methods In 2009–10, the study team interviewed 1482 adults with diabetes and 1553 adults with glucose tolerance in the normal range from population-based random samples at 12 sites in China. The response rate was 67%. Findings After adjusting for age, sex, and urban/rural location, people with diabetes received 1.93 times more days of inpatient treatment, 2.40 times more outpatient visits, and 3.35 times more medications than people with normal glucose tolerance (all p<0.05). Adjusted expenditures for medical care were 3.38 times higher among people with diabetes than among people with normal glucose tolerance (p<0.01, unadjusted 3.97). Persons who were diagnosed with ≥10 years prior to the survey paid 3.75 times as much for medical care as those with ≤5 years of diagnosed diabetes. Among persons with diabetes, 45.2% took medication to control blood sugar, 21.1% took an antihypertensive medicine, 22.4% took daily aspirin, and 1.8% took a statin. Over the three months before the interview, 46.1% of persons with diabetes recalled seeing a doctor, 48.9% recalled a blood pressure measurement, and 54.5% recalled a blood sugar test. Over the year preceding the interview, 32.1% recalled a retinal screening and 17.9% recalled a foot examination. Conclusions In China, health care use and costs were dramatically higher for people with diabetes than for people with normal glucose tolerance and, in relative terms, much higher than in industrialized countries. Low-cost generic medicines that would reduce diabetes expenditures were not fully used.

Free Fatty Acid Induces Endoplasmic Reticulum Stress and Apoptosis of β-cells by Ca2+/Calpain-2 Pathways

Dysfunction of β-cells is a major characteristic in the pathogenesis of type 2 diabetes mellitus (T2DM). The combination of obesity and T2DM is associated with elevated plasma free fatty acids (FFAs). However, molecular mechanisms linking FFAs to β-cell dysfunction remain poorly understood. In the present study, we identified that the major endoplasmic reticulum stress (ERS) marker, Grp78 and ERS-induced apoptotic factor, CHOP, were time-dependently increased by exposure of β-TC3 cells to FFA. The expression of ATF6 and the phosphorylation levels of PERK and IRE1, which trigger ERS signaling, markedly increased after FFA treatments. FFA treatments increased cell apoptosis by inducing ERS in β-TC3 cells. We also found that FFA-induced ERS was mediated by the store-operated Ca2+ entry through promoting the association of STIM1 and Orai1. Moreover, calpain-2 was required for FFA-induced expression of CHOP and activation of caspase-12 and caspase-3, thus promoting cell apoptosis in β-TC3 cells. Together, these results reveal pivotal roles for Ca2+/calpain-2 pathways in modulating FFA-induced β-TC3 cell ERS and apoptosis.

Risk of non-fatal cardiovascular diseases in early-onset versus late-onset type 2 diabetes in China: a cross-sectional study

BACKGROUND The age of onset of type 2 diabetes is decreasing. Because non-Chinese patients with early-onset type 2 diabetes (defined here as diagnosis at <40 years) have increased risk of vascular complications, we investigated effects of early-onset versus late-onset type 2 diabetes on risk of non-fatal cardiovascular diseases in China. METHODS We did a cross-sectional survey using data from the China National HbA1c Surveillance System (CNHSS), including 222,773 Chinese patients with type 2 diabetes in 630 hospitals from 106 cities in 30 provinces of China in 2012. We documented demographic information and clinical profiles. Non-fatal cardiovascular disease was defined as non-fatal coronary heart disease or non-fatal stroke. Prevalence of non-fatal cardiovascular diseases was standardised to the Chinese population in 2011. We did logistic regression analysis to obtain odds ratios (ORs) for the risk of cardiovascular disease in patients with early-onset versus late-onset type 2 diabetes. Because the CNHSS did not contain patients on diet or lifestyle treatment alone, and did not capture information on smoking or lipid or antihypertensive treatment, we validated our findings in another dataset from a cross-sectional, multicentre observational study (the 3B study) of outpatients with type 2 diabetes to confirm that exclusion of patients with diet treatment only and non-adjustment for lipid-lowering and antihypertensive drugs did not introduce major biases in the main analysis. FINDINGS Of 222,773 patients recruited from April 1, 2012, to June 30, 2012, 24,316 (11%) had non-fatal cardiovascular disease. Patients with early-onset diabetes had a higher age-adjusted prevalence of non-fatal cardiovascular disease than did patients with late-onset diabetes (11·1% vs 4·9%; p<0·0001). After adjustment for age and sex, patients with early-onset type 2 diabetes had higher risk of non-fatal cardiovascular disease than did those with late-onset type 2 diabetes (OR 1·91, 95% CI 1·81-2·02). Adjustment for duration of diabetes greatly attenuated the effect size for risk of non-fatal cardiovascular disease (1·13, 1·06-1·20). Results of the validation study showed that exclusion of patients with diet only and non-adjustment for lipid-lowering and antihypertensive drugs resulted in marginal changes in ORs for risk of non-fatal cardiovascular disease in patients with early-onset versus late-onset type 2 diabetes. Early-onset type 2 diabetes remained associated with increased risk of cardiovascular disease, attributable to longer duration of diabetes. INTERPRETATION Chinese patients with early-onset type 2 diabetes are at increased risk of non-fatal cardiovascular disease, mostly attributable to longer duration of diabetes. FUNDING Novo Nordisk China (for the China National HbA1c Surveillance System [CNHSS]) and Merck Sharp & Dohme China (for the 3B study).

Liraglutide inhibits autophagy and apoptosis induced by high glucose through GLP-1R in renal tubular epithelial cells

Tubular atrophy and dysfunction is a critical process underlying diabetic nephropathy (DN). Understanding the mechanisms underlying renal tubular epithelial cell survival is important for the prevention of kidney failure associated with glucotoxicity. Autophagy is a cellular pathway involved in protein and organelle degradation. It is associated with many types of cellular homeostasis and human diseases. To date, little is known of the association between high concentrations of glucose and autophagy in renal tubular cells. In the present study, we investigated high glucose-induced toxicity in renal tubular epithelial cells by means of several complementary assays, including cell viability, cell death assays and changes in ultrastructure in an immortalized human kidney cell line, HK-2 cells. The extent of apoptosis was significantly increased in the HK-2 cells following treatment with high levels of glucose. In addition, in in vivo experiments using diabetic rats, high glucose exerted harmful effects on the tissue structure of the kidneys in the diabetic rats. Chronic exposure of the HK-2 cells and tubular epithelial cells of nephritic rats to high levels of glucose induced autophagy. Liraglutide inhibited these effects; however, treatment witht a glucagon-like peptide-1 receptor (GLP-1R) antagonist enhanced these effects. Our results also indicated that the exposure of the renal tubular epithelial cells to high glucose concentrations in vitro led to the downregulation of GLP-1R expression. Liraglutide reversed this effect, while the GLP-1R antagonist promoted it, promoting autophagy, suggesting that liraglutide exerts a renoprotective effect in the presence of high glucose, at least in part, by inhibiting autophagy and increasing GLP-1R expression in the HK-2 cells and kidneys of diabetic rats.