Guangwei Li

The long-term effect of lifestyle interventions to prevent diabetes in the China Da Qing Diabetes Prevention Study: a 20-year follow-up study.

BACKGROUND Intensive lifestyle interventions can reduce the incidence of type 2 diabetes in people with impaired glucose tolerance, but how long these benefits extend beyond the period of active intervention, and whether such interventions reduce the risk of cardiovascular disease (CVD) and mortality, is unclear. We aimed to assess whether intensive lifestyle interventions have a long-term effect on the risk of diabetes, diabetes-related macrovascular and microvascular complications, and mortality. METHODS In 1986, 577 adults with impaired glucose tolerance from 33 clinics in China were randomly assigned to either the control group or to one of three lifestyle intervention groups (diet, exercise, or diet plus exercise). Active intervention took place over 6 years until 1992. In 2006, study participants were followed-up to assess the long-term effect of the interventions. The primary outcomes were diabetes incidence, CVD incidence and mortality, and all-cause mortality. FINDINGS Compared with control participants, those in the combined lifestyle intervention groups had a 51% lower incidence of diabetes (hazard rate ratio [HRR] 0.49; 95% CI 0.33-0.73) during the active intervention period and a 43% lower incidence (0.57; 0.41-0.81) over the 20 year period, controlled for age and clustering by clinic. The average annual incidence of diabetes was 7% for intervention participants versus 11% in control participants, with 20-year cumulative incidence of 80% in the intervention groups and 93% in the control group. Participants in the intervention group spent an average of 3.6 fewer years with diabetes than those in the control group. There was no significant difference between the intervention and control groups in the rate of first CVD events (HRR 0.98; 95% CI 0.71-1.37), CVD mortality (0.83; 0.48-1.40), and all-cause mortality (0.96; 0.65-1.41), but our study had limited statistical power to detect differences for these outcomes. INTERPRETATION Group-based lifestyle interventions over 6 years can prevent or delay diabetes for up to 14 years after the active intervention. However, whether lifestyle intervention also leads to reduced CVD and mortality remains unclear.

Prevalence of diabetes and its risk factors in China, 1994. National Diabetes Prevention and Control Cooperative Group

OBJECTIVE To determine the prevalence of diabetes and impaired glucose tolerance (IGT) and its risk factors in the Chinese population. RESEARCH DESIGN AND METHODS This study was a population-based cross-sectional study of 224,251 residents aged 25–64 years in 19 provinces and areas, including cities and rural areas of the north, south, east, and middle part of China. RESULTS Using the 1985 World Health Organization criteria, the prevalence of diabetes and IGT was 2.5 and 3.2%, respectively, in 213,515 subjects aged 25–64 years. Two thirds (70.3%) of the cases had newly recognized diabetes. The prevalence of diabetes in China is about three times higher than it was 10 years ago. On average, subjects with diabetes are older, have higher personal annual incomes, and more often have a family history of diabetes. They also have higher mean BMI, waist-to-hip ratio (WHR), systolic blood pressure, diastolic blood pressure, and a greater prevalence of hypertension. They perform less physical activity and have less education than people with normal oral glucose tolerance test results. Multiple logistic stepwise regression analysis shows that age, BMI (or WHR), family history of diabetes, hypertension, less physical activity, and higher annual income are independent risk factors of NIDDM, and that low education is also an independent risk factor of NIDDM in people with higher personal annual income. CONCLUSIONS The prevalence of diabetes in China is increasing with economic development and changes from traditional to modernized lifestyle, especially where people had lower level of education and socioeconomic development. Therefore, Chinese people should attempt to retain certain features of their traditional lifestyle (physical activity, healthy food, moderate body weight). Increased knowledge of risk factors for diabetes may help to prevent a further rapid increase in the prevalence of diabetes in China.

Cardiovascular mortality, all-cause mortality, and diabetes incidence after lifestyle intervention for people with impaired glucose tolerance in the Da Qing Diabetes Prevention Study: a 23-year follow-up study

BACKGROUND Lifestyle interventions among people with impaired glucose tolerance reduce the incidence of diabetes, but their effect on all-cause and cardiovascular disease mortality is unclear. We assessed the long-term effect of lifestyle intervention on long-term outcomes among adults with impaired glucose tolerance who participated in the Da Qing Diabetes Prevention Study. METHODS The study was a cluster randomised trial in which 33 clinics in Da Qing, China-serving 577 adults with impaired glucose tolerance-were randomised (1:1:1:1) to a control group or lifestyle intervention groups (diet or exercise or both). Patients were enrolled in 1986 and the intervention phase lasted for 6 years. In 2009, we followed up participants to assess the primary outcomes of cardiovascular mortality, all-cause mortality, and incidence of diabetes in the intention-to-treat population. FINDINGS Of the 577 patients, 439 were assigned to the intervention group and 138 were assigned to the control group (one refused baseline examination). 542 (94%) of 576 participants had complete data for mortality and 568 (99%) contributed data to the analysis. 174 participants died during the 23 years of follow-up (121 in the intervention group vs 53 in the control group). Cumulative incidence of cardiovascular disease mortality was 11.9% (95% CI 8.8-15.0) in the intervention group versus 19.6% (12.9-26.3) in the control group (hazard ratio [HR] 0.59, 95% CI 0.36-0.96; p=0.033). All-cause mortality was 28.1% (95% CI 23.9-32.4) versus 38.4% (30.3-46.5; HR 0.71, 95% CI 0.51-0.99; p=0.049). Incidence of diabetes was 72.6% (68.4-76.8) versus 89.9% (84.9-94.9; HR 0.55, 95% CI 0.40-0.76; p=0.001). INTERPRETATION A 6-year lifestyle intervention programme for Chinese people with impaired glucose tolerance can reduce incidence of cardiovascular and all-cause mortality and diabetes. These findings emphasise the long-term clinical benefits of lifestyle intervention for patients with impaired glucose tolerance and provide further justification for adoption of lifestyle interventions as public health measures to control the consequences of diabetes. FUNDING Centers for Disease Control and Prevention, WHO, the China-Japan Friendship Hospital, Da Qing First Hospital.

Obesity, coronary heart disease risk factors and diabetes in Chinese: an approach to the criteria of obesity in the Chinese population.

The aim of this work was to study the relationship between excess body weight and the risks of hypertension and diabetes in the population of northeastern China. Subsections of a cross‐sectional survey in Da Qing City were used to assess the relationship of excess weight to risk factors for coronary heart disease (CHD). A 6‐year prospective study also assessed the probability of developing Type 2 diabetes. A total of 2856 adults (25–70 years of age) were assessed cross‐sectionally and 629 non‐diabetic subjects of similar age were followed‐up for 6 years. Blood pressure, plasma fasting glucose, triglycerides, high‐density lipoporotein (HDL) cholesterol and fibrinogen levels were measured as well as weight, height and waist and hip circumferences. About 45% of adults had a body mass index (BMI) of ≥25.0. Risk factors increased with increasing BMI from a baseline value of 21.0: at a BMI of 23.0–24.9, the risk of hypertension and hypertriglyceridaemia doubled; the risk increased threefold at a BMI of 25.0–26.9. The prevalence of Type 2 diabetes increased progressively in women within the normal BMI range and in men from a BMI of 25.0. Type 2 diabetes was four times as common if the BMI was >27.0. Increasing waist measurements predicted 10‐fold increases in hypertension and a three‐to‐five times increased risk of diabetes. Suitable waist cut‐off points were 85 cm for men and 80 cm for women, with statistical analysis showing waist as the more dominant predictor of risk than age, waist‐to‐hip ratios or BMIs. Hence, small increases in BMI, and particularly in waist circumference, predict a substantial increase in the risk of diabetes and risk for CHD, especially hypertension, in Chinese adults.

Effects of insulin resistance and insulin secretion on the efficacy of interventions to retard development of type 2 diabetes mellitus: the DA Qing IGT and Diabetes Study

OBJECTIVE To investigate the effects of insulin resistance (IR) and insulin secretion (IS) on the development of diabetes mellitus in individuals with impaired glucose tolerance (IGT) who underwent lifestyle interventions. METHODS 284 out of 577 individuals with IGT identified by population-based screening in Da Qing, China, who were randomized to undergo diet change and/or increased physical activity had baseline fasting and 2 h post-load insulin determinations. They were followed for 6 years for the development of diabetes. IR and IS were assessed using calculated indices based on fasting plasma insulin and glucose. The interactions of IR, IS, obesity and plasma glucose and the effects of the lifestyle interventions were evaluated using Cox Proportional Hazards analysis. RESULTS Both IR and IS were significantly associated with the development of diabetes. Lifestyle interventions were more effective in those with lower IT and higher IS at baseline. Diet plus exercise interventions resulted in significantly lower incidence of diabetes, even after controlling for IR, IS, BMI and 2hrPG. CONCLUSION Both IR and beta-cell function were predictors of diabetes in Chinese with IGT. Lifestyle intervention reduced the incidence of DM and these interventions were more effective in those with less IR.

Involvement of chronic stresses in rat islet and INS-1 cell glucotoxicity induced by intermittent high glucose

In order to investigate the toxic effect of intermittent high glucose (IHG) and sustained high glucose (SHG) on rat pancreatic beta cell functions and the potential involved mechanisms, isolated rat islets and INS-1 beta cells were exposed to SHG (25 mmol/l) or IHG (11.1 and 25 mmol/l glucose alternating every 12 h) for 72 h. The results showed that IHG induced a more significant impairment of insulin release response in rat islets and INS-1 cell than SHG. Simultaneously, the intracellular levels of endoplasmic reticulum and oxidative stress were more markedly increased in islets and INS-1 cells exposed to IHG. However, there was no significant difference between reducing cell viability, insulin content and gene expression induced by SHG and IHG. Taken together, this study suggested the more serious toxic effect on rat pancreatic beta cell function induced by IHG treatment may be due to excessive activation of cellular stress.

Cardiovascular and All-Cause Mortality Over a 23-Year Period Among Chinese With Newly Diagnosed Diabetes in the Da Qing IGT and Diabetes Study

OBJECTIVE Despite its growing prevalence in China, the extent to which diabetes leads to excess cardiovascular disease (CVD) mortality and all-cause mortality is unclear. RESEARCH DESIGN AND METHODS We compared death rates and causes of death among 630 people with newly diagnosed diabetes (NDD) and 519 with normal glucose tolerance (NGT) who, in 1986, were identified as a result of screening 110,660 adults aged 25–74 years for diabetes in Da Qing, China. RESULTS During 23 years of follow-up, 338 (56.5%) participants with NDD and 100 (20.3%) with NGT died. CVD was the predominant cause of death in those with diabetes (47.5% in men and 49.7% in women), almost half of which was due to stroke (52.3% in men and 42.3% in women). The age-standardized incidence of all-cause death was three times as high in those with NDD as in those with NGT with incidences (per 1,000 person-years) of 36.9 (95% CI 31.5–42.3) vs. 13.3 (10.2–16.5) in men (P < 0.0001) and 27.1 (22.9–31.4) vs. 9.2 (7.8–10.6) in women (P < 0.0001). The incidence of CVD deaths in men and women with NDD (17.5 [13.8–21.2] vs. 13.5 [10.5–16.5]) did not differ significantly. Significantly higher death rates attributable to renal disease and infection were also found in the NDD group. CONCLUSIONS Diabetes is associated with a substantially increased risk of death in Chinese adults, especially from CVD, almost half of which is due to stroke.

Role of oxidative stress in elevated blood pressure induced by high free fatty acids

The aim of the study is to investigate the possible mechanism of oxidative stress in the high free fatty acids (FFAs)-induced hypertension. Male Sprague–Dawley rat models were established and classified into three groups, namely the control group (NC group), the FFA group, and the N-acetylcysteine (NAC) group. Blood pressure (BP) was recorded. An organ chamber experiment was performed to determine endothelium-dependent/-independent vasodilation (EDV/EIV). Reactive oxygen species (ROS), nitrotyrosine, reduced glutathione hormone (GSH) and NO2−/NO3− levels were measured in plasma. Endothelial nitric oxide synthase (eNOS) mRNA expression in endothelial cells was evaluated by real-time PCR. The following results were observed: (1) In the FFA group, BP increased after 4 h infusion of Intralipid+heparin. In the NAC group, systolic and diastolic BP remained the same. (2) In the FFA group, the aortic rings tended to show impaired EDV in response to acetylcholine (ACh). There was no difference of EDV response in the NAC and NC groups. (3) In the FFA group, NO2−/NO3− levels were significantly reduced, and eNOS mRNA expression and activity were significantly decreased compared with the NC group. NAC administration increased eNOS mRNA expression and activity. (4) ROS and nitrotyrosine concentrations in the FFA group were higher than in the NC group, and GSH concentrations in the FFA group were lower than in the NC group. Elevated FFAs can induce elevated BP, potentially through FFA-induced impairment of EDV resulting from decreased eNOS mRNA expression and activity. Oxidative stress may also play an important role in potential mechanisms of this high FFA-induced elevated BP.

Changes in Mortality in People With IGT Before and After the Onset of Diabetes During the 23-Year Follow-up of the Da Qing Diabetes Prevention Study

OBJECTIVE People with impaired glucose tolerance (IGT) have increased risk of mortality and a high risk of progression to diabetes, but the extent that the excess mortality is associated with IGT per se or is the result of subsequent diabetes is unclear. RESEARCH DESIGN AND METHODS We compared mortality before and after the development of diabetes among 542 persons with IGT initially who participated in a 6-year lifestyle diabetes prevention trial and were followed-up from 1986 to 2009. RESULTS During the 23-year follow-up, 174 (32.1%) died, with an overall death rate of 15.9/1,000 person-years. The majority of deaths (74.7%; 130 of 174) occurred after progression to type 2 diabetes, with age-adjusted death rates of 11.1/1,000 person-years (95% CI 8.2–12.0) before and 19.4/1,000 person-years (95% CI 11.9–23.3) after the development of type 2 diabetes. The cumulative mortality was 37.8% (95% CI 33.1–42.2%) in participants who developed type 2 diabetes during first 10 years of follow-up, 28.6% (95% CI 21.6–35.0%) in those who progressed to type 2 diabetes in 10–20 years, and 13.9% (95% CI 7.0–20.3%) in those who did not develop to type 2 diabetes within 20 years. Time-dependent multivariate Cox proportional hazards analyses, with adjustment for baseline age, sex, intervention, and other potential confounding risk factors, showed that the development of type 2 diabetes was associated with a 73% higher risk of death (hazard ratio 1.73 [95% CI 1.18–2.52]). CONCLUSIONS As elsewhere, IGT is associated with increased risk of mortality in China, but much of this excess risk is attributable to the development of type 2 diabetes.

Longitudinal study of childhood adiposity and the risk of developing components of metabolic syndrome-the Da Qing children cohort study.

Childhood adiposity is increasingly recognized as a significant predictor of cardiometabolic risks in later life. The aim of this study was to investigate factors associated with longitudinal changes in weight during childhood and the development of metabolic disease risk factors. Four hundred twenty-four children from DaQing city, China, were recruited at 5 y old and followed up for 5 y. Birth weight, television (TV) viewing time at 5 y old, blood pressure, anthropometric measurements, fasting plasma insulin (FI), and triglycerides (TG) levels were measured at 5 and 10 y old. Both birth weight and TV viewing time at 5 y old significantly correlated with percentage of ideal weight for height (WFH) at 5 y old (WFH5; p = 0.0032 and p = 0.01), but only TV time was significantly correlated with WFH at 10 y old (WFH10; p < 0.0001). Blood pressures, FI, homeostasis model assessment for insulin resistance (HOMA-IR), and TG at 10 y old were significantly greater in those children who had greater change in WFH from 5 to 10 y old (ΔWFH). We concluded that TV viewing time was the stronger determinant of later childhood adiposity. A greater ΔWFH was associated with increased cardiometabolic risk factors at 10 y old.