Effects of temporal changes in resting heart rate on future diabetes-related outcomes.

Background and aims: Most studies have analyzed the relationship between resting heart rate (RHR) measured at only one time point and future clinical events. The current study aims to investigate the impact of long-term RHR changes on future clinical outcomes in a decade-long cohort with type 2 diabetes mellitus (T2DM). Methods: The two-staged follow-up involved 2,513 T2DM participants. The first stage (2008-2014) intended to identify levels and trends in RHR changes, while the second stage (2014-2018) attempted to collect new occurrence records of clinical results. Cox proportional hazards models were applied to predict hazard ratios (HRs), along with 95% confidence interval (CI) for the correlation between RHR changes and future events. Results: There is no significant correlation between baseline RHR levels and long-term clinical events. According to the range of RHR change, compared with the stable RHR group, the adjusted HRs for cardiovascular events and all-cause death in the large increase group were 3.40 (95% CI: 1.33-8.71, p=0.010) and 3.22 (95% CI: 1.07-9.64, p=0.037), respectively. While the adjusted HRs for all-cause death and major adverse cardiac and cerebrovascular events (MACCE) in the moderate decrease group were 0.55 (95% CI: 0.31-0.96, p=0.037) and 0.51 (95% CI: 0.26-0.98, p=0.046). According to the trend of RHR, compared with the normal-normal group, the adjusted HRs for composite endpoint events and cerebrovascular events in the normal-high group were 1.64 (95% CI: 1.00-2.68, p=0.047) and 2.82 (95% CI: 1.03-7.76, p=0.043), respectively. Conclusion: Changes in RHR had predictive value for long-term clinical events in diabetic populations. Individuals with significantly elevated RHR over a particular period of time showed an increased risk of adverse events.

Neck circumference and waist circumference associated with cardiovascular events in type 2 diabetes (Beijing Community Diabetes Study 23).

Obesity increases the risk of developing cardiovascular disease and other metabolic diseases. We intended to compare three different anthropometric indicators of obesity, in predicting the incidence of cardiovascular events in Chinese type 2 diabetes. Beijing Community Diabetes Study was a prospective multi-center study conducted in Beijing community health centers. Type 2 diabetes patients from fourteen community health centers were enrolled at baseline. The primary endpoint was cardiovascular events. The upper quartile of neck circumference (NC) was set as greater NC. A total of 3299 diabetes patients were enrolled. In which, 941 (28.52%) had cardiovascular disease at baseline. Logistic analysis showed that central obesity (waist circumference (WC) above 90 cm in men and 85 cm in women) and greater NC were all related to baseline cardiovascular disease (adjusted OR = 1.49, and 1.55). After 10-year follow-up, 340 (10.31%) had cardiovascular events. Compared with patients without cardiovascular events, those having cardiovascular events had higher BMI, larger WC and NC. Cox regression analysis showed that greater WC and NC were all associated with the occurrence of cardiovascular events (adjusted HR = 1.41, and 1.38). A higher NC and WC might increase the risk of cardiovascular events by about 40% in type 2 diabetes patients in Beijing communities.

The effects of acarbose therapy on reductions of myocardial infarction and all-cause death in T2DM during 10-year multifactorial interventions (The Beijing Community Diabetes Study 24).

To investigate the potential benefits of acarbose therapy on cardiovascular events (CVD) in Type 2 diabetes (T2DM) in an urban community over 10-year follow-up. The study population of Beijing Community Diabetes Study (BCDS) were type 2 diabetes (T2DM) living in 21 communities in Beijing. All patients received comprehensive intervention in accordance with the Chinese guidelines for the prevention and treatment of diabetes. Professors in endocrinology from top tier hospitals regularly visited the communities for consultations, which was a feature of this study. A total of 1797 T2DM in BCDS study had complete screening data, including blood glucose, blood pressure, lipid profiles and acarbose continuous therapy. After 10-year follow-up, the risks of CVD outcomes were assessed according to whether patients had received acarbose therapy or not. All patients were followed-up to assess the long-term effects of the multifactorial interventions. At baseline, compared with the acarbose therapy free in T2DM, there was no significant difference in achieving the joint target control in patients with acarbose therapy. From the beginning of 8th year follow-up, the joint target control rate in patients with acarbose therapy was significantly higher than that of acarbose therapy free. During the 10-year follow-up, a total of 446 endpoint events occurred, including all-cause death, cardiovascular events, cerebrovascular events. The incidences of myocardial infarction (from the 4th year of follow-up) and all-cause death (from the 2nd year of follow-up) in patients who received acarbose therapy were significantly lower than that of acarbose therapy free respectively. In Cox multivariate analyses, there were significant differences in incidences of myocardial infarction and all-cause death between afore two groups during the 10-year follow-up, and the adjusted HRs were 0.50 and 0.52, respectively. After multifactorial interventions, T2DM with acarbose therapy revealed significant reductions of myocardial infarction and all-cause death. The long-term effects of with acarbose therapy on improving joint target control might be one of the main reasons of myocardial infarction and all-cause death reduction.Trial Registration: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.

Improved Framingham Risk Scores of Patients with Type 2 Diabetes Mellitus in the Beijing Community: A 10-Year Prospective Study of the Effects of Multifactorial Interventions on Cardiovascular Risk Factors (The Beijing Communities Diabetes Study 22).

INTRODUCTION: To date, research is lacking on the development of a cardiovascular disease (CVD) risk assessment tool for people with diabetes mellitus, in general, and for Chinese patients with diabetes in particular. We have explored CVD risk assessment tools for Chinese patients with diabetes. Here, we report our investigation of cardiovascular risk assessment using the improved Framingham Risk Score (I-FRS) in patients with type 2 diabetes mellitus (T2DM) in Beijing communities. METHODS: A total of 3232 patients with T2DM attending Beijing community health centers were enrolled in this study. FRS were used to predict CVD risk in all patients at baseline using the following risk scores for glycated hemoglobin (HbA1c) categories: 0 = HbA1c ≤ 7.0%; 1 = 7.0% < HbA1c ≤ 7.9%;      2 = 8.0% < HbA1c ≤ 8.9%; and 3 = HbA1c > 9.0%. The I-FRS was use to stratify all patients into low (I-FRS < 10%), medium (I-FRS 10-20%), and high (I-FRS > 20%) FRS strata. All treatments administered in the Beijing Communities Diabetes Study were in accordance with national guidelines for T2DM in China, and patients regularly attended clinical consultations with professors in endocrinology, who were experts in their respective speciality, from top tier hospitals. After 10 years, patients were followed-up to assess the long-term effects of the multifactorial interventions. Statistical analysis was performed using SAS® software (SAS Institute, Inc., Cary, NC, USA). RESULTS: The receiver operating characteristic curve of the I-FRS showed significant prediction accuracy for the actual incidence of CVD events. At baseline, subjects in the high FRS stratum for diabetes were more prone to be elderly and to have a longer duration of T2DM, higher systolic blood pressure, and higher lipid profiles. Subjects in the medium and high FRS strata had a higher incidence of CVD events than those in the no-complications group (DM group with no blood pressure issues) (P < 0.001). The 10-year hazard ratios for CVD events in diabetic patients with I-FRS score > 20% was 12.5-fold higher than that of patients with I-FRS score < 10%. Multifactorial intervention significantly reduced the I-FRS of the three FRS strata in patients with T2DM. The post-intervention I-FRS for the hypertension and CVD groups of patients were significantly lower than the respective baseline I-FRS. Cox multivariate analyses revealed that patients in the medium and high FRS strata had higher incidences of endpoint events than those in the low FRS stratum. CONCLUSIONS: The I-FRS plays an important role in predicting CVD in patients with T2DM. Multifactorial interventions for CVD risk factors over 10-year follow-up lowered the estimated 10-year risk for CVD events in persons with diabetes. We suggest the use of the I-FRS score to stratify a patient's risk of CVD when analyzing the efficacy of diabetes management. Aggressive risk reduction should be focused on those individuals with a high I-FRS score. TRIAL REGISTRATION: ChiCTR-TRC-13003978 and ChiCTR-OOC-15006090.

Association between Neck Circumference and the Occurrence of Cardiovascular Events in Type 2 Diabetes: Beijing Community Diabetes Study 20 (BCDS-20).

BACKGROUND: Neck circumference (NC) was found to be related to the risk factors of cardiovascular disease. However, the effects of NC on cardiovascular disease are still controversial. A prospective study of Chinese patients with type 2 diabetes was performed to evaluate the relationship between NC and cardiovascular disease. METHODS: A multicenter prospective study with eight-year follow-up was conducted in Beijing communities. Cardiovascular events were defined as myocardial infarction, unstable angina pectoris, hospitalization for heart failure, coronary revascularization, cardiac death, stroke, transient ischemic attack, and cerebral hemorrhage. RESULTS: A total of 3,009 diabetic patients were recruited. Following an eight-year follow-up, 211 patients with cardiovascular events (105 in men and 106 in women) were identified. All patients were categorized into two groups according to the upper quartile of NC (43 cm in men and 39 cm in women). The prevalence of cardiovascular events in men with an NC >43 cm (16.48%) was higher than that in the group with an NC <43 cm (8.16%, p=0.007). The prevalence of cardiovascular events in women with the NC >39 cm (10.67%) was higher compared to the group with NC <39 cm (5.31%, p=0.004). The longitudinal prevalence of cardiovascular events in groups with different NC increased with the increasing duration of follow-up (p < 0.001). Cox regression analysis showed that higher NC was associated with the occurrence of cardiovascular events after adjusting for confounding variables (adjusted HR = 2.305 (1.535-3.460)). CONCLUSIONS: NC was associated with the occurrence of cardiovascular events in type 2 diabetes in Chinese communities, and greater NC may increase the risk of cardiovascular events by about 2.3-fold.

The Association between Metabolic Syndrome and Morbid Events in Type 2 Diabetes after a 7-Year Community Management: Beijing Community Diabetes Study 17.

BACKGROUND: To examine the association between morbid events and metabolic syndrome (MS) in patients with type 2 diabetes mellitus (T2DM). METHODS: A prospective, longitudinal, multicenter study was conducted at 13 community health centers associated with Beijing Tongren Hospital. From 2008 to 2015, there have been 3,525 T2DM patients being managed based on the Chinese guideline for T2DM. The morbid events included macrovascular events, diabetic kidney disease, ophthalmologic events, cancer, and all-cause death. RESULTS: At baseline, there were 2,708 people with MS and 817 without MS. After a seven-year management, there were 351 (12.96%) events in MS people and 74 (9.06%) events in people without MS (p = 0.003). The prevalence of macrovascular events (6.06%) was much higher in MS people than in people without MS (3.79%, p = 0.013). Cox regression analysis showed an association between MS and morbid events even after adjusting for confounding variables (adjusted hazard ratio = 1.44). MS was also associated with macrovascular events (adjusted hazard ratio = 1.96). The occurrence of morbid events and macrovascular events was increased when the numbers of metabolic abnormalities were 1, 2, 3, and 4 (p < 0.001). There was no continuously statistically significant difference in the cumulative prevalence of morbid events between patients with MS and patients without MS during the first five years. However, after six or seven years, the cumulative prevalence of morbid events in patients with MS was continuously significantly higher than that in patients without MS (11.00% vs. 8.20%, 12.96% vs. 9.06%, p < 0.05). CONCLUSIONS: T2DM with MS had higher incidence of morbid events, especially cardiovascular events, even after integrated management. The occurrence of morbid and macrovascular events increased as the number of metabolic abnormalities increased. MS was associated with increased risk of morbid events by 44% and macrovascular events by 96%. It would take at least six years to observe the association between MS and morbid events in T2DM.

The effects of cardiovascular risk factor combined anti-platelet therapy and the risk of cerebrovascular events in patients with T2DM in an urban community over 96-months follow-up: The Beijing communities diabetes study 19.

OBJECTIVE: We investigated the prognostic significance of metabolic risk scores and aspirin with respect to cerebrovascular events. METHODS: A total of 25 communities of diabetic patients were enrolled in Beijing Community Diabetes Study (BCDS) from 2008. 3413 patients with T2DM in BCDS have complete screening data, including blood glucose, blood pressure, lipid profiles and anti-platelet therapy, which were assigned metabolic score (MS) and add up to the total metabolic score (TMS). According to the total metabolic score (TMS), the patients were divided into four equal groups: Group 1 (24 < TMS < 40), Group 2 (40 < TMS < 47), Group 3 (47 < TMS < 55) and Group 4 (55 < TMS < 87). After 96 months, patients were followed-up to assess the long-term effects of the multifactorial interventions. RESULTS: During 96-months follow-up, a total of 91 cerebrovascular events occurred, including acute cerebral infarction, acute cerebral hemorrhage and transient ischemic attack (TIA). The incidence of cerebrovascular events was higher in the Group 4 than in the Group 1. In Cox multivariate analyses, there are significant differences in incidences of cerebral infarction events among the four groups during the 96-months follow-up. Cox proportional hazards analysis revealed that, HbA1c (p ≤ 0.001), systolic pressure (p ≤ 0.001), aspirin free treatment (P = 0.0023) are independent predictor for cerebrovascular events in diabetic patients. CONCLUSIONS: This study indicates that total metabolic score (TMS) influences the incidence of cerebrovascular events in diabetic patients. In addition to good control of blood glucose, blood pressure and lipid profiles, anti-platelet therapy is important for the prevention of cerebrovascular events in T2DM. TRIAL REGISTRATION: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.

The effects of AER and eGFR on outcomes of CVD in patients with T2DM in an urban community over 8 years of multifactorial treatment: the Beijing Communities Diabetes Study 18.

OBJECTIVE: It is well known that diabetic kidney disease is a risk factor for cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM). In this study, the effects of urine albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR) on CVD outcomes were analyzed in a population of T2DM. METHODS: The study was carried out using recorded information of a cohort study. A total of 1,914 patients with T2DM with no prevalent CVD were enrolled in an 8 years prospective study and received multifactorial intervention. The risk of CVD outcomes was assessed according to chronic kidney disease staging, which was categorized using AER (mg/d) and eGFR (mL/min/1.73 m2). The effects of AER and eGFR on risk of CVD onset were also analyzed. RESULTS: During the follow-up period (median 6.8 years), 71 CVD events occurred. At baseline, those with AER ≥300 mg/d and coexisting eGFR 60-89 mL/min/1.73 m2 or <60 mL/min/1.73 m2 showed increased risk for CVD outcomes when compared with "no chronic kidney disease" (AER <30 mg/d and eGFR ≥90 mL/min/1.73 m2). The increased CVD risk was observed in patients who progressed to AER ≥30 mg/d during the follow-up period, whereas patients who progressed to eGFR <90 mL/min/1.73 m2 alone showed no increased CVD risk. During the follow-up period, after multifactorial intervention, 8.7% patients with microalbuminuria and 1.8% patients with overt nephropathy reversed to normoalbuminuria or microalbuminuria. CONCLUSION: AER is a more sensitive predictor than eGFR for CVD outcomes in T2DM patients. Overt nephropathy can be reversed after multifactorial intervention.

Influence of educational attainments on long term glucose control and morbid events in patients with type 2 diabetes receiving integrated care from 15 China urban communities: The Beijing Community Diabetes Study 11.

AIM: To investigate the effects of educational attainment on glucose control and morbid events in patients with type 2 diabetes in Beijing communities. METHODS: In this prospective multi-center study, 2866 type 2 diabetes patients receiving integrated care from 15 Beijing urban communities were investigated. Educational attainment was categorized into three levels: low, medium, and high. After a 42-month management, glucose control parameters and morbid events were analyzed. RESULTS: At baseline, the percentages of patients with good glucose control (HbA1c ≤ 7.0%) in the low, medium and high educational groups were 49.09%, 54.82% and 62.59%, respectively (P<0.001). After the 42-month management, fasting plasma glucose and HbA1c values were the highest in the low educational group (7.51 ± 2.05 mmol/l and 7.20 ± 1.27%, respectively). Percentages of patients with good glucose control in the three groups were 49.6%, 55.83% and 67.23%, respectively, and the incidences of combined morbid events were 4.5%, 2.4% and 1.5%, respectively. Cox regression analysis showed that educational level was related to the incidence of combined morbid events (medium level, HR=0.572; high level, HR=0.351; P<0.05). CONCLUSIONS: Educational level was associated with long-term glucose control, and seemed to be related to the incidence of combined morbid events in people with type 2 diabetes.

Prevalence and risk factors for diabetic retinopathy: the Beijing Communities Diabetes Study 6.

BACKGROUND: To examine prevalence and associated factors of diabetic retinopathy in patients with Type 2 diabetes mellitus in urban communities of Beijing. METHODS: The community health care center-based study included subjects with diabetes mellitus and an age of 20 years to 80 years, who were recruited from 15 community health centers in urban Beijing. Diabetes mellitus was defined using the World Health Organization criteria. Fundus photographs were graded using the modified Airlie House classification system. RESULTS: Of 2,642 eligible patients, 2,007 (76.0%) subjects (1,199 women) with a mean age of 64.1 ± 9.0 years participated. The overall prevalence of diabetic retinopathy was 24.7 ± 1.0% (95% confidence interval [CI], 22.8-26.6). In binary logistic analysis, presence of diabetic retinopathy was associated with younger age (odds ratio [OR], 0.97; 95% CI, 0.95-0.98), longer duration of diabetes (OR, 1.10; 95% CI, 1.08-1.12), higher concentration of glycosylated hemoglobin HbA1c (OR, 1.23; 95% CI, 1.14-1.33), higher systolic blood pressure (OR, 1.01; 95% CI, 1.01-1.02), lower body mass index (OR, 0.95; 95% CI, 0.92-0.98), and elevated blood urea concentration (OR, 1.01; 95% CI, 1.00-1.01). Microalbuminuria was an additional associated factor (OR, 1.55; 95% CI, 1.16-2.08). Patients with microalbuminuria were 4.7 times more likely to have a severe or proliferating diabetic retinopathy than those without microalbuminuria. CONCLUSION: In the urban population of Beijing, prevalence of diabetic retinopathy in diabetic patients was 25%. As in whites, increased blood pressure besides elevated plasma glucose concentrations was highly significantly associated with diabetic retinopathy in Chinese. It suggests that in Chinese as also in whites, blood pressure control beside control of plasma glucose levels is important to prevent development or progression of diabetic retinopathy.

The importance of γ-Glutamyltransferase (GGT) activity: a potential marker of Left Ventricular (LV) diastolic function in diabetic patients with cardiovascular disease.

OBJECTIVES: To examine the relation between left ventricular (LV) diastolic function and γ-glutamyltransferase (GGT) in diabetic individuals with or without previously diagnosed cardiovascular disease. DESIGN: A cross-sectional population-based study. SETTING: A university hospital. SUBJECTS: A total of 205 diabetic patients were included in the study. Patients who had cardiovascular disease constituted the study group (CD group; n = 112) and patients who had no complications constituted the control group (ND group; n = 93). Left ventricular diastolic function was assessed by pulsed Doppler tissue imaging and was determined by ratio E wave/A wave. MAIN OUTCOME MEASURES: GGT levels were higher in CD Group than ND Group (25.9 ± 2.1 vs. 20.1 ± 1.5 units/L, p = 0.023). Significant difference between mean diastolic function parameters, such as E wave/A wave (0.86 ± 0.27 vs. 1.01 ± 0.36, p = 0.015), of the diabetic patients with and without cardiovascular disease was present. In this study, E wave/A wave correlated with age, waist-to-hip ratio (WHR), systolic blood pressure, and total cholesterol. Negative correlations were also found between LV diastolic function and GGT (ß = -0.009, p = 0.008). CONCLUSION: The data showed that in type 2 diabetic patients, with evident cardiac disease, metabolic parameters affect diastolic functions more than systolic functions. Besides known cardiovascular disease risk factors, GGT might be an additional marker of diastolic dysfunction in diabetes patients with cardiovascular disease.

Neck circumference positively related with central obesity, overweight, and metabolic syndrome in Chinese subjects with type 2 diabetes: Beijing Community Diabetes Study 4.

OBJECTIVE: To investigate the association between neck circumference and central obesity, overweight, and metabolic syndrome in Chinese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 3,182 diabetic subjects (aged 20-80 years) were recruited from 15 community health centers in Beijing using a multistage random sampling approach. RESULTS: Receiver operating characteristic analysis showed that the area under the curve for neck circumference and central obesity was 0.77 for men and 0.75 for women (P<0.001). Furthermore, a neck circumference of ≥38 cm for men and ≥35 cm for women was the best cutoff point for determining overweight subjects. A neck circumference of ≥39 cm for men and ≥35 cm for women was the best cutoff point to determine subjects with metabolic syndrome. CONCLUSIONS: In the present study, neck circumference is positively related with BMI, waist circumference, and metabolic syndrome in Chinese individuals with type 2 diabetes.

Effects of impaired fasting glucose and impaired glucose tolerance on predicting incident type 2 diabetes in a Chinese population with high post-prandial glucose.

AIMS: To ascertain which impaired glucose homeostasis at baseline is predictive of conversion to type 2 diabetes in both men and women in a high-risk non-diabetic population. METHODS: The screening survey for type 2 diabetes was conducted in 1994, and a follow-up study of 627 high-risk non-diabetic individuals at baseline was carried out in 1999 in Beijing area. A total of 70 men and 76 women developed diabetes during the 5-year follow-up. RESULTS: After adjustment for age, body mass index, smoking, systolic blood pressure, family history of diabetes, total cholesterol, triglycerides, antihypertensive medication, occupation, education, urine albumin excretion rate, and fasting insulin, the odds ratios for incidence of diabetes were 1.00, 2.04 (95% CI 0.84-4.97), 7.82 (2.66-23.00), 9.38 (3.30-26.69) in men with normal glucose, isolated IFG, isolated IGT, and both IFG and IGT, respectively. In women, the corresponding odds ratios were 1.00, 2.19 (0.91-5.30), 1.62 (0.72-3.67), and 8.79 (2.98-25.93), respectively. CONCLUSIONS: This study shows that combined IFG and IGT at baseline is a strong risk predictor for the development of diabetes in both men and women. Isolated IGT is also a predictor of diabetes in Chinese men.