Declining Trends of Cardiovascular-Renal Complications and Mortality in Type 2 Diabetes: The Hong Kong Diabetes Database.

OBJECTIVE: Nationwide studies on secular trends of diabetes complications are not available in Asia. We examined changes in risk factor control and incidence of complications from diabetes and death in a large longitudinal cohort of Chinese adults with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS: Between 1 January 2000 and 31 December 2012, 338,908 Chinese adults with type 2 diabetes underwent metabolic and complication assessment in 16 diabetes centers operated by Hong Kong Hospital Authority that provided care to a large majority of diagnosed patients. Patients were followed for incident acute myocardial infarction (AMI), stroke, end-stage renal disease (ESRD), and death until 31 December 2012. Risk factor levels between enrollment periods were compared. Incidence of clinical events, stratified by diabetes duration, was examined over time. RESULTS: Incidence of complications from diabetes and death declined over the observation period in patients at varying disease duration. Among the high-risk group with diabetes for at least 15 years, crude incidence of AMI decreased from 8.7 to 5.8, stroke from 13.5 to 10.1, ESRD from 25.8 to 22.5, and death from 29.0 to 26.6 per 1,000 person-year between the periods 2000 to 2002 and 2010 to 2012. Improvements in levels of metabolic risk factors were detected. Proportion of patients achieving HbA1c <7.0% (53 mmol/mol) was increased from 32.9 to 50.0%, blood pressure ≤130/80 mmHg from 24.7 to 30.7%, and LDL cholesterol <2.6 mmol/L from 25.8 to 38.1%. CONCLUSIONS: From this territory-wide Hong Kong Diabetes Database, we observed decreases in incidence of cardiovascular-renal complications and death and corresponding improvements in risk factor control over a 13-year period.

Premature mortality and comorbidities in young-onset diabetes: a 7-year prospective analysis.

BACKGROUND: There is an increasing prevalence of young-onset diabetes, especially in developing areas. We compared the clinical outcomes and predictors for cardiovascular-renal events between Chinese patients with type 2 diabetes with young- or late-onset of disease diagnosed before or after the age of 40 years, respectively. METHODS: The Hong Kong Diabetes Registry was established in 1995 as an ongoing quality improvement initiative with consecutive enrollment of diabetic patients from ambulatory settings for documentation of risk factors, microvascular and macrovascular complications, and clinical outcomes using a structured protocol. RESULTS: In 9509 Chinese patients with type 2 diabetes with a median (interquartile range) follow-up period of 7.5 (3.9-10.8) years, 21.3% (n = 2066) had young-onset diabetes. Despite 20 years difference in age, patients with young-onset diabetes (mean age, 41.3 years) had a similar or worse risk profile than those with late-onset disease (mean age, 61.9 years). Compared with the patients with late-onset diabetes, those with young-onset diabetes had lower rates of cardiovascular disease and chronic kidney disease for the same disease duration but a higher cumulative incidence of clinical events at any given age. With the use of stepwise Cox proportional hazard analysis, patients with young-onset diabetes had higher risks for cardiovascular and renal events when adjusted by age, but no difference in risks than in the patients with late-onset diabetes when further adjusted by disease duration. CONCLUSIONS: Patients with young-onset diabetes had a similar or worse metabolic risk profile compared with those with late-onset disease. This group had higher risks for cardiovascular-renal complications at any given age, driven by longer disease duration.

Risk association of HbA1c variability with chronic kidney disease and cardiovascular disease in type 2 diabetes: prospective analysis of the Hong Kong Diabetes Registry.

BACKGROUND: In type 2 diabetes, tight glycaemic control lowers the risk of diabetic complications, but it remains uncertain whether variability of glycaemia influences outcomes. We examined the association of glycated haemoglobin (HbA1c ) variability with incident chronic kidney disease and cardiovascular disease in a prospective cohort of 8439 Chinese patients with type 2 diabetes recruited from 1994 to 2007. METHODS: Intrapersonal mean and SD of serially measured HbA1c were calculated. Chronic kidney disease was defined as estimated glomerular filtration rate <60 ml/min per 1.73 m². Cardiovascular disease was defined as events of ischemic heart disease, heart failure, ischemic stroke or peripheral vascular disease. RESULTS: Over a median follow-up period of 7.2 years, 19.7 and 10.0% of patients developed chronic kidney disease and cardiovascular disease, respectively. Patients who progressed to chronic kidney disease had higher mean HbA1c (7.8 ± 1.3% vs 7.4 ± 1.2%, p < 0.001) and SD (1.0 ± 0.8% vs 0.8 ± 0.6%, p < 0.001) than nonprogressors. Similarly, patients who developed cardiovascular disease had higher mean HbA1c (7.7 ± 1.3% vs 7.4 ± 1.2%, p < 0.001) and SD (1.4 ± 1.1% vs 1.1 ± 0.8%, p < 0.001) than patients who did not develop cardiovascular disease. By using multivariate-adjusted Cox regression analysis, adjusted SD was associated with incident chronic kidney disease and cardiovascular disease with corresponding hazard ratios of 1.16 (95% CI 1.11-1.22), p < 0.001) and 1.27 (95% CI 1.15-1.40, p < 0.001), independent of mean HbA1c and other confounding variables. CONCLUSIONS: Long-term glycaemic variability expressed by SD of HbA1c predicted development of renal and cardiovascular complications.

Use of thiazolidinedione and cancer risk in Type 2 diabetes: the Hong Kong diabetes registry.

We examined possible anticancer effects of thiazolidinediones (TZDs) in 6074 Chinese with Type 2 diabetes free of cancer at enrolment. During a median follow-up of 4.93 years, 270 patients developed cancer. Use of TZDs was associated with reduced risk of cancer in a dose-response manner in multivariable analysis.

Low triglyceride and nonuse of statins is associated with cancer in type 2 diabetes mellitus: the Hong Kong Diabetes Registry.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) have increased cancer risks. The authors reported nonlinear associations of cancer with triglyceride and other lipids in T2DM. Crosstalk between lipid metabolism and the renin-angiotensin system may increase cancer risk via activation of insulin-like growth factor-1 pathway in T2DM. In this analysis, the authors explored associations of cancer risk with high/low triglyceride in T2DM and possible modifying effects of statins on this risk association, if any. METHODS: A consecutive cohort of 5166 Chinese patients with T2DM, free of cancer at enrollment and not using statins at or before enrollment, was analyzed using Cox models. Biological interactions were estimated using relative excess risk because of interaction, attributable proportion because of interaction, and synergy index. Relative excess risk because of interaction > 0, attributable proportion because of interaction > 0, or synergy index > 1 indicates biological interaction. RESULTS: During 5.25 years of follow-up (median), 4.7% (n = 243) patients developed cancer. Triglyceride < 1.70 mmol/L was associated with increased cancer risk in the entire cohort and in statin nonusers, but not in statin users. Patients with triglyceride < 1.70 mmol/L plus nonuse of statins during follow-up had 2.74-fold increased cancer risk compared with their counterparts with either triglyceride ≥ 1.70 mmol/L or use of statins or both. There was significant interaction between triglyceride < 1.70 mmol/L and nonuse of statins (relative excess risk because of interaction, 0.99; 95% confidence interval [CI], 0.07-1.90 and attributable proportion because of interaction, 0.36; 95% CI, 0.02-0.70). CONCLUSIONS: In Chinese T2DM patients, triglyceride < 1.70 mmol/L might be associated with increased cancer risk, which was attenuated in the presence of use of statins.

Low HDL cholesterol, metformin use, and cancer risk in type 2 diabetes: the Hong Kong Diabetes Registry.

OBJECTIVE: The AMP-activated protein kinase (AMPK) pathway is a master regulator in energy metabolism and may be related to cancer. In type 2 diabetes, low HDL cholesterol predicts cancer, whereas metformin usage is associated with reduced cancer risk. Both metformin and apolipoprotein A1 activate the AMPK signaling pathway. We hypothesize that the anticancer effects of metformin may be particularly evident in type 2 diabetic patients with low HDL cholesterol. RESEARCH DESIGN AND METHODS: In a consecutive cohort of 2,658 Chinese type 2 diabetic patients enrolled in the study between 1996 and 2005, who were free of cancer and not using metformin at enrollment or during 2.5 years before enrollment and who were followed until 2005, we measured biological interactions for cancer risk using relative excess risk as a result of interaction (RERI) and attributable proportion (AP) as a result of interaction. A statistically significant RERI >0 or AP >0 indicates biological interaction. RESULTS: During 13,808 person-years of follow-up (median 5.51 years), 129 patients developed cancer. HDL cholesterol <1.0 mmol/L was associated with increased cancer risk among those who did not use metformin, but the association was not significant among those who did. Use of metformin was associated with reduced cancer risk in patients with HDL cholesterol <1.0 mmol/L and, to a lesser extent, in patients with HDL cholesterol ≥ 1.0 mmol/L. HDL cholesterol <1.0 mmol/L plus nonuse of metformin was associated with an adjusted hazard ratio of 5.75 (95% CI 3.03-10.90) compared with HDL cholesterol ≥ 1.0 mmol/L plus use of metformin, with a significant interaction (AP 0.44 [95% CI 0.11-0.78]). CONCLUSIONS: The anticancer effect of metformin was most evident in type 2 diabetic patients with low HDL cholesterol.

Lipid control and use of lipid-regulating drugs for prevention of cardiovascular events in Chinese type 2 diabetic patients: a prospective cohort study.

BACKGROUND: Dyslipidaemia is an important but modifiable risk factor of cardiovascular disease (CVD) in type 2 diabetes. Yet, the effectiveness of lipid regulating drugs in Asians is lacking. We examined the effects of lipid control and treatment with lipid regulating drugs on new onset of CVD in Chinese type 2 diabetic patients. METHODS: In this prospective cohort consisting of 4521 type 2 diabetic patients without history of CVD and naïve for lipid regulating treatment recruited consecutively from 1996 to 2005, 371 developed CVD after a median follow-up of 4.9 years. We used Cox proportional hazard regression to obtain the hazard ratios (HR) of lipids and use of lipid regulating drugs for risk of CVD. RESULTS: The multivariate-adjusted HR (95% confidence interval) of CVD in patients with high LDL-cholesterol (≥ 3.0 mmol/L) was 1.36 (1.08 - 1.71), compared with lower values. Using the whole range value of HDL-cholesterol, the risk of CVD was reduced by 41% with every 1 mmol/L increase in HDL-cholesterol. Plasma triglyceride did not predict CVD. Statins use was associated with lower CVD risk [HR = 0.66 (0.50 - 0.88)]. In sub-cohort analysis, statins use was associated with a HR of 0.60 (0.44 - 0.82) in patients with high LDL-cholesterol (≥ 3.0 mmol/L) and 0.49 (0.28 - 0.88) in patients with low HDL-cholesterol. In patients with LDL-cholesterol < 3.0 mmol/L, use of fibrate was associated with HR of 0.34 (0.12 - 1.00). Only statins were effective in reducing incident CVD in patients with metabolic syndrome [(HR = 0.58(0.42 - 0.80)]. CONCLUSIONS: In Chinese type 2 diabetic patients, high LDL-cholesterol and low HDL-cholesterol predicted incident CVD. Overall, patients treated with statins had 40-50% risk reduction in CVD compared to non-users.

Associations of hyperglycemia and insulin usage with the risk of cancer in type 2 diabetes: the Hong Kong diabetes registry.

OBJECTIVE Insulin has mitogenic effects, although hyperglycemia may be a risk factor for cancer in type 2 diabetes. It remains uncertain whether use of insulin increases cancer risk because of its effect on cell growth and proliferation or decreases cancer risk because of its glucose-lowering effect. RESEARCH DESIGN AND METHODS A 1:2-matched new insulin user cohort on age (+/-3 years), smoking status, and likelihood of initiating insulin therapy (+/-0.05) was selected from a cohort of 4,623 Chinese patients with type 2 diabetes, free of cancer, and naive to insulin at enrollment. Stratified Cox regression analysis on the matched pairs was used to obtain hazard ratios (HRs) of insulin therapy and A1C for cancer risk. A structured adjustment scheme was used to adjust for covariates. RESULTS Of 973 new insulin users, 971 had matched nonusers (n = 1935). The cancer incidence in insulin nonusers was much higher than that in insulin users (49.2 vs. 10.2, per 1,000 person-years, P < 0.0001). After further adjustment for all other covariates with a P value less than 0.3 and nonlinear associations with cancer, A1C was associated with an increased cancer risk (HR per percentage 1.26, 95% CI 1.03-1.55), whereas use of insulin was associated with a decreased cancer risk (HR of insulin users vs. nonusers: 0.17, 0.09-0.32). Consistent results were found in analyses including all 973 insulin users and 3,650 nonusers. CONCLUSIONS In Chinese patients with type 2 diabetes, hyperglycemia predicts cancer, whereas insulin usage was associated with a reduced cancer risk.

Metabolic syndrome predicts new onset of chronic kidney disease in 5,829 patients with type 2 diabetes: a 5-year prospective analysis of the Hong Kong Diabetes Registry.

OBJECTIVE: Type 2 diabetes is the leading cause of end-stage renal disease worldwide. Aside from hyperglycemia and hypertension, other metabolic factors may determine renal outcome. We examined risk associations of metabolic syndrome with new onset of chronic kidney disease (CKD) in 5,829 Chinese patients with type 2 diabetes enrolled between 1995 and 2005. RESEARCH DESIGN AND METHODS: Metabolic syndrome was defined by National Cholesterol Education Program Adult Treatment Panel III criteria with the Asian definition of obesity. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease formula modified for the Chinese population. New onset of CKD was defined as eGFR <60 ml/min per 1.73 m(2) at the time of censor. Subjects with CKD at baseline were excluded from the analysis. RESULTS: After a median follow-up duration of 4.6 years (interquartile range: 1.9-7.3 years), 741 patients developed CKD. The multivariable-adjusted hazard ratio (HR) of CKD was 1.31 (95% CI 1.12-1.54, P = 0.001) for subjects with metabolic syndrome compared with those without metabolic syndrome. Relative to subjects with no other components of metabolic syndrome except for diabetes, those with two, three, four, and five metabolic syndrome components had HRs of an increased risk of CKD of 1.15 (0.83-1.60, P = 0.407) 1.32 (0.94-1.86, P = 0.112), 1.64 (1.17-2.32, P = 0.004), and 2.34 (1.54-3.54, P < 0.001), respectively. The metabolic syndrome traits of central obesity, hypertriglyceridemia, hypertension, and low BMI were independent predictors for CKD. CONCLUSIONS: The presence of metabolic syndrome independently predicts the development of CKD in subjects with type 2 diabetes.