Risa Ozaki

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 m2 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.

Phenotypic and genetic clustering of diabetes and metabolic syndrome in Chinese families with type 2 diabetes mellitus

The aim of this study was to investigate the familiality and clustering of type 2 diabetes (T2DM) and metabolic syndrome (MES) predominantly in families with young‐onset diabetes from the Hong Kong Family Diabetes Study.

BMI and Waist Circumference in Predicting Cardiovascular Risk Factor Clustering in Chinese Adolescents

Objective: To derive the optimal BMI and waist circumference (WC) cut‐off values to predict clustering of cardiovascular risk factors in Hong Kong Chinese adolescents.

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.

Use of sulphonylurea and cancer in type 2 diabetes—The Hong Kong Diabetes Registry

BACKGROUND Hyperglycaemia is a risk factor for cancer and some sulphonylureas have anti-oxidant properties. This study examined associations between use of sulphonylureas and cancer. METHODS A consecutive cohort of 6103 Hong Kong Chinese patients with T2DM, free of cancer, was analysed using Cox models. Sulphonylurea usage was defined as use of the drugs at or within 2.5 years before enrolment and/or during follow-up periods. We adjusted for identified risk factors of cancer, use of other drugs, non-linear associations of lipids with cancer and probabilities of use of these drugs at different times and doses where appropriate. RESULTS During a median of 4.91 years of follow-up, 271 developed cancer. Glibenclamide, gliclazide and glipizide were ever used in 32.5% (n = 1983), 47.8% (n = 2920) and 13.5% (n = 823). After adjustment for covariates, use of gliclazide and glibenclamide was associated with reduced cancer risk in a dose-dependent manner. In addition, there were interactions between metformin and glibenclamide/glipizide use towards lower adjusted cancer risks. CONCLUSIONS In T2DM, use of glibenclamide and gliclazide may be associated with reduced cancer risk.

Effects of Telephone-Based Peer Support in Patients With Type 2 Diabetes Mellitus Receiving Integrated Care: A Randomized Clinical Trial

IMPORTANCE In type 2 diabetes mellitus (T2DM), team management using protocols with regular feedback improves clinical outcomes, although suboptimal self-management and psychological distress remain significant challenges. OBJECTIVE To investigate if frequent contacts through a telephone-based peer support program (Peer Support, Empowerment, and Remote Communication Linked by Information Technology [PEARL]) would improve cardiometabolic risk and health outcomes by enhancing psychological well-being and self-care in patients receiving integrated care implemented through a web-based multicomponent quality improvement program (JADE [Joint Asia Diabetes Evaluation]). DESIGN, SETTING, AND PARTICIPANTS Between 2009 and 2010, 628 of 2766 Hong Kong Chinese patients with T2DM from 3 publicly funded hospital-based diabetes centers were randomized to the JADE + PEARL (n = 312) or JADE (n = 316) groups, with comprehensive assessment at 0 and 12 months. INTERVENTIONS Thirty-three motivated patients with well-controlled T2DM received 32 hours of training (four 8-hour workshops) to become peer supporters, with 10 patients assigned to each. Peer supporters called their peers at least 12 times, guided by a checklist. MAIN OUTCOMES AND MEASURES Changes in hemoglobin A(1c) (HbA(1c)) level (primary), proportions of patients with attained treatment targets (HbA(1c) <7%; blood pressure <130/80 mm Hg; low-density lipoprotein cholesterol <2.6 mmol/L [to convert to milligrams per deciliter, divide by 0.0256]) (secondary), and other health outcomes at month 12. RESULTS Both groups had similar baseline characteristics (mean [SD] age, 54.7 [9.3] years; 57% men; disease duration, 9.4 [7.7] years; HbA(1c) level, 8.2% [1.6%]; systolic blood pressure, 136 [19] mm Hg; low-density lipoprotein cholesterol level, 2.89 [0.82] mmol/L; 17.4% cardiovascular-renal complications; and 34.9% insulin treated). After a mean (SD) follow-up period of 414 (55) days, 5 patients had died, 144 had at least 1 hospitalization, and 586 had repeated comprehensive assessments. On intention-to-treat analysis, both groups had similar reductions in HbA(1c) (JADE + PEARL, 0.30% [95% CI, 0.12%-0.47%], vs JADE, 0.29% [95% CI, 0.12%-0.47%] [P = .97]) and improvements in treatment targets and psychological-behavioral measures. In the JADE + PEARL group, 90% of patients maintained contacts with their peer supporters, with a median of 20 calls per patient. Most of the discussion items were related to self-management. CONCLUSIONS AND RELEVANCE In patients with T2DM receiving integrated care, peer support did not improve cardiometabolic risks or psychological well-being. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00950716.

Overweight, family history of diabetes and attending schools of lower academic grading are independent predictors for metabolic syndrome in Hong Kong Chinese adolescents

Background: Overweight and metabolic syndrome (MES) are emerging in both adult and paediatric populations. Aims: To study the prevalence of and associated risk factors for the MES, using the National Cholesterol Education Program definition, among Hong Kong Chinese adolescents studying in secondary schools. Methods: This was a cross-sectional, population-based study. A sample of 2115 Chinese adolescents was randomly selected from 14 secondary schools throughout Hong Kong. Data on anthropometric parameters, fasting blood and urine samples were collected in the school setting. Information regarding the adolescent’s family history of diabetes, perinatal history, socioeconomic status and school grading was evaluated. Results: The prevalence of MES was 2.4% (95% confidence interval (CI) 1.8 to 3.1), with no significant difference between boys (2.9%) and girls (2%). The prevalence of various components of MES was 32.2% (30.2 to 34.2) for hypertension, 10.9% (9.6 to 12.2) for increased triglyceride, 9.0% (7.8 to 10.2) for central adiposity, 2.4% (1.7 to 3) for low high-density lipoprotein cholesterol and 0.3% (0.1 to 0.6) for impaired fasting glucose. On multivariate analysis, overweight (odds ratio 32.2; 95% CI 13.2 to 78.4), positive family history of diabetes (4.3; 1.3 to 14.1) and studying at schools of lower academic grading (5.5; 2.2 to 13.7) were found to be independent risk factors for MES. Conclusion: A comparable prevalence of MES (2%) is observed in our study group Chinese adolescent girls and in US girls (2.1%), but a lower prevalence in Chinese boys (2.9%) than in US boys (6.1%). In our study, 41.8% harbour at least one component of the syndrome. Both families and schools should be alerted to this growing epidemic.

Prospective Study on the Incidences of Cardiovascular-Renal Complications in Chinese Patients With Young-Onset Type 1 and Type 2 Diabetes

OBJECTIVE We examined metabolic profiles and cardiovascular-renal outcomes in a prospective cohort of Chinese patients with young-onset diabetes defined by diagnosis age <40 years. Patients with type 1 diabetes and normal-weight (BMI <23 kg/m2) and overweight (BMI ≥23 kg/m2) patients with type 2 diabetes were compared. RESEARCH DESIGN AND METHODS Between 1995 and 2004, 2,323 patients (type 1 diabetes, n = 209; normal-weight type 2 diabetes, n = 636; and overweight type 2 diabetes, n = 1,478) underwent detailed clinical assessment. Incident cardiovascular disease (CVD) including coronary heart disease, stroke, and peripheral vascular disease were identified using hospital discharge diagnoses. End-stage renal disease (ESRD) was defined by glomerular filtration rate <15 mL/min/1.73 m2 or dialysis. RESULTS Overweight patients with type 2 diabetes had the worst metabolic profile and highest prevalence of microvascular complications. Over a median follow-up of 9.3 years, incidences of CVD were 0.6, 5.1, and 9.6 per 1,000 person-years in patients with type 1 diabetes, normal-weight patients with type 2 diabetes, and overweight patients with type 2 diabetes. The respective figures for ESRD were 2.2, 6.4, and 8.4 per 1,000 person-years. Compared with type 1 diabetes, the overweight type 2 diabetes group had a greater hazard of progression to CVD (hazard ratio [HR] 15.3 [95% CI 2.1–112.4]) and ESRD (HR 5.4 [95% CI 1.8–15.9]), adjusted for age, sex, and disease duration. The association became nonsignificant upon additional adjustment for BMI, blood pressure, and lipid. CONCLUSIONS Young patients with type 2 diabetes had greater risks of developing cardiovascular-renal complications compared with patients with type 1 diabetes. The increased risk was driven primarily by accompanying metabolic risk factors.

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.

Severe Hypoglycemia Identifies Vulnerable Patients With Type 2 Diabetes at Risk for Premature Death and All-Site Cancer: The Hong Kong Diabetes Registry

OBJECTIVE We examined the associations of clinical profiles in type 2 diabetic patients who developed severe hypoglycemia and their clinical outcomes, including death and all-site cancer. RESEARCH DESIGN AND METHODS A consecutive cohort of 8,767 type 2 diabetic patients with and without severe hypoglycemia in the 12 months before enrollment were recruited between 1995 and 2007, with follow-up until 2009. Severe hypoglycemia was defined by ICD-9 codes as hospitalizations resulting from hypoglycemia. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% CIs of clinical factors collected at enrollment for severe hypoglycemia. RESULTS In this cohort, mean age was 57.4 (SD 13.2) years and median disease duration of diabetes was 5 (interquartile range [IQR] 1–11) years. During a median follow-up of 6.71 (IQR 3.47–10.38) years, 235 patients had severe hypoglycemia (incidence 3.96 [95% CI 3.45–4.46] per 1,000 patient-years). At enrollment, patients with and without severe hypoglycemia had similar cancer rates. During follow-up, patients with severe hypoglycemia had a higher incidence of all-site cancer (13.4 vs. 6.4%, P < 0.0001) and mortality (32.8 vs. 11.2%, P < 0.0001) than those without severe hypoglycemia. After adjusting for confounders, old age, low BMI, high glycated hemoglobin, low triglyceride (TG), low LDL cholesterol (LDL-C), albuminuria, and chronic kidney disease were independent predictors for severe hypoglycemia. CONCLUSIONS In type 2 diabetes, severe hypoglycemia is associated with advanced age, renal dysfunction, poor glycemic control, and cancer subphenotypes (low BMI, low LDL-C, and low TG).