Association of technologically assisted integrated care with clinical outcomes in type 2 diabetes in Hong Kong using the prospective JADE Program: A retrospective cohort analysis.

BACKGROUND: Diabetes outcomes are influenced by host factors, settings, and care processes. We examined the association of data-driven integrated care assisted by information and communications technology (ICT) with clinical outcomes in type 2 diabetes in public and private healthcare settings. METHODS AND FINDINGS: The web-based Joint Asia Diabetes Evaluation (JADE) platform provides a protocol to guide data collection for issuing a personalized JADE report including risk categories (1-4, low-high), 5-year probabilities of cardiovascular-renal events, and trends and targets of 4 risk factors with tailored decision support. The JADE program is a prospective cohort study implemented in a naturalistic environment where patients underwent nurse-led structured evaluation (blood/urine/eye/feet) in public and private outpatient clinics and diabetes centers in Hong Kong. We retrospectively analyzed the data of 16,624 Han Chinese patients with type 2 diabetes who were enrolled in 2007-2015. In the public setting, the non-JADE group (n = 3,587) underwent structured evaluation for risk factors and complications only, while the JADE (n = 9,601) group received a JADE report with group empowerment by nurses. In a community-based, nurse-led, university-affiliated diabetes center (UDC), the JADE-Personalized (JADE-P) group (n = 3,436) received a JADE report, personalized empowerment, and annual telephone reminder for reevaluation and engagement. The primary composite outcome was time to the first occurrence of cardiovascular-renal diseases, all-site cancer, and/or death, based on hospitalization data censored on 30 June 2017. During 94,311 person-years of follow-up in 2007-2017, 7,779 primary events occurred. Compared with the JADE group (136.22 cases per 1,000 patient-years [95% CI 132.35-140.18]), the non-JADE group had higher (145.32 [95% CI 138.68-152.20]; P = 0.020) while the JADE-P group had lower event rates (70.94 [95% CI 67.12-74.91]; P < 0.001). The adjusted hazard ratios (aHRs) for the primary composite outcome were 1.22 (95% CI 1.15-1.30) and 0.70 (95% CI 0.66-0.75), respectively, independent of risk profiles, education levels, drug usage, self-care, and comorbidities at baseline. We reported consistent results in propensity-score-matched analyses and after accounting for loss to follow-up. Potential limitations include its nonrandomized design that precludes causal inference, residual confounding, and participation bias. CONCLUSIONS: ICT-assisted integrated care was associated with a reduction in clinical events, including death in type 2 diabetes in public and private healthcare settings.

Diet quality is inversely associated with obesity in Chinese adults with type 2 diabetes.

BACKGROUND: Diet quality has been linked to obesity, but this relationship remains unclear in individuals with type 2 diabetes (T2D). The aim of this study is to examine the association between diet quality and obesity in Chinese adults with T2D. METHODS: Between April and November 2016, a total of 211 Chinese T2D adults who underwent assessment of diabetes-related treatment goals and metabolic control were recruited into two groups based on their body mass index (BMI): obese group (BMI ≥30 kg/m2) and non-obese group (BMI = 18.5-24.9 kg/m2). Diet quality indices including Alternate Healthy Eating Index-2010 (AHEI-2010), Diet Quality Index-International (DQI-I), and Dietary Approach to Stop Hypertension (DASH) score, were derived from a validated food frequency questionnaire. RESULTS: Obese T2D patients had significantly lower AHEI-2010 (P < 0.001), DQI-I (P < 0.001), and DASH total scores (P = 0.044) than their non-obese counterparts, independent of age and sex. They also had higher total energy (P < 0.001), protein percentage of energy (P = 0.023), and meat, poultry and organ meat (P < 0.001), but lower vegetable (P = 0.014) intakes. Our multivariate logistic regression analyses demonstrated that the AHEI-2010, but not DQI-I and DASH, total score had an inverse association with obesity, independent of sociodemographics, anti-diabetic medication use, physical activity level and total energy intake (odds ratio [OR] per standard deviation (1-SD) increase: 0.95, 95% confidence interval [CI]: 0.91-0.99, P = 0.020). This association remained significant after further adjustment for glycemic control. Inverse associations were also found between obesity and multivariate-adjusted component scores, including AHEI-2010 red/processed meat (OR per 1-SD: 0.71, 95% CI: 0.51-0.99, P = 0.044), DQI-I variety (OR per 1-SD: 0.63, 95% CI: 0.46-0.86, P = 0.004), and DASH red/processed meat (OR per 1-SD: 0.57, 95% CI: 0.38-0.84, P = 0.005). CONCLUSIONS: Better diet quality, as characterized by higher AHEI-2010 scores, was associated with lower odds of obesity in Chinese adults with T2D. Dietary patterns reflecting high consumption of plant-based foods and low consumption of animal-based, high-fat, and processed foods may be imperative to optimize nutritional guidance for obesity management in this population.

Association of self-reported recurrent mild hypoglycemia with incident cardiovascular disease and all-cause mortality in patients with type 2 diabetes: Prospective analysis of the Joint Asia Diabetes Evaluation Registry.

Severe hypoglycemia is an established risk marker for cardiovascular complications of diabetes, but whether mild hypoglycemia confers similar risks is unclear. We examined the association of self-reported recurrent mild hypoglycemic events with cardiovascular disease (CVD) and all-cause mortality in a prospective cohort of Chinese adults with type 2 diabetes.From June 2007 to May 2015, 19,019 patients in Hong Kong underwent comprehensive assessment of metabolic and complication status using the Joint Asia Diabetes Evaluation program. Recurrent mild hypoglycemic event was determined by self-report of mild-to-moderate hypoglycemic symptoms at least once monthly in previous 3 months. Incident cardiovascular events were identified using hospital discharge diagnosis codes and death using Hong Kong Death Registry.Patients reporting recurrent mild hypoglycemia (n = 1501, 8.1%) were younger, had longer disease duration, worse glycemic control, and higher frequencies of vascular complications at baseline. Over 3.9 years of follow-up, respective incidences of CVD and all-cause death were 18.1 and 10.3 per 1000 person-years and 15.4 and 9.9 per 1000 person-years in patients with and without recurrent mild hypoglycemia. Using multivariate Cox regression analysis, recurrent mild hypoglycemia was not associated with CVD or all-cause mortality. In subgroup analysis, mild hypoglycemia was related to CVD in patients with chronic kidney disease (hazard ratio 1.36, 95% confidence interval 1.01-1.84, P = 0.0435) and those on insulin (hazard ratio 1.37, 95% confidence interval 1.01-1.86, P = 0.0402) adjusted for confounders.Mild hypoglycemia by self-report was frequent in patients with type 2 diabetes and was associated with increased risk of CVD in susceptible groups.

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.

Delivery of integrated diabetes care using logistics and information technology--the Joint Asia Diabetes Evaluation (JADE) program.

Diabetes is a global epidemic, and many affected individuals are undiagnosed, untreated, or uncontrolled. The silent and multi-system nature of diabetes and its complications, with complex care protocols, are often associated with omission of periodic assessments, clinical inertia, poor treatment compliance, and care fragmentation. These barriers at the system, patient, and care-provider levels have resulted in poor control of risk factors and under-usage of potentially life-saving medications such as statins and renin-angiotensin system inhibitors. However, in the clinical trial setting, use of nurses and protocol with frequent contact and regular monitoring have resulted in marked differences in event rates compared to epidemiological data collected in the real-world setting. The phenotypic heterogeneity and cognitive-psychological-behavioral needs of people with diabetes call for regular risk stratification to personalize care. Quality improvement initiatives targeted at patient education, task delegation, case management, and self-care promotion had the largest effect size in improving cardio-metabolic risk factors. The Joint Asia Diabetes Evaluation (JADE) program is an innovative care prototype that advocates a change in clinic setting and workflow, coordinated by a doctor-nurse team and augmented by a web-based portal, which incorporates care protocols and a validated risk engine to provide decision support and regular feedback. By using logistics and information technology, supported by a network of health-care professionals to provide integrated, holistic, and evidence-based care, the JADE Program aims to establish a high-quality regional diabetes database to reflect the status of diabetes care in real-world practice, confirm efficacy data, and identify unmet needs. Through collaborative efforts, we shall evaluate the feasibility, acceptability, and cost-effectiveness of this "high tech, soft touch" model to make diabetes and chronic disease care more accessible, affordable, and sustainable.

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.

Associations of sleep duration with obesity and serum lipid profile in children and adolescents.

INTRODUCTION: The association between sleep duration, obesity, and serum lipid profile in the youth population is under-explored. OBJECTIVE: To evaluate the association between sleep duration, obesity and serum lipid profile in the youth population. METHODS: We conducted a cross-sectional population-based study with students recruited from primary and secondary schools in Hong Kong. Anthropometric measurements, fasting lipid profiles and validated questionnaires on sleep duration were performed. A subgroup (n=138) was randomly selected for both questionnaires and actigraphy to assess the agreement between subjective and objective measurements of sleep duration. RESULTS: We studied 2053 healthy children and adolescents aged 6-20 years. Their mean ages were 13.0±3.3 (boys) and 13.6±3.3 (girls) years. The average sleep duration during schooldays, weekends, and long holidays was 8.0±1.1, 9.6±1.2, and 9.8±1.2h in boys and 7.7±1.1, 9.9±1.2, and 10.1±1.2h in girls, respectively. Using logistic regression, age, and pubertal stage were associated with obesity in secondary school students, whereas male gender and short sleep duration were associated with obesity in primary school children. In secondary school children, those with long sleep duration, as compared to those with short sleep duration, were significantly associated with reduced risk to have high TC and LDL-C levels after adjustment for age, gender, BMI, and pubertal stage. There was no significant association between sleep duration and lipid levels in primary school children. CONCLUSION: Reduced sleep duration was associated with obesity and atherogenic dyslipidemia in young school children in Hong Kong.

Serum concentrations of insulin-like growth factor-I, insulin-like growth factor binding protein-3 and cardiovascular risk factors in adolescents.

BACKGROUND: The risk association between the insulin like growth factor-I (IGF-I) system and cardiovascular risk is inconclusive in adults and under-explored in adolescents. We aimed to investigate the associations between serum concentrations of IGF-I and IGF binding protein-3 (IGFBP-3) and cardiovascular risk factors in adolescents. METHODS: This was a cross-sectional, population-based, observational study in a school setting with 2102 Hong Kong Chinese adolescents aged 12-19 years. Serum IGF-I and IGFBP-3 concentrations were measured by chemiluminescence immunoassays. Anthropometric indices and traditional cardiovascular risk factors were assessed. RESULTS: After excluding participants with abnormal thyroid and liver test results, 765 boys and 877 girls, mean (±SD) age of 15.3 (±2.0) and 15.7 (±2.0) years, respectively, were included in the analysis. Multivariable regression analyses revealed that both IGF-I and IGFBP-3 concentrations were independently associated with waist circumference, fasting insulin and haemoglobin concentrations in boys (all P < 0.05), systolic blood pressure, serum creatinine, fasting insulin and haemoglobin concentrations in girls (all P < 0.05). In girls, IGF-I was also associated with C-reactive protein concentration (P < 0.001) and IGFBP-3 was associated with fasting triglyceride concentration (P < 0.001). Compared with adolescents with the lowest tertile, the top tertile of both IGF-I and IGFBP-3 concentrations were associated with increased odds of having overweight/obesity, top tertiles of insulin and haemoglobin in both boys and girls (P for trend, all <0.05). CONCLUSIONS: The associations between serum IGF-I, IGFBP-3, obesity, cardiovascular risk factors, insulin and haemoglobin suggest that dysregulation of the IGF system may play a linking role for the clustering of cardiovascular risk factors.

Diabetes-related distress and physical and psychological health in chinese type 2 diabetic patients.

OBJECTIVE: To validate a Chinese version of the Diabetes Distress Scale (CDDS). RESEARCH DESIGN AND METHODS: The CDDS was derived using forward-backward translation and administered in 189 Chinese type 2 diabetic patients with evaluation of its psychometric properties. RESULTS: On the basis of principal-component analysis, three factors of the 15-item version of the CDDS (CDDS-15) accounted for 63% of the variance. The correlation coefficient between the original 17-item and 15-item scales was 0.99. The Cronbach α for internal consistency was 0.90, and the test-retest reliability coefficient was 0.74. The CDDS-15 score was significantly associated with glycemic control, obesity, depressive symptoms, and quality of life. CONCLUSIONS: The CDDS-15 is a valid and reliable instrument to assess diabetes-related distress.

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.

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.

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.

Pharmacogenetic analysis of lipid responses to rosuvastatin in Chinese patients.

Lipid changes with statin treatments vary greatly between individuals for reasons which are largely unknown. This study was performed to examine the genetic determinants of lipid responses to rosuvastatin in Chinese patients. A total of 125 polymorphisms in 61 candidate genes from 386 Chinese patients were analyzed for association with the lipid responses to rosuvastatin 10 mg daily. The polymorphisms most highly associated with the low-density lipoprotein cholesterol (LDL-C) response were 421C>A in the ATP-binding cassette G2 gene (P=9.2×10), followed by 18281G>A (V257M) in the flavin-containing monooxygenase 3 gene (P=0.0002), 1421C>G in the lipoprotein lipase gene (P=0.002), and rs4420638 in the apolipoprotein E/C-I/C-IV/C-II gene cluster (P=0.004). Patients with familial hypercholesterolemia had 2.6% smaller reductions in LDL-C compared with patients without familial hypercholesterolemia. This study identified some genetic determinants of LDL-C response to rosuvastatin in Chinese patients, which need to be replicated in other populations.

Association between physical activity and cardiovascular risk in Chinese youth independent of age and pubertal stage.

BACKGROUND: Childhood and adolescence are critical periods of habit formation with substantial tracking of lifestyle and cardiovascular risk into adulthood. There are various guidelines on recommended levels of physical activity in youth of school-age. Despite the epidemic of obesity and diabetes in China, there is a paucity of data in this regard in Chinese youth. We examined the association of self-reported level of physical activity and cardiovascular risk in Hong Kong Chinese youth of school-age. METHODS: This was a cross-sectional study conducted in 2007-8 in a school setting with 2119 Hong Kong Chinese youth aged 6-20 years. Physical activity level was assessed using a validated questionnaire, CUHK-PARCY (The Chinese University of Hong Kong: Physical Activity Rating for Children and Youth). A summary risk score comprising of waist circumference, blood pressure, fasting plasma glucose and lipids was constructed to quantify cardiovascular risk. RESULTS: In this cohort, 21.5% reported high level of physical activity with boys being more active than girls (32.1% versus 14.1%, p < 0.001). Regression analysis showed physical activity level, sex and pubertal stage were independently associated with cardiovascular risk score. CONCLUSION: Self-reported level of physical activity is associated with cardiovascular risk factors in Chinese youth after adjusting for sex and pubertal stage.

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.

White blood cell count and renin-angiotensin system inhibitors for the risk of cancer in type 2 diabetes.

BACKGROUND: High white blood cell (WBC) predicted cancer-associated mortality and renin-angiotensin system (RAS) inhibitors have immunomodulating effects. We hypothesize that RAS inhibitors may reduce cancer risk associated with high WBC in type 2 diabetes mellitus (T2DM). METHODS: A prospective cohort of 4570 Chinese T2DM patients, free of cancer at enrolment, were analyzed. Biological interaction between WBC groups and use of RAS inhibitors was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (S). RERI>0, AP>0 or S>1 indicates biological interaction. RESULTS: During 4.89 years of follow-up, 205 (4.49%) patients developed cancer. WBC > or = 8.2 x 10(9) counts/L plus non-use of RAS inhibitors was associated with elevated cancer risks in multivariable models. The RERI and AP for interaction between WBC > or = 8.2 x 10(9) counts/L and non-use of RAS inhibitors were, respectively, 1.26 (95% CI: 0.22-2.31) and 0.50 (0.23-0.78). In patients with WBC > or = 8.2 x 10(9) counts/L, use of RAS inhibitors was associated with 64% (31-81%) cancer risk reduction in multivariable analysis. CONCLUSIONS: In T2DM, increased WBC predicts cancer while use of RAS inhibitors may reduce cancer risks associated with high WBC count.

Low LDL cholesterol, albuminuria, and statins for the risk of cancer in type 2 diabetes: the Hong Kong diabetes registry.

OBJECTIVE: LDL cholesterol <2.80 mmol/l was associated with increased cancer risk in type 2 diabetes. We explored the 1) interaction between low LDL cholesterol and albuminuria and 2) interaction between copresence of these two risk factors and statin use for cancer in type 2 diabetes. RESEARCH DESIGN AND METHODS: We analyzed prospective data for 3,793 Chinese type 2 diabetic patients who remained naive for statin treatment and 1,483 patients in whom statin treatment was initiated during a median follow-up period of 5.24 years. All patients were free of cancer at baseline. Biological interactions were estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). RERI > 0, AP > 0, or S > 1 indicates biological interaction. RESULTS: In 3,793 statin-naive type 2 diabetic patients, copresence of low LDL cholesterol and albuminuria increased cancer risk by 2.8-fold (hazard ratio 2.77 [95% CI 1.78-4.31]) with significant biological interactions (RERI 1.05 [0.04-2.06]; AP 0.38 [0.09-0.66]). In the whole cohort of 5,276 type 2 diabetic patients, there was interaction between nonuse of statins and copresence of low LDL cholesterol and albuminuria with increased cancer risk (RERI 2.87 [0.64-5.09] and AP 0.60 [0.29-0.90]). Statin nonusers with LDL cholesterol <2.80 mmol/l and albumunuria had a 4.9-fold risk of cancer compared with statin users with or without both risk factors. CONCLUSIONS: In type 2 diabetes, there was interaction between low LDL cholesterol and albuminuria with increased cancer risks. The latter was attenuated in the presence of statin treatment.

Effect of interactions between C peptide levels and insulin treatment on clinical outcomes among patients with type 2 diabetes mellitus.

BACKGROUND: A recently halted clinical trial showed that intensive treatment of type 2 diabetes mellitus was associated with increased mortality. Given the phenotypic heterogeneity of diabetes, therapy targeted at insulin status may maximize benefits and minimize harm. METHODS: In this longitudinal cohort study, we followed 503 patients with type 2 diabetes who were free of cardiovascular disease from 1996 until data on mortality and cardiovascular outcomes were censored in 2005. Phenotype-targeted therapy was defined as use of insulin therapy in patients with a fasting plasma C peptide level of 0.2 nmol/L or less and no insulin therapy in patients with higher C peptide levels. RESULTS: The mean age of the cohort was 54.4 (standard deviation 13.1) years, and 56% were women. The mean duration of diabetes was 4.6 years (range 0-35.9 years). Of the 503 patients, 110 (21.9%) had a low C peptide level and 111 (22.1%) were given insulin. Based on their C peptide status, 338 patients (67.2%) received phenotype-targeted therapy (non-insulin-treated, high C peptide level [n = 310] or insulin-treated, low C peptide level [n = 28]), and 165 patients (32.8%) received non-phenotype-targeted therapy (non-insulin-treated, low C peptide level [n = 82] or insulin-treated, high C peptide level [n = 83]). Compared with the insulin-treated, low-C-peptide referent group, the insulin-treated, high-C-peptide group was at a significantly higher risk of cardiovascular events (hazard ratio [HR] 2.85, p = 0.049) and death (HR 3.43, p = 0.043); the risk was not significantly higher in the other 2 groups. These differences were no longer significant after adjusting for age, sex and diabetes duration. INTERPRETATION: Patients with low C peptide levels who received insulin had the best clinical outcomes. Patients with normal to high C peptide levels who received insulin had the worst clinical outcomes. The results suggest that phenotype-targeted insulin therapy may be important in treating diabetes.