Type 2 diabetes and chronic kidney disease (CKD) may share common risk factors. Here we used a 3-stage procedure to discover novel predictors of CKD by repeatedly applying a stepwise selection based on the Akaike information criterion to subsamples of a prospective complete-case cohort of 2755 patients. This cohort encompassed 25 clinical variables and 36 genetic variants associated with type 2 diabetes, obesity, or fasting plasma glucose. We compared the performance of the clinical, genetic, and clinico-genomic models and used net reclassification improvement to evaluate the impact of top selected genetic variants to the clinico-genomic model. Associations of selected genetic variants with CKD were validated in 2 independent cohorts followed by meta-analyses. Among the top 6 single-nucleotide polymorphisms selected from clinico-genomic data, three (rs478333 of G6PC2, rs7754840 and rs7756992 of CDKAL1) contributed toward the improvement of prediction performance. The variant rs478333 was associated with rapid decline (over 4% per year) in estimated glomerular filtration rate. In a meta-analysis of 2 replication cohorts, the variants rs478333 and rs7754840 showed significant associations with CKD after adjustment for conventional risk factors. Thus, this novel 3-stage approach to a clinico-genomic data set identified 3 novel genetic predictors of CKD in type 2 diabetes. This method can be applied to similar data sets containing clinical and genetic variables to select predictors for clinical outcomes.

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.

The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear.

To evaluate the performance of a real-time continuous glucose monitor (CGM) in individuals with diabetes on peritoneal dialysis (PD).

Recent genome-wide association studies (GWAS) identified more than 70 novel loci for type 2 diabetes (T2D), some of which have been widely replicated in Asian populations. In this study, we investigated their individual and combined effects on T2D in a Chinese population.

To explore the pattern of insulin use and glycaemic control in Asian people with type 2 diabetes, stratified by gender, young-onset diabetes (YOD; diagnosed before age 40 years), and diabetic kidney disease (DKD; estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2 ).

Several studies support associations between relative leukocyte telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates the relationship between rLTL and the risk of glycemic progression in patients with type 2 diabetes.

To explore the patterns of use of oral glucose-lowering drugs (OGLDs) in Asian patients with type 2 diabetes (T2D), focusing on sulphonylureas (SUs), and to describe patient profiles according to treatment regimen.

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.

Sulfonylureas (SUs) are predominantly metabolized by cytochrome p450 2C9 (CYP2C9) and cytochrome p450 2C19 (CYP2C19) enzymes. CYP2C9 polymorphisms are associated with greater treatment response and hypoglycemic risk in SU users. However, there are no large scale pharmacogenetic studies investigating the effect of loss-of-function alleles CYP2C19*2 and CYP2C19*3, which occur frequently in East Asians. Retrospective pharmacogenetic analysis was performed in 11,495 genotyped patients who were enrolled in the Hong Kong Diabetes Register between 1995 and 2017, with follow-up to December 31, 2019. The associations of CYP2C19 polymorphisms with SU treatment failure, early HbA1c response, and severe hypoglycemia were analyzed by Cox regression or logistic regression assuming an additive genetic model. There were 2341 incident SU users that were identified (mean age 59 years, median diabetes duration 9 years), of which 324 were CYP2C19 poor metabolizers (CYP2C19 *2/*2 or *2/*3 or *3/*3). CYP2C19 poor metabolizers had lower risk of SU treatment failure (hazard ratio 0.83, 95% confidence interval (CI) 0.72-0.97, P = 0.018) and were more likely to reach the HbA1c treatment target < 7% (odds ratio 1.52, 95% CI 1.02-2.27, P = 0.039) than wild-type carriers (CYP2C19 *1/*1) following adjustment for multiple covariates. There were no significant differences in severe hypoglycemia rates among different CYP2C19 genotype groups. CYP2C19 polymorphisms should be considered during personalization of SU therapy.

Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes.

Insulin deficiency (ID) and resistance (IR) contribute to progression from normal glucose tolerance to diabetes to insulin requirement although their relative contributions in young-onset diabetes is unknown.

Diabetic kidney disease (DKD) and its comorbidities can be prevented by treating multiple targets. Technology-assisted team-based care with regular feedback and patient empowerment can improve the attainment of multiple targets and clinical outcomes in patients with type 2 diabetes, but the effects of this intervention on patients with DKD are unclear.

Early detection and risk factor control prevent chronic kidney disease (CKD) progression. Evaluation of peripheral autonomic dysfunction may detect incident cardiovascular-renal events in type 2 diabetes (T2D).