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Glycated hemoglobin A1c (HbA1c) has reduced reliability in advanced chronic kidney disease (CKD) owing to factors influencing red cell turnover. Recent guidelines support the use of continuous glucose monitoring (CGM) in glycemic assessment in these patients. We evaluated relationships between HbA1c and CGM metrics of average glycemia and glucose variability (GV) in moderate-to-advanced CKD.There were a total of 90 patients with diabetes in CKD stages G3b (Correlations between glucose management indicator (GMI) and HbA1c attenuated with advancing CKD (G3b [CGM-derived indices might serve as an adjunct to HbA1c monitoring to guide glycemic management, especially in those with eGFR 30 ml/min per 1.73 m

Renin-angiotensin-system inhibitors (RASi), that include angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) reduce proteinuria, delay chronic kidney disease (CKD) progression, protect against cardiovascular events and heart failure hospitalizations. We examined the associations of discontinuation of ACEi/ARBs with risk of clinical outcomes in Chinese patients with type 2 diabetes (T2D) and advanced-CKD (estimated-glomerular filtration rate [eGFR]30 ml/min/1.73 mWe conducted a prospective, population-based cohort study including 10,400 patients with T2D in Hong Kong stratified by continuation of ACEi/ARBs within 6 months after reaching eGFR30 ml/min/1.73 mIn the population-based cohort of 10,400 ACEi/ARBs users with new-onset eGFR30 ml/min/1.73 mDiscontinuation of ACEi/ARBs was associated with increased risk of cardiovascular-renal events supporting their continued use in patients with T2D and advanced-CKD.CUHK Impact Research Fellowship Scheme.

Cancer is replacing cardiovascular-disease as a leading cause of death in type 2 diabetes (T2D). The association of RAS-inhibitors (RASi) and cancer, including differences between angiotensin-converting-enzyme-inhibitor (ACEi) and angiotensin-receptor-blocker (ARBs) as well as their associations independent of blood pressure lowering, remains inconclusive in T2D.We conducted a cohort study with new-user design in 253,491 patients in the Hong-Kong-Diabetes-Surveillance-Database (HKDSD) in 2002-2019. We evaluated the associations of time-varying RASi use (ACEi and ARBs) with all-site cancer, diabetes-related cancers, and cancer-specific mortality including comparison with new-users of calcium-channel-blockers (CCBs) as an active-comparator group.Of 253,491, 133,730 (52.8%) were new-RASi and 119,761 (47.2%) were non-RASi users with a median follow-up period of 6.3 (interquartile ragne: 3.4-9.2) years (1,678,719 patient-years). After propensity-score weighting and adjustment for time-varying covariables, RASi use was associated with lower risk of all-site cancer (HR=0.76, 95%CI: 0.74-0.79), diabetes-related cancer (HR=0.79, 95%CI: 0.75-0.84), cancer-specific mortality (HR=0.50, 95%CI: 0.47-0.53), and diabetes-related cancer mortality (HR=0.49, 95%CI: 0.45-0.54) versus non-RASi. Amongst RASi users, ARBs use was associated with lower risk of cancer-specific mortality versus ACEi (HR=0.77, 95%CI: 0.66-0.91). Use of RASi was associated with an estimated-prevention of 2.6 (95%CI: 2.3-3.0) all-site cancer per-1000-person-years and 2.2 (95%CI: 2.0-2.5) cancer-related mortality per-1000-person-years. Lower risk of cancer-specific mortality was similarly observed in new-RASi compared with new-CCBs users.RASi use was independently associated with lower cancer risk in T2D with stronger associations in users of ARBs than ACEi. The benefits of RASi in patients with diabetes might go beyond cardiovascular-renal protection if confirmed by other real-world studies and trials.Dr. Aimin Yang was supported by a CUHK Impact-Research-Fellowship Scheme.

This systematic review aims to assess the incidence of chronic kidney disease (CKD), cardiovascular disease (CVD) and mortality in people with type 2 diabetes diagnosed20 years.We searched MEDLINE, Embase and Cochrane Library for longitudinal studies published between 1 January 2000 and 31 November 2021.Seventeen studies (15 reporting CKD, 3 reporting CVD, 5 reporting mortality) from seven countries of sample size ranging between 96 and 4,141 were eligible. Most studies were conducted in North America and Europe (n = 14). Diabetes duration at enrolment varied from 0 to 8.3 years and follow-up duration from 1 to 12.6 years. The incidence rates (per 1,000 person-year) of albuminuria ranged between 12.4 and 114.8, macroalbuminuria or proteinuria between 10 and 35.0, end-stage kidney disease (ESKD) between 0.4 and 25.0, CVD between 3.7 and 19.5, and mortality between 1.0 and 18.6. The highest incidence rates of albuminuria, ESKD and mortality were recorded in Australian Aboriginal and Pima Indian populations. Youth-onset type 2 diabetes was associated with greater risk of developing CKD compared with type 1 diabetes in most studies.Studies reporting CVD in youth-onset type 2 diabetes are scarce. Estimated incidence rates of CKD and mortality in youth-onset type 2 diabetes varied across different study populations, potentially higher in indigenous people. Youth with type 2 diabetes are at higher risk of adverse kidney outcomes than their type 1 counterparts. More studies are needed in regions outside of North America and Europe.

Nonalbuminuric diabetic kidney disease (DKD) has become the prevailing DKD phenotype. We compared the risks of adverse outcomes among patients with this phenotype compared with other DKD phenotypes.Multicenter prospective cohort study.19,025 Chinese adults with type 2 diabetes enrolled in the Hong Kong Diabetes Biobank.DKD phenotypes defined by baseline estimated glomerular filtration rate (eGFR) and albuminuria: no DKD (no decreased eGFR or albuminuria), albuminuria without decreased eGFR, decreased eGFR without albuminuria, and albuminuria with decreased eGFR.All-cause mortality, cardiovascular disease (CVD) events, hospitalization for heart failure (HF), and chronic kidney disease (CKD) progression (incident kidney failure or sustained eGFR reduction ≥40%).Multivariable Cox proportional or cause-specific hazards models to estimate the relative risks of death, CVD, hospitalization for HF, and CKD progression. Multiple imputation was used for missing covariates.Mean participant age was 61.1 years, 58.3% were male, and mean diabetes duration was 11.1 years. During 54,260 person-years of follow-up, 438 deaths, 1,076 CVD events, 298 hospitalizations for HF, and 1,161 episodes of CKD progression occurred. Compared with the no-DKD subgroup, the subgroup with decreased eGFR without albuminuria had higher risks of all-cause mortality (hazard ratio [HR], 1.59 [95% CI, 1.04-2.44]), hospitalization for HF (HR, 3.08 [95% CI, 1.82-5.21]), and CKD progression (HR, 2.37 [95% CI, 1.63-3.43]), but the risk of CVD was not significantly greater (HR, 1.14 [95% CI, 0.88-1.48]). The risks of death, CVD, hospitalization for HF, and CKD progression were higher in the setting of albuminuria with or without decreased eGFR. A sensitivity analysis that excluded participants with baseline eGFR 30 mL/min/1.73 mPotential misclassification because of drug use.Nonalbuminuric DKD was associated with higher risks of hospitalization for HF and of CKD progression than no DKD, regardless of baseline eGFR.

Background Obesity, cancer and diabetes frequently coexist. The association of glycaemic variability (GV) and obesity with cancer events had not been explored in diabetes. Methods In the prospective Hong Kong Diabetes Register cohort (1995-2019), we used cox proportional hazards models to examine the risk associations of GV with all-site cancer (primary outcome) and cause-specific death (secondary outcome). We also explored the joint association of obesity and GV with these outcomes and site-specific cancer. We expressed GV using HbA1c variability score (HVS) defined as percentage of HbA1c values varying by 0.5% compared with values in preceding visit. Findings We included 15,286 patients (type 2 diabetes: n=15,054, type 1 diabetes: n=232) with ≥10 years of diabetes and ≥3 years of observation (51.7% men, age (mean±SD): 61.04±10.73 years, HbA1c: 7.54±1.63%, body mass index [BMI]: 25.65±3.92 kg/m2, all-site cancer events: n=928, cancer death events: n=404). There were non-linear relationships between HVS and outcomes but there was linearity within the high and low HVS groups stratified by the median (IQR) value of HVS (42.31 [27.27, 56.28]). In the high HVS group, the adjusted hazard ratios (aHR) of each SD of HVS was 1.15 (95% CI: 1.04, 1.26) for all-site cancer (n=874). The respective aHRs for breast (n=77), liver (n=117) and colorectal (n=184) cancer were 1.44 (1.07, 1.94), 1.37 (1.08, 1.74), and 1.09 (0.90, 1.32). In the high GV group, the respective aHRs were 1.21 (1.06, 1.39), 1.27 (1.15, 1.40), and 1.15 (1.09, 1.22) for cancer, vascular, and noncancer nonvascular death. When stratified by obesity (BMI ≥25 kg/m2), the high HVS & obese group had the highest aHRs of 1.42 (1.16, 1.73), 2.44 (1.24, 4.82), and 2.63 (1.45, 4.74) respectively for all-site, breast, and liver cancer versus the low GV & non-obese group. The respective aHRs were 1.45 (1.07, 1.96), 1.47 (1.12, 1.93), and 1.35 (1.16, 1.57) for cancer, vascular, and noncancer nonvascular death. Interpretation Obesity and high GV were associated with increased risk of all-site, breast, liver cancer, and cancer-specific death in T2D. Funding The Chinese University of Hong Kong Diabetes Research Fund

Background & Aims Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for chronic kidney disease (CKD). Given the high prevalence of NAFLD among patients with diabetes who are also at risk of CKD, we aimed to investigate the association between NAFLD and albuminuria, a marker commonly found in diabetic nephropathy. Methods This study included a cohort of Chinese patients with type 2 diabetes from the Hong Kong Diabetes Registry recruited between March 2013 and May 2014. Liver stiffness measurement (LSM), with probe-specific cut-offs, was used to detect advanced liver fibrosis. While controlled attenuation parameter (CAP) was used to assess liver steatosis using transient elastography. Results A total of 1,763 Chinese patients with type 2 diabetes were recruited in this analysis. The mean (standard deviation) age and duration of diabetes were 60.7 (11.5) years and 10.8 (8.5) years, respectively. The prevalence of albuminuria was higher in diabetic patients with liver steatosis and those with advanced fibrosis (no NAFLD vs. liver steatosis vs. advanced fibrosis: 41.4% vs. 46.2% vs. 64.2%, p p = 0.039) in patients with eGFR ≥60 ml/min/1.73 m 2 . The odds of albuminuria increased with greater severity of liver fibrosis in a dose dependent manner, with the highest odds observed in patients with LSM scores ≥11.5 kPa assessed by M probe or ≥11.0 kPa assessed by XL probe (adjusted OR 1.53; 95% CI 1.07–2.20; p = 0.021). Conclusions Advanced liver fibrosis, but not steatosis, is independently associated with albuminuria in Chinese patients with type 2 diabetes. Attention should be paid to liver fibrosis in patients with obesity and type 2 diabetes complicated with albuminuria. Lay summary In this study, we assessed the link between non-alcoholic fatty liver disease (NAFLD) and albuminuria in a cohort of 1,763 Chinese patients with type 2 diabetes. This study shows that advanced liver fibrosis, a severe form of NAFLD, was independently associated with increased risk of albuminuria. The risk of albuminuria increased with greater severity of liver fibrosis.

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.

Depression is known to be associated with premature mortality and cardiovascular disease (CVD) in type 2 diabetes, although there is a paucity of similar data in Chinese population. In this study, we examined the risk association of major depression with premature mortality and CVD in a hospital clinic-based cohort.In a prospective cohort of 7835 Hong Kong Chinese with type 2 diabetes but without CVD at baseline, 153 patients were diagnosed with major depression by psychiatrists in public hospitals. After a median follow-up period of 7.4 years, 827 patients died and 829 patients developed CVD mainly due to stroke (n=384). We used Cox proportional hazard regression to obtain the hazard ratio (HR, 95% confidence interval, CI) of depression for the risk of mortality and CVD.Depressed patients were younger (51.6 versus 56.6 years, p0.001), more likely to be female (78.4% versus 53.0%, p0.001), had higher LDL-cholesterol (3.2 versus 3.0 mmol/L, p=0.038) at baseline and longer hospitalization stays per year (median:0.8 nights per 100-person-years versus 0.1 nights per 100-person-years, p0.001). After adjusting for conventional risk factors, depression independently predicted CVD [HR=2.18(95% CI=1.45-3.27)], mainly due to stroke [HR=3.55(95% CI=2.15-5.84)].The young age and small sample size of patients with depression did not give sufficient power to confirm risk association of depression with premature mortality and myocardial infarction.In Chinese type 2 diabetic patients, depression was associated with a 2-3 fold increase in the risk of incident CVD, especially stroke.