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OBJECTIVE We examined the associations of GAD antibodies (GADA) and C-peptide (CP) with insulin initiation, glycemic responses, and severe hypoglycemia in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS In 5,230 Chinese patients (47.6% men) with T2D (mean ± SD age: 56.5 ± 13.9 years; median diabetes duration: 6 [interquartile range 1, 12] years), enrolled consecutively in 1996–2012 and prospectively observed until 2019, we retrospectively measured fasting CP and GADA in stored serum and examined their associations with aforementioned outcomes. RESULTS At baseline, 28.6% (n = 1,494) had low CP ( CONCLUSIONS There is considerable heterogeneity in autoimmunity and β-cell dysfunction in T2D with GADA+ and high CP associated with early insulin initiation, while GADA+ and low CP, increased the risk of severe hypoglycemia. Extended phenotyping is warranted to increase the precision of classification and treatment in T2D.

OBJECTIVE To evaluate the performance of a real-time continuous glucose monitor (CGM) in individuals with diabetes on peritoneal dialysis (PD). RESEARCH DESIGN AND METHODS Thirty participants with type 2 diabetes on continuous ambulatory PD wore a Guardian Sensor 3 on the upper arm paired with Guardian Connect for 14 days. We compared CGM readings against Yellow Springs Instrument (YSI) venous glucose during an 8-h in-clinic session with glucose challenge. RESULTS The mean absolute relative difference (MARD) was 10.4% (95% CI 9.6, 11.7) from 941 CGM-YSI matched pairs; 81.3% of readings were within %15/15 of YSI values in the full glycemic range. Consensus error grid analysis showed 99.9% of sensor values in zones A and B. There were no correlations between pH, uremia, hydration status, and MARD. CONCLUSIONS We showed satisfactory performance of a real-time CGM sensor in PD patients with diabetes, supporting future use to facilitate treatment decisions.

Objective: This study aims to unravel genetic determinants of coronary heart disease (CHD) in type 2 diabetes (T2D) and explore their applications. Research Design and Methods: We performed a two-stage genome-wide association studies for CHD in Chinese patients with T2D (3,596 cases and 8,898 controls), followed by replications in European patients with T2D (764 cases and 4,276 controls) and general populations (n=51,442-547,261). Each identified variant was examined for its association with a wide range of phenotypes, and its interactions with glycaemic, blood pressure (BP) and lipid controls on incident cardiovascular diseases. Results: We identified a novel variant (rs10171703) for CHD (OR [95% CI] = 1.21 [1.13–1.30]; P=2.4×10-8) and BP (β±SE = 0.130±0.017; P = 4.1×10-14) at PDE1A in Chinese T2D patients, but found only a modest association with CHD in general populations. This variant modulated the effects of BP goal attainment (130/80 mmHg) on CHD (Pinteraction = 0.0155) and myocardial infarction (MI) (Pinteraction = 5.1×10-4). Patients with CC-genotype of rs10171703 had >40% reduction in either cardiovascular events in response to BP control (2.9×10-8 < P < 3.6×10-5), those with CT-genotype had no difference (0.0726 < P < 0.2614), and those with TT-genotype had a threefold increase in MI risk (P = 6.7×10-3). Conclusions: We discovered a novel CHD- and BP-related variant at PDE1A which interacted with BP goal attainment with divergent effects on CHD risk in Chinese patients with T2D. Incorporating this information may facilitate individualized treatment strategies for precision care in diabetes only when our findings are validated.

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

Objective We examined the associations of glutamic acid decarboxylase antibodies (GADA) and C-peptide (CP) with insulin initiation, glycemic responses and severe hypoglycemia in type 2 diabetes (T2D). Research Design and Methods In 5230 Chinese patients with T2D (mean±SD age: 56.5±13.9 years, diabetes duration (median, IQR): 6 (1-12) years, 47.6% men) enrolled consecutively in 1996-2012 and prospectively observed till 2019, we retrospectively measured fasting CP and GADA in stored serum and examined their associations with aforementioned outcomes. Results At baseline, 28.6% had low CP (p=0.002) for insulin initiation versus the GADA- group, while the low-CP group had an aHR of 0.88 (0.77-1.00, p=0.051) versus the high-CP group. Following insulin initiation, the GADA+ plus low-CP group had the largest decrements in HbA1c (-1.9% at month 6; -1.5% at month 12) versus -1% in the other 3 groups. The aHR of severe hypoglycemia was 1.29 [(95% CI 1.10-1.52), p=0.002] in the low-CP and 1.38 [(95% CI 1.04-1.83) p=0.024] in the GADA+ group. Conclusions There is considerable heterogeneity in autoimmunity and beta-cell dysfunction in T2D with GADA+ and high CP associated with early insulin initiation while GADA+ and low CP, increased risk of severe hypoglycemia. Extended phenotyping is warranted to increase the precision of classification and treatment in T2D.

OBJECTIVE 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. RESEARCH DESIGN AND METHODS In this cohort study, consecutive Chinese patients with type 2 diabetes (N = 5,506) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative PCR. Glycemic progression was defined as the new need for exogenous insulin. RESULTS The mean (SD) age of the 5,349 subjects was 57.0 (13.3) years, and mean (SD) follow-up was 8.8 (5.4) years. Baseline rLTL was significantly shorter in the 1,803 subjects who progressed to insulin requirement compared with the remaining subjects (4.43 ± 1.16 vs. 4.69 ± 1.20). Shorter rLTL was associated with a higher risk of glycemic progression (hazard ratio [95% CI] for each unit decrease [to ∼0.2 kilobases]: 1.10 [1.06–1.14]), which remained significant after adjusting for confounders. Baseline rLTL was independently associated with glycemic exposure during follow-up (β = −0.05 [−0.06 to −0.04]). Each 1-kilobase decrease in absolute LTL was on average associated with a 1.69-fold higher risk of diabetes progression (95% CI 1.35–2.11). Two-sample Mendelian randomization analysis showed per 1-unit genetically decreased rLTL was associated with a 1.38-fold higher risk of diabetes progression (95% CI 1.12–1.70). CONCLUSIONS Shorter rLTL was significantly associated with an increased risk of glycemic progression in individuals with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for glycemic progression in people with type 2 diabetes.

Intensive lifestyle modification showed variable success in the prevention of major clinical events and mortality among people with prediabetes. We propose that age may partly explain the heterogeneity and that health hazards related to prediabetes are age-specific.We conducted a retrospective analysis of a territory-wide diabetes surveillance dataset from the Hong Kong Hospital Authority between 2000 and 2019. Prediabetes was defined according to the American Diabetes Association criteria. Proportional Cox regression was performed, stratified by baseline age categories (20-39, 40-59, 60-79 and ≥80 years).1,630,942 individuals were included in the analysis. Compared with normoglycaemia, prediabetes was associated with greater hazards for cardiovascular disease (CVD) and all-cause mortality in most age groups but the effect size attenuated with ascending age (Prediabetes is associated with higher risk of major clinical events, even excluding subsequent development of diabetes and adjusting for metabolic factors. The risk relationships are stronger in young than older people.This study did not receive any specific funding.

To examine the association of initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) at lower glycemic threshold with decline in estimated-glomerular filtration rate (eGFR).We analyzed a prospective cohort of Chinese patients with type 2 diabetes from Hong Kong. Patients initiating SGLT2i at HbA1c 7.5 % (lower-HbA1c) versus ≥ 7.5 % (higher-HbA1c) were matched using 1:1 propensity score. We compared annual eGFR changes in the lower-HbA1c and higher-HbA1c groups using linear mixed-effect models. Binary logistic regression was used to explore associations of SGLT2i initiation at lower HbA1c with odds of rapid eGFR decline (4% per year).Among 3384 patients with a median follow-up of 1.9 years, the mean age was 60.2 ± 11.5 years and 62.1 % were male. The lower-HbA1c and higher-HbA1c groups had baseline HbA1c (%) of 6.9 ± 0.5 and 9.0 ± 1.3 respectively, with similar pre-index annual eGFR decline. The lower-HbA1c group had a slower post-index annual eGFR decline than the higher-HbA1c group (-0.99 versus -1.63 mL/min/1.73 mIn this real-world study, SGLT2i initiation at HbA1c 7.5 % was associated with slower eGFR decline especially in high risk patients, supporting the potential renal benefits of SGLT2i initiation at lower glycemic thresholds.

Introduction: Improvements in glycemic outcomes have stalled since 20in some international surveys. We examined the latest trends in drug use and glycemic outcomes following recent introduction of newer classes of glucose lowering drugs (GLDs) in a territory-wide analysis. Methods: Using data from the Hong Kong Diabetes Surveillance Database, we estimated age-specific trends in the proportion of patients reaching different glycemic targets, and rates of severe hypoglycemia (SH) in 963,612 patients between 2002-2019. We assessed patterns of GLDs use by age, sex, presence of atherosclerotic cardiovascular disease (ASCVD) and estimated glomerular filtration rate (eGFR) . Results: HbA1c improved most markedly between 2007-2014 but plateaued since 2014, with 53.1% patients achieving HbA1c Conclusions: Following rapid improvement in 2007-2014, glycemic control and SH rates had plateaued despite the increasing use of SGLT2is and GLP-1RA in Hong Kong. Disclosure A.Yang: None. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. H.Wu: None. E.S.H.Lau: None. X.Zhang: None. M.Shi: None. B.Fan: None. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. A.Luk: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc.

Background: Prediabetes is associated with increased risk of cardiovascular disease (CVD) , kidney disease and death but the extent to which the risk associations between prediabetes and clinical events are modified by age is not known. Methods: We conducted a retrospective analysis of a territory-wide diabetes surveillance dataset from the Hong Kong Hospital Authority including 2,692,880 individuals with at least one glycaemic measurement between 2000 and 2019. Prediabetes was defined according to the American Diabetes Association criteria. Proportional Cox regression was used to derive hazard ratios (HR) and 95% CI of prediabetes vs. normoglycaemic for incident CVD, end-stage kidney disease (ESKD) , all-site infection and all-cause death, stratified by baseline age categories (20-39, 40-59, 60-79 and ≥80 years) . Results: Compared with people with normoglycaemia, people with prediabetes had greater hazards for clinical events in all age groups but the effect size attenuated with ascending age. In the youngest and in the oldest age categories, the respective HRs (95% CI) of prediabetes vs. normoglycaemia were 1.93 (1.71-2.17) and 1. (1.01-1.12) for CVD, 1.72 (1.42-2.08) and 1. (1.03-1.17) for ESKD, 1.48 (1.36-1.62) and 1. (1.00-1.08) for all-site infection, and, 1.52 (1.33-1.73) and 1. (1.04-1.10) for all-cause death. The associations remained after excluding people who later developed diabetes and after adjusting for metabolic factors. Conclusion: Prediabetes increases the risk of major clinical events and death independent of subsequent development of diabetes and metabolic factors. The risk relationships between prediabetes and clinical events are stronger in young than older people. Disclosure X.Zhang: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. A.Luk: None. H.Wu: None. E.S.H.Lau: None. M.Shi: None. B.Fan: None. A.Yang: None. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd.

Background: In patients with type 2 diabetes (T2D) negative for glutamic acid decarboxylase antibodies (GADA-) , the prognostic significance of insulin deficiency (ID) and insulin resistance (IR) remained uncertain. Methods: In 4590 patients with T2D consecutively enrolled to the Hong Kong Diabetes Register in 1995-2012 followed up till 2019, we measured GADA and fasting C peptide (CP) in stored samples at baseline. Using the updated homeostasis model assessment (HOMA2) , we defined below-median HOMA2-%B as ID and above-median HOMA2-IR as IR. We defined incident insulin use as the first insulin prescription of at least 28 days and used ICD-9 codes to define cardiovascular-renal diseases, severe hypoglycemia event (SHE) and all-cause mortality. We used Cox regression model to examine the associations between HOMA2 and clinical outcomes. Results: Amongst 3198 GADA- patients with available HOMA2 data, the median of HOMA2-%B was 52.4 (33.1, 60.9) and that of HOMA2-IR was 1.6 (1.1, 1.8) . The ID group was more likely to initiate insulin treatment [adjusted HR (95%CI) 1.26 (1.11-1.42) ] but less likely to progress to chronic kidney disease (CKD) , end-stage kidney disease (ESKD) and all-cause mortality than the non-ID group. The IR group had increased risks of incident insulin therapy [HR 1.13 (1.00-1.27) ], CKD, ESKD, and all-cause mortality than the non-IR group. Compared with the ID-/IR- group, the ID/IR group had the highest hazard of incident insulin use [HR 1.59 (1.30, 1.94) ], SHE and cardiovascular-renal diseases with HRs ranging from 1.45 to 2.09, although the associations for complications became insignificant after adjusting for metabolic factors and baseline treatments. Conclusions: In GADA- patients with T2D, ID and IR contributed differently to clinical outcomes with the co-existence of ID and IR associated with the highest risk of insulin requirement and adverse clinical outcomes. The assessment of ID and IR using HOMA2 improved risk stratification to identify high risk people for individualized intervention. Disclosure B.Fan: None. A.Luk: None. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. E.S.H.Lau: None. H.Wu: None. M.Shi: None. A.Yang: None. C.K.Lim: None. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. Funding The HKG Health Medical and Research Fund and RGC Research Impact Fund

Background: In patients with type 2 diabetes (T2D) and non-ketotic presentation, low C-peptide (CP) and positivity for glutamic acid decarboxylase antibodies (GADA+) indicate early insulin requirement. In GADA- patients, the associations of CP with insulin use, glycemic response and severe hypoglycemia event (SHE) are unknown. Methods: We measured fasting CP and GADA in 4590 Chinese patients with T2D enrolled in the Hong Kong Diabetes Register in 1995-2012 followed up till 2019. The updated homeostasis model assessment (HOMA2) was derived from fasting CP and plasma glucose. We defined incident insulin use as the first insulin prescription of at least 28 days, glycemic response as HbA1c reduction at one year after insulin initiation, and SHE using ICD-9 codes. Linear and Cox regression models were applied for association analyses. Results: At enrolment, 32% had low CP ( Conclusions: In patients with T2D, CP interacted with GADA to influence disease progressions including early insulin therapy and SHE. C-peptide might be correlated with IR in patients with GADA-. These subphenotypes allowed more precise classification of beta cell function to guide personalized treatment. Disclosure B.Fan: None. A.Luk: None. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. E.S.H.Lau: None. H.Wu: None. M.Shi: None. A.Yang: None. C.K.P.Lim: None. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. Funding The HKG Health Medical and Research Fund and RGC Research Impact Fund

Background: Few studies reported incidence rates of late-stage complications in people with youth-onset type 2 diabetes. We compared the clinical characteristics and incidence of cardiovascular disease (CVD) , end-stage kidney disease (ESKD) and death in a cohort of Chinese youth with type 2 and type 1 diabetes. Method: We performed a retrospective analysis of 1221 people with type 2 diabetes and 641 with type 1 diabetes diagnosed at age Result: At baseline, people with youth-onset type 2 diabetes were older at diagnosis (16 [14-18] vs. [8-15] years, p Conclusion: People with youth-onset type 2 diabetes had 2-fold increased risk of CVD and ESKD, in part driven by greater burden of obesity and other metabolic risk factors in this group. Disclosure Y.Fan: None. E.S.H.Lau: None. H.Wu: None. A.Yang: None. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. A.Luk: None.

Introduction: Whether angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) should be discontinued in advanced diabetic kidney disease (DKD) remains controversial. We examined the association of discontinuation of ACEi/ARBs when estimated glomerular filtration rate (eGFR) reached Methods: We performed a prospective analysis of a register including 11,323 patients stratified by continuation of ACEi/ARBs within 6 months of reaching eGFR Results: Of 11,323 ACEi/ARBs users with new-onset eGFR Conclusions: Discontinuation of ACEi/ARBs was associated with increased risk of cardiovascular-renal events in support of their continued use in patients with advanced DKD. Disclosure M.Shi: None. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp & Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. A.Yang: None. E.S.H.Lau: None. H.Wu: None. X.Zhang: None. B.Fan: None. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. A.Luk: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc.

To evaluate the effect of a team-based multi-component intervention care (MIC) program in obese patients with type 2 diabetes (T2D) and poor glycemic control.Patients with T2D and HbAOf 207 eligible patients [age (mean ± standard deviation): 56.9 ± 8.8 years, 47.4 % men, disease duration: 13.5 ± 8.2 years, HbATeam-based MIC for 1 year improved glycemic control in obese T2D which was sustained at 3-year.

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