1-year weight change after diabetes diagnosis and long-term incidence and sustainability of remission of type 2 diabetes in real-world settings in Hong Kong: An observational cohort study.

BACKGROUND: Clinical trials have demonstrated that remission of type 2 diabetes can be achieved following sustained weight loss. However, the feasibility of achieving diabetes remission through weight management in real-world settings remains unclear. In this study, we aimed to examine the association of weight change at 1 year after diabetes diagnosis with long-term incidence and sustainability of type 2 diabetes remission in real-world settings in Hong Kong. METHODS AND FINDINGS: This was a population-based observational cohort study. The territory-wide Risk Assessment and Management Programme for Diabetes Mellitus (RAMP-DM) provides regular comprehensive assessments of metabolic control and complication screening for people with diabetes in Hong Kong. We included 37,326 people with newly diagnosed type 2 diabetes who were enrolled in the RAMP-DM between 2000 and 2017, followed until 2019. Diabetes remission was defined as 2 consecutive HbA1c <6.5% measurements at least 6 months apart in the absence of glucose-lowering drugs (GLDs) and with no record of GLDs at least 3 months before these measurements. During a median follow-up of 7.9 years, 6.1% (2,279) of people achieved diabetes remission, with an incidence rate of 7.8 (95% CI: 7.5, 8.1) per 1,000 person-years. After adjusting for age at diabetes diagnosis, sex, assessment year, body mass index, other metabolic indices, smoking, alcohol drinking, and medication use, the hazard ratio (HR) for diabetes remission was 3.28 (95% CI: 2.75, 3.92; p < 0.001) for people with ≥10% weight loss within 1 year of diagnosis, 2.29 (95% CI: 2.03, 2.59; p < 0.001) for those with 5% to 9.9% weight loss, and 1.34 (95% CI: 1.22, 1.47; p < 0.001) for those with 0% to 4.9% weight loss compared to people with weight gain. During a median follow-up of 3.1 years, 67.2% (1,531) of people who had achieved diabetes remission returned to hyperglycaemia, with an incidence rate of 184.8 (95% CI: 175.5, 194.0) per 1,000 person-years. The adjusted HR for returning to hyperglycaemia was 0.52 (95% CI: 0.41, 0.65; p < 0.001) for people with ≥10% weight loss, 0.78 (95% CI: 0.68, 0.92; p = 0.002) for those with 5% to 9.9% weight loss, and 0.90 (95% CI: 0.80, 1.01; p = 0.073) for those with 0% to 4.9% weight loss compared to people with weight gain. Diabetes remission was associated with a 31% (HR: 0.69, 95% CI: 0.52, 0.93; p = 0.014) decreased risk of all-cause mortality. The main limitation of the study is that the reliability of HbA1c used to define diabetes remission can be affected by other medical conditions. Furthermore, we did not have data on bariatric surgery. CONCLUSIONS: In this study, greater weight loss within the first year of diabetes diagnosis was associated with an increased likelihood of achieving diabetes remission and a decreased risk of returning to hyperglycaemia among those who had achieved diabetes remission. However, both the incidence of diabetes remission and the probability of its long-term sustainability were low with conventional management in real-world settings, in an era when the importance of weight loss was not fully appreciated. Our study provides evidence for policymakers to design and implement early weight management interventions and diabetes remission initiatives.

Age-specific population attributable risk factors for all-cause and cause-specific mortality in type 2 diabetes: An analysis of a 6-year prospective cohort study of over 360,000 people in Hong Kong.

BACKGROUND: The prevalence of type 2 diabetes has increased in both young and old people. We examined age-specific associations and population attributable fractions (PAFs) of risk factors for all-cause and cause-specific mortality in people with type 2 diabetes. METHODS AND FINDINGS: We analysed data from 360,202 Chinese with type 2 diabetes who participated in a territory-wide diabetes complication screening programme in Hong Kong between January 2000 and December 2019. We compared the hazard ratios and PAFs of eight risk factors, including three major comorbidities (cardiovascular disease [CVD], chronic kidney disease [CKD], all-site cancer) and five modifiable risk factors (suboptimal HbA1c, suboptimal blood pressure, suboptimal low-density lipoprotein cholesterol, smoking, and suboptimal weight), for mortality across four age groups (18 to 54, 55 to 64, 65 to 74, and ≥75 years). During a median 6.0 years of follow-up, 44,396 people died, with cancer, CVD, and pneumonia being the leading causes of death. Despite a higher absolute mortality risk in older people (crude all-cause mortality rate: 59.7 versus 596.2 per 10,000 person-years in people aged 18 to 54 years versus those aged ≥75 years), the relative risk of all-cause and cause-specific mortality associated with most risk factors was higher in younger than older people, after mutually adjusting for the eight risk factors and other potential confounders including sex, diabetes duration, lipid profile, and medication use. The eight risk factors explained a larger proportion of mortality events in the youngest (PAF: 51.6%, 95% confidence interval [CI] [39.1%, 64.0%], p < 0.001) than the oldest (PAF: 35.3%, 95% CI [27.2%, 43.4%], p < 0.001) age group. Suboptimal blood pressure (PAF: 16.9%, 95% CI [14.7%, 19.1%], p < 0.001) was the leading attributable risk factor for all-cause mortality in the youngest age group, while CKD (PAF: 15.2%, 95% CI [14.0%, 16.4%], p < 0.001) and CVD (PAF: 9.2%, 95% CI [8.3%, 10.1%], p < 0.001) were the leading attributable risk factors in the oldest age group. The analysis was restricted to Chinese, which might affect the generalisability to the global population with differences in risk profiles. Furthermore, PAFs were estimated under the assumption of a causal relationship between risk factors and mortality. However, reliable causality was difficult to establish in the observational study. CONCLUSIONS: Major comorbidities and modifiable risk factors were associated with a greater relative risk for mortality in younger than older people with type 2 diabetes and their associations with population mortality burden varied substantially by age. These findings highlight the importance of early control of blood pressure, which could reduce premature mortality in young people with type 2 diabetes and prevent the onset of later CKD and related mortality at older ages.

Age- and sex-specific hospital bed-day rates in people with and without type 2 diabetes: A territory-wide population-based cohort study of 1.5 million people in Hong Kong.

BACKGROUND: Type 2 diabetes affects multiple systems. We aimed to compare age- and sex-specific rates of all-cause and cause-specific hospital bed-days between people with and without type 2 diabetes. METHODS AND FINDINGS: Data were provided by the Hong Kong Hospital Authority. We included 1,516,508 one-to-one matched people with incident type 2 diabetes (n = 758,254) and those without diabetes during the entire follow-up period (n = 758,254) between 2002 and 2018, followed until 2019. People with type 2 diabetes and controls were matched for age at index date (±2 years), sex, and index year (±2 years). We defined hospital bed-day rate as total inpatient bed-days divided by follow-up time. We constructed negative binominal regression models to estimate hospital bed-day rate ratios (RRs) by age at diabetes diagnosis and sex. All RRs were stratified by sex and adjusted for age and index year. During a median of 7.8 years of follow-up, 60.5% (n = 459,440) of people with type 2 diabetes and 56.5% (n = 428,296) of controls had a hospital admission for any cause, with a hospital bed-day rate of 3,359 bed-days and 2,350 bed-days per 1,000 person-years, respectively. All-cause hospital bed-day rate increased with increasing age in controls, but showed a J-shaped relationship with age in people with type 2 diabetes, with 38.4% of bed-days in those diagnosed <40 years caused by mental health disorders. Type 2 diabetes was associated with increased risks for a wide range of medical conditions, with an RR of 1.75 (95% CI [confidence interval] [1.73, 1.76]; p < 0.001) for all-cause hospital bed-days in men and 1.87 (95% CI [1.85, 1.89]; p < 0.001) in women. The RRs were greater in people with diabetes diagnosed at a younger than older age and varied by sex according to medical conditions. Sex differences were most notable for a higher RR for urinary tract infection and peptic ulcer, and a lower RR for chronic kidney disease and pancreatic disease in women than men. The main limitation of the study was that young people without diabetes in the database were unlikely to be representative of those in the Hong Kong general population with potential selection bias due to inclusion of individuals in need of medical care. CONCLUSIONS: In this study, we observed that type 2 diabetes was associated with increased risks of hospital bed-days for a wide range of medical conditions, with an excess burden of mental health disorders in people diagnosed at a young age. Age and sex differences should be considered in planning preventive and therapeutic strategies for type 2 diabetes. Effective control of risk factors with a focus on mental health disorders are urgently needed in young people with type 2 diabetes. Healthcare systems and policymakers should consider allocating adequate resources and developing strategies to meet the mental health needs of young people with type 2 diabetes, including integrating mental health services into diabetes care.

Real world evidence of clinical predictors of glycaemic response to glucose-lowering drugs among Chinese with type 2 diabetes.

AIMS: To examine whether simple clinical features can predict the 1-year glycaemic response to glucose-lowering drugs (GLDs) among Chinese with type 2 diabetes. MATERIALS AND METHODS: We used data from a diabetes risk assessment and complication screening programme and electronic medical records. We used linear regression models to examine the association between clinical features and 1-year glycaemic response to GLDs. RESULTS: Use of metformin (n = 15,433), sulphonylureas (SU) (n = 15,190), dipeptidyl peptidase-4 inhibitor (DPP-4i) (n = 7947), thiazolidinedione (TZD) (n = 4107), and sodium-glucose cotransporter 2 inhibitors (SGLT-2i) (n = 1883) were associated with a mean reduction of HbA1c ranging from 0.7% to 1.3% at one year. Men had a greater response to SU but a poorer response to metformin and TZD. Older age predicted a better response to all GLDs but not SGLT-2i, whereas increasing diabetes duration was associated with a poorer response to all GLDs except for DPP-4i. Obese patients responded greater to TZD and SGLT-2i but poorer to SU than those with normal weight. Patients with a higher level of triglycerides to high-density lipoprotein cholesterol ratio had a greater glycaemic response to TZD but a smaller response to SU and DPP-4i. CONCLUSIONS: Glycaemic response to GLDs differed considerably by clinical features among Chinese patients with type 2 diabetes.

Young age at diabetes diagnosis amplifies the effect of diabetes duration on risk of chronic kidney disease: a prospective cohort study.

AIMS/HYPOTHESIS: We postulated that the increased lifetime risk of chronic kidney disease (CKD) in young-onset diabetes is attributable to both long disease duration and more aggressive disease. We examined whether age at diabetes diagnosis modifies the effect of diabetes duration on risk of CKD. METHODS: We included 436,744 people with incident type 2 diabetes in the Hong Kong Diabetes Surveillance Database (HKDSD) and 16,979 people with prevalent type 2 diabetes in the Hong Kong Diabetes Register (HKDR). We used Poisson models to describe joint effects of age at diabetes diagnosis, diabetes duration and attained age on incidence of CKD in HKDSD. We used Cox proportional hazards models to examine interaction effect of age at diabetes diagnosis and diabetes duration on risk of CKD with adjustment for confounders in HKDR. RESULTS: During a median follow-up of 5.3 years, 134,043 cases of CKD were recorded in the HKDSD. The incidence rate ratio for CKD comparing people of the same attained age but diagnosed with diabetes at ages 5 years apart was higher for people with a younger age at diabetes diagnosis, but decreased with increasing age at diabetes diagnosis. During a median follow-up of 6.3 years, 6500 people developed CKD in the HKDR. The increased risk of CKD with longer diabetes duration decreased with older age at diabetes diagnosis. The adjusted HR for CKD associated with 5 year increase in diabetes duration was 1.37 (95% CI 1.13, 1.65) in people with diabetes diagnosed at 20-29 years and 1.01 (95% CI 0.87, 1.18) in those diagnosed at ≥70 years. CONCLUSIONS/INTERPRETATION: Young age at diabetes diagnosis amplified the effect of increasing diabetes duration on increased risk of CKD.

Temporal trends in rates of infection-related hospitalisations in Hong Kong people with and without diabetes, 2001-2016: a retrospective study.

AIMS/HYPOTHESIS: Infection is an under-recognised but important complication in people with diabetes. Studies on temporal trends in incidence of infection in this population are limited. We report the trends in infection-related hospitalisation in people with diabetes and compared hospitalisation rates between people with and without diabetes in Hong Kong. METHODS: Hospital admissions with infection, including pneumonia, influenza, tuberculosis, kidney infection, urinary tract infection, cellulitis, osteomyelitis, foot infection and sepsis, listed as principal diagnosis occurring between 2001 and 2016 were identified from people with diabetes in the electronic medical record system of the Hong Kong Hospital Authority. Data on hospitalisation for a subset of these infections in the general population between 2007 and 2016 were obtained from the Department of Health. The number of people with diabetes ranged between 117,322 in 2001 and 570,929 in 2016, and the number without diabetes ranged between 5,242,614 in 2007 and 5,593,153 in 2016. Joinpoint regression was used to describe the trends. RESULTS: In people with diabetes, over a period of 16 years, the age-standardised annual rates of hospitalisation decreased for tuberculosis but increased for influenza; rates of hospitalisation for pneumonia increased up until 2004/2005 and declined in men and stabilised in women. The rates of hospitalisation for most infection types were unchanged or increased in the 20-44 year and 45-64 year age groups and decreased in those aged 65 years or above. Trends for most of the infections were similar when comparing sexes. Between 2007 and 2016, the rate ratios of hospitalisation for most infection types between people with and without diabetes were stable, and the rate ratios remained higher in people with diabetes, ranging from 1.3-1.4 for pneumonia to 3.2-4.9 for kidney infections in 2016 compared with non-diabetic individuals. CONCLUSIONS/INTERPRETATION: Despite advances in medical care, hospitalisation due to infections remains a major healthcare burden in people with diabetes. Graphical abstract.

Secular trends in all-cause and cause-specific mortality rates in people with diabetes in Hong Kong, 2001-2016: a retrospective cohort study.

AIMS/HYPOTHESIS: The aim of the study was to describe trends in all-cause and cause-specific mortality rates in Hong Kong Chinese people with diabetes from 2001 to 2016. METHODS: The Hong Kong Diabetes Surveillance Database (HKDSD) is a territory-wide diabetes cohort identified from the Hong Kong Hospital Authority electronic medical record system. Deaths between 2001 and 2016 were identified from linkage to the Hong Kong Death Registry. We used Joinpoint regression analysis to describe mortality patterns among people with diabetes by age and sex, and standardised mortality ratios (SMRs) to compare all-cause mortality rates in people with and without diabetes. RESULTS: Between 2001 and 2016, a total of 390,071 men and 380,007 women aged 20 years or older with diabetes were included in the HKDSD. There were 96,645 deaths among men and 88,437 deaths among women. Mortality rates for all-cause, cardiovascular disease and cancer among people with diabetes declined by 52.3%, 72.2% and 65.1% in men, respectively, and by 53.5%, 78.5% and 59.6% in women, respectively. Pneumonia mortality rates remained stable. The leading cause of death in people with diabetes has shifted from cardiovascular disease to pneumonia in the oldest age group, with cancer remaining the most common cause of death in people aged 45-74 years. The all-cause SMRs for men declined from 2.82 (95% CI 2.72, 2.94) to 1.50 (95% CI 1.46, 1.54), and for women, they declined from 3.28 (95% CI 3.15, 3.41) to 1.67 (95% CI 1.62, 1.72). However, among people aged 20-44 years, the declines in all-cause mortality rates over the study period were not statistically significant for both men (average annual per cent change [AAPC]: -3.2% [95% CI -7.3%, 1.0%]) and women (AAPC: -1.2% [95% CI -6.5%, 4.4%]). The SMRs in people aged 20-44 years fluctuated over time, between 7.86 (95% CI 5.74, 10.5) in men and 6.10 (95% CI 3.68, 9.45) in women in 2001, and 4.95 (95% CI 3.72, 6.45) in men and 4.92 (95% CI 3.25, 7.12) in women in 2016. CONCLUSIONS/INTERPRETATION: Absolute and relative mortality has declined overall in people with diabetes in Hong Kong, with less marked improvements in people under 45 years of age, calling for urgent action to improve care in young people with diabetes.

Secular trends in rates of hospitalisation for lower extremity amputation and 1 year mortality in people with diabetes in Hong Kong, 2001-2016: a retrospective cohort study.

AIMS/HYPOTHESIS: We aimed to describe trends in rates of hospitalisation for lower extremity amputation (LEA) and 1 year mortality rates after LEA in people with diabetes in Hong Kong between 2001 and 2016. METHODS: The Hong Kong Diabetes Surveillance Database is a territory-wide population-based diabetes cohort (N = 770,078) identified from the Hong Kong Hospital Authority electronic medical system. We identified LEA events using ICD-9 procedure codes and 1 year mortality after LEA from linkage to the Hong Kong Death Registry. Joinpoint regression models were used to describe the trends. RESULTS: Between 2001 and 2016, 6113 hospitalisations for LEAs in men and 4149 in women were recorded in the Hong Kong Diabetes Surveillance Database. The rates of minor LEAs declined by 48.6% (average annual per cent change [AAPC]: -3.8; 95% CI -5.7, -1.9) in men and by 59.5% (AAPC: -6.3; 95% CI -10.6, -1.8) in women. The rates of major LEAs declined by 77.9% (AAPC: -8.0; 95% CI -9.6, -6.5) in men and by 79.3% (AAPC: -10.4; 95% CI -13.1, -7.6) in women. The cumulative 1 year mortality rates after minor and major LEAs were 18.5% and 41.8% in men, and 21.3% and 42.0% in women, respectively, for the whole period. No change was detected in 1 year mortality rates during the surveillance in both sexes. CONCLUSIONS/INTERPRETATION: Although hospitalisation rates for LEAs have declined overall in people with diabetes, there were no improvements in 1 year mortality rates after LEA. Continuous efforts are needed to further prevent LEAs and improve the survival rate of people undergoing LEAs. Graphical abstract.

Age at diagnosis, glycemic trajectories, and responses to oral glucose-lowering drugs in type 2 diabetes in Hong Kong: A population-based observational study.

BACKGROUND: Lifetime glycemic exposure and its relationship with age at diagnosis in type 2 diabetes (T2D) are unknown. Pharmacologic glycemic management strategies for young-onset T2D (age at diagnosis <40 years) are poorly defined. We studied how age at diagnosis affects glycemic exposure, glycemic deterioration, and responses to oral glucose-lowering drugs (OGLDs). METHODS AND FINDINGS: In a population-based cohort (n = 328,199; 47.2% women; mean age 34.6 and 59.3 years, respectively, for young-onset and usual-onset [age at diagnosis ≥40 years] T2D; 2002-2016), we used linear mixed-effects models to estimate the association between age at diagnosis and A1C slope (glycemic deterioration) and tested for an interaction between age at diagnosis and responses to various combinations of OGLDs during the first decade after diagnosis. In a register-based cohort (n = 21,016; 47.1% women; mean age 43.8 and 58.9 years, respectively, for young- and usual-onset T2D; 2000-2015), we estimated the glycemic exposure from diagnosis until age 75 years. People with young-onset T2D had a higher mean A1C (8.0% [standard deviation 0.15%]) versus usual-onset T2D (7.6% [0.03%]) throughout the life span (p < 0.001). The cumulative glycemic exposure was >3 times higher for young-onset versus usual-onset T2D (41.0 [95% confidence interval 39.1-42.8] versus 12.1 [11.8-12.3] A1C-years [1 A1C-year = 1 year with 8% average A1C]). Younger age at diagnosis was associated with faster glycemic deterioration (A1C slope over time +0.08% [0.078-0.084%] per year for age at diagnosis 20 years versus +0.02% [0.016-0.018%] per year for age at diagnosis 50 years; p-value for interaction <0.001). Age at diagnosis ≥60 years was associated with glycemic improvement (-0.004% [-0.005 to -0.004%] and -0.02% [-0.027 to -0.0244%] per year for ages 60 and 70 years at diagnosis, respectively; p-value for interaction <0.001). Responses to OGLDs differed by age at diagnosis (p-value for interaction <0.001). Those with young-onset T2D had smaller A1C decrements for metformin-based combinations versus usual-onset T2D (metformin alone: young-onset -0.15% [-0.105 to -0.080%], usual-onset -0.17% [-0.179 to -0.169%]; metformin, sulfonylurea, and dipeptidyl peptidase-4 inhibitor: young-onset -0.44% [-0.476 to -0.405%], usual-onset -0.48% [-0.498 to -0.459%]; metformin and α-glucosidase inhibitor: young-onset -0.40% [-0.660 to -0.144%], usual-onset -0.25% [-0.420 to -0.077%]) but greater responses to other combinations containing sulfonylureas (sulfonylurea alone: young-onset -0.08% [-0.099 to -0.065%], usual-onset +0.06% [+0.059 to +0.072%]; sulfonylurea and α-glucosidase inhibitor: young-onset -0.10% [-0.266 to 0.064%], usual-onset: 0.25% [+0.196% to +0.312%]). Limitations include possible residual confounding and unknown generalizability outside Hong Kong. CONCLUSIONS: In this study, we observed excess glycemic exposure and rapid glycemic deterioration in young-onset T2D, indicating that improved treatment strategies are needed in this setting. The differential responses to OGLDs between young- and usual-onset T2D suggest that better disease classification could guide personalized therapy.

Secular trends in incidence of type 1 and type 2 diabetes in Hong Kong: A retrospective cohort study.

BACKGROUND: There is very limited data on the time trend of diabetes incidence in Asia. Using population-level data, we report the secular trend of the incidence of type 1 and type 2 diabetes in Hong Kong between 2002 and 2015. METHODS AND FINDINGS: The Hong Kong Diabetes Surveillance Database hosts clinical information on people with diabetes receiving care under the Hong Kong Hospital Authority, a statutory body that governs all public hospitals and clinics. Sex-specific incidence rates were standardised to the age structure of the World Health Organization population. Joinpoint regression analysis was used to describe incidence trends. A total of 562,022 cases of incident diabetes (type 1 diabetes [n = 2,426]: mean age at diagnosis is 32.5 years, 48.4% men; type 2 diabetes [n = 559,596]: mean age at diagnosis is 61.8 years, 51.9% men) were included. Among people aged <20 years, incidence of both type 1 and type 2 diabetes increased. For type 1 diabetes, the incidence increased from 3.5 (95% CI 2.2-4.9) to 5.3 (95% CI 3.4-7.1) per 100,000 person-years (average annual percentage change [AAPC] 3.6% [95% CI 0.2-7.1], p < 0.05) in boys and from 4.3 (95% CI 2.7-5.8) to 6.4 (95% CI 4.3-8.4) per 100,000 person-years (AAPC 4.7% [95% CI 1.7-7.7], p < 0.05] in girls; for type 2 diabetes, the incidence increased from 4.6 (95% CI 3.2-6.0) to 7.5 (95% CI 5.5-9.6) per 100,000 person-years (AAPC 5.9% [95% CI 3.4-8.5], p < 0.05) in boys and from 5.9 (95% CI 4.3-7.6) to 8.5 (95% CI 6.2-10.8) per 100,000 person-years (AAPC 4.8% [95% CI 2.7-7.0], p < 0.05) in girls. In people aged 20 to <40 years, incidence of type 1 diabetes remained stable, but incidence of type 2 diabetes increased over time from 75.4 (95% CI 70.1-80.7) to 110.8 (95% CI 104.1-117.5) per 100,000 person-years (AAPC 4.2% [95% CI 3.1-5.3], p < 0.05) in men and from 45.0 (95% CI 41.4-48.6) to 62.1 (95% CI 57.8-66.3) per 100,000 person-years (AAPC 3.3% [95% CI 2.3-4.2], p < 0.05) in women. In people aged 40 to <60 years, incidence of type 2 diabetes increased until 2011/2012 and then flattened. In people aged ≥60 years, incidence was stable in men and declined in women after 2011. No trend was identified in the incidence of type 1 diabetes in people aged ≥20 years. The present study is limited by its reliance on electronic medical records for identification of people with diabetes, which may result in incomplete capture of diabetes cases. The differentiation of type 1 and type 2 diabetes was based on an algorithm subject to potential misclassification. CONCLUSIONS: There was an increase in incidence of type 2 diabetes in people aged <40 years and stabilisation in people aged ≥40 years. Incidence of type 1 diabetes continued to climb in people aged <20 years but remained constant in other age groups.

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.

Trends in diabetes-related complications in Hong Kong, 2001-2016: a retrospective cohort study.

BACKGROUND: Nationwide studies on contemporary trends in incidence of diabetes-related complications in Asia are lacking. We describe trends in incident coronary heart disease (CHD), stroke, heart failure, hyperglycaemic crisis, and lower-extremity amputation (LEA) in people with diabetes in Hong Kong between 2001 and 2016. METHODS: The Hong Kong Diabetes Surveillance Database (HKDSD) is a territory-wide diabetes cohort identified from Hong Kong Hospital Authority electronic medical record system. We identified events of CHD, stroke, heart failure and hyperglycaemic crisis using hospital principal diagnosis codes at discharge and that of LEA using inpatient procedure codes. We used Joinpoint regression analysis to describe incidence trends by age and sex. RESULTS: Between 2001 and 2016, a total of 390,071 men and 380,007 women aged 20 years or older with diabetes were included in the HKDSD. Event rates of CHD, stroke, heart failure, hyperglycaemic crisis and LEA declined by 69.4% (average annual percent change: - 7.6, 95% CI - 10.2, - 5.0), 70.3% (- 8.7, 95% CI - 9.8, - 7.5), 63.6% (- 6.4, 95% CI - 8.0, - 4.7), 59.1% (- 6.6, 95% CI - 12.4, - 0.44), and 67.5% (- 5.8, 95% CI - 7.2, - 4.4), in men and by 77.5% (- 9.9, 95% CI - 11.8, - 7.9), 74.5% (- 9.0, 95% CI - 9.6, - 8.4), 65.8% (- 7.0, 95% CI - 8.0, - 6.0), 81.7% (- 8.5, 95% CI - 10.5, - 6.5), and 72.7% (- 9.1. 95% CI - 12.2, - 5.8) in women, respectively, over a 16-year period in people with diabetes in Hong Kong. Joinpoint analysis identified greater declines in event rates of the five diabetes-related complications in the earlier one-third of study period and slowed down but remained significant until 2016. Event rates decreased for all age groups above 45 years for both sexes. There was no significant change in event rates in the group aged 20-44 years except for decline in hyperglycaemic crisis. CONCLUSIONS: The event rates of diabetes-related complications have declined substantially with no evidence of stabilization or increase in Hong Kong up to 2016. Improvements in outcome were observed for all age subgroups but not in young people with diabetes, calling for urgent action to improve quality of care to prevent complications in young people at risk.

Development and validation of algorithms to classify type 1 and 2 diabetes according to age at diagnosis using electronic health records.

BACKGROUND: Validated algorithms to classify type 1 and 2 diabetes (T1D, T2D) are mostly limited to white pediatric populations. We conducted a large study in Hong Kong among children and adults with diabetes to develop and validate algorithms using electronic health records (EHRs) to classify diabetes type against clinical assessment as the reference standard, and to evaluate performance by age at diagnosis. METHODS: We included all people with diabetes (age at diagnosis 1.5-100 years during 2002-15) in the Hong Kong Diabetes Register and randomized them to derivation and validation cohorts. We developed candidate algorithms to identify diabetes types using encounter codes, prescriptions, and combinations of these criteria ("combination algorithms"). We identified 3 algorithms with the highest sensitivity, positive predictive value (PPV), and kappa coefficient, and evaluated performance by age at diagnosis in the validation cohort. RESULTS: There were 10,196 (T1D n = 60, T2D n = 10,136) and 5101 (T1D n = 43, T2D n = 5058) people in the derivation and validation cohorts (mean age at diagnosis 22.7, 55.9 years; 53.3, 43.9% female; for T1D and T2D respectively). Algorithms using codes or prescriptions classified T1D well for age at diagnosis < 20 years, but sensitivity and PPV dropped for older ages at diagnosis. Combination algorithms maximized sensitivity or PPV, but not both. The "high sensitivity for type 1" algorithm (ratio of type 1 to type 2 codes ≥ 4, or at least 1 insulin prescription within 90 days) had a sensitivity of 95.3% (95% confidence interval 84.2-99.4%; PPV 12.8%, 9.3-16.9%), while the "high PPV for type 1" algorithm (ratio of type 1 to type 2 codes ≥ 4, and multiple daily injections with no other glucose-lowering medication prescription) had a PPV of 100.0% (79.4-100.0%; sensitivity 37.2%, 23.0-53.3%), and the "optimized" algorithm (ratio of type 1 to type 2 codes ≥ 4, and at least 1 insulin prescription within 90 days) had a sensitivity of 65.1% (49.1-79.0%) and PPV of 75.7% (58.8-88.2%) across all ages. Accuracy of T2D classification was high for all algorithms. CONCLUSIONS: Our validated set of algorithms accurately classifies T1D and T2D using EHRs for Hong Kong residents enrolled in a diabetes register. The choice of algorithm should be tailored to the unique requirements of each study question.

Excess Burden of Mental Illness and Hospitalization in Young-Onset Type 2 Diabetes: A Population-Based Cohort Study.

Background: Type 2 diabetes (T2D) increases hospitalization risk. Young-onset T2D (YOD) (defined as onset before age 40 years) is associated with excess morbidity and mortality, but its effect on hospitalizations is unknown. Objective: To determine hospitalization rates among persons with YOD and to examine the effect of age at onset on hospitalization risk. Design: Prospective cohort study. Setting: Hong Kong. Participants: Adults aged 20 to 75 years in population-based (2002 to 2014; n = 422 908) and registry-based (2000 to 2014; n = 20 886) T2D cohorts. Measurements: All-cause and cause-specific hospitalization rates. Negative binomial regression models estimated effect of age at onset on hospitalization rate and cumulative bed-days from onset to age 75 years for YOD. Results: Patients with YOD had the highest hospitalization rates by attained age. In the registry cohort, 36.8% of YOD bed-days before age 40 years were due to mental illness. The adjusted rate ratios showed increased hospitalization in YOD versus usual-onset T2D (onset at age ≥40 years) (all-cause, 1.8 [95% CI, 1.7 to 2.0]; renal, 6.7 [CI, 4.2 to 10.6]; diabetes, 3.7 [CI, 3.0 to 4.6]; cardiovascular, 2.1 [CI, 1.8 to 2.5]; infection, 1.7 [CI, 1.4 to 2.1]; P < 0.001 for all). Models estimated that intensified risk factor control in YOD (hemoglobin A1c level <6.2%, systolic blood pressure <120 mm Hg, low-density lipoprotein cholesterol level <2.0 mmol/L [<77.3 mg/dL], triglyceride level <1.3 mmol/L [<115.1 mg/dL], waist circumference of 85 cm [men] or 80 cm [women], and smoking cessation) was associated with a one-third reduction in cumulative bed-days from onset to age 75 years (97 to 65 bed-days). Limitation: Possible residual confounding. Conclusion: Adults with YOD have excess hospitalizations across their lifespan compared with persons with usual-onset T2D, including an unexpectedly large burden of mental illness in young adulthood. Efforts to prevent YOD and intensify cardiometabolic risk factor control while focusing on mental health are urgently needed. Primary Funding Source: Asia Diabetes Foundation.

Glycaemia control and the risk of hospitalisation for infection in patients with type 2 diabetes: Hong Kong Diabetes Registry.

BACKGROUND: Infection occurs more commonly in diabetic patients compared with the general population and is an under-recognised but important morbidity in patients with diabetes. We examined the impact of glycaemic control on hospitalisation for infection in a large prospective cohort of Chinese adults with type 2 diabetes. METHODS: Between July 1994 and June 2014, 22 846 patients with type 2 diabetes underwent detailed assessment of metabolic control and diabetes complications. Patients were followed for occurrence of infection requiring hospitalisation as identified using discharge diagnosis codes. RESULTS: Over a median follow-up of 4.8 years, 20.3% of patients were hospitalised for any infection type, with respiratory tract, genitourinary tract, and skin being the most commonly affected sites. In multivariate Cox regression, time-dependent HbA1c was associated with all-site infection (hazard ratio [HR] 1.07 [95% confidence interval {CI}:1.05-1.09, P < 0.001]), genitourinary tract infection (HR 1.09 [95% CI: 1.04-1.14], P < 0.001), and skin infection (HR 1.16 [95% CI 1.12-1.21]. P < 0.001), but not infection of respiratory tract, and was independent of age, gender, disease duration, smoking, body mass index, glomerular filtration rate, haemoglobin, history of stroke, congestive heart failure, coronary heart disease, peripheral artery disease, diabetic neuropathy and cancer, and baseline drug use. Against an arbitrary HbA1c interval of >7.0-8.0% (53-64 mmol/mol), patients with HbA1c ≤6.0% (42 mmol/mol) and >8.0% (64 mmol/mol) had excess risks of infection-related hospitalisation adjusted for other factors. CONCLUSIONS: In patients with type 2 diabetes, burden of serious infection is high. In the diabetic population, a U-shape relationship between glycaemia and infection-related hospitalisation was detected.

Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus.

We carried out a multistage genome-wide association study of type 2 diabetes mellitus in Japanese individuals, with a total of 1,612 cases and 1,424 controls and 100,000 SNPs. The most significant association was obtained with SNPs in KCNQ1, and dense mapping within the gene revealed that rs2237892 in intron 15 showed the lowest Pvalue (6.7 x 10(-13), odds ratio (OR) = 1.49). The association of KCNQ1 with type 2 diabetes was replicated in populations of Korean, Chinese and European ancestry as well as in two independent Japanese populations, and meta-analysis with a total of 19,930 individuals (9,569 cases and 10,361 controls) yielded a P value of 1.7 x 10(-42) (OR = 1.40; 95% CI = 1.34-1.47) for rs2237892. Among control subjects, the risk allele of this polymorphism was associated with impairment of insulin secretion according to the homeostasis model assessment of beta-cell function or the corrected insulin response. Our data thus implicate KCNQ1 as a diabetes susceptibility gene in groups of different ancestries.

A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.

We conducted a genome-wide association study for type 2 diabetes (T2D) in Icelandic cases and controls, and we found that a previously described variant in the transcription factor 7-like 2 gene (TCF7L2) gene conferred the most significant risk. In addition to confirming two recently identified risk variants, we identified a variant in the CDKAL1 gene that was associated with T2D in individuals of European ancestry (allele-specific odds ratio (OR) = 1.20 (95% confidence interval, 1.13-1.27), P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR = 1.25 (1.11-1.40), P = 0.00018). The genotype OR of this variant suggested that the effect was substantially stronger in homozygous carriers than in heterozygous carriers. The ORs for homozygotes were 1.50 (1.31-1.72) and 1.55 (1.23-1.95) in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers, suggesting that this variant confers risk of T2D through reduced insulin secretion.

Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes.

We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1beta), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.

Diabetic kidney disease: a clinical update from Kidney Disease: Improving Global Outcomes.

The incidence and prevalence of diabetes mellitus (DM) continue to grow markedly throughout the world, due primarily to the increase in type 2 DM (T2DM). Although improvements in DM and hypertension management have reduced the proportion of diabetic individuals who develop chronic kidney disease (CKD) and progress to end-stage renal disease (ESRD), the sheer increase in people developing DM will have a major impact on dialysis and transplant needs. This KDIGO conference addressed a number of controversial areas in the management of DM patients with CKD, including aspects of screening for CKD with measurements of albuminuria and estimated glomerular filtration rate (eGFR); defining treatment outcomes; glycemic management in both those developing CKD and those with ESRD; hypertension goals and management, including blockers of the renin-angiotensin-aldosterone system; and lipid management.