OBJECTIVE: Multifaceted care has been shown to reduce mortality and complications in type 2 diabetes. We hypothesized that structured care would reduce renal complications in type 2 diabetes. ...RESEARCH DESIGN AND METHODS: A total of 205 Chinese type 2 diabetic patients from nine public hospitals who had plasma creatinine levels of 150-350 μmol/l were randomly assigned to receive structured care (n = 104) or usual care (n = 101) for 2 years. The structured care group was managed according to a prespecified protocol with the following treatment goals: blood pressure <130/80 mmHg, A1C <7%, LDL cholesterol <2.6 mmol/l, triglyceride <2 mmol/l, and persistent treatment with renin-angiotensin blockers. The primary end point was death and/or renal end point (creatinine >500 μmol/l or dialysis). RESULTS: Of these 205 patients (mean ± SD age 65 ± 7.2 years; disease duration 14 ± 7.9 years), the structured care group achieved better control than the usual care group (diastolic blood pressure 68 ± 12 vs. 71 ± 12 mmHg, respectively, P = 0.02; A1C 7.3 ± 1.3 vs. 8.0 ± 1.6%, P < 0.01). After adjustment for age, sex, and study sites, the structured care (23.1%, n = 24) and usual care (23.8%, n = 24; NS) groups had similar end points, but more patients in the structured care group attained greater-than-or-equal3 treatment goals (61%, n = 63, vs. 28%, n = 28; P < 0.001). Patients who attained greater-than-or-equal3 treatment targets (n = 91) had reduced risk of the primary end point (14 vs. 34; relative risk 0.43 95% CI 0.21-0.86 compared with that of those who attained less-than or equal to2 targets (n = 114). CONCLUSIONS: Attainment of multiple treatment targets reduced the renal end point and death in type 2 diabetes. In addition to protocol, audits and feedback are needed to improve outcomes.
Familial hypocalciuric hypercalcaemia (FHH) is a genetic disorder of altered calcium homeostasis. Mutations in the
CASR,
GNA11 and
AP2S1 genes have been reported to cause FHH. We report a Hong Kong ...Chinese kindred with FHH type 3 (FHH3) caused by mutations in
AP2S1. The proband, a 51-year-old woman with hypercalcaemia, was initially diagnosed to have primary hyperparathyroidism but repeated parathyroidectomy failed to normalize her plasma calcium concentrations. Later, FHH was suspected and yet no mutations were identified in the
CASR gene which causes FHH type 1 (FHH1), the most common form of FHH. Genetic testing of
AP2S1 revealed a heterozygous c.43C>T (p.Arg15Cys) mutation, confirming the diagnosis of FHH3. The elder brother and niece of the proband, who both have hypercalcaemia, were found to harbour the same mutation. To our knowledge, this is the first Chinese kindred of FHH3 reported in the English literature.
The aim of this study was to describe the association between educational level and incident cardiovascular disease (CVD) and all-cause mortality in Hong Kong Chinese patients with type 2 diabetes.
...We included 12,634 patients with type 2 diabetes who were enrolled into the Joint Asia Diabetes Evaluation Program between June 1, 2007, and June 30, 2017. We classified patients' educational level into the following three groups: ≤6 years, 6-13 years, and >13 years. Incident CVD events were identified using hospital discharge diagnoses. Death was identified from Hong Kong Death Register. We estimated HRs for incident CVD and all-cause mortality using Cox regression models.
Patients with the highest educational level were younger and had shorter diabetes duration and better glycemic control at enrollment than those with the lowest educational level. During the median follow-up of 6.2 years for CVD and 6.4 years for all-cause mortality, 954 CVD events and 833 deaths were recorded. HRs for CVD and all-cause mortality were 0.73 (95% CI: 0.57, 0.94) and 0.71 (95% CI: 0.54, 0.94) for the highest educational level compared to the lowest educational level, after adjustment for age, sex, diabetes duration, and family history of diabetes.
Educational level is inversely associated with the risk of CVD and all-cause mortality among Hong Kong Chinese patients with type 2 diabetes. Hong Kong Chinese patients with type 2 diabetes and low educational level should be given special attention for the prevention of key complications of diabetes.
Borderline ankle–brachial index is increasingly recognised as a marker of cardiovascular risk. We evaluated the impact of borderline ankle–brachial index in 12,772 Chinese type 2 diabetes patients ...from the Joint Asia Diabetes Evaluation Program between 2007 and 2012. Cardiovascular risk factors, complications and health-related quality of life were compared between patients with normal ankle–brachial index (1.0–1.4), borderline ankle–brachial index (0.90–0.99) and peripheral arterial disease (ankle–brachial index < 0.9). The prevalence of peripheral arterial disease and borderline ankle–brachial index was 4.6% and 9.6%, respectively. Borderline ankle–brachial index patients were older, more likely to be smokers and hypertensive, had longer duration of diabetes, poorer kidney function and poorer health-related quality of life than patients with normal ankle–brachial index. After adjustment for traditional cardiovascular risk factors, borderline ankle–brachial index was an independent predictor of diabetes-related micro- and macrovascular complications including retinopathy (odd ratios: 1.19 (95% confidence interval: 1.04–1.37)), macroalbuminuria (1.31 (1.10–1.56)), chronic kidney disease (1.22 (1.00–1.50)) and stroke (1.31 (1.05–1.64)). These findings suggest that patients with diabetes and borderline ankle–brachial index are at increased cardiovascular risk and may benefit from more intensive management.
We aim to assess the long-term impact of acute kidney injury (AKI) on progression of diabetic kidney disease (DKD) and all-cause mortality and investigate determinants of AKI in Chinese patients with ...type 2 diabetes (T2D). A consecutive cohort of 9,096 Chinese patients with T2D from the Hong Kong Diabetes Register was followed for 12 years (mean ± SD age 57 ± 13.2 years; 46.9% men; median duration of diabetes 5 years). AKI was defined based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria using serum creatinine. Estimated glomerular filtration rate measurements were used to identify the first episode with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Polygenic risk score (PRS) composed of 27 single nucleotide polymorphisms (SNPs) known to be associated with serum uric acid (SUA) in European populations was used to examine the role of SUA in pathogenesis of AKI, CKD, and ESRD. Validation was sought in an independent cohort including 6,007 patients (age 61.2 ± 10.9 years; 59.5% men; median duration of diabetes 10 years). Patients with AKI had a higher risk for developing incident CKD (hazard ratio 14.3 95% CI 12.69-16.11), for developing ESRD (12.1 10.74-13.62), and for all-cause death (7.99 7.31-8.74) compared with those without AKI. Incidence rate for ESRD among patients with no episodes of AKI and one, two, and three or more episodes of AKI was 7.1, 24.4, 32.4, and 37.3 per 1,000 person-years, respectively. Baseline SUA was a strong independent predictor for AKI. A PRS composed of 27 SUA-related SNPs was associated with AKI and CKD in both discovery and replication cohorts but not ESRD. Elevated SUA may increase the risk of DKD through increasing AKI. The identification of SUA as a modifiable risk factor and PRS as a nonmodifiable risk factor may facilitate the identification of individuals at high risk to prevent AKI and its long-term impact in T2D.
The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear.
We used data from Biobank Japan (n = ...70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-media thickness (cIMT) in adult women (n = 781), dyslipidemia (n = 7723), and coronary heart disease (CHD) (n = 2374 cases and 6246 controls) in type 2 diabetes (T2D) patients.
Our PRSs aggregating 84-549 genetic variants (0.251 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10
< P < 1.3 × 10
) and 3-year lipid changes (1.4 × 10
< P < 0.0130) which started to emerge in childhood and adolescence. With the adjustments for principal components (PCs), sex, age, and body mass index, there was an elevation of 5.3% in TC (β ± SE = 0.052 ± 0.002), 11.7% in TG (β ± SE = 0.111 ± 0.006), 5.8% in HDL-C (β ± SE = 0.057 ± 0.003), and 8.4% in LDL-C (β ± SE = 0.081 ± 0.004) per one standard deviation increase in the corresponding PRS. However, their predictive power was attenuated in T2D patients (0.183 < r < 0.231). When we included each PRS (for TC, TG, and LDL-C) in addition to the clinical factors and PCs, the AUC for dyslipidemia was significantly increased by 0.032-0.057 in the general population (7.5 × 10
< P < 0.0400) and 0.029-0.069 in T2D patients (2.1 × 10
< P < 0.0428). Moreover, the quintile of TC-related PRS was moderately associated with cIMT in adult women (β ± SE = 0.011 ± 0.005, P
= 0.0182). Independent of conventional risk factors, the quintile of PRSs for TC OR (95% CI) = 1.07 (1.03-1.11), TG OR (95% CI) = 1.05 (1.01-1.09), and LDL-C OR (95% CI) = 1.05 (1.01-1.09) were significantly associated with increased risk of CHD in T2D patients (4.8 × 10
< P < 0.0197). Further adjustment for baseline lipid drug use notably attenuated the CHD association.
The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.
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