Nephrinuria associates with multiple renal traits in type 2 diabetes.

BACKGROUND: The involvement of nephrin in controlling renal function is unclear with the literature only emphasizing its role in albuminuria. We therefore investigated the potential association between nephrinuria as evidenced by the appearance of urinary immunopositive nephrin fragments, with multiple renal traits. METHODS: Western blot analysis of the urine samples from a cross-sectional study of 381 Chinese type 2 diabetic patients revealed four distinct protein fragments, indicative of nephrinuria. Albuminuria was measured in random spot urine samples using the albumin/creatinine ratio (ACR), while estimated glomerular filtration rate (eGFR) was calculated using the creatinine-based Modification of Diet in Renal Disease formula. RESULTS: Each nephrin fragment was associated with a decline in eGFR (smallest P = 0.001). Even with the inclusion of logarithmic form of ACR (ln ACR) in the multivariate model, nephrinuria still remained significantly associated with lower eGFR (smallest P < 0.05). Nephrinuria was also strongly associated with lnACR and this finding was independent of eGFR (smallest P < 0.001). Thus, nephrinuria was independently associated with both renal traits in the form of lnACR and eGFR. Furthermore, nephrinuria was significantly associated with lower eGFR even among normoalbuminuric patients (ACR ≤ 30 mg/g) (smallest P = 0.002), potentially implicating nephrinuria in the development of normoalbuminuric renal insufficiency. Apart from the renal traits under investigation, the presence of nephrinuria did not associate with other patient clinical characteristics. CONCLUSIONS: Nephrinuria was associated with multiple renal traits in type 2 diabetes even in normoalbuminuric patients who are traditionally perceived as having a low risk of chronic kidney disease.

Polymorphisms identified through genome-wide association studies and their associations with type 2 diabetes in Chinese, Malays, and Asian-Indians in Singapore.

CONTEXT: Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized. OBJECTIVE: To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore. DESIGN: We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians. RESULTS: In Chinese, SNPs in CDKAL1 [odds ratio (OR) = 1.19; P = 2 x 10(-4)], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 x 10(-4)) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 x 10(-4)), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19-1.25; P = 0.003-2.5 x 10(-4)) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 x 10(-4)), CDKN2A/B (OR = 1.16; P = 9 x 10(-5)), HHEX (OR = 1.14; P = 6 x 10(-4)), and KCNQ1 (OR = 1.16-1.20; P = 3 x 10(-4) to 3 x 10(-6)) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry. CONCLUSIONS: SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.

Development of a diabetes registry to improve quality of care in the National Healthcare Group in Singapore.

In Singapore, chronic care is provided by both ambulatory primary care clinics and specialist clinics in hospitals. In 2005, the National Healthcare Group (NHG) embarked to build a diabetes registry to enhance the continuity of care for patients with diabetes and facilitate greater efficiency in outcome measurement. This Chronic Disease Management System (CDMS) links administrative and key clinical data of patients with diabetes mellitus across the healthcare cluster. At the point of patient care, clinicians view a summary of each patient's chronic disease records, consolidated chart with physical parameters, laboratory investigation results and the "patient reminders" listing the clinical decision support prompts when key laboratory and screening tests are due for each patient. The CDMS provides reports of clinical outcomes in a systematic and efficient manner for quality improvement and evidenced-based population management. These include process indicators consisting of the rates of glycated haemoglobin (HbA1c), low-density lipoprotein-cholesterol (LDL-c) and nephropathy tests; and intermediate outcome indicators of the proportion of patients with poor HbA1c (>9%) and optimal LDL-c (<2.6 mmol/L) control. From January 2007 to December 2008, the rates of the 3 process indicators were relatively unchanged and that of HbA1c and LDL-c tests were high. There was gradual improvement in the proportion of patients achieving target level of LDL-c in both primary care clinics and hospitals. Fewer patients at primary care clinics had poorly-controlled HbA1c. As a tool for chronic care delivery, the NHG diabetes registry has made clinical monitoring and outcome management for patients with diabetes mellitus more efficient.