Renal effects and safety between Asian and non-Asian chronic kidney disease and type 2 diabetes treated with nonsteroidal mineralocorticoid antagonists.

BACKGROUND: Asians bear a heavier burden of chronic kidney disease (CKD), a common comorbidity of type 2 diabetes mellitus (T2DM), than non-Asians. Nonsteroidal mineralocorticoid receptor antagonists (MRAs) have garnered attention for their potential advantages in renal outcomes. Nevertheless, the impact on diverse ethnic groups remains unknown. METHODS: The PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database, and clinical trial registries were searched through August 2023 with the following keywords: nonsteroidal MRAs (finerenone, apararenone, esaxerenone, AZD9977, KBP-5074), CKD, T2DM, and randomized controlled trial (RCT). A random effects model was used to calculate overall effect sizes. RESULTS: Seven RCTs with 14 997 participants were enrolled. Nonsteroidal MRAs reduced urinary albumin to creatinine ratio (UACR) significantly more in Asians than non-Asians: (weighted mean difference [WMD], -0.59, 95% CI, -0.73 to -0.45, p < .01) vs (WMD, -0.29, 95% CI, -0.32 to -0.27, p < .01), respectively. The average decline of estimated glomerular filtration rate (eGFR) was similar in Asians and non-Asians (p > .05). Regarding systolic blood pressure (SBP), nonsteroidal MRAs had a better antihypertension performance in Asians (WMD, -5.12, 95% CI, -5.84 to -4.41, p < .01) compared to non-Asians (WMD, -3.64, 95% CI, -4.38 to -2.89, p < .01). A higher incidence of hyperkalemia and eGFR decrease ≥30% was found in Asians than non-Asians (p < .01). CONCLUSIONS: Nonsteroidal MRAs exhibited significant renal benefits by decreasing UACR and lowering SBP in Asian than that of non-Asian patients with CKD and T2DM, without increase of adverse events except hyperkalemia and eGFR decrease ≥30%.

Pima Indian Contributions to Our Understanding of Diabetic Kidney Disease.

Prospective studies in informative populations are crucial to increasing our knowledge of disease. In this perspective, we describe a half century of studies in an American Indian population that transformed our understanding of kidney disease in type 2 diabetes, now recognized as the leading cause of kidney failure worldwide. Serial examinations conducted for many years that included the collection of data and samples across multiple domains captured an unprecedented volume of clinical, physiologic, morphometric, genomic, and transcriptomic data. This work permitted us to extensively characterize the course and determinants of diabetic kidney disease, its pathophysiologic underpinnings, and important secular trends of urgent concern to populations worldwide, including the emergence of youth-onset type 2 diabetes and its effect on development of diabetic kidney disease in midlife. By combining these data using the tools of integrative biology, we are developing new mechanistic insights into the development and progression of diabetic kidney disease in type 2 diabetes. These insights have already contributed to the identification and successful therapeutic targeting of a novel pathway in DKD. We anticipate that this work will continue to expand our understanding of this complex disease and influence its management in the coming years.

Associations between macrovascular and renal microvascular dysfunction in type 2 diabetes and non-diabetes: the HELIUS study.

BACKGROUND: Although the associations between measures of macrovascular and microvascular dysfunctions are well characterized in diabetes, there is limited data on these associations in individuals without diabetes. We compared the associations between macrovascular dysfunction and renal microvascular dysfunction in individuals with type 2 diabetes (T2D) and without diabetes. METHODS: Cross-sectional analyses of baseline data from the multiethnic Healthy Life in an Urban Setting (HELIUS) study (Amsterdam, the Netherlands), including 986 participants with T2D and 7680 participants without diabetes were done. Logistic regression analyses were used to examine the associations between macrovascular dysfunction [aortic stiffness, coronary artery disease (CAD), peripheral artery disease (PAD), and stroke] and renal microvascular dysfunction [albuminuria] with adjustments for age, sex, ethnicity, waist-to-hip ratio, systolic blood pressure, LDL-cholesterol, and smoking (and HbA1c and diabetes duration for the T2D group). RESULTS: In the fully adjusted models, aortic stiffness was associated with albuminuria in individuals with T2D [OR 2.55; 95% CI,1.30-4.98], but not without diabetes [0.96; 0.63-1.45]; stroke was associated with albuminuria in T2D [2.40;1.10-5.25], but not in non-diabetes [1.39;0.83-2.33]. In age-sex adjusted models, CAD was associated with albuminuria in T2D [1.65;1.09-2.50] and in non-diabetes [1.56;1.13-2.15]; the associations were no longer significant in the fully adjusted model. There were no associations between PAD and albuminuria in T2D and non-diabetes. CONCLUSIONS: Our study shows important differences in the associations between measures of macrovascular and renal microvascular dysfunction in T2D and non-diabetes. These findings provide opportunities for future research aimed at prevention and treatment strategies for individuals with vascular dysfunction.

Prevalence and risk factors of chronic kidney disease among Palestinian type 2 diabetic patients: a cross-sectional study.

BACKGROUND: Chronic kidney disease (CKD) is a global public health concern and diabetes is one of the main risk factors for its occurrence and progression. The aim of this research is to determine the prevalence of chronic kidney disease in a cross-sectional population of patients with type 2 diabetes in primary health centers in North West Bank. METHODS: Patient data including patient characteristics, creatinine level, blood pressure, HbA1c, and hypertension and period of diabetes were obtained from primary health care centers. The eGFR has been determined using the CKD-EPI equation. CKD was staged according to the 2012 Kidney Disease Improving Global Outcomes Framework (KDIGO) guideline. Both univariable and multivariable statistical analysis was conducted using SPSS. RESULTS: The prevalence of chronic kidney disease among diabetic adults in North West Bank was found to be 23.6% (95% CI: 19.4-28.1%) divided as follows: 19.7% had stage 3 CKD, 2.6% had stage 4 CKD and 1.3% had stage 5 CKD. In multivariable logistic regression, CKD was significantly associated with Age ≥ 60 years [adjusted OR: 3.2, 95% CI: 1.8-5.9], hypertension [adjusted OR: 5.7, 95% CI: 2.2-15.2], and smoking [adjusted OR: 2.3, 95% CI: 1.3-4.2]. CONCLUSIONS: CKD is very prevalent among diabetic adults in Palestine. Co-morbid hypertension, smoking and older age has been shown to increase the risk of developing CKD. Extensive screening for diabetic patients to diagnose CKD at an early stage and to follow more aggressive treatment methods for diabetes as well as other important risk factors, especially hypertension and smoking, is recommended.

Racial Differences in the Effectiveness of a Multifactorial Telehealth Intervention to Slow Diabetic Kidney Disease.

BACKGROUND: African Americans are significantly more likely than non-African Americans to have diabetes, chronic kidney disease, and uncontrolled hypertension, increasing their risk for kidney function decline. OBJECTIVE: The objective of this study was to compare how African Americans and non-African Americans with diabetes responded to a multifactorial telehealth intervention designed to slow kidney function decline. RESEARCH DESIGN: Secondary analysis of a randomized trial. Primary care patients (N=281, 56% African American) were allocated to either: (1) a multifactorial, pharmacist-delivered phone-based telehealth intervention focused on behavioral and medication management of diabetic kidney disease; or (2) an education control. MEASURES: The primary study outcome was change in estimated glomerular filtration rate (eGFR). Linear mixed models were used to explore the moderating effect of race on the relationship between study arm and eGFR decline over time; the mean annual rate of eGFR decline was estimated by race and study arm. RESULTS: Findings demonstrated a differential intervention effect on kidney function over time by race (Pinteraction=0.005). Among African Americans, the intervention arm had significantly greater preservation of eGFR over time than the control arm (difference in the annual rate of eGFR decline=1.5 mL/min/1.73 m; 95% confidence interval: 0.04, 3.02). For non-African Americans, the intervention arm had a faster decline in eGFR over time than the control arm (difference in the annual rate of eGFR decline=-1.7 mL/min/1.73 m; 95% confidence interval: -3.3, -0.02). CONCLUSION: A multifactorial, pharmacist-delivered telehealth intervention for diabetic kidney disease may be more effective for slowing eGFR decline among African Americans than non-African Americans.

Sustained Lower Incidence of Diabetes-Related End-Stage Kidney Disease Among American Indians and Alaska Natives, Blacks, and Hispanics in the U.S., 2000-2016.

OBJECTIVE: Diabetes-related end-stage kidney disease (ESKD-D) disproportionately affects U.S. racial/ethnic minority populations compared with whites. However, from 1996 to 2013, ESKD-D incidence among American Indians and Alaska Natives (AIANs) and blacks declined. We assessed recent ESKD-D incidence data to determine whether trends by race/ethnicity have changed since 2013. RESEARCH DESIGN AND METHODS: United States Renal Data System data from 2000 to 2016 were used to determine the number of whites, blacks, AIANs, Asians, and Hispanics aged ≥18 years with newly treated ESKD-D (with diabetes listed as primary cause). Using census population estimates as denominators, annual ESKD-D incidence rates were calculated and age adjusted to the 2000 U.S. standard population. Joinpoint regression was used to analyze trends and estimate an average annual percent change (AAPC) in incidence rates. RESULTS: For adults overall, from 2000 to 2016, age-adjusted ESKD-D incidence rates decreased by 53% for AIANs (66.7-31.2 per 100,000, AAPC -4.5%, P < 0.001), by 33% for Hispanics (50.0-33.3, -2.1%, P < 0.001), and by 20% for blacks (56.2-44.7, -1.6%, P < 0.001). However, during the study period, age-adjusted ESKD-D incidence rates did not change significantly for Asians and increased by 10% for whites (15.4-17.0, 0.6%, P = 0.01). In 2016, ESKD-D incidence rates in AIANs, Hispanics, and blacks were ∼2.0-2.5 times higher than whites. CONCLUSIONS: ESKD-D incidence declined for AIANs, Hispanics, and blacks and increased for whites. Continued efforts might be considered to reverse the trend in whites and sustain and lower ESKD-D incidence in the other populations.

Role of aromatic amino acids in pathogeneses of diabetic nephropathy in Chinese patients with type 2 diabetes.

BACKGROUND: We aimed to estimate the associations between aromatic amino acids (AAAs) and diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). METHODS: We collected clinical and metabolomic data from 132 healthy subjects (HS group), 132 type 2 diabetes patients without diabetic nephropathy (T2D group) and 132 diabetic nephropathy patients (DN group) in tertiary hospital from May 2015 to August 2016. The odds ratio (OR) and 95% confidence interval (CI) were obtained by logistic regression. RESULTS: The odds ratio of tyrosine for DN increased gradually. High tyrosine was associated with an increased OR of DN (model 3, OR:0.329, 95%CI, 0.144-0.750) when comparing extreme quantiles. CONCLUSION: In Chinese patients with T2D, elevated tyrosine was associated with increased risk of DN.

Elevated circulating luteinizing hormone levels are associated with diabetic macroalbuminuria in Chinese men and postmenopausal women: A cross-sectional study.

BACKGROUND: Associations between sex hormones and diabetic vascular complications have recently been studied, but the role luteinizing hormone (LH) plays in diabetic kidney disease (DKD) remains uncertain. We aimed to investigate the relationship of LH and DKD in Chinese men and postmenopausal women with type 2 diabetes mellitus (T2DM). METHODS: Data were collected from 1775 T2DM men and postmenopausal women in hospital. The odds ratios (OR) and corresponding 95% confidence intervals (CI) in relation to LH quartiles were obtained by multiple logistic regression analysis. RESULTS: LH levels were significantly higher in patients with macroalbuminuria than in those with microalbuminuria, but were not higher in patients with microalbuminuria than in those with normoalbuminuria. Consistently, LH in those with an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 were significantly higher than in those with eGFR≥60 mL/min/1.73m2 . The prevalence of macroalbuminuria was obviously increased for subjects of the fourth quartile of LH vs the first to third quartile (20.4% vs 6.2%, 8.0%, 12.2% in men; 25.3% vs 5.5%, 3.8%, 9.3% in postmenopausal women). Multivariate logistic regression demonstrated that subjects within the highest quartile of LH had higher odds of macroalbuminuria than those within the lowest quartile (OR 4.00, 95% CI, 1.87-8.55 for men; OR 9.62, 95% CI, 3.42-27.08 for postmenopausal women), independent of age, diabetes duration, or other metabolic factors. The area under the curve for detecting macroalbuminuria based on LH was 0.662 for men, and 0.767 for postmenopausal women. CONCLUSION: High LH levels are positively associated with established DKD among Chinese men and postmenopausal women. Elevated LH may be a promising clinical factor for identifying established DKD.

Association between PPARgammars1801282 polymorphism with diabetic nephropathy and type-2 diabetes mellitus susceptibility in south India and a meta-analysis / Asociación entre el polimorfismo rs1801282 de PPAR con nefropatía diabética y sensibilidad a la diabetes mellitus de tipo 2 en el sur de India y un metaanálisis

ANTECEDENTES: La nefropatía diabética (ND) es una complicación importante de la diabetes mellitus de tipo 2 (DMT2) con altas tasas de morbilidad mundial. OBJETIVO: Determinar la asociación del polimorfismo rs1801282 de PPAR en la DMT2 y la ND en la población del sur de India. MÉTODOS: Hemos llevado a cabo un estudio de casos y controles para analizar la asociación del polimorfismo rs1801282 con la DMT2 y la ND en 424 sujetos (ND = 128; DMT2 = 148 y controles = 148) pertenecientes a la población del sur de India mediante RCP-ARMS y método de secuenciación de Sanger. Además, se realizó un metaanálisis para el polimorfismo de rs1801282 a partir de la literatura publicada en varias bases de datos electrónicas para determinar la sensibilidad entre la DMT2 y la ND en varias poblaciones étnicas con 5 modelos genéticos. RESULTADOS: El genotipado de polimorfismo rs1801282 demostró una asociación significativa (valor de p < 0,05) con la ND y la DMT2 en comparación con los controles. En el metaanálisis no se observó asociación significativa (valor de p > 0,05) de rs1801282 con la ND frente a los controles en modelos genéticos homocigóticos, heterocigóticos, alélicos, recesivos y dominantes. Sin embargo, se observó una asociación significativa entre el polimorfismo de nucleótido único (PNU) rs1801282 SNP y la DMT2 en el modelo genético heterocigótico (Jj frente a JJ) con OR = 0,56, (IC del 95%: 0,43-0,74; p ≤ 0,0001 de poblaciones asiáticas y caucásicas. CONCLUSIÓN: El análisis general sugiere que el polimorfismo rs1801282 puede asociarse a ND y a DMT2. Se precisan más estudios de casos y controles sobre el gen PPAR con un taman˜ o de la muestra mayor que incluya todos los factores de confusión para corroborar los resultados de este metaanálisis

BACKGROUND: Diabetic Nephropathy (DN) is a major complication of Type 2 Diabetes Mellitus (T2DM) with high morbidity rates worldwide. OBJECTIVE: To determine the association of PPAR rs1801282 polymorphism in T2DM and DN in south Indian population. METHODS: We have conducted a case-control study to test the association of rs1801282 polymorphism with T2DM and DN in 424 subjects (DN = 128; T2DM = 148 and controls = 148) belonging to the south Indian population using ARMS-PCR and Sanger sequencing method. Further, a meta-analysis was performed for rs1801282 polymorphism from the published literature retrieved from various electronic databases to determine the susceptibility among T2DM and DN across various ethnic populations under five genetic models. RESULTS: The genotyping of rs1801282 polymorphism showed significant (p-value < 0.05) association with DN and T2DM compared to controls. In the meta-analysis, no significant association (p-value > 0.05) was noticed for rs1801282 with DN vs. controls in homozygote, heterozygote, allelic, recessive and dominant genetic models. However, a significant association was observed between rs1801282 SNP and T2DM under heterozygote (Jj vs JJ) genetic model with OR = 0.56, (95%CI [0.43-0.74]), p ≤ 0.0001 of Asian and Caucasian populations. CONCLUSION: Overall analysis suggests that the rs1801282 polymorphism might be associated with DN and T2DM. More case-control studies on the PPAR gene with a larger sample size including all the confounding factors are required to corroborate the findings from this meta-analysis

Incidence of ESKD Among Native Hawaiians and Pacific Islanders Living in the 50 US States and Pacific Island Territories.

RATIONALE & OBJECTIVE: Native Hawaiians and Pacific Islanders (NHPI) have been reported to have the highest rates of incident end-stage kidney disease (ESKD) compared with other races in the United States. However, these estimates were likely biased upward due to the exclusion of nearly half the NHPI population that reports multiple races in the US Census. We sought to estimate the incidence rate of ESKD, including individuals reporting multiple races, and describe the clinical characteristics of incident cases by race and location. STUDY DESIGN: Health care database study. SETTING & PARTICIPANTS: US residents of the 50 states and 3 Pacific Island territories of the United States whose ESKD was recorded in the US Renal Data System (USRDS) between 2007 and 2016, as well as US residents recorded in the 2010 Census. PREDICTORS: Age, sex, race, body mass index, primary cause of ESKD, comorbid conditions, estimated glomerular filtration rate, pre-ESKD nephrology care, and hemoglobin A1c level among ESKD cases. OUTCOME: Initiation of maintenance dialysis or transplantation for kidney failure. ANALYTICAL APPROACH: Crude ESKD incidence rates (cases/person-years) were estimated using both single- and multiple-race reporting. RESULTS: Even after inclusion of multirace reporting, NHPI had the highest ESKD incidence rate among all races in the 50 states (921 [95% CI, 904-938] per million population per year)-2.7 times greater than whites and 1.2 times greater than blacks. Also using multirace reporting, the NHPI ESKD incident rate in the US territories was 941 (95% CI, 895-987) per million population per year. Diabetes was listed as the primary cause of ESKD most frequently for NHPI and American Indians/Alaska Natives. Sensitivity analysis adjusting for age and sex demonstrated greater differences in rates between NHPI and other races. Diabetes was the primary cause of ESKD in 60% of incident NHPI cases. Patients with ESKD living in the territories had received less pre-ESKD nephrology care than had patients living in the 50 states. LIMITATIONS: Different methods of race classification in the USRDS versus the US Census. CONCLUSIONS: NHPI living in the 50 US states and Pacific territories had the highest rates of ESKD incidence compared with other races. Further research and efforts are required to understand the reasons for and define how best to address this racial disparity.

Association between PPARγrs1801282 polymorphism with diabetic nephropathy and type-2 diabetes mellitus susceptibility in south India and a meta-analysis.

BACKGROUND: Diabetic Nephropathy (DN) is a major complication of Type 2 Diabetes Mellitus (T2DM) with high morbidity rates worldwide. OBJECTIVE: To determine the association of PPARγ rs1801282 polymorphism in T2DM and DN in south Indian population. METHODS: We have conducted a case-control study to test the association of rs1801282 polymorphism with T2DM and DN in 424 subjects (DN=128; T2DM=148 and controls=148) belonging to the south Indian population using ARMS-PCR and Sanger sequencing method. Further, a meta-analysis was performed for rs1801282 polymorphism from the published literature retrieved from various electronic databases to determine the susceptibility among T2DM and DN across various ethnic populations under five genetic models. RESULTS: The genotyping of rs1801282 polymorphism showed significant (p-value<0.05) association with DN and T2DM compared to controls. In the meta-analysis, no significant association (p-value>0.05) was noticed for rs1801282 with DN vs. controls in homozygote, heterozygote, allelic, recessive and dominant genetic models. However, a significant association was observed between rs1801282 SNP and T2DM under heterozygote (Jj vs JJ) genetic model with OR=0.56, (95%CI [0.43-0.74]), p≤0.0001 of Asian and Caucasian populations. CONCLUSION: Overall analysis suggests that the rs1801282 polymorphism might be associated with DN and T2DM. More case-control studies on the PPARγ gene with a larger sample size including all the confounding factors are required to corroborate the findings from this meta-analysis.

The prevalence of microvascular complications in Waikato children and youth with type 1 diabetes has reduced since 2003.

AIMS: To determine whether glycaemic control and the prevalence of microvascular complications in Waikato children/youth with type 1 diabetes (T1D) has changed since 2003. METHODS: A retrospective review was performed of clinical records of children and youth with T1D who were under the care of the Waikato Paediatric and Young Adult Diabetes Services between March 2016 and March 2017. Comparisons were made to published data from the same service in 2003. RESULTS: Despite a more than two-fold increase in insulin-pump therapy since 2003, glycaemic control was not significantly improved in either children or youth. However, since 2003 there has been a significant reduction in the prevalence of diabetic retinopathy (24.6% vs 6.0%; P=0.003) and nephropathy (6.0% vs 25.4%; P=0.002), while symptomatic diabetic neuropathy remains rare. This reduction occurred despite a significant increase in obesity and hypertension, and no significant difference in the rates of dyslipidaemia or smoking. CONCLUSIONS: There has been a marked reduction in microvascular complications in Waikato youth and young adults with type 1 diabetes, but the reasons for the reduction are not clear given there has been no significant improvements in glycaemic control.

Association between LXR-α and ABCA1 Gene Polymorphisms and the Risk of Diabetic Kidney Disease in Patients with Type 2 Diabetes Mellitus in a Chinese Han Population.

We designed a case-control study and selected LXR-α rs7120118 C>T and ABCA1 rs2230806 A>G polymorphisms to determine the correlation between these polymorphisms and diabetic kidney disease (DKD) susceptibility in a Chinese Han population. Three hundred DKD patients and 346 type 2 diabetes mellitus (DM) patients without kidney disease were recruited. Our results showed that rs7120118 was associated with DKD (genotype, P = .027; allele, P < .011). rs7120118 was associated with a higher risk of DKD under a dominant model adjustment by age and sex (P = .015) and an additive model (P = .040); rs2230806 was associated with a higher risk of DKD under an recessive model (P < .03); the combined effect of rs7120118 CC+rs2230806 GG genotype showed an association of DKD adjustment for age and sex (P = .009). In subgroup analysis of patients without hypercholesterolemia, the rs2230806 genotype frequencies were different between the two groups (P = .042). rs2230806 was associated with increased risk of DKD under a recessive model adjustment for age and sex (P = .013) and an additive model (P = .031). Our results suggest that LXR-α rs7120118 is significantly associated with a higher risk of DKD, and ABCA1 rs2230806 is significantly associated with a higher risk of DKD without hypercholesterolemia in Chinese Han individuals.

Evaluation of lipoprotein-associated phospholipase A2 as a marker for renal microvasculopathy in adolescents with Type 1 diabetes.

AIM: To assess the relevance of lipoprotein-associated phospholipase A2 activity as a diagnostic and prognostic marker for renal microvascular diseases. METHODS: We analysed lipoprotein-associated phospholipase A2 activity and lysophosphatidylcholine levels (as a surrogate marker of oxidative stress) in 165 adolescents (aged 17.0 ± 2.3 years) with a history of Type 1 diabetes greater than 10 years. Clinical data were obtained from the German/Austrian nationwide Diabetes-Patients Follow-up (DPV) registry at blood collection and on average 2.4 ± 1.3 years later at follow-up. Relationships between lipoprotein-associated phospholipase A2 activity and clinical, demographic and laboratory variables, lysophosphatidylcholine levels and presence of albuminuria were evaluated by multivariable linear and logistic regression. RESULTS: Lipoprotein-associated phospholipase A2 activity was higher in male than female adolescents (P = 0.002). Albuminuria was present in 14% (22/158) of participants at baseline, and 5% (4/86) of participants without albuminuria at baseline developed albuminuria until follow-up. Lipoprotein-associated phospholipase A2 activity was associated neither with present nor with incident albuminuria. Lysophosphatidylcholine did not correlate with lipoprotein-associated phospholipase A2 activity. Cross-sectional bivariate correlation as well as multivariable linear regression analysis revealed a negative correlation of lipoprotein-associated phospholipase A2 activity with HbA1c and HDL-cholesterol. CONCLUSIONS: Lipoprotein-associated phospholipase activity was not associated with surrogate markers for oxidative stress and early diabetic nephropathy. The association of decreased lipoprotein-associated phospholipase A2 activity with poor glucose control might limit its function as a predictor of micro- and macrovascular diseases in Type 1 diabetes.

The increased risk of microvascular complications in South Asians with type 1 diabetes is influenced by migration.

AIM: We aimed to explore the association between South Asian ethnicity and complications of type 1 diabetes, and whether this is affected by migration. METHODS: In this retrospective cohort study, data on diabetes control and complications were obtained for South Asians in India (South AsiansIndia , n = 2592) and the UK (South AsiansUK , n = 221) and white Europeans in the UK (n = 1431). Multivariable logistic regression was used to identify associations between ethnicity and diabetic kidney disease, retinopathy and neuropathy adjusting for age, sex, BMI, disease duration, HbA1c , blood pressure (BP) and cholesterol. RESULTS: South AsiansIndia had significantly greater adjusted odds of diabetic kidney disease [odds ratio (OR) 5.0, 95% confidence intervals (CI) 3.6-7.1] and retinopathy (OR 1.8, 95% CI 1.2-2.5), but lower odds of neuropathy (OR 0.5, 95% CI 0.4-0.6) than white Europeans. South AsiansIndia had significantly greater adjusted odds of diabetic kidney disease (OR 3.0, 95% 1.8-5.3) than South AsiansUK , but there was no significant difference in the odds of other complications. CONCLUSIONS: In this hypothesis-generating study, we report that South Asian ethnicity is associated with greater risk of diabetic kidney disease and retinopathy, and lower risk of neuropathy than white European ethnicity. Part of the excess diabetic kidney disease risk is reduced in South AsiansUK . These associations cannot be accounted for by differences in vascular risk factors. Our findings in South Asians with type 1 diabetes mirror previous findings in type 2 diabetes and now need to be validated in a study of the effect of ethnicity on type 1 diabetes complications where healthcare is provided in the same setting.

Genetic risk score for risk prediction of diabetic nephropathy in Han Chinese type 2 diabetes patients.

We evaluated whether genetic information could offer improvement on risk prediction of diabetic nephropathy (DN) while adding susceptibility variants into a risk prediction model with conventional risk factors in Han Chinese type 2 diabetes patients. A total of 995 (including 246 DN cases) and 519 (including 179 DN cases) type 2 diabetes patients were included in derivation and validation sets, respectively. A genetic risk score (GRS) was constructed with DN susceptibility variants based on findings of our previous genome-wide association study. In derivation set, areas under the receiver operating characteristics (AUROC) curve (95% CI) for model with clinical risk factors only, model with GRS only, and model with clinical risk factors and GRS were 0.75 (0.72-0.78), 0.64 (0.60-0.68), and 0.78 (0.75-0.81), respectively. In external validation sample, AUROC for model combining conventional risk factors and GRS was 0.70 (0.65-0.74). Additionally, the net reclassification improvement was 9.98% (P = 0.001) when the GRS was added to the prediction model of a set of clinical risk factors. This prediction model enabled us to confirm the importance of GRS combined with clinical factors in predicting the risk of DN and enhanced identification of high-risk individuals for appropriate management of DN for intervention.

Glycemia affects glomerular filtration rate in people with type 2 diabetes.

BACKGROUND: In type 2 diabetes (T2DM), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for estimated glomerular filtration rate (eGFR) systematically underestimates the measured adjusted glomerular filtration rate (aGFR) when aGFR is high. We studied the extent to which glycemic variables associate with kidney function, and developed equations including these variables that estimate aGFR in people with T2DM. METHODS: Diabetic Pima people had aGFR measured from iothalamate clearance divided by body surface area. eGFRs < 60 ml/min/1.73m2 were excluded. Multivariate linear regression identified variables correlated with kidney function. We constructed equations for approximating aGFR. Correlation analysis and 10-fold cross-validation were used to compare the CKD-EPI equation and the new approximating equations to the measured aGFR. Ability to detect hyperfiltration, defined as aGFR > 120 ml/min/1.73m2, was compared by analysis of receiver-operating (ROC) curves. RESULTS: aGFR was measured 2798 times in 269 individuals. HbA1c, fasting plasma glucose (FPG), age, and serum creatinine (SCR) were significantly associated with aGFR. The best equations for approximating aGFR used HbA1c and FPG in addition to age and SCR. They approximate aGFR in this cohort of obese people with T2DM more precisely than the CKD-EPI equation. Analysis of ROC curves show that these equations detect hyperfiltration better than does the CKD-EPI equation. CONCLUSIONS: HbA1c, FPG, age, and SCR yielded the best equations for estimating aGFR in these subjects. The new equations identify hyperfiltration better than the CKD-EPI equation in this cohort and may inform clinical decisions regarding hyperfiltration in individuals with T2DM.

hs-CRP Is Associated With Incident Diabetic Nephropathy: Findings From the Jackson Heart Study.

OBJECTIVE: African Americans (AA) suffer disproportionately from diabetic nephropathy (DN). C-reactive protein (CRP) has been associated with prevalent DN, but its association with incident DN in AA is unknown. We examined hs-CRP and incident DN in AA. RESEARCH DESIGN AND METHODS: We conducted a longitudinal analysis of data from exams 1, 2, and 3 in 4,043 eligible Jackson Heart Study (JHS) participants. Participants with DN or without hs-CRP at exam 1 were excluded. Incident DN was defined as urinary albumin-to-creatinine ratio (ACR) >30 mg/g or self-reported dialysis/transplantation and type 2 diabetes mellitus (DM) or HbA1c >6.5% by exam 2 or 3 among participants free of DN at exam 1. Kaplan-Meier curves examined DN event-free survival probability by hs-CRP. With Cox proportional hazards regression we estimated hazard ratios (HRs) and 95% CI for DN by hs-CRP tertiles, adjusting for demographics and clinical and laboratory data. RESULTS: During 7.8 years of median follow-up time, participants who developed DN had significantly higher baseline hs-CRP, age, fasting glucose, triglycerides, ACR, systolic blood pressure, waist circumference, and duration of DM (P < 0.05). The overall incident rate of DN was 7.9%. The mean time to incident DN was shorter for participants with hs-CRP in the high tertile (>4.24 mg/L) than in the low tertile (<1.46 mg/L); P < 0.001. Participants with high hs-CRP had higher incidence of DN (HR 2.34, 95% CI 1.04-5.24) versus the reference group. CONCLUSIONS: Inflammation, as measured by hs-CRP levels, may be associated with incident DN in AA. Further studies are warranted to replicate and elucidate the basis for this association.

Genetic Variants Flanking the FGF21 Gene Were Associated with Renal Function in Chinese Patients with Type 2 Diabetes.

AIMS: Fibroblast growth factor 21 (FGF21) is closely linked with metabolic disorders including diabetes. Evidences suggested that FGF21 may play a protective role against diabetic kidney disease (DKD). However, the relationship between genetic variants in the FGF21 gene region and DKD remains unknown. In our study, we aimed to investigate the association of genetic variations in this gene region with DKD and DKD-related clinical traits. MATERIALS AND METHODS: We recruited 1340 Han Chinese participants with type 2 diabetes, including 596 DKD patients and 744 patients who was diagnosed with diabetes for more than 5 years but did not progress to DKD. Three single-nucleotide polymorphisms were selected (rs2071699, rs838136, and rs499765) and genotyped. The association between these SNPs and DKD as well as DKD-related quantitative traits was analyzed. RESULTS: We did not find any significant association between these SNPs and susceptibility to DKD in the present study. However, a significant association with estimated glomerular filtration rate (eGFR) was detected: in the non-DKD group, rs838136 was significantly associated with eGFR under an additive model (ß = 0.013 ± 0.006, P = 0.0295, ß was calculated for log10eGFR) as well as a recessive model (P = 0.0385) and rs499765 was associated with eGFR under a dominant model (P = 0.0411) and in the DKD group, rs499765 showed a trend toward association with eGFR under an additive model (ß = -0.022 ± 0.012, P = 0.0820, ß was calculated for log10eGFR) and showed a significant association with eGFR under a dominant model (P = 0.0182). CONCLUSIONS: Our findings indicated that genetic variations adjacent to FGF21 were associated with eGFR in Chinese diabetic patients.