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Synergistic interaction between prolonged increased glycemic exposure and mildly increased urinary albumin excretion on diabetic retinopathy.

ABSTRACT: The association of mild increase in urinary albumin excretion with diabetic retinopathy (DR) in clinical studies is controversial. The aim of this study is to clarify the interaction between increased glycemic exposure and mild increase in urinary albumin excretion on risk of DR.Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2012. Overall, data from 953 participants without microalbuminuria (477 men and 476 women) were assessed. Logistic regression analysis was constructed to evaluate the association between DR and related clinical parameters, including urinary albumin-creatinine ratio (UACR, mg/g creatinine). The biological interaction of glycemic status and UACR on DR was evaluated by 3 indices: RERI, the relative excess risk due to the interaction; AP, the attributable proportion due to the interaction; and S, the additive interaction index of synergy.We found that UACR, glycated hemoglobin (HbA1c), and diabetic duration were deeply associated with increased risk of DR (UACR, odds ratio [OR]?=?1.04, 95% confidence interval [CI]?=?1.02-1.07; HbA1c, OR?=?1.16, 95% CI?=?1.04-1.30; diabetic duration, OR?=?1.06, 95% CI?=?1.04-1.07). Furthermore, our interaction analysis demonstrated that synergistic interaction between HbA1c and UACR on development of DR was prominent in participants with diabetic duration of ?10 years (adjusted RERI?=?0.92, 95% CI?=?0.10-1.74; adjusted AP?=?0.29, 95% CI?=?-0.82-1.41; adjusted S?=?1.76, 95% CI?=?1.27-2.25), but not subjects with shorter diabetic duration.These findings imply that there is the interaction between prolonged hyperglycemic exposure and increased urinary albumin excretion may exert additive synergistic effect on vascular endothelial dysfunction in the eye, even before the appearance of overt diabetic nephropathy.

SUBMITTER: Moon S

PROVIDER: S-EPMC5779738 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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Synergistic interaction between prolonged increased glycemic exposure and mildly increased urinary albumin excretion on diabetic retinopathy.

Moon Shinje S Yoo Hyung-Joon HJ Ahn You-Hern YH Kim Gheun-Ho GH Yu Jae Myung JM Park Joon-Sung JS

Medicine 20180101 3

The association of mild increase in urinary albumin excretion with diabetic retinopathy (DR) in clinical studies is controversial. The aim of this study is to clarify the interaction between increased glycemic exposure and mild increase in urinary albumin excretion on risk of DR.Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2012. Overall, data from 953 participants without microalbuminuria (477 men and 476 women) were assessed. Logistic regre ...[more]

PMID: 29504969

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Project description:The role of retinal vasculature's dysfunction in the physiopathology of Diabetic Retinopathy (DR) has been extensively described. Recently, the existence of a diabetic choroidal vasculopathy has been proposed. The purpose of this study was to compare choroidal thickness (CT) in nondiabetic patients and in type 2 diabetic patients without retinopathy, using EDI SD-OCT. Additionally, considering the diabetic patient group, compare CT in patients with and without microalbuminuria. This retrospective study selected patients sent from primary health-care centers as part of the national screening of diabetic retinopathy. Inclusion criteria were diagnosis of type 2 diabetes mellitus, absence of diabetic retinopathy, and a 24 hours urinary albumin measurement in the last 3 months at the primary health-care center. Nondiabetic patients were selected from a database in the ophthalmology department, and only healthy patients were included. At the screening visit, all patients performed a complete ophthalmologic examination by the same examiner. All eyes were examined with SD- OCT, and all scans were performed in the EDI mode. Measurements were made at three points: subfoveal, 1500??m temporally and nasally to the foveal center. We included 110 eyes of 110 diabetic patients without diabetic retinopathy and 30 eyes of 30 healthy controls. Mean subfoveal CT was greater in diabetic patients without retinopathy (with normoalbuminuria or microalbuminuria) when compared with nondiabetic patients (p < 0.05). In diabetic patients without retinopathy, the subfoveal and temporal choroid was thicker among patients with microalbuminuria when compared with those of normoalbuminuric patients (p < 0.05). The subfoveal and temporal choroid was thicker among diabetic patients with microalbuminuria compared with nondiabetic patients. (p < 0.05). This study suggests that choroidal changes are present in type 2 diabetic patients even before the clinical development of retinopathy.

Project description:Excess urinary albumin excretion is more common in black than white individuals and is more strongly associated with incident stroke risk in black vs white individuals. Whether similar associations extend to coronary heart disease (CHD) is unclear.To determine whether the association of urinary albumin excretion with CHD events differs by race.Prospective cohort study of black and white US adults aged 45 years and older who were enrolled within the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007 with follow-up through December 31, 2009. We examined race-stratified associations of urinary albumin-to-creatinine ratio (ACR) in 2 groups: (1) incident CHD among 23,273 participants free of CHD at baseline; and (2) first recurrent CHD event among 4934 participants with CHD at baseline.Expert-adjudicated incident and recurrent myocardial infarction and acute CHD death.A total of 616 incident CHD events (421 nonfatal MIs and 195 CHD deaths) and 468 recurrent CHD events (279 nonfatal MIs and 189 CHD deaths) were observed over a mean time of 4.4 years of follow-up. Among those free of CHD at baseline, age- and sex-adjusted incidence rates of CHD per 1000 person-years of follow-up increased with increasing categories of ACR in black and white participants, with rates being nearly 1.5-fold greater in the highest category of ACR (>300 mg/g) in black participants (20.59; 95% CI, 14.36-29.51) vs white participants (13.60; 95% CI, 7.60-24.25). In proportional hazards models adjusted for traditional cardiovascular risk factors and medications, higher baseline urinary ACR was associated with greater risk of incident CHD among black participants (hazard ratio [HR] comparing ACR >300 vs <10 mg/g, 3.21 [95% CI, 2.02-5.09]) but not white participants (HR comparing ACR >300 vs <10 mg/g, 1.49 [95% CI, 0.80-2.76]) (P value for interaction?=?.03). Among those with CHD at baseline, fully adjusted associations of baseline urinary ACR with first recurrent CHD event were similar between black participants (HR comparing ACR >300 vs <10 mg/g, 2.21 [95% CI, 1.22-4.00]) vs white participants (HR comparing ACR >300 vs <10 mg/g, 2.48 [95% CI, 1.61-3.78]) (P value for interaction?=?.53).Higher urinary ACR was associated with greater risk of incident but not recurrent CHD in black individuals when compared with white individuals. These data confirm that black individuals appear more susceptible to vascular injury.

Project description:Background and hypothesisEven within accepted normal ranges, higher serum phosphorus, dietary phosphorus density, parathyroid hormone (PTH) and alkaline phosphatase (ALP) are independent predictors of cardiovascular mortality. Lower serum 25-hydroxy vitamin D (25(OH)D) also predicts adverse cardiovascular outcomes. We hypothesized that vascular dysfunction accompanying subtle disturbances of these bone metabolism parameters would result in associations with increased low grade albuminuria.Study population and measuresWe examined participants in the National Health and Nutrition Examination Surveys 1999-2010 (N = 19,383) with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m² and without severe albuminuria (urine albumin:creatinine ratio (ACR) <300 mg/g). Albuminuria was quantified as ACR and fractional albumin excretion (FE(alb)).ResultsIncreasing quintiles of dietary phosphorus density, serum phosphorus and ALP were not associated with higher ACR or FE(alb). The lowest versus highest quintile of 25(OH)D was associated with greater albuminuria, but not after adjustment for other covariates including cardiovascular risk factors. An association between the highest versus lowest quintile of bone-specific ALP and greater ACR persisted after covariate adjustment, but was not accompanied by an independent association with FE(alb). Increasing quintiles of PTH demonstrated associations with both higher ACR and FE(alb) that were not abolished by adjusting for covariates including age, gender, race, body mass index, diabetes, blood pressure, history of cardiovascular disease, smoking, eGFR, 25(OH)D, season of measurement, lipids, hemoglobin and C-reactive protein. Adjusted increases in ACR and FE(alb) associated with the highest versus lowest quintile of PTH were 19% (95% confidence interval 7-28% p<0.001) and 17% (8-31% p = 0.001) respectively.ConclusionIn this population, of the bone mineral parameters associated with cardiovascular outcomes, only PTH is independently associated with ACR and FE(alb).

Dataset Information

Synergistic interaction between prolonged increased glycemic exposure and mildly increased urinary albumin excretion on diabetic retinopathy.

Publications

Synergistic interaction between prolonged increased glycemic exposure and mildly increased urinary albumin excretion on diabetic retinopathy.

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