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      Direct association of visit-to-visit HbA1c variation with annual decline in estimated glomerular filtration rate in patients with type 2 diabetes

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          Abstract

          Background/Aims

          This study examined associations of visit-to-visit variability of glycemic control with annual decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes attending an outpatient clinic.

          Methods

          Intrapersonal mean and coefficient of variation (CV) of 8-12 measurements of HbA1c and those of 4-6 measurements of fasting and post-breakfast plasma glucose (FPG and PPG, respectively) during the first 12 months after enrollment were calculated in a cohort of 168 patients with type 2 diabetes. Annual changes in eGFR were computed using 52 (median) creatinine measurements obtained over a median follow-up of 6.0 years. Multivariate linear regressions assessed the independent correlates of changes in eGFR.

          Results

          CV-HbA1c (standardized β、-0.257、 p = 0.004) were significantly and log urine albumin/creatinine ratio (standardized β、-0.155、 p = 0.085) and smoking (standardized β、-0.186、 p = 0.062) tended to be associated with annual eGFR decline independently of mean HbA1c, age, sex, BMI, waist circumference, diabetes duration and therapy, means and CVs of FPG, PPG and systolic blood pressure, baseline eGFR, and uses of anti-hypertensive and lipid-lowering medications. Association between HbA1c variability and renal function decline was stronger in patients with albumin/creatinine ratio ≧ 30 mg/g than in those with normoalbuminuria (r = -0.400, p = 0.003 and r = -0.169, p = 0.07, respectively).

          Conclusions

          Consistency of glycemic control is important to preserve kidney function in type 2 diabetic patients, in particular, in those with nephropathy.

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          Most cited references18

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          Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study.

          To determine the relation between systolic blood pressure over time and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. Prospective observational study. 23 hospital based clinics in England, Scotland, and Northern Ireland. 4801 white, Asian Indian, and Afro-Caribbean UKPDS patients, whether randomised or not to treatment, were included in analyses of incidence; of these, 3642 were included in analyses of relative risk. Primary predefined aggregate clinical outcomes: any complications or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes: myocardial infarction, stroke, lower extremity amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photocoagulation). Single end points: non-fatal heart failure and cataract extraction. Risk reduction associated with a 10 mm Hg decrease in updated mean systolic blood pressure adjusted for specific confounders. The incidence of clinical complications was significantly associated with systolic blood pressure, except for cataract extraction. Each 10 mm Hg decrease in updated mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes (95% confidence interval 10% to 14%, P<0.0001), 15% for deaths related to diabetes (12% to 18%, P<0.0001), 11% for myocardial infarction (7% to 14%, P<0.0001), and 13% for microvascular complications (10% to 16%, P<0.0001). No threshold of risk was observed for any end point. In patients with type 2 diabetes the risk of diabetic complications was strongly associated with raised blood pressure. Any reduction in blood pressure is likely to reduce the risk of complications, with the lowest risk being in those with systolic blood pressure less than 120 mm Hg.
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            A1C Variability and the Risk of Microvascular Complications in Type 1 Diabetes

            OBJECTIVE—Debate remains as to whether short- or long-term glycemic instability confers a risk of microvascular complications in addition to that predicted by mean glycemia alone. In this study, we analyzed data from the Diabetes Control and Complications Trial (DCCT) to assess the effect of A1C variability on the risk of retinopathy and nephropathy in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS—A1C was collected quarterly during the DCCT in 1,441 individuals. The mean A1C and the SD of A1C variability after stabilization of glycemia (from 6 months onwards) were compared with the risk of retinopathy and nephropathy with adjustments for age, sex, disease duration, treatment group, and baseline A1C. RESULTS—Multivariate Cox regression showed that the variability in A1C added to mean A1C in predicting the risk of development or progression of both retinopathy (hazard ratio 2.26 for every 1% increase in A1C SD [95% CI 1.63–3.14], P < 0.0001) and nephropathy (1.80 [1.37–2.42], P < 0.0001), with the relationship a feature in conventionally treated patients in particular. CONCLUSIONS—This study has shown that variability in A1C adds to the mean value in predicting microvascular complications in type 1 diabetes. Thus, in contrast to analyses of DCCT data investigating the effect of short-term glucose instability on complication risk, longer-term fluctuations in glycemia seem to contribute to the development of retinopathy and nephropathy in type 1 diabetes.
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              Effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial--revisited.

              The Diabetes Control and Complications Trial (Diabetes 44:968-983, 1995) presented statistical models suggesting that subjects with similar A1C levels had a higher risk of retinopathy progression in the conventional treatment group than in the intensive treatment group. That analysis has been cited to support the hypothesis that specific patterns of glucose variation, in particular postprandial hyperglycemia, contribute uniquely to an increased risk of microvascular complications above and beyond that explained by the A1C level. We performed statistical evaluations of these models and additional analyses to assess whether the original analyses were flawed. Statistically, we show that the original results are an artifact of the assumptions of the statistical model used. Additional analyses show that virtually all (96%) of the beneficial effect of intensive versus conventional therapy on progression of retinopathy is explained by the reductions in the mean A1C levels, similarly for other outcomes. Furthermore, subjects within the intensive and conventional treatment groups with similar A1C levels over time have similar risks of retinopathy progression, especially after adjusting for factors in which they differ. A1C explains virtually all of the difference in risk of complications between the intensive and conventional groups, and a given A1C level has similar effects within the two treatment groups. While other components of hyperglycemia, such as glucose variation, may contribute to the risk of complications, such factors can only explain a small part of the differences in risk between intensive and conventional therapy over time.
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                Author and article information

                Contributors
                acotake1991@gmail.com
                a---chan.8.smile@hotmail.co.jp
                mayunabe.0125@hotmail.co.jp
                mkura@mukogawa-u.ac.jp
                fukuo@mukogawa-u.ac.jp
                kazumi@mukogawa-u.ac.jp
                Journal
                J Diabetes Metab Disord
                J Diabetes Metab Disord
                Journal of Diabetes and Metabolic Disorders
                BioMed Central (London )
                2251-6581
                14 September 2015
                14 September 2015
                2015
                : 14
                : 69
                Affiliations
                [ ]Postgraduate School of Food Sciences and Nutrition, Nishinomiya, Japan
                [ ]Department of Food Sciences and Nutrition, School of Human Environmental Sciences, Nishinomiya, Japan
                [ ]Research Institute for Nutrition Sciences, Mukogawa Women’s University, 6-46, Ikebiraki-cho, Nishinomiya, Hyogo 663-8558 Japan
                [ ]Diabetes Division, Sadamitsu Hospital, Kakogawa, Hyogo 675-0005 Japan
                Article
                201
                10.1186/s40200-015-0201-y
                4570746
                26380227
                26a92459-15c9-4050-aa93-1a251820bee9
                © Takenouchi et al. 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 21 June 2015
                : 1 September 2015
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2015

                hba1c,standard deviation,kidney function,egfr
                hba1c, standard deviation, kidney function, egfr

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