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      Postmeal triglyceridemia and variability of HbA1c and postmeal glycemia were predictors of annual decline in estimated glomerular filtration rate in type 2 diabetic patients with different stages of nephropathy

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          Abstract

          Background

          This study examined associations of annual glycemic variability and postprandial dysmetabolism with annual decline in estimated glomerular filtration rate (eGFR) in type 2 diabetic patients with different stages of nephropathy.

          Methods

          Intrapersonal mean and coefficient of variation (CV) of HbA1c, fasting and postmeal concentrations of plasma glucose (FPG and PMPG, respectively) and serum triglycerides (FTG and PMTG, respectively) during the first 12 months after enrollment were calculated in a cohort of 168 type 2 diabetic patients: 53 with optimal albumin/creatinine ratio (ACR < 10 mg/g), 62 with high normal ACR (10–29 mg/g) and 53 with elevated ACR (≧30 mg/g). 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

          Kidney function declined faster in patients with high normal and elevated ACR (−1.47 and −2.01 ml/min/1.73 m 2/year, respectively) compared to patients with optimal ACR (0.08 ml/min/1.73 m 2/year, p < 0.05). In patients with high normal ACR, age (standardized β、-0.30、 p = 0.01), CV-HbA1c (standardized β、-0.66、 p < 0.001) and CV-PMPG (standardized β、-0.27、 p = 0.01) was associated with annual eGFR decline independently of mean HbA1c and PMPG, sex, BMI, waist circumference, diabetes duration and therapy, means and CVs of FPG and systolic blood pressure, baseline eGFR, log ACR and uses of anti-hypertensive medications (R 2 = 0.47). In patients with elevated ACR, PMTG (standardized β、-0.408, p = 0.007) was associated with annual eGFR decline (R 2 = 0.15).

          Conclusions

          Consistency of glycemic control and management of postprandial glycemia and lipidemia are important to preserve kidney function in type 2 diabetic patients.

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          Most cited references 20

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          Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study.

          Animal and in vitro data suggest that dyslipidemia plays an important role in the initiation and progression of chronic renal disease, but few prospective studies have been conducted in humans. We studied the relationship of plasma lipids to a rise in serum creatinine of 0.4 mg/dL or greater in 12,728 Atherosclerosis Risk in Communities (ARIC) participants with baseline serum creatinine that was less than 2.0 mg/dL in men and less than 1.8 mg/dL in women. During a mean follow-up of 2.9 years, 191 persons had a rise in creatinine of 0.4 mg/dL or greater, yielding an incidence rate of 5.1 per 1000 person years. Individuals with higher triglycerides and lower high-density lipoprotein (HDL) and HDL-2 cholesterol at baseline were at increased risk for a rise in creatinine after adjustment for race, gender, baseline age, diabetes, serum creatinine, systolic blood pressure, and antihypertensive medication use (all P trends
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            Renal insufficiency and subsequent death resulting from cardiovascular disease in the United States.

            Several epidemiologic studies reported that persons with renal insufficiency might have increased cardiovascular disease-related mortality rates in select populations. The association between renal insufficiency and increased cardiovascular disease-related and all-cause mortality rates during 16 yr of follow-up monitoring was examined among participants who were 30 to 74 yr of age at the baseline examinations in 1976 to 1980, with urinary protein dipstick measurements (n = 8786) or serum creatinine levels of or=300 mg/dl and were 4.1, 8.6, and 20.5 deaths/1000 person-yr among participants with estimated GFR of >or=90, 70 to 89, and or=300 mg/dl, respectively, compared with or=90 ml/min, those with estimated GFR of <70 ml/min exhibited higher relative risks of death from cardiovascular disease and all causes [1.68 (1.33 to 2.13) and 1.51 (1.19 to 1.91), respectively]. This study indicates that, in a representative sample of the United States general population, renal insufficiency is independently associated with increased cardiovascular disease-related and all-cause mortality rates.
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              Evidence for an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial dysfunction and oxidative stress generation: effects of short- and long-term simvastatin treatment.

              Postprandial hypertriglyceridemia and hyperglycemia are considered risk factors for cardiovascular disease. Evidence suggests that postprandial hypertriglyceridemia and hyperglycemia induce endothelial dysfunction through oxidative stress; however, the distinct role of these two factors is a matter of debate. Thirty type 2 diabetic patients and 20 normal subjects ate 3 different meals: a high-fat meal; 75 g glucose alone; and high-fat meal plus glucose. Glycemia, triglyceridemia, nitrotyrosine, and endothelial function were assayed during the tests. Subsequently, diabetics took 40 mg/d simvastatin or placebo for 12 weeks. The 3 tests were performed again at baseline, between 3 to 6 days after the start, and at the end of each study. High-fat load and glucose alone produced a decrease of endothelial function and an increase of nitrotyrosine in normal and diabetic subjects. These effects were more pronounced when high fat and glucose were combined. Short-term simvastatin treatment had no effect on lipid parameters but reduced the effect on endothelial function and nitrotyrosine observed during each different test. Long-term simvastatin treatment was accompanied by a lower increase in postprandial triglycerides, which was followed by smaller variations of endothelial function and nitrotyrosine during the tests. This study shows an independent and cumulative effect of postprandial hypertriglyceridemia and hyperglycemia on endothelial function, suggesting oxidative stress as common mediator of such effect. Simvastatin shows a beneficial effect on oxidative stress and endothelial dysfunction, which may be ascribed to a direct effect as well as the lipid-lowering action of the drug.
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                Author and article information

                Contributors
                a---chan.8.smile@hotmail.co.jp
                acotake1991@gmail.com
                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
                11 January 2017
                11 January 2017
                2017
                : 16
                Affiliations
                [1 ]Research Institute for Nutrition Sciences, Mukogawa Women’s University, 6-46, Ikebiraki-cho, Nishinomiya, Hyogo 663-8558 Japan
                [2 ]Department of Nutrition, Osaka City Juso Hospital, Osaka, 532-0034 Japan
                [3 ]Department of Food Sciences and Nutrition, School of Human Environmental Sciences, Mukogawa Women’s University, 6-46, Ikebiraki-cho, Nishinomiya, Hyogo 663-8558 Japan
                [4 ]Diabetes Division, Kohnan Kakogawa Hospital, Kakogawa, Hyogo, 675-0005 Japan
                Article
                284
                10.1186/s40200-016-0284-0
                5225506
                © The Author(s). 2016

                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.

                Funding
                Funded by: No
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

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