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      Population-based studies of relationships between dietary acidity load, insulin resistance and incident diabetes in Danes

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          Abstract

          Background

          It has been suggested that the acidity of the diet may be related to increased risk of type 2 diabetes. To investigate this hypothesis, we tested if the acidity of the diet, measured as the Potential Renal Acid Load (PRAL) score, was associated with incident diabetes and diabetes-related intermediary traits.

          Methods

          A total of 54,651 individuals from the Danish Diet, Cancer and Health (DCH) cohort were included in the prospective cox regression analyses of incident diabetes over a 15 years follow-up period. Moreover, 5724 Danish individuals with baseline data from the Inter99 cohort were included in the cross sectional, multivariate and logistic regression analyses of measures of insulin sensitivity, insulin release and glucose tolerance status derived from an oral glucose tolerance test (OGTT).

          Results

          In the DCH cohort a trend analysis showed that quintiles of PRAL score were, after multifactorial adjustment, associated with a higher incidence of diabetes ( p trend = 6 × 10 − 7). HR for incident diabetes was 1.24 (1.14; 1.35) ( p = 7 × 10 − 7) between first and fifth PRAL score quintile.

          In Inter99 higher PRAL score associated with insulin resistance as estimated by lower BIGTT-Si (an OGTT-derived index of insulin sensitivity) ( p = 4 × 10 − 7) and Matsuda index of insulin sensitivity ( p = 2 × 10 − 5) as well as higher HOMA-IR ( p = 0.001). No association was observed for measures of insulin release, but higher PRAL score was associated with lower OGTT-based disposition index.

          Conclusions

          A high dietary acidity load is associated with a higher risk of diabetes among middle-aged Danes. Although adjustment for BMI attenuated the effect sizes the association remained significant. The increased risk of diabetes may be related to our finding that a high dietary acidity load associates with impaired insulin sensitivity.

          Electronic supplementary material

          The online version of this article (10.1186/s12937-018-0395-1) contains supplementary material, which is available to authorized users.

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          Most cited references21

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          Assessment of insulin sensitivity/resistance

          Insulin resistance is one pretty troublesome entity which very commonly aggravates metabolic syndrome. Many methods and indices are available for the estimation of insulin resistance. It is essential to test and validate their reliability before they can be used as an investigation in patients. At present, hyperinsulinemic euglycemic clamp and intravenous glucose tolerance test are the most reliable methods available for estimating insulin resistance and are being used as a reference standard. Some simple methods, from which indices can be derived, have been validated e.g. homeostasis model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI). For the clinical uses HOMA-insulin resistance, QUIKI, and Matsuda are suitable, while HES, McAuley, Belfiore, Cederholm, Avignon and Stumvoll index are suitable for epidemiological/research purposes. With increasing number of these available indices of IR, it may be difficult for clinicians to select the most appropriate index for their studies. This review provides guidelines that must be considered before performing such studies.
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            Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein.

            F Manz, T Remer (1994)
            The object of this study was to determine whether it is possible to reliably estimate the renal net acid excretion (NAE) produced by adults consuming different amounts of dietary protein. A physiologically based calculation model that corrects for intestinal absorption of minerals and sulfur-containing protein and assumes a rate of urinary excretion of organic acids proportional to body surface area was used to estimate NAE. Urinary excretion of different minerals and NAE was measured during the last 48 h of each of four separate 5-d diet periods in six healthy adults. On the basis of food tables, the four nearly isoenergetic diets (one lacto-vegetarian and one high- and two moderate-protein diets) were estimated to yield the following NAE values: 3.7, 117.5, 62.2, and 102.2 mEq/d, respectively. The analytically determined urinary NAE (24.1 +/- 10.7, 135.5 +/- 16.4, 69.7 +/- 21.4, and 112.6 +/- 10.9 mEq/d) corresponded reasonably well to these estimates, suggesting that the calculation model is appropriate to predict the renal NAE from nutrient intake and anthropometric data.
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              Diet-induced metabolic acidosis.

              The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products, generating the accumulation of non-metabolizable anions and a lifespan state of overlooked metabolic acidosis, whose magnitude increases progressively with aging due to the physiological decline in kidney function. In response to this state of diet-derived metabolic acidosis, the kidney implements compensating mechanisms aimed to restore the acid-base balance, such as the removal of the non-metabolizable anions, the conservation of citrate, and the enhancement of kidney ammoniagenesis and urinary excretion of ammonium ions. These adaptive processes lower the urine pH and induce an extensive change in urine composition, including hypocitraturia, hypercalciuria, and nitrogen and phosphate wasting. Low urine pH predisposes to uric acid stone formation. Hypocitraturia and hypercalciuria are risk factors for calcium stone disease. Even a very mild degree of metabolic acidosis induces skeletal muscle resistance to the insulin action and dietary acid load may be an important variable in predicting the metabolic abnormalities and the cardiovascular risk of the general population, the overweight and obese persons, and other patient populations including diabetes and chronic kidney failure. High dietary acid load is more likely to result in diabetes and systemic hypertension and may increase the cardiovascular risk. Results of recent observational studies confirm an association between insulin resistance and metabolic acidosis markers, including low serum bicarbonate, high serum anion gap, hypocitraturia, and low urine pH. Copyright © 2011 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
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                Author and article information

                Contributors
                jgaede@sund.ku.dk
                Trine.nielsen@sund.ku.dk
                vqz109@alumni.ku.dk
                ulla.toft@regionh.dk
                torben.joergensen@regionh.dk
                ko@ph.au.dk
                annet@cancer.dk
                torben.hansen@sund.ku.dk
                kristine.allin@regionh.dk
                +45 29382526 , Oluf@sund.ku.dk
                Journal
                Nutr J
                Nutr J
                Nutrition Journal
                BioMed Central (London )
                1475-2891
                6 October 2018
                6 October 2018
                2018
                : 17
                : 91
                Affiliations
                [1 ]ISNI 0000 0001 0674 042X, GRID grid.5254.6, The Novo Nordisk Foundation Center for Basic Metabolic Research, Section of Metabolic Genetics, Faculty of Health and Medical Sciences, , University of Copenhagen, ; Blegdamsvej 3B, DK-2200 Copenhagen, Denmark
                [2 ]ISNI 0000 0004 0441 3048, GRID grid.415878.7, Research Centre for Prevention and Health, ; Copenhagen, the Capital Region of Denmark Denmark
                [3 ]ISNI 0000 0001 0674 042X, GRID grid.5254.6, Department of Public Health, Faculty of Health and Medical Sciences, , University of Copenhagen, ; Copenhagen, Denmark
                [4 ]ISNI 0000 0001 0742 471X, GRID grid.5117.2, Faculty of Medicine, , Aalborg University, ; Aalborg, Denmark
                [5 ]ISNI 0000 0001 2175 6024, GRID grid.417390.8, Danish Cancer Society Research Center, ; Copenhagen, Denmark
                [6 ]ISNI 0000 0000 9350 8874, GRID grid.411702.1, Department of Clinical Epidemiology, , Bispebjerg and Frederiksberg Hospital, ; Copenhagen, the Capital Region of Denmark Denmark
                Author information
                http://orcid.org/0000-0002-3321-3972
                Article
                395
                10.1186/s12937-018-0395-1
                6173920
                30292239
                b80307ec-e1f7-4b6c-8969-30ebcd874f67
                © The Author(s). 2018

                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 2018
                : 14 September 2018
                Categories
                Research
                Custom metadata
                © The Author(s) 2018

                Nutrition & Dietetics
                dietary acid load,pral,glucose,insulin resistance,disposition index,type 2 diabetes

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