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Original Investigation |

Diet and Kidney Disease in High-Risk Individuals With Type 2 Diabetes Mellitus

Daniela Dunkler, PhD1,2,3; Mahshid Dehghan, PhD1; Koon K. Teo, PhD1; Georg Heinze, PhD3; Peggy Gao, MSc1; Maria Kohl, MSc1,2,3; Catherine M. Clase, MB4; Johannes F. E. Mann, MD2,5; Salim Yusuf, DPhil1; Rainer Oberbauer, MD6 ; for the ONTARGET Investigators
[+] Author Affiliations
1Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
2Department of Nephrology, Universitaetsklinikum Erlangen, Erlangen, Germany
3Section of Clinical Biometrics, Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria
4Department of Medicine, McMaster University, Hamilton, Ontario, Canada
5Schwabing General Hospital, and KfH Kidney Center, Munich, Germany
6Krankenhaus der Elisabethinen, Linz, Austria, and Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria
JAMA Intern Med. 2013;173(18):1682-1692. doi:10.1001/jamainternmed.2013.9051.
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Importance  Type 2 diabetes mellitus and associated chronic kidney disease (CKD) have become major public health problems. Little is known about the influence of diet on the incidence or progression of CKD among individuals with type 2 diabetes.

Objective  To examine the association between (healthy) diet, alcohol, protein, and sodium intake, and incidence or progression of CKD among individuals with type 2 diabetes.

Design, Setting, and Participants  All 6213 individuals with type 2 diabetes without macroalbuminuria from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET) were included in this observational study. Recruitment spanned from January 2002 to July 2003, with prospective follow-up through January 2008.

Main Outcomes and Measures  Chronic kidney disease was defined as new microalbuminuria or macroalbuminuria or glomerular filtration rate decline of more than 5% per year at 5.5 years of follow-up. We assessed diet using the modified Alternate Healthy Eating Index (mAHEI). The analyses were adjusted for known risk factors, and competing risk of death was considered.

Results  After 5.5 years of follow-up, 31.7% of participants had developed CKD and 8.3% had died. Compared with participants in the least healthy tertile of mAHEI score, participants in the healthiest tertile had a lower risk of CKD (adjusted odds ratio [OR], 0.74; 95% CI, 0.64-0.84) and lower risk of mortality (OR, 0.61; 95% CI, 0.48-0.78). Participants consuming more than 3 servings of fruits per week had a lower risk of CKD compared with participants consuming these food items less frequently. Participants in the lowest tertile of total and animal protein intake had an increased risk of CKD compared with participants in the highest tertile (total protein OR, 1.16; 95% CI, 1.05-1.30). Sodium intake was not associated with CKD. Moderate alcohol intake reduced the risk of CKD (OR, 0.75; 95% CI, 0.65-0.87) and mortality (OR, 0.69; 95% CI, 0.53-0.89).

Conclusions and Relevance  A healthy diet and moderate intake of alcohol may decrease the incidence or progression of CKD among individuals with type 2 diabetes. Sodium intake, within a wide range, and normal protein intake are not associated with CKD.

Trial Registration  clinicaltrials.gov Identifier: NCT00153101

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Figure 1.
Flowchart of Number of Participants and Outcomes at 5.5 Years of Follow-up

GFR indicates glomerular filtration rate; ONTARGET, Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial; and UACR, urinary albumin-creatinine ratio.

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Figure 2.
Single-Variable Multinomial Logit Models Adjusted With Known Confounders

Confounders (at study entry) are age, duration of type 2 diabetes mellitus, albuminuria status, glomerular filtration rate, sex, Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial randomization arms, and urinary-albumin-creatinine ratio (UACR) to progression, which was defined as the difference between the participant-specific cutoff point of developing new microalbuminuria or macroalbuminuria and UACR at baseline on the log scale. Association of modified Alternate Healthy Eating Index (mAHEI) and 24-hour urinary sodium and relative odds (solid line) with 95% CI (shaded area) with chronic kidney disease (CKD) (A) or death (B) and respective histograms. The horizontal line on the top shows tertiles, and the numbers within each tertile give the percentage of participants experiencing the respective event.

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Figure 3.
Forest Plot for Single-Variable Multinomial Logit Models Adjusted With Known Confounders

For confounders, see the legend to Figure 2. If not stated otherwise, food items are given in servings per week. Renal Outcome column gives odds ratios (ORs) comparing participants alive with chronic kidney disease (CKD) with participants alive but without CKD; Death column reports ORs comparing participants who died during follow-up with participants alive without CKD. For continuous independent variables, the ORs for the median of the second tertile (50.0th percentile [solid circle]) and the median of the third tertile (83.3rd percentile [open circle]) compared with the median of the first tertile (16.7th percentile) as reference are given. Independent variables in bold type have a significant association with CKD. The last column states the P value of inclusion of the respective variable. mAHEI indicates modified Alternate Healthy Eating Index.

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Figure 4.
Multivariable Multinomial Logit Model Adjusted With Known Confounders

Association of animal protein, fruits and fruit juices, and leafy green vegetables and relative odds with 95% CI with chronic kidney disease (CKD) (A) or death (B) and respective histograms. For confounders, see the legend to Figure 2. The horizontal line on top shows tertiles, and the numbers within each tertile give the percentage of participants experiencing the respective event. The remaining independent variables of the adjusted multivariable model are depicted in the Supplement (eFigure 3).

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Figure 5.
Multivariable Multinomial Logit Model Adjusted With Known Confounders

Association of alcohol, 24-hour urinary sodium, and 24-hour urinary potassium and relative odds with 95% CI with CKD (A) or death (B) and respective histograms. For confounders, see the legend to Figure 2. The horizontal line on top shows tertiles, and the numbers within each tertile give the percentage of participants experiencing the respective event. The remaining independent variables of the adjusted multivariable model are depicted in the Supplement (eFigure 3).

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Place holder to copy figure label and caption
Figure 6.
Forest Plot for the Multivariable Multinomial Logit Model Adjusted With Known Confounders

For confounders, see legend to Figure 2. If not stated otherwise, food items are given in servings per week. Renal outcome column gives odds ratios (ORs) comparing participants alive with chronic kidney disease (CKD) with participants alive but without CKD; column death reports ORs comparing participants who died during follow-up with participants alive without CKD. For continuous independent variables, the ORs for the median of the second tertile (50.0th percentile [solid circle]) and the median of the third tertile (83.3rd percentile [open circle]) compared with the median of the first tertile (16.7th percentile) as reference are given. Independent variables in bold type have a significant association with CKD. The last column states the P value of inclusion of the respective variable.

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