Effects of a highly controlled carbohydrate-reduced high-protein diet on markers of oxidatively generated nucleic acid modifications and inflammation in weight stable participants with type 2 diabetes; a randomized controlled trial

Abstract

Carbohydrate-restricted diets are increasingly recognized as options for dietary management of type 2 diabetes mellitus (T2DM). We investigated the effects of a carbohydrate-reduced high-protein (CRHP) and a conventional diabetes (CD) diet on oxidative stress and inflammation in weight stable individuals with T2DM. We hypothesized that the CRHP diet would improve markers of oxidatively generated RNA and DNA modifications as well as inflammatory parameters. Thirty participants with T2DM were randomized to 6 weeks of CRHP or CD dietary treatment (30/50 energy percentage (E%) carbohydrate, 30/17E% protein, 40/33E% fat), followed by a cross-over to the opposite diet for a subsequent 6-week period. All meals were provided during the study and body weight was controlled. Diurnal urine samples were collected after 4 weeks on each diet and oxidatively generated RNA and DNA modifications were measured as 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), respectively. Fasting concentrations of soluble urokinase plasminogen activator receptor, high-sensitivity C-reactive protein, tumor necrosis factor alpha and interleukin-6 were measured before and after 6 weeks of interventions. Compared with the CD diet, the CRHP diet increased 24-hour urinary excretion of 8-oxoGuo by 9.3% (38.6 ± 12.6 vs. 35.3 ± 11.0 nmol/24 h, p = .03), whereas 8-oxodG did not differ between diets (24.0 ± 9.5 vs. 24.8 ± 11.1 nmol/24 h, p = .17). Changes in plasma inflammatory parameters did not differ between CRHP and CD diets, all p ≥ .2. The clinical implications of increased RNA oxidation following a CRHP diet as well as long-term effects of carbohydrate-restriction on markers of oxidatively generated nucleic acid modifications should be a field of future study.

Keywords:

• Type 2 diabetes mellitus
• diet
• nutrition therapy
• low-grade inflammation
• soluble urokinase plasminogen activator receptor
• oxidative stress
• 8-oxo-7
• 8-dihydroguanosine; 8-oxo-7
• 8-dihydro-2′-deoxyguanosine

Acknowledgement

We thank Centre for Physical Activity Research, Rigshospitalet, Denmark for kindly analyzing IL-6 and TNF-α, laboratory technician Katja L. Christensen for the analysis of 8-oxoGuo and 8-oxodG, and Clinical Research Center, University Hospital Amager and Hvidovre, Denmark for analyzing suPAR. Foremost, we are grateful for the participants contribution making this study possible.

Disclosure statement

Steen Bendix Haugaard and Ove Andersen are co-inventors on a patent on suPAR owned by University Hospital Hvidovre, Denmark. Arne Astrup (AA) is member of advisory boards/consultant for: Acino, Switzerland; BioCare Copenhagen, DK; Dutch Beer Institute, NL; Gelesis, USA; Groupe Éthique et Santé, France; IKEA Food Scientific Health Advisory Board, SE; McCain Foods Limited, USA; Navamedic, DK; Novo Nordisk, DK; Pfizer, USA; Saniona, DK; Weight Watchers, USA; Zaluvida, Switzerland. Recipient of travel grants and honoraria as speaker for a wide range of Danish and international concerns. AA is co-owner and member of the board of the consultancy company Dentacom Aps, Denmark, co-founder and co-owner of UCPH spin-outs Mobile Fitness A/S, Flaxslim ApS, & Personalized Weight Management Research Consortium ApS, (Gluco-diet.dk). AA is co-inventor of a number of patents owned by UCPH, in accordance with Danish law. AA is co-author of a number of diet and cookery books, including books on personalized diet. AA is not advocate or activist for specific diets, and is not strongly committed to any specific diet, e.g. veganism, Atkins diet, gluten-free diet, high animal protein diet, or dietary supplements. Thomas Meinert Larsen is advisor for ‘Sense’ diet program. None of the other authors have conflicts of interest to declare.

Additional information

Funding

The study was funded by a grant from Arla Food for Health, Institute of Clinical Medicine, Aarhus University, Aarhus, Denmark, Novo Nordisk Foundation Center for Basic Metabolic Research, and Department of Biomedical Sciences University of Copenhagen, Copenhagen, Denmark, Dept. of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark and Copenhagen University Hospital Bispebjerg. Arla Foods, JAN Import A/S, Royal Greenland and Danish Crown contributed with ingredients included in the study meal production.