Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2017

Using the geometric framework to explore the longitudinal effects of dietary macronutrient consumption on markers of diabetic kidney disease (#104)

Amelia K Fotheringham 1 2 , Samantha M Solon-Biet 3 4 5 , Aisling C McMahon 3 4 6 , Bill O Ballard 7 , Kari Ruohonen 8 , Danielle J Borg 1 2 , David Raubenheimer 3 9 , David G Le Couteur 3 4 6 , Stephen J Simpson 3 5 , Josephine M Forbes 1 2
  1. Mater Research-UQ, Woolloongabba, QLD, Australia
  2. Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia
  3. Charles Perkins Centre, University of Sydney, Sydney, New South Wales, Australia
  4. Centre for Education and Research on Aging, and Aging and Alzheimers Institute, Concord Hospital, Sydney, Queensland, Australia
  5. School of Life and Environmental Sciences, , University of Sydney, Sydney, Queensland, Australia
  6. ANZAC Research Institute, Concord Hospital, University of Sydney, , Sydney, New South Wales, Australia
  7. School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia
  8. Cargill Aqua Nutrition, Sandnes, Norway
  9. Faculty of Veterinary Science, University of Sydney, Sydney, New South Wales, Australia

Background: Diabetic kidney disease (DKD), a progressive disorder characterised by changes in glomerular filtration rate (GFR) and structural abnormalities such as tubulointerstitial fibrosis (TIF) and glomerulosclerosis (GS), all of which predict disease progression. Here, we use the geometric framework [1] to assess the effects of 25 macronutrient and caloric combinations on markers of DKD. 

 

Methods: C57BL/6J mice (♂/♀; N=4/group) were given 15 months ad-libitum access to 1 of 25 diets representing a spectrum of macronutrient combinations (protein, (5-60%) carbohydrate (20-75%) and fat (20-75%)), stratified by energy content (low, medium or high). Serum cystatin C (a surrogate for GFR) and DKD risk factors (TIF and GS) were assessed histologically. Three-dimensional models were used to visualise and quantify the impacts of macronutrients, as main effects and interactions using the mgcv package for R. This data was considered in conjunction with existing data for body composition, glucose tolerance, blood pressure, and lipids [1].

 

Results: Serum cystatin C (126 - 1006 ng/ml) was significantly influenced by dietary protein , whereby GFR increased with protein intake (P<.0001). TIF (0.5 - 9%) was influenced by protein consumption in conjunction with either a high fat, or high carbohydrate intake (P=0.0005, P= 0.016; respectively). Overall, lower protein intake in conjunction with higher fat consumption, and therefore calories, resulted in a phenotype with the lowest GFR and the most structural damage, as assessed by TIF and GS. Surprisingly, macronutrient combinations which elevated blood pressure or lipids, or induced glucose intolerance did not associate with adverse kidney outcomes.

 

Conclusions: Macronutrients, individually and in combination influence risk factors for DKD, seemingly independent of other known risk factors.

 

 

 

  1. Solon-Biet, S.M., et al., The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab, 2014. 19(3): p. 418-30.