The effect of traditional diet on glucose homeostasis in carriers and non-carriers of a common TBC1D4 variant in Greenlandic Inuit: A randomized crossover study

Jack Ivor Lewis, Mads Vendelbo Lind, Grith Møller, Torben Hansen, Hanne Pedersen, Marie M B Christensen, Jens C Laursen, Sara Nielsen, Charlotte B Ottendahl, Christina V L Larsen, Ken D Stark, Peter Bjerregaard, Marit E Jørgensen, Lotte Lauritzen*

*Corresponding author for this work

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Abstract

Consumption of traditional foods is decreasing amid a lifestyle transition in Greenland as incidence of type-2 diabetes (T2D) increases. In homozygous carriers of a TBC1D4 variant, conferring postprandial insulin resistance, the risk of developing T2D is markedly higher. We investigated the effects of traditional marine diets on glucose homeostasis and cardio-metabolic health in Greenlandic Inuit carriers and non-carriers of the variant. We conducted a randomized, crossover study consisting of two 4-week dietary interventions; Traditional (marine-based, low-carbohydrate) and Western (high in imported meats and carbohydrates). Oral glucose tolerance (OGTT, 2-h), 14-day continuous glucose and cardio-metabolic markers were assessed to investigate the effect of diet and genotype. Compared to the westernized diet, the Traditional diet reduced mean and maximum daily blood glucose by 0.17 mmol/L [95% CI;0.05, 0.29; P=0.006] and 0.26 mmol/L [95% CI;0.06, 0.46; P=0.010], respectively, with dose-dependency. Furthermore, it gave rise to a weight loss of 0.5 kg [95% CI; 0.09, 0.90; P=0.016] relative to the Western diet and 4% [95% CI;1, 9; P=0.018] lower LDL:HDL-cholesterol, which after adjustment for weight-loss appeared to be driven by HDL elevation (0.09 mmol/L [0.03, 0.15], P=0.006). A diet-gene interaction was indicated on insulin sensitivity in the OGTT (p=0.093), which seemed to reflect a non-significant increase of 1.4 [-0.6, 3.5] mmol/L in carrier 2-h glucose. A Traditional diet marginally improved daily glycaemic control and plasma lipid profile compared to a Western diet in Greenlandic Inuit. Possible adverse effects on glucose tolerance in carriers of the TBC1D4 variant warrants further studies of diet-gene interactions.

Original languageEnglish
JournalBritish Journal of Nutrition
Volume130
Issue number11
Pages (from-to)1871-1884
ISSN0007-1145
DOIs
Publication statusPublished - 2023

Keywords

  • Faculty of Science
  • Marine diet
  • TBC1D4
  • TBC1D4 genotype/p.Arg684er
  • Insulin sensitivity
  • Cardiometabolic markers
  • N-3 LCPUFA
  • Lifestyle transition
  • Greenland

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