TY - JOUR

T1 - 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

AU - Lewis, Jack Ivor

AU - Lind, Mads Vendelbo

AU - Møller, Grith

AU - Hansen, Torben

AU - Pedersen, Hanne

AU - Christensen, Marie M B

AU - Laursen, Jens C

AU - Nielsen, Sara

AU - Ottendahl, Charlotte B

AU - Larsen, Christina V L

AU - Stark, Ken D

AU - Bjerregaard, Peter

AU - Jørgensen, Marit E

AU - Lauritzen, Lotte

N1 - CURIS 2023 NEXS 131

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Faculty of Science

KW - Marine diet

KW - TBC1D4

KW - TBC1D4 genotype/p.Arg684er

KW - Insulin sensitivity

KW - Cardiometabolic markers

KW - N-3 LCPUFA

KW - Lifestyle transition

KW - Greenland

U2 - 10.1017/S000711452300106X

DO - 10.1017/S000711452300106X

M3 - Journal article

C2 - 37129117

VL - 130

SP - 1871

EP - 1884

JO - British Journal of Nutrition

JF - British Journal of Nutrition

SN - 0007-1145

IS - 11

ER -