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

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.

Adiposity Phenotypes and Associated Cardiometabolic Risk Profile in the Inuit Population of Nunavik

“…Beyond body fat distribution, other factors seem to play a significant role in the complex physiological interactions connecting obesity and glucose homeostasis in the Inuit of Nunavik. Among other factors, the traditional diet of Nunavimmiut (low in glucose and rich in protein and long-chain n-3 polyunsaturated fatty acids) might afford protection against cardiometabolic disorders including T2D [ 50 , 51 , 52 ]. Significant differences in Inuit’s microbiota [ 53 ], physical activity level [ 11 ], exposure to persistent organic pollutants [ 52 , 54 ] and genetic variants [ 51 ] might also impact significantly on their cardiometabolic health.…”

“…Among other factors, the traditional diet of Nunavimmiut (low in glucose and rich in protein and long-chain n-3 polyunsaturated fatty acids) might afford protection against cardiometabolic disorders including T2D [ 50 , 51 , 52 ]. Significant differences in Inuit’s microbiota [ 53 ], physical activity level [ 11 ], exposure to persistent organic pollutants [ 52 , 54 ] and genetic variants [ 51 ] might also impact significantly on their cardiometabolic health. For example, a population-specific nonsense genetic variant in TBC1D4, which has a large impact on T2D risk, has recently been identified in Greenlandic, Canadian and Alaskan Inuit [ 51 , 55 ].…”

“…Significant differences in Inuit’s microbiota [ 53 ], physical activity level [ 11 ], exposure to persistent organic pollutants [ 52 , 54 ] and genetic variants [ 51 ] might also impact significantly on their cardiometabolic health. For example, a population-specific nonsense genetic variant in TBC1D4, which has a large impact on T2D risk, has recently been identified in Greenlandic, Canadian and Alaskan Inuit [ 51 , 55 ]. Mutations on TBC1D4 are associated with higher post-prandial glucose and insulin levels.…”