Reproducibility and validity of a 45 item food-frequency questionnaire for inuit in Greenland.

Since 1993, dietary assessment has been carried out in Greenland as part of recurrent population health surveys. In preparation for the next survey in 2024, 91 participants from the survey in 2018 were selected for a validation study of the Food Frequency Questionnaire (FFQ). The 91 participants were reinterviewed 38-50 months after the first FFQ and invited to complete a food diary. As part of the 2018 survey, blood was analysed for mercury. The food diary was completed by 65 participants. The agreement between the two FFQ interviews was very good for macronutrients and fatty acids (p > 0.20), whereas the calculated intake of mercury was 22% higher in the second FFQ (p = 0.04) due to a higher intake of whale meat and muktuk (whale skin). The agreement between the second FFQ and the food diary was good for local food, imported meat and cakes/sweets/snacks but fruit and vegetables, dairy products, beverages and added sugar were significantly underreported in the food diary. Food items not included in the FFQ were identified from the food diaries. The correlation between the intake of marine mammals and blood mercury was moderate (Spearman's rho = 0.41-0.50; p < 0.0001). The results will inspire future dietary studies in the circumpolar North.

Increasing health inequality among Inuit in Greenland from 1993 to 2018: Different patterns for household assets, urbanization and a sociocultural index as indicators of social position.

Income inequality affects population health and wellbeing negatively. In Greenland, health inequality has been shown to exist among social groups, regionally and according to urbanization, and between Inuit and migrants from Denmark. The purpose of the study was to compare the changes in health inequality from 1993 to 2018 according to three measures of social position, i.e. a socioeconomic measure (household assets), a measure of urbanization and a composite sociocultural index. We hypothesized that social inequality in health increased parallel to the increasing economic inequality in Greenland. The sample was based on four population health surveys conducted among the Inuit in Greenland in 1993, 2005-2010, 2014 and 2018. The total number of interviews was 9024 and the total number of individuals interviewed was 5829, as participants were invited to several surveys as part of a cohort. As statistical measure of social disparity we used the slope index of inequality (SII) adjusted for age and sex. Analyses were performed with daily smoking, suicidal thoughts and obesity as health outcomes. Daily smoking was most prevalent among participants with low social position whereas obesity was most prevalent among participants with high social position. With household assets as indicator of social position, the results showed high and increasing social inequality for both daily smoking and obesity. Social inequality for daily smoking increased over time also for urbanization and the sociocultural index. The hypothesis that social inequality increased over time was thus confirmed for daily smoking and obesity but not for suicidal thoughts. With the results from the present study there is solid evidence to guide prevention and health care towards social equality in health.

GWAS of lipids in Greenlanders finds association signals shared with Europeans and reveals an independent PCSK9 association signal.

Perturbation of lipid homoeostasis is a major risk factor for cardiovascular disease (CVD), the leading cause of death worldwide. We aimed to identify genetic variants affecting lipid levels, and thereby risk of CVD, in Greenlanders. Genome-wide association studies (GWAS) of six blood lipids, triglycerides, LDL-cholesterol, HDL-cholesterol, total cholesterol, as well as apolipoproteins A1 and B, were performed in up to 4473 Greenlanders. For genome-wide significant variants, we also tested for associations with additional traits, including CVD events. We identified 11 genome-wide significant loci associated with lipid traits. Most of these loci were already known in Europeans, however, we found a potential causal variant near PCSK9 (rs12117661), which was independent of the known PCSK9 loss-of-function variant (rs11491147). rs12117661 was associated with lower LDL-cholesterol (ßSD(SE) = -0.22 (0.03), p = 6.5 × 10-12) and total cholesterol (-0.17 (0.03), p = 1.1 × 10-8) in the Greenlandic study population. Similar associations were observed in Europeans from the UK Biobank, where the variant was also associated with a lower risk of CVD outcomes. Moreover, rs12117661 was a top eQTL for PCSK9 across tissues in European data from the GTEx portal, and was located in a predicted regulatory element, supporting a possible causal impact on PCSK9 expression. Combined, the 11 GWAS signals explained up to 16.3% of the variance of the lipid traits. This suggests that the genetic architecture of lipid levels in Greenlanders is different from Europeans, with fewer variants explaining the variance.

Developing the ACEIG-scale: An adverse childhood experience scale for Inuit youth in Greenland.

BACKGROUND: Adverse Childhood Experiences (ACEs) have been identified as a major public health challenge in Greenland. No previous studies have created a multi-item ACE- scale among an Arctic Indigenous population. OBJECTIVE: To develop a multi-item ACE-scale among Inuit youth in Greenland (the ACEIG scale). METHODS: The ACEIG scale was created with data from the 'Wellbeing among Inuit youth in Greenland'-survey. Scale items were based on a recognised ACE-scale and further adapted to the context of Inuit youth in Greenland by adding items relevant for the population. The scale was validated through item response theory (IRT) and reliability was assessed by Cronbach's alpha. RESULTS: Four items relevant for Inuit youth in Greenland were added to the recognised ACE scale (bullying, death of parent, gambling problems in close family, and suicide in close relations). The scale was reduced by IRT, as three items (bullying, divorce of parents and parents passing away) exceeded the difficulty index threshold. The ACEIG scale therefore consists of 10 items: alcohol problems in close family, marijuana use in close family, domestic violence, being victim of physical violence, being victim of psychological violence, any type of sexual abuse, sexual abuse (intercourse), sexual abuse (more than once), suicide in close relations, and gambling problems in close family. Cronbach's alpha was 0.7. CONCLUSION: The ACEIG scale includes 10 items with acceptable reliability. The scale can inform future screening tools to identify vulnerable youth and target interventions. Future studies should investigate the association between the ACEIG scale and health outcomes.

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.

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 T2D is markedly higher. We investigated the effects of traditional marine diets on glucose homoeostasis and cardio-metabolic health in Greenlandic Inuit carriers and non-carriers of the variant in a randomised 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 test (OGTT, 2-h), 14-d continuous glucose and cardio-metabolic markers were assessed to investigate the effect of diet and genotype. Compared with the Western 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 reflected 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 with a Westernised diet in Greenlandic Inuit. Possible adverse effects on glucose tolerance in carriers of the TBC1D4 variant warrant further studies.

The effect of diabetes and the diabetogenic TBC1D4 p.Arg684ter variant on kidney function in Inuit in Greenland.

The aim of this study was to examine the effect of diabetes and the diabetogenic TBC1D4 variant on kidney function in Greenland in a population-based setting. Health survey data and TBC1D4 genotypes from 5,336 Greenlanders were used to estimate odds ratios (ORs) of albuminuria (>30 mg/g creatinine) and chronic kidney disease (CKD, eGFR <60 ml/min/1.73m2), comparing individuals with and without diabetes, including the effect of TBC1D4 variant. Of the 3,909 participants with complete data, 9.3% had diabetes. Albuminuria was found in 27.6% and 9.5% and CKD was found in 10.8% and 6.3% among those with and without diabetes, respectively. Diabetes was cross-sectionally associated with an increased risk of albuminuria (OR (95% CI) = 2.37 (1.69,3.33); p < 0.001) and the TBC1D4 variant protected against albuminuria (OR (95% CI) = 0.44 (0.22,0.90); p = 0.02) in a multivariable model. Neither diabetes nor the TBC1D4 variant significantly associated with CKD. The presence/absence of diabetes did not predict changes in eGFR and UACR in longitudinal analyses. Diabetes conferred an increased risk of albuminuria, and the TBC1D4 variant was associated with a decreased risk of albuminuria, but neither was associated with CKD. The potential renoprotective association of the TBC1D4 variant on albuminuria calls for further studies.

Time trends and geographical patterns in suicide among Greenland Inuit.

BACKGROUND: Between 1980 and 2018 Greenland has had one of the highest suicide rates in the world with an average rate of 96 suicides per 100,000 people annually. The aim of this study is to investigate suicide rates in Greenland according to age, birth cohort, period, sex, place of residence and suicide method from 1970 until 2018. METHODS: Suicide rates were examined using register and census data from 1970-2018 among Greenland Inuit. Rates were calculated by Poisson regression in Stata and by use of Excel. In analyses of the period trends, rates were standardized according to the World Standard Population 2000-2025. RESULTS: The suicide rate has been declining since a peak at 120 suicides per 100,000 people annually in the 1980s but remained high at a rate of 81.3 suicides per 100,000 people annually from 2015-2018. Descriptive analyses point to the decrease in male suicides as the primary factor for the overall decreasing rates while the rate among women has been increasing. Simultaneously, the proportion of women who used a violent suicide method increased from 60% in 1970-1979 to 90% in 2010-2018. The highest rates are seen among young people, especially young men aged 20-24 years and youth suicide rates increased with later birth cohorts. When the rates started to increase in the 1980s both the capital Nuuk and East Greenland had the highest rates. Since then, the rate in Nuuk has declined while the rate in East Greenland was three times the national rate from 2015-2018. CONCLUSIONS: From 1970 to 1989 the suicide rate increased from 28.7 to 120.5 per 100,000 people mirroring a rapid societal transition in the post-colonial period. The rate has slowly declined from the peak in the 1980s but remains at a very high level. Young people in general are at risk, but the steady increase in the rate among women is worrying and there is a need to investigate underlying causes for this development.

Muscular strength, mobility in daily life and mental wellbeing among older adult Inuit in Greenland. The Greenland population health survey 2018.

The purpose was to analyse the association of muscular strength, muscle pain and reduced mobility in daily life with mental wellbeing among older Inuit men and women in Greenland. Data (N = 846) was collected as part of a countrywide cross-sectional health survey in 2018. Hand grip strength and 30-seconds chair stand test were measured according to established protocols. Mobility in daily life was assessed by five questions about the ability to perform specific activities of daily living. Mental wellbeing was assessed by questions about self-rated health, life satisfaction and Goldberg's General Health Questionnaire. In binary multivariate logistic regression models adjusted for age and social position, muscular strength (OR 0.87-0.94) and muscle pain (OR 1.53-1.79) were associated with reduced mobility. In fully adjusted models, muscle pain (OR 0.68-0.83) and reduced mobility (OR 0.51-0.55) but were associated with mental wellbeing. Chair stand score was associated with life satisfaction (OR 1.05). With an increasingly sedentary lifestyle, increasing prevalence of obesity and increasing life expectancy the health consequences of musculoskeletal dysfunction are expected to grow. Prevention and clinical handling of poor mental health among older adults need to consider reduced muscle strength, muscle pain and reduced mobility as important determinants.

A novel splice-affecting HNF1A variant with large population impact on diabetes in Greenland.

Background: The genetic disease architecture of Inuit includes a large number of common high-impact variants. Identification of such variants contributes to our understanding of the genetic aetiology of diseases and improves global equity in genomic personalised medicine. We aimed to identify and characterise novel variants in genes associated with Maturity Onset Diabetes of the Young (MODY) in the Greenlandic population. Methods: Using combined data from Greenlandic population cohorts of 4497 individuals, including 448 whole genome sequenced individuals, we screened 14 known MODY genes for previously identified and novel variants. We functionally characterised an identified novel variant and assessed its association with diabetes prevalence and cardiometabolic traits and population impact. Findings: We identified a novel variant in the known MODY gene HNF1A with an allele frequency of 1.9% in the Greenlandic Inuit and absent elsewhere. Functional assays indicate that it prevents normal splicing of the gene. The variant caused lower 30-min insulin (ß = -232 pmol/L, ßSD = -0.695, P = 4.43 × 10-4) and higher 30-min glucose (ß = 1.20 mmol/L, ßSD = 0.441, P = 0.0271) during an oral glucose tolerance test. Furthermore, the variant was associated with type 2 diabetes (OR 4.35, P = 7.24 × 10-6) and HbA1c (ß = 0.113 HbA1c%, ßSD = 0.205, P = 7.84 × 10-3). The variant explained 2.5% of diabetes variance in Greenland. Interpretation: The reported variant has the largest population impact of any previously reported variant within a MODY gene. Together with the recessive TBC1D4 variant, we show that close to 1 in 5 cases of diabetes (18%) in Greenland are associated with high-impact genetic variants compared to 1-3% in large populations. Funding: Novo Nordisk Foundation, Independent Research Fund Denmark, and Karen Elise Jensen's Foundation.

An LDLR missense variant poses high risk of familial hypercholesterolemia in 30% of Greenlanders and offers potential of early cardiovascular disease intervention.

The common Arctic-specific LDLR p.G137S variant was recently shown to be associated with elevated lipid levels. Motivated by this, we aimed to investigate the effect of p.G137S on metabolic health and cardiovascular disease risk among Greenlanders to quantify its impact on the population. In a population-based Greenlandic cohort (n = 5,063), we tested for associations between the p.G137S variant and metabolic health traits as well as cardiovascular disease risk based on registry data. In addition, we explored the variant's impact on plasma NMR measured lipoprotein concentration and composition in another Greenlandic cohort (n = 1,629); 29.5% of the individuals in the cohort carried at least one copy of the p.G137S risk allele. Furthermore, 25.4% of the heterozygous and 54.7% of the homozygous carriers had high levels (>4.9 mmol/L) of serum LDL cholesterol, which is above the diagnostic level for familial hypercholesterolemia (FH). Moreover, p.G137S was associated with an overall atherosclerotic lipid profile, and increased risk of ischemic heart disease (HR [95% CI], 1.51 [1.18-1.92], p = 0.00096), peripheral artery disease (1.69 [1.01-2.82], p = 0.046), and coronary operations (1.78 [1.21-2.62], p = 0.0035). Due to its high frequency and large effect sizes, p.G137S has a marked population-level impact, increasing the risk of FH and cardiovascular disease for up to 30% of the Greenlandic population. Thus, p.G137S is a potential marker for early intervention in Arctic populations.

Exploring sex-specific time trends in drinking patterns in the Greenlandic population from 1993 to 2014 - a large Arctic Indigenous population.

A drinking pattern characterised by occasional excessive drinking is a key challenge for public health in Greenland. The objective was to examine sex-specific time trends in drinking patterns among Greenland Inuit. Cross-sectional and cohort data from geographically representative health surveys in 1993, 2005-2010 and 2014 were included (n = 4,938). Drinking patterns were defined as abstainer, non-problematic and occasional binge drinking. Patterns were analysed by sex-specific crude proportions and logistical analyses according to age, birth cohort and calendar time, accounting for region and settlement type. More than half of the men and one-third of the women had an occasional binge drinking pattern, while 22.6% of females and 15.1% of men were abstainers. Abstention increased with increasing age, while occasional binge drinking decreased among men. Younger male birth cohorts were less likely to have an occasional binge drinking pattern, while the youngest females had the highest odds ratio. A drinking pattern characterised by occasional excessive use remains a key challenge for public health in Greenland with age as a strong predictor. A high prevalence of abstainers co-exists with a high prevalence of occasional binge drinking. The increased odds ratio for occasional binge drinking among younger females should be addressed further.

The Greenland population health survey 2018 - methods of a prospective study of risk factors for lifestyle related diseases and social determinants of health amongst Inuit.

Since 1993, regular population health surveys in Greenland have supported and monitored the public health strategy of Greenland and have monitored cardiometabolic and lung diseases. The most recent of these surveys included 2539 persons aged 15+ from 20 communities spread over the whole country. The survey instruments included personal interviews, self-administered questionnaires, blood sampling, anthropometric measurements, blood pressure, ECG, oral glucose test, pulmonary function, hand grip strength and chair stand test. Blood samples were analysed for glucose, glycated haemoglobin (HbA1c), insulin, incretin hormones, cholesterol, kidney function, fatty acids in erythrocyte membranes and mercury, urine for albumin-creatinine ratio, and aliquots were stored at -80°C for future use. Data were furthermore collected for studies of the gut microbiome and diabetes complications. Survey participants were followed up with register data. The potential of the study is to contribute to the continued monitoring of risk factors and health conditions as part of Greenland's public health strategy and to study the epidemiology of cardiometabolic diseases and other chronic diseases and behavioural risk factors. The next population health survey is planned for 2024. The emphasis of the article is on the methods of the study and results will be presented in other publications.

Background 210Po activity concentrations in Greenland marine biota and dose assessment.

Polonium-210 (210Po) is a radionuclide sentinel as it bioaccumulates in marine organisms, thereby being the main contributor to committed dietary doses in seafood consumers. Although seafood and marine mammals are an important part of the traditional Inuit diet, there is a general lack of information on the 210Po concentrations in the Greenlandic marine food chain leading to the human consumer. Here, we determine background 210Po concentrations in edible parts of different marine organisms from Greenland and provide a dose assessment. Blue mussels (Mytilus edulis), organs of ringed seal (Pusa hispida) and polar bear (Ursus maritimus) displayed significantly elevated 210Po concentrations in respect to all other studied organisms (p < 0.001). 210Po concentrations ranged from 0.02 Bq kg-1, w.w. in Greenland halibut (Reinhardtius hippoglossoides) muscle to 78 Bq kg-1, w.w. and 202 Bq kg-1, w.w. in ringed seal muscle and kidneys, respectively. 210Po concentration ratio for edible parts increases in the order bladderwrack (Fucus Vesiculosus), northern shrimp (Pandalus borealis), blue mussels, and from fish species to ringed seal and polar bear. 210Po distribution in fish, ringed seal, and polar bear follows a general pattern, the lowest concentrations were in muscle, and the highest concentrations were in the organs involved in metabolism. The derived 210Po annual absorbed dose in edible parts of studied marine organisms are several orders of magnitude lower than the recommended dose rate screening value of 10 µGy h-1. Effective doses from intake of 210Po to Greenland average children (1.4 mSv y-1), and high seafood and marine mammal consumers (2 mSv y-1 for adults and 3.6 mSv y-1 for children) are higher than the world average annual effective dose due to ingestion of naturally occurring radionuclides.

Loss of Sucrase-Isomaltase Function Increases Acetate Levels and Improves Metabolic Health in Greenlandic Cohorts.

BACKGROUND & AIMS: The sucrase-isomaltase (SI) c.273_274delAG loss-of-function variant is common in Arctic populations and causes congenital sucrase-isomaltase deficiency, which is an inability to break down and absorb sucrose and isomaltose. Children with this condition experience gastrointestinal symptoms when dietary sucrose is introduced. We aimed to describe the health of adults with sucrase-isomaltase deficiency. METHODS: The association between c.273_274delAG and phenotypes related to metabolic health was assessed in 2 cohorts of Greenlandic adults (n = 4922 and n = 1629). A sucrase-isomaltase knockout (Sis-KO) mouse model was used to further elucidate the findings. RESULTS: Homozygous carriers of the variant had a markedly healthier metabolic profile than the remaining population, including lower body mass index (ß [standard error], -2.0 [0.5] kg/m2; P = 3.1 × 10-5), body weight (-4.8 [1.4] kg; P = 5.1 × 10-4), fat percentage (-3.3% [1.0%]; P = 3.7 × 10-4), fasting triglyceride (-0.27 [0.07] mmol/L; P = 2.3 × 10-6), and remnant cholesterol (-0.11 [0.03] mmol/L; P = 4.2 × 10-5). Further analyses suggested that this was likely mediated partly by higher circulating levels of acetate observed in homozygous carriers (ß [standard error], 0.056 [0.002] mmol/L; P = 2.1 × 10-26), and partly by reduced sucrose uptake, but not lower caloric intake. These findings were verified in Sis-KO mice, which, compared with wild-type mice, were leaner on a sucrose-containing diet, despite similar caloric intake, had significantly higher plasma acetate levels in response to a sucrose gavage, and had lower plasma glucose level in response to a sucrose-tolerance test. CONCLUSIONS: These results suggest that sucrase-isomaltase constitutes a promising drug target for improvement of metabolic health, and that the health benefits are mediated by reduced dietary sucrose uptake and possibly also by higher levels of circulating acetate.

Concentrations of tetanus and diphtheria antibodies in vaccinated Greenlandic children aged 7-12 years exposed to marine pollutants, a cross sectional study.

Previous studies have shown immunotoxic effects of environmental chemicals, and the European Food Safety Authority (EFSA) recently identified a need for more studies on PFAS immunotoxicity in different populations. In the Arctic, populations are exposed to several environmental chemicals through marine diet, and the objective of this study was therefore to examine the association between Greenlandic children's exposure to major environmental chemicals and their concentrations of diphtheria and tetanus vaccine antibodies after vaccination. The study includes cross-sectional data from Greenlandic children aged 7-12 years examined during 2012-2015. A total of 338 children were eligible for the study, and 175 of these had available vaccination records. A parent or guardian participated in a structured interview, and a blood sample from the child was analyzed for specific antibodies against diphtheria and tetanus as well as perfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs) and total mercury. Furthermore, for a subgroup, blood samples from pregnancy were available and analyzed for environmental contaminants. The associations between the environmental exposures and antibody concentrations and odds of having antibody concentrations below the protective level were examined in linear and logistic regression models. In crude analyses, elevated concentrations of some of the contaminants were associated with higher concentrations of diphtheria and tetanus antibodies, but the associations were reversed when adjusting for area of residence, and duration of being breastfed and including children with a known vaccination date only. Each 1 ng/mL increase in serum concentrations of perfluorohexane sulfonic acid (PFHxS) and perfluorooctane sulfonic acid (PFOS) was associated with decreases of 78 % (95 % CI: 25-94 %) and 9 % (95 % CI: 2-16 %), respectively, in diphtheria antibody concentrations. Exposure to PCBs and all PFASs was associated with markedly increased odds of having diphtheria antibody concentrations below the protective level. For each 1 ng/mL increase in serum concentrations of PFHxS, PFOS, perfluorononanoic acid (PFNA), and perfluorodecanoic acid (PFDA), odds of not having protective levels of diphtheria antibodies were increased 6.44 times (95 % CI: 1.51-27.36), 1.14 times (95 % CI: 1.04-1.26), 1.96 times (95 % CI: 1.07-3.60), and 5.08 times (95 % CI: 1.32-19.51, respectively. No consistent associations were seen between maternal contaminant concentrations and vaccine antibody concentrations. In conclusion, we found that increased exposure to environmental chemicals among children in this Arctic population were associated with a decrease in post-vaccination antibody concentrations and with increased odds of not being protected against diphtheria despite appropriate vaccination. These findings emphasize the risk of environmental chemical exposures also in this Arctic population.

Hand grip strength and chair stand test amongst Greenlandic Inuit: reference values and international comparisons.

Muscle strength is an important predictor for function and mortality among older adults. We measured hand grip strength among 1442 participants aged 15+ years and carried out a 30 second chair stand test among 786 participants aged 55+ years. Neither test has been carried out among the Inuit before. We present reference values for men and women as means with standard deviations and medians with 10th, 25th, 75th and 90th percentiles. Hand grip strength was higher among men than among women (means 45.2 kg and 25.8 kg; p < 0.0001), in linear regression analyses it increased with height (ßmen = 0.69; ßwomen = 0.46), weight (ßmen = 0.24; ßwomen = 0.08) and body mass index (ßmen = 0.56; ßwomen = 0.24), and decreased with age (ßmen = -0.49; ßwomen = -0.29) and Inuit genetic ancestry (ßmen = -0.96; ßwomen = -0.59). Chair stand score showed similar associations with sex (mean score for men and women 13.8 and 11.5; p < 0.0001), age (ßmen = -0.22; ßwomen = -0.20) and Inuit genetic ancestry (ßmen = -0.38; ßwomen = -0.41). The hand grip strength of the Inuit was at the same level as in European and North American populations whereas chair stand score was lower than that of a mostly white US population.

Diet and physical activity in Greenland: genetic interactions and associations with obesity and diabetes.

The Inuit in Greenland have gone through dramatic lifestyle changes during the last half century. More time is spent being sedentary and imported foods replaces traditional foods like seal and whale. The population has also experienced a rapid growth in obesity and metabolic disturbances and diabetes is today common despite being almost unknown few decades ago. In this paper, we describe and discuss the role of lifestyle changes and genetics for Inuit metabolic health. Novelty: Cardiometabolic disease risk has increased in Greenland. Lifestyle changes and possibly gene-lifestyle interactions play a role.

Association of food insecurity with dietary patterns and expenditure on food, alcohol and tobacco amongst indigenous Inuit in Greenland: results from a population health survey.

BACKGROUND: Amongst the indigenous Greenlandic Inuit, the experience of food insecurity has been attributed to a lack of money to buy enough food of sufficient quality to sustain a family, although a preference for alcohol and tobacco over food has also been cited. The purpose of the article was to compare dietary patterns and expenditure on food, alcoholic beverages and tobacco between survey participants who reported food insecurity and those who did not. METHODS: A countrywide cross-sectional health survey was carried out among 1886 adult Greenlandic Inuit in 2018. Diet was estimated by a food frequency questionnaire. Food insecurity status was based on the household hunger scale. Analyses were carried out by univariate general linear models adjusted for age, sex and social position. RESULTS: Nine percent of the participants reported food insecurity. Food insecurity was higher among younger participants, men and participants with low social position. Food insecure participants more often chose an unhealthy dietary pattern (43% vs. 32%) and they reported a higher energy intake. The food insecure spent the same amount of money on food as other participants but less on nutritious food and more on non-nutritious food. The cost per kilojoule (kJ) of the food of the food insecure was lower than that of the food secure (DKK 8.0 and 9.0 per 1000 kJ, respectively). The food insecure participants also spent considerably more on alcohol and tobacco. CONCLUSIONS: The results suggest that it is not only unemployment and lack of money that creates food insecurity and unhealthy dietary patterns in Greenland. Food insecure participants gave higher priority to buying non-nutritious food, alcohol and tobacco than did food secure participants. There seems to be at least two population subgroups in Greenland with poverty and substance use, respectively, as the immediate determinants for food insecurity. The results are important for the design of interventions against food insecurity and unhealthy dietary patterns.

Physical activity attenuates postprandial hyperglycaemia in homozygous TBC1D4 loss-of-function mutation carriers.

AIMS/HYPOTHESIS: The common muscle-specific TBC1D4 p.Arg684Ter loss-of-function variant defines a subtype of non-autoimmune diabetes in Arctic populations. Homozygous carriers are characterised by elevated postprandial glucose and insulin levels. Because 3.8% of the Greenlandic population are homozygous carriers, it is important to explore possibilities for precision medicine. We aimed to investigate whether physical activity attenuates the effect of this variant on 2 h plasma glucose levels after an oral glucose load. METHODS: In a Greenlandic population cohort (n = 2655), 2 h plasma glucose levels were obtained after an OGTT, physical activity was estimated as physical activity energy expenditure and TBC1D4 genotype was determined. We performed TBC1D4-physical activity interaction analysis, applying a linear mixed model to correct for genetic admixture and relatedness. RESULTS: Physical activity was inversely associated with 2 h plasma glucose levels (ß[main effect of physical activity] -0.0033 [mmol/l] / [kJ kg-1 day-1], p = 6.5 × 10-5), and significantly more so among homozygous carriers of the TBC1D4 risk variant compared with heterozygous carriers and non-carriers (ß[interaction] -0.015 [mmol/l] / [kJ kg-1 day-1], p = 0.0085). The estimated effect size suggests that 1 h of vigorous physical activity per day (compared with resting) reduces 2 h plasma glucose levels by an additional ~0.7 mmol/l in homozygous carriers of the risk variant. CONCLUSIONS/INTERPRETATION: Physical activity improves glucose homeostasis particularly in homozygous TBC1D4 risk variant carriers via a skeletal muscle TBC1 domain family member 4-independent pathway. This provides a rationale to implement physical activity as lifestyle precision medicine in Arctic populations. DATA REPOSITORY: The Greenlandic Cardio-Metabochip data for the Inuit Health in Transition study has been deposited at the European Genome-phenome Archive ( https://www.ebi.ac.uk/ega/dacs/EGAC00001000736 ) under accession EGAD00010001428.