Personal experiences of living with sucrose intolerance and attitudes towards genetic research in Greenland - a user study.

There is high prevalence of the genetic SI variant c.273_274delAG in the sucrase-isomaltase-encoding gene in Greenland, resulting in congenital sucrase-isomaltase deficiency and thereby an inability to digest sucrose, the most common dietary sugar. There are no studies of Greenlanders' everyday experiences of sucrose intolerance related to this genetic variant. This study therefore explored, how Greenlandic people experience sucrose intolerance influences life and their attitudes towards research in health and genetics. The study is qualitative, using semi-structured focus groups and/or individual telephone interviews. The analysis was based on the phenomenological-hermeneutic approach of Paul Ricoeur, consisting naïve reading, structural analysis, interpretation and discussion. We identified two themes; "Sucrose intolerance impacts daily living", dealt with physical and emotional reactions and coping with social adaption to activities. And "openness to participate in genetic and health research" were caused by participants wanting more knowledge to improve their people and family's life. The study concluded that most of the participants with symptoms of sucrose intolerance experienced the impact in their daily life, both physically, emotionally, and socially. Further, they expressed openness to participate in health and genetic research. There is a need for more accessible health knowledge and support from health care to manage sucrose intolerance.

Vision screening and refraction of Greenlandic schoolchildren.

PURPOSE: To estimate the prevalence of amblyopia and refractive errors among 6-year-old children in Greenland and to assess the impact of incorporating autorefraction, stereoacuity and near visual acuity testing into vision screening. METHODS: In this cross-sectional study, 517 children (238 girls and 279 boys) from 21 locations in Greenland were screened using HOTV charts for distance and near visual acuity (VA), stereoacuity test and non-cycloplegic autorefraction. Referral criteria for further ophthalmological examination included a VA of ≥0.2 logMAR on the worse-seeing eye or an interocular VA difference of ≥2 lines. RESULTS: Initial screening identified amblyopia (defined as VA of ≥0.3 logMAR) in 7% (unilateral) and 3% (bilateral) of children. However, subsequent ophthalmological examinations confirmed amblyopia in under 40% of referrals. Significant interocular VA differences were found in 9%. The prevalence of refractive errors at the screening was 3% for myopia (≤-0.5 dioptres), 10% for hyperopia (>+2.0 dioptres) and 14% for astigmatism (≤-1.00 dioptres), while the corresponding prevalences at the ophthalmological examination were 4% for myopia, 8% for hyperopia and 6% for astigmatism. Combining screening measurements increased the positive predictive values, thereby enhancing screening accuracy. Specifically, the incorporation of autorefraction or stereoacuity with distance VA demonstrated to be the most effective combination. Six percent of the children were prescribed glasses after the screening procedure. CONCLUSION: This study provides the first visual profile of Greenlandic schoolchildren. Incorporating autorefraction, stereoacuity and near visual acuity in vision screenings enhanced the efficacy of detection of vision anomalies. Although this may lead to more false positives, accurate screening is crucial in regions with limited ophthalmological resources.

Analysis of admixed Greenlandic siblings shows that the mean genotypic values for metabolic phenotypes differ between Inuit and Europeans.

BACKGROUND: Disease prevalence and mean phenotype values differ between many populations, including Inuit and Europeans. Whether these differences are partly explained by genetic differences or solely due to differences in environmental exposures is still unknown, because estimates of the genetic contribution to these means, which we will here refer to as mean genotypic values, are easily confounded, and because studies across genetically diverse populations are lacking. METHODS: Leveraging the unique genetic properties of the small, admixed and historically isolated Greenlandic population, we estimated the differences in mean genotypic value between Inuit and European genetic ancestry using an admixed sibling design. Analyses were performed across 26 metabolic phenotypes, in 1474 admixed sibling pairs present in a cohort of 5996 Greenlanders. RESULTS: After FDR correction for multiple testing, we found significantly lower mean genotypic values in Inuit genetic ancestry compared to European genetic ancestry for body weight (effect size per percentage of Inuit genetic ancestry (se), -0.51 (0.16) kg/%), body mass index (-0.20 (0.06) kg/m2/%), fat percentage (-0.38 (0.13) %/%), waist circumference (-0.42 (0.16) cm/%), hip circumference (-0.38 (0.11) cm/%) and fasting serum insulin levels (-1.07 (0.51) pmol/l/%). The direction of the effects was consistent with the observed mean phenotype differences between Inuit and European genetic ancestry. No difference in mean genotypic value was observed for height, markers of glucose homeostasis, or circulating lipid levels. CONCLUSIONS: We show that mean genotypic values for some metabolic phenotypes differ between two human populations using a method not easily confounded by possible differences in environmental exposures. Our study illustrates the importance of performing genetic studies in diverse populations.

Trends in cardiovascular disease among Inuit in Greenland from 1994 to 2021.

Background and aims: Cardiovascular disease (CVD) poses significant health challenges globally. While substantial data exists for most populations, the Arctic Inuit's CVD incidence rates remain understudied. This research aimed to change this by estimating CVD incidence and mortality rates in Greenland from 1994 to 2021. Methods: Using nationwide registers, a retrospective observational study was conducted, focusing on individuals born in Greenland to Greenlandic-born parents. Data were sourced from the Greenlandic Hospital Discharge Register and the nationwide electronic medical record. Results: A total of 65,824 individuals were included. the age- and sex-specific incidence rates (IR) of ischemic heart disease, stroke, and heart failure (HF) declined from 1994 to 2021, with the most substantial decline observed for HF among women. Conversely, the IR of atrial fibrillation/flutter increased in both men and women, while the IR of myocardial infarction rose among men. The IR for stroke was particularly elevated compared to other CVD subgroups. Mortality rates for those diagnosed with CVD were 2.4 times higher than those without. Men exhibited a 40 % elevated mortality risk relative to women. Conclusion: The study provides pivotal insights into CVD trends within the Arctic Inuit population, highlighting both positive developments and areas of concern. Given the increasing elderly demographic in Greenland, proactive health strategies are crucial. Emphasizing primary prevention and addressing specific CVD risks, particularly the elevated stroke IR, is imperative for future public health efforts.

Burden of selected chronic non-communicable diseases in a primary healthcare setting in Nuuk, Greenland, compared to a Danish suburb.

INTRODUCTION: Noncommunicable diseases (NCDs) constitute a massive global burden and are the leading cause of death and disability worldwide. In Greenland, the prevalence of NCDs has historically been low. However, during the past approximately 70 years, life circumstances have changed dramatically resulting in increased life expectancy. Today, the proportion of inhabitants in Greenland ≥65 years has nearly tripled since the 1980s, and the prevalence of obesity and diabetes has increased rapidly within the past decades. The aim of this study was to describe the burden of selected NCDs in a primary care setting in Nuuk and compare it to a modern westernized suburban general practice in Denmark. METHODS: The study was performed as a cross sectional register-based study using data extracted from the electronic medical records (EMR) based on diagnosis codes from inhabitants living in Nuuk, Greenland, and a suburb in Denmark. Estimates of prevalence were age-standardized to the WHO world standard population. RESULTS: In both Nuuk and the Danish suburb, the highest prevalence was observed for hypertension (13.2% for both populations), followed by asthma (4.4 and 9.5%, respectively) and diabetes (4.3 and 2.9%, respectively). The age-standardized prevalences of diabetes, COPD, atrial fibrillation, and heart failure, were significantly higher in Nuuk, while seven NCDs including asthma, ischemic heart disease, arthritis urica, psoriasis, hyperthyreosis, hypothyreosis and osteoporosis were significantly higher in the Danish suburb. CONCLUSION: In contrast to the disease pattern observed in Greenland in the last century, the prevalence of diagnosed NCDs in Nuuk is no longer rare. Thus, the overall prevalence of NCDs in the population of Nuuk is now comparable to or even higher than in the suburb in Denmark. This calls for increased focus on all NCDs in the primary healthcare system in Greenland and adaption of the primary healthcare services to a changed disease spectrum.

Trends in Incidence of Hospitalization for Hypoglycemia and Diabetic Ketoacidosis in Individuals With Type 1 or Type 2 Diabetes With and Without Severe Mental Illness in Denmark From 1996 to 2020: A Nationwide Study.

OBJECTIVE: To examine trends in incidence of acute diabetes complications in individuals with type 1 or type 2 diabetes with and without severe mental illness (SMI) in Denmark by age and calendar year. RESEARCH DESIGN AND METHODS: We conducted a cohort study using nationwide registers from 1996 to 2020 to identify individuals with diabetes, ascertain SMI status (namely, schizophrenia, bipolar disorder, or major depression) and identify the outcomes: hospitalization for hypoglycemia and diabetic ketoacidosis (DKA). We used Poisson regression to estimate incidence rates (IRs) and incidence rate ratios (IRRs) of recurrent hypoglycemia and DKA events by SMI, age, and calendar year, accounting for sex, diabetes duration, education, and country of origin. RESULTS: Among 433,609 individuals with diabetes, 8% had SMI. Risk of (first and subsequent) hypoglycemia events was higher for individuals with SMI than for those without SMI (for first hypoglycemia event, IRR: type 1 diabetes, 1.77 [95% CI 1.56-2.00]; type 2 diabetes, 1.64 [95% CI 1.55-1.74]). Individuals with schizophrenia were particularly at risk for recurrent hypoglycemia events. The risk of first DKA event was higher in individuals with SMI (for first DKA event, IRR: type 1 diabetes, 1.78 [95% CI 1.50-2.11]; type 2 diabetes, 1.85 [95% CI 1.64-2.09]). Except for DKA in the type 2 diabetes group, IR differences between individuals with and without SMI were highest in younger individuals (<50 years old) but stable across the calendar year. CONCLUSIONS: SMI is an important risk factor for acute diabetes complication and effective prevention is needed in this population, especially among the younger population and those with schizophrenia.

Effects of 3 months of 10-h per-day time-restricted eating and 3 months of follow-up on bodyweight and cardiometabolic health in Danish individuals at high risk of type 2 diabetes: the RESET single-centre, parallel, superiority, open-label, randomised controlled trial.

BACKGROUND: Time-restricted eating (TRE) has been suggested to be a simple, feasible, and effective dietary strategy for individuals with overweight or obesity. We aimed to investigate the effects of 3 months of 10-h per-day TRE and 3 months of follow-up on bodyweight and cardiometabolic risk factors in individuals at high risk of type 2 diabetes. METHODS: This was a single-centre, parallel, superiority, open-label randomised controlled clinical trial conducted at Steno Diabetes Center Copenhagen (Denmark). The inclusion criteria were age 30-70 years with either overweight (ie, BMI ≥25 kg/m2) and concomitant prediabetes (ie, glycated haemoglobin [HbA1c] 39-47 mmol/mol) or obesity (ie, BMI ≥30 kg/m2) with or without prediabetes and a habitual self-reported eating window (eating and drinking [except for water]) of 12 h per day or more every day and of 14 h per day or more at least 1 day per week. Individuals were randomly assigned 1:1 to 3 months of habitual living (hereafter referred to as the control group) or TRE, which was a self-selected 10-h per-day eating window placed between 0600 h and 2000 h. Randomisation was done in blocks varying in size and was open for participants and research staff, but outcome assessors were masked during statistical analyses. The randomisation list was generated by an external statistician. The primary outcome was change in bodyweight, assessed after 3 months (12 weeks) of the intervention and after 3 months (13 weeks) of follow-up. Adverse events were reported and registered at study visits or if participants contacted study staff to report events between visits. This trial is registered on ClinicalTrials.gov (NCT03854656). FINDINGS: Between March 12, 2019, and March 2, 2022, 100 participants (66 [66%] were female and 34 [34%] were male; median age 59 years [IQR 52-65]) were enrolled and randomly assigned (50 to each group). Of those 100, 46 (92%) in the TRE group and 46 (92%) in the control group completed the intervention period. After 3 months of the intervention, there was no difference in bodyweight between the TRE group and the control group (-0·8 kg, 95% CI -1·7 to 0·2; p=0·099). Being in the TRE group was not associated with a lower bodyweight compared with the control group after subsequent 3-month follow-up (-0·2 kg, -1·6 to 1·2). In the per-protocol analysis, participants who completed the intervention in the TRE group lost 1·0 kg (-1·9 to -0·0; p=0·040) bodyweight compared with the control group after 3 months of intervention, which was not maintained after the 3-month follow-up period (-0·4 kg, -1·8 to 1·0). During the trial and follow-up period, one participant in the TRE group reported a severe adverse event: development of a subcutaneous nodule and pain when the arm was in use. This side-effect was evaluated to be related to the trial procedures. INTERPRETATION: 3 months of 10-h per-day TRE did not lead to clinically relevant effects on bodyweight in middle-aged to older individuals at high risk of type 2 diabetes. FUNDING: Novo Nordisk Foundation, Aalborg University, Helsefonden, and Innovation Fund Denmark.

Healthcare Burden in Greenland of Gastrointestinal Symptoms in Adults with Inherited Loss of Sucrase-Isomaltase Function.

Background: Congenital sucrase isomaltase deficiency (CSID) is in general a very rare disease. However, 2-3% of the Greenlandic population are homozygous (HO) carriers of an Arctic-specific loss-of-function (LoF) variant in the sucrase-isomaltase (SI) encoding gene, causing CSID. The condition is characterized by gastrointestinal symptoms such as stomachache, diarrhea, and weight loss when consuming sucrose, the most common dietary sugar. However, the awareness of the condition in the population and the healthcare system seems to be limited, potentially leading to a higher healthcare burden. Hence, we aimed to investigate whether HO-carriers visit the healthcare system more with gastrointestinal symptoms compared to the control groups by using registry data. Methods: We performed a case-control study identifying cases and controls using genotype information from the 1999-2001 and 2005-2010 Greenlandic health population cohorts. The cases were defined as HO LoF SI-carriers and controls were defined as non-carriers and were matched (1:1) on sex, age, place of residence, and European genetic admixture. We used electronic medical records to assess the number of electronic medical record contacts (EMRc) related to gastrointestinal symptoms and the number of gastrointestinal-related diagnostic procedures. Results: A total of 80 HO-carriers and 80 non-carriers were included. The HO-carriers had 19% more EMRc related to gastrointestinal symptoms (IRR, 1.19, 95% CI [1.02;1.40], p=0.02) and had a 41% higher incidence of gastrointestinal related diagnostic procedures compared to controls (IRR, 1.41, 95% CI [1.05-1.92], p=0.02). Only one HO-carrier was aware of the condition according to the electronic medical records. Conclusion: HO-carriers of the LoF SI-variant had both significantly more gastrointestinal-related EMRc and significantly more diagnostic procedures conducted due to gastrointestinal symptoms. Only one HO-carrier was aware of the condition. Given the high prevalence of HO-carriers in the Greenlandic population, we anticipate that diagnosing more patients with CSID and providing dietary advice could potentially reduce symptom burden and healthcare visits among HO-carriers.

The use of artificial intelligence to assess diabetic eye disease among the Greenlandic population.

Background: Retina fundus images conducted in Greenland are telemedically assessed for diabetic retinopathy by ophthalmological nurses in Denmark. Applying an AI grading solution, in a Greenlandic setting, could potentially improve the efficiency and cost-effectiveness of DR screening.Method: We developed an AI model using retina fundus photos, performed on persons registered with diabetes in Greenland and Denmark, using Optos® ultra wide-field scanning laser ophthalmoscope, graded according to ICDR.Using the ResNet50 network we compared the model's ability to distinguish between different images of ICDR severity levels in a confusion matrix.Results: Comparing images with ICDR level 0 to images of ICDR level 4 resulted in an accuracy of 0.9655, AUC of 0.9905, sensitivity and specificity of 96.6%.Comparing ICDR levels 0,1,2 with ICDR levels 3,4, we achieved a performance with an accuracy of 0.8077, an AUC of 0.8728, a sensitivity of 84.6% and a specificity of 78.8%. For the other comparisons, we achieved a modest performance.Conclusion: We developed an AI model using Greenlandic data, to automatically detect DR on Optos retina fundus images. The sensitivity and specificity were too low for our model to be applied directly in a clinical setting, thus optimising the model should be prioritised.

Frost survival and gene expression in timothy (Phleum pratense L.) cultivars as affected by age and selection in diverse field environments.

The sustainable production of perennial grasses in Northern Norway is at risk due to the ongoing climate change. The predicted increase in temperatures and variable weather patterns are further expected to create challenges for winter survival of timothy (Phleum pratense L.). Knowledge about the molecular mechanisms underlying freezing tolerance is crucial for developing robust cultivars. The current study is aimed at identifying genes involved in freezing stress response of timothy and studying gene expression differentiation due to field selection in contrasting environments using RNAseq. Four timothy cultivars were field tested for three years in Tromsø and Vesterålen, in Northern Norway. The surviving material from the field tests, along with plants raised from the original seed lots, were subjected to freezing tests. LT50 values varied across cultivars and materials. Many genes coding for transcription factors and proteins known to play an important role in freezing tolerance, like dehydrins, c-repeat binding factors, and late embryogenesis abundant proteins were upregulated with decreasing temperatures. Moreover, genes associated with glycolysis/gluconeogenesis, TCA cycle, glutathione metabolism, proteasome pathways and genes encoding autophagy-related proteins, plasma membrane-associated proteins, sugar and amino acid transporters had elevated expression in field survivors compared to plants raised from the original material. The lower freezing stress tolerance of field survivors despite the elevated expression of several stress-responsive genes might be due to a combination of selection in the field and the age effect. Furthermore, differences in freezing stress response between northern and southern adapted cultivars and surviving material from two field trial locations are discussed.

Ethnic differences in CT derived abdominal body composition measures: a comparative retrospect pilot study between European and Inuit study population.

Understanding ethnic variations in body composition is crucial for assessing health risks. Universal models may not suit all ethnicities, and there is limited data on the Inuit population. This study aimed to compare body composition between Inuit and European adults using computed tomography (CT) scans and to investigate the influence of demographics on these measurements. A retrospective analysis was conducted on 50 adults (29 Inuit and 21 European) who underwent standard trauma CT scans. Measurements focused on skeletal muscle index (SMI), various fat indices, and densities at the third lumbar vertebra level, analyzed using the Wilcoxon-Mann-Whitney test and multiple linear regression. Inuit women showed larger fat tissue indices and lower muscle and fat densities than European women. Differences in men were less pronouncehd, with only Intramuscular fat density being lower among Inuit men. Regression indicated that SMI was higher among men, and skeletal muscle density decreased with Inuit ethnicity and age, while visceral fat index was positively associated with age. This study suggests ethnic differences in body composition measures particularly among women, and indicates the need for Inuit-specific body composition models. It higlights the importance of further research into Inuit-specific body composition measurements for better health risk assessment.

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.

Heterogeneity in glycaemic control in children and adolescents with type 1 diabetes: A latent class trajectory analysis of Danish nationwide data.

AIMS: Suboptimal glycaemic control in children and adolescents with type 1 diabetes is prevalent and associated with increased risk of diabetes-related complications and mortality later in life. First, we aimed to identify distinct glycated haemoglobin (HbA1c) trajectories in children and adolescents (2-19 years) with type 1 diabetes. Second, we examined their associations with clinical and socio-demographic factors. METHODS: Data were obtained from the Danish Registry of Childhood and Adolescent Diabetes (DanDiabKids) comprising all Danish children and adolescents diagnosed with type 1 diabetes from 1996 to 2019. Subgroups of distinct mean trajectories of HbA1c were identified using data-driven latent class trajectory modelling. RESULTS: A total of 5889 children (47% female) had HbA1c measured a median of 6 times (interquartile range 3-8) and contributing to 36,504 measurements. We identified four mean HbA1c trajectories, referred to as 'Stable but elevated HbA1c' (83%), 'Increasing HbA1c' (5%), 'Late HbA1c peak' (7%), and 'Early HbA1c peak' (5%). Compared to the 'Stable but elevated HbA1c' group, the three other groups presented rapidly deteriorating glycaemic control during late childhood or adolescence, had higher HbA1c at study entry, and included fewer pump users, higher frequency of inadequate blood glucose monitoring, more severe hypoglycaemic events, lower proportions with Danish origin, and worse educational status of parents. The groups also represented significant differences by healthcare region. CONCLUSIONS: Children and adolescents with type 1 diabetes experience heterogenous trajectories with different timings and magnitudes of the deterioration of HbA1c levels, although the majority follow on average a stable, yet elevated HbA1c trajectory. The causes and long-term health implications of these heterogenous trajectories need to be addressed.

The effect of metformin treatment on volumes of free-living physical activity and sedentary behaviour: A post-hoc analysis of the PRE-D trial.

Perceived physical exertion is increased when exercise is performed on metformin treatment, but the clinical relevance of this is unknown. In this post hoc analysis of a randomized, controlled trial, we investigated whether metformin treatment was associated with lower levels of free-living physical activity. Ninety individuals with overweight/obesity (BMI>25 m2/kg) and HbA1c-defined prediabetes (39-47 mmol/mol) were randomized to treatment with dapagliflozin (SGLT2-inhibitor; 10 mg once daily, n=30), metformin (850 mg twice daily, n=30) or no treatment (control, n=30) for 13 weeks in a parallel-group, open-label trial. Before (baseline), during (6 weeks) and immediately after (13 weeks) cessation of treatment, a 6-day assessment of physical activity and sedentary behaviour was performed using accelerometer-based physical activity monitors. Intention-to-treat analyses revealed no within-group changes or differences in change between the groups for any measures of physical activity or sedentary behaviour at neither 6 nor 13 weeks. Short-term metformin treatment does not reduce free-living physical activity level in individuals with overweight/obesity and HbA1c-defined prediabetes.

High quality of diabetes care in Greenland since the launch of Steno Diabetes Center Greenland 2020 - geographical disparities need attention.

The aim of this study was to estimate the prevalence of diagnosed diabetes in Greenland and evaluate quality of care according to sex, region and healthcare unit within regions. Data on all inhabitants registered with diabetes were extracted from the electronic medical record. We found a crude prevalence of diagnosed diabetes in the population aged ≥ 20 years to be 4.7%, and the prevalence of diabetes standardised to the WHO world population was 4.0%. Compared to males, a significantly higher proportion of females had mean glycated haemoglobin (HbA1c) level below 7% (68.9% vs. 57.5%) and blood pressure below 140/90 mmHg (83.4% vs. 73.5%). Regarding healthcare unit within regions, quality of care was higher in regional cities compared to smaller cities, concerning proportion of persons having blood pressure measured regularly (86.0% vs. 71.7%), urine tested for albuminuria (70.6% vs. 51.2%), receiving eye examination (86.9% vs. 79.5%) and foot examination (87.9% vs. 79.4%). In conclusion, the prevalence of diagnosed diabetes in Greenland is the highest reported yet. The overall quality of diabetes care was high and significantly improved compared to 2018. We observed geographical inequality in diabetes care and improvements in the quality of care in specific remote locations are necessary to minimise health care disparities.

The effect of sucrase-isomaltase deficiency on metabolism, food intake and preferences: protocol for a dietary intervention study.

In Greenland, traditional marine foods are increasingly being replaced by sucrose- and starch-rich foods. A knock-out c.273_274delAG variant in the sucrase-isomaltase (SI) gene is relatively common in Greenland, with homozygous carriers being unable to digest sucrose and some starch. The variant is associated with a healthier metabolic phenotype in Greenlanders, which is confirmed by SI-knockout mice. We aim to assess if the healthy phenotype is explained by metabolic and microbial differences and if food and taste preferences differ between SI-genotypes. This paper describes the protocol for a randomised cross-over trial conducted in Greenland in 2022 with two dietary interventions of three days; a traditional meat- and fish-rich diet and a starch-rich Western diet with 11 energy% sucrose. The power calculation showed that 22 homozygous SI-carriers and 22 non-carriers were sufficient to detect a 0.5 mmol/L difference in glycaemic variability (80% power, α=0.05). We enrolled 18 carriers and 20 non-carriers. We examined food preferences at baseline and collected samples before and after each intervention for metabolic, metabolome, and microbiome profiling. Analyses of samples have not been completed yet. The Ethics Committee of Greenland approved the study. Results will be disseminated in international peer-reviewed journals and to the general Greenlandic population. NCT05375656.

Patient referrals from Greenland to Rigshospitalet in Denmark.

INTRODUCTION: Patients from Greenland are transferred overseas for highly specialised treatment, mainly to the National University Hospital, Rigshospitalet, Denmark. We aimed to investigate the pattern of transfers from Greenland to Denmark, focusing on cardiology. METHODS: This descriptive quality assurance study included all Greenlandic citizens receiving healthcare services at Rigshospitalet from 2017-2021. Unique patients and disease courses were accounted for and patients were stratified across specialties. RESULTS: A total of 3,201 unique patients (56% males, mean age 51.0 years, 325 were 18 years or younger) from Greenland received healthcare services at Rigshospitalet. As some patients were seen two or more times, this corresponds to almost 900 patients (approximately 1,500 disease courses) or 1.2% of the entire Greenlandic population being referred annually. The referrals increased by 52% during the period. The Centre of Head and Orthopaedics received most referrals, followed by the Heart Centre. A modest increase in referrals due to heart diseases was observed with ischaemic heart disease being the more prevalent diagnosis. Coronary artery revascularisation rates in Greenlandic citizens aged 55-74 years were at least as high as in the same age-group for all Danes. CONCLUSION: During the past five years, a 52% increase has been observed in the referral rate from Greenland to Rigshospitalet for diagnostics and treatment. In cardiology, ischaemic heart disease represented the largest share with a high revascularisation rate being observed in older Greenlandic citizens. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Time Trends in the Incidence of Diabetic Ketoacidosis Leading to Hospital Admission Among Adults With Type 1 Diabetes: A Nationwide Danish Register Study.

OBJECTIVE: Diabetic ketoacidosis (DKA) is a life-threatening but preventable complication in people with type 1 diabetes. We aimed to quantify the incidence of DKA according to age and describe the time trend of DKA among adults with type 1 diabetes in Denmark. RESEARCH DESIGN AND METHODS: Individuals aged ≥18 years with type 1 diabetes were identified from a nationwide Danish diabetes register. Hospital admissions due to DKA were ascertained from the National Patient Register. The follow-up period was from 1996 to 2020. RESULTS: The cohort consisted of 24,718 adults with type 1 diabetes. The incidence rate of DKA per 100 person-years (PY) decreased with increasing age for both men and women. From 20 to 80 years of age, the DKA incidence rate decreased from 3.27 to 0.38 per 100 PY. From 1996 to 2008, the incidence rate of DKA increased for all age-groups, with a subsequent minor decrease in incidence rate until 2020. From 1996 to 2008, the incidence rates increased from 1.91 to 3.77 per 100 PY for a 20-year-old individual and from 0.22 to 0.44 per 100 PY for an 80-year-old individual living with type 1 diabetes. From 2008 to 2020 the incidence rates decreased from 3.77 to 3.27 and from 0.44 to 0.38 per 100 PY, respectively. CONCLUSIONS: The incidence rates of DKA are declining for all ages, with an overall decline from 2008 for both men and women. This likely reflects improved diabetes management for individuals with type 1 diabetes in Denmark.

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.

Predicting the HbA1c level following glucose-lowering interventions in individuals with HbA1c-defined prediabetes: a post-hoc analysis from the randomized controlled PRE-D trial.

PURPOSE: To investigate whether the prediction of post-treatment HbA1c levels can be improved by adding an additional biomarker of the glucose metabolism in addition to baseline HbA1c. METHODS: We performed an exploratory analysis based on data from 112 individuals with prediabetes (HbA1c 39-47 mmol) and overweight/obesity (BMI ≥ 25 kg/m2), who completed 13 weeks of glucose-lowering interventions (exercise, dapagliflozin, or metformin) or control (habitual living) in the PRE-D trial. Seven prediction models were tested; one basic model with baseline HbA1c as the sole glucometabolic marker and six models each containing one additional glucometabolic biomarker in addition to baseline HbA1c. The additional glucometabolic biomarkers included: 1) plasma fructosamine, 2) fasting plasma glucose, 3) fasting plasma glucose × fasting serum insulin, 4) mean glucose during a 6-day free-living period measured by a continuous glucose monitor 5) mean glucose during an oral glucose tolerance test, and 6) mean plasma glucose × mean serum insulin during the oral glucose tolerance test. The primary outcome was overall goodness of fit (R2) from the internal validation step in bootstrap-based analysis using general linear models. RESULTS: The prediction models explained 46-50% of the variation (R2) in post-treatment HbA1c with standard deviations of the estimates of ~2 mmol/mol. R2 was not statistically significantly different in the models containing an additional glucometabolic biomarker when compared to the basic model. CONCLUSION: Adding an additional biomarker of the glucose metabolism did not improve the prediction of post-treatment HbA1c in individuals with HbA1c-defined prediabetes.