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.

Whole blood mercury and the risk of cardiovascular disease among the Greenlandic population.

BACKGROUND: Studies have found mercury to be associated with cardiovascular disease (CVD), however, primarily in populations with low exposure. The highest levels, and variations in the levels, of whole blood mercury (WBM) worldwide have been found in Greenland. We prospectively assessed the association between WBM and the risk of developing CVD in the Greenlandic population. METHODS: We assessed the effects of WBM levels on incident CVD among 3083 Greenlandic Inuit, participating in a population-based cohort study conducted from 2005 to 2010. WBM was measured at baseline. Participants were followed in the National Patient Registries for Denmark and Greenland and in the causes of death register for CVD events from inclusion in the study until CVD event, emigration, death or end of follow-up (30/9-2013). Using Cox regression analyses, we calculated the incidence rates and the hazard ratio of CVD events according to WBM levels. Potential interactions with sex were also investigated. RESULTS: The highest levels of WBM were found in men, who had a significantly higher median level (19 µg/L (IQR:1-44)), compared with women (15 µg/L (IQR: 1-32), (p < 0.001)). The crude hazard ratio (HR) for incident CVD was 1.00 (95% CI 1.00-1.00) for 5 µg/l increase in WBM. After adjusting for several potential confounders, there was still no association between WBM and incident CVD (HR 0.99; 95%CI:0.99-1.00). We found no interactions with sex. CONCLUSIONS: In a population with high levels of WBM, we found no association between WBM and the risk of developing CVD in Greenland.

Christmas article: Snacking preferences at the office during the Christmas season ­ a secret intervention study among diabetes researchers.

Introduction To quantify the effect of Christmas vs. New Year's resolutions season on snacking preferences by measuring intake of four different snacks. Methods Prospective ad libitum intervention snacking study with four combinations of sweet/savory and fatty/non-fatty snacks: cookies, candy, TUC crackers, and rye crackers. A snacking buffet, continuously refilled by a secret Santa, was provided during the Christmas season and New Year's Resolutions season by the secret Santas of the office. Participants were diabetes researchers and were not informed about the study before the end of data collection. The main outcome was daily intake (g) of the four snacks. Results In general, the intake of candy was high compared to the other snacks. The average intake of cookies was significantly higher during the Christmas season compared to New Year's resolution season (8 g/day/participant, p = 0.03), but decreased when approaching Christmas and increased again as time passed by after Christmas (although not significantly). The strongest correlation between the intake of snacks was found between the two sweet snacks, i.e., candy and cookies. Conclusion Researchers have a high preference for sweet foods, especially candy. Irrespective of the type of snack, the preference for cookies was high during the Christmas season but seemed to decrease with decreasing proximity to Christmas, hence, canceling Christmas will unlikely improve diet quality. In fact, we encourage further research to consider whether having Christmas all year could be a potential prevention strategy in the combat of the obesity pandemic. Funding none. Trial registration none.

Endotrophin as a risk marker of mortality and kidney complications in a type 1 diabetes cohort.

Hyperglycemia triggers pathological pathways leading to fibrosis, where extracellular matrix (ECM) components are accumulated. We investigated the potential of endotrophin, a pro-fibrotic molecule generated during collagen type VI formation, as a risk marker for complications to type 1 diabetes. Endotrophin was measured in serum and urine from 1,468 persons with type 1 diabetes. Outcomes included a composite kidney endpoint, first major adverse cardiovascular event (MACE), all-cause mortality, progression of albuminuria, incident heart failure, and sight-threatening diabetic eye disease. Cox proportional hazards models adjusted for conventional risk factors were applied. A doubling of serum endotrophin was independently associated with the kidney endpoint (n = 30/1,462; hazard ratio 3.39 [95% CI: 1.98-5.82]), all-cause mortality (n = 93/1,468; 1.44 [1.03-2.0]), and progression of albuminuria (n = 80/1,359; 1.82 [1.32-2.52]), but not with first MACE, heart failure, or sight-threatening diabetic eye disease after adjustment. Urinary endotrophin was not associated with any outcome after adjustment. Serum endotrophin was a risk marker for mortality and kidney complications in type 1 diabetes. Biomarkers of ECM remodeling, such as serum endotrophin, may identify persons with active pro-fibrotic processes at risk for complications in diabetes and where antifibrotic agents may reduce this risk.

Endotrophin as a Marker of Complications in a Type 2 Diabetes Cohort.

OBJECTIVE: We investigated endotrophin, a profibrotic signaling molecule reflecting collagen VI formation, in serum and urine as risk marker for complications to type 2 diabetes. RESEARCH DESIGN AND METHODS: Endotrophin was measured in 774 individuals with type 2 diabetes. Outcomes included a composite kidney end point, first major adverse cardiovascular event (MACE), mortality, progression of albuminuria, incident heart failure, and sight-threatening eye disease. Adjusted Cox proportional hazards models were applied. RESULTS: Doubling of serum endotrophin was associated with the kidney end point (n = 49; hazard ratio 1.80 [95% CI 1.13-2.87]), first MACE (n = 66; 1.54 [1.04-2.28]), mortality (n = 156; 1.69 (1.31-2.19]), and incident heart failure (n = 42; 1.63 [1.02-2.60]). A doubling of urine endotrophin was associated with progression of albuminuria (n = 85; 1.20 [1.04-1.39]). CONCLUSIONS: Serum endotrophin was a risk marker for mortality and kidney and cardiovascular complications in type 2 diabetes. Urine endotrophin was a marker for albuminuria progression.

Lifetime risk and years lost to type 1 and type 2 diabetes in Denmark, 1996-2016.

INTRODUCTION: Lifetime risk and lifetime lost to diabetes are measures of current diabetes burden in a population. We aimed at quantifying these measures in the Danish population. RESEARCH DESIGN AND METHODS: We modeled incidence and mortality of type 1 diabetes (T1D) and type 2 diabetes (T2D) and non-diabetes mortality based on complete follow-up of the entire population of Denmark in 1996-2016. A multistate model with these transition rates was used to assess the lifetime risk of diabetes, as well as the difference in expected lifetime between persons with type 1 and T2D and persons without. RESULTS: In 2016, the lifetime risk of T1D was 1.1% and that for T2D 24%, the latter a 50% increase from 1996. For 50-year-old persons, the lifetime lost was 6.6 years for T1D and 4.8 years for T2D. These figures have been declining over the study period.At 2016, the total foreseeable lives lost in Denmark among patients with T1D were 182 000 years, and those among patients with T2D were 766 000 years, corresponding to 6.6 and 3.0 years per person, respectively. CONCLUSION: At the individual level, improvements in the disease burden for both T1D and T2D have occurred. At the population level, the increasing number of patients with T2D has contributed to a large increase in the total loss of lifetime.

Components of diabetes prevalence in Denmark 1996-2016 and future trends until 2030.

INTRODUCTION: Incidence rates of diabetes have been increasing and mortality rates have been decreasing. Our aim is the quantification of the effects of these on the prevalence and prediction of the future burden of diabetes. RESEARCH DESIGN AND METHODS: From population-based registers of Denmark, we derived diabetes incidence and mortality rates and mortality rates for persons without diabetes for the period 1996-2016. Rates were modeled by smooth parametric terms using Poisson regression. Estimated rates were used to assess the relative contribution of incidence and mortality to changes in prevalence over the study period as well as for prediction of future rates and prevalence 2017-2040. RESULTS: The major contributors to prevalence was increasing incidence (22%) and epidemiological imbalance between incidence and mortality (27%). The decrease in mortality rates over the period 1996-2016 contributes only 9% of the prevalent cases at 2016. We estimated that 467 000 persons in Denmark would be living with diabetes in 2030. The age distribution of patients in the period 2017-2030 is predicted to change toward older ages. The total number of persons needing diabetes care will increase by 67% over the next 13 years, an average annual increase of 4.0%. CONCLUSIONS: Lowering mortality among patients with diabetes even further is not likely to influence the prevalence substantially. Since the size and the increase in incidence of diabetes are major drivers of the increasing prevalence, the prevention of new cases of diabetes is required.

Prevalence, incidence and mortality of type 1 and type 2 diabetes in Denmark 1996-2016.

INTRODUCTION: The objective of this study was to give an overview of prevalence, incidence and mortality of type 1 (T1D) and type 2 diabetes (T2D) in Denmark, and their temporal trends. RESEARCH DESIGN AND METHODS: We constructed a diabetes register from existing population-based healthcare registers, including a classification of patients as T1D or T2D, with coverage from 1996 to 2016. Using complete population records for Denmark, we derived prevalence, incidence, mortality and standardized mortality ratio (SMR). RESULTS: The overall prevalence of diabetes at 2016 was 0.5% for T1D and 4.4% for T2D, with annual increases since 1996 of 0.5% for T1D and 5.5% for T2D. Incidence rates of T1D decreased by 3.5% per year, with increase for persons under 25 years of age and a decrease for older persons. T2D incidence increased 2.5% per year until 2011, decreased until 2014 and increased after that, similar in all ages. The annual decrease in mortality was 0.3% for T1D and 2.9% for T2D. The mortality rate ratio between T1D and T2D was 1.9 for men and 1.6 for women. SMR decreased annually 2% for T1D and 0.5% for T2D. CONCLUSIONS: Incidence and prevalence of diabetes is increasing, but mortality among patients with diabetes in Denmark is decreasing faster than the mortality among persons without diabetes. T1D carries a 70% higher mortality than T2D.

Abdominal visceral and subcutaneous adipose tissue and associations with cardiometabolic risk in Inuit, Africans and Europeans: a cross-sectional study.

OBJECTIVES: Abdominal fat has been identified as a risk marker of cardiometabolic disease independent of overall adiposity. However, it is not clear whether there are ethnic disparities in this risk. We investigated the associations of visceral adipose tissue (VAT) and abdominal subcutaneous adipose tissue (SAT) with cardiometabolic risk factors in three ethnic diverse populations of Inuit, Africans and Europeans. DESIGN: Cross-sectional pooled study. SETTING: Greenland, Kenya and Denmark. METHODS: A total of 5113 participants (2933 Inuit, 1397 Africans and 783 Europeans) from three studies in Greenland, Kenya and Denmark were included. Measurements included abdominal fat distribution assessed by ultrasound, oral glucose tolerance test, hepatic insulin resistance, blood pressure and lipids. The associations were analysed using multiple linear regressions. RESULTS: Across ethnic group and gender, an increase in VAT of 1 SD was associated with higher levels of hepatic insulin resistance (ranging from 14% to 28%), triglycerides (8% to 16%) and lower high-density lipoprotein cholesterol (HDL-C, -1.0 to -0.05 mmol/L) independent of body mass index. VAT showed positive associations with most of the other cardiometabolic risk factors in Inuit and Europeans, but not in Africans. In contrast, SAT was mainly associated with the outcomes in Inuit and Africans. Of notice was that higher SAT was associated with higher HDL-C in African men (0.11 mmol/L, 95% CI: 0.03 to 0.18) and with lower HDL-C in Inuit (-0.07 mmol/L, 95% CI: -0.12 to -0.02), but not in European men (-0.02 mmol/L, 95% CI: -0.09 to 0.05). Generally weaker associations were observed for women. Furthermore, the absolute levels of several of the cardiometabolic outcomes differed between the ethnic groups. CONCLUSIONS: VAT and SAT were associated with several of the cardiometabolic risk factors beyond overall adiposity. Some of these associations were specific to ethnicity, suggesting that ethnicity plays a role in the pathway from abdominal fat to selected cardiometabolic risk factors.

Associations between birth weight and glucose intolerance in adulthood among Greenlandic Inuit.

AIMS: To examine the association between birth weight and glucose intolerance in adult Greenlandic Inuit. METHODS: We examined 1429 participants aged 18-56 years from two population-based, cross-sectional studies in Greenland with information on birth weight. Oral glucose tolerance tests, anthropometric measures and ultrasound of abdominal tissue were performed. Associations of birth weight with glucose markers were analysed using linear or logistic regressions. Spline analyses were conducted to examine u-shaped associations. Adjustments were done for age, sex, birth place, family history of diabetes, genetic admixture, TBC1D4 p.Arg684Ter carrier status, BMI and visceral adipose tissue. RESULTS: The median birthweight was 3300 g and 3.9% had type 2 diabetes, T2DM. Spline analyses indicated overall linear associations. In fully adjusted analyses, an increase in birth weight of 1 kg was associated with a change in fasting plasma glucose of -0.06 mmol/L (95%CI: -0.11, -0.01), 2-h plasma glucose of -0.16 mmol/L (95%CI: -0.35, 0.02), HOMA-IR of -5.45% (95%CI: -10.34, -0.29), insulin sensitivity index of 7.04% (95%CI: 1.88, 12.45) and a trend towards a reduced risk of hyperglycaemia and T2DM, although statistically insignificant. CONCLUSIONS: Birth weight was inversely associated with hepatic and peripheral insulin resistance independently of adult adiposity. Thus, the findings support low birth weight as a contributing factor for glucose intolerance in adult Inuit in Greenland.

Validation of cardiovascular diagnoses in the Greenlandic Hospital Discharge Register for epidemiological use.

Cardiovascular disease (CVD) is one of the leading causes of death worldwide. In Greenland, valid estimates of prevalence and incidence of CVD do not exist and can only be calculated if diagnoses of CVD in the Greenlandic Hospital Discharge Register (GHDR) are correct. Diagnoses of CVD in GHDR have not previously been validated specifically. The objective of the study was to validate diagnoses of CVD in GHDR. The study was conducted as a validation study with primary investigator comparing information in GHDR with information in medical records. Diagnoses in GHDR were considered correct and thus valid if they matched the diagnoses or the medical information in the medical records. A total of 432 online accessible medical records with a cardiovascular diagnosis according to GHDR from Queen Ingrid's Hospital from 2001 to 2013 (n=291) and from local health care centres from 2007 to 2013 (n=141) were reviewed. Ninety-nine and ninety-two percent of discharge diagnosis in GHDR from Queen Ingrid's Hospital and local health care centres were correct in comparison with diagnoses in the medical record indicating valid registration practice. The correctness of cardiovascular diagnoses in GHDR was considered high in terms of acceptable agreement between medical records and diagnoses in GHDR. Cardiovascular diagnoses are valid for epidemiological use.

The obesity-associated risk of cardiovascular disease and all-cause mortality is not lower in Inuit compared to Europeans: A cohort study of Greenlandic Inuit, Nunavik Inuit and Danes.

BACKGROUND AND AIMS: Inuit populations have lower levels of cardiometabolic risk factors for the same level of body mass index (BMI) or waist circumference (WC) compared to Europeans in cross-sectional studies. We aimed to compare the longitudinal associations of anthropometric measures with cardiovascular disease (CVD) and all-cause mortality in Inuit and Europeans. METHODS: Using pooled data from three population-based studies in Canada, Greenland and Denmark, we conducted a cohort study of 10,033 adult participants (765 Nunavik Inuit, 2960 Greenlandic Inuit and 6308 Europeans). Anthropometric measures collected at baseline included: BMI, WC, waist-to-hip-ratio (WHR), waist-to-height-ratio (WHtR) and a body shape index (ABSI). Information on CVD and death was retrieved from national registers or medical files. Poisson regression analyses were used to calculate incidence rates for CVD and all-cause mortality. RESULTS: During a median follow-up of 10.5 years, there were 642 CVD events and 594 deaths. Slightly higher absolute incidence rates of CVD for a given anthropometric measure were found in Nunavik Inuit compared with Greenlandic Inuit and the Europeans; however, no cohort interactions were observed. For all-cause mortality, all anthropometric measures were positively associated in the Europeans, but only ABSI in the two Inuit populations. In contrast, BMI and WC were inversely associated with mortality in the two Inuit populations. CONCLUSIONS: Inuit and Europeans have different absolute incidences of CVD and all-cause mortality, but the trends in the associations with the anthropometric measures only differ for all-cause mortality. Previous findings of a lower obesity-associated cardiometabolic risk among Inuit were not confirmed.

Birth weight and risk of adiposity among adult Inuit in Greenland.

OBJECTIVE: The Inuit population in Greenland has undergone rapid socioeconomic and nutritional changes simultaneously with an increasing prevalence of obesity. Therefore, the objective was to examine fetal programming as part of the aetiology of obesity among Inuit in Greenland by investigating the association between birth weight and measures of body composition and fat distribution in adulthood. METHODS: The study was based on cross-sectional data from a total of 1,473 adults aged 18-61 years in two population-based surveys conducted in Greenland between 1999-2001 and 2005-2010. Information on birth weight was collected from birth records. Adiposity was assessed by anthropometry, fat mass index (FMI), fat-free mass index (FFMI), and visceral (VAT) and subcutaneous adipose tissue (SAT) estimated by ultrasound. The associations to birth weight were analyzed using linear regression models and quadratic splines. Analyses were stratified by sex, and adjusted for age, birthplace, ancestry and family history of obesity. RESULTS: Spline analyses showed linear relations between birth weight and adult adiposity. In multiple regression analyses, birth weight was positively associated with BMI, waist circumference, FMI, FFMI and SAT with generally weaker associations among women compared to men. Birth weight was only associated with VAT after additional adjustment for waist circumference and appeared to be specific and inverse for men only. CONCLUSIONS: Higher birth weight among Inuit was associated with adiposity in adulthood. More studies are needed to explore a potential inverse association between birth size and VAT.