Publications

Ca homoeostasis is important to human health and tightly controlled by powerful hormonal mechanisms that display ethnic variation. Ethnic variations could occur also in Arctic populations where the traditional Inuit diet is low in Ca and sun exposure is limited. We aimed to assess factors important to parathyroid hormone (PTH) and Ca in serum in Arctic populations. We included Inuit and Caucasians aged 50–69 years living in the capital city in West or in rural East Greenland. Lifestyle factors were assessed by questionnaires. The intake of Inuit diet was assessed from a FFQ. 25-Hydroxyvitamin D (25OHD2 and 25OHD3) levels were measured in serum as was albumin, Ca and PTH. The participation rate was 95 %, with 101 Caucasians and 434 Inuit. Median serum 25OHD (99·7 % was 25OHD3) in Caucasians/Inuit was 42/64 nmol/l (25, 75 percentiles 25, 54/51, 81) (P<0·001). Total Ca in serum was 2·33/2·29 mmol/l (25, 75 percentiles 2·26, 2·38/2·21, 2·36) (P=0·01) and PTH was 2·7/2·2 pmol/l (25, 75 percentiles 2·2, 4·1/1·7, 2·7) (P<0·001). The 69/97 Caucasians/Inuit with serum 25OHD <50 nmol/l differed in PTH (P=0·001) that rose with lower 25OHD levels in Caucasians, whereas this was not the case in Inuit. Ethnic origin influenced PTH (β=0·27, P<0·001) and Ca (β=0·22, P<0·001) in multivariate linear regression models after adjustment for age, sex, BMI, smoking, alcohol and diet. In conclusion, ethnic origin influenced PTH, PTH response to low vitamin D levels and Ca levels in populations in Greenland. Recommendations are to evaluate mechanisms underlying the ethnic influence on Ca homoeostasis and to assess the impact of transition in dietary habits on Ca homoeostasis and skeletal health in Arctic populations.

We previously showed that a common genetic variant leads to a remarkably increased risk of type 2 diabetes (T2D) in the small and historically isolated Greenlandic population. Motivated by this, we aimed at discovering novel genetic determinants for glycated hemoglobin (HbA1C) and at estimating the effect of known HbA1C-associated loci in the Greenlandic population. We analyzed genotype data from 4049 Greenlanders generated using the Illumina Cardio-Metabochip. We performed the discovery association analysis by an additive linear mixed model. To estimate the effect of known HbA1C-associated loci, we modeled the effect in the European and Inuit ancestry proportions of the Greenlandic genome (EAPGG and IAPGG, respectively). After correcting for multiple testing, we found no novel significant associations. When we investigated loci known to associate with HbA1C levels, we found that the lead variant in the GCK locus associated significantly with HbA1C levels in the IAPGG (PIAPGG=4.8×10−6,βIAPGG=0.13SD). Furthermore, for 10 of 15 known HbA1C loci, the effects in IAPGG were similar to the previously reported effects. Interestingly, the ANK1 locus showed a statistically significant ancestral population differential effect, with opposing directions of effect in the two ancestral populations. In conclusion, we found only 1 of the 15 known HbA1C loci to be significantly associated with HbA1C levels in the IAPGG and that two-thirds of the loci showed similar effects in Inuit as previously found in European and East Asian populations. Our results shed light on the genetic effects across ethnicities.

Aims: The aim was to investigate the prevalence of diabetic sensorimotor polyneuropathy (DSPN) and cardiovascular autonomic neuropathy (CAN) in a Danish population of young adults with type 1 diabetes (T1D) using both established and novel measuring modalities. Furthermore, to investigate the association between continuous subcutaneous insulin infusion (CSII) treatment and these complications.

Materials and Methods: CAN was assessed by cardiovascular autonomic reflex tests. DSPN was assessed not only by perception of light touch and pain, vibration perception threshold (VPT), Brief Pain Inventory (BPI), and Michigan Neuropathy Screening Instrument questionnaires but also by novel modalities: electrochemical skin conductance (ESC), sural nerve conduction velocity (SNCV), and sural nerve amplitude potential (SNAP).

Results: The study comprised 156 young adults with a mean age of 22 years (standard deviation 1.6). The prevalence of CAN and early CAN was 9% and 28.1%, respectively. Subclinical DSPN was 55.1% and confirmed DSPN was 2.6%. Prevalence of abnormal SNAP was 23.8%, SNCV was 37.1%, ESC on the hands and feet was 4% and 8%, respectively, VPT was 1.3%, and BPI questionnaire was 1.9%. No association was found between CSII treatment and the measures of DSPN and CAN.

Conclusion: DSPN and CAN are prevalent in young adults with T1D with no association found with CSII treatment. The use of novel measuring modalities identified a higher number of subjects with DSPN compared with established measures. Screening for diabetic neuropathy in young adults may be beneficial to detect and prevent nerve damages at early stages.

Background and aims: Low levels of vitamin D are suspected to be a risk factor for cardiovascular disease and atherosclerosis. The aim of this study was to assess the prevalence of subclinical atherosclerosis among Inuit in Greenland, and to evaluate the association with vitamin D status. We hypothesized that low vitamin D status could be associated with higher carotid intima-media thickness (IMT) as a marker of atherosclerosis.

Methods: 756 adults from the Inuit Health in Transition (IHIT) study carried out in Greenland in the period 2005–2010 were included. A blood sample donated in 1987 was available for a sub-sample of 102 individuals. Serum 25(OH)D3 from the IHIT study and the 1987 survey was used as a measure of vitamin D status. IMT measurements were conducted by ultrasound scanning. The prevalence of atherosclerosis was estimated, and the association between serum 25(OH)D3 and IMT measurements was examined by linear regression.

Results: The overall prevalence of subclinical atherosclerosis was 20.1% (n = 152). The linear regression analyses indicated a weak positive association between serum 25(OH)D3 level and IMT measurements from the IHIT study, though not statistically significant after adjustment for potential confounders (β = 0.35% per 10 nmoL/L 25(OH)D3, p = 0.06). Linear regression analyses of the association between serum 25(OH)D3 level in the 1987 survey and IMT measurements also indicated a positive, though not statistically significant, association after adjustment (β = 0.07% per 10 nmoL/L 25(OH)D3, p = 0.86).

Conclusions: Our findings did not support the hypothesis of an association between low vitamin D levels and risk of atherosclerosis.

We have identified a variant in ADCY3 (encoding adenylate cyclase 3) associated with markedly increased risk of obesity and type 2 diabetes in the Greenlandic population. The variant disrupts a splice acceptor site, and carriers have decreased ADCY3 RNA expression. Additionally, we observe an enrichment of rare ADCY3 loss-of-function variants among individuals with type 2 diabetes in trans-ancestry cohorts. These findings provide new information on disease etiology relevant for future treatment strategies.