Trace elements in whole blood in the general population in Trøndelag County, Norway: The HUNT3 Survey.

BACKGROUND: Biomonitoring of a cohort within a large health survey can provide reliable information on trace element status. The main aims of this study were 1) to determine the concentrations of 28 trace elements in whole blood samples from the general population of the Nord-Trøndelag region, Norway, and 2) to investigate how trace element concentrations vary with geographical area, lifestyle, and socio-demographic factors. METHODS: Whole blood samples were collected in the third survey of the Trøndelag Health Survey (HUNT3), a large population-based study in Norway. In total, 1011 whole blood samples from individuals aged 20-91 years were analyzed using high resolution inductively coupled plasma-mass spectrometry (HR-ICP-MS). We compared trace element concentrations (As, B, Be, Br, Ca, Cd, Cr, Cs, Cu, Ga, Au, In, Fe, Pb, Hg, Tl, Mg, Mn, Mo, Ni, Rb, Sc, Se, Ag, Sr, Sn, W and Zn) between three geographical areas (coastal, fjord/town, inland/mountain) using multivariable linear regression and assessed differences in trace element concentrations with socio-demographic and lifestyle factors using general linear models. RESULTS: Trace element concentrations were generally comparable to levels reported in other recent studies and suggest low exposure to toxic trace elements in the region. We found geographical differences in concentrations of 19 trace elements. As, Br, Hg, and Se concentrations were higher on the coast compared to the fjord/town and inland/mountain areas, suggesting that the marine environment is an important source of exposure for these trace elements. In addition, socio-demographic and lifestyle characteristics, particularly age and sex, were associated with differences in trace element concentrations. CONCLUSIONS: We report concentrations of 28 trace elements in the general population of a rural region with low exposure to pollution. Whole blood concentrations of trace elements varied with geographical area, the participants' lifestyle, and socio-demographic characteristics, highlighting the importance of considering these factors when evaluating trace element status in a population.

Risk of hip and forearm fracture in subjects with type 2 diabetes mellitus and latent autoimmune diabetes of adults. The HUNT Study, Norway.

Type 1 and type 2 diabetes mellitus incur an increased risk of fracture, with a generally higher risk among individuals with type 1 diabetes. The fracture risk among individuals with latent autoimmune diabetes of adulthood (LADA) is not known. The present cohort study aimed to estimate the risk of hip and forearm fracture among individuals with LADA, alongside type 1 and type 2 diabetes, using data from the second survey of the Trøndelag Health Study (HUNT2) in 1995-97. All inhabitants aged 20 years or older (N = 92,936) were invited to attend, of whom 65,234 (70%) participated. A total of 1972 (3%) reported to have diabetes; 1399 were found to have type 2 diabetes, 144 to have LADA, and 138 to have type 1 diabetes. All participants were followed prospectively with respect to hip- and forearm fractures by linkage to the local fracture registry. During a median follow-up of 16.2 years, 2695 persons with hip fractures and 3533 persons with forearm fractures were identified. There was an increased risk of hip fracture in women with type 2 diabetes (HR = 1.51, 95% CI 1.24-1.85) and LADA (HR = 2.15, 95% CI 1.25-3.72), whereas women with type 1 diabetes did not have a significantly increased risk (HR = 2.13, 95% CI 0.89-5.14). Among men, only LADA was associated with an increased risk of hip fracture (HR = 2.69, 95% CI 1.34-5.41). There was no statistically significant association between any of the diabetes types and forearm fracture. In women with type 2 diabetes, the highest risks of hip fracture were observed among those with highest HbA1c level at baseline, longest time since diagnosis, and most visual and movement impairment. We found that individuals with LADA had an increased risk of hip fracture similar to that previously reported for individuals with type 1 diabetes, and no increased risk of forearm fracture.

Validity of the FINDRISC as a prediction tool for diabetes in a contemporary Norwegian population: a 10-year follow-up of the HUNT study.

Objective: The Finnish Diabetes Risk Score (FINDRISC) is a recommended tool for type 2 diabetes prediction. There is a lack of studies examining the performance of the current 0-26 point FINDRISC scale. We examined the validity of FINDRISC in a contemporary Norwegian risk environment. Research design and methods: We followed 47 804 participants without known diabetes and aged ≥20 years in the HUNT3 survey (2006-2008) by linkage to information on glucose-lowering drug dispensing in the Norwegian Prescription Database (2004-2016). We estimated the C-statistic, sensitivity and specificity of FINDRISC as predictor of incident diabetes, as indicated by incident use of glucose-lowering drugs. We estimated the 10-year cumulative diabetes incidence by categories of FINDRISC. Results: The C-statistic (95% CI) of FINDRISC in predicting future diabetes was 0.77 (0.76 to 0.78). FINDRISC ≥15 (the conventional cut-off value) had a sensitivity of 38% and a specificity of 90%. The 10-year cumulative diabetes incidence (95% CI) was 4.0% (3.8% to 4.2%) in the entire study population, 13.5% (12.5% to 14.5%) for people with FINDRISC ≥15 and 2.8% (2.6% to 3.0%) for people with FINDRISC <15. Thus, FINDRISC ≥15 had a positive predictive value of 13.5% and a negative predictive value of 97.2% for diabetes within the next 10 years. To approach a similar sensitivity as in the study in which FINDRISC was developed, we would have to lower the cut-off value for elevated FINDRISC to ≥11. This would yield a sensitivity of 73%, specificity of 67%, positive predictive value of 7.7% and negative predictive value of 98.5%. Conclusions: The validity of FINDRISC and the risk of diabetes among people with FINDRISC ≥15 is substantially lower in the contemporary Norwegian population than assumed in official guidelines. To identify ~3/4 of those developing diabetes within the next 10 years, we would have to lower the threshold for elevated FINDRISC to ≥11, which would label ~1/3 of the entire adult population as having an elevated FINDRISC necessitating a glycemia assessment.

Basic lifestyle advice to individuals at high risk of type 2 diabetes: a 2-year population-based diabetes prevention study. The DE-PLAN intervention in the HUNT Study, Norway.

OBJECTIVE: Among individuals at high risk for diabetes identified through a population survey, we performed an intervention study with basic lifestyle advice aiming to prevent diabetes. RESEARCH DESIGN AND METHODS: Among 50 806 participants in the HUNT3 Survey (2006-2008), 5297 individuals with Finnish Diabetes Risc Score (FINDRISC ≥15 were invited to an oral glucose tolerance test (OGTT) and an education session with lifestyle advice, and 2634 (49.7%) attended. Among them, 2380 people without diabetes were included in the prevention study with repeated examinations and education sessions after 6, 12, and 24 months. We examined participation, diabetes incidence, glycemia, and adiposity during follow-up. RESULTS: Of 2380 participants, 1212 (50.9%) participated in ≥3 of the four examinations. Diabetes was detected in 3.5%, 3.1%, and 4.0% of individuals at the 6-month, 12-month, and 24-month examinations, respectively, indicating a 10.3% 2-year diabetes incidence. Mean (95% CI) increases from baseline to 2-year follow-up were 0.30 (0.29 to 0.32) percentage points (3.3 (3.2 to 3.5) mmol/mol) for Hemoglobin A1c, 0.13 (0.10 to 0.16) mmol/L for fasting serum-glucose, 0.46 (0.36 to 0.56) mmol/L for 2-hour OGTT s-glucose, 0.30 (0.19 to 0.40) kg/m2 forbody mass index (BMI) (all p<0.001) and -0.5 (-0.9 to -0.2) cm for waist circumference (p=0.004), with broadly similar estimates by baseline age, sex, education, depressive symptoms, BMI, physical activity, and family history of diabetes. Only 206 (8.7%) participants had evidence of >5% weight loss during follow-up; their fasting and 2-hour s-glucose did not increase, and HbA1c increased less than in other participants. CONCLUSION: Basic lifestyle advice given to high-risk individuals during three group sessions with 6-month intervals was not effective in reducing 2-year diabetes risk.

Inverse relationship between type 1 diabetes mellitus and migraine. Data from the Nord-Trøndelag Health Surveys 1995-1997 and 2006-2008.

Aims The aim of this cross-sectional population-based study was to investigate the associations between migraine and type 1 and type 2 diabetes mellitus (DM). Methods We used data from the second (1995-1997) and third survey (2006-2008) in the Nord-Trøndelag Health Study. Analyses were made for the 26,121 participants (30-97 years of age, median 58.3 years) with known headache and DM status in both surveys, and for the 39,584 participants in the third survey (20-97 years, median 54.1 years). The diagnosis of migraine was given to those who fulfilled the questionnaire-based migraine diagnosis in the second and/or third survey. Associations were assessed using multiple logistic regression, estimating prevalence odds ratio (OR) with 95% confidence intervals (CIs). Results In the multivariate analysis of the 26,121 participants in both surveys, adjusting for age, gender, years of education, and smoking, classical type 1 DM (n = 81) was associated with a lower prevalence of any headache (OR = 0.55, 95% CI 0.34-0.88),and migraine (OR = 0.47, 95% CI 0.26-0.96) compared to those without DM (n = 24,779). Correspondingly, the merged group of classical type 1 DM and latent autoimmune diabetes of adults (LADA) (n = 153) were less likely to have migraine (OR = 0.53, 95% CI 0.31-0.91). Similarly, an inverse relationship between type 1 DM and migraine was found in analyses of 39,584 participants in the third survey. No clear association was found between headache and type 2 DM. Conclusions In this cross-sectional population-based study of mainly middle-aged participants, type 1 DM was inversely associated with headache, in particular migraine.

Individuals at high risk for type 2 diabetes invited to a lifestyle program: characteristics of participants versus non-participants (the HUNT Study) and 24-month follow-up of participants (the VEND-RISK Study).

OBJECTIVE: Prevention of type 2 diabetes mellitus is possible through lifestyle programs, but the effect depends on the program's content, resources, and setting. Lifestyle programs are often confronted with high rates of non-participation and attrition. This study invited individuals at high risk for type 2 diabetes to a lifestyle program in the Norwegian primary healthcare setting. The aims were to investigate possible differences in characteristics between participants and non-participants and to study the effect of the lifestyle program at 24-month follow-up for participants. RESEARCH DESIGN AND METHODS: Individuals identified at high risk for type 2 diabetes during the third survey of the Nord-Trøndelag Health Study (HUNT3) from two municipalities (n=332) were invited to a lifestyle program (the VEND-RISK Study). A cross-sectional design was used to explore if the participants' characteristics differed from non-participants. A non-randomized, single-arm, pre-post examination was used to examine the effect of the lifestyle program on participants' characteristics at 24-month follow-up. RESULTS: Of all individuals at high risk for type 2 diabetes invited to the lifestyle program, 86% (287/332) declined to participate. Non-participating women had fewer years of education (p<0.001), compared with participating women. For men, no differences were seen between non-participants and participants. Among all participants (n=45) at 24-month follow-up, none had developed type 2 diabetes, and HbA1c (p<0.001) had decreased significantly. There was a small reduction in mean body mass index from baseline to 24 months that was not statistically significant. For women, waist circumference (-4.0 cm, p<0.001) decreased significantly. CONCLUSIONS: Future research regarding individuals at high risk for type 2 diabetes in the primary healthcare lifestyle program should focus on how to promote recruitment of women with low education. Participants attending this study's lifestyle program improved their cardiometabolic markers. CLINICAL TRIALS REGISTRATION: NCT01135901; Results.

Trace element status in patients with type 2 diabetes in Norway: The HUNT3 Survey.

Several epidemiological studies have indicated that a number of trace elements may play a role in type 2 diabetes (T2D). We investigated the association between prevalent T2D and the concentrations of 25 trace elements in whole blood, and the relationships between T2D duration and blood levels of the trace elements that we found to be related to T2D prevalence. In this population based case-control study, 267 patients with self-reported T2D and 609 controls (frequency matched), were selected from the third Nord-Trøndelag Health Survey. Trace element blood levels were determined by high resolution inductively coupled plasma-mass spectrometry. Multivariable conditional logistic regression and multivariable linear regression were used to estimate associations. The prevalence of T2D was positively associated with boron, calcium and silver, and inversely associated with indium, lead and magnesium (Ptrend<0.05). We found no statistical evidence for associations between blood levels of arsenic, bromine, cadmium, cesium, chromium, copper, gallium, gold, manganese, mercury, molybdenum, nickel, rubidium, selenium, strontium, tantalum, thallium, tin and zinc and T2D prevalence. After corrections for multiple testing, associations remained significant for calcium and lead (Qtrend<0.05), and borderline significant for magnesium, silver and boron. With increasing disease duration, higher calcium levels were observed (P<0.05). This study suggests an association between prevalent T2D and blood levels of boron, calcium, indium, lead, magnesium and silver.

Trace elements in early phase type 2 diabetes mellitus-A population-based study. The HUNT study in Norway.

Differences in trace elements levels between individuals with type 2 diabetes and controls have been reported in several studies in various body fluids and tissues, but results have been inconsistent. In order to examine trace element levels in the early phase of type 2 diabetes, we investigated the association between whole blood levels of 26 trace elements and the prevalence of previously undiagnosed, screening-detected type 2 diabetes. The study was conducted as a case-control study nested within the third survey of the population-based Nord-Trøndelag Health Study (HUNT3 Survey). Among participants without previously known diabetes, 128 cases of type 2 diabetes were diagnosed in people with a high diabetes risk score (FINDRISC≥15), and frequency-matched for age and sex with 755 controls. Blood samples were analyzed by high resolution inductively coupled plasma mass spectrometry. Associations between trace element levels and the prevalence of previously undiagnosed type 2 diabetes were evaluated with multivariable conditional logistic regression controlling for age, sex, body mass index, waist-to-hip ratio, education, income, smoking and family history of diabetes. The prevalence of previously undiagnosed type 2 diabetes increased across tertiles/quartiles for cadmium, chromium, iron, nickel, silver and zinc, and decreased with increasing quartiles of bromine (Ptrend<0.05). After corrections for multiple testing, associations for chromium remained significant (Qtrend<0.05), while associations for iron and silver were borderline significant. No associations were found for arsenic, boron, calcium, cesium, copper, gallium, gold, indium, lead, magnesium, manganese, mercury, molybdenum, rubidium, selenium, strontium, tantalum, thallium and tin. Our results suggest a possible role of bromine, cadmium, chromium, iron, nickel, silver and zinc in the development of type 2 diabetes.

Prolonged sitting may increase diabetes risk in physically inactive individuals: an 11 year follow-up of the HUNT Study, Norway.

AIMS/HYPOTHESIS: We examined the association between sitting time and diabetes incidence, overall and by strata of leisure-time physical activity and BMI. METHODS: We followed 28,051 adult participants of the Nord-Trøndelag Health Study (the HUNT Study), a population-based study, for diabetes incidence from 1995-1997 to 2006-2008 and estimated HRs of any diabetes by categories of self-reported total daily sitting time at baseline. RESULTS: Of 28,051 participants, 1253 (4.5%) developed diabetes during 11 years of follow-up. Overall, sitting ≥8 h/day was associated with a 17% (95% CI 2, 34) higher risk of developing diabetes compared with sitting ≤4 h/day, adjusted for age, sex and education. However, the association was attenuated to a non-significant 9% (95% CI -5, 26) increase in risk after adjustment for leisure-time physical activity and BMI. The association between sitting time and diabetes risk differed by leisure-time physical activity (p Interaction = 0.01). Among participants with low leisure-time physical activity (≤2 h light activity per week and no vigorous activity), sitting 5-7 h/day and ≥8 h/day were associated with a 26% (95% CI 2, 57) and 30% (95% CI 5, 61) higher risk of diabetes, respectively, compared with sitting ≤4 h/day. There was no corresponding association among participants with high leisure-time physical activity (≥3 h light activity or >0 h vigorous activity per week). There was no statistical evidence that the association between sitting time and diabetes risk differed by obesity (p Interaction = 0.65). CONCLUSIONS/INTERPRETATION: Our findings suggest that total sitting time has little association with diabetes risk in the population as a whole, but prolonged sitting may contribute to an increased diabetes risk among physically inactive people.

Anxiety and Depressive Symptoms as Predictors of All-Cause Mortality among People with Insulin-Naïve Type 2 Diabetes: 17-Year Follow-Up of the Second Nord-Trøndelag Health Survey (HUNT2), Norway.

AIM: To examine whether elevated anxiety and/or depressive symptoms are related to all-cause mortality in people with Type 2 diabetes, not using insulin. METHODS: 948 participants in the community-wide Nord-Trøndelag Health Survey conducted during 1995-97 completed the Hospital Anxiety and Depression Scale with subscales of anxiety (HADS-A) and depression (HADS-D). Elevated symptoms were defined as HADS-A or HADS-D ≥8. Participants with type 2 diabetes, not using insulin, were followed until November 21, 2012 or death. Cox regression analyses were used to estimate associations between baseline elevated anxiety symptoms, elevated depressive symptoms and mortality, adjusting for sociodemographic factors, HbA1c, cardiovascular disease and microvascular complications. RESULTS: At baseline, 8% (n = 77/948) reported elevated anxiety symptoms, 9% (n = 87/948) elevated depressive symptoms and 10% (n = 93/948) reported both. After a mean follow-up of 12 years (SD 5.1, range 0-17), 541 participants (57%) had died. Participants with elevated anxiety symptoms only had a decreased mortality risk (unadjusted HR 0.66, 95% CI 0.46-0.96). Adjustment for HbA1c attenuated this relation (HR 0.73, 95% CI 0.50-1.07). Those with elevated depression symptoms alone had an increased mortality risk (fully adjusted model HR 1.39, 95% CI 1.05-1.84). Having both elevated anxiety and depressive symptoms was not associated with increased mortality risk (adjusted HR 1.30, 95% CI 0.96-1.74). CONCLUSIONS: Elevated depressive symptoms were associated with excess mortality risk in people with Type 2 diabetes not using insulin. No significant association with mortality was found among people with elevated anxiety symptoms. Having both elevated anxiety and depressive symptoms was not associated with mortality. The hypothesis that elevated levels of anxiety symptoms leads to behavior that counteracts the adverse health effects of Type 2 diabetes needs further investigation.

Exploring lifestyle and risk in preventing type 2 diabetes-a nested qualitative study of older participants in a lifestyle intervention program (VEND-RISK).

BACKGROUND: Lifestyle intervention may reduce the development of type 2 diabetes among high-risk individuals. The aim of this study was to explore how older adults perceived their own lifestyle and being at increased risk for type 2 diabetes while they participated in a lifestyle intervention programme. METHODS: A nested qualitative study was performed with 26 participants (mean age 68 years) in the VEND-RISK Study. Participants had previously participated in the HUNT3 Study and the HUNT DE-PLAN Study, where their risk for developing type 2 diabetes (FIND-RISC ≥ 15) had been identified. The data were analysed using systematic text condensation. RESULTS: Two main themes were identified. The first theme was having resources available for an active lifestyle, which included having a family and being part of a social network, having a positive attitude toward life, and maintaining established habits from childhood to the present. The second theme was being at increased risk for type 2 diabetes, which included varied reactions to the information on increased risk, how lifestyle intervention raised awareness about risk behaviour, and health-related worries and ambitions as type 2 diabetes prevention. CONCLUSIONS: Assessing a participant's resources could improve the outcomes of lifestyle intervention programmes. Both family history and risk perception could be used in preventive strategies to enhance changes in lifestyle. TRIAL REGISTRATION: The VEND-RISK Study was registered in ClinicalTrials.gov on April 26, 2010, with the registration number NCT01135901 .

Impact of sex and age on the performance of FINDRISC: the HUNT Study in Norway.

OBJECTIVE: The Finnish Diabetes Risk Score (FINDRISC) is recommended as a screening tool for diabetes risk. However, there is a lack of well-powered studies examining the performance of FINDRISC by sex and age. We aim to estimate, by sex and age, the prevalence of elevated FINDRISC and positive predictive value (PPV) of FINDRISC for identifying impaired glucose metabolism (IGM) in a general Norwegian population. RESEARCH DESIGN AND METHODS: We estimated the prevalence of elevated FINDRISC (≥15) among 47 694 adults in the third survey of the Nord-Trøndelag Health Study (HUNT3, 2006-08). Among 2559 participants who participated in oral glucose tolerance testing, we estimated the PPV of elevated FINDRISC for identifying unknown prevalent diabetes and other forms of IGM. RESULTS: The prevalence of elevated FINDRISC was 12.1% in women, 9.6% in men, and increased from 1.5% at age 20-39 to 25.1% at age 70-79 years. The PPVs of elevated FINDRISC were 9.8% for diabetes, 16.9% for impaired glucose tolerance, 8.2% for impaired fasting glucose, and 34.9% for any form of IGM. The PPV for IGM was lower in women (31.2%) than in men (40.4%), and increased from 19.1% at age 20-39 to 55.5% at age ≥80 years. CONCLUSIONS: FINDRISC identified more women than men as high-risk individuals for diabetes. FINDRISC had a high PPV for detecting prevalent IGM, and the PPV was higher in men than in women and in the older individuals. Our data indicate that the impact of sex and age on diabetes risk is not fully captured by FINDRISC, and that refinements to it might improve diabetes prediction.

Blood pressure changes during 22-year of follow-up in large general population - the HUNT Study, Norway.

BACKGROUND: While hypertension still is a major health problem worldwide, some studies have indicated that the blood pressure level has decreased in some populations. This population based cohort study aims at analysing blood pressure changes in a large Norwegian population over a 22 year period. METHODS: Data is acquired from three comprehensive health surveys of the HUNT Study conducted from 1984-86 to 2006-08. All citizens of Nord-Trøndelag County, Norway, >20 years were invited: 74,549 individuals participated in 1984-86; 64,523 in 1995-97; and 43,905 in 2006-08. RESULTS: Both systolic and diastolic blood pressure levels decreased substantially from mid 1980s to mid 2000s, with the most pronounced decrease from 1995-97 to 2006-08 (from 136.0/78.9 to 128.3/70.9 mmHg in women and from 140.1/82.1 to 133.7/76.5 mmHg in men). Although the use of blood pressure lowering medication increased, there was a considerable decrease even in those who reported never use of medication (mean decrease 6.8/7.2 mmHg in women and 6.3/5.3 mmHg in men), and the decrease was most pronounced in the elderly (mean decrease 16.1/12.4 mmHg in women and 14.7/10.4 mmHg in men aged 80+). Mean heart rate, total cholesterol and daily smoking decreased, self-reported hard physical activity increased, while body weight and the prevalence of diabetes increased during the same period. CONCLUSIONS: The BP decrease might seem paradoxically, as body weight and prevalence of diabetes increased during the same period. Salt consumption might have decreased, but no salt data is available. The parallel decrease in mean heart rate might indicate reduction in the white-coat phenomenon, or increased use of beta blockers or calcium channel blockers for other diagnosis than hypertension. Additionally, the data could support the "healthy obese" hypothesis, i.e., that subgroups in the population can sustain obesity without serious health consequences.

Prevalence of Thyroid Dysfunction in Autoimmune and Type 2 Diabetes: The Population-Based HUNT Study in Norway.

CONTEXT: Associations between autoimmune diabetes and autoimmune thyroid disease are known but insufficiently characterized. Some evidence suggests that type 2 diabetes may also be associated with hypothyroidism. OBJECTIVE: The objective of the study was to investigate associations of autoimmune and type 2 diabetes with the prevalence of hypo- and hyperthyroidism. DESIGN AND SETTING: This was a cross-sectional, population-based study of adults in two surveys of the Nord-Trøndelag Health (HUNT) Study. PARTICIPANTS: A total of 34 235 participants of HUNT2 (1995-1997) and 48 809 participants of HUNT3 (2006-2008) participated in the study. MAIN OUTCOME MEASURES: Prevalence of hypo- and hyperthyroidism was estimated, assessed by self-report, serum measurements, and linkage with the Norwegian Prescription Database. RESULTS: In HUNT2, autoimmune diabetes was associated with a higher age-adjusted prevalence of hypothyroidism among both women (prevalence ratio 1.79, 95% confidence interval [CI] 1.30-2.47) and men (prevalence ratio 2.71, 95% CI 1.76-4.19), compared with having no diabetes. For hyperthyroidism, the corresponding cumulative prevalence ratios were 2.12 (95% CI 1.36-3.32) in women and 2.54 (95% CI 1.24-5.18) in men with autoimmune diabetes. The age-adjusted excess prevalence of hypothyroidism (∼6 percentage points) and the presence of thyroid peroxidase antibodies (8-10 percentage points) associated with autoimmune diabetes was similar in women and men. Type 2 diabetes was not associated with the prevalence of hypothyroidism. In HUNT3, associations were broadly similar to those in HUNT2. CONCLUSIONS: Autoimmune diabetes, but not type 2 diabetes, was strongly and gender neutrally associated with an increased prevalence of hypo- and hyperthyroidism and the presence of thyroid peroxidase antibodies. Increased surveillance for hypothyroidism appears not necessary in patients with type 2 diabetes.

The Chromosome 9p21 CVD- and T2D-Associated Regions in a Norwegian Population (The HUNT2 Survey).

Background. Two adjacent regions upstream CDKN2B on chromosome 9p21 have been associated with type 2 diabetes (T2D) and progression of cardiovascular disease (CVD). The precise location and number of risk variants have not been completely delineated and a possible synergistic relationship between the adjacent regions is not fully addressed. By a population based cross-sectional case-control design, we genotyped 18 SNPs upstream of CDKN2B tagging 138 kb in and around two LD-blocks associated with CVD and T2D and investigated associations with T2D, angina pectoris (AP), myocardial infarction (MI), coronary heart disease (CHD; AP or AMI), and stroke using 5,564 subjects from HUNT2. Results. Single point and haplotype analysis showed evidence for only one common T2D risk haplotype (rs10757282∣rs10811661: OR = 1.19, P = 2.0 × 10(-3)) in the region. We confirmed the strong association between SNPs in the 60 kb CVD region with AP, MI, and CHD (P < 0.01). Conditioning on the lead SNPs in the region, we observed two suggestive independent single SNP association signals for MI, rs2065501 (P = 0.03) and rs3217986 (P = 0.04). Conclusions. We confirmed the association of known variants within the 9p21 interval with T2D and CHD. Our results further suggest that additional CHD susceptibility variants exist in this region.

Glycaemic control in people with diabetes influences the beneficial role of physical activity on cardiovascular mortality. Prospective data from the HUNT Study, Norway.

AIM: To examine whether glycaemic control in people with diabetes, measured as glycated haemoglobin (HbA1c), influences the role of leisure time physical activity on the increased risk of death from cardiovascular disease. METHODS: We prospectively examined the joint association of diabetes according to glycemic control, measured as glycated haemoglobin (HbA1c), and physical activity with cardiovascular mortality. A total of 53,549 were followed up for 12 years through the Norwegian Cause of Death Registry. Cox proportional adjusted hazard ratios (HRs) with 95% confidence intervals (CI) were estimated. RESULTS: Overall, 1710 people died from cardiovascular disease during the follow-up. Compared to the reference group of inactive people without diabetes, people with diabetes and HbA1c<8.0%, had a hazard ratio (HR) of 1.46 (95% CI: 0.96, 2.21) if they were physically inactive and a HR of 1.33 (95% CI: 0.81, 2.19) if they were physically active. Among people with diabetes and HbA1c ≥ 8.0%, the corresponding comparison gave HRs 2.69 (95% CI: 2.11, 3.42) and 0.93 (95% CI: 0.64, 1.36), respectively. CONCLUSIONS: The data suggest that physical activity should be more strongly encouraged as a therapeutic measure additional to medical treatment, especially among those with most severe hyperglycemia.

Sedentary behaviour and risk of mortality from all-causes and cardiometabolic diseases in adults: evidence from the HUNT3 population cohort.

BACKGROUND: Sedentary behaviour is a potential risk factor for chronic-ill health and mortality, that is, independent of health-enhancing physical activity. Few studies have investigated the risk of mortality associated with multiple contexts of sedentary behaviour. OBJECTIVE: To examine the prospective associations of total sitting time, TV-viewing time and occupational sitting with mortality from all causes and cardiometabolic diseases. METHODS: Data from 50,817 adults aged ≥20 years from the Nord-Trøndelag Health Study 3 (HUNT3) in 2006-2008 were linked to the Norwegian Cause of Death Registry up to 31 December 2010. Cox proportional hazards models examined all-cause and cardiometabolic disease-related mortality associated with total sitting time, TV-viewing and occupational sitting, adjusting for multiple potential confounders including physical activity. RESULTS: After mean follow-up of 3.3 years (137,315.8 person-years), 1068 deaths were recorded of which 388 were related to cardiometabolic diseases. HRs for all-cause mortality associated with total sitting time were 1.12 (95% CI 0.89 to 1.42), 1.18 (95% CI 0.90 to 1.57) and 1.65 (95% CI 1.24 to 2.21) for total sitting time 4-<7, 7-<10 and ≥10 h/day, respectively, relative to <4 h/day after adjusting for confounders (p-trend=0.001). A similar pattern of associations was observed between total sitting time and mortality from cardiometabolic diseases, but TV-viewing time and occupational sitting showed no or borderline significant associations with all-cause or cardiometabolic disease-related mortality over the same follow-up period. CONCLUSIONS: Total sitting time is associated with all-cause and cardiometabolic disease-related mortality in the short term. However, prolonged sitting in specific contexts (ie, watching TV, at work) do not adversely impact health in the same timeframe. These findings suggest that adults should be encouraged to sit less throughout the day to reduce their daily total sitting time.

Is depression a risk factor for diabetic foot ulcers? 11-years follow-up of the Nord-Trøndelag Health Study (HUNT).

AIM: To prospectively examine whether depressive symptoms increase the risk of diabetes and a diabetic foot ulcer. METHODS: The Nord-Trøndelag Health Study (HUNT) is a community-based longitudinal study. The Hospital Anxiety and Depression Scale (HADS-D subscale) assessed depressive symptoms. We followed individuals with complete HADS-D data from HUNT2 (1995-97) and assessed whether they reported diabetes with or without a history of diabetic foot ulcer (DFU) in HUNT3 (2006-08) (n=36,031). Logistic regression was used to investigate the effect of depressive symptoms on subsequent development of diabetes and of DFU. RESULTS: Unadjusted odds for reporting diabetes at follow-up was higher among individuals who reported a HADS-D score≥8 at baseline (OR 1.30 95% CI, 1.07-1.57) than among those reporting a lower score. After adjusting for age, gender and BMI, this association was no longer significant. The odds of developing a DFU was almost two-fold (OR=1.95 95% CI, 1.02-3.74) for those reporting a HADS-D score of 8-10, and 3-fold (OR=3.06 95% CI, 1.24-7.54) for HADS-D scores≥11, compared to HADS-D scores<8, after adjusting for age, gender and serum glucose. CONCLUSIONS: Symptoms of depression at baseline are associated with an increased risk of a diabetic foot ulcer in a dose response manner during this 11-year follow-up.

No increase in new users of blood glucose-lowering drugs in Norway 2006-2011: a nationwide prescription database study.

BACKGROUND: National estimates for the occurrence of diabetes are difficult to obtain, particularly time trends in incidence. The aim was to describe time trends in prevalent and incident use of blood glucose-lowering drugs by age group and gender in Norway during 2005-2011. METHODS: Data were obtained from the nationwide Norwegian Prescription Database. We defined prevalent users of "insulins only" as individuals having no oral antidiabetic drugs (OAD) dispensed from a pharmacy during the previous 24 months or in the subsequent 12 months. Incident users had no blood glucose-lowering drugs dispensed in the previous 24 months; incident "insulins only" users also had no OAD in the subsequent 12 months. RESULTS: In 2011, 3.2% of the population had blood glucose-lowering drugs dispensed, and the incidence rate was 313 per 100,000 person years. The prevalence of OAD use increased from 1.8% in 2005 to 2.4% in 2011; however a decreasing trend in incidence of OAD use was observed, particularly in those aged 70 years and older. In 2010, 0.64% of the population had insulins only dispensed, with an overall incidence rate in the total population of 33 per 100,000 person years which was stable over time. CONCLUSIONS: In this nationwide study, we found that although the prevalent use of OAD had increased in recent years, incident use was stable or had decreased. This may indicate that the increase in diabetes occurrence in Norway is levelling off, at least temporarily.

The prevalence of metabolic syndrome and metabolically healthy obesity in Europe: a collaborative analysis of ten large cohort studies.

BACKGROUND: Not all obese subjects have an adverse metabolic profile predisposing them to developing type 2 diabetes or cardiovascular disease. The BioSHaRE-EU Healthy Obese Project aims to gain insights into the consequences of (healthy) obesity using data on risk factors and phenotypes across several large-scale cohort studies. Aim of this study was to describe the prevalence of obesity, metabolic syndrome (MetS) and metabolically healthy obesity (MHO) in ten participating studies. METHODS: Ten different cohorts in seven countries were combined, using data transformed into a harmonized format. All participants were of European origin, with age 18-80 years. They had participated in a clinical examination for anthropometric and blood pressure measurements. Blood samples had been drawn for analysis of lipids and glucose. Presence of MetS was assessed in those with obesity (BMI ≥ 30 kg/m2) based on the 2001 NCEP ATP III criteria, as well as an adapted set of less strict criteria. MHO was defined as obesity, having none of the MetS components, and no previous diagnosis of cardiovascular disease. RESULTS: Data for 163,517 individuals were available; 17% were obese (11,465 men and 16,612 women). The prevalence of obesity varied from 11.6% in the Italian CHRIS cohort to 26.3% in the German KORA cohort. The age-standardized percentage of obese subjects with MetS ranged in women from 24% in CHRIS to 65% in the Finnish Health2000 cohort, and in men from 43% in CHRIS to 78% in the Finnish DILGOM cohort, with elevated blood pressure the most frequently occurring factor contributing to the prevalence of the metabolic syndrome. The age-standardized prevalence of MHO varied in women from 7% in Health2000 to 28% in NCDS, and in men from 2% in DILGOM to 19% in CHRIS. MHO was more prevalent in women than in men, and decreased with age in both sexes. CONCLUSIONS: Through a rigorous harmonization process, the BioSHaRE-EU consortium was able to compare key characteristics defining the metabolically healthy obese phenotype across ten cohort studies. There is considerable variability in the prevalence of healthy obesity across the different European populations studied, even when unified criteria were used to classify this phenotype.