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.

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.

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.

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 .

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.

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.

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.

Does diabetes have a protective effect on migraine?

BACKGROUND: Diabetes is associated with an increased risk of several other chronic diseases. In contrast, a previous study found an inverse relation between diabetes and migraine, whereas another large population-based study showed that the prevalence of migraine among patients with diabetes varied strongly depending on age. We aimed to investigate how the prevalence of medically treated migraine in patients with diabetes varied depending on diabetic drug treatment, sex, and age in the complete Norwegian population. METHODS: Data on all persons in Norway being prescribed medication for diabetes (n =124,649) or migraine (n = 81,225) in 2006 were obtained from the National Register of Prescriptions and analyzed in a cross-sectional design. RESULTS: Persons using diabetic drugs had an overall reduced prevalence of medically treated migraine when compared with the nondiabetic population (odds ratio [OR] = 0.72 [95% confidence interval = 0.68-0.75]). The OR was strongly associated with age. Although young persons receiving oral diabetic medication had, in fact, an increased prevalence of medically treated migraine, the prevalence declined with increasing age to about the same reduced prevalence (OR = 0.4-0.6) for all types of diabetes treatment in patients 60 to 69 years of age. The prevalence was equally decreased between men and women. CONCLUSIONS: The results suggest a markedly reduced prevalence of migraine among older patients with diabetes, when compared with the general population. One may speculate that the seemingly protective effect of diabetes on migraine could be a result of neuropathy.

Long-term tracking of plasma phospholipid fatty acid concentrations and their correlation with the dietary intake of marine foods in newly diagnosed diabetic patients: results from a follow-up of the HUNT Study, Norway.

Analysis of long-chain n-3 and n-6 fatty acid (FA) concentrations is used to evaluate their potential health effects in epidemiological studies, and, recently, also to counsel patients with a suboptimal intake of n-3 FA. Data on the method's ability to track and detect differences within and between individuals in appropriate populations are, however, lacking. The present study provides such data for twenty-nine plasma phospholipid (PL) FA concentrations and indices measured in 214 newly diagnosed type 2 diabetic patients at baseline and after 3 years. 20 : 3n-6 and the 20 : 4n-6:20 : 3n-6 ratio showed the highest tracking coefficients (Spearman's r 0.68), while DHA, EPA and PLN3-index (EPA+DHA) coefficients were 0.60, 0.47 and 0.55, respectively. Fish consumption measured simultaneously with EPA, DHA, sum n-3 and PLN3 index showed Spearman's correlation coefficients of 0.47, 0.44, 0.48 and 0.49, respectively, decreasing to 0.20, 0.19, 0.22 and 0.21 when measured 3 years apart. The within-subject CV of EPA, DHA and PLN3 index were 39.9, 14.3 and 18.0 %, respectively. The corresponding between-subject CV were 33.6, 16.5 and 18.7 %, while the reference change values were 112, 41 and 52 %. In conclusion, PL n-3 FA concentrations showed a significant long-term tracking and were positively correlated with marine food intake. Analytical precision, biological variability, reference change value and the index of individuality of EPA, DHA and PLN3 index are similar to commonly used clinical biomarkers, supporting their validity as dietary markers in clinical and epidemiological work.

Social and spatial patterns of obesity diffusion over three decades in a Norwegian county population: the HUNT Study.

BACKGROUND: In order to develop effective preventive strategies, knowledge of trends in socioeconomic and geographical differences in risk factor levels is important. The objective of this study was to examine social and spatial patterns of obesity diffusion in a Norwegian population during three decades. METHODS: Data on adults aged 30-69 years from three cross-sectional health surveys eleven years apart in the Nord-Trøndelag Health Study, Norway, HUNT1 (1984-1986), HUNT2 (1995-1997) and HUNT3 (2006-2008) were utilized. Body mass index (BMI) was used as a measure of obesity. Height and weight were measured clinically. Age standardized prevalences, absolute prevalence differences and ratios, prevalence odds ratios for BMI and the Relative Index of Inequality (RII) were calculated. Multilevel statistical models were fitted for analysing geographical patterns. RESULTS: The prevalence of obesity was systematically higher in groups with lower socio-economic status and increased successively in all groups in the population during the three decades. The relative socioeconomic inequalities in obesity measured by level of education did not change substantially in the period. In HUNT1 (1984-86) obesity was most prevalent among low educated women (14.1%) and in HUNT3 (2006-08) among low educated men (30.4%). The RII for men changed from 2.60 to 1.91 and 2.36 in HUNT1, HUNT2 and HUNT3. In women the RIIs were 1.71, 2.28 and 2.30 correspondingly. However, the absolute obesity prevalence inequalities increased, and a geographical diffusion from central to distal districts was observed from HUNT2 to HUNT3. CONCLUSIONS: The prevalence of obesity increased in all socioeconomic groups in this Norwegian adult county population from the 1980ies up to present time. The data did not suggest increasing relative inequalities, but increasing absolute socioeconomic differences and a geographical diffusion towards rural districts. Public health preventive strategies should be oriented to counteract the obesity epidemic in the population.

A prospective population-based cohort study of lactation and cardiovascular disease mortality: the HUNT study.

BACKGROUND: Recent studies suggest that lactation has long-term effects on risk for cardiovascular disease in women, but the effects on cardiovascular mortality are less well known. METHOD: In a Norwegian population-based prospective cohort study, we studied the association of lifetime duration of lactation with cardiovascular mortality in 21,889 women aged 30 to 85 years who attended the second Nord-Trøndelag Health Survey (HUNT2) in 1995-1997. The cohort was followed for mortality through 2010 by a linkage with the Cause of Death Registry. Adjusted hazard ratios (HR) for death from all causes and cardiovascular disease were calculated using Cox regression. RESULTS: During follow-up, 1,246 women died from cardiovascular disease. Parous women younger than 65 years who had never lactated had a higher cardiovascular mortality than the reference group of women who had lactated 24 months or more (HR 2.77, 95% confidence interval [CI]: 1.28, 5.99). There was some evidence of a U-shaped association, where women who reported lactating 7-12 months had a HR of 0.55 (95% CI: 0.27, 1.09). No clear associations were observed among women 65 years or older. CONCLUSIONS: Excess cardiovascular mortality rates were observed among parous women younger than 65 years who had never lactated. These findings support the hypothesis that lactation may have long-term influences on maternal cardiovascular health.

Is physical activity maintenance from adolescence to young adulthood associated with reduced CVD risk factors, improved mental health and satisfaction with life: the HUNT Study, Norway.

BACKGROUND: Little is known about the effect maintaining physical activity throughout adolescence has on cardiovascular risk factors and health status in early adulthood. This ten-year prospective longitudinal study investigated whether differences in physical activity patterns from adolescence to young-adulthood showed different associations with subsequent cardio-metabolic risk factors and mental health in young-adulthood. METHODS: Based on the second and third Norwegian Nord-Trøndelag Health Surveys (HUNT2 and 3), we included 1869 individuals (838 males) participating in Young-HUNT (1995-97), aged 13-19 years and followed-up at HUNT3 (2006-08), aged 23-31. Self-reported physical activity (PA), mental health and perceived health were recorded, along with measurements of body mass index (BMI), waist circumference (WC), total cholesterol (TC), HDL cholesterol, glucose, triglycerides, resting heart rate (HR) and blood pressure. We used separate linear regressions models to investigate associations between physical activity and each CVD risk factor, and logistic regression analysis to examine PA patterns and subsequent mental health. Physically active maintainers were compared to inactive maintainers. Adopters (inactive as adolescents and physically active as young adults) were compared to inactive maintainers and to those who discontinued activity (relapsers). RESULTS: Active maintainers had significantly lower HR, compared to all other PA patterns. Active maintaining men had significantly lower WC than relapsers and inactive maintainers. When adjusted for age and gender, WC, BMI, HR, diastolic blood pressure and HDL-C showed significant differences comparing active maintaining to other PA patterns. Comparing inactive maintainers against adopters, only HR was significantly lower. Male adopters did not differ significantly in CVD risk compared to inactive maintainers and relapsers. Among females adopting was associated with lower HR and TC compared to inactive maintainers. Active maintainers showed better mental health than inactive maintainers. Active maintaining males had an increased likelihood of good mental health compared to adopters. Active maintaining females reported greater satisfaction with life compared to adopters. CONCLUSIONS: Those who maintained their physical activity from adolescence to young adulthood demonstrated a significantly lower CVD risk and better mental health, compared to inactive maintainers. Compared to inactivity maintainers and relapsers, adopting physical activity was not significantly associated with lowered CVD risk. Adopting physical activity between adolescence and young adulthood may not necessarily protect against mental distress.

Abnormal glucose regulation and gender-specific risk of fatal coronary artery disease in the HUNT 1 study.

OBJECTIVES: To assess fatal coronary artery disease (CAD) by gender and glucose regulation status. DESIGN: 47,951 people were followed up according to fatal CAD identified in the National Cause of Death Registry. Gender-effects of fatal CAD in people with impaired glucose regulation (IGR), newly diagnosed diabetes (NDM) or known diabetes (KDM) compared with people with normal glucose regulation (NGR) were calculated using Cox regression. RESULTS: Using NGR as reference, the hazard ratios (HR, 95% confidence intervals) associated with IGR was 1.2 (0.8-1.9) for women and 1.2 (0.9-1.6) for men. The corresponding HRs were 1.6 (1.2-2.2) and 1.4 (1.1.-1.9) for NDM, and 2.5 (2.1-2.8) and 1.8 (1.6-2.1) for KDM. The gender-difference in mortality varied by category (P(interaction) = 0.003). Using women as the reference, the HRs for men were 2.1 (2.0-2.3) for NGR, 1.8 (1.0-3.3) for IGR, 1.6 (1.0-2.5) for NDM, and 1.2 (1.0-1.5) for KDM. CONCLUSIONS: Diabetes mellitus, but not IGR, was associated with fatal CAD in both genders. The known gender-difference in CAD mortality was attenuated in people with abnormal glucose regulation, evident already in people with IGR.

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.

Evaluation of four novel genetic variants affecting hemoglobin A1c levels in a population-based type 2 diabetes cohort (the HUNT2 study).

BACKGROUND: Chronic hyperglycemia confers increased risk for long-term diabetes-associated complications and repeated hemoglobin A1c (HbA1c) measures are a widely used marker for glycemic control in diabetes treatment and follow-up. A recent genome-wide association study revealed four genetic loci, which were associated with HbA1c levels in adults with type 1 diabetes. We aimed to evaluate the effect of these loci on glycemic control in type 2 diabetes. METHODS: We genotyped 1,486 subjects with type 2 diabetes from a Norwegian population-based cohort (HUNT2) for single-nucleotide polymorphisms (SNPs) located near the BNC2, SORCS1, GSC and WDR72 loci. Through regression models, we examined their effects on HbA1c and non-fasting glucose levels individually and in a combined genetic score model. RESULTS: No significant associations with HbA1c or glucose levels were found for the SORCS1, BNC2, GSC or WDR72 variants (all P-values > 0.05). Although the observed effects were non-significant and of much smaller magnitude than previously reported in type 1 diabetes, the SORCS1 risk variant showed a direction consistent with increased HbA1c and glucose levels, with an observed effect of 0.11% (P = 0.13) and 0.13 mmol/l (P = 0.43) increase per risk allele for HbA1c and glucose, respectively. In contrast, the WDR72 risk variant showed a borderline association with reduced HbA1c levels (ß = -0.21, P = 0.06), and direction consistent with decreased glucose levels (ß = -0.29, P = 0.29). The allele count model gave no evidence for a relationship between increasing number of risk alleles and increasing HbA1c levels (ß = 0.04, P = 0.38). CONCLUSIONS: The four recently reported SNPs affecting glycemic control in type 1 diabetes had no apparent effect on HbA1c in type 2 diabetes individually or by using a combined genetic score model. However, for the SORCS1 SNP, our findings do not rule out a possible relationship with HbA1c levels. Hence, further studies in other populations are needed to elucidate whether these novel sequence variants, especially rs1358030 near the SORCS1 locus, affect glycemic control in type 2 diabetes.

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.

Glycaemic control in newly diagnosed diabetes patients and mortality from ischaemic heart disease: 20-year follow-up of the HUNT Study in Norway.

AIMS: To assess the influence of glycaemic control on long-term mortality from ischaemic heart disease (IHD) in patients with newly diagnosed diabetes. METHODS AND RESULTS: In a large population study in Norway, people > or =40 years with non-fasting glucose > or =8 mmol/L were invited to a fasting glucose test, and if the fasting value was <7 mmol/L, an oral glucose tolerance test was also performed. Among people who were diagnosed with diabetes, 205 patients were followed with annual measurements of HbA1c in order to monitor glycaemic control. Stratified Cox regression analysis was used to compare IHD mortality rates during 20 years of follow-up, with comparison of newly diagnosed diabetes patients and a matched group of 205 individuals without diabetes. Among patients, we also assessed the relation of HbA1c with IHD mortality. After adjustment for potentially confounding factors, IHD mortality in the total diabetes group was substantially higher (HR 1.8, 95% CI, 1.0-3.4) compared with the comparison group. However, the increased risk was particularly high in patients with HbA1c in the highest quartile (HR 4.2, 95% CI, 2.1-8.1). Analysing HbA1c as a continuous time-varying variable showed 30% (HR 1.3, CI 1.1-1.5) higher risk per increment of HbA1c among diabetes patients without known CVD at baseline. CONCLUSION: Poor long-term glycaemic control is associated with a substantial increase in the risk of dying from IHD in patients with diabetes, whereas in patients with reasonably good control, risk of dying from IHD may not substantially differ from that of people without diabetes.

The association between history of diabetic foot ulcer, perceived health and psychological distress: the Nord-Trøndelag Health Study.

BACKGROUND: While the adverse impact of a history of a foot ulcer on physical health among persons with diabetes is well known, little is known about the association between foot ulcer, perceived health and psychological distress. Results from various studies are difficult to compare as different study designs, samples and/or different questionnaires have been used. The aim of this study was to compare levels of anxiety and depression, psychological well-being and perceived health between persons with diabetes, with or without a history of foot ulcer, and persons without diabetes in a large study of community-dwelling individuals. METHODS: This study included 65,126 persons, of whom 63,632 did not have diabetes, 1,339 had diabetes without a history of foot ulcer and 155 had diabetes and a history of foot ulcer. Levels of anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS). Psychological well-being was measured on a four-item scale, and perceived health was measured with a one-item question. We investigated whether levels of anxiety, depression, psychological well-being and perceived health were different in the three study groups using multiple regression models controlling for demographic factors, body mass index, smoking and cardiovascular conditions. Separate multivariate analyses comparing the two diabetes samples were additionally adjusted for diabetes-specific variables. RESULTS: A history of foot ulcer was significantly associated with more depressive symptoms, poorer psychological well-being and poorer perceived health compared to participants without diabetes. In multivariate analyses, perceived health and psychological well-being were significantly poorer among those with a history of foot ulcer compared to those without diabetes. Among persons with diabetes, perceived health was significantly worse among those with a history of foot ulcer. After multivariate adjustment, levels of anxiety and depression and psychological well-being did not differ between the two diabetes groups. CONCLUSION: Perceived health and psychological well-being were significantly poorer among participants with diabetes and a history of foot ulcer compared to those without diabetes. Among people with diabetes, a history of foot ulcer had significant negative impact on perceived health but did not independently contribute to psychological distress.

Diabetes related risk factors did not explain the increased risk for urinary incontinence among women with diabetes. The Norwegian HUNT/EPINCONT study.

BACKGROUND: Previous studies have shown an association between diabetes mellitus (DM) and urinary incontinence (UI) in women, especially severe UI. The purpose of this study was to investigate whether diabetes related variables could explain this association. METHODS: The study is part of the EPINCONT study, which is based on the large Nord-Trøndelag Health Study 2 (HUNT 2), performed in the county of Nord-Trøndelag, Norway, during the years 1995 - 1997. Questions on diabetes and UI were answered by a total of 21 057 women aged 20 years and older. Of these 685 were identified as having diabetes, and thus comprise the population of our study. A variety of clinical and biochemical variables were recorded from the participants. RESULTS: Blood-glucose, HbA1c, albumine:creatinine ratio (ACR), duration of diabetes, diabetes treatment, type of diabetes, cholesterol and triglycerides did not significantly differ in women with and without UI in crude analyses. However, the diabetic women with UI had more hospitalizations during the last 12 months, more homecare, and a higher prevalence of angina and use of oestrogene treatment (both local and oral/patch). After adjusting for age, BMI, parity and smoking, there were statistically significant associations between any UI and angina (OR 1.89; 95% CI: 1.22 - 2.93), homecare (OR 1.72; 95% CI: 1.02 - 2.89), and hospitalization during the last 12 months (OR 1.67; 95% CI: 1.18 - 2.38). In adjusted analyses severe UI was also significantly associated with the same variables, and also with diabetes drug treatment (OR 2.10; 95% CI: 1.07 - 4.10) and stroke (OR 2.47; 95% CI: 1.09 - 5.59). CONCLUSION: No single diabetes related risk factor seems to explain the increased risk for UI among women with diabetes. However, we found associations between UI and some clinical correlates of diabetes.

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.