High Levels of Education Are Associated With an Increased Risk of Latent Autoimmune Diabetes in Adults: Results from the Nord-Trøndelag Health Study

Although autoimmune diabetes in adults is a common form of diabetes, knowledge on risk factors and long term consequences of the disease is limited. The aims of this thesis were to investigate the influence of socioeconomic factors (education and occupation), sleep disturbances and psychological well-being on the risk of developing autoimmune diabetes in adults, to investigate whether genetic variation in the melatonin receptor 1B (MTNR1B) contributes to the association between poor sleep and type 2 diabetes which has been previously suggested, and finally to investigate the risk of mortality from all causes, cardiovascular disease and ischemic heart disease in adult-onset autoimmune diabetes, with consideration of the possible influence of metabolic risk factors, glycaemic control, lifestyle factors and socioeconomic position. These studies are based on data from the Norwegian HUNT Study, to date the largest population-based study where incident cases of autoimmune diabetes in adults can be separated from cases of type 2 diabetes. The HUNT Study consists of three separate surveys performed on three occasions in 1984-2008 and contains information from questionnaires, clinical examinations and blood samples. Information on mortality was obtained by linkage to the national Cause of Death Registry. Individuals who were positive for antibodies against glutamic acid decarboxylase and with onset of diabetes at ≥35 years were classified as having autoimmune diabetes in adults. The main finding of Study I was that high educational levels (university versus primary school) were associated with an increased risk of autoimmune diabetes in adults (HR 1.98, 95% CI 1.21-3.26) after adjustment for BMI, physical activity, smoking, alcohol consumption, and family history of diabetes, whereas type 2 diabetes was more common in those with low education. An increased risk of autoimmune diabetes in adults was also seen in individuals who reported having sleep disturbances and low psychological well-being (HR 1.84, 95% CI 1.10-3.09), a risk similar to that seen in type 2 diabetes (HR 1.31, 95% CI 1.13-1.50) (Study II). The results from Study III indicated that there was no influence of the MTNR1B genetic variant on the association between poor sleep and type 2 diabetes. The association remained after adjustment for genotype and was seen in non-carriers as well as in carriers of the risk allele. Mortality from all causes (HR 1.55, 95% CI 1.25-1.92), cardiovascular disease (HR 1.87, 95% CI 1.40-2.48) and ischemic heart disease (HR 2.39, 95% CI 1.57-3.64) was increased in autoimmune diabetes in adults compared to individuals without diabetes. Importantly, mortality risk was as high as in type 2 diabetes, despite a more favourable metabolic risk profile in patients with autoimmune diabetes. In these patients, excess mortality appeared to be primarily associated with poor glycaemic control. These findings suggest, for the first time, that socioeconomic and psychosocial factors contribute to the development of autoimmune diabetes in adults. The results are in line with previous data indicating that the aetiology of autoimmune diabetes is partly similar to that of type 2 diabetes but suggest, also, that there are other, currently unidentified, environmental risk factors for autoimmune diabetes that remain to be explored. Finally, the results indicate that survival in individuals with autoimmune diabetes with adult onset would be improved by a more effective treatment

Body mass index and mortality in elderly men and women: the Tromsø and HUNT studies

The impact of body mass index (BMI; kg/m2) and waist circumference (WC) on mortality in elderly individuals is controversial and previous research has largely focused on obesity. With special attention to the lower BMI categories, associations between BMI and both total and cause-specific mortality were explored in 7604 men and 9107 women aged ≥65 years who participated in the Tromsø Study (1994–1995) or the North-Trøndelag Health Study (1995–1997). A Cox proportional hazards model adjusted for age, marital status, education and smoking was used to estimate HRs for mortality in different BMI categories using the BMI range of 25–27.5 as a reference. The impact of each 2.5 kg/m2 difference in BMI on mortality in individuals with BMI<25.0 and BMI≥25.0 was also explored. Furthermore, the relations between WC and mortality were assessed. We identified 7474 deaths during a mean follow-up of 9.3 years. The lowest mortality was found in the BMI range 25–29.9 and 25–32.4 in men and women, respectively. Mortality was increased in all BMI categories below 25 and was moderately increased in obese individuals. U-shaped relationships were also found between WC and total mortality. About 40% of the excess mortality in the lower BMI range in men was explained by mortality from respiratory diseases. BMI below 25 in elderly men and women was associated with increased mortality. A modest increase in mortality was found with increasing BMI among obese men and women. Overweight individuals (BMI 25–29.9) had the lowest mortality

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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).</p> <p>Conclusion</p> <p>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.</p

History of Foot Ulcer Increases Mortality Among Individuals With Diabetes: Ten-year follow-up of the Nord-Trøndelag Health Study, Norway

OBJECTIVE To compare mortality rates for individuals with diabetes with and without a history of foot ulcer (HFU) and with that for the nondiabetic population. RESEARCH DESIGN AND METHODS This population-based study included 155 diabetic individuals with an HFU, 1,339 diabetic individuals without an HFU, and 63,632 nondiabetic individuals who were all followed for 10 years with mortality as the end point. RESULTS During the follow-up period, a total of 49.0% of diabetic individuals with an HFU died, compared with 35.2% of diabetic individuals without an HFU and 10.5% of those without diabetes. In Cox regression analyses adjusted for age, sex, education, current smoking, and waist circumference, having an HFU was associated with more than a twofold (2.29 [95% CI 1.82–2.88]) hazard risk for mortality compared with that of the nondiabetic group. In corresponding analyses comparing diabetic individuals with and without an HFU, an HFU was associated with 47% increased mortality (1.47 [1.14–1.89]). Significant covariates were older age, male sex, and current smoking. After inclusion of A1C, insulin use, microalbuminuria, cardiovascular disease, and depression scores in the model, each was significantly related to life expectancy. CONCLUSIONS AN HFU increased mortality risk among community-dwelling adults and elderly individuals with diabetes. The excess risk persisted after adjustment for comorbidity and depression scores, indicating that close clinical monitoring might be warranted among individuals with an HFU, who may be particularly vulnerable to adverse outcomes. Hospital-based studies have shown that mortality rates in individuals with diabetic foot ulcers are about twice those observed in individuals with diabetes without foot ulcers (1,2). A diabetic foot ulcer reflects the presence of underlying pathological conditions, and the risk of recurrent ulcers is high (3,4). It has been suggested that the elevated mortality rate among individuals with diabetic foot ulcers is related to comorbid disease such as cardiovascular disease and nephropathy (5) or to psychological factors including depression (6). Although the mortality rate in individuals with diabetes is high, no large population-based studies have examined the impact on mortality of a history of foot ulcers (HFU) among individuals with diabetes. The purpose of this study was to compare mortality rates for individuals with diabetes reporting an HFU with those for individuals without an HFU and the nondiabetic population. These issues were investigated in the Nord-Trøndelag Health Study (HUNT 2), which includes a very large population-based sample of men and women from a well-defined geographic area. Participants with self-reported diabetes were well characterized with regard to their diabetes, and information on demographics, lifestyle, and prevalent disease including depression was available

Diabetes: cost of illness in Norway

<p>Abstract</p> <p>Background</p> <p>Diabetes mellitus places a considerable burden on patients in terms of morbidity and mortality and on society in terms of costs. Costs related to diabetes are expected to increase due to increasing prevalence of type 2 diabetes. The aim of this study was to estimate the health care costs attributable to type 1 and type 2 diabetes in Norway in 2005.</p> <p>Methods</p> <p>Data on inpatient hospital services, outpatient clinic visits, physician services, drugs, medical equipment, nutrition guidance, physiotherapy, acupuncture, foot therapy and indirect costs were collected from national registers and responses to a survey of 584 patients with diabetes. The study was performed with a prevalence approach. Uncertainty was explored by means of bootstrapping.</p> <p>Results</p> <p>When hospital stays with diabetes as a secondary diagnosis were excluded, the total costs were €293 million, which represents about 1.4% of the total health care expenditure. Pharmaceuticals accounted for €95 million (32%), disability pensions €48 million (16%), medical devices €40 million (14%) and hospital admissions €21 million (7%). Patient expenditures for acupuncture, physiotherapy and foot therapy were many times higher than expenditure for nutritional guidance. Indirect costs (lost production from job absenteeism) accounted for €70.1 million (24% of the €293 million) and included sick leave (€16.7 million), disability support and disability pensions (€48.2 million) and other indirect costs (€5.3 million). If all diabetes related hospital stays are included (primary- and secondary diagnosis) total costs amounts to €535 million, about 2.6% of the total health care expenditure in Norway.</p> <p>Conclusions</p> <p>Diabetes represents a considerable burden to society in terms of health care costs and productivity losses.</p

Heterogeneity of Patients With Latent Autoimmune Diabetes in Adults: Linkage to Autoimmunity Is Apparent Only in Those With Perceived Need for Insulin Treatment: Results from the Nord-Trøndelag Health (HUNT) study

OBJECTIVE—Subjects with the diagnosis of latent autoimmune diabetes in adults (LADA) are more prone to need insulin treatment than those with type 2 diabetes. However, not all patients with LADA develop the need for insulin treatment, indicating the heterogeneity of LADA. We investigated this heterogeneity by comparing phenotypes of LADA with and without perceived need for insulin treatment (data obtained at times when diagnosis of LADA was not investigated) and also compared LADA and type 2 diabetes phenotypes

FTO, Type 2 Diabetes, and Weight Gain Throughout Adult Life: A Meta-Analysis of 41,504 Subjects From the Scandinavian HUNT, MDC, and MPP Studies

OBJECTIVE—FTO is the most important polygene identified for obesity. We aimed to investigate whether a variant in FTO affects type 2 diabetes risk entirely through its effect on BMI and how FTO influences BMI across adult life span. RESEARCH DESIGN AND METHODS—Through regression models, we assessed the relationship between the FTO single nucleotide polymorphisms rs9939609, type 2 diabetes, and BMI across life span in subjects from the Norwegian population-based HUNT study using cross-sectional and longitudinal perspectives. For replication and meta-analysis, we used data from the Malmö Diet and Cancer (MDC) and Malmö Preventive Project (MPP) cohorts, comprising a total sample of 41,504 Scandinavians.RESULTS—The meta-analysis revealed a highly significant association for rs9939609 with both type 2 diabetes (OR 1.13; P = 4.5 3 1028) and the risk to develop incident type 2 diabetes (OR 1.16; P = 3.2 3 1028). The associations remained also after correction for BMI and other anthropometric measures. Furthermore, we confirmed the strong effect on BMI (0.28 kg/m2 per risk allele; P = 2.0 3 10226), with no heterogeneity between different age-groups. We found no differences in change of BMI over time according to rs9939609 risk alleles, neither overall (ΔBMI = 0.0[20.05, 0.05]) nor in any individual age stratum, indicating no further weight gain attributable to FTO genotype in adults. CONCLUSIONS—We have identified that a variant in FTO alters type 2 diabetes risk partly independent of its observed effect on BMI. The additional weight gain as a result of the FTO risk variant seems to occur before adulthood, and the BMI difference remains stable thereafter

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, = 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 ( &lt; 0.01). Conditioning on the lead SNPs in the region, we observed two suggestive independent single SNP association signals for MI, rs2065501 ( = 0.03) and rs3217986 ( = 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