J. Ostman

Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS)

Aims/hypothesisLow plasma vitamin D concentrations may promote the development of type 1 diabetes. To test this hypothesis, we measured plasma 25-hydroxyvitamin D (25OHD) in young adults with type 1 diabetes.MethodsThe nationwide Diabetes Incidence Study in Sweden (DISS) covers 15- to 34-year-old people with newly diagnosed diabetes. Blood samples at diagnosis were collected during the 2-year period 1987/1988. Patients with islet antibodies (islet cell antibodies, GAD antibodies or tyrosine phosphatase-like protein antibodies) were defined as having autoimmune type 1 diabetes. Plasma 25OHD was measured in samples taken from 459 patients at the time of diagnosis, and in 138 of these subjects 8xa0years later. The results were compared with age- and sex-matched control subjects (n=208).ResultsAt diagnosis, plasma 25OHD levels were significantly lower in patients with type 1 diabetes than in control subjects (82.5±1.3 vs 96.7±2.0xa0nmol/l; p<0.0001). Eight years later, plasma 25OHD had decreased in patients (81.5±2.6xa0nmol/l; p=0.04). Plasma 25OHD levels were significantly lower in diabetic men than in diabetic women at diagnosis (77.9±1.4 vs 90.1±2.4xa0nmol/l; p<0.0001) and at follow-up (77.1±2.8xa0nmol/l vs 87.2±4.5xa0nmol/l; p=0.048).Conclusions/interpretationThe plasma 25OHD level was lower at diagnosis of autoimmune type 1 diabetes than in control subjects, and may have a role in the development of type 1 diabetes. Plasma 25OHD levels were lower in men than in women with type 1 diabetes. This difference may be relevant to the high incidence of type 1 diabetes among young adult men.

Human Adipose Tissue Dynamics and Regulation

Publisher Summary The main functions of adipose tissue are to store and release fat. The exogenous fat via intestinal absorption reaches adipose tissue mainly as chylomicrons, and the triglyceride of these particles is hydrolyzed by lipoprotein lipase before incorporation into adipose tissue fat. The lipoproteins from the liver, synthesized from blood glucose and free fatty acids, are also incorporated into adipose tissue triglycerides. The fat is mobilized from adipose tissue by the action of a hormone-sensitive lipase that splits the depot triglycerides into free glycerol and free fatty acids. The activation of this lipolysis is mediated by the cyclase system. The main hormonal effect on fat storage is elicited by insulin, which enhances the storage of exogenous lipids by activating lipoprotein lipase, and increases de novo fatty acid synthesis. The outflow of fatty acids is diminished effectively by inhibition of lipolysis on one hand and on the other by enhancing the adipose tissue capturing of fatty acids by the re-esterification process. The main hormonal effects on fatty acid mobilization are elicited by the catecholamines and glucocorticoids and growth hormone.

Gender differences and temporal variation in the incidence of type 1 diabetes: results of 8012 cases in the nationwide Diabetes Incidence Study in Sweden 1983-2002.

Objectives.u2002 To establish the gender difference amongst newly diagnosed type 1 diabetic patients aged 15–34u2003years, considering age at diagnosis, temporal trend and seasonal variation at time of diagnosis.

Effect of nicotinic acid on plasma lipids in patients with hyperlipoproteinemia during the first week of treatment

Summary Thirteen patients with hyperlipoproteinemia were treated with nicotinic acid. The fasting plasma lipid level was followed before treatment and daily during the first 5 days of treatment with 1 g of nicotinic acid three times a day. After treatment for 1 day the average triglyceride level was significantly reduced, whilst the cholesterol concentration was unaffected. The triglycerides then remained fairly stable at this new level. The cholesterol level, however, was not significantly reduced until the 4th and 5th days of treatment. The concentration of phospholipids behaved in a similar way to that of cholesterol. These findings suggest that the concentration of the triglyceride-rich very low density lipoproteins (VLDLP) is reduced after 1 days treatment, whereas the level of the cholesterol and phospholipid-rich low density lipoproteins (LDLP) is not lowered until the 4th to 5th days. This type of lipoprotein change was confirmed by analysis of plasma lipoproteins, separated in the preparative ultracentrifuge, from a case of essential hypercholesterolemia. The following working hypothesis for the action of nicotinic acid on plasma lipids is suggested. Nicotinic acid inhibits mobilization of free fatty acids from adipose tissue. This reduces the uptake of free fatty acids in the liver, which is followed in turn by decreased hepatic formation of VLDLP. The consequences would be reduced conversion of VLDLP to LDLP and, eventually, diminution of the LDLP level in plasma; thus plasma cholesterol and phospholipids would be lowered. Further work is required to confirm this hypothesis and to determine whether nicotinic acid has other effects on fatty acid transport than that of inhibiting lipolysis in adipose tissue.

Excess mortality in incident cases of diabetes mellitus aged 15 to 34 years at diagnosis: a population-based study (DISS) in Sweden

Aims/hypothesisThe objective of the study was to analyse the mortality, survival and cause of death patterns in incident cases of diabetes in the 15–34-year age group that were reported to the nationwide prospective Diabetes Incidence Study in Sweden (DISS).Materials and methodsDuring the study period 1983–1999, 6,771 incident cases were reported. Identification of deaths was made by linking the records to the nationwide Cause of Death Register.ResultsWith an average follow-up of 8.5xa0years, resulting in 59,231 person-years, 159 deaths were identified. Diabetes was reported as the underlying cause of death in 51 patients (32%), and as a contributing cause of death in another 42 patients (26%). The standardised mortality ratio (SMR) was significantly elevated (RR=2.4; 95% CI: 2.0–2.8). The SMR was higher for patients classified by the reporting physician as having type 2 diabetes at diagnosis than for those classified as type 1 diabetic (2.9 and 1.8, respectively). Survival analysis showed significant differences in survival curves between males and females (p=0.0003) as well as between cases with different types of diabetes (p=0.005). This pattern was also reflected in the Cox regression model showing significantly increased hazard for males vs females (p=0.0002), and for type 2 vs type 1 (p=0.015) when controlling for age.Conclusions/interpretationThis study shows a two-fold excess mortality in patients with type 1 diabetes and a three-fold excess mortality in patients with type 2 diabetes. Thus, despite advances in treatment, diabetes still carries an increased mortality in young adults, even in a country with a good economic and educational patient status and easy access to health care.

Islet antibodies and remaining beta-cell function 8 years after diagnosis of diabetes in young adults : a prospective follow-up of the nationwide Diabetes Incidence Study in Sweden.

Objectives.u2002 To establish the prevalence of remaining β‐cell function 8u2003years after diagnosis of diabetes in young adults and relate the findings to islet antibodies at diagnosis and 8u2003years later.

Appearance of islet cell autoantibodies after clinical diagnosis of diabetes mellitus.

Islet cell antibodies (ICA) and glutamic acid decarboxylase antibodies (GAD65Ab) are often present at diagnosis of insulin dependent diabetes mellitus (type I diabetes) and are supposed to decline in level and frequency during the first years of disease. We have analysed ICA and GAD65Ab at onset and after one year in 395 population based randomly selected 15-34 year old patients newly diagnosed with diabetes mellitus, to study how these autoantibodies persist, disappear and appear and their relation to C-peptide levels. Of the 395 samples 212 (54%) were positive for ICA, 250 (63%) were positive for GAD65Ab and 170 (43%) were positive for both. At follow up after one year, 27/183 (15%) of the ICA negative patients and 25/145 (17%) of the GAD65Ab negative patients had converted to positivity. Among the 103 patients negative for both ICA and GAD65Ab, 16 turned positive for one or both antibodies after one year. Patients converting to positivity for one or the other antibody after one year, had lower C-peptide levels after one year than patients who initially were and remained negative, supporting the hypothesis that these patients have a genuine type I diabetes. In conclusion, newly diagnosed patients may be negative for autoantibodies at diagnosis but develop these antibodies later on during the disease.

Diabetes duration and health-related quality of life in individuals with onset of diabetes in the age group 15—34 years – a Swedish population-based study using EQ-5D

BackgroundDiabetes with onset in younger ages affects both length of life and health status due to debilitating and life-threatening long-term complications. In addition, episodes and fear of hypoglycaemia and of long-term consequences may have a substantial impact on health status. This study aims to describe and analyse health-related quality of life (HRQoL) in individuals with onset of diabetes at the age of 15—34xa0years and with a disease duration of 1, 8, 15 and 24xa0years compared with control individuals matched for age, sex and county of residence.MethodsCross-sectional study of 839 individuals with diabetes and 1564 control individuals. Data on socioeconomic status and HRQoL using EQ-5D were collected by a postal questionnaire. Insulin treatment was self-reported by 94% of the patients, the majority most likely being type 1.ResultsIndividuals with diabetes reported lower HRQoL, with a significantly lower mean EQ VAS score in all cohorts of disease duration compared with control individuals for both men and women, and with a significantly lower EQ-5Dindex for women, but not for men, 15xa0years (0.76, pu2009=u20090.022) and 24xa0years (0.77, pu2009=u20090.016) after diagnosis compared with corresponding control individuals. Newly diagnosed individuals with diabetes reported significantly more problems compared with the control individuals in the dimension usual activities (women: 13.2% vs. 4.0%, pu2009=u20090.048; men: 11.4% vs. 4.1%, pu2009=u20090.033). In the other dimensions, differences between individuals with diabetes and control individuals were found 15 and 24xa0years after diagnosis: for women in the dimensions mobility, self-care, usual activities and pain/discomfort and for men in the dimension mobility. Multivariable regression analysis showed that diabetes duration, being a woman, having a lower education and not being married or cohabiting had a negative impact on HRQoL.ConclusionsOur study confirms the negative impact of diabetes on HRQoL and that the difference to control individuals increased by disease duration for women with diabetes. The small difference one year after diagnosis could imply a good management of diabetes care and a relatively quick adaptation. Our results also indicate that gender differences still exist in Sweden, despite modern diabetes treatment and management in Sweden.

Normal weight promotes remission and low number of islet antibodies prolong the duration of remission in Type 1 diabetes

Aimu2003 To identify clinical, immunological and biochemical factors that predict remission, and its duration in a large cohort of young adults with Type 1 diabetes mellitus (DM).

Long-term detrimental consequences of the onset of type 1 diabetes on annual earnings—evidence from annual registry data in 1990–2005

Aims/hypothesisYoung adults in the early stages of their participation in the labour market may be particularly vulnerable to the effects of onset of a chronic disease. Our aim was to quantify the consequences of the onset of type 1 diabetes in young adults on annual earnings, using individual-level longitudinal data before and after the onset of diabetes.MethodsThe Econ-DISS database contains annual socioeconomic information for 1990–2005 from Statistics Sweden. Econ-DISS includes data for persons with diabetes onset at the age of 15–34xa0years between 1983 and 2005, registered in the national Diabetes Incidence Study in Sweden (DISS) database, and for controls. Considering the onset of type 1 diabetes as an unanticipated and significant life event, we compared the progression of annual earnings for 3,650 cases born between 1949 and 1970 before and after onset of diabetes with that of 14,629 controls. Possible confounders—education, participation in the labour market, sick leave and parental education—were analysed.ResultsWe found no differences between the groups in annual earnings or participation in the labour market before onset of diabetes. After onset, persons with type 1 diabetes gradually lagged behind the controls. Their median annual earnings were lower in each year from 1995 to 2005 (pu2009<u20090.01). The difference in 2005 was euro (EUR) 1,411 (5.3%). Controlling for confounders, duration of type 1 diabetes ≥10xa0years was associated with 4.2% (men) and 8.1% (women) lower average annual earnings for persons with upper secondary education only who were active in the labour market.Conclusion/interpretationThe onset of type 1 diabetes in young adults has long-term detrimental consequences on earnings that cannot be attributed to confounders.