Physician-led medication reviews in polypharmacy patients treated with at least 12 medications in a type 2 diabetes outpatient clinic: A randomised trial.

AIMS: Medication reviews can be used to promote appropriate pharmacotherapy and negate the harmful consequences of polypharmacy. This study aimed to evaluate the effect of physician-led medication reviews and increased cross-sectoral communication as a supplement to standard care in a type 2 diabetes outpatient clinic. METHODS: This pragmatic randomised clinical trial enrolled patients with type 2 diabetes treated with at least 12 medications. The subjects were randomised to either standard care (standard care consultation at the outpatient clinic) or standard care plus a medication review consultation and increased cross-sectoral communication. The primary outcome was the number of medications used after six months. Health-related quality of life was quantified using the EuroQoL 5-dimension 5-level (EQ5D-5 L) questionnaire. RESULTS: We recruited 50 participants with a median age of 72 (IQR 67-75) years. The mean number of medications per patient changed from 17.9 to 14.3 in the intervention group and 17.6 to 17.2 in the control group (rate ratio 0.81). The reasons for discontinuations were medication no longer indicated (60%), safety issues (20%), efficacy issues (15%) or patient preferences (5%). There was a significant difference in the change in health-related quality of life (EQ5D-5 L index score) in favour of the intervention (0.111, 95% CI 0.001 to 0.221). CONCLUSIONS: Physician-led medication reviews and increased cross-sectoral communication in patients with type 2 diabetes treated with at least 12 medications reduced the number of medications used and improved health-related quality of life. Implementing and further investigating similar interventions as standard care seems reasonable.

Adjusting health care: practicing care for socially vulnerable type 2 diabetes patients.

BACKGROUND: Type 2 diabetes cluster in lower social groups and people with type 2 diabetes from lower social groups experience more complications, benefit less from health services and live shorter lives than people with type 2 diabetes from higher social groups. Different logics govern diabetes care and potentially influence the possibility of socially vulnerable type 2 diabetes patients to access and benefit from health services. In order to understand which practice and underlying logic enable socially vulnerable type 2 diabetes patients to access and benefit from diabetes care we aim to describe what professionals at a specialized diabetes clinic do to adjust services to patient's needs and make the tasks involved in diabetes care doable for socially vulnerable patients and how this work is embedded in an organizational and moral context. METHODS: Ethnographic fieldwork combining participant observation and interviews was carried out between February 2017 and March 2018 in a specialized diabetes clinic located in a socially deprived area in the capital region of Denmark. Sixteen patients (9 male, 7 female, aged 35-73 years) and 12 professionals (7 doctors, 4 nurses, 1 secretary) participated in the study. We used Annemarie Mol's concept of "the logic of care" to guide our analysis. RESULTS: Our analysis shows that the logic of care and the care practices in this clinic are characterized by a needs-based approach to treatment involving adjustment of services (permeability, timing, and content) and seeing the patient as a person with many needs. Throughout our description of selected care practices, we both characterize how health professionals practice this particular logic of care and the organizational and normative conditions that this logic is entangled with. CONCLUSIONS: Practicing diabetes care based on patients' needs involves individualization, something often described as an element of patient centred care. Our study shows that this ideal of individualization and adjustment of treatment is possible in practice. Organizational flexibility and an organizational culture that values patient needs enable needs-based care. In order for socially vulnerable type 2 diabetes patients to benefit from health services it is necessary to create conditions under which professionals can attend to these patients' multiple and complex needs. Adjusting care to these needs demand a variety of professional efforts some of which are hardly predictable or standardisable.

Effect of Metformin vs. Placebo in Combination with Insulin Analogues on Bone Markers P1NP and CTX in Patients with Type 2 Diabetes Mellitus.

Preclinical studies have shown a potential osteoanabolic effect of metformin but human studies of how metformin affects bone turnover are few. A post hoc sub-study analysis of an 18-month multicenter, placebo-controlled, double-blinded trial in type 2 diabetes mellitus (T2DM), randomizing participants to metformin versus placebo both in combination with different insulin analogue regimens (Metformin + Insulin vs. Placebo + Insulin). Patients were not treatment naive at baseline, 83% had received metformin, 69% had received insulin, 57.5% had received the combination of metformin and insulin before entering the study. Bone formation and resorption were assessed by measuring, N-terminal propeptide of type I procollagen (P1NP) and C-terminal telopeptide of type I collagen (CTX) at baseline and end of study. The influence of gender, age, smoking, body mass index (BMI), T2DM duration, glycosylated hemoglobin A1c (HbA1c), c-reactive protein (CRP) and insulin dosage was also included in the analyses. The levels of bone formation marker P1NP and bone resorption marker CTX increased significantly in both groups during the trial. P1NP increased less in the Metformin + Insulin compared to the placebo + insulin group (p = 0.001) (between group difference change), while the increases in CTX levels (p = 0.11) were not different. CRP was inversely associated (p = 0.012) and insulin dosage (p = 0.011) was positively related with change in P1NP levels. BMI (p = 0.002) and HbA1C (p = 0.037) were inversely associated with change in CTX levels. During 18 months of treatment with metformin or placebo, both in combination with insulin, bone turnover increased in both groups. But the pattern was different as the bone formation marker (P1NP) increased less during Metformin + Insulin treatment, while change in bone resorption (CTX) was not significantly different between the two groups.

Changes in subtypes of overt thyrotoxicosis and hypothyroidism following iodine fortification.

OBJECTIVE: To investigate the impact of mandatory iodine fortification (IF) on the incidence of nosological subtypes of overt thyrotoxicosis and hypothyroidism. DESIGN: We identified and scrutinized all possible new cases of overt thyrotoxicosis and hypothyroidism in an open cohort in Northern Jutland (n = 309 434; 1 January 1997) during the years 2014-2016. Individual medical history was evaluated to verify and detail the incidence of overt thyroid dysfunction and for classification into nosological subtypes. A number of cases were excluded during final verification due to spontaneous normalization of thyroid function, as they had no medical history suggesting a known condition, which could transiently affect thyroid function (subacute/silent thyroiditis, PPTD and iatrogenic thyroid dysfunction). An identical survey was conducted in 1997-2000 prior to mandatory IF of salt (13 µg/g) that was in effect from year 2001. RESULTS: The standardized incidence rate (SIR) of verified overt thyrotoxicosis decreased markedly from 97.5/100 000/year in 1997-2000 to 48.8 in 2014-2016 (SIRR: 0.50 [95% CI: 0.45-0.56]). This was due to a distinct decrease in the SIR of multinodular toxic goitre (SIRR: 0.18 [0.15-0.23]), solitary toxic adenoma (SIRR: 0.26 [0.16-0.43]) and to a lesser degree Graves' disease (SIRR: 0.67 [0.56-0.79]). SIR for overt hypothyroidism was unaltered by 2014-2016 (SIRR: 1.03 [0.87-1.22]). However, age distribution shifted with more young and fewer elderly cases of verified overt hypothyroidism. CONCLUSION: Mandatory IF caused a substantial reduction in SIR of verified overt thyrotoxicosis (especially of nodular origin) while avoiding an increase in SIR of verified overt hypothyroidism.

Thyrotoxicosis after iodine fortification. A 21-year Danish population-based study.

OBJECTIVE: Monitoring the influence of cautious iodine fortification (IF) on the incidence rate of overt thyrotoxicosis in Denmark with formerly frequent multinodular toxic goitre. DESIGN: A 21-year (1997-2017) prospective population-based study identified all new cases of overt biochemical thyrotoxicosis in two open cohorts: a Western cohort with moderate iodine deficiency (ID) and an Eastern cohort with mild ID (total n = 533 969 by 1 January 1997). A diagnostic algorithm was applied to all thyroid function tests performed within the study areas. Mandatory IF of salt was initiated in mid-2000 (13 ppm). This study is a part of DanThyr. RESULTS: The standardized incidence rate (SIR) of thyrotoxicosis at baseline (1997-1998) was 128.5/100.000/year in the cohort with moderate ID and 80.1 in the cohort with mild ID. SIR increased markedly in both cohorts during the initial years of IF (moderate/mild ID: +39/+52% in 2000-2001/2004-2005) and subsequently decreased to baseline level (mild ID) or below (moderate ID) by 2008. The decline was due to a marked decrease in the incidence rate among elderly subjects and a moderate decrease among the middle aged. The follow-up period for the mildly iodine deficient cohort was restricted to 2008. A continuous decline in SIR was observed for the remainder of the study period in the area with moderate ID (33% below baseline in 2016-2017). CONCLUSION: The rise in thyrotoxicosis incidence with cautious mandatory IF returned to baseline level after 7-8 years and levelled out at 33% below baseline in the population with previously moderate ID after 16-17 years.

Serum thyroglobulin as a biomarker of iodine deficiency in adult populations.

OBJECTIVE: To clarify which factors may influence the serum Tg level in an adult population and how this may affect Tg as a biomarker of iodine deficiency (ID). DESIGN AND METHODS: Two identical cross-sectional studies were performed before (C1a: 1997-98, n = 4649) and after (C2: 2004-05, n = 3570) the Danish mandatory iodine fortification (IF) of salt (2000). Additionally, a follow-up study of C1a was performed after IF (C1b: 2008-10, n = 2465). The studies took place in two regions with mild (Copenhagen) and moderate (Aalborg) ID before IF. Serum Tg was measured by immunoradiometric method and investigated as outcome variable in multivariate models. RESULTS: Multiple factors were associated with serum Tg. Some were directly related to iodine intake (cohort, urinary iodine concentration (UIC) level and region), and some were likely mediators of iodine intake effects on Tg (thyroid nodularity, thyroid size and autonomy with low TSH). Others were caused by Tg assay interference (Tg-Ab positivity), aggravation of ID (childbirths and smoking) or TSH stimulation of the thyroid. Estimated 24-h urinary iodine excretion was a more sensitive predictor of Tg than UIC. Iodine supplement users had low median Tg values compared with nonusers both before and after IF. CONCLUSIONS: Multiple factors should be taken into consideration when evaluating Tg as a marker of ID in adult populations, and the Tg results may depend on the assay used. Still, Tg is a sensitive marker of ID. We suggest including a reference population with known sufficient iodine intake when Tg is used to evaluate ID.

Gender differences in symptoms of hypothyroidism: a population-based DanThyr study.

OBJECTIVES: We examined the gender-specific symptom prevalences in hypothyroidism and in healthy controls and explored the extent to which symptoms indicative of thyroid status may be different in women and men. DESIGN AND METHODS: Patients newly diagnosed with overt autoimmune hypothyroidism (n = 140) and controls free of thyroid disease (n = 560) recruited from the same population participated in a population-based study of The Danish Investigation of Iodine Intake and Thyroid Diseases (DanThyr). Participants underwent a comprehensive programme including blood tests and completion of questionnaires. The gender-specific distribution of 13 hypothyroidism-associated symptoms and a simple combined score (0-13) was explored in conditional uni- and multivariate models taking into account a broad spectrum of possible confounders. Diagnostic odds ratios (DORs) were calculated as measures for the association between participant status (case vs control) and presence of symptoms (yes vs no). RESULTS: In overt autoimmune hypothyroidism, 94·9% of women and 91·3% of men (P = 0·62) reported at least one of the hypothyroidism-associated symptoms, with tiredness as the most common symptom followed by dry skin and shortness of breath. In contrast, women free of thyroid disease self-reported at least one hypothyroidism-associated symptom considerably more often than men (73·7% vs 51·1%, P < 0·001). DORs (±SEM) for 0-1/2-3/4-13 symptoms were 0·07 (0·04-0·10)/2·15 (1·57-2·94)/7·99 (6·15-10·4) in men and 0·21 (0·16-0·28)/0·62 (0·58-0·66)/1·99 (1·90-2·09) in women. CONCLUSION: The presence of symptoms is more indicative for overt autoimmune hypothyroidism in men than in women, and presumably persistent symptoms after therapy of hypothyroidism will be more common in women.

Interleukin-1 antagonism in type 1 diabetes of recent onset: two multicentre, randomised, double-blind, placebo-controlled trials.

BACKGROUND: Innate immunity contributes to the pathogenesis of autoimmune diseases, such as type 1 diabetes, but until now no randomised, controlled trials of blockade of the key innate immune mediator interleukin-1 have been done. We aimed to assess whether canakinumab, a human monoclonal anti-interleukin-1 antibody, or anakinra, a human interleukin-1 receptor antagonist, improved ß-cell function in recent-onset type 1 diabetes. METHODS: We did two randomised, placebo-controlled trials in two groups of patients with recent-onset type 1 diabetes and mixed-meal-tolerance-test-stimulated C peptide of at least 0·2 nM. Patients in the canakinumab trial were aged 6-45 years and those in the anakinra trial were aged 18-35 years. Patients in the canakinumab trial were enrolled at 12 sites in the USA and Canada and those in the anakinra trial were enrolled at 14 sites across Europe. Participants were randomly assigned by computer-generated blocked randomisation to subcutaneous injection of either 2 mg/kg (maximum 300 mg) canakinumab or placebo monthly for 12 months or 100 mg anakinra or placebo daily for 9 months. Participants and carers were masked to treatment assignment. The primary endpoint was baseline-adjusted 2-h area under curve C-peptide response to the mixed meal tolerance test at 12 months (canakinumab trial) and 9 months (anakinra trial). Analyses were by intention to treat. These studies are registered with ClinicalTrials.gov, numbers NCT00947427 and NCT00711503, and EudraCT number 2007-007146-34. FINDINGS: Patients were enrolled in the canakinumab trial between Nov 12, 2010, and April 11, 2011, and in the anakinra trial between Jan 26, 2009, and May 25, 2011. 69 patients were randomly assigned to canakinumab (n=47) or placebo (n=22) monthly for 12 months and 69 were randomly assigned to anakinra (n=35) or placebo (n=34) daily for 9 months. No interim analyses were done. 45 canakinumab-treated and 21 placebo-treated patients in the canakinumab trial and 25 anakinra-treated and 26 placebo-treated patients in the anakinra trial were included in the primary analyses. The difference in C peptide area under curve between the canakinumab and placebo groups at 12 months was 0·01 nmol/L (95% CI -0·11 to 0·14; p=0·86), and between the anakinra and the placebo groups at 9 months was 0·02 nmol/L (-0·09 to 0·15; p=0·71). The number and severity of adverse events did not differ between groups in the canakinumab trial. In the anakinra trial, patients in the anakinra group had significantly higher grades of adverse events than the placebo group (p=0·018), which was mainly because of a higher number of injection site reactions in the anakinra group. INTERPRETATION: Canakinumab and anakinra were safe but were not effective as single immunomodulatory drugs in recent-onset type 1 diabetes. Interleukin-1 blockade might be more effective in combination with treatments that target adaptive immunity in organ-specific autoimmune disorders. FUNDING: National Institutes of Health and Juvenile Diabetes Research Foundation.

Iodine excretion has decreased in Denmark between 2004 and 2010--the importance of iodine content in milk.

Fortification with the essential trace element iodine is widespread worldwide. In the present study, results on iodine excretion and intake of iodine-rich foods from a cross-sectional study carried out in 2004-5, 4 to 5 years after the implementation of mandatory iodine fortification, were compared with data in a study carried out in 2008-10. The 2008-10 study was a follow-up of a cross-sectional study carried out before iodine fortification was implemented. Participants in the cross-sectional studies were randomly selected. Both studies were carried out in the cities of Aalborg and Copenhagen in Denmark. The median urinary iodine concentration decreased in women from 97 µg/l (n 2862) to 78 µg/l (n 2041) (P< 0.001). The decrease persisted after adjustment for age, city and education, and if expressed as estimated 24 h iodine excretion. The prevalence of users of iodine containing dietary supplements increased from 29.4 to 37.3 % (P< 0.001). The total fluid intake increased in women (P< 0.001), but the intake of other iodine-rich foods did not change. The median urinary iodine concentration did not change in men (114 µg/l (n 708) and 107 µg/l (n 424), respectively), while the total fluid intake decreased (P= 0.001). Iodine content was measured in milk sampled in 2000-1 and in 2013. The iodine content was lower in 2013 (12 (sd 3) µg/100 g) compared with that in 2000-1 (16 (sd 6) µg/100 g) (P< 0.001). In conclusion, iodine excretion in women has decreased below the recommended level. The reason might probably, at least partly, be a decreased content of iodine in milk.

The Danish investigation on iodine intake and thyroid disease (DanThyr): history and implications.

Due to mild-to-moderate iodine deficiency in Denmark, health authorities initiated a voluntary iodine fortification (IF) program in 1998, which became mandatory in 2000. In line with recommendations from the World Health Organization, the Danish investigation on iodine intake and thyroid disease (DanThyr) was established to monitor the effect on thyroid health and disease. The program involved different study designs and followed two Danish sub-populations in the years before IF and up till 20 years after. Results showed that the IF was successfully implemented and increased the level of iodine intake from mild-moderate iodine deficiency to low adequacy. The level of thyroglobulin and thyroid volume decreased following IF, and there was an indication of fewer thyroid nodules. The incidence of hyperthyroidism increased transiently following IF but subsequently decreased below the pre-fortification level. Conversely, thyroid-stimulating hormone levels and the prevalence of thyroid autoimmunity increased along with an increase in the incidence of hypothyroidism. These trends were mirrored in the trends in treatments for thyroid disease. Most differences in thyroid health and disease between regions with different iodine intake levels before IF attenuated. This review illustrates the importance of a monitoring program to detect both beneficial and adverse effects and exemplifies how a monitoring program can be conducted when a nationwide health promotion program - as IF - is initiated.

Graves' hyperthyroidism and moderate alcohol consumption: evidence for disease prevention.

BACKGROUND: We recently demonstrated that moderate alcohol consumption is associated with a considerable reduction in the risk of autoimmune hypothyroidism, similar to findings in other autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. We aimed to study a possible association between alcohol intake and autoimmune Graves' hyperthyroidism. DESIGN: This is a population-based, case-control study. METHODS: In a well-defined Danish population (2,027,208 person-years of observation), we prospectively identified patients with new overt thyroid dysfunction and studied 272 patients with Graves' hyperthyroidism. For each patient, we recruited four age-gender-region-matched controls with normal thyroid function (n = 1088). MEASUREMENTS: Participants gave detailed information on current and previous alcohol intake as well as other factors to be used for analyses. The association between alcohol intake and development of hyperthyroidism was analysed in conditional multivariate Cox regression models. RESULTS: Graves' patients had a lower reported alcohol consumption than controls (median units of alcohol (12 g) per week: 2 vs 4, P < 0·001). In a multivariate regression model, alcohol consumption was associated with a dose-dependent reduction in risk for development of overt Graves' hyperthyroidism. Odds ratios (95% confidence interval) compared with the reference group with a recent (last year) consumption of 1-2 units of alcohol per week were as follows: 0 units/week 1·73 (1·17-2·56), 3-10 units/week 0·56 (0·39-0·79), 11-20 units/week 0·37 (0·21-0·65), ≥21 units/week 0·22 (0·08-0·60). Similar results were found for maximum previous alcohol consumption during a calendar year. No interaction was found with the type of alcohol consumed (wine vs beer), smoking habit, age, gender or region of inhabitancy. CONCLUSIONS: Moderate alcohol consumption is associated with a considerable reduction in the risk of Graves' disease with hyperthyroidism--irrespective of age and gender. Autoimmune thyroid disease seems to be much more dependent on environmental factors than hitherto anticipated.

Smoking cessation is followed by a sharp but transient rise in the incidence of overt autoimmune hypothyroidism - a population-based, case-control study.

BACKGROUND: Current smoking is associated with a low prevalence of thyroid autoantibodies. On the other hand, smoking withdrawal enhances thyroid autoantibody level and may be a risk factor for the development of hypothyroidism. The aim of this study was to assess the association between smoking habits (smoking cessation in particular) and development of autoimmune hypothyroidism. DESIGN: Population-based, case-control study. PARTICIPANTS: Cases (n = 140) newly diagnosed with primary autoimmune overt hypothyroidism were identified prospectively by population monitoring (2,027,208 person-years of observation) of all thyroid function tests performed in the two well-defined geographical areas. Individually, age-, sex- and region-matched euthyroid controls (n = 560) were simultaneously included from the same population. MEASUREMENTS: Participants gave details on smoking habits including smoking withdrawal and other lifestyle factors. Smoking habits were verified by measuring urinary cotinine (a nicotine metabolite). RESULTS: Incident hypothyroidism was very common in people who had recently stopped smoking: OR vs never smokers (95%-CI); quit smoking <1 years, 7·36 (2·27-23·9); 1-2 years, 6·34 (2·59-15·3); 3-10 years, 0·75 (0·30-1·87); >10 years, 0·76 (0·38-1·51). Results were consistent in both sexes and irrespective of age. Within two years after smoking cessation, the percentage of hypothyroid cases attributable to cessation of smoking was 85%. The current smoking was not associated with altered risk of developing overt hypothyroidism [OR, 0·92 (0·57-1·48)]. CONCLUSIONS: The risk of having overt autoimmune hypothyroidism diagnosed is more than 6-fold increased the first 2 years after cessation of smoking. Clearly, smoking cessation is vital to prevent death and severe disease. However, awareness of hypothyroidism should be high in people who have recently quit smoking, and virtually any complaint should lead to thyroid function testing.

A prospective randomised cross-over study of the effect of insulin analogues and human insulin on the frequency of severe hypoglycaemia in patients with type 1 diabetes and recurrent hypoglycaemia (the HypoAna trial): study rationale and design.

BACKGROUND: Severe hypoglycaemia still represents a significant problem in insulin-treated diabetes. Most patients do not experience severe hypoglycaemia often. However, 20% of patients with type 1 diabetes experience recurrent severe hypoglycaemia corresponding to at least two episodes per year. The effect of insulin analogues on glycaemic control has been documented in large trials, while their effect on the frequency of severe hypoglycaemia is less clear, especially in patients with recurrent severe hypoglycaemia. The HypoAna Trial is designed to investigate whether short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing the occurrence of severe hypoglycaemic episodes in patients with recurrent hypoglycaemia. This paper reports the study design of the HypoAna Trial. METHODS/DESIGN: The study is a Danish two-year investigator-initiated, prospective, randomised, open, blinded endpoint (PROBE), multicentre, cross-over trial investigating the effect of insulin analogues versus human insulin on the frequency of severe hypoglycaemia in subjects with type 1 diabetes. Patients are randomised to treatment with basal-bolus therapy with insulin detemir / insulin aspart or human NPH insulin / human regular insulin in random order. The major inclusion criterion is history of two or more episodes of severe hypoglycaemia in the preceding year. DISCUSSION: In contrast to almost all other studies in this field the HypoAna Trial includes only patients with major problems with hypoglycaemia. The HypoAna Trial will elucidate whether basal-bolus regimen with short-acting and long-acting insulin analogues in comparison with human insulin are superior in reducing occurrence of severe hypoglycaemic episodes in hypoglycaemia prone patients with type 1 diabetes. http://www.clinicaltrials.gov: NCT00346996.

Effects of 18-months metformin versus placebo in combination with three insulin regimens on RNA and DNA oxidation in individuals with type 2 diabetes: A post-hoc analysis of a randomized clinical trial.

Formation of reactive oxygen species has been linked to the development of diabetes complications. Treatment with metformin has been associated with a lower risk of developing diabetes complications, including when used in combination with insulin. Metformin inhibits Complex 1 in isolated mitochondria and thereby decreases the formation of reactive oxygen species. Thus, we post-hoc investigated the effect of metformin in combination with different insulin regimens on RNA and DNA oxidation in individuals with type 2 diabetes. Four hundred and fifteen individuals with type 2 diabetes were randomized (1:1) to blinded treatment with metformin (1,000 mg twice daily) versus placebo and to (1:1:1) open-label biphasic insulin, basal-bolus insulin, or basal insulin therapy in a 2 × 3 factorial design. RNA and DNA oxidation were determined at baseline and after 18 months measured as urinary excretions of 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), respectively. Urinary excretion of 8-oxoGuo changed by +7.1% (95% CI: 0.5% to 14.0%, P = 0.03) following metformin versus placebo, whereas changes in 8-oxodG were comparable between intervention groups. Biphasic insulin decreased urinary excretion of 8-oxoGuo (within-group: -9.6% (95% CI: -14.4% to -4.4%)) more than basal-bolus insulin (within-group: 5.2% (95% CI: -0.5% to 11.2%)), P = 0.0002 between groups, and basal insulin (within-group: 3.7% (95% CI: -2.0% to 9.7%)), P = 0.0007 between groups. Urinary excretion of 8-oxodG decreased more in the biphasic insulin group (within-group: -9.9% (95% CI: -14.4% to -5.2%)) than basal-bolus insulin (within group effect: -1.2% (95% CI: -6.1% to 3.9%)), P = 0.01 between groups, whereas no difference was observed compared with basal insulin. In conclusion, eighteen months of metformin treatment in addition to different insulin regimens increased RNA oxidation, but not DNA oxidation. Biphasic insulin decreased both RNA and DNA oxidation compared with other insulin regimens.

A cautious iodization programme bringing iodine intake to a low recommended level is associated with an increase in the prevalence of thyroid autoantibodies in the population.

UNLABELLED: Autoantibodies against the thyroid gland with thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) as the most common can often be demonstrated in serum. The effect of public iodization programmes on antibody prevalence is uncertain. AIM: To measure the concentrations of thyroid autoantibodies in the Danish population before and after mandatory iodization of salt. METHODS: Two identical cross-sectional population studies were performed before (Cohort 1 (C1), year 1997-1998, n = 4649, median urinary iodine 61 µg/l) and 4-5 years after (Cohort 2 (C2), year 2004-2005, n = 3570, median urinary iodine 101 µg/l) mandatory iodine fortification of salt was implemented in Denmark. Blood tests were analysed for TPO-Ab and Tg-Ab using sensitive assays. RESULTS: Antibodies were more frequent in C2 than in C1: TPO-Ab > 30 U/ml, C1 vs C2: 14·3 vs 23·8% (P < 0·001) and Tg-Ab > 20 U/ml, C1 vs C2: 13·7 vs 19·9% (P < 0·001). The C2 vs C1 effect was confirmed in multivariate regression models (C1 reference): TPO-Ab: OR (95% CI): 1·80 (1·59-2·04) and Tg-Ab: 1·49 (1·31-1·69). The increase in the frequency of thyroid antibodies was most pronounced in young women and especially observed at low concentrations of antibodies. CONCLUSION: The prevalence of both TPO-Ab and Tg-Ab was higher 4-5 years after a cautious iodine fortification of salt was introduced in Denmark. The increase was most pronounced in young women and in the low concentrations of antibody. Further studies are needed to evaluate the long-term effects of increased iodine intake on thyroid autoimmunity in the population.

Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy.

BACKGROUND: Treatment of patients with perioxisome proliferator-activated receptor-γ full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-γ agonists has not been established in a clinical trial. The BALaglitazone glucose Lowering Efficacy Trial aimed to establish the glucose-lowering effects and safety parameters of the perioxisome proliferator-activated receptor-γ partial agonist balaglitazone in diabetic patients on stable insulin therapy. METHODS: Four hundred and nine subjects from three countries with type 2 diabetes on stable insulin therapy were randomized to 26 weeks of double-blind treatment with once daily doses of 10 or 20 mg balaglitazone, 45 mg pioglitazone, or matching placebo (n ≥ 99 in each group). The primary endpoint was the efficacy of balaglitazone 10 and 20 mg versus placebo on the absolute change in haemoglobin A(1c) . Secondary endpoints included levels of fasting serum glucose, and changes in body composition and bone mineral density as measured by dual energy X-ray absorptiometry, in comparison to pioglitazone 45 mg. This study is registered with Clinicaltrials.gov identifier: NCT00515632. RESULTS: In the 10- and 20-mg balaglitazone groups, and in the 45-mg pioglitazone group, significant reductions in haemoglobin A(1c) levels were observed (−0.99, −1.11, and −1.22%, respectively; p < 0.0001) versus placebo. Fasting serum glucose was similarly reduced in all treatment arms. Dual energy X-ray absorptiometry analyses showed that, while balaglitazone at 10 mg caused weight gain and fluid retention compared to placebo, the magnitude of these effects was significantly smaller than that of pioglitazone 45 mg and balaglitazone 20mg. Balaglitazone at either dose did not appear to reduce bone mineral density, while Pioglitazone showed a trend towards a reduction. CONCLUSION: Patients treated with balaglitazone at 10 mg and 20 mg and pioglitazone at 45 mg showed clinically meaningful improvements in glucose levels and HbA(1c) . With the 10 mg dose, the benefits (glucose & HgA(1c) lowering) and untoward effects (fluid and fat accumulation) were less, results that encourage further studies of this drug candidate.

Doubling in the use of thyroid hormone replacement therapy in Denmark: association to iodization of salt?

Iodization of salt is an effective strategy to prevent iodine deficiency disorders. Recent studies, however, indicate that increasing the iodine intake in a population may give rise to an increased incidence of hypothyroidism, but the association has not been fully clarified. In Denmark, iodization of salt was initiated in 1998 because of mild-to-moderate iodine deficiency. The aim of this study was to evaluate the effect of the raised iodine intake on the nationwide incident use of thyroid hormone replacement therapy (levothyroxine) to treat hypothyroidism. Data on all use of levothyroxine was extracted from the Register of Medicinal Product Statistics during the period 1995-2009 and linked to other nationwide registers by use of the Danish identification number. Persons with previous thyroid surgery were excluded. In the studied period 71,565 incident users were identified. The incidence rate increased 75% in the moderately iodine deficient region (72.2 incident users/100,000 person-years in 1997 to 126.6 in 2008) and 87% in the mildly deficient region (86.9-162.9). When stratified by sex and age-group (00-39, 40-64, 65+) the largest relative increase was seen among women in the youngest age-group, where more than a doubling was seen. The mechanisms behind the increase may be a result of iodine-induced hypothyroidism, although a higher diagnostic activity with regard to thyroid dysfunction and intensified treatment of subclinical hypothyroidism may also play a role. Our findings stress the need for caution when initiating iodine fortification programs to keep the intake within the optimal range, and the need for continuous monitoring.

Health-related quality of life and self-related health in patients with type 2 diabetes: effects of group-based rehabilitation versus individual counselling.

BACKGROUND: Type 2 diabetes can seriously affect patients' health-related quality of life and their self-rated health. Most often, evaluation of diabetes interventions assess effects on glycemic control with little consideration of quality of life. The aim of the current study was to study the effectiveness of group-based rehabilitation versus individual counselling on health-related quality of life (HRQOL) and self-rated health in type 2 diabetes patients. METHODS: We randomised 143 type 2 diabetes patients to either a six-month multidisciplinary group-based rehabilitation programme including patient education, supervised exercise and a cooking-course or a six-month individual counselling programme. HRQOL was measured by Medical Outcomes Study Short Form 36-item Health Survey (SF-36) and self-rated health was measured by Diabetes Symptom Checklist - Revised (DCS-R). RESULTS: In both groups, the lowest estimated mean scores of the SF36 questionnaire at baseline were "vitality" and "general health". There were no significant differences in the change of any item between the two groups after the six-month intervention period. However, vitality-score increased 5.2 points (p = 0.12) within the rehabilitation group and 5.6 points (p = 0.03) points among individual counselling participants.In both groups, the highest estimated mean scores of the DSC-R questionnaire at baseline were "Fatigue" and "Hyperglycaemia". Hyperglycaemic and hypoglycaemic distress decreased significantly after individual counselling than after group-based rehabilitation (difference -0.3 points, p = 0.04). No between-group differences occurred for any other items. However, fatigue distress decreased 0.40 points within the rehabilitation group (p = 0.01) and 0.34 points within the individual counselling group (p < 0.01). In the rehabilitation group cardiovascular distress decreased 0.25 points (p = 0.01). CONCLUSIONS: A group-based rehabilitation programme did not improve health-related quality of life and self-rated health more than an individual counselling programme. In fact, the individual group experienced a significant relief in hyper- and hypoglycaemic distress compared with the rehabilitation group.However, the positive findings of several items in both groups indicate that lifestyle intervention is an important part of the management of type 2 diabetes patients.

Nurse-administered early warning score system can be used for emergency department triage.

INTRODUCTION: Studies have shown that early warning score systems can identify in-patients at high risk of catastrophic deterioration and this may possibly be used for an emergency department (ED) triage. Bispebjerg Hospital has introduced a multidisciplinary team (MT) in the ED activated by the Bispebjerg Early Warning Score (BEWS). The BEWS is calculated on the basis of respiratory frequency, pulse, systolic blood pressure, temperature and level of consciousness. The aim of this study is to evaluate the ability of the BEWS to identify critically ill patients in the ED and to examine the feasibility of using the BEWS to activate an MT response. MATERIAL AND METHODS: This study is based on an evaluation of retrospective data from a random sample of 300 emergency patients. On the basis of documented vital signs, a BEWS was calculated retrospectively. The primary end points were admission to an intensive care unit (ICU) and death within 48 hours of arrival at the ED. This study was registered at clinicaltrials.gov (NCT01243021). RESULTS: A BEWS ≥ 5 is associated with a significantly increased risk of ICU admission within 48 hours of arrival (relative risk (RR) 4.1; 95% confidence interval (CI) 1.5-10.9) and death within 48 hours of arrival (RR 20.3; 95% CI 6.9-60.1). The sensitivity of the BEWS in identifying patients who were admitted to the ICU or who died within 48 hours of arrival was 63%. The positive predictive value of the BEWS was 16% and the negative predictive value 98% for identification of patients who were admitted to the ICU or who died within 48 hours of arrival. CONCLUSION: The BEWS is a simple scoring system based on readily available vital signs. It is a sensitive tool for detecting critically ill patients and may be used for ED triage and activation of an MT response.

Quality of care using a multidisciplinary team in the emergency room.

INTRODUCTION: Bispebjerg Hospital has implemented a multidisciplinary team reception of critically ill and severely injured patients at the Emergency Department (ED), termed emergency call (EC) and trauma call (TC). The aim of this study was to describe the course, medical treatment and outcome for patients received by this multidisciplinary team and to evaluate the quality of acute medical treatment of these patients. MATERIAL AND METHODS: A retrospective evaluation was made of all ECs and TCs registered during a six-month period. Information on sex, age, interventions at the ED, time spent at the ED and outcome measures (admission, Intensive Care Unit (ICU) admission and death) were obtained. The quality of the acute medical treatment during the ED stay and the first 48 hours of admission were evaluated by senior consultants from the departments receiving the patients. RESULTS: A total of 150 ECs and 47 TCs were included. The median time spent at the ED was 65 minutes for ECs and 95 minutes for TCs. In EC patients a median of eight interventions were performed at the ED, while a median of five interventions were performed in TC patients. A total of 137 EC patients were admitted to hospital including 32 patients admitted to the ICU. In all, 49 EC patients died during admission. Forty percent of TC patients were discharged to their homes. Only one trauma patient died and none were admitted to the ICU. The acute medical treatment was found to be satisfactory in 87% of EC patients and 96% of TC patients. CONCLUSION: A multidisciplinary team reception ensures early initiation of diagnostic procedures and treatment, short ED stays and admission to relevant departments in critically ill and severely injured patients.