Insulin initiation in patients with type 2 diabetes is often delayed, but access to a diabetes nurse may help-insights from Norwegian general practice.

Objective: We opted to study how support staff operational capacity and diabetes competences may impact the timeliness of basal insulin-initiation in general practice patients with type 2 diabetes (T2D).Design/Setting/Outcomes: This was an observational and retrospective study on Norwegian primary care patients with T2D included from the ROSA4-dataset. Exposures were (1) support staff size, (2) staff size relative to number of GPs, (3) clinic access to a diabetes nurse and (4) share of staff with diabetes course (1 and 2 both relate to staff operational capacity, whereas 3 and 4 are both indicatory of staff diabetes competences). Outcomes were 'timely basal insulin-initiation' (primary) and 'attainment of HbA1c<7%' after insulin start-up (secondary). Associations were analyzed using multiple linear regression, and directed acyclic graphs guided statistical adjustments.Subjects: Insulin naïve patients with 'timely' (N = 294), 'postponed' (N = 219) or 'no need of' (N = 3,781) basal insulin-initiation, respectively.Results: HbA1c [median (IQR)] increased to 8.8% (IQR, 8.0, 10.2) prior to basal insulin-initiation, which reduced HbA1c to 7.3 (6.8-8.1) % by which only 35% of the subjects reached HbA1c <7%. Adjusted risk of 'timely basal insulin-initiation' was more than twofold higher if access to a diabetes nurse (OR = 2.40, [95%CI, 1.68, 3.43]), but related only vaguely to staff size (OR = 1.01, [95%CI, 1.00, 1.03]). No other staff factors related significantly to neither the primary nor the secondary outcome.Conclusion: In Norwegian general practice, insulin initiation in people with T2D may be affected by therapeutic inertia but access to a diabetes nurse may help facilitating more timely insulin start-up.

In patients with type 2 diabetes (T2D) cared for by their general practice physician (GP), insulin therapy was susceptible to therapeutic inertia.In Norwegian general practice, chance of timely basal insulin-initiation was found more than two-fold higher if the GP had access to a diabetes nurse.In contrast, the timeliness of basal insulin-initiation in general practice patients with T2D seemed unaffected by share of support staff with diabetes course and by factors indicatory of support staff overall operational capacity.In Norwegian general practice, a diabetes nurse seems to offer unique clinical benefits to the care of insulin treated patients with T2D.

Metabolic predictors of pain, fatigue, depression and quality of life in people with long-term type 1 diabetes-the Dialong study.

AIM: To examine associations of metabolic parameters (mean 30 years' time-weighted HbA1c and low-density lipoprotein-cholesterol [LDL-c], current methionine sulfoxide [MetSO], advanced glycation end products [AGEs], inflammatory markers and hypoglycaemia) with pain, fatigue, depression and quality of life (QoL) in people with long-term type 1 diabetes. METHODS: A total of 104 persons with type 1 diabetes ≥45 years duration were included. Participants completed questionnaires measuring bodily pain (RAND-36 bodily pain domain with lower scores indicate higher levels of bodily pain), fatigue (Fatigue Questionnaire), depression (Patient Health Questionnaire), overall QoL (World Health Organization Quality of Life-BREF) and diabetes-related QoL (Audit of Diabetes-Dependent Quality of Life). In this observational study, mean time-weighted HbA1c and LDL-c were calculated based on longitudinal measures obtained from medical records of up to 34 years, while current HbA1c , LDL-c and inflammatory markers were analysed in blood samples and collagen MetSO and AGEs in skin biopsies. History of hypoglycaemia was self reported. Associations between metabolic parameters and questionnaire scores were analysed using linear regression analyses and are reported as standardized regression coefficients (beta). RESULTS: Of the metabolic variables, higher mean time-weighted HbA1c was associated with higher levels of bodily pain and total fatigue (beta [p-value]) -0.3 (<0.001) and 0.2 (0.001). CONCLUSIONS: Long-term chronic hyperglycaemia may have a negative influence on pain and fatigue in people with type 1 diabetes. These results may assist health care workers in emphasizing the importance of strict glycaemic control in people with diabetes and identifying and treating type 1 diabetes-related pain and fatigue.

Undiagnosed diabetes: Prevalence and cardiovascular risk profile in a population-based study of 52,856 individuals. The HUNT Study, Norway.

AIMS: We investigated the current extent of undiagnosed diabetes and prediabetes and their associated cardiovascular risk profile in a population-based study. METHODS: All residents aged ≥20 years in the Nord-Trøndelag region, Norway, were invited to the HUNT4 Survey in 2017-2019, and 54% attended. Diagnosed diabetes was self-reported, and in those reporting no diabetes HbA1c was used to classify undiagnosed diabetes (≥48 mmol/mol [6.5%]) and prediabetes (39-47 mmol/mol [5.7%-6.4%]). We estimated the age- and sex-standardized prevalence of these conditions and their age- and sex-adjusted associations with other cardiovascular risk factors. RESULTS: Among 52,856 participants, the prevalence of diabetes was 6.0% (95% CI 5.8, 6.2), of which 11.1% were previously undiagnosed (95% CI 10.1, 12.2). The prevalence of prediabetes was 6.4% (95% CI 6.2, 6.6). Among participants with undiagnosed diabetes, 58% had HbA1c of 48-53 mmol/mol (6.5%-7.0%), and only 14% (i.e., 0.1% of the total study population) had HbA1c >64 mmol/mol (8.0%). Compared with normoglycaemic participants, those with undiagnosed diabetes or prediabetes had higher body mass index, waist circumference, systolic blood pressure, triglycerides and C-reactive protein but lower low-density lipoprotein cholesterol (all p < 0.001). Participants with undiagnosed diabetes had less favourable values for every measured risk factor compared with those with diagnosed diabetes. CONCLUSIONS: The low prevalence of undiagnosed diabetes suggests that the current case-finding-based diagnostic practice is well-functioning. Few participants with undiagnosed diabetes had very high HbA1c levels indicating severe hyperglycaemia. Nonetheless, participants with undiagnosed diabetes had a poorer cardiovascular risk profile compared with participants with known or no diabetes.

Availability and analytical quality of hemoglobin A1c point-of-care testing in general practitioners' offices are associated with better glycemic control in type 2 diabetes.

Background It is not clear if point-of-care (POC) testing for hemoglobin A1c (HbA1c) is associated with glycemic control in type 2 diabetes. Methods In this cross-sectional study, we linked general practitioner (GP) data on 22,778 Norwegian type 2 diabetes patients to data from the Norwegian Organization for Quality Improvement of Laboratory Examinations. We used general and generalized linear mixed models to investigate if GP offices' availability (yes/no) and analytical quality of HbA1c POC testing (average yearly "trueness score", 0-4), as well as frequency of participation in HbA1c external quality assurance (EQA) surveys, were associated with patients' HbA1c levels during 2014-2017. Results Twenty-eight out of 393 GP offices (7%) did not perform HbA1c POC testing. After adjusting for confounders, their patients had on average 0.15% higher HbA1c levels (95% confidence interval (0.04-0.27) (1.7 mmol/mol [0.5-2.9]). GP offices participating in one or two yearly HbA1c EQA surveys, rather than the maximum of four, had patients with on average 0.17% higher HbA1c levels (0.06, 0.28) (1.8 mmol/mol [0.6, 3.1]). For each unit increase in the GP offices' HbA1c POC analytical trueness score, the patients' HbA1c levels were lower by 0.04% HbA1c (-0.09, -0.001) (-0.5 mmol/mol [-1.0, -0.01]). Conclusions Novel use of validated patient data in combination with laboratory EQA data showed that patients consulting GPs in offices that perform HbA1c POC testing, participate in HbA1c EQA surveys, and maintain good analytical quality have lower HbA1c levels. Accurate HbA1c POC results, available during consultations, may improve diabetes care.

Coronary plaque characteristics and epicardial fat tissue in long term survivors of type 1 diabetes identified by coronary computed tomography angiography.

OBJECTIVES: The aim was to assess coronary atherosclerosis, plaque morphology and associations to cardiovascular risk factors and epicardial adipose tissue (EAT) in patients with long duration of type 1 diabetes mellitus (T1DM). MATERIALS AND METHODS: Eighty-eight patients with ≥ 45 year T1DM duration and 60 controls underwent coronary CT angiography (CCTA) for evaluation of coronary artery plaque volume (total, calcified or mixed/soft), coronary artery calcification score (CAC) and EAT. RESULTS: Plaques were detected in 75 (85%) T1DM patients and 28 (47%) controls, p < 0.01. Median (interquartile range) plaque volume (mm3) in T1DM vs. controls was: 21.0 (1.0-66.0) vs. 0.2 (0.0-7.1), p < 0.01 for calcified, 0.0 (0.0-8.7) vs. 0.0 (0.0-0.0), p < 0.01 for soft/mixed and 29.5 (3.9-95.8) vs. 0.4 (0.0-7.4), p < 0.01 for total plaque volume. Median CAC was 128 (13-671) vs. 1 (0.0-39.0), p < 0.01 in T1DM vs. controls. Median EAT volume did not differ between the groups; 52.3 (36.1-65.5) cm3 vs. 55 (38.3-79.6), p = 0.20. No association between CAC or plaque volumes and EAT were observed. Low time-weighted LDL-cholesterol and HbA1c for 30 years were associated with having plaque volume < 25th percentile, OR (95% CI) 0.18 (0.05-0.70), p = 0.01 and 0.45 (0.20-1.00), p < 0.05, respectively. Time-weighted LDL-c was linearly associated with CAC (beta 0.82 (95% CI 0.03-1.62), p = 0.04) and total plaque volume (beta 0.77 (95% CI 0.19-1.36), p = 0.01). CONCLUSION: Long-term survivors of T1DM have a higher prevalence of coronary atherosclerosis compared to controls. Low LDL-cholesterol and HbA1c over time have a protective effect on coronary atherosclerosis. EAT volume was not associated with coronary atherosclerosis in T1DM patients.

Ethnic and gender differences in the management of type 2 diabetes: a cross-sectional study from Norwegian general practice.

BACKGROUND: Ethnic minority groups from Asia and Africa living in Western countries have a higher prevalence of type 2 diabetes (T2DM) than the general population. We aimed to assess ethnic differences in diabetes care by gender. METHODS: Population-based, cross-sectional study identified 10,161 individuals with T2DM cared for by 282 General Practitioners (GP) in Norway. Ethnicity was based on country of birth. Multilevel regression models adjusted for individual and GP factors were applied to evaluate ethnic differences by gender. RESULTS: Diabetes was diagnosed at a younger mean age in all other ethnic groups compared with Westerners (men: 45.9-51.6 years vs. 56.4 years, women: 44.9-53.8 years vs. 59.1 years). Among Westerners mean age at diagnosis was 2.7 years higher in women compared with men, while no gender difference in age at diagnosis was found in any minority group. Daily smoking was most common among Eastern European, South Asian and Middle East/North African men. In both genders, we found no ethnic differences in processes of care (GPs' measurement of HbA1c, blood pressure, LDL-cholesterol, creatinine). The proportion who achieved the HbA1c treatment target was higher in Westerners (men: 62.3%; women: 66.1%), than in ethnic minorities (men 48.2%; women 53.5%). Compared with Western men, the odds ratio (OR) for achieving the target was 0.45 (95% CI 0.27 to 0.73) in Eastern European; 0.67 (0.51 to 0.87) in South Asian and 0.62 (0.43 to 0.88) in Middle Eastern/North African men. Compared with Western women, OR was 0.49 (0.28 to 0.87) in Eastern European and 0.64 (0.47 to 0.86) South Asian women. Compared with Westerners, the blood pressure target was more often achieved in South Asians and Middle Easterners/North Africans in both genders. Small ethnic differences in achieving the LDL-cholesterol treatment target by gender were found. CONCLUSION: Diabetes was diagnosed at a considerably earlier age in both minority men and minority women compared with Westerners. Several minority groups had worse glycaemic control compared with Westerners in both genders, which implies that it is necessary to improve glucose lowering treatment for the minority groups. Smoking cessation advice should particularly be offered to men in most minority groups.

Very High Prevalence of Frozen Shoulder in Patients With Type 1 Diabetes of ≥45 Years' Duration: The Dialong Shoulder Study.

OBJECTIVES: To compare the prevalence of shoulder disorders and self-reported shoulder disability in patients with long-term type 1 diabetes mellitus and diabetes-free subjects; and to explore the association between the long-term glycemic burden and shoulder disability in the diabetes group. DESIGN: Cross-sectional study of shoulder diagnoses with 30 years' historical data on glycemic burden in patients with diabetes. SETTING: Diabetics center and a university hospital. PARTICIPANTS: Subjects attending the Norwegian Diabetics Center in 2015 with type 1 diabetes since 1970 or earlier were eligible (N=136). One hundred and five patients were included, and 102 (50% women; mean age, 61.9y) completed the study together with 73 diabetes-free subjects (55% women; mean age, 62.5y). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Shoulder diagnoses decided through clinical examination according to scientific diagnostic criteria. RESULTS: Frozen shoulder was diagnosed in 60 (59%) patients with diabetes and 0 diabetes-free subjects, with a lifetime prevalence of 76% in the diabetes group versus 14% in the diabetes-free subjects. Patients with diabetes had higher disability and higher mean QuickDASH scores (23.0±19.9) than diabetes-free subjects (8.9±12.0), with a mean difference of -14.2 (95% confidence interval, -19.3 to -9.0) points (P<.001). We found an association between chronic hyperglycemia and QuickDASH scores, with a 6.16-point increase in QuickDASH scores per unit increase in glycated hemoglobin A1c (HbA1c) (P=.014). CONCLUSIONS: The point prevalence of frozen shoulder in patients with long-lasting type 1 diabetes was 59%, and the lifetime prevalence was 76%. The diabetes group had more shoulder disability than diabetes-free subjects. The historical HbA1c level was associated with increased shoulder disability.

Diabetic foot ulcer teams in Norwegian hospitals. / Diabetiske fotsårteam i norske sykehus.

BACKGROUND: The national clincial guidelines for diabetes recommend that diabetic foot ulcers be treated by interdisciplinary diabetic foot ulcer teams. This study aims to survey the extent of diabetic foot ulcer teams in the specialist health service in Norwegian hospitals and to describe their clinical composition, organisation and working routines. MATERIAL AND METHOD: The study is cross-sectional with the use of a questionnaire survey. The criteria for participating were somatic hospitals with 24-hour operations and a specialist function for patients with diabetes mellitus. A total of 41 hospitals participated of the 51 that fulfilled the criteria. RESULTS: Altogether 17 of 41 hospitals had diabetic foot ulcer teams. The teams had a broad clinical composition and followed national recommendations for surveying risk factors and treatment of diabetic foot ulcers. Nine foot ulcer teams had written routines for assessment, five used the Noklus diabetes patient records to document ulcer treatment, and ten had planned interdisciplinary meetings. Only one-quarter of the teams included both medical and surgical competence in the planned interdisciplinary collaboration. INTERPRETATION: The diabetic foot ulcer teams had broad clinical competence and followed national clinical guidelines. The teams had a short waiting time for the initial consultation, half had written guidelines, and 60 % had planned interdisciplinary meetings. Far fewer had included both medical and surgical competence in the planned interdisciplinary collaboration.

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.

[Sources of error when using haemoglobin A1c]. / Feilkilder ved bruk av hemoglobin A1c.

BACKGROUND: Measurement of glycated haemoglobin A1 in whole blood (b-HbA1c) can be used in both diagnosing and following up patients with diabetes. Correct interpretation of analytical results is contingent on agreement between average plasma glucose (p-glucose) and b-HbA1c. This article provides an overview of factors that may result in a discrepancy between average glucose concentration and b-HbA1c. METHOD: Literature search in PubMed to identify scientific articles that describe strengths and weaknesses of b-HbA1c. RESULTS: The b-HbA1c reading usually provides a good picture of average p-glucose for the preceding two to three months. Patients who are being treated with iron/vitamin B12 supplements, have liver failure, haemolytic anaemia or bleeding usually have a lower b-HbA1c than their p-glucose level would suggest. With increasing patient age, B12 deficiency or iron deficiency anaemia, higher values of b-HbA1c are seen for the same p-glucose level. Some ethnic groups have a higher b-HbA1c than their average p-glucose would suggest, but the risk of long-term complications appears generally to be more closely associated with b-HbA1c than with the glucose level. Pregnancy, renal failure or haemoglobinopathies may make the b-HbA1c value unreliable as an expression of average p-glucose. INTERPRETATION: Correct interpretation of b-HbA1c is conditional on the requisitioner being aware of possible sources of error. If the patient is suspected to have a condition that leads to lack of consistency between b-HbA1c and average p-glucose, glucose-based criteria must be used in diagnosing diabetes.

High prevalence of retinopathy in young-onset type 2 diabetes and possible sex differences: insights from Norwegian general practice.

INTRODUCTION: People with young-onset type 2 diabetes (YOD), defined as diabetes diagnosis before age 40, have a high lifetime risk of vascular complications. We aimed to estimate the prevalence of YOD among adults with type 2 diabetes (T2D) in Norwegian general practice and explore associations between age at diabetes diagnosis and retinopathy overall and in men and women. RESEARCH DESIGN AND METHODS: We collected cross-sectional data from general practice electronic medical records of 10 241 adults with T2D in 2014, and repeated measurements of hemoglobin A1c (HbA1c) from 2012 to 2014. Using multivariate logistic regression, we assessed associations between YOD and later-onset T2D, sex and retinopathy. RESULTS: Of all individuals with T2D, 10% were diagnosed before 40 years of age in both sexes. Compared with later-onset T2D, HbA1c increased faster in YOD, and at the time of diagnosis HbA1c was higher in men, particularly in YOD. Retinopathy was found in 25% with YOD, twice as frequently as in later onset. After adjustments for confounders (age, country of origin, education, body mass index), OR of retinopathy was increased in both men with YOD (OR 2.6 (95% CI 2.0 to 3.5)) and women with YOD (OR 2.2 (1.5 to 3.0)). After further adjustments for potential mediators (diabetes duration and HbA1c), the higher OR persisted in men with YOD (OR 1.8 (1.3 to 2.4)) but was attenuated and no longer significant for women with YOD. CONCLUSIONS: Retinopathy prevalence was more than twice as high in YOD as in later-onset T2D. The increased likelihood of retinopathy in YOD was partly mediated by higher HbA1c and longer T2D duration, but after accounting for these factors it remained higher in men with YOD.

How valid is a prescription-based multimorbidity index (Rx-risk) in predicting mortality in the Outcomes and Multimorbidity In Type 2 diabetes (OMIT) study? A nation-wide registry-based cohort study from Norway.

OBJECTIVE: The prescription-based Rx-risk index has previously been developed to measure multimorbidity. We aimed to adapt and evaluate the validity of the Rx-risk index in prediction of mortality among persons with type 2 diabetes. DESIGN: Registry-based study. SETTING: Adults with type 2 diabetes in Norway identified within the 'Outcomes and Multimorbidity In Type 2 diabetes' cohort, with linkage to prescriptions from the Norwegian Prescription Database and mortality from the Population Registry. PARTICIPANTS: We defined a calibration sample of 42 290 adults diagnosed with type 2 diabetes 1950-2013, and a temporal validation sample of 7085 adults diagnosed 2014-2016 to evaluate the index validity over time PRIMARY OUTCOME MEASURE: All-cause mortality METHODS: For the calibration sample, dispensed drug prescriptions in 2013 were used to define 44 morbidity categories. Weights were estimated using regression coefficients from a Cox regression model with 5 year mortality as the outcome and all morbidity categories, age and sex included as covariates. The Rx-risk index was computed as a weighted sum of morbidities. The validity of the index was evaluated using C-statistic and calibration plots. RESULTS: In the calibration sample, mean (SD) age at start of follow-up and duration of diabetes was 63.8 (12.4) and 10.1 (7.0) years, respectively. The overall C-statistic was 0.82 and varied from 0.74 to 0.85 when stratifying on age groups, sex, level of education and country of origin. In the validation sample, mean (SD) age and duration of diabetes was 59.7 (13.0) and 2.0 (0.8) years, respectively. Despite younger age, shorter duration of diabetes and later time period, the C-index was high both in the total sample (0.84) and separately for men (0.83) and women (0.84). CONCLUSIONS: The Rx-risk index showed good discrimination and calibration in predicting mortality and thus presents a valid tool to assess multimorbidity among persons with type 2 diabetes.

Vascular Function in Norwegian Female Elite Runners: A Cross-Sectional, Controlled Study.

In general, aerobic exercise has a positive impact on the vascular system, but the syndrome of relative energy-deficiency in sports (RED-S) makes this impact less clear for the athlete. The present cross-sectional controlled study aimed to investigate the vascular function in female elite long-distance runners, compared to inactive women. Sixteen female elite long-distance runners and seventeen healthy controls were recruited. Assessments of vascular function and morphology included endothelial function, evaluated by flow-mediated dilatation (FMD), vascular stiffness, evaluated with pulse wave velocity (PWV), carotid artery reactivity (CAR %), and carotid intima-media thickness (cIMT). Blood samples included hormone analyses, metabolic parameters, lipids, and biomarkers reflecting endothelial activation. RED-S risk was assessed through the low energy availability in female questionnaire (LEAF-Q), and body composition was measured by dual-energy X-ray absorptiometry (DXA). We found no significant differences in brachial FMD, PWV, CAR %, cIMT, or biomarkers reflecting endothelial activation between the two groups. Forty-four percent of the runners had a LEAF-Q score consistent with being at risk of RED-S. Runners showed significantly higher HDL-cholesterol and insulin sensitivity compared to controls. In conclusion, Norwegian female elite runners had an as good vascular function and morphology as inactive women of the same age.

Thyroid Signaling Biomarkers in Female Symptomatic Hypothyroid Patients on Liothyronine versus Levothyroxine Monotherapy: A Randomized Crossover Trial.

Background: Levels of thyroid-stimulating hormone (TSH) are believed to reflect degree of disease in patients with hypothyroidism, and normalization of levels is the treatment goal. However, despite adequate levels of TSH after starting levothyroxine (LT4) therapy, 5-10% of hypothyroid patients complain of persisting symptoms with a significant negative impact on quality of life. This indicates that TSH is not an optimal indicator of intracellular thyroid hormone effects in all patients. Our aim was to investigate different effects of LT3 and LT4 monotherapy on other biomarkers of the thyroid signaling pathway, in addition to adverse effects, in patients with residual hypothyroid symptoms. Methods: Fifty-nine female hypothyroid patients, with residual symptoms on LT4 monotherapy or LT4/liothyronine (LT3) combination therapy, were randomly assigned in a non-blinded crossover study and received LT4 or LT3 monotherapy for 12 weeks each. Measurements, including serum analysis of a number of biochemical and hormonal parameters, were obtained at the baseline visit and after both treatment periods. Results: Free thyroxine (FT4) was higher in the LT4 group, while free triiodothyronine (FT3) was higher in the LT3 group. The levels of reverse triiodothyronine (rT3) decreased after LT3 treatment compared with LT4 treatment. Both low-density lipoprotein (LDL) and total cholesterol levels were reduced, while sex hormone-binding globulin (SHBG) increased after LT3 treatment compared with LT4 treatment. The median TSH levels for both treatment groups were within the reference range, however, lower in the LT4 group than in the LT3 group. We did not find any differences in pro-B-type natriuretic peptide (NT pro-BNP), handgrip strength, bone turnover markers, or adverse events between the two treatment groups. Conclusion: We have demonstrated that FT4, FT3, rT3, cholesterol, and SHBG show significantly different values on LT4 treatment compared with LT3 treatment in women with hypothyroidism and residual symptoms despite normal TSH levels. No differences in general or bone-specific adverse effects were demonstrated. This trial is registered with NCT03627611 in May 2018.

Effect of Liothyronine Treatment on Quality of Life in Female Hypothyroid Patients With Residual Symptoms on Levothyroxine Therapy: A Randomized Crossover Study.

Objective: The effects of levothyroxine (LT4)/liothyronine (LT3) combination therapy on quality of life (QoL) in hypothyroid patients former on LT4 monotherapy have been disappointing. We therefore wanted to test the effects of LT3 monotherapy on QoL in hypothyroid patients with residual symptoms despite thyroid stimulating hormone (TSH) values within the reference range. Design: Female hypothyroid patients with residual symptoms on LT4 monotherapy or combination LT4/LT3 therapy received LT3 and LT4 monotherapy, respectively for 12 weeks in a non-blinded randomized crossover study. Methods: Fifty-nine patients aged 18-65 years were included. QoL was assessed using one disease-specific questionnaire (ThyPRO) and two generic questionnaires (Fatigue Questionnaire and SF-36) at baseline and at the end of the two treatment periods. Clinical indices of cardiovascular health (resting heart rate and blood pressure), as well as thyroid tests, were assessed at baseline and at the end of the two treatment periods. Results: After 12 weeks of LT3 treatment, 12 of the 13 domains of the ThyPRO questionnaire (physical, mental and social domains) showed significant improvements. The most pronounced improvements were less tiredness (mean -21 ± 26; P<0.0001) and cognitive complaints (mean -20 ± 20; P<0.0001). LT4 monotherapy exerted minor effects on two domains only (cognitive complaints and impaired daily life). All three dimensions' scores in the Fatigue Questionnaire (physical, mental and total fatigue) improved after LT3 treatment compared to baseline (P<0.001), and in the SF-36 questionnaire 7 of 8 scales showed significantly better scores after LT3 treatment compared to baseline. There were no differences in blood pressure or resting heart rate between the two treatment groups. TSH in patients on LT3 was slightly higher (median 1.33 mU/L (interquartile range (IQR) 0.47-2.26)) than in patients on LT4 (median 0.61 mU/L (IQR 0.25-1.20; P<0.018). Five patients on LT3 dropped out of the study due to subjectively reported side effects, compared to only one on LT4. Conclusions: LT3 treatment improved QoL in women with residual hypothyroid symptoms on LT4 monotherapy or LT4/LT3 combination therapy. Short-term LT3 treatment did not induce biochemical or clinical hyperthyroidism, and no cardiovascular adverse effects were recorded. Further studies are needed to assess the long-term safety and efficacy of LT3 monotherapy. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03627611.

Level of education is associated with coronary heart disease and chronic kidney disease in individuals with type 2 diabetes: a population-based study.

INTRODUCTION: To study the relationship between education level and vascular complications in individuals with type 2 diabetes in Norway. RESEARCH DESIGN AND METHODS: Multiregional population-based cross-sectional study of individuals with type 2 diabetes in primary care. Data were extracted from electronic medical records in the period 2012-2014. Information on education level was obtained from Statistics Norway. Using multivariable multilevel regression analyses on imputed data we analyzed the association between education level and vascular complications. We adjusted for age, sex, HbA1c, low-density lipoprotein cholesterol, systolic blood pressure, smoking and diabetes duration. Results are presented as ORs and 95% CIs. RESULTS: Of 8192 individuals with type 2 diabetes included, 34.0% had completed compulsory education, 49.0% upper secondary education and 16.9% higher education. The prevalence of vascular complications in the three education groups was: coronary heart disease 25.9%, 23.0% and 16.9%; stroke 9.6%, 7.4% and 6.6%; chronic kidney disease (estimated glomerular filtration rate <60 mL/min/1.73 m2) 23.9%, 16.8% and 12.6%; and retinopathy 13.9%, 11.5% and 11.7%, respectively. Higher education was associated with lower odds for coronary heart disease (OR 0.59; 95% CI 0.49 to 0.71) and chronic kidney disease (OR 0.75; 95% CI 0.60 to 0.93) compared with compulsory education when adjusting for age, sex, HbA1c, low-density lipoprotein cholesterol, systolic blood pressure, smoking and diabetes duration. CONCLUSIONS: In a country with equal access to healthcare, high education level was associated with lower odds for coronary heart disease and chronic kidney disease in individuals with type 2 diabetes.

Cohort profile: Outcomes & Multi-morbidity In Type 2 diabetes (OMIT) - a national registry-based observational cohort with focus on care and treatment of key high-risk groups in Norway.

PURPOSE: The 'Outcomes & Multi-morbidity in Type 2 Diabetes' (OMIT) is an observational registry-based cohort of Norwegian patients with type 2 diabetes (T2D) established to study high-risk groups often omitted from randomised clinical trials. PARTICIPANTS: The OMIT cohort includes 57 572 patients with T2D identified via linkage of Norwegian Diabetes Register for Adults and the Rogaland-Oslo-Salten-Akershus-Hordaland study, both offering data on clinical patient characteristics and drug prescriptions. Subsequently these data are further linked to the Norwegian Prescription Database for dispensed medications, the Norwegian Population Register for data on death and migration, Statistics Norway for data on socioeconomic factors and ethnicity and the Norwegian Directorate of Health for data on the general practices and clinical procedures involved in the care of cohort patients. OMIT offers large samples for key high-risk patient groups: (1) young-onset diabetes (T2D at age <40 years) (n=6510), (2) elderly (age >75 years) (n=15 540), (3) non-Western ethnic minorities (n=9000) and (4) low socioeconomic status (n=20 500). FINDINGS TO DATE: On average, patient age and diabetes duration is 67.4±13.2 and 12.3±8.3 years, respectively, and mean HbA1c for the whole cohort through the study period is 7.6%±1.5% (59.4±16.3 mmol/mol), mean body mass index (BMI) and blood pressure is 30.2±5.9 kg/m2 and 135±16.1/78±9.8 mm Hg, respectively. Prevalence of retinopathy, coronary heart disease and stroke is 10.1%, 21% and 6.7%, respectively. FUTURE PLANS: The OMIT cohort features 5784 subjects with T2D in 2006, a number that has grown to 57 527 in 2019 and is expected to grow further via repeated linkages performed every third to fifth year. At the next wave of data collection, additional linkages to Norwegian Patient Registry and Norwegian Cause of Death Registry for data on registered diagnoses and causes of death, respectively, will be performed.

Reduced leukocyte telomere lengths and sirtuin 1 gene expression in long-term survivors of type 1 diabetes: A Dialong substudy.

AIMS/INTRODUCTION: The shortening of leukocyte telomere length with age has been associated with coronary disease, whereas the association with type 1 diabetes is unclear. We aimed to explore telomere lengths in diabetes patients with regard to coronary artery disease, compared with healthy controls. The longevity factors sirtuin 1 and growth-differentiating factor 11 were investigated accordingly. MATERIALS AND METHODS: We carried out a cross-sectional study of 102 participants with long-term type 1 diabetes and 75 controls (mean age 62 and 63 years, respectively), where 88 cases and 60 controls without diagnosed coronary artery disease completed computed tomography coronary angiography. Telomere lengths and gene expression of sirtuin 1 and growth-differentiating factor 11 were quantified in leukocytes. RESULTS: Telomere lengths and sirtuin 1 were reduced in diabetes patients versus controls, medians (25th to 75th percentiles): 0.97 (0.82-1.15) versus 1.08 (0.85-1.29) and 0.88 (0.65-1.14) vs 1.01 (0.78-1.36), respectively, adjusted P < 0.05, both. Previous coronary artery disease in diabetes patients (n = 15) was associated with lower sirtuin 1 and growth-differentiating factor 11 messenger ribonucleic acid expression (adjusted P < 0.03, both). In the combined diabetes and control group, previous artery coronary disease (n = 18) presented with significantly shorter telomeres (adjusted P = 0.038). Newly diagnosed obstructive coronary artery disease, defined as >50% stenosis, was not associated with the investigated variables. CONCLUSIONS: Long-term type 1 diabetes presented with reduced telomeres and sirtuin 1 expression, with additional reduction in diabetes patients with previous coronary artery disease, showing their importance for cardiovascular disease development with potential as novel biomarkers in diabetes and coronary artery disease.

NETosis in Long-Term Type 1 Diabetes Mellitus and Its Link to Coronary Artery Disease.

Background: Neutrophil extracellular traps NETs have been linked to glucose and the pathogenesis of type 1 diabetes mellitus (T1DM). NETs also play a role in vascular inflammation and the development of coronary artery disease (CAD). The role of NETs in CAD progression in patients with long-term T1DM is unclear. We aimed to 1) investigate whether levels of circulating NETs markers were elevated in long-term T1DM subjects compared to controls, and 2) explore whether levels of NETs were related to the presence of CAD. Material and Methods: 102 patients with > 45 years of T1DM and 75 age-matched controls were enrolled in a cross-sectional study. Median age was 62 years. Computed tomography coronary angiography (CTCA) was performed in 148 subjects without established coronary heart disease. For the current study, CAD was defined as a coronary artery stenosis >50%. Double-stranded deoxyribonucleic acid (dsDNA) was measured by a nucleic acid stain, myeloperoxidase-DNA (MPO-DNA), citrullinated histone 3 (H3Cit) and peptidylarginine deiminase 4 (PAD4) by ELISAs, while gene expression of PAD4 was measured in leukocytes from PAXgene tubes. Results: Circulating MPO-DNA levels were significantly lower in patients with T1DM than in controls (0.17 vs 0.29 OD, p<0.001), while dsDNA, H3Cit, PAD4 and gene expression of PAD4 did not differ with respect to the presence of T1DM. There were no significant associations between NETs markers and HbA1c in the T1DM group. None of the NETs markers differed according to the presence of CAD in patients with T1DM. While all circulating NETs markers correlated significantly with circulating neutrophils in the control group (r=0.292-393, p<0.014), only H3Cit and PAD4 correlated with neutrophils in the T1DM group (r= 0.330-0.449, p ≤ 0.001). Conclusions: In this cross-sectional study of patients with long-term T1DM and age-matched controls, circulating NETs levels were not consistently associated with the presence of T1DM or glycemic status, and did not differ according to the presence of CAD in patients with T1DM. Our results entail the possibility of altered neutrophil function and reduced NETosis in T1DM. This warrants further investigation.

Effect of Liothyronine Treatment on Dermal Temperature and Activation of Brown Adipose Tissue in Female Hypothyroid Patients: A Randomized Crossover Study.

Background: Thyroid hormones are essential for the full thermogenic response of brown adipose tissue (BAT) and have been implicated in dermal temperature regulation. Nevertheless, persistent cold-intolerance exists among a substantial proportion of hypothyroid patients on adequate levothyroxine (LT4) substitution. Materials and Methods: To assess if skin temperature and activation of BAT during treatment with liothyronine (LT3) differs from that of LT4 treatment, fifty-nine female hypothyroid patients with residual symptoms on LT4 or LT4/LT3 combination therapy were randomly assigned in a non-blinded crossover study to receive monotherapy with LT4 or LT3 for 12 weeks each. Change in supraclavicular (SCV) skin temperature overlying BAT, and sternal skin temperature not overlying BAT, during rest and cold stimulation were assessed by infrared thermography (IRT). In addition, abundance of exosomal miR-92a, a biomarker of BAT activation, was estimated as a secondary outcome. Results: Cold stimulated skin temperatures decreased less with LT3 vs. LT4 in both SCV (mean 0.009°C/min [95% CI: 0.004, 0.014]; P<0.001) and sternal areas (mean 0.014°C/min [95% CI: 0.008, 0.020]; P<0.001). No difference in serum exosomal miR-92a abundance was observed between the two treatment groups. Conclusion: LT3 may reduce dermal heat loss. Thermography data suggested increased BAT activation in hypothyroid patients with cold-intolerance. However, this finding was not corroborated by assessment of the microRNA biomarker of BAT activation. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03627611.