A comparison in women with newly diagnosed diabetes between those with and without a history of gestational diabetes: a new perspective.

AIMS: Previous gestational diabetes mellitus (GDM) entails increased risk of future diabetes. We describe the characteristics of women with previous GDM and compare with no previous GDM from the cohort Diabetes in Kalmar and Kronoberg (DKK) of 1248 adults, 40% women, with new diabetes, and factors affecting age and C-peptide levels at diagnosis of diabetes. METHODS: Age-at-diagnosis of diabetes, BMI, hypertension, hyperlipidemia, smoking, physical activity, and pre-existing myocardial infarction, stroke, or peripheral arterial insufficiency were registered at ordinary care visits close to diagnosis of diabetes, for the 43 women (9.4% of 456 from DKK with complete data for this analysis) with self-reported previous GDM (yes/no) and 86 controls without it, matched for date of diagnosis of diabetes. Blood samples were centrally analyzed for GADA and C-peptide for classification of diabetes. RESULTS: Women with previous GDM had lower mean age-at-diagnosis of diabetes, 53.4 vs 65.0 years, lower systolic blood pressure (SBP), 131.2 vs 137.5 mmHg, and fewer had pre-existing hypertension than without previous GDM (p < 0.001-0.05). Among antibody negative women with previous GDM, BMI (p = 0.024), hypertension (p = 0.023) and hyperlipidemia (p < 0.001) were associated with higher levels of C-peptide, while physical activity was inversely associated (p = 0.035), and SBP (p = 0.02) and hypertension (p = 0.016) were associated with age-at-diagnosis of diabetes. CONCLUSIONS: Women with previous GDM were a decade younger and had lower prevalence of hypertension at diagnosis of diabetes; C-peptide levels were associated with BMI, hypertension, and hyperlipidemia and showed a tendency to be lower, possibly indicating a phenotype with higher risk of overt cardiovascular disease later in life.

Depression was associated with younger age, female sex, obesity, smoking, and physical inactivity, in 1027 patients with newly diagnosed type 2 diabetes: a Swedish multicentre cross-sectional study.

BACKGROUND: Depression is a risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The aims were to explore the prevalence of depression, anxiety, antidepressant use, obesity, Hemoglobin A1c > 64 mmol/mol, life-style factors, pre-existing CVD, in patients with newly diagnosed T2D; to explore associations with depression; and to compare with Swedish general population data. METHODS: Multicentre, cross-sectional study. INCLUSION CRITERIA: adults with serologically verified newly diagnosed T2D. Included variables: age, sex, current depression and anxiety (Hospital Anxiety and Depression Scale), previous depression, antidepressant use, obesity (BMI ≥ 30 and ≥ 40 kg/m2), Hemoglobin A1c, pre-existing CVD. Logistic regression analyses were performed. RESULTS: In 1027 T2D patients, aged 18-94 years, depression was associated with age (per year) (inversely) (odds ratio (OR) 0.97), anxiety (OR 12.2), previous depression (OR 7.1), antidepressant use (OR 4.2), BMI ≥ 30 kg/m2 (OR 1.7), BMI ≥ 40 kg/m2 (OR 2.3), smoking (OR 1.9), physical inactivity (OR 1.8), and women (OR 1.6) (all p ≤ 0.013). Younger women (n = 113), ≤ 59 years, compared to younger men (n = 217) had higher prevalence of current depression (31% vs 12%), previous depression (43 vs 19%), anxiety (42% vs 25%), antidepressant use (37% vs 12%), BMI ≥ 30 kg/m2 (73% vs 60%) and BMI ≥ 40 kg/m2) (18% vs 9%), and smoking (26% vs 16%) (all p ≤ 0.029). Older women (n = 297), ≥ 60 years, compared to older men (n = 400) had higher prevalence of previous depression (45% vs 12%), anxiety (18% vs 10%), antidepressant use (20% vs 8%), BMI ≥ 30 kg/m2 (55% vs 47%), BMI ≥ 40 kg/m2 (7% vs 3%) (all p ≤ 0.048), but not of current depression (both 9%). Compared to the Swedish general population (depression (women 11.2%, men 12.3%) and antidepressant use (women 9.8%, men 5.3%)), the younger women had higher prevalence of current depression, and all patients had higher prevalence of antidepressant use. CONCLUSIONS: In patients with newly diagnosed T2D, the younger women had the highest prevalence of depression, anxiety, and obesity. The prevalence of depression in young women and antidepressant use in all patients were higher than in the Swedish general population. Three risk factors for CVD, obesity, smoking, and physical inactivity, were associated with depression.

A novel index to assess low energy fracture risks in patients prescribed antiepileptic drugs.

OBJECTIVE: To develop an index assessing the risks of low energy fractures (LEF) in patients prescribed antiepileptic drugs (AED) by exploring five previously suggested risk factors; age, gender, AED-type, epilepsy diagnosis and BMI. METHODS: In a population-based retrospective open cohort study we used real world data from the Electronic Health Register (EHR) in Region Kalmar County, Sweden. 23 209 patients prescribed AEDs at any time from January 2008 to November 2018 and 23 281 matching controls were followed from first registration in the EHR until the first documented LEF, disenrollment (or death) or until the end of the study period, whichever came first. Risks of LEF measured as hazard rate ratios in relation to the suggested risk factors and in comparison to matched controls were analyzed using Cox regression. The index was developed using a linear combination of the statistically significant variables multiplied by the corresponding regression coefficients. RESULTS: Data from 23 209 patients prescribed AEDs and 2084 documented LEFs during a follow-up time of more than 10 years resulted in the Kalmar Epilepsy Fracture Risk Index (KEFRI). KEFRI = Age-category x (1.18) + Gender x (-0.51) + AED-type x (0.29) + Epilepsy diagnosis-category x (0.31) + BMI-category x (-0.35). All five previously suggested risk factors were confirmed. Women aged 75 years and older treated with an inducing AED against epilepsy and BMIs of 25 kg/m2 or below had 48 times higher LEF rates compared to men aged 50 years or younger, treated with a non-inducing AED for a condition other than epilepsy and BMIs above 25 kg/m2. CONCLUSION: The KEFRI is the first weighted multifactorial assessment tool estimating risks of LEF in patients prescribed AEDs and could serve as a feasible guide within clinical practice.

Modestly degraded microarchitecture and high serum levels of osteopontin in Swedish females with anorexia nervosa.

PURPOSE: Adult women with long-time anorexia nervosa (AN) are believed to have osteopenia (T-score ≤ 1.0) in 93 % and osteoporosis (T-score ≤ 2.5) in 38 %. Bone microarchitecture assessed by Trabecular Bone Score (TBS) predicts osteoporotic fractures. Our aim was to evaluate the microarchitecture in adult females with AN by determining TBS and to identify factors potentially associated with TBS, such as bone turnover markers. METHODS: 20 female patients with AN (DSM IV), aged 27.8 ± 4.4 years, BMI 16.6 ± 0.6 kg/m2 and duration of illness of 8.5 ± 5 years had previously been evaluated with dual-energy X-ray absorptiometry (DXA). TBS measurements were now obtained, using iNsight software, from spinal DXA images. Serum levels of bone turnover markers were determined in patients and healthy normal-weight controls. RESULTS: Compared to controls serum values of osteopontin were higher (p = 0.009). BMD in patients with AN was reduced by at least 1.0 SD at one or more skeletal sites in 65 % of patients and by at least 2.5 SD in 20 %. Only one of the patients (5%) had suffered a fracture. TBS (mean 1.35 ± 0.06; median 1.36 (1.23-1.44) was in the lower normal range (≥ 1.35). 40 % of patients showed partially (> 1.20 and < 1.35) but none showed a fully degraded micro-architecture. CONCLUSIONS: In Swedish AN patients we found a low reduction of BMD and fracture history. The bone microarchitecture, evaluated for the first time for this group by TBS, was only modestly compromised, and to a lesser extent than expected for this group of patients with AN. LEVEL OF EVIDENCE: Level V; cross-sectional descriptive study.

Assessing heart rate variability in type 1 diabetes mellitus-Psychosocial stress a possible confounder.

BACKGROUND: Autonomic neuropathy (AN) commonly arises as a long-term complication in diabetes mellitus and can be diagnosed from heart rate variability (HRV), calculated from electrocardiogram recordings. Psychosocial stress also affects HRV and could be one of several confounders for cardiac AN. The present work investigated the impact of psychosocial stress on HRV in individuals with type 1 diabetes mellitus (T1DM) and assessed the use of salivary cortisol as a biomarker for psychosocial stress in this context. METHODS: A total of 167 individuals 6-60 years old (113 with T1DM and 54 healthy controls) underwent 24-hr ECG recordings with HRV analysis. Salivary cortisol was sampled thrice during the registration day. Perceived psychosocial stress along with other factors of possible importance for the interpretation of HRV was documented in a diary. RESULTS: Heart rate variability (high-frequency power during sleep) was reduced (p < .05) with older age, longer diabetes duration, higher mean glucose levels, physical inactivity, and perceived psychosocial stress. Salivary cortisol levels in the evening were increased (p < .05) in women in ovulation phase, in individuals with preceding hypoglycemia or with hyperglycemia. The amplitude of salivary cortisol was reduced (p < .05) with the presence of perceived psychosocial stress, but only in adult healthy controls, not in individuals with diabetes. CONCLUSION: Psychosocial stress might be a confounder for reduced HRV when diagnosing cardiac AN in T1DM. Salivary cortisol is, however, not a useful biomarker for psychosocial stress in diabetes since the physiological stress of both hypoglycemia and hyperglycemia seems to overrule the effect of psychosocial stress on cortisol.

Adherence to risk management guidelines for drugs which cause vitamin D deficiency - big data from the Swedish health system.

PURPOSE: Several medications are known to cause vitamin D deficiency. The aim of this study is to describe vitamin D testing and supplementation in patients using these "risk medications", thereby assessing adherence to medical guidelines. PATIENTS AND METHODS: A database with electronic health records for the population in a Swedish County (≈240,000 inhabitants) was screened for patients prescribed the pre-defined "risk medications" during a 2-year period (2014-2015). In total, 12,194 patients were prescribed "risk medications" pertaining to one of the three included pharmaceutical groups. Vitamin D testing and concomitant vitamin D supplementation, including differences between the included pharmaceutical groups, was explored by matching personal identification numbers. RESULTS: Corticosteroids were prescribed to 10,003 of the patients, antiepileptic drugs to 1,101, and drugs mainly reducing vitamin D uptake to 864. Two hundred twenty-six patients were prescribed >1 "risk medication". Seven hundred eighty-seven patients (6.5%) had been tested during the 2-year period. There were no differences regarding testing frequency between groups. Concomitant supplements were prescribed to 3,911 patients (32.1%). It was more common to be prescribed supplements when treated with corticosteroids. Vitamin D supplementation was more common among tested patients in all three groups. Women were tested and supplemented to a higher extent. The mean vitamin D level was 69 nmol/L. Vitamin D deficiency was found in 24.1% of tested patients, while 41.3% had optimal levels. It was less common to be deficient and more common to have optimal levels among patients prescribed corticosteroids. CONCLUSION: Adherence to medical guidelines comprising testing and supplementation of patients prescribed drugs causing vitamin D deficiency needs improvement in Sweden.

Directly measured free 25-hydroxy vitamin D levels show no evidence of vitamin D deficiency in young Swedish women with anorexia nervosa.

PURPOSE: Anorexia nervosa (AN) is an eating disorder characterized by low fat mass complicated by osteoporosis. The role of circulating vitamin D in the development of bone loss in AN is unclear. Fat mass is known to be inversely associated with vitamin D levels measured as serum levels of total, protein-bound 25-hydroxyvitamin D, but the importance of directly measured, free levels of 25(OH)D has not been determined in AN. The aim of this study was to investigate vitamin D status, as assessed by serum concentrations of total and free serum 25(OH)D in patients with AN and healthy controls. METHODS: In female AN patients (n = 20), and healthy female controls (n = 78), total 25(OH)D was measured by LC-MS/MS, and free 25(OH)D with ELISA. In patients with AN bone mineral density (BMD) was determined with DEXA. RESULTS: There were no differences between patients and controls in total or free S-25(OH)D levels (80 ± 31 vs 72 ± 18 nmol/L, and 6.5 ± 2.5 vs 5.6 ± 1.8 pg/ml, respectively), and no association to BMD was found. In the entire group of patients and controls, both vitamin D parameters correlated with BMI, leptin, and PTH. CONCLUSIONS: The current study did not demonstrate a vitamin D deficiency in patients with AN and our data does not support vitamin D deficiency as a contributing factor to bone loss in AN. Instead, we observed a trend toward higher vitamin D levels in AN subjects compared to controls. Measurement of free vitamin D levels did not contribute to additional information.

Erythrocyte fatty acid composition does not influence levels of free, bioavailable, and total 25-hydroxy vitamin D.

In vitro, mono- and polyunsaturated fatty acids (FAs) may decrease the binding affinity of vitamin D metabolites for vitamin D-binding protein, which in turn may influence their bioavailability. FAs incorporated as phospholipids in erythrocyte (ery-) cell membranes reflect dietary intake. The purpose of this study was to investigate ery-FA composition in relation to markers for vitamin D. In healthy females (age 22.6 ± 2.0 years) total 25(OH)D was measured by LC-MS/MS (n = 78), free 25(OH)D with ELISA (n = 64 of 78), and bioavailable 25(OH)D was calculated. Analysis of ery-FA composition was by gas chromatography (n = 56 of 78). A strong correlation between total 25(OH)D and free 25(OH)D was seen (r = .66, p < .001), and between total-25(OH)D and bioavailable 25(OH)D (r = .68, p < .001). No correlations between 25(OH)D fractions and specific fatty acids were found, and in particular, no associations with mono- and poly-unsaturated FA compositions. All 25(OH)D fractions were correlated with leptin (total 25(OH)D (r = -.33, p < .003); bioavailable 25(OH)D (r = -.47, p < .001); free 25(OH)D (r = -.44, p < .001). Associations were found between PTH and total 25(OH)D (r = -.35, p = .002) and weaker between bioavailable 25(OH)D (r = -.35, p = .040) and free 25(OH)D (r = -.28, p = .079). All fractions of 25(OH)D appear to correlate in a similar way to PTH, BMI and body fat (leptin). No association was found between ery-FA composition and free/bioavailable 25(OH)D. It is unlikely that FAs are a strong uncoupling factor of DBP-bound 25(OH)D.

Older Swedish Adults with High Self-Perceived Health Show Optimal 25-Hydroxyvitamin D Levels Whereas Vitamin D Status Is Low in Patients with High Disease Burden.

Controversy pervades the definition of adequate and optimal vitamin D status. The Institutes of Medicine have recommended serum 25(OH)D levels above 50 nmol/L based upon evidence related to bone health, but some experts, including the Endocrine Society and International Osteoporosis Foundation, suggest a minimum serum 25(OH)D level of 75 nmol/L to reduce the risk of falls and fractures in older adults. In a cross-sectional study, we compared vitamin D status in people ≥75 years selected from four groups with a frailty phenotype, combined with a control group free from serious illness, and who considered themselves completely healthy. Only 13% of the 169 controls were vitamin D deficient (S-25(OH)D) < 50 nmol/L), in contrast with 49% of orthopedic patients with hip fractures (n = 133), 31% of stroke patients (n = 122), 39% of patients visiting the hospital's emergency department ≥4 times a year (n = 81), and 75% of homebound adult residents in long-term care nursing homes (n = 51). The mean vitamin D concentration of the healthy control group (74 nmol/L) was similar to a suggested optimal level based on physiological data and mortality studies, and much higher than that of many officially recommended cut-off levels for vitamin D deficiency (<50 nmol/L). The present study provides a basis for planning and implementing public guidelines for the screening of vitamin D deficiency and vitamin D treatment for frail elderly patients.

Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes.

PURPOSE: Gitelman's syndrome (GS) is an inherited autosomal recessive disorder due to loss of function mutations in the SLC12A3 gene encoding the Na-Cl co-transporter (NCCT), the target of thiazide diuretics. The defective function of the NCCT, which normally is expressed in the apical membrane of the distal convolute tubule in the kidney, leads to mild hypotension, hypokalemia, hyperreninemic hyperaldosteronism, mild metabolic alkalosis, hypomagnesemia and hypocalciuria. Up to now, more than 100 mutations of the SLC12A3 gene have been described in GS patients. METHODS: We have collected 30 patients from Sweden with a clinical diagnosis of GS and undertaken a mutation screening by SSCP and successive sequencing of the 26 exons and intronic boundaries. Both mutations were identified in most (n = 28, 93%) and at least one mutation was identified in all patients. RESULTS: We found 22 different mutations evenly distributed throughout the gene, 11 of which have not been described previously. The new variants include 8 missense mutations (Glu68Lys, His69Asn, Argl45His, Vall53Met, Gly230Asp, Gly342Ala, Val677Leu and Gly867Ser), 1 insertion (c.834_835insG on exon 6) and 2 splice-site mutations (c.2667 + lT>G substitution in splicing donor site after exon 22, c.1569-1G>A substitution in the splicing acceptor site before exon 13). CONCLUSION: In Swedish patients with the clinical features of GS, disease-causing mutations in the SLC12A3 gene were identified in most patients. The spectrum of GS mutations is wide making full mutation screening of the SLC12A3 gene necessary to confirm the diagnosis.

Genetic variation of the intestinal fatty acid-binding protein 2 gene in carotid atherosclerosis.

The alanine (A) to threonine (T) substitution at codon 54 of the intestinal fatty acid-binding protein 2 (FABP2) has been associated with dyslipidaemia and other characteristics of the metabolic syndrome, which in turn is a risk factor for cerebrovascular disease. The aim of this study was to investigate whether the A54T polymorphism in the FABP2 gene is associated with internal carotid artery (ICA) stenosis in stroke patients. Swedish subjects initially diagnosed with acute cerebrovascular disease (n=196) that had been assessed with ultrasound of the carotid arteries were identified and grouped depending on whether a stenosis was found. The subjects were genotyped for the A54T polymorphism using a PCR-RFLP method. In a multivariate logistic-regression analysis, where known risk factors for atherosclerosis were fixed (diabetes, systolic blood pressure, age and smoking), having the FABP2 T allele was a significant risk factor for ICA stenosis (odds ratio 2.9; 95% confidence interval, 1.1-7.7; p = 0.04) together with diabetes (odds ratio 4.9; 95% confidence interval, 1.8-14; p < 0.01). Age, smoking and blood pressure did not reach statistical significance. In conclusion, our result supports the hypothesis that the FABP2 A54T polymorphism is associated with ICA stenosis.