Högskolan i Skövde

Background: Type 2 diabetes mellitus is a metabolic disorder characterized by the rise of fasting plasma glucose from its normal range (≥125mg/dl). It is marked by insufficient production of insulin from pancreatic β-cells as a result of failed compensation due to insulin resistance. Several treatments are available for the disorder, which mainly focus on improving the sensitivity of insulin in different body tissues. Recently, probiotics were suggested as candidate treatments for type 2 diabetes and for extending lifespan as well. This experiment aims to investigate such claims using Drosophila melanogaster as a disease model.

Results: Other than the observed low average weights in treated larva samples, probiotics did not show any other significant results in affecting the length, glucose, glycogen, and trehalose levels (One-Way ANOVA and Kruskal-Wallis, p>0.05). Real-time PCR was only carried out once. Thus, no statistical tests were reliable enough to analyse the data obtained. The longevity study, on the other hand, did show significance (Log-rank (Mantel-Cox) test and Gehan-Breslow-Wilcoxon test, p<0.0001), as the probiotic Bifidobacterium lactis extended the lifespan of adult flies feeding on a high sugar diet significantly when compared to the control ones feeding on only high sugar diet without probiotics.

Conclusion: Except for weight measurements, none of the other results was reliable enough to make a concrete conclusion on whether the treatments indeed worked in reversing type 2 diabetes symptoms or not. Real-time PCR results did show some effects of some of the treatments at different developmental stages. However, unless Real-time PCR is repeated at least once using the same protocol, no deduction can be made. Additionally, the data obtained hint that the dosage used (0.025 g) was too high for larvae and adult flies and might have caused malnutrition by blocking their midgut and decreasing food absorption. Hence, false significant or non-significant results were acquired instead.

Further studies are required using a much lower probiotic dosage if Drosophila is used as a disease model. Although, other models such as mice or rats are recommended in this case, in order to reach a solid conclusion about the effectiveness of probiotics in treating type 2 diabetes mellitus. Baring these thoughts in mind and based on the results of this experiment, the null hypothesis indicating that there is no significant relationship between the use of probiotics and reversing type 2 diabetes mellitus symptoms is therefore accepted.

Background: The increased incidence of impaired glucose tolerance (IGT), are serious public health issues, and several studies link sleeping disorders with increased risk of developing type 2 diabetes, impaired glucose tolerance and insulin resistance (IR). This study explore how self-reported lack of sleep and low vitality, are associated with IGT in a representative Swedish population. Methods. A cross-sectional survey conducted in two municipalities in South-western Sweden. Participants aged 30-75 were randomly selected from the population in strata by sex and age. Altogether, 2,816 participants were surveyed with a participation rates at 76%. Participants with normal glucose tolerance (n=2,314), and those with IGT (n=213) were retained for analyses. The participants answered a questionnaire before the oral glucose tolerance test (OGTT). Associations for questions concerning sleeping disorders, vitality and IGT were analysed using logistic regression and were expressed as odds ratios (OR) with 95% CI. Results: In men a statistically significant age-adjusted association was found between self-reported lack of sleep and IGT: OR 2.4 (95% CI: 1.1-5.4). It did not weaken after further adjustment for body mass index (BMI), smoking, education, and leisure time physical activity 2.3 (1.0-5.5, p=0.044). No such associations were found in females. Corresponding age-adjusted associations between low vitality and IGT in both men 2.8 (1.3-5.8), and women 2.0 (1.2-3.4) were successively lost with increasing adjustment. Conclusions: Insufficient sleep seems independently associated with IGT in men, while low vitality was not independently associated with IGT neither in men nor women, when multiple confounders are considered. IGT should be considered in patients presenting these symptoms, and underlying mechanisms further explored. © 2013 Andersson et al.; licensee BioMed Central Ltd.

Objective. To investigate gender differences in the association between self-rated health (SRH) and impaired glucose tolerance (IGT) in subjects unaware of their glucose tolerance. Design. A cross-sectional population-based study. Setting. The two municipalities of Vara and Skovde in south-western Sweden. Subjects. A total of 2502 participants (1301 women and 1201 men), aged 30-75, were randomly selected from the population. Main outcome measures. IGT was regarded as the outcome measure and SRH as the main risk factor. Results. The prevalence of IGT was significantly higher in women (11.9%) than in men (10.1%), (p = 0.029), as was the prevalence of low SRH (women: 35.4%; men: 22.1%, p = 0.006). Both men and women with low SRH had a poorer risk factor profile than those with high SRH, and a statistically significant crude association between SRH and IGT was found in both men (OR = 2.8, 95% CI 1.8-4.4) and women (OR = 1.5, 95% CI 1.0-2.2, p = 0.033). However, after controlling for several lifestyle factors and biomedical variables, the association was attenuated and remained statistically significant solely in men (OR = 2.3, 95% CI 1.2-4.3). Conclusion. The gender-specific associations found between SRH and IGT suggest that SRH may be a better indicator of IGT in men than in women. Future studies should evaluate the utility of SRH in comparison with objective health measures as a potential aid to health practitioners when deciding whether to screen for IGT and T2DM.

Immigrants from the Middle East have higher prevalence and incidence of type 2 diabetes (T2D) compared with native Swedes. The aim of the study was to describe and understand health beliefs in relation to T2D as well as attitudes regarding participation in a screening process in a local group of Assyrian immigrants living in Sweden. A qualitative and quantitative method was chosen in which 43 individuals participated in a health check-up and 13 agreed to be interviewed. Interviews were conducted, anthropometric measurements and blood tests were collected, and an oral glucose tolerance test was performed. In total, 13 of the 43 participants were diagnosed with impaired glucose metabolism, 4 of these 13 had TD2. The interviewed participants perceived that screening was an opportunity to discover more about their health and to care for themselves and their families. Nevertheless, they were not necessarily committed to taking action as a consequence of the screening. Instead, they professed that their health was not solely in their own hands and that they felt safe that God would provide for them. Assyrians' background and religion affect their health beliefs and willingness to participate in screening for TD2.

OBJECTIVE: Adiposity predictors, body mass index (BMI), waist circumference (WC), and blood leptin and total adiponectin levels were associated with components of cerebral small vessel disease (CSVD) and brain volumetry in 503 adults with CSVD who were ≥50 years of age and enrolled in the Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort (RUN DMC).

METHODS: RUN DMC participants were followed up for 9 years (2006-2015). BMI, WC, brain imaging, and dementia diagnoses were evaluated at baseline and follow-up. Adipokines were measured at baseline. Brain imaging outcomes included CSVD components, white matter hyperintensities, lacunes, microbleeds, gray and white matter, hippocampal, total brain, and intracranial volumes.

RESULTS: Cross-sectionally among men at baseline, higher BMI, WC, and leptin were associated with lower gray matter and total brain volumes, and higher BMI and WC were associated with lower hippocampal volume. At follow-up 9 years later, higher BMI was cross-sectionally associated with lower gray matter volume, and an obese WC (>102 cm) was protective for ≥1 lacune or ≥1 microbleed in men. In women, increasing BMI and overweight or obesity (BMI ≥25 kg/m² or WC >88 cm) were associated with ≥1 lacune. Longitudinally, over 9 years, a baseline obese WC was associated with decreasing hippocampal volume, particularly in men, and increasing white matter hyperintensity volume in women and men.

CONCLUSIONS: Anthropometric and metabolic adiposity predictors were differentially associated with CSVD components and brain volumetry outcomes by sex. Higher adiposity is associated with a vascular-neurodegenerative spectrum among adults at risk for vascular forms of cognitive impairment and dementias.

White adipose tissue browning, defined by accelerated mitochondrial metabolism and biogenesis, is considered a promising mean to treat or prevent obesity-associated metabolic disturbances. We hypothesize that redox stress acutely leads to increased production of reactive oxygen species (ROS), which activate electrophile sensor nuclear factor erythroid 2-Related Factor 2 (NRF2) that over time results in an adaptive adipose tissue browning process. To test this, we have exploited adipocyte-specific NRF2 knockout mice and cultured adipocytes and analyzed time- and dose-dependent effect of NAC and lactate treatment on antioxidant expression and browning-like processes. We found that short-term antioxidant treatment with N-acetylcysteine (NAC) induced reductive stress as evident from increased intracellular NADH levels, increased ROS-production, reduced oxygen consumption rate (OCR), and increased NRF2 levels in white adipocytes. In contrast, and in line with our hypothesis, longer-term NAC treatment led to a NRF2-dependent browning response. Lactate treatment elicited similar effects as NAC, and mechanistically, these NRF2-dependent adipocyte browning responses in vitro were mediated by increased heme oxygenase-1 (HMOX1) activity. Moreover, this NRF2-HMOX1 axis was also important for β3-adrenergic receptor activation-induced adipose tissue browning in vivo. In conclusion, our findings show that administration of exogenous antioxidants can affect biological function not solely through ROS neutralization, but also through reductive stress. We also demonstrate that NRF2 is essential for white adipose tissue browning processes. 

Context

Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture but the mechanisms are largely unknown.

Objective

To identify the molecular mechanisms underlying electroacupuncture-induced glucose uptake in skeletal muscle in insulin-resistant overweight/obese women with and without polycystic ovary syndrome (PCOS).

Design/Participants

In a case-control study, skeletal muscle biopsies were collected from 15 women with PCOS and 14 controls before and after electroacupuncture. Gene expression and methylation was analyzed using Illumina BeadChips arrays.

Results

A single bout of electroacupuncture restores metabolic and transcriptional alterations and induces epigenetic changes in skeletal muscle. Transcriptomic analysis revealed 180 unique genes (q < 0.05) whose expression was changed by electroacupuncture, with 95% of the changes towards a healthier phenotype. We identified DNA methylation changes at 304 unique sites (q < 0.20), and these changes correlated with altered expression of 101 genes (P < 0.05). Among the 50 most upregulated genes in response to electroacupuncture, 38% were also upregulated in response to exercise. We identified a subset of genes that were selectively altered by electroacupuncture in women with PCOS. For example, MSX1 and SRNX1 were decreased in muscle tissue of women with PCOS and were increased by electroacupuncture and exercise. siRNA-mediated silencing of these 2 genes in cultured myotubes decreased glycogen synthesis, supporting a role for these genes in glucose homeostasis.

Conclusion

Our findings provide evidence that electroacupuncture normalizes gene expression in skeletal muscle in a manner similar to acute exercise. Electroacupuncture might therefore be a useful way of assisting those who have difficulties performing exercise.

Background: Class IA phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) is an integral mediator of insulin signaling. The p110 catalytic and p85 regulatory subunits of PI3K are the products of separate genes, and while they come together to make the active heterodimer, they have opposing roles in insulin signaling and action. Deletion of hepatic p110α results in an impaired insulin signal and severe insulin resistance, whereas deletion of hepatic p85α results in improved insulin sensitivity due to sustained levels of phosphatidylinositol (3,4,5)-trisphosphate. Here, we created mice with combined hepatic deletion of p110α and p85α (L-DKO) to study the impact on insulin signaling and whole body glucose homeostasis.Methods: Six-week old male flox control and L-DKO mice were studied over a period of 18 weeks, during which weight and glucose levels were monitored, and glucose tolerance tests, insulin tolerance test and pyruvate tolerance test were performed. Fasting insulin, insulin signaling mediators, PI3K activity and insulin receptor substrate (IRS)1-associated phosphatidylinositol kinase activity were examined at 10 weeks. Liver, muscle and white adipose tissue weight was recorded at 10 weeks and 25 weeks.Results: The L-DKO mice showed a blunted insulin signal downstream of PI3K, developed markedly impaired glucose tolerance, hyperinsulinemia and had decreased liver and adipose tissue weights. Surprisingly, however, these mice displayed normal hepatic glucose production, normal insulin tolerance, and intact IRS1-associated phosphatidylinositol kinase activity without compensatory upregulated signaling of other classes of PI3K.Conclusions: The data demonstrate an unexpectedly overall mild metabolic phenotype of the L-DKO mice, suggesting that lipid kinases other than PI3Ks might partially compensate for the loss of p110α/p85α by signaling through other nodes than Akt/Protein Kinase B.

Insulin resistance and lower muscle quality (strength divided by mass) are hallmarks of type 2 diabetes (T2D). Here, we explore whether alterations in muscle stem cells (myoblasts) from individuals with T2D contribute to these phenotypes. We identify VPS39 as an important regulator of myoblast differentiation and muscle glucose uptake, and VPS39 is downregulated in myoblasts and myotubes from individuals with T2D. We discover a pathway connecting VPS39-deficiency in human myoblasts to impaired autophagy, abnormal epigenetic reprogramming, dysregulation of myogenic regulators, and perturbed differentiation. VPS39 knockdown in human myoblasts has profound effects on autophagic flux, insulin signaling, epigenetic enzymes, DNA methylation and expression of myogenic regulators, and gene sets related to the cell cycle, muscle structure and apoptosis. These data mimic what is observed in myoblasts from individuals with T2D. Furthermore, the muscle of Vps39+/− mice display reduced glucose uptake and altered expression of genes regulating autophagy, epigenetic programming, and myogenesis. Overall, VPS39-deficiency contributes to impaired muscle differentiation and reduced glucose uptake. VPS39 thereby offers a therapeutic target for T2D. 

Aims: There are few cohorts of type 1 diabetes that follow individuals over more than half a century in terms of health outcomes. The aim of this study was to examine associations between type 1 diabetes, diagnosed before age 18, and long-term morbidity and mortality, and to investigate whether cognitive ability plays a role in long-term morbidity and mortality risk. Methods: In a Swedish cohort, 120 men with type 1 diabetes and 469 without type 1 diabetes were followed between 18 and 77 years of age as regards morbidity and mortality outcomes, and impact of cognitive ability at military conscription for the outcomes. In Cox regression analyses and Kaplan-Meier analyses with log-rank tests, associations between diabetes and cognitive ability respectively, and outcomes (mortality, cardiovascular morbidity and diabetes complications) were investigated. Results: Men with type 1 diabetes suffered from dramatically higher mortality (HR 4.62, 95% CI: 3.56–5.60), cardiovascular mortality (HR 5.60, 95% CI: 3.27–9.57), and cardiovascular events (HR 3.97, 95% CI: 2.79–5.64) compared to men without diabetes. Higher cognitive ability at military conscription was associated with lower mortality in men without diabetes, but was not associated with any outcome in men with diabetes. Conclusions: In this historical cohort study with 60 years of follow-up time and a less effective treatment of diabetes than today, mortality rates and cardiovascular outcomes were high for men with type 1 diabetes. Morbidity or mortality did not differ between those that had low to normal or high cognitive ability among men with type 1 diabetes.

Background: Laparoscopic sleeve gastrectomy (SG) achieves type 2 diabetes (T2D) remission to various extents, and reasons for such variations are unknown. Objectives: We assessed patients’ characteristics associated with T2D remission 1 year post SG. Setting: University hospital. Methods: Retrospective study of 230 T2D patients (18–64 yr) who underwent SG at our institution. We examined pre- and postoperative demographic, anthropometric, biochemical, and clinical characteristics associated with T2D complete remission, partial remission, improvement, or unchanged status. Independent predictors of T2D complete remission were assessed by binary logistic regression and then included in 7 predictive models. Logistic regression assessed the pre- and postoperative predictors of T2D complete remission and their predictive performance was measured with the area under the curve of the receiver operating characteristic curve. Results: A total of 230 patients were included in the study, females comprised 69%, and mean age was 45.66 ± 8.84 years. Mean preoperative weight and body mass index were 115.69 ± 20.76 kg and 43.53 ± 6.98 kg/m2, respectively. Approximately two thirds (64.4%) of the sample had diabetes for &gt;5 years. Insulin therapy users comprised 36.9% of the sample and 29.6% of patients were on ≥2 oral hypoglycemic agents (OHA). At 1 year, mean body mass index was 32.77 ± 6.09 kg/m2, percent excess weight loss (%EWL) was 62.29 ± 23.60% and glycosylated hemoglobin (HbA1C) improved from 8.1% to 6.18%. Approximately 42.2% of the sample achieved T2D complete remission. Compared with those with no remission, patients with complete remission were significantly younger, had shorter duration of diabetes, were not on insulin therapy, took fewer OHA, had higher C-peptide, lower preoperative HbA1C, were less likely to have had hypertension or dyslipidemia, and more likely to have achieved higher %EWL. Seven proposed models for prediction of complete remission showed the most useful model comprised diabetes duration + pre-HbA1C + %EWL + insulin therapy + age + OHA (area under the curve = .81). Independent predictors of complete remission were preoperative HbA1C, %EWL, insulin therapy, age, and OHA (but not diabetes duration). Conclusion: SG results in significant weight reduction and various extents of T2D remission. HbA1C, %EWL, insulin therapy, age, and OHA were independent predictors of complete remission. Assessing these factors before bariatric surgery is important to identify any modifiable characteristics that can be altered to increase the likelihood of remission. © 2020 American Society for Bariatric Surgery

Background: Long-term durability of weight loss and comorbidity resolution beyond 7 years after laparoscopic sleeve gastrectomy (LSG) among adolescents is completely lacking. Methods: Retrospective review of adolescents aged ≤ 18 years who underwent primary LSG at our institution between 2011 and 2015 (N = 146). We assessed anthropometric and cardiometabolic outcomes at 1, 3, 5, 7, and 9 years. Results: Follow-up rates were 57.53%, 82.87%, 85.24%, 83.92%, and 83.33% at the five time points. The preoperative mean body mass index (BMI) (45.60 ± 6.50 kg/m2) decreased at year 1 (30.04 ± 4.96 kg/m2, P=0.001) and was maintained up to 9 years (30.20 ± 3.92 kg/m2, P = 0.001). Remission rates were triglycerides, 100% (11/11) at 5 years, and 100% (1/1) at 9 years; high density lipoprotein, 89.4% (17/19) at 5 years, and 100% (3/3) at 7 years; low density lipoprotein, 71.4% (11/14) and 100% (3/3) at 5 and 7 years; total cholesterol, 70% (7/10) at 5 years, and 100% (2/2) at 9 years; uric acid, 100% (3/3) at 5 years. Remission of liver enzymes was 84.6–100% (22/26–2/2) at 5–9 years. Prediabetes remission was 87.5% (14/16 and 7/8) at 5 and 7 years and 100% (3/3) at year 9. Type 2 diabetes complete remission was 50% (3/6, 1/2) at years 5 and 7, with all cases resolved at 9 years. The only case of hypertension completely resolved. Conclusions: LSG achieved substantial weight loss and remission of cardiometabolic risk factors that were sustained on the long term. This is the first study among adolescents to assess such outcomes beyond 7 years. Graphical abstract: [Figure not available: see fulltext.]. 

Background: Globally, only two studies appraised the long-term nutritional status of adolescents after laparoscopic sleeve gastrectomy (LSG). Methods: Retrospective chart review of all adolescents aged ≤ 18 years who underwent LSG with ≥ 5 years follow-up and had no subsequent revisional surgery (N = 146). We assessed 15 nutritional parameters preoperatively and at 1, 3, 5, 7, and 9 years post surgery. Results: Mean age was 16.51 ± 1.29 years, 51% were males. We identified three patterns:1) Significant worsening of preoperative deficiencies: 4.7% and 0.8% of the sample exhibited zinc and vitamin B12 deficiencies, worsening to 20.8% and 12.8% at 1 year, respectively. Likewise, 0.7% of the sample had low total protein, worsening to 8.3% at year 3. A total of 32.4% of females had preoperative low hemoglobin worsening to 57.9% at year 5.2) Significant improvement: the percentage of males with preoperative low hemoglobin (5.6%) was reduced to 4.1% and 5.1% at years 1 and 3, respectively.3) Persistent deficiency: all (100%) of adolescents had preoperative vitamin D deficiency that persisted through years 3 and 9 at 90.5% and 100%, respectively. The most common complications were food intolerance (51%), vomiting (47.5%), gastritis/ esophagitis (35.7%), and gastroesophageal reflux disease (20.3%). We observed one case of Wernicke’s encephalopathy. Across the 9 years, 15.4% of the adolescents underwent intra-abdominal surgeries where 12.6% had cholecystectomy and one patient had appendectomy. Conclusion: Adolescents had several preoperative nutritional deficiencies, most of which worsened or persisted on the long term. This is the first study among adolescents to assess such deficiencies beyond 5 years. Graphical Abstract: [Figure not available: see fulltext.]. 

Aims: Dapagliflozin is a selective inhibitor of sodium glucose co-transporter 2 (SGLT2). This study assessed the efficacy and safety of dapagliflozin 10 mg vs placebo in patients with type 2 diabetes (T2D) and moderate renal impairment (estimated glomerular filtration rate [eGFR], 45-59 mL/min/1.73 m(2); chronic kidney disease [CKD] stage 3A). Materials and methods: In this double-blind, parallel group, Phase 3 study (NCT02413398, ) patients with inadequately controlled T2D (HbA1c 7.0%-11.0%) were randomized (1:1) to dapagliflozin 10 mg once daily (N = 160) or matching placebo (N = 161) for 24 weeks. Randomization was stratified by pre-enrolment glucose-lowering therapy. The primary endpoint was change from baseline in HbA1c at Week 24. Results: At Week 24, compared with placebo, dapagliflozin significantly decreased HbA1c (difference [95% CI], -0.34% [-0.53, -0.15]; P < 0.001), body weight (difference [95% CI], -1.25 kg [-1.90, -0.59]; P < 0.001), fasting plasma glucose (difference [95% CI], -0.9 mmol/L [-1.5, -0.4]; P = 0.001) and systolic blood pressure (difference [95% CI], -3.1 mmHg [-6.3, 0.0]; P < 0.05). Decreases from baseline in eGFR were greater with dapagliflozin than placebo at Week 24 (-2.49 mL/min/1.73 m(2) [-4.96, -0.02]), however, eGFR returned to baseline levels at Week 27 (3 weeks post-treatment) (0.61 mL/min/1.73 m(2) [-1.59, 2.81]). No increase in adverse events (AEs; 41.9% vs 47.8%) or serious AEs (5.6% vs 8.7%) were reported with dapagliflozin versus placebo. No AEs of bone fractures, amputations or DKA were reported. Conclusions: The findings of this study (NCT02413398, ) support the positive benefit/risk profile of dapagliflozin for the treatment of patients with T2D and CKD 3A.

Adipose tissue is the largest organ in the human body and, in excess, contributes to dyslipidemias and the dysregulation of other vascular and metabolic processes. Adipose tissue is heterogeneous, comprised of several cell types based on morphology, cellular age, and endocrine and paracrine function. Adipose tissue depots are also regional, primarily due to sex differences and genetic variation. Adipose tissue is also characterized as subcutaneous vs. visceral. In addition, fatty deposits exist outside of adipose tissue, such as those surrounding the heart, or as infiltration of skeletal muscle. This review focuses on adipose tissue and its contribution to dyslipidemias. Dyslipidemias are defined as circulating blood lipid levels that are too high or altered. Lipids include both traditional and nontraditional species. Leaving aside traditional definitions, adipose tissue contributes to dyslipidemias in a myriad of ways. To address a small portion of this topic, we reviewed (a) adipose tissue location and cell types, (b) body composition, (c) endocrine adipose, (d) the fat-brain axis, and (e) genetic susceptibility. The influence of these complex aspects of adipose tissue on dyslipidemias and human health, illustrating that, once again, that adipose tissue is a quintessential, multifunctional tissue of the human body, will be summarized.

The sodium glucose co-transporter-2 inhibitor dapagliflozin has been shown to decrease urinary albumin-to-creatinine ratio (UACR). This effect, however, varies among individual patients. In this study, we assessed the baseline characteristics and concurrent changes in other cardiovascular risk markers that might be associated with UACR response to dapagliflozin. A pooled analysis of 11 phase 3 randomized, controlled clinical trials was performed. UACR change from baseline after 24 weeks treatment with dapagliflozin 10 mg/d in 531 patients with type 2 diabetes and UACR ≥30 mg/g at baseline was determined. UACR response was defined as >30% reduction from baseline at 24 weeks, whereas UACR non-response was defined as ≤30% reduction at 24 weeks. A total of 288 (54%) patients were classified as responders and 243 (46%) as non-responders. At 24 weeks, the UACR-adjusted mean change from baseline was −71.2% and 25.9% in responders and non-responders, respectively. Baseline characteristics were similar between both groups. Changes in HbA1c and body weight were comparable across groups. Responders showed a numerically larger reduction in estimated glomerular filtration rate and systolic blood pressure versus non-responders. UACR reduction to dapagliflozin is an individual characteristic that cannot be predicted by baseline clinical features or changes in metabolic variables. Whether UACR response would improve long-term renal and cardiovascular outcomes remains to be determined. 

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women that is associated with an increased risk of anxiety and depression and with a lower health-related quality of life (HRQoL). PCOS is closely associated with obesity, which per se can lead to symptoms of anxiety and depression and lower HRQoL. The first-line treatment for PCOS is weight loss through lifestyle intervention, which has been shown to improve all symptoms of the syndrome. The aim of this study was to investigate symptoms of anxiety and depression and HRQoL in women with severe obesity (BMI ≥ 35) with and without PCOS, and to evaluate the effect of a one-year structured weight loss intervention. A total of 246 women with severe obesity (PCOS n = 63, non-PCOS n = 183) were included. The comprehensive psychopathological rating scale self-rating scale for affective symptoms (CPRS-S-A) and the short form-36 (SF-36) were used to assess symptoms of anxiety and depression and HRQoL. In total 72 women of the 246 women with severe obesity completed a one-year weight loss programme and were followed up and compared with baseline data. In women with severe obesity, there were no differences in symptoms of anxiety and depression and HRQoL between women with and without PCOS at baseline. Clinically relevant anxiety symptoms were present in 71.3% (PCOS) and 65.6% (non-PCOS), and depression symptoms were present in 56.4% (PCOS) and 52.2% (non-PCOS). Significant weight loss improved physical HRQoL in all women, but reduced symptoms of anxiety and depression only in women without PCOS. There were no differences when comparing the changes between the groups. Women with severe obesity are severely affected by symptoms of anxiety and depression, independent of PCOS. Weight loss improved symptoms of anxiety and depression in women without PCOS, but there were no differences between groups in change from baseline to follow-up.Trial registration number: Clinical trial.gov: NCT01319162, March 18, 2011. Date of registration and enrolment of the first subject September 2011.

Background: Patients with insulin-treated diabetes occur frequently in the home care setting. This care isn’t always easy which results in complex situations. Previous research describes patients with diabetes experiences of being cared for. There is a lack of knowledge regarding the district nurse’s experiences of caring for patients with insulin-treated diabetes in the home. Aim: The aim of this study was to describe the district nurse’s experiences of caring for patients with insulin-treated diabetes in the home. Method: A qualitative method with an inductive approach was used. As analysis method qualitative content analysis was used. Seven district nurses within the municipal home care was interviewed. Results: From the analysis two themes arose; Shared responsibility of caring is a balance between the patient and other professionals and The care in a home environment is a risky situation. Conclusion: There is insecurity and uncertainty among the district nurses regarding the care of these patients. District nurses are seldom alone in the care situation but rarely have the opportunity to be with the patient. This leads to requirements of confidence in other professions. The district nurses are forced to act in difficult situations in ways that are not always allowed

Women with polycystic ovary syndrome (PCOS) exhibit sustained elevation incirculating androgens during pregnancy, an independent risk factor linked topregnancy complications and adverse outcomes in offspring. Yet, furtherstudies are required to understand the effects of elevated androgens on celltype-specific placental dysfunction and fetal development. Therefore, aPCOS-like mouse model induced by continuous androgen exposure isexamined. The PCOS-mice exhibited impaired placental and embryonicdevelopment, resulting in mid-gestation lethality. Co-treatment with theandrogen receptor blocker, flutamide, prevents these phenotypes includinggerm cell specification . Comprehensive profiling of the placenta bywhole-genome bisulfite and RNA sequencing shows a reduced proportion oftrophoblast precursors, possibly due to the downregulation of Cdx2expression. Reduced expression of Gcm1, Synb, and Prl3b1 is associated withreduced syncytiotrophoblasts and sinusoidal trophoblast giant cells, impairsplacental labyrinth formation. Importantly, human trophoblast organoidsexposed to androgens exhibit analogous changes, showing impairedtrophoblast differentiation as a key feature in PCOS-related pregnancycomplications. These findings provide new insights into the potential cellulartargets for future treatments.

Background Diabetes has been linked to dementia risk; however, the cognitive trajectories in older adults with diabetes remain unclear. We aimed to investigate the effect of prediabetes and diabetes on cognitive trajectories among cognitively intact older adults in a long-term follow-up study.

Methods Within the Swedish Adoption/Twin Study of Aging, 793 cognitively intact older adults aged ≥50 were identified at baseline and followed for up to 23 years. Based on standardized scores from 11 cognitive tests, administered at baseline and up to seven follow-ups, four cognitive domains (verbal abilities, spatial/fluid, memory, perceptual speed) were identified by principal-component analysis. Prediabetes was defined according to blood glucose levels in diabetes-free participants. Diabetes was ascertained based on self-report, hypoglycemic medication use and blood glucose levels. Data were analyzed with linear mixed-effect models adjusting for potential confounders.

Results At baseline, 68 participants (8.6%) had prediabetes and 45 (5.7%) had diabetes. Compared to diabetes-free individuals, people with diabetes had a steeper decline over time in perceptual speed and verbal abilities. The annual declines in these domains were greater than the annual decline in memory. Prediabetes was associated with lower performance in memory in middle-age, but also associated with a less steep memory decline over the follow-up.

Conclusions Diabetes is associated with a faster decline in perceptual speed and verbal abilities, while prediabetes is associated with lower memory performance in middle-age. However, the detrimental effects of hyperglycemia seem to not affect memory over time.

High blood cholesterol is typically considered a feature of wealthy western countries1,2. However, dietary and behavioural determinants of blood cholesterol are changing rapidly throughout the world3 and countries are using lipid-lowering medications at varying rates. These changes can have distinct effects on the levels of high-density lipoprotein (HDL) cholesterol and non-HDL cholesterol, which have different effects on human health4,5. However, the trends of HDL and non-HDL cholesterol levels over time have not been previously reported in a global analysis. Here we pooled 1,127 population-based studies that measured blood lipids in 102.6 million individuals aged 18 years and older to estimate trends from 1980 to 2018 in mean total, non-HDL and HDL cholesterol levels for 200 countries. Globally, there was little change in total or non-HDL cholesterol from 1980 to 2018. This was a net effect of increases in low- and middle-income countries, especially in east and southeast Asia, and decreases in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe. As a result, countries with the highest level of non-HDL cholesterol—which is a marker of cardiovascular risk—changed from those in western Europe such as Belgium, Finland, Greenland, Iceland, Norway, Sweden, Switzerland and Malta in 1980 to those in Asia and the Pacific, such as Tokelau, Malaysia, The Philippines and Thailand. In 2017, high non-HDL cholesterol was responsible for an estimated 3.9 million (95% credible interval 3.7 million–4.2 million) worldwide deaths, half of which occurred in east, southeast and south Asia. The global repositioning of lipid-related risk, with non-optimal cholesterol shifting from a distinct feature of high-income countries in northwestern Europe, north America and Australasia to one that affects countries in east and southeast Asia and Oceania should motivate the use of population-based policies and personal interventions to improve nutrition and enhance access to treatment throughout the world.

Background:Continued refinement of resources for patient information, education and support is needed. Considering the rapid development of new communication practices, the perspectives of young people themselves warrant more attention using a wide research focus. The purpose of this study was to understand information-seeking behaviours, Internet use and social networking online in adolescents with type 1 diabetes (T1DM). This applied to their everyday life, including the context of diabetes and their experiences and need of contact with T1DM peers.Methodology/Principal Findings:Twenty-four adolescents aged 10-17 years with T1DM were recruited from a county hospital in the south-east of Sweden. Qualitative data were obtained using eight focus groups, wherein each participant engaged in a 60-90 minute video/audio-recorded session. The focus group data were transcribed and analysed using qualitative content analysis. Some demographic and medical information was also collected. The three main categories that were identified; Aspects of Security, Updating, and Plainness and their sub-categories gave significant information about how to enhance information retrieval and peer contacts related to T1DM. Regarding the persons' information-seeking behaviour, Internet use, and use of social media some differences could be identified depending on gender and age.Conclusions/Significance:Sensitivity and adaptation to users' needs and expectations seem crucial in the development of future online resources for adolescents with T1DM. To start with, this could mean applying a wider range of already existing information and communication technologies. Health practitioners need to focus on the areas of security of information and communication, frequency of updating, and simplicity of design-less is more. © 2013 Nordfeldt et al.

Aims: About 10%–30% of individuals with obesity are metabolically healthy, but the specific characteristics of the metabolically healthy obesity (MHO) phenotype remain unclear. We aimed to examine how physical activity, education, depressive symptoms and genetic predisposition to obesity differ between individuals with MHO and those with metabolically unhealthy obesity (MUO), and whether these factors predict stability in MHO or conversion to a metabolically unhealthy state.

Materials and Methods: We retrieved data on 9809 individuals with obesity from the Health and Retirement Study collected between 2006 and 2016. We compared how physical activity, education, depressive symptoms and a polygenic score for higher body mass index (BMI) (PGSBMI) differed cross-sectionally between MHO and MUO using logistic regression. We then examined if the same factors predict conversion to a metabolically unhealthy state over 4 years in individuals with MHO.

Results: Individuals with MHO had higher physical activity (odds ratio [OR] = 0.81), higher education (OR = 0.83) and lower depressive symptoms (OR = 1.14) compared to those with MUO but did not differ in the PGSBMI. The associations were slightly attenuated in mutually adjusted models. None of the factors were associated with conversion from MHO to a metabolically unhealthy state. However, a higher PGSBMI indicated 24% lower risk of conversion to a metabolically unhealthy state (p = 0.07).

Conclusions: Physical activity, education and depressive symptoms differed between MHO and MUO, even when mutually adjusted for, but did not predict conversion from a metabolically healthy to unhealthy state. Although not statistically significant, the results indicated that those with genetically predicted high BMI are more likely to maintain MHO and not convert to a metabolically unhealthy state.

If and how obesity and elevated androgens in women with polycystic ovary syndrome (PCOS) affect their offspring’s psychiatric health is unclear. Using data from Swedish population health registers, we showed that daughters of mothers with PCOS have a 78% increased risk of being diagnosed with anxiety disorders. We next generated a PCOS-like mouse (F0) model induced by androgen exposure during late gestation, with or without diet-induced maternal obesity, and showed that the first generation (F1) female offspring develop anxiety-like behavior, which is transgenerationally transmitted through the female germline into the third generation of female offspring (F3) in the androgenized lineage. In contrast, following the male germline, F3 male offspring (mF3) displayed anxiety-like behavior in the androgenized and the obese lineages. Using a targeted approach to search for molecular targets within the amygdala, we identified five differentially expressed genes involved in anxiety-like behavior in F3 females in the androgenized lineage and eight genes in the obese lineage. In mF3 male offspring, three genes were dysregulated in the obese lineage but none in the androgenized lineage. Finally, we performed in vitro fertilization (IVF) using a PCOS mouse model of continuous androgen exposure. We showed that the IVF generated F1 and F2 offspring in the female germline did not develop anxiety-like behavior, while the F2 male offspring (mF2) in the male germline did. Our findings provide evidence that elevated maternal androgens in PCOS and maternal obesity may underlie the risk of a transgenerational transmission of anxiety disorders in children of women with PCOS.

We studied the effect of microbiota on the transcriptome and weight of the urinary bladder by comparing germ-free (GF) and specific pathogen-free (SPF) housed mice. In total, 97 genes were differently expressed (fold change > ±2; false discovery rate (FDR) p-value < 0.01) between the groups, including genes regulating circadian rhythm (Per1, Per2 and Per3), extracellular matrix (Spo1, Spon2), and neuromuscular synaptic transmission (Slc18a3, Slc5a7, Chrnb4, Chrna3, Snap25). The highest increase in expression was observed for immunoglobulin genes (Igkv1-122, Igkv4-68) of unknown function, but surprisingly the absence of microbiota did not change the expression of the genes responsible for recognizing microbes and their products. We found that urinary bladder weight was approximately 25% lighter in GF mice (p = 0.09 for males, p = 0.005 for females) and in mice treated with broad spectrum of antibiotics (p = 0.0002). In conclusion, our data indicate that microbiota is an important determinant of urinary bladder physiology controlling its gene expression and size.

Polycystic ovary syndrome (PCOS) is associated with symptoms of moderate to severe anxiety and depression. Hyperandrogenism is a key feature together with lower levels of the adipocyte hormone adiponectin. Androgen exposure leads to anxiety-like behavior in female offspring while adiponectin is reported to be anxiolytic. Here we test the hypothesis that elevated adiponectin levels protect against the development of androgen-induced anxiety-like behavior. Pregnant mice overexpressing adiponectin (APNtg) and wildtypes were injected with vehicle or dihydrotestosterone to induce prenatal androgenization (PNA) in the offspring. Metabolic profiling and behavioral tests were performed in 4-month-old female offspring. PNA offspring spent more time in the closed arms of the elevated plus maze, indicating anxiety-like behavior. Intriguingly, neither maternal nor offspring adiponectin overexpression prevented an anxiety-like behavior in PNA-exposed offspring. However, adiponectin overexpression in dams had metabolic imprinting effects, shown as lower fat mass and glucose levels in their offspring. While serum adiponectin levels were elevated in APNtg mice, cerebrospinal fluid levels were similar between genotypes. Adiponectin overexpression improved metabolic functions but did not elicit anxiolytic effects in PNA-exposed offspring. These observations might be attributed to increased circulating but unchanged cerebrospinal fluid adiponectin levels in APNtg mice. Thus, increased adiponectin levels in the brain are likely needed to stimulate anxiolytic effects. 

Aims: Renin-angiotensin system inhibitors (RASi) are the most effective treatments for diabetic kidney disease but significant residual renal risk remains, possibly because of other mechanisms of kidney disease progression unrelated to RAS that may be present. Sodium-glucose co-transporter-2 inhibitors reduce albuminuria and may complement RASi by offering additional renal protection. This post hoc analysis investigated the effects of dapagliflozin on cardio-renal risk factors in patients with type 2 diabetes (T2D) with increased albuminuria treated with or without RASi at baseline. Materials and methods: We evaluated the effects of dapagliflozin 10 mg/day over 12–24 weeks across 13 placebo-controlled studies in patients with T2D with a urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g at baseline. Patients were divided into two subgroups based on treatment with or without RASi at baseline. Results: Compared with patients with RASi at baseline (n = 957), patients without RASi (n = 302) were younger, had a shorter duration of diabetes (7 vs. 12 years), higher estimated glomerular filtration rate (eGFR) and lower UACR, serum uric acid (sUA), body weight and systolic blood pressure. Placebo-adjusted treatment effects of dapagliflozin on UACR, eGFR, glycated haemoglobin and haematocrit over 24 weeks were similar across groups. Mean reductions in body weight and sUA were more distinct in patients without RASi treatment at baseline. Conclusions: Treatment with dapagliflozin over 24 weeks provides similar clinically relevant improvements in metabolic and haemodynamic parameters, and similar reductions in UACR, in patients with T2D with elevated albuminuria treated with or without RASi at baseline. © 2019 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

BACKGROUND: Although evidence indicates that Type II Diabetes is related to abnormal brain aging, the influence of elevated blood glucose on long-term cognitive change is unclear. In addition, the relationship between diet-based glycemic load and cognitive aging has not been extensively studied. The focus of this study was to investigate the influence of diet-based glycemic load and blood glucose on cognitive aging in older adults followed for up to 16 years.

METHODS: Eight-hundred and thirty-eight cognitively healthy adults aged ≥50 years (M = 63.1, SD = 8.3) from the Swedish Adoption/Twin Study of Aging were studied. Mixed effects growth models were utilized to assess overall performance and change in general cognitive functioning, perceptual speed, memory, verbal ability, and spatial ability as a function of baseline blood glucose and diet-based glycemic load.

RESULTS: High blood glucose was related to poorer overall performance on perceptual speed as well as greater rates of decline in general cognitive ability, perceptual speed, verbal ability, and spatial ability. Diet-based glycemic load was related to poorer overall performance in perceptual speed and spatial ability.

CONCLUSION: Diet-based glycemic load and, in particular, elevated blood glucose appear important for cognitive performance/cognitive aging. Blood glucose control (perhaps through low glycemic load diets) may be an important target in the detection and prevention of age-related cognitive decline.

Aims: Anemia is common in type 2 diabetes (T2D), particularly in patients with kidney impairment, and often goes unrecognized. Dapagliflozin treatment increases hemoglobin and serum erythropoietin levels. We investigated the effect of dapagliflozin 10-mg/day on hemoglobin in T2D patients with and without anemia. Methods: Data from 5325 patients from 14 placebo-controlled, dapagliflozin-treatment studies of at least 24-weeks duration were pooled. Dapagliflozin's effects (vs. placebo) on hemoglobin, serum albumin, estimated glomerular filtration rate (eGFR), systolic blood pressure, body weight, and safety in patients with and without anemia were evaluated. Results: At baseline, 13% of all T2D patients and 28% of those with chronic kidney disease (eGFR &lt;60 mL/min/1.73 m2) had anemia. Hemoglobin increased continuously to at least week 8 and was sustained throughout 24-weeks follow-up in dapagliflozin-treated patients. Serum albumin increased in dapagliflozin-treated patients at week 4 and remained stable thereafter. Dapagliflozin was well tolerated and corrected anemia in 52% of patients with anemia at baseline (placebo: 26%). Incidences of new-onset anemia were lower in dapagliflozin-treated (2.3%) versus placebo-treated (6.5%) patients. Conclusions: Treatment with dapagliflozin can correct and prevent anemia in T2D patients. A gradual increase in hemoglobin beyond week 4 may indicate an erythropoiesis-stimulating effect of sodium-glucose cotransporter 2 inhibition. 

Background: Polycystic ovary syndrome’s (PCOS) main feature is hyperandrogenism, which is linked to a higher risk of metabolic disorders in women. Gene expression analyses in adipose tissue and skeletal muscle reveal dysregulated metabolic pathways in women with PCOS, but these differences do not necessarily lead tochanges in protein levels and biological function. Methods: To advance our understanding of the molecular alterations in PCOS, we performed global proteomic and phosphorylation site analysis using tandem mass spectrometry. Adipose tissue and skeletal muscle were collected at baseline from 10 women with and without PCOS, and in women with PCOS after 5 weeks of treatment with electrical stimulation. Results: Perilipin-1, a protein that typically coats the surface of lipid droplets in adipocytes, was increased whereas proteins involved in muscle contraction and type I muscle fiber function were downregulated in PCOS muscle. Proteins in the thick and thin filaments had many altered phosphorylation sites, indicating differences in protein activity and function. The upregulated proteins in muscle post treatment were enriched in pathways involved in extracellular matrix organization and wound healing, which may reflect a protective adaptation to repeated contractions and tissue damage due to needling. A similar, albeit less pronounced, upregulation in extracellular matrix organization pathways was also seen in adipose tissue. Conclusions: Our results suggest that hyperandrogenic women with PCOS have higher levels of extramyocellular lipids and fewer oxidative insulin-sensitive type I muscle fibers. These could be key factors leading insulin resistance in PCOS muscle while electric stimulation-induced tissue remodeling may be protective.

Aim

Insulin sensitivity is ~40% lower in women with polycystic ovary syndrome (PCOS) than in controls. We tested the hypothesis that 5weeks of electroacupuncture treatment improves glucose regulation and androgen levels in overweight/obese women with PCOS.

Material and Methods

Seventeen women with PCOS, aged 18 to 38years, with a body mass index (BMI) ≥25 kg/m2 and diagnosed with PCOS were included in this experimental and feasibility study and subjected to five weeks of electroacupuncture treatments three times/week. The primary outcome was changes in whole‐body glucose homeostasis measured by euglycemic hyperinsulinemic clamp before and after the intervention. Secondary outcome were changes in HbA1c, circulating catecholamines, adipocyte size and adipose tissue expression of sex steroids and nerve growth factor (NGF).

Results

No significant change in glucose homeostasis was observed, but HbA1c decreased by 9.5% (p=0.004), circulating testosterone decreased by 22% (p=0.0007) and dihydrotestosterone decreased by 12% (p=0.007). The two vagal activity markers of plasma serotonin levels and the dopamine metabolite homovanillic acid decreased by 21% (p=0.027) and 20% (p=0.011), respectively. Adipose tissue concentrations of testosterone decreased by 18% (p=0.049), and androstenedione decreased by 13% (p=0.035), and mature NGF/proNGF ratio, a marker of sympathetic activity, increased (p=0.04). These changes occurred without changes in anthropometrics.

Conclusion

Five weeks of electroacupuncture treatment improves HbA1c and circulating and adipose tissue androgens in women with PCOS. This effect is mediated, at least in part, via modulation of vagal activity and adipose tissue sympathetic activity. Based on these findings, we have recently initiated a randomized controlled study (NTC02647827).

Background: Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1). Methods: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination. Results: The combination of VEGF-A and FGF1 demonstrated increased vascular sprouting in the ex vivo mouse aortic ring model, and topical administration of a combination of VEGF-A and FGF1 mRNAs formulated in lipid nanoparticles (LNPs) in mouse skin wounds promoted faster wound closure and increased neovascularization seven days post-surgical wound creation. RNA-sequencing analysis of skin samples at day three post-wound creation revealed a strong transcriptional response of the wound healing process, with the combined treatment showing significant enrichment of genes linked to skin growth. Conclusion: f-LNPs encapsulating VEGF-A and FGF1 mRNAs present a promising approach to improving the scarring process in DFU.

Aims: Hypomagnesemia (serum magnesium [Mg] <0.74 mmol/L [<1.8 mg/dL]) is commonly observed in patients with type 2 diabetes (T2D). This study investigated the effect of treatment with dapagliflozin 10 mg on Mg concentrations in patients with T2D. Methods: In this post hoc analysis, we used pooled data from 10 placebo-controlled studies of dapagliflozin over 24 weeks of treatment in patients with T2D. We evaluated the change in Mg in patients receiving dapagliflozin vs. placebo overall, and in subgroups with baseline hypomagnesemia and normal/hypermagnesemia (≥0.74 mmol/L [≥1.8 mg/dL]). We determined the proportion of patients with baseline hypomagnesemia who achieved Mg ≥0.74 mmol/L (≥1.8 mg/dL). Results: A total of 4398 patients with T2D were included. The mean change from baseline to week 24 in Mg was significantly larger with dapagliflozin vs. placebo; difference, 0.06 mmol/L (95% confidence interval [CI]: 0.05, 0.06). The proportion of patients with Mg within the population reference range after 24 weeks of treatment was significantly higher with dapagliflozin vs. placebo; difference, 47.8% (95% CI: 41.4, 53.9). The proportion of patients displaying hypermagnesemia did not increase with dapagliflozin treatment. Conclusions: Treatment with dapagliflozin 10 mg resulted in correction of Mg concentrations in patients with T2D and hypomagnesemia. 

Questions remain about whether the increased risk of fractures in patients with type 2 diabetes (T2DM) is related mainly to increased risk of falling or to bone-specific properties. The primary aim of this study was to investigate the risk of hip fractures and non-skeletal fall injuries in older men and women with and without T2DM. We included 429,313 individuals (80.8 ± 8.2 years (mean ± SD), 58% women) from the Swedish registry "Senior Alert" and linked the data to several nation-wide registers. We identified 79,159 individuals with T2DM (45% with insulin (T2DM-I), 41% with oral antidiabetics (T2DM-O), and 14% with no antidiabetic treatment (T2DM-none)), and 343,603 individuals without diabetes. During a follow-up of approximately 670,000 person-years we identified in total 36,132 fractures (15,572 hip fractures) and 20,019 non-skeletal fall injuries. In multivariable Cox-regression models where the reference group was patients without diabetes and the outcome was hip fracture, T2DM-I was associated with increased risk (adjusted Hazard Ratio (HR) [95% CI] 1.24 [1.16-1.32]), T2DM-O with unaffected risk (1.03 [0.97-1.11]) and T2DM-none with reduced risk (0.88 [0.79-0.98]). Both the diagnosis of T2DM-I (HR 1.22 [1.16-1.29]) and T2DM-O (HR 1.12 [1.06-1.18]) but not T2DM-none (1.07 [0.98-1.16]) predicted non-skeletal fall injury. The same pattern was seen regarding other fractures (any, upper arm, ankle and major osteoporotic fracture) but not for wrist fracture. Subset-analyses revealed that in men, the risk of hip fracture was only increased in those with T2DM-I but in women, both the diagnosis of T2DM-O and T2DM-I were related to increased hip fracture risk. In conclusion, the risk of fractures differs substantially among patients with T2DM and an increased risk of hip fracture was primarily seen in insulin-treated patients, while the risk of non-skeletal fall injury was consistently increased in T2DM with any diabetes medication. This article is protected by copyright. All rights reserved.

OBJECTIVE: To compare consultations carried out via video with those performed in person for patients with painful, hard-to-heal ulcers, with a focus on ulcer pain and pain treatment. A further aim was to investigate predictors for pain and pain treatment. METHOD: This was a register-based, quasi-experimental study based on data from the Swedish Registry of Ulcer Treatment (RUT). A total of 100 patients with hard-to-heal ulcers diagnosed via video consultation were compared with 1888 patients diagnosed in person with regard to pain assessment, intensity and treatment. Ulcer pain intensity was assessed by the visual analogue scale (VAS). Normally distributed variables (age, VAS) were compared between consultation groups using Student's t-test. Non-normally distributed variables (ulcer size, ulcer duration) were compared using the Mann-Whitney U-test, except for healing time, which was analysed with a log-rank test. Categorical variables (gender, ulcer aetiology and prescribed analgesics) were compared using Pearson's chi-square test (χ2). A p value of less than 0.05 was considered to indicate statistical significance. Predictors for pain and pain treatment were analysed in multiple regression analyses. RESULTS: The results showed a high presence of pain; 71% of patients with pain reported severe ulcer pain. There was no significant difference in ability to assess pain by VAS in the group diagnosed via video consultation (90%) compared with the group diagnosed in person (86%) (χ2, p=0.233). A significantly higher amount of prescribed analgesics was found for patients diagnosed via video (84%) compared with patients diagnosed by in-person assessment (68%) (χ2, p=0.044). Predictors for high-intensity pain were female gender or ulcers due to inflammatory vessel disease, while the predictors for receiving analgesics were older age, longer healing time and being diagnosed via video consultation. CONCLUSION: To identify, assess and treat ulcer pain is equally possible via video as by in-person consultation. The results of this study confirm that patients with hard-to-heal ulcers suffer from high-intensity ulcer pain, with a discrepancy between pain and pain relief. Further well-designed randomised controlled studies are necessary to understand how best to deploy telemedicine in ulcer pain treatment.

Hyperandrogenism is the main characteristic of polycystic ovary syndrome, which affects placental function and fetal growth, and leads to reproductive and metabolic dysfunction in female offspring. Adiponectin acts on the placenta and may exert endocrine effects on the developing fetus. This study aims to investigate if maternal and/or fetal adiponectin can prevent metabolic and reproductive dysfunction in prenatal androgenized (PNA) female offspring. Adiponectin transgenic (APNtg) and wild-type dams received dihydrotestosterone/vehicle injections between gestational days 16.5-18.5 to induce PNA offspring, which were followed for 4 months. Offspring from APNtg dams were smaller than offspring from wild-type dams, independent of genotype. Insulin sensitivity was higher in wild-type mice from APNtg dams compared to wild-types from wild-type dams, and insulin sensitivity correlated with fat mass and adipocyte size. PNA increased visceral fat% and adipocyte size in wild-type offspring from wild-type dams, while wild-type and APNtg offspring from APNtg dams were protected against this effect. APNtg mice had smaller adipocytes than wild-types and this morphology was associated with an increased expression of genes regulating adipogenesis (Ppard, Pparg, Cebpa, and Cebpb) and metabolism (Chrebp and Lpl). Anogenital distance was increased in all PNA-exposed wild-type offspring, but there was no increase in PNA APNtg offspring, suggesting that adiponectin overexpression protects against this effect. In conclusion, elevated adiponectin levels in utero improve insulin sensitivity, reduce body weight and fat mass gain in the adult offspring and protect against PNA-induced visceral adiposity. In conclusion, these data suggest that PNA offspring benefit from prenatal adiponectin supplementation.