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Background: Longitudinal studies including parental distress when examining adverse health outcomes in adolescents with type 1 diabetes are lacking. This study examined whether parental depression and anxiety predict adolescent emotional distress and glycated hemoglobin A1c (HbA1c) 1 year later and whether a relation between parental distress and HbA1c is mediated by the level of parental involvement in diabetes care and by treatment behaviors.Methods: Longitudinal path modeling was applied to data from 154 adolescents and parents from diabetes centers participating in the Longitudinal study of Emotional problems in Adolescents with type 1 diabetes and their Parents/caregivers (Diabetes LEAP). At baseline and 1-year follow-up, participants completed measures of depression and anxiety. HbA1c was extracted from medical charts. Responsibility and treatment behavior questionnaires were completed by adolescents at baseline.Results: Baseline parental depressive and anxiety symptoms were not associated with 1-year adolescent depressive symptoms, anxiety symptoms, and HbA1c. Responsibility division and treatment behaviors did not mediate associations between parental emotional distress and 1-year HbA1c.Conclusions: Parental depressive and anxiety symptoms did not predict adolescent health outcomes 1 year later. Future studies may determine whether the link is present in case of mood/anxiety disorders or severe diabetes-specific distress, or whether adolescents are resilient in the face of parental distress.Impact: Adolescents with T1D are a vulnerable group in terms of psychological and health outcomes. Whether parental emotional distress (i.e., depressive and anxiety symptoms) is prospectively associated with adolescent emotional distress and/or HbA1c has been understudied. Our results show that parental distress was not related to adolescent distress or HbA1c 1 year later. Responsibility division and treatment behaviors did not mediate associations between parental emotional distress and 1-year HbA1c. Future studies could determine whether these links are present in case of mood/anxiety disorders or severe diabetes-specific distress, or whether adolescents are resilient in the face of parental distress.

Background The empirical evidence remains inconclusive for an association between diabetes mellitus (DM) in children and early-onset kidney disease later in life, and little is known about the effects of DM types (i.e., type 1 diabetes [T1DM] and type 2 diabetes [T2DM]) in childhood on type-specific kidney diseases. We aimed to evaluate the association of childhood DM with overall and type-specific early-onset kidney diseases later in life. Methods The population-based matched cohort study included 9356 individuals with DM (T1DM: 8470, T2DM: 886) diagnosed in childhood ( Results During a median follow-up of 13 years, children with DM had a 154% increased risk of early-onset kidney diseases than children without DM (adjusted hazard ratios 2.54, 95% confidence intervals 2.38–2.72), and T1DM (2.48, 2.31–2.67) and T2DM (2.75, 2.28–3.31) showed similar results. Children with DM also had a higher risk of multiple specific kidney diseases including glomerular diseases, renal tubulo-interstitial diseases, renal failure, and urolithiasis. The risks of type-specific kidney diseases including glomerular diseases and renal failure tended to be higher for children with T2DM (glomerular diseases: 5.84, 3.69–9.24; renal failure: 14.77, 8.53–25.59) than those with T1DM (glomerular diseases: 3.14, 2.57–3.83; renal failure: 8.24, 6.66–10.20). Conclusions Children with DM had a higher increased risk of early-onset overall and specific kidney diseases later in life. Early prevention and treatment of both T1DM and T2DM in childhood may significantly reduce the risk of kidney diseases later in life.

Aims: To estimate the incidence rates of genital warts (GWs) in women and men with type 1 diabetes compared to persons without diabetes. Methods: In this nationwide registry-based cohort study, we included the entire population aged 15 to 49 years living in Denmark between 1996 and 2016. From national registries, we retrieved individual level information on diabetes status, diagnoses and treatment of GWs, and potential confounding variables. We used Poisson regression to model sex- and age-specific incidence rates of GWs in persons with type 1 diabetes and persons without diabetes. Based on the models, we computed sex-specific incidence rate ratios (IRRs) of GWs in persons with type 1 diabetes compared to persons without diabetes, overall and according to age. Results: The analysis included 3,514,824 persons without type 2 diabetes and no GW diagnoses before baseline. The incidence rate of GWs in persons with type 1 diabetes was higher than in those without diabetes, both among women (IRR = 1.59; 95% CI, 1.42–1.78) and men (IRR = 1.36; 95% CI, 1.25–1.48). The pattern of increased incidence rates of GWs in persons with type 1 diabetes was seen at all ages. Conclusions: Persons with type 1 diabetes have higher incidence rates of GWs than persons without diabetes. This supports the importance of HPV vaccination of young girls and boys with type 1 diabetes.

PURPOSE OF REVIEW: To discuss the spectrum of diabetes related to acute and chronic pancreatitis (which are types of pancreatogenic diabetes) and its overlapping features with type 1 and type 2 diabetes.RECENT FINDINGS: Patients with diabetes related to acute and chronic pancreatitis present clinically within a spectrum of overlapping features with other forms of diabetes. In this spectrum, glucose metabolism alterations range from increased insulin resistance following acute pancreatitis (resembling type 2 diabetes) towards a permanent loss of beta-cell function and impaired insulin secretion in end-stage chronic pancreatitis. Overlapping features with type 1 diabetes (beta cell autoantibodies) and type 2 diabetes (obesity, dyslipidemia, and hereditary/genetic factors) contribute to the heterogeneity of this spectrum.SUMMARY: Pancreatogenic diabetes secondary to acute or chronic pancreatitis is a heterogeneous entity with a variable clinical presentation, including many cases that are misdiagnosed and treated as type 2 diabetes. This is problematic as pancreatogenic diabetes is associated with a poor prognosis and entails special considerations for management. Recent discoveries showing overlapping features with type 1 and type 2 diabetes along with an improved understanding of its pathophysiology are expected to improve the diagnosis and treatment of these and other forms of pancreatogenic diabetes.

Background People with type 1 diabetes often live for many years with different combinations of diabetes-related complications. We aimed to quantify how complication duration and total complication burden affect mortality, using data from national registers. Methods This study included 33 396 individuals with type 1 diabetes, registered in the Swedish National Diabetes Register at any time between 2001 and 2012. Each individual was followed and classified according to their time-updated diabetes-related complication status. The main outcomes were all-cause mortality, cardiovascular (CV) mortality and non-CV mortality. Poisson models were used to estimate the rate of these outcomes as a function of the time-updated complication duration. Results Overall, 1748 of the 33 396 individuals died during 198 872 person-years of follow-up. Overall, the time-updated all-cause mortality rate ratio (MRR) was 2.25 [95% confidence interval (CI): 1.99–2.54] for patients with diabetic kidney disease, 0.98 (0.82–1.18) for patients with retinopathy and 4.00 (3.56–4.50) for patients with cardiovascular disease relative to individuals without complications. The excess rate was highest in the first period after a diagnosis of CVD, with an 8-fold higher mortality rate, and stabilized after some 5 years. After diagnosis of diabetic kidney disease, we observed an increase in all-cause mortality with an MRR of around 2 compared with individuals without diabetic kidney disease, which stabilized after few years. Conclusions In this cohort we show that duration of diabetes-related complications is an important determinant of mortality in type 1 diabetes, for example the MRR associated with CVD is highest in the first period after diagnosis of CVD. A stronger focus on time-updated information and thorough consideration of complication duration may improve risk stratification in routine clinical practice.

IntroductionDepressive disorders are more common among persons with diabetes, as compared with persons without diabetes. The burden of glucose management is known to associate with depressive symptoms. This study aims to assess the effects of commencement of FreeStyle Libre flash glucose monitoring (FSL-FGM) on the mental health status of persons with diabetes.Research design and methodsPost-hoc analysis of data from a 1-year prospective nationwide FSL-FGM registry. Participants who used FSL-FGM for 12 months and completed the 12-Item Short Form Health Survey version 2 (SF-12v2) questionnaires at baseline, 6 and 12 months were included. An SF-12v2 Mental Component Score (MCS) of ≤45 was used as a cut-off to discriminate between persons with and without a depressive disorder.ResultsA total of 674 patients were included with a mean age of 48.2 (±15.8) years, 51.2% men, 78.2% type 1 diabetes and baseline HbA1c 62.8 (±13.4) mmol/mol (7.9±1.2%). At baseline, 235 (34.9%) persons had an SF-12 MCS ≤45 while after 6 and 12 months these numbers decreased: 202 (30.0%, pConclusionsThis analysis suggests that use of FSL-FGM is associated with a decreased rate of depressive disorders among persons with diabetes. Future studies are needed to corroborate these findings.

AIMS: This study aimed to investigate cortical source activity and identify source generators in people with type 1 diabetes during rest and tonic cold pain.METHODS: Forty-eight participants with type 1 diabetes and neuropathy, and 21 healthy controls were investigated with electroencephalography (EEG) during 5-minutes resting and 2-minutes tonic cold pain (immersing the hand into water at 2 °C). EEG power was assessed in eight frequency bands, and EEG source generators were analyzed using standardized low-resolution electromagnetic tomography (sLORETA).RESULTS: Compared to resting EEG, cold pain EEG power differed in all bands in the diabetes group (all p < 0.001) and six bands in the controls (all p < 0.05). Source generator activity in the diabetes group was increased in delta, beta2, beta3, and gamma bands and decreased in alpha1 (all p < 0.006) with changes mainly seen in the frontal and limbic lobe. Compared to controls, people with diabetes had decreased source generator activity during cold pain in the beta2 and beta3 bands (all p < 0.05), mainly in the frontal lobe.CONCLUSIONS: Participants with type 1 diabetes had altered EEG power and source generator activity predominantly in the frontal and limbic lobe during tonic cold pain. The results may indicate modulated central transmission and neuronal impairment.

IntroductionCardiovascular disease (CVD) is the leading cause of mortality in individuals with type 1 diabetes mellitus (T1DM). Cardiovascular risk management is therefore essential in the management of individuals with T1DM. This study describes the performance of lipid and blood pressure management in individuals with T1DM using three guidelines.Research design and methodsIndividuals ≥18 years with T1DM, treated with insulin for ≥1 year, visiting Diabeter or the University Medical Center Groningen between January 1, 2018 and December 31, 2018, were included. Lipid and blood pressure management were examined using the Dutch, American Diabetes Association (ADA) and National Institute for Health and Care Excellence (NICE) guidelines. Concordance of recommended and prescribed lipid-lowering (LLM) or antihypertensive medication (AHM) was assessed per guideline and 10-year age groups. Achievement of treatment targets was assessed for those prescribed medication.ResultsA total of 1855 individuals with T1DM were included. LLM and AHM was prescribed in 19% and 17%, respectively. In individuals recommended LLM, this was prescribed in 22%–46% according to Dutch, ADA or NICE guideline recommendations. For individuals recommended AHM, this was prescribed in 52%–75%. Recommended and actual prescription of LLM and AHM increased over age for all three guidelines. However, discordance between treatment recommendation and medication prescribed was higher in younger, compared with older, age groups. Low-density lipoprotein-cholesterol targets were achieved by 50% (without CVD) and 31% (with CVD) of those prescribed LLM. The blood pressure target was achieved by 46% of those prescribed AHM.ConclusionThis study suggests that there is undertreatment of lipid and blood pressure according to guideline recommendations, particularly in younger age groups. Treatment targets are not met by most individuals prescribed medication, while guidelines recommendations differ considerably. We recommend to investigate the factors influencing undertreatment of lipid and blood pressure management in individuals with T1DM.

Peripheral neuropathy is one of the most common complications of both type 1 and type 2 diabetes. Up to half of patients with diabetes develop neuropathy during the course of their disease, which is accompanied by neuropathic pain in 30–40% of cases. Peripheral nerve injury in diabetes can manifest as progressive distal symmetric polyneuropathy, autonomic neuropathy, radiculo-plexopathies, and mononeuropathies. The most common diabetic neuropathy is distal symmetric polyneuropathy, which we will refer to as DN, with its characteristic glove and stocking like presentation of distal sensory or motor function loss. DN or its painful counterpart, painful DN, are associated with increased mortality and morbidity; thus, early recognition and preventive measures are essential. Nevertheless, it is not easy to diagnose DN or painful DN, particularly in patients with early and mild neuropathy, and there is currently no single established diagnostic gold standard. The most common diagnostic approach in research is a hierarchical system, which combines symptoms, signs, and a series of confirmatory tests. The general lack of long-term prospective studies has limited the evaluation of the sensitivity and specificity of new morphometric and neurophysiological techniques. Thus, the best paradigm for screening DN and painful DN both in research and in clinical practice remains uncertain. Herein, we review the diagnostic challenges from both clinical and research perspectives and their implications for managing patients with DN. There is no established DN treatment, apart from improved glycaemic control, which is more effective in type 1 than in type 2 diabetes, and only symptomatic management is available for painful DN. Currently, less than one-third of patients with painful DN derive sufficient pain relief with existing pharmacotherapies. A more precise and distinct sensory profile from patients with DN and painful DN may help identify responsive patients to one treatment versus another. Detailed sensory profiles will lead to tailored treatment for patient subgroups with painful DN by matching to novel or established DN pathomechanisms and also for improved clinical trials stratification. Large randomized clinical trials are needed to identify the interventions, i.e. pharmacological, physical, cognitive, educational, etc., which lead to the best therapeutic outcomes.

Background Cardiac adipose tissue may have local paracrine effects on epicardial arteries and the underlying myocardium, promoting calcification and affecting myocardial microcirculation. We explored whether the total amount of cardiac adipose tissue was associated with coronary artery calcium score (CAC) and myocardial flow reserve in persons with type 1 or type 2 diabetes and healthy controls. Methods We studied three groups: (1) 30 controls, (2) 60 persons with type 1 diabetes and (3) 60 persons with type 2 diabetes. The three groups were matched for sex and age. The three groups derived from retrospective analysis of two clinical studies. All underwent cardiac 82Rb positron emission tomography/computed tomography (PET/CT) scanning. Cardiac adipose tissue volume (the sum of epicardial and pericardial fat), CAC, and myocardial flow reserve (ratio of pharmacological stress flow and rest flow) were evaluated using semiautomatic software. We applied linear regression to assess the association between cardiac adipose tissue, CAC and myocardial flow reserve. Results Mean (SD) cardiac adipose tissue volume was 99 (61) mL in the control group, 106 (78) mL in the type 1 diabetes group and 228 (97) mL in the type 2 diabetes group. Cardiac adipose tissue was positively associated with body mass index in all three groups (p ≤ 0.02). In the controls, cardiac adipose tissue was positively associated with CAC score (p = 0.008) and negatively associated with myocardial flow reserve (p = 0.005). However, cardiac adipose tissue was not associated with CAC or myocardial flow reserve in the groups including persons with type 1 or type 2 diabetes (p ≥ 0.50). Conclusions In contrast to what was found in healthy controls, we could not establish a relation between cardiac adipose tissue and coronary calcification or myocardial microvascular function in person with type 1 or type 2 diabetes. The role of cardiac adipose tissue in cardiovascular disease in diabetes remains unclear.

Background Type 1 diabetes mellitus (T1DM) in children and adolescents is associated with significant cardiovascular morbidity and mortality. Early detection of vascular dysfunction is key to patient management yet current assessment techniques are invasive and not suitable for pediatric patient populations. A novel approach using isometric handgrip exercise during magnetic resonance imaging (IHE-MRI) has recently been developed to evaluate coronary endothelial function non-invasively in adults. This project aimed to assess endothelium-dependent coronary arterial response to IHE-MRI in children with T1DM and in age matched healthy controls. Materials and methods Healthy volunteers and children with T1DM (>5 years) were recruited. IHE-MRI cross-sectional coronary artery area measurements were recorded at rest and under stress. Carotid intima media thickness (CIMT) and aortic pulse wave velocity (PWV) were assessed for comparison. Student’s t-tests were used to compare results between groups. Results and discussion Seven children with T1DM (3 female, median 14.8 years, mean 14.8 ± 1.9 years) and 16 healthy controls (7 female, median 14.8 years, mean 14.2 ± 2.4 years) participated. A significant increase in stress-induced cross-sectional coronary area was measured in controls (5.4 mm2 at rest to 6.39 mm2 under stress, 18.8 ± 10.7%, p = 0.0004). In contrast, mean area change in patients with T1DM was not significant (7.17 mm2 at rest to 7.59 mm2 under stress, 10.5% ± 28.1%, p = n.s.). There was no significant difference in the results for neither PWV nor CIMT between patients and controls, (5.3±1.5 m/s vs.4.8±0.7 m/s and 0.4±0.03mm vs.0.46 mm ± 0.03 respectively, both p = n.s.). Conclusions Our pilot study demonstrates the feasibility of using a totally non-invasive IHE-MRI technique in children and adolescents with and without T1DM. Preliminary results suggest a blunted endothelium-dependent coronary vasomotor function in children with T1DM (>5 years). Better knowledge and new methodologies may improve surveillance and care for T1DM patients to reduce cardiovascular morbidity and mortality.

Supplemental Digital Content is available in the text., Background: The role of diabetes mellitus, liver disease, and epilepsy as risk factors for Dupuytren disease remains unclear. In this systematic review and meta-analysis, the strength and consistency of these associations were examined. Methods: The MEDLINE, EMBASE, and Web of Science databases were searched for articles reporting an association between Dupuytren disease and diabetes mellitus, liver disease, and epilepsy published before September 26, 2016. The frequencies of Dupuytren disease and diabetes mellitus, liver disease, and epilepsy were extracted, as was information on potential confounders. Generalized linear mixed models were applied to estimate pooled odds ratios, adjusted for confounders. Heterogeneity between studies was quantified using an intraclass correlation coefficient and was accounted for by a random effect for study. Results: One thousand two hundred sixty unique studies were identified, of which 32 were used in the meta-analyses. An association between Dupuytren disease and diabetes mellitus was observed (OR, 3.06; 95 percent CI, 2.69 to 3.48, adjusted for age), which was stronger for type 1 diabetes mellitus than for type 2 diabetes mellitus but was not statistically significant (p = 0.24). An association between Dupuytren disease and liver disease was observed (OR, 2.92; 95 percent CI, 2.08 to 4.12, adjusted for sex). Dupuytren disease and epilepsy were associated, yielding an OR of 2.80 (95 percent CI, 2.49 to 3.15). Heterogeneity between studies was moderate to low. Conclusions: These findings demonstrate an association between Dupuytren disease and diabetes mellitus, liver disease, and epilepsy. Prospective, longitudinal studies are needed to elucidate the pathways causing these associations.

Background: To examine the association between plasma uric acid (UA) and the presence of diabetic complications including diabetic nephropathy and cardiovascular risk factors in patients with type 1 diabetes.Methods: This study, which is cross-sectional in design, included 676 Caucasian type 1 diabetes patients from the Steno Diabetes Center Copenhagen. Participants with UA within the three lowest sex-specific quartiles were compared with participants with levels in the highest quartile. Unadjusted and adjusted linear regression analyses were applied. Adjustment included sex, age, diabetes duration, body mass index, high-density lipoprotein cholesterol, smoking, haemoglobin A1c, 24-h pulse pressure, urinary albumin excretion rate (UAER), estimated glomerular filtration rate (eGFR) and treatment with renin-angiotensin-aldosterone system blockers.Results: Of the 676 patients, 372 (55%) were male, mean ± SD age was 55 ± 13 years and eGFR was 82 ± 26 mL/min/1.73 m2. The median UA was 0.30 (interquartile range 0.23-0.37) mmol/L. UA in the upper sex-specific quartile was associated with lower eGFR, higher UAER and carotid-femoral pulse wave velocity and lower 24 h and daytime diastolic blood pressure (BP) in unadjusted analyses (P Conclusions: In type 1 diabetes patients, higher UA was associated with lower kidney function and other diabetic complications. The association between higher UA and lower eGFR and lower diastolic BP was independent of traditional risk factors.

ObjectivesTo investigate the frequency of coeliac disease (CD)-specific human leucocyte antigen (HLA) genotypes in paediatric patients with type 1 diabetes (T1D), who are known to have a higher prevalence of CD than the general population, and to evaluate whether HLA genotyping is a suitable first-line screening method for CD.Study designThe study was a multicentre observational analysis of patients with T1D aged ResultsIn March 2017, the database contained 75 202 patients with T1D (53% male, mean age (SD) 14.6 (4.1) years, mean age at diagnosis 8.8 (4.3) years and mean diabetes duration 5.8 (4.3) years). 1624 patients had undergone coeliac-specific HLA genotyping, of whom 1344 (82.8%) were positive for HLA-DQ2, HLA-DQ8 or both, while 17.2% had no coeliac-specific HLA-markers. 26.6% of at-risk patients had a clinical suspected diagnosis of CD, and 3.6% had biopsy-proven CD.ConclusionsGenotyping for HLA-DQ2, HLA-DQ8 or both is positive in the vast majority (>80%) of patients with T1D. Therefore, screening for coeliac-specific HLA genotypes as a first-line test is not a suitable method to exclude CD in T1D. Regular screening for coeliac-specific antibodies in T1D is still recommended.

Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk.

AIMS/HYPOTHESIS: We examined the hypothesis that elevation in urinary albumin creatinine ratio (ACR) in adolescents with type 1 diabetes is associated with abnormal retinal vascular geometry (RVG) phenotypes.METHODS: A cross-sectional study at baseline of the relationship between ACR within the normoalbuminuric range and RVG in 963 adolescents aged 14.4 ± 1.6 years with type 1 diabetes (median duration 6.5 years) screened for participation in AdDIT. A validated algorithm was used to categorise log10 ACR into tertiles: upper tertile ACR was defined as 'high-risk' for future albuminuria and the lower two tertiles were deemed 'low-risk'. RVG analysis, using a semi-automated computer program, determined retinal vascular calibres (standard and extended zones) and tortuosity. RVG measures were analysed continuously and categorically (in quintiles: Q1-Q5) for associations with log10 ACR and ACR risk groups.RESULTS: Greater log10 ACR was associated with narrower vessel calibres and greater tortuosity. The high-risk group was more likely to have extended zone vessel calibres in the lowest quintile (arteriolar Q1 vs Q2-Q5: OR 1.67 [95% CI 1.17, 2.38] and venular OR 1.39 [0.98, 1.99]) and tortuosity in the highest quintile (Q5 vs Q1-Q4: arteriolar OR 2.05 [1.44, 2.92] and venular OR 2.38 [1.67, 3.40]). The effects of retinal vascular calibres and tortuosity were additive such that the participants with the narrowest and most tortuous vessels were more likely to be in the high-risk group (OR 3.32 [1.84, 5.96]). These effects were independent of duration, blood pressure, BMI and blood glucose control.CONCLUSIONS/INTERPRETATION: Higher ACR in adolescents is associated with narrower and more tortuous retinal vessels. Therefore, RVG phenotypes may serve to identify populations at high risk of diabetes complications during adolescence and well before onset of clinical diabetes complications.

Objective: To compare the prevalence of asymptomatic bacteriuria (ASB) and the incidence of urinary tract infection (UTI) in pregnant women with and without diabetes mellitus (DM) or gestational DM (GDM).Study design: We performed a cohort study in five hospitals and two midwifery clinics in the Netherlands. Pregnant women with and without DM or GDM were screened for the presence of ASB around 12 and 32 weeks' gestation. Characteristics of participants as well as outcome data were collected from questionnaires and medical records. ASB was defined as the growth of at least 10e5 cfu/ml isolated from the urine of a woman without UTI complaints. UTI was considered to be present when a treating physician had diagnosed UTI and prescribed antibiotics.Results: We studied 202 women with and 272 women without DM or GDM. Of all women 31.7% with and 94.9% without DM or GDM provided a week 12 sample. The prevalence of ASB was comparable in women with and without DM or GDM (12 weeks' n = 322; 4.7% and 2.3%; relative risk (RR) 2.02; 95% confidence interval (CI) 0.52-7.84; 32 weeks' n = 422; 3.2% and 3.0%; RR 1.06; 95% CI 0.36-3.09), as was the incidence of UTI (16.8% and 12.9%; RR 1.31; 95% CI 0.85-2.02). Neither ASB nor UTI were associated with preterm birth or babies being small for gestational age.Conclusion: In pregnant women with and women without DM or GDM, the overall prevalence of ASB was low. Neither ASB nor UTI did differ significantly between the groups. Our data discourage a routine ASB screen and treat policy in pregnant women with DM or GDM. (C) 2017 Published by Elsevier Ireland Ltd.

BACKGROUND: Adolescents with type 1 diabetes are at an increased risk of disturbed eating behaviors (DEBs).OBJECTIVE: The aims of this study are to (i) explore the prevalence of DEBs and associated 'yellow flags', and (ii) establish concordance between adolescents-parents and adolescents-clinicians with respect to DEBs.METHODS: Adolescents (11-16 yr) and parents completed questionnaires. A stepwise approach was used to assess DEBs: only adolescents whose answers raised psychological yellow flags for DEBs completed the Diabetes Eating Problems Scale - Revised and questions from the AHEAD study. Parents and clinicians shared their observations regarding possible DEBs. Kruskal-Wallis tests, post hoc Mann-Whitney U test, and chi-squared tests were utilized to examine clinical yellow flags. Cohen's kappa was used to assess concordance.RESULTS: Of 103 adolescents participated (51.5% girls), answers of 47 (46.5%) raised psychological yellow flags, indicating body and weight concerns. A total of 8% scored above cut-off for DEBs. Clinical yellow flags were elevated glycated hemoglobin A1c (p = 0.004), older age (p = 0.034), dieting frequency (p = 0.001), reduced quality of life (p = 0.007), less diabetes self-confidence (p = 0.015), worsened diabetes management (p DISCUSSION: Half of the adolescents reported body and weight concerns, less than 1 in 10 reported DEBs. Screening for yellow flags for DEBs as a part of clinical routine using a stepwise approach and early assistance is recommended to prevent onset or deterioration of DEBs.

Diabetes mellitus is associated with an increased risk of fracture. The risk of a hip fracture is up to sevenfold increased in patients with type 1 diabetes and about 1.3-fold increased in patients with type 2 diabetes. However, these relative risk estimates may depend on the age and gender distribution of the population in question. Bone mineral density and the fracture risk assessment tool do not explain the increased fracture risk in patients with diabetes. Shared risk factors as pancreatitis, alcohol use, smoking and oral glucocorticoids may influence the observed fracture risk in patients with diabetes. This review examines the association between diabetes and fracture and attempts to disentangle the tight connection between diabetes per se, diabetes-related complications, comorbidities and shared risk factors. This is of great importance as the number of diabetes patients' increases with growing and aging populations and putting even more at risk of fracture.

Diabetic neuropathy, nephropathy, and retinopathy cause significant morbidity in patients with type 1 diabetes, even though improvements in treatment modalities delay the appearance and reduce the severity of these complications. To prevent or further delay the onset, it is necessary to better understand common underlying pathogenesis and to discover preclinical biomarkers of these complications. Retinal vessel calibers have been associated with the presence of microvascular complications, but their long-term predictive value has only been sparsely investigated. We examined retinal vessel calibers as 16-year predictors of diabetic nephropathy, neuropathy, and proliferative retinopathy in a young population-based Danish cohort with type 1 diabetes. We used semiautomated computer software to analyze vessel diameters on baseline retinal photos. Calibers of all vessels coursing through a zone 0.5–1 disc diameter from the disc margin were measured and summarized as the central artery and vein equivalents. In multiple regression analyses, we found wider venular diameters and smaller arteriolar diameters were both predictive of the 16-year development of nephropathy, neuropathy, and proliferative retinopathy. Early retinal vessel caliber changes are seemingly early markers of microvascular processes, precede the development of microvascular complications, and are a potential noninvasive predictive test on future risk of diabetic retinopathy, neuropathy, and nephropathy.

Aims: Data on the impact of hypoglycaemia on patients' daily lives and diabetes self-management, particularly in developing countries, are lacking. The aim of this study was to assess fear of, and responses to, hypoglycaemia experienced by patients globally. Materials and methods: This non-interventional, multicentre, 4-week prospective study using self-assessment questionnaires and patient diaries consisted of 27,585 patients, >= 18 years, with type 1 diabetes (n = 8022) or type 2 diabetes (n = 19,563) treated with insulin for > 12 months, at 2004 sites in 24 countries worldwide. Results: Increased blood glucose monitoring (69.7%) and seeking medical assistance (62.0%) were the most common responses in the 4 weeks following hypoglycaemic events for patients with type 1 diabetes and type 2 diabetes, respectively. Approximately 44% of patients with type 1 diabetes or type 2 diabetes increased calorie intake in response to a hypoglycaemic episode. Following hypoglycaemia, 3.9% (type 1 diabetes) and 6.2% (type 2 diabetes) of patients took leave from work or study. Regional differences in fear of, and responses to, hypoglycaemia were evident - in particular, a lower level of hypoglycaemic fear and utilisation of healthcare resources in Northern Europe and Canada. Conclusions: Hypoglycaemia has a major impact on patients and their behaviour. These global data for the first time reveal regional variations in response to hypoglycaemia and highlight the importance of patient education and management strategies. (C) 2017 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the

Background: Hypoglycemic events in patients with type 1 diabetes (T1D) are associated with measurable electroencephalography (EEG) changes. Previous studies have, however, evaluated these changes on a single EEG channel level, whereas multivariate analysis of several EEG channels has been scarcely investigated. The aim of the present work is to use a coherence approach to quantitatively assess how hypoglycemia affects mutual connectivity of different brain areas. Materials and Methods: EEG multichannel data were obtained from 19 patients with T1D (58% males; mean age, 55 ± 2.4 years; diabetes duration, 28.5 ± 2.6 years; glycated hemoglobin, 8.0 ± 0.2%) who underwent a hyperinsulinemic-hypoglycemic clamp study. The information partial directed coherence (iPDC) function was computed through multivariate autoregressive models during eu- and hypoglycemia in the theta and alpha bands. Results: In passing from eu- to hypoglycemia, absolute values of the iPDC function tend to decrease in both bands in all combinations of the considered channels. In particular, the scalar indicator , which summarizes iPDC information, significantly decreased (P < 0.01) in 17 of 19 subjects: from T5-A1A2 to C3-A1A2 from O1-A1A2 to C4-A1A2 and from O2-A1A2 to Cz-A1A2 in the theta band and from O1-A1A2 to T4-A1A2 and from O1-A1A2 to C4-A1A2 in the alpha band. Conclusions: The coherence decrease measured by iPDC in passing from eu- to hypoglycemia is likely related to the progressive loss of cognitive function and altered cerebral activity in hypoglycemia. This result encourages further quantitative investigation of EEG changes in hypoglycemia and of how EEG acquisition and real-time processing can support hypoglycemia alert systems.

Previous studies have indicated that women with diabetes mellitus are at higher risk to develop sexual dysfunctions. In the current study, we hypothesized that lower genital arousal response-as a consequence of diabetes-related damage to nerves and blood vessels-might play a part in these higher prevalence rates. Vaginal blood flow, subjective sexual response, and clitoral sensitivity were compared between women with diabetes and healthy controls, and associations with diabetes complications were investigated. In pre- and postmenopausal women with type 1 diabetes (n = 42) and healthy controls (n = 46), vaginal blood flow was measured as vaginal pulse amplitude (VPA). VPA was assessed at rest, during erotic film viewing, and during vibrotactile clitoral stimulation. Subjective sexual arousal was measured using a questionnaire. Clitoral sensitivity was assessed by a vibration perception test. Data on diabetes complications were obtained from medical records, and neuropathy was assessed by quantitative sensory testing. VPA, subjective sexual arousal, and clitoral sensitivity were not significantly different between women with diabetes and controls. Nevertheless, women with diabetes who had retinopathy showed significantly lower VPA than women without retinopathy, and women with diabetes who had neuropathy showed significantly higher sensation thresholds for vibrotactile clitoral stimulation. The results do not support the hypothesis of a disrupted genital arousal response in women with diabetes. However, the observed associations between retinopathy and vaginal blood flow, and between neuropathy and clitoral sensitivity, suggest that diabetes-related complications might adversely affect the physiological basis of female sexual response.

In the late 1980s all Danish children with type 1 diabetes were invited for a nationwide evaluation of glycemic control. Approximately 75% (n = 720) participated and have later been referred to as The Danish Cohort of Pediatric Diabetes 1987 (DCPD1987). The results were surprisingly poor glycemic control among these young patients which lead to a great emphasis on glycemic control in the Danish Pediatric Departments. In 1995 the participants were invited for yet another evaluation but this time with main focus on early signs of microvascular complications - 339 participated. The mean HbA1c had remained at high levels (9.6%) and 60% of the participants had some level of Diabetic Retinopathy (DR). However, as the patients with DR mostly had the very milder forms it was believed that stricter glycemic control would reverse or at least stop progression of the disease in accordance with results from the large intervention study DCCT. This was investigated further at follow-up in 2011. The first study in the present thesis aimed to describe the 16-year incidence, progression and regression of DR in 185 participants from the DCPD1987 cohort. The 16-year incidence of proliferative retinopathy (PDR), 2-step progression and regression of DR was 31.0, 64.4, and 0.0%, respectively. As expected, the participants with PDR at follow-up had significantly higher HbA1c-values at both baseline and follow-up than those without PDR. However; a significantly larger decrease in HbA1c was also observed in the group with PDR over the study period, which in accordance with DCCT should have prevented the development of PDR to some extent. A surprisingly high incidence of proliferative retinopathy amongst young patients with type 1 diabetes in Denmark was found despite improvements in HbA1c over time. The improvement in HbA1c was either too small or happened too late. This study highlights that sight-threatening diabetic retinopathy remain a major concern in type 1 diabetes and the importance of early glycemic control. Identifying high-risk patients at a very early stage is not only desired for prevention of diabetic retinopathy - neuropathy and nephropathy similarly remain frequent in type 1 diabetes. Early risk stratification will allow for timely implementation of effective interventions and for individualized screening and diabetes care. The second and third studies of this thesis provide the longest prospective studies to date on both retinal vessel calibers and retinal fractal dimensions and their predictive value on diabetic microvascular complications. Semi-automated computer software has been developed to measure smaller changes in the retinal vessels on retinal photographs. Two of the first parameters to be reliably estimated by these programs were retinal vessel calibers and retinal vascular fractal dimensions (a quantitative measure on vascular complexity). There is very limited knowledge on their predictive value on diabetic complications thus far. In the second and third study, a consistent relation between narrower retinal arteriolar calibers, wider retinal venular calibers, lower fractal dimensions and the 16-year incidences of diabetic neuropathy, nephropathy and proliferative retinopathy was found. This has never been shown before. The results on vessel analyzes provides indications of a common pathogenic pathway for diabetic microvascular complications and therefore a possibility of universal risk estimation for development of neuropathy, nephropathy and retinopathy in type 1 diabetes.

The objective was to identify the presence of cardiovascular autonomic neuropathy (CAN) in a cohort of individuals with diabetes in outpatient clinics from 4 different parts of Denmark and to explore the difference between type 1 and type 2 diabetes in relation to CAN. The DAN-Study is a Danish multicenter study focusing on diabetic autonomic neuropathy. Over a period of 12 months, 382 type 1 and 271 type 2 individuals with diabetes were tested for CAN. Patients were randomly recruited and tested during normal visits to outpatient clinics at 4 Danish hospitals. The presence of CAN was quantified by performing 3 cardiovascular reflex tests (response to standing, deep breathing, and valsalva). To describe possible associations, multivariate analysis with CAN as the dependent variable was performed. The prevalence of CAN was higher among patients with type 2 diabetes (35%) compared to patients with type 1 diabetes (25%). Multivariate analysis revealed significant associations between CAN and different risk markers in the 2 populations. In type 1 diabetes patients CAN was associated with microalbuminuria (P < .001), macroalbuminuria (P = .011), simplex retinopathy (P < .001), proliferative retinopathy (P < .001), and peripheral neuropathy (P = .041). Among type 2 diabetes patients CAN was independently associated with high pulse pressure (P < .01), BMI (P = .006), and smoking (P = .025). In this cross-sectional observational study CAN was independently associated with microvascular complication in type 1, whereas in type 2 CAN was associated with macrovascular risk factors. The objective was to identify the presence of cardiovascular autonomic neuropathy (CAN) in a cohort of individuals with diabetes in outpatient clinics from 4 different parts of Denmark and to explore the difference between type 1 and type 2 diabetes in relation to CAN. The DAN-Study is a Danish multicenter study focusing on diabetic autonomic neuropathy. Over a period of 12 months, 382 type 1 and 271 type 2 individuals with diabetes were tested for CAN. Patients were randomly recruited and tested during normal visits to outpatient clinics at 4 Danish hospitals. The presence of CAN was quantified by performing 3 cardiovascular reflex tests (response to standing, deep breathing, and valsalva). To describe possible associations, multivariate analysis with CAN as the dependent variable was performed. The prevalence of CAN was higher among patients with type 2 diabetes (35%) compared to patients with type 1 diabetes (25%). Multivariate analysis revealed significant associations between CAN and different risk markers in the 2 populations. In type 1 diabetes patients CAN was associated with microalbuminuria (P < .001), macroalbuminuria (P = .011), simplex retinopathy (P < .001), proliferative retinopathy (P < .001), and peripheral neuropathy (P = .041). Among type 2 diabetes patients CAN was independently associated with high pulse pressure (P < .01), BMI (P = .006), and smoking (P = .025). In this cross-sectional observational study CAN was independently associated with microvascular complication in type 1, whereas in type 2 CAN was associated with macrovascular risk factors.

We describe the case of a 22-year-old man with insulin-dependent diabetes, who was admitted to the emergency department with hypotension, unconsciousness and a severe combined diabetic ketoacidosis (DKA) and lactic acid acidosis. In the discussion, we focus on the pathophysiological mechanisms underlying lactic acidosis in DKA, and we elaborate on the prognostic value of hyperlactataemia on such occasion.

We describe five patients with IgA-nephropathy complicating diabetes mellitus. In four cases, diabetic glomerulosclerosis was present at the same time. One patient suffered from dermatitis herpetiformis. The observation of the present five cases together with the notion of an increased prevalence in diabetes mellitus of celiac disease and dermatitis herpetiformis suggests that the occurrence of IgA-nephropathy in diabetic patients is not mere coincidence.

AIMS/HYPOTHESIS: The excess mortality in diabetes is mainly due to cardiovascular causes and almost confined to patients with abnormal albuminuria. Compared to healthy subjects, diabetic patients have a prolonged QT interval and increased QT dispersion. In non-diabetic subjects, as well as in Type 1 diabetic patients with overt nephropathy, a prolonged QT interval and increased QT dispersion are associated with cardiac morbidity and mortality. There is an increasing number of studies on effects of beta blocker treatment on QT interval and QT dispersion in non-diabetic subjects. In contrast, there are no studies on the effects of beta blocker treatment on QT interval and QT dispersion in patients with diabetes. The aim of our study was to describe the effects of metoprolol treatment on QT interval and QT dispersion in a group of well-characterised Type 1 diabetic patients with elevated urine albumin excretion.METHODS: We studied the effects of 6 weeks of treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in a randomised, placebo-controlled, double blind, crossover trial including 20 Type 1 diabetic patients. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, 24-h ambulatory blood pressure recording and 24-h fractionated urine collections. On days of investigation 12-lead electrocardiograms were recorded and autonomic tests performed.RESULTS: We found strong associations between both daytime and night-time blood pressure and heart-rate-corrected QT interval dispersion (QTc dispersion). Heart rate variability parameters indicating sympathetic and parasympathetic modulation showed strong correlations with heart-rate-corrected QT interval (QTc interval) and with QTc dispersion. Beta blocker treatment caused a decrease in QTc interval but no change in QTc dispersion.CONCLUSIONS/INTERPRETATION: This study is the first to address the QTc interval and QTc dispersion in Type 1 diabetic patients treated with metoprolol. Beta blocker treatment caused a decrease in QTc interval but no change in QTc dispersion. These results may in part explain the pronounced cardioprotective effect of beta blocker treatment in diabetic patients with cardiovascular disease.

OBJECTIVES: The aim of the study was to estimate the prevalence of silent ischaemia in diabetic subjects in the population, to compare the prevalence of silent ischaemia in diabetics and non-diabetics and to attempt to predict the presence of silent ischaemia in diabetic subjects.METHODS: A random sample of 120 users of insulin and 120 users of oral hypoglycaemic agents aged 40-75 years living in the Danish municipality of Horsens were asked to participate in the study. Corresponding to the youngest half of the sample two non-diabetic controls were randomly selected from the Central Population Register. ST-depression of horizontal or descending character of at least 0.1 mV measured 80 ms after the J-point on either exercise ECG or Holter ECG was considered indicative of myocardial ischaemia. Angina pectoris was considered present if the Rose questionnaire was positive, or chest pain was registered simultaneously with ECG evidence of ischaemia. Individuals with ischaemia, but without angina pectoris, were defined as persons with silent ischaemia.RESULTS: Seventy-four percent of the invited group were included. The observed prevalence of silent ischaemia in diabetics was 13.5% (95% CI = 8.5-19.8%). No association was found between silent ischaemia and gender (P = 0.83) or diabetes type (P = 0.67). In the group of diabetics who had controls, the prevalence was 11.4%, and among the controls the prevalence was 6.4% (OR = 1.87, one-sided P = 0.079). Systolic blood pressure was highly predictive of silent ischaemia in the diabetic subjects (P = 0.005). No predictive value could be shown for other variables.CONCLUSION: This is the first population-based study of silent ischaemia in diabetes. The prevalence of silent ischaemia in diabetic subjects was 13.5%. The frequency of silent ischaemia did not differ significantly between diabetics and non-diabetics. Systolic blood pressure was predictive of silent ischaemia in diabetes.