Cost-effectiveness of a Novel Hypoglycaemia Programme: The 'HARPdoc vs BGAT' RCT.

AIMS: To assess the cost-effectiveness of HARPdoc (Hypoglycaemia Awareness Restoration Programme for adults with type 1 diabetes and problematic hypoglycaemia despite optimised care), focussed upon cognitions and motivation, versus BGAT (Blood Glucose Awareness Training), focussed on behaviours and education, as adjunctive treatments for treatment-resistant problematic hypoglycaemia in type 1 diabetes, in a randomised controlled trial. METHODS: Eligible adults were randomised to either intervention. Quality of life (QoL, measured using EQ-5D-5L); cost of utilisation of health services (using the adult services utilization schedule, AD-SUS) and of programme implementation and curriculum delivery were measured. A cost-utility analysis was undertaken using quality-adjusted life years (QALYs) as a measure of trial participant outcome and cost-effectiveness was evaluated with reference to the incremental net benefit (INB) of HARPdoc compared to BGAT. RESULTS: Over 24 months mean total cost per participant was £194 lower for HARPdoc compared to BGAT (95% CI: -£2498 to £1942). HARPdoc was associated with a mean incremental gain of 0.067 QALYs/participant over 24 months post-randomisation: an equivalent gain of 24 days in full health. The mean INB of HARPdoc compared to BGAT over 24 months was positive: £1521/participant, indicating comparative cost-effectiveness, with an 85% probability of correctly inferring an INB > 0. CONCLUSIONS: Addressing health cognitions in people with treatment-resistant hypoglycaemia achieved cost-effectiveness compared to an alternative approach through improved QoL and reduced need for medical services, including hospital admissions. Compared to BGAT, HARPdoc offers a cost-effective adjunct to educational and technological solutions for problematic hypoglycaemia.

A cognitive behavioural model of the bidirectional relationship between disordered eating and diabetes self care in adult men with Type 1 diabetes mellitus.

AIMS: This qualitative study aimed to develop the first cognitive behavioural (CBT) model outlining the development and maintenance of disordered eating in adult men living with Type 1 diabetes to improve on previous theoretical models of Type 1 diabetes and disordered eating and to draw comparisons to women with Type 1 diabetes and disordered eating. METHODS: Twenty-seven men (n = 16 with Type 1 diabetes and disordered eating, n = 11 with Type 1 diabetes without disordered eating) participated in semi-structured interviews. Data were analysed using thematic analysis and individual CBT formulations were developed for each participant to inform the model. RESULTS: Men with Type 1 diabetes and disordered eating experience negative thoughts about food, insulin, weight/shape and diabetes itself, which cause negative emotions such as fear and vulnerability and difficulties with diabetes self care such as problems with hyper and hypoglycaemia and problems accessing structured education and technology result in men feeling more dissatisfied about their body weight/shape. CONCLUSIONS: This CBT model of disordered eating in men with Type 1 diabetes can guide new interventions.

Protocol for the STEADY intervention for type 1 diabetes and disordered eating: Safe management of people with Type 1 diabetes and EAting Disorders studY.

This paper describes the protocol to test the feasibility of the Safe management of people with Type 1 diabetes and EAting Disorders studY (STEADY) intervention. STEADY is a novel complex intervention for people with type 1 diabetes and disordered eating (T1DE) of mild to moderate severity. The STEADY intervention integrates cognitive behavioural therapy (CBT) with diabetes education, and was developed using Experience-Based Co-Design. METHODS: The feasibility of STEADY will be tested using a randomised controlled feasibility trial. Forty adults with T1DE will be recruited and randomised into the STEADY intervention or treatment as usual control group. We will collect demographic, biomedical and psychometric data, routine glucose metrics and conduct the Structured Clinical Interview for DSM-5. Participants randomised to the STEADY intervention will receive 12 STEADY therapy sessions with a diabetes specialist nurse trained in CBT, delivered via videoconference and an optional smartphone app. The main outcome at 6 months will be the feasibility of STEADY (recruitment, dropout rates, feasibility of delivery). The secondary outcomes are biomedical (HbA1c and glucose time in range) and psychological (person-reported outcome measures in disordered eating, diabetes distress, depression and anxiety). A process evaluation will evaluate the fidelity, feasibility, acceptability and appropriateness of STEADY, and participant experiences. ETHICS AND DISSEMINATION: The protocol was approved by the East of England-Essex Research Ethics Committee (21/EE/0235). Study findings will be shared with study participants and disseminated through peer-reviewed publications and conference presentations.

A parallel randomised controlled trial of the Hypoglycaemia Awareness Restoration Programme for adults with type 1 diabetes and problematic hypoglycaemia despite optimised self-care (HARPdoc).

Impaired awareness of hypoglycaemia (IAH) is a major risk for severe hypoglycaemia in insulin treatment of type 1 diabetes (T1D). To explore the hypothesis that unhelpful health beliefs create barriers to regaining awareness, we conducted a multi-centre, randomised, parallel, two-arm trial (ClinicalTrials.gov NCT02940873) in adults with T1D and treatment-resistant IAH and severe hypoglycaemia, with blinded analysis of 12-month recall of severe hypoglycaemia at 12 and/or 24 months the primary outcome. Secondary outcomes included cognitive and emotional measures. Adults with T1D, IAH and severe hypoglycaemia despite structured education in insulin adjustment, +/- diabetes technologies, were randomised to the "Hypoglycaemia Awareness Restoration Programme despite optimised self-care" (HARPdoc, n = 49), a psychoeducation programme uniquely focussing on changing cognitive barriers to avoiding hypoglycaemia, or the evidence-based "Blood Glucose Awareness Training" (BGAT, n = 50), both delivered over six weeks. Median [IQR] severe hypoglycaemia at baseline was 5[2-12] per patient/year, 1[0-5] at 12 months and 0[0-2] at 24 months, with no superiority for HARPdoc (HARPdoc vs BGAT incident rate ratios [95% CI] 1.25[0.51, 3.09], p = 0.62 and 1.26[0.48, 3.35], p = 0.64 respectively), nor for changes in hypoglycaemia awareness scores or fear. Compared to BGAT, HARPdoc significantly reduced endorsement of unhelpful cognitions (Estimated Mean Difference for Attitudes to Awareness scores at 24 months, -2.07 [-3.37,-0.560], p = 0.01) and reduced scores for diabetes distress (-6.70[-12.50,-0.89], p = 0.02); depression (-1.86[-3.30, -0.43], p = 0.01) and anxiety (-1.89[-3.32, -0.47], p = 0.01). Despite positive impact on cognitive barriers around hypoglycaemia avoidance and on diabetes-related and general emotional distress scores, HARPdoc was not more effective than BGAT at reducing severe hypoglycaemia.

Developing a novel intervention for type 1 diabetes and disordered eating using a participatory action design process: Safe management of people with Type 1 diabetes and EAting Disorders studY (STEADY).

AIMS: To develop a cognitive behavioural therapy-based intervention for people with type 1 diabetes and disordered eating using Experience-Based Co-Design as part of the Safe management of people with Type 1 diabetes and EAting Disorders studY (STEADY). METHODS: Fifteen people with type 1 diabetes and experience of disordered eating (33 ± 11 years old, 22 ± 12 years diabetes duration) and 25 healthcare professionals working in type 1 diabetes or eating disorders (44 ± 9 years old; 14 ± 10 years of professional experience) attended six Experience-Based Co-Design workshops from July 2019 to March 2020 to collaboratively develop intervention content. RESULTS: We developed a cognitive behaviour therapy intervention 'toolkit' that can be tailored for individual patient needs. Participants designed and revised toolkit materials to ensure acceptability and relevance for people with diabetes and disordered eating by engaging in guided discussion, brainstorming, and rapid testing to review toolkit prototypes in an iterative process. Workshop themes were 'Insulin titration'; 'Hypoglycaemia'; 'Coming to terms with diabetes'; 'Fear of weight gain'; 'Toolkit revision'; and 'Practical elements of STEADY therapy'. The intervention is focussed on improving diabetes self-care and embedded in a multidisciplinary healthcare approach. The intervention will be delivered in 12 sessions by a diabetes specialist nurse trained in cognitive behavioural therapy. CONCLUSIONS: Through an iterative co-design process, people with type 1 diabetes and healthcare professionals collaboratively developed a novel intervention toolkit that can be used with a wide range of disordered eating presentations. The intervention will be tested in the STEADY feasibility randomised controlled trial.

A cognitive behavioural model of the bidirectional relationship between disordered eating and diabetes self care in people with type 1 diabetes mellitus.

AIMS: This qualitative study aimed to develop the first cognitive behavioural therapy model outlining the development and maintenance of disordered eating in type 1 diabetes and report on recovery strategies and resilience factors to improve previous theoretical models of type 1 diabetes and disordered eating. METHODS: Twenty-three women (n = 9 with type 1 diabetes and disordered eating, n = 5 with type 1 diabetes recovering from disordered eating, and n = 9 with type 1 diabetes without disordered eating) participated in semi-structured interviews. Data were analysed using grounded theory and individual cognitive-behavioural formulations were developed for each participant to inform the development/maintenance and resilience models. RESULTS: The development/maintenance model summarises commonly experienced vicious cycles of thoughts, feelings and behaviours in type 1 diabetes and disordered eating. The resilience model summarises strategies and knowledge acquired by those with type 1 diabetes in recovery from disordered eating and individuals with type 1 diabetes who did not develop disordered eating. Early adverse life events, past psychiatric history, perfectionist personality traits, difficult experiences around type 1 diabetes diagnosis and its relentless daily management sensitise individuals to eating, weight and shape cues. Alongside physical symptoms/complications, unhelpful interpersonal reactions and inadequate healthcare, vicious cycles of thoughts, feelings and behaviours develop. 'Good enough' psychological adaptation to type 1 diabetes, integrating type 1 diabetes into one's identity, self care and compassion around eating, weight and shape were key protective/post-traumatic resilience factors. CONCLUSIONS: This first cognitive behavioural therapy model of type 1 diabetes and disordered eating informed by personal experience will inform an intervention for type 1 diabetes and disordered eating.

Elevated levels of serum PCSK9 in male patients with symptomatic peripheral artery disease: The CAVASIC study.

BACKGROUND AND AIMS: Peripheral artery disease (PAD) affects more than 200 million people worldwide. Increased low-density lipoprotein cholesterol (LDL-C)levels are a risk factor for PAD and the concentrations are influenced by proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 regulates the recycling of the LDL receptors to the cell membrane surface. Only a limited number of mostly small studies investigated the association between serum PCSK9 concentrations and PAD of different definition, which revealed contrasting results. METHODS: Serum PCSK9, lipoprotein(a) [Lp(a)] and other lipoprotein concentrations were measured in male participants of the CAVASIC study, a case-control study of 248 patients with intermittent claudication and 251 age and diabetes-matched controls. RESULTS: PAD patients had significantly higher PCSK9 concentrations when compared to controls (250 ± 77 vs. 222 ± 68 ng/mL, p < 0.001). Logistic regression analysis with adjustment for age revealed that an increase in PCSK9 concentrations of 100 ng/mL was associated with a 1.78-fold higher risk for PAD (95%CI 1.38-2.33, p = 1.43 × 10-5). The association attenuated, but was still significant when adjusting additionally for age, Lp(a)-corrected LDL cholesterol, HDL cholesterol, high-sensitivity-CRP, statin treatment, hypertension, diabetes mellitus and smoking (OR = 1.49, 95%CI 1.03-2.18, p = 0.035). The strongest association was observed when both PCSK9 concentrations were above the median and Lp(a) concentrations were above 30 mg/dL (OR = 3.35, 95%CI 1.49-7.71, p = 0.0038). CONCLUSIONS: Our findings suggest an association of higher PCSK9 concentrations with PAD, which was independent of other lipid parameters and classical cardiovascular risk factors.

The impact of pharmacological and lifestyle interventions on body weight in people with type 1 diabetes: A systematic review and meta-analysis.

AIM: To systematically review the effects of pharmacological and lifestyle interventions on body weight as a secondary outcome in people with type 1 diabetes. METHODS: The Ovid Medline, Embase and Cochrane Library databases were searched for relevant pharmacological (glucagon-like peptide-1 [GLP-1] receptor agonist, sodium-glucose co-transporter-2 [SGLT-2] inhibitor, dipeptidyl peptidase-4 [DPP-4] inhibitor and metformin) and lifestyle intervention studies (diet and exercise) for adults with type 1 diabetes reporting body weight change and HbA1c published from January 2000 to May 2020. Meta-analyses were performed for 16 randomized controlled trials (RCTs). RESULTS: Thirty-three RCTs (n = 9344 participants), 26 pharmacological (on average 43.9 years, 83.1 kg, HbA1c 8.1%; 55.8% male) and seven lifestyle-based interventions (on average 37.0 years, 85.0 kg, HbA1c 8.1%; 84.6% male), were analysed. The GLP-1 receptor agonist liraglutide 0.6 mg (mean difference [MD]: -2.22 kg [95% CI: -2.55 to -1.90]), 1.2 mg (MD: -3.74 kg [95% CI: -4.16 to -3.33]) and 1.8 mg (MD: -4.85 kg [95% CI: -5.29 to -4.41]), and the SGLT-2 inhibitors empagliflozin 2.5 mg (MD: -1.47 kg [95% CI: -2.23 to -0.71]), 10 mg (MD: -2.77 kg [95% CI: -3.24 to -2.31]) and 25 mg (MD: -3.06 kg [95% CI: -3.57 to -2.55]) and sotagliflozin 200 mg (MD: -2.40 kg [95% CI: -2.87 to -1.94]) and 400 mg (MD: -3.23 [95% CI: -3.73 to -2.72]) were associated with significant reductions in body weight. No significant effect on body weight was found for DPP-4 inhibitors, other GLP-1-receptor agonists, metformin, or for lifestyle interventions (i.e. exercise and diet). CONCLUSIONS: In people with type 1 diabetes, several adjuvant pharmacological interventions showed weight reduction as a secondary outcome. Future studies in overweight people with type 1 diabetes are needed to establish whether the lifestyle and pharmacological interventions reviewed here have potential as components of complex interventions aimed at body weight reduction as a primary outcome.

Disordered eating in women with type 1 diabetes: Continuous glucose monitoring reveals the complex interactions of glycaemia, self-care behaviour and emotion.

OBJECTIVES: Glycaemia in people with type 1 diabetes and disordered eating is not well characterised. We explored the glycaemia, self-care behaviour and emotional state of women with type 1 diabetes and disordered eating. RESEARCH DESIGN AND METHODS: In all, 13 women with and 10 without disordered eating and type 1 diabetes participated in this case-control study. We used a mixed-methods approach with a 7-day blinded continuous glucose monitoring and real-time record of non-prompted capillary glucose (CG), emotion, activity and physical symptoms on a diabetes diary using a smartphone application (mySugr®). We compared groups using Mann-Whitney U test or Fisher's exact test. We conducted thematic analyses of free-text diary entries (NVivo®) and quantitative analysis of emotion/symptom tags. RESULTS: People with type 1 diabetes and disordered eating spent longer time above range in level 2 hyperglycaemia (>13.9 mmol/L, Median [interquartile range]: 21% [16,60] vs 5% [2,17], p = 0.015). They had lower time in range and similar time below range compared to those without disordered eating. The standard deviation of CG was significantly higher in the disordered eating group (4.7 mmol/L [4.5, 6.1] vs 3 [2.8, 3.2], p = 0.018). The median of the percentage of rising sensor glucose trends was three times higher in the disordered eating group. They also had higher negative emotional and physical symptoms associated with high blood glucose (>15 mmol/L). CONCLUSIONS: Disordered eating has a significant impact on the glycaemia and emotion of a person with type 1 diabetes.

Insulin clearance as the major player in the hyperinsulinaemia of black African men without diabetes.

AIM: To investigate relationships between insulin clearance, insulin secretion, hepatic fat accumulation and insulin sensitivity in black African (BA) and white European (WE) men. METHODS: Twenty-three BA and twenty-three WE men with normal glucose tolerance, matched for age and body mass index, underwent a hyperglycaemic clamp to measure insulin secretion and clearance, hyperinsulinaemic-euglycaemic clamp with stable glucose isotope infusion to measure whole-body and hepatic-specific insulin sensitivity, and magnetic resonance imaging to quantify intrahepatic lipid (IHL). RESULTS: BA men had higher glucose-stimulated peripheral insulin levels (48.1 [35.5, 65.2] × 103 vs. 29.9 [23.3, 38.4] × 103 pmol L-1 × min, P = .017) and lower endogeneous insulin clearance (771.6 [227.8] vs. 1381 [534.3] mL m-2 body surface area min -1 , P < .001) compared with WE men. There were no ethnic differences in beta-cell insulin secretion or beta-cell responsivity to glucose, even after adjustment for prevailing insulin sensitivity. In WE men, endogenous insulin clearance was correlated with whole-body insulin sensitivity (r = 0.691, P = .001) and inversely correlated with IHL (r = -0.674, P = .001). These associations were not found in BA men. CONCLUSIONS: While normally glucose-tolerant BA men have similar insulin secretory responses to their WE counterparts, they have markedly lower insulin clearance, which does not appear to be explained by either insulin resistance or hepatic fat accumulation. Low insulin clearance may be the primary mechanism of hyperinsulinaemia in populations of African origin.

Metformin to reduce metabolic complications and inflammation in patients on systemic glucocorticoid therapy: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial.

BACKGROUND: An urgent need to reduce the metabolic side-effects of glucocorticoid overexposure has been recognised, as glucocorticoid excess can lead to Cushing's syndrome, which is associated with high morbidity. We aimed to evaluate the potential of metformin to reverse such effects while sparing the anti-inflammatory benefits of glucocorticoids. METHODS: We did a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial involving four hospitals in the UK. Patients without diabetes were eligible if they were between the ages of 18 and 75 years with an inflammatory disease treated with continuous prednisolone (≥20 mg/day for ≥4 weeks and remaining on ≥10 mg/day for the subsequent 12 weeks, or its cumulative dose-equivalent). Eligible patients were randomly allocated (1:1) to either the metformin or placebo groups, using a computer-generated randomisation table stratified according to age and BMI. Metformin and placebo were administered orally for 12 weeks in escalating doses: 850 mg/day for the first 5 days, 850 mg twice a day for the next 5 days, and 850 mg three times a day subsequently. The primary outcome was the between-group difference in visceral-to-subcutaneous fat area ratio over 12 weeks, assessed by CT. Secondary outcomes included changes in metabolic, bone, cardiovascular, and inflammatory parameters over 12 weeks. Our analysis followed a modified intention-to-treat principle for the primary outcome. This study is registered with ClinicalTrials.gov, NCT01319994. FINDINGS: Between July 17, 2012, and Jan 14, 2014, 849 patients were assessed for study eligibility, of which 53 were randomly assigned to receive either metformin (n=26) or placebo (n=27) for 12 weeks. 19 patients in the metformin group and 21 in the placebo group were eligible for the primary outcome analysis. Both groups received an equivalent cumulative dose of glucocorticoids (1860 mg prednisolone-equivalent [IQR 1060-2810] in the metformin group vs 1770 mg [1020-2356] in the placebo group); p=0·76). No change in the visceral-to-subcutaneous fat area ratio between the treatment groups was observed (0·11, 95% CI -0·02 to 0·24; p=0·09), but patients in the metformin group lost truncal subcutaneous fat compared with the placebo group (-3835 mm2, 95% CI -6781 to -888; p=0·01). Improvements in markers of carbohydrate, lipid, liver, and bone metabolism were observed in the metformin group compared with the placebo group. Additionally, those in the metformin group had improved fibrinolysis, carotid intima-media thickness, inflammatory parameters, and clinical markers of disease activity. The frequency of pneumonia (one event in the metformin group vs seven in the placebo group; p=0·01), overall rate of moderate-to-severe infections (two vs 11; p=0·001), and all-cause hospital admissions due to adverse events (one vs nine; p=0·001) were lower in the metformin group than in the placebo group. Patients in the metformin group had more events of diarrhoea than the placebo group (18 events vs eight; p=0·01). INTERPRETATION: No significant changes in the visceral-to-subcutaneous fat area ratio between the treatment groups were observed; however, metformin administration did improve some of the metabolic profile and clinical outcomes for glucocorticoid-treated patients with inflammatory disease, which warrants further investigation. FUNDING: Barts Charity and Merck Serono.

Hypoglycaemia Awareness Restoration Programme for People with Type 1 Diabetes and Problematic Hypoglycaemia Persisting Despite Optimised Self-care (HARPdoc): protocol for a group randomised controlled trial of a novel intervention addressing cognitions.

INTRODUCTION: Severe hypoglycaemia (SH), when blood glucose falls too low to support brain function, is the most feared acute complication of insulin therapy for type 1 diabetes mellitus (T1DM). 10% of people with T1DM contribute nearly 70% of all episodes, with impaired awareness of hypoglycaemia (IAH) a major risk factor. People with IAH may be refractory to conventional approaches to reduce SH, with evidence for cognitive barriers to hypoglycaemia avoidance. This paper describes the protocol for the Hypoglycaemia Awareness Restoration Programme for People with Type 1 Diabetes and Problematic Hypoglycaemia Persisting Despite Optimised Self-care (HARPdoc) study, a trial to assess the impact on hypoglycaemia experience of a novel intervention that addresses cognitive barriers to hypoglycaemia avoidance, compared with an existing control intervention, recommended by the National Institute of Health and Care Excellence. METHODS AND ANALYSIS: A randomised parallel two-arm trial of two group therapies: HARPdoc versus Blood Glucose Awareness Training, among 96 adults with T1DM and problematic hypoglycaemia, despite attendance at education with or without technology use, in four centres providing specialist T1DM services. The primary outcome will be the SH rate at 12 and/or 24 months after randomisation to either course. Secondary outcomes include rates of SH requiring parenteral therapy, involving unconsciousness or needing emergency services; hypoglycaemia awareness status, overall diabetes control and quality of life measures. An implementation study to evaluate how the interventions are delivered and how implementation impacts on clinical effectiveness is planned as a parallel study, with its own protocol. ETHICS AND DISSEMINATION: The protocol was approved by the London Dulwich Research Ethics Committee, the Health Research Authority, National Health Service R&D and the Institutional Review Board of the Joslin Diabetes Center in the USA. Study findings will be disseminated to study participants and through peer-reviewed publications and conference presentations, including user groups. TRIAL REGISTRATION NUMBER: NCY02940873; Pre-results.

[Insulin pump therapy in children, adolescents and adults, guidelines (Update 2019)]. / Insulinpumpentherapie bei Kindern, Jugendlichen und Erwachsenen (Update 2019).

This position statement is based on current evidence available on the safety and benefits of continuous subcutaneous insulin infusion therapy (CSII, pump therapy) in diabetes with an emphasis on the effects of CSII on glycemic control, hypoglycaemia rates, occurrence of ketoacidosis, quality of life and the use of insulin pump therapy in pregnancy. The current article represents the recommendations of the Austrian Diabetes Association for the clinical praxis of insulin pump treatment in children, adolescents and adults.

[CGM-Continuous Glucose Monitoring-Statement of the Austrian Diabetes Association (Update 2019)]. / Kontinuierliche Glukosemessung (CGM ­ Continuous Glucose Monitoring) bei Diabetes mellitus (Update 2019).

This position statement represents the recommendations of the Austrian Diabetes Association regarding the clinical diagnostic and therapeutic application, safety and benefits of continuous subcutaneous glucose monitoring systems in patients with diabetes, based on current evidence.

The metabolic underpinning of eating disorders: A systematic review and meta-analysis of insulin sensitivity.

BACKGROUND: A recent study reported a positive genetic correlation between anorexia nervosa and insulin sensitivity using data from genome-wide association studies. Epidemiological studies have, on the other hand, suggested that bulimia nervosa and binge-eating disorder are associated with decreased insulin sensitivity. The aim of this study was to conduct a systematic review and meta-analysis of insulin sensitivity across the spectrum of eating disorders. METHODS: EMBASE, Medline, and PsycINFO were searched for all relevant studies published until January 2017, and retrieved studies were assessed for eligibility by two independent reviewers as per predefined inclusion criteria. The associations between eating disorder subtypes and insulin sensitivity were analysed separately. Individual effect sizes were standardized, and a meta-analysis was performed to calculate a pooled effect size using random effects. RESULTS: Of 296 citations retrieved, 22 studies met the inclusion criteria, and 12 studies had appropriate data for meta-analysis. Using the random effects model, the pooled effect size (95% confidence interval) was 1.66 (0.79, 2.54) in people with anorexia nervosa (n = 340) and -0.57 (-0.80, -0.34) in people with bulimia nervosa (n = 120) and binge-eating disorders (n = 3241). INTERPRETATION: Anorexia nervosa is associated with increased insulin sensitivity whilst bulimia nervosa and binge-eating disorders are associated with decreased insulin sensitivity. The possible mechanism underpinning these findings needs to be determined.

The fate of patients with intermittent claudication in the 21st century revisited - results from the CAVASIC Study.

Patients with intermittent claudication carry a high risk for cardiovascular complications. The TransAtlantic Inter-Society Consensus (TASC) Group estimated a five-year overall mortality of 30% for these patients, the majority dying from cardiovascular causes. We investigated whether this evaluation is still applicable in nowadays patients. We therefore prospectively followed 255 male patients with intermittent claudication from the CAVASIC Study during 7 years for overall mortality, vascular morbidity and mortality and local PAD outcomes. Overall mortality reached 16.1% (n = 41). Most patients died from cancer (n = 20). Half of patients (n = 22; 8.6%) died within the first five years. Incident cardiovascular events were observed among 70 patients (27.5%), 54 (21.2%) during the first five years. Vascular mortality was low with 5.1% (n = 13) for the entire and 3.1% for the first five years of follow-up. Prevalent coronary artery disease did not increase the risk to die from all or vascular causes. PAD symptoms remained stable or improved in the majority of patients (67%). In summary, compared to TASC, the proportion of cardiovascular events did not markedly decrease over the last two decades. Vascular mortality, however, was low among our population. This indicates that nowadays patients more often survive cardiovascular events and a major number dies from cancer.

Prevalence of elevated liver enzymes in adults with type 1 diabetes: A multicentre analysis of the German/Austrian DPV database.

AIMS: To assess the prevalence of elevated liver enzymes in adults with type 1 diabetes mellitus (T1DM) in routine clinical care and the association with cardiovascular risk profile in the Diabetes-Prospective-Documentation (DPV) network in Germany and Austria. SUBJECTS AND METHODS: This cross sectional observational study from the DPV registry includes data from 45 519 adults with T1DM at 478 centres up to September 2016. Liver enzyme measurements were available in 9226 (29%) patients at 270 centres and were analysed for increased alanine aminotransferase (ALT; men >50 U/L, women >35U/L) and/or aspartate aminotransferase (AST; men >50 U/L, women >35U/L) and/or gamma-glutamyltransferase (GGT; men >60U/L, women >40 U/L). A subgroup analysis in patients for whom 2 or more ALT measurements were available (n = 2335, 25%) and whose ALT was increased at least twice (men >30 U/L, women >19U/L) was performed. Associations with glycaemic control, cardiovascular risk factors and late complications were investigated with multiple regression analyses. RESULTS: Twenty percent (19.8%, n = 1824) had increased liver enzyme(s) on one or more occasions. Increased liver enzymes were associated with worse glycaemic control and higher BMI (both P < .0001), dyslipidemia (OR, 1.75; 95% CI, 1.54-2.0), hypertension (OR, 1.48; 95% CI: 1.31-1.68), myocardial infarction (OR, 1.49; 95% CI, 1.17-1.91) and end stage renal disease (OR, 1.59; 95% CI, 1.17-2.17). ALT was increased twice in 29% and was associated with worse glycaemic control (P < .0001), higher BMI (P < .0001), hypertension (OR, 1.58; 95% CI, 1.26-1.97) and dyslipidemia (OR, 1.89; 95% CI, 1.51-2.37). CONCLUSIONS: In this clinical audit in adults with T1DM, elevated liver enzymes on routine assessment were associated with a less favourable cardiovascular risk profile and with poorer glycaemic control.

[Type 2 Diabetes mellitus-screening and prevention: Update 2016]. / Typ 2 Diabetes mellitus - Screening und Prävention : Update 2016.

The prevalence of diabetes is increasing in westernized countries. In addition, about half of all patients suffering from diabetes are not diagnosed. The current article represents the recommendations of the Austrian Diabetes Association for the screening and prevention of type 2 diabetes, based on currently available evidence.