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Torsten Roed,1 Ulrik Sloth Kristoffersen,2 Andreas Knudsen,1,2 Niels Wiinberg,3 Anne-Mette Lebech,1 Thomas Almdal,4 Reimar W Thomsen,5 Andreas Kjær,2 Nina Weis1,61Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre, Denmark; 2Department of Clinical Physiology, Nuclear Medicine and PET and Cluster for Molecular Imaging, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; 3Department of Clinical Physiology, Frederiksberg Hospital, Copenhagen, Denmark; 4Steno Diabetes Center, Copenhagen, Denmark; 5Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark; 6Faculty of Health Sciences, University of Copenhagen, Copenhagen, DenmarkObjective: Chronic hepatitis C is a global health problem and has been associated with coronary artery disease. Our aim was to examine the prevalence of coronary artery disease risk markers including endothelial biomarkers in patients with chronic hepatitis C and matched comparisons without manifest cardiovascular disease or diabetes in a cross-sectional design.Methods: Sixty patients with chronic hepatitis C (mean age 51 years) were recruited from the Department of Infectious Diseases at Copenhagen University Hospital, and compared with 60 age-matched non-hepatitis C virus-infected individuals from a general population survey. We examined traditional coronary artery disease risk factors, metabolic syndrome, carotid intima media thickness, and a range of endothelial biomarkers.Results: Patients with chronic hepatitis C had more hypertension (40% versus 25%, prevalence ratio [PR] 1.6; 95% confidence interval [CI] 0.9–2.7) and smoked more (53% versus 38%, PR 1.4; 95% CI 0.9–2.1). The two groups had similar body mass index (mean 25.0 versus 25.7 kg/m2), whereas those with chronic hepatitis C had less dyslipidemia (including significantly lower low-density lipoprotein and cholesterol/high-density lipoprotein ratio), higher glycosylated hemoglobin level (mean 6.2 versus 5.7, difference of means 0.5; 95% CI 0.3–0.8), and a higher prevalence of metabolic syndrome (28% versus 18%, PR 1.6; 95% CI 0.8–3.0). Increased carotid intima media thickness above the standard 75th percentile was seen more frequently in chronic hepatitis C (9% versus 3%, PR 1.7; 95% CI 0.4–6.7), though difference of means was only 0.04 mm (95% CI 0.00–0.10). Patients with chronic hepatitis C had increased hsCRP (high-sensitivity C-reactive protein), sICAM-1 (soluble intercellular adhesion molecule-1), sVCAM-1 (soluble vascular cell adhesion molecule-1), and soluble E-selectin, but lower levels of tPAI-1 (tissue-type plasminogen activator inhibitor-1), MMP9 (matrix metallopeptidase 9), and MPO (myeloperoxidase) than their comparisons.Conclusion: Our findings indicate that patients with chronic hepatitis C have increased prevalence of several coronary artery disease risk markers. These results may be important when evaluating the appropriateness of screening for coronary artery disease and its risk factors in chronic hepatitis C.Keywords: risk factors, atherosclerosis, endothelial dysfunction, biomarkers, metabolic syndrome, intima media thickness

Background: Metformin has been shown to have both neuroprotective and neurodegenerative effects. The aim of this study was to investigate the effect of metformin in combination with insulin on cardiovascular autonomic neuropathy (CAN) and distal peripheral neuropathy (DPN) in individuals with type 2 diabetes (T2DM). Methods: The study is a sub-study of the CIMT trial, a randomized placebo-controlled trial with a 2 × 3 factorial design, where 412 patients with T2DM were randomized to 18 months of metformin or placebo in addition to open-labelled insulin. Outcomes were measures of CAN: Changes in heart rate response to deep breathing (beat-to-beat), orthostatic blood pressure (OBP) and heart rate and vibration detection threshold (VDT) as a marker DPN. Serum levels of vitamin B12 and methyl malonic acid (MMA) were analysed. Results: After 18 months early drop in OBP (30 s after standing) was increased in the metformin group compared to placebo: systolic blood pressure drop increased by 3.4 mmHg (95% CI 0.6; 6.2, p = 0.02) and diastolic blood pressure drop increased by 1.3 mmHg (95% CI 0.3; 2.6, p = 0.045) compared to placebo. Beat-to-beat variation decreased in the metformin group by 1.1 beats per minute (95% CI − 2.4; 0.2, p = 0.10). Metformin treatment did not affect VDT group difference − 0.33 V (95% CI − 1.99; 1.33, p = 0.39) or other outcomes. Changes in B12, MMA and HbA1c did not confound the associations. Conclusions: Eighteen months of metformin treatment in combination with insulin compared with insulin alone increased early drop in OBP indicating an adverse effect of metformin on CAN independent of vitamin B12, MMA HbA1c. Trial registration The protocol was approved by the Regional Committee on Biomedical Research Ethics (H–D-2007-112), the Danish Medicines Agency and registered with ClinicalTrials.gov (NCT00657943). [ABSTRACT FROM AUTHOR]

Aims To test whether concomitant use of an automated bolus calculator for people with Type 1 diabetes carrying out advanced carbohydrate counting would induce further improvements in metabolic control. Methods We conducted a 12-month, randomized, parallel-group, open-label, single-centre, investigator-initiated clinical study. We enrolled advanced carbohydrate counting-naïve adults with Type 1 diabetes and HbA1c levels 64-100 mmol/mol (8.0-11.3%), who were receiving multiple daily insulin injection therapy. In a 1:1-ratio, participants were randomized to receive training in either advanced carbohydrate counting using mental calculations ( MC group) or advanced carbohydrate counting using an automated bolus calculator ( ABC group) during a 3.5-h group training course. For 12 months after training, participants attended a specialized diabetes centre quarterly. The primary outcome was change in HbA1c from baseline to 12 months. Results Between August 2012 and September 2013, 168 participants (96 men and 72 women) were recruited and randomly assigned to the MC group ( n = 84) and the ABC group ( n = 84). Drop-out rates were 23.8 and 21.4%, respectively ( P = 0.712); 130 participants completed the study. The baseline HbA1c was 75 ± 9 mmol/mol (9.0 ± 0.8%) in the MC group and 74 ± 8 mmol/mol (8.9 ± 0.7%) in the ABC group. At 12 months, change in HbA1c was significant within both groups: MC group: -2 mmol/mol (95% CI -4 to -1) or -0.2% (95% CI -0.4 to -0.1; P = 0.017) and ABC group: -5 mmol/mol (95% CI -6 to -3) or -0.5% (95% CI -0.6 to -0.3; P < 0.0001), but HbA1c reductions were significantly greater in the ABC group ( P = 0.033). No episodes of severe hypoglycaemia were reported. Conclusions People with Type 1 diabetes initiating advanced carbohydrate counting obtained significantly greater HbA1c reductions when guided by an automated bolus calculator ( NCT02084498). [ABSTRACT FROM AUTHOR]

The cerebral serotonin (5-HT) system shows distinct differences in obesity compared with the lean state. Here, it was investigated whether serotonergic neurotransmission in obesity is a stable trait or changes in association with weight loss induced by Roux-in-Y gastric bypass (RYGB) surgery. In vivo cerebral 5-HT2A receptor and 5-HT transporter binding was determined by positron emission tomography in 21 obese [four men; body mass index (BMI), 40.1 ± 4.1 kg/m²] and 10 lean (three men; BMI, 24.6 ± 1.5kg/m²) individuals. Fourteen obese individuals were re-examined after RYGB surgery. First, it was confirmed that obese individuals have higher cerebral 5-HT2A receptor binding than lean individuals. Importantly, we found that higher presurgical 5-HT2A receptor binding predicted greater weight loss after RYGB and that the change in 5-HT2A receptor and 5-HT transporter binding correlated with weight loss after RYGB. The changes in the 5-HT neurotransmission before and after RYGB are in accordance with a model wherein the cerebral extracellular 5-HT level modulates the regulation of body weight. Our findings support that the cerebral 5-HT system contributes both to establish the obese condition and to regulate the body weight in response to RYGB. [ABSTRACT FROM AUTHOR]

Aims The aim of this study was to investigate associations between HbA1c recall by patients with Type 2 diabetes and self-management behaviours, patient activation, perception of care and diabetes distress. Methods In a cross-sectional survey, 993 patients with Type 2 diabetes reported their latest HbA1c. Validated scales measured self-management behaviours, patient activation, perception of care and diabetes distress. Self-reported HbA1c was compared with latest measured HbA1c. Using logistic regressions, associations between HbA1c recall and the variables of interest were investigated. Results Sixty-four per cent of patients recalled their latest HbA1c. Poor HbA1c recall was significantly associated with unhealthy eating behaviour, low level of exercise, low level of patient activation, poor glycaemic control, not knowing target HbA1c level, low educational level and being female. There were no associations between recall of HbA1c and diabetes distress or perceived care. Conclusions Recall of HbA1c level may increase patient activation and health-promoting behaviours. However, low educational level may be a barrier for using HbA1c as a motivator for health-promoting behaviours. This study indicates a need for studies of causal relationships, as well as mechanisms and challenges in using patient awareness of HbA1c as a driver for health-promoting behaviours. [ABSTRACT FROM AUTHOR]

Aims To develop risk scores for diabetes and diabetes or impaired glycaemia for individuals living in the Middle East and North Africa region. In addition, to derive national risk scores for Algeria, Saudi Arabia and the United Arab Emirates and to compare the performance of the regional risk scores with the national risk scores. Methods An opportunistic sample of 6588 individuals aged 30-75 years was screened. Screening consisted of a questionnaire and a clinical examination including measurement of HbA1c. Two regional risk scores and national risk scores for each of the three countries were derived separately by stepwise backwards multiple logistic regression with diabetes [HbA1c ≥ 48 mmol/mol (≥ 6.5%)] and diabetes or impaired glycaemia [HbA1c ≥ 42 mmol/mol (≥ 6.0%)] as outcome. The performance of the regional and national risk scores was compared in data from each country by receiver operating characteristic analysis. Results The eight risk scores all included age and BMI, while additional variables differed between the scores. The areas under the receiver operating characteristic curves were between 0.67 and 0.70, and for sensitivities approximately 75%; specificities varied between 50% and 57%. The regional and the national risk scores performed equally well in the three national samples. Conclusions Two regional risk scores for diabetes and diabetes or impaired glycaemia applicable to the Middle East and North Africa region were identified. The regional risk scores performed as well as the national risk scores derived in the same manner. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 654-661 (2012) Abstract Aims To investigate the relationship between structural and functional social support and patient activation, diabetes-related emotional distress, perceived diabetes care, self-management behaviour and HbA1c levels among patients with Type 2 diabetes. Methods Self-administered questionnaires were collected from 2572 patients with Type 2 diabetes. After adjusting for gender, age and education, Tobit and logistic regression models were used to examine associations between social network and patient activation, psychosocial problems, self-management behaviours and HbA1c levels. Results Frequent contact with friends was associated with more positive scores for activation, fewer psychosocial problems, more positive assessment of care and health-promoting self-management behaviours such as frequent exercising and frequent foot examinations. Frequent contact with family was associated with more positive assessments of care. Living with a partner was associated with lower prevalence of smoking, a higher frequency of foot examinations and higher HbA1c levels. A poor functional social network, measured as perceived lack of help in the event of severe illness, was associated with low patient activation, greater emotional distress, negative assessment of care, less health-promoting eating habits and less frequent foot examinations. Conclusions Good social support is significantly associated with health-promoting behaviours and well-being among patients with Type 2 diabetes. However, HbA1c levels are higher for cohabitant persons, indicating barriers for social support. Intervention research is needed to investigate the causal relationship between social networks and health-promoting behaviours. This knowledge should be used in clinical practice when targeting and designing education, support and care for patients with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Patients with type 2 diabetes (T2DM) have an increased mortality rate primarily because of macrovascular disease. Where T2DM patients cannot be managed sufficiently through diet, exercise and peroral antidiabetic drugs, that is when haemoglobin A1c (HbA1c) is above 7.0%, it is yet unknown whether a combination of metformin and insulin analogues is superior to insulin analogues alone. Nor is it known which insulin analogue regimen is the optimal. Objective: The primary objective of this trial is to evaluate the effect of an 18-month treatment with metformin vs. placebo in combination with one of three insulin analogue regimens, the primary outcome measure being carotid intima-media thickness (CIMT) in T2DM patients. Design: A randomized, stratified, multicentre trial having a 2 × 3 factorial design. The metformin part is double masked and placebo controlled. The insulin treatment is open. The intervention period is 18 months. Patient Population: Nine hundred and fifty patients with T2DM and HbA1c ≥ 7.5% on treatment with oral hypoglycaemic agents or on insulin treatment and deemed able, by the investigator, to manage once-daily insulin therapy with a long-acting insulin analogue. Randomization: Central randomization stratified for age (above 65 years), previous insulin treatment and treatment centre. Interventions: Metformin 1 g × two times daily vs. placebo (approximately 475 patients vs. 475 patients) in combination with • Insulin detemir before bedtime (approximately 315 patients) or • Biphasic insulin aspart 30 before dinner with the possibility to increase to two or three injections daily (approximately 315 patients) or • Insulin aspart before the main meals (three times daily) and insulin detemir before bedtime (approximately 315 patients). Intervention follows a treat-to-target principle in all six arms aiming for an HbA1c ≤ 7.0%. Outcome measures: Primary outcome measure is the change in CIMT from baseline to 18 months. Secondary outcome measures comprises the composite outcome of death, acute myocardial infarction, stroke or amputation assessed by an adjudication committee blinded to intervention, other cardiovascular clinical outcomes, average postprandial glucose increment from 0 to 18 months, hypoglycaemia and any inadvertent medical episodes. In addition, change in plaque formation in the carotids, HbA1c, cardiovascular biomarkers, body composition, progression of microvascular complications and quality of life will be assessed as tertiary outcome measures. Time schedule: Patient enrolment started May 2008. Follow-up is expected to finish in March 2011. Conclusion: CIMT is designed to provide evidence as to whether metformin is advantageous even during insulin treatment and to provide evidence regarding which insulin analogue regimen is most advantageous with regard to cardiovascular disease. [ABSTRACT FROM AUTHOR]

BACKGROUND & AIMS: It has been suggested that serving from a buffet system may increase food intake. This observational study estimates the energy intake in a representative group of patients admitted to a hospital, where the food is served from a buffet system. MATERIAL: One hundred and sixteen random patients were screened according to the NRS-2002 system and the energy requirements were calculated. The type of food ordered for the patients and the energy intake were determined. RESULT: Eighty had an NRS score of 0-2, i.e. not at nutritional risk and 36 a score > or = 3, i.e. at nutritional risk. Among patients with NRS score > or = 3 only 50% were ordered the correct menu. Only 50% of the patients had an energy intake < 75% of their requirements. In the group of patients, who took < 50% of energy requirement more than 90% came from the main courses and very little from snacks. CONCLUSION: In-patients at nutritional risk focus should be on ordering the correct type of food for the main courses and especially on increasing the intake from snacks. [ABSTRACT FROM AUTHOR]

Rationale: Low body mass index (BMI) is a marker of poor prognosis in chronic obstructive pulmonary disease (COPD). In the general population, the harmful effect of low BMI is due to the deleterious effects of a low fat-free mass index (FFMI; fat-free mass/weight[2]).Objectives: We explored distribution of low FFMI and its association with prognosis in a population-based cohort of patients with COPD.Methods: We used data on 1,898 patients with COPD identified in a population-based epidemiologic study in Copenhagen. FFM was measured using bioelectrical impedance analysis. Patients were followed up for a mean of 7 yr and the association between BMI and FFMI and mortality was examined taking age, sex, smoking, and lung function into account.Main Results: The mean FFMI was 16.0 kg/m[2] for women and 18.7 kg/m[2] for men. Among subjects with normal BMI, 26.1% had an FFMI lower than the lowest 10th percentile of the general population. BMI and FFMI were significant predictors of mortality, independent of relevant covariates. Being in the lowest 10th percentile of the general population for FFMI was associated with a hazard ratio of 1.5 (95% confidence interval, 1.2-1.8) for overall mortality and 2.4 (1.4-4.0) for COPD-related mortality. FFMI was also a predictor of overall mortality when analyses were restricted to subjects with normal BMI.Conclusions: FFMI provides information in addition to BMI and assessment of FFM should be considered in the routine assessment of COPD. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of the present study was to test the hypothesis that glucocorticoid receptor mRNA concentrations decreased with increasing fatness in normal subjects. MEASUREMENTS: Serum leptin concentrations, fat distribution parameters, lymphocyte glucocorticoid (GCR) mRNA, β[sub 2]-adrenoceptor mRNA and c-fos mRNA concentrations measured by RT-PCR-HPLC. SUBJECTS: Fifteen healthy non-obese young subjects with a mean body mass index (BMI) of 23.5 ± 0.3 (± s.e.m.) kg/m². RESULTS: Lymphocyte GCR and β[sub 2]-adrenoceptor mRNA concentrations averaged 4.2 ± 0.2 (± s.e.m.) amol/µg total RNA and 1.4 ± 0.1 amol/µg total RNA, respectively. There was a significant negative correlation between serum leptin and lymphocyte GCR mRNA (P < 0.01). Serum leptin correlated positively with the waist-hip ratio (P < 0.03), whereas lymphocyte GCR mRNA correlated negatively to the waist-hip ratio (P < 0.04). Serum cortisol correlated with the weight of the subjects but not the waist-hip ratio or GCR mRNA. CONCLUSIONS: It is suggested that the decrease in lymphocyte GCR mRNA concentration with increasing serum leptin concentrations is a counterregulatory response to an increased body fat content. Further studies are warranted, especially to elucidate the relationship between GCR mRNA in lymphocytes and in fat cells and to clarify the mechanism of the decrease in GCR mRNA. [ABSTRACT FROM AUTHOR]

It is unknown whether interleukin-1 exerts a bimodal effect on Beta-cell function in vivo, and whether interleukin-1 has a diabetogenic action in normal animals. We therefore studied: (a) acute effects 2 h after an intraperitoneal bolus injection of 4 μg of recombinant human interleukin-1 β per kg body weight on blood glucose, plasma levels of insulin, glucagon and corticosterone in Wistar Kyoto rats, either untreated or pre-treated with 4 μg/kg of interleukin-1 daily for 3 or 5 days; (b) the cumulative effects of repetitive intraperitoneal injections of 4 μg/kg interleukin-1 on blood glucose, glucose tolerance, plasma levels of insulin, glucagon and corticosterone, pancreatic insulin content and pancreatic ultrastructure; and (c) blood glucose and plasma concentrations of insulin, glucagon and corticosterone 10 h after the last of five intraperitoneal injections of interleukin-1, at which time point the inhibitory effect of short-term interleukin-1 exposure on insulin secretion reaches its nadir in vitro. A single injection of 4 μg/kg of interleukin-1 caused a slight, but significant lowering of blood glucose 2 h after interleukin-1 injection with no significant changes in plasma insulin and in spite of increases in plasma glucagon and corticosterone. A lowering of blood glucose 2 h after interleukin-1 administration was reproduced with 40, but not 0.4 μg/kg of interleukin-1, and was also seen in interleukin-1 pre-treated rats. Two hours after the fifth injection of interleukin-1, intraperitoneal glucose tolerance was impaired with elevated plasma insulin and corticosterone levels and increased pancreatic insulin content, indicating a state of insulin resistance. Blood glucose levels significantly increased time-dependently 4-10 h after the third and fifth injection of interleukin-1, and diabetic values (blood glucose >11.0 mmol/l) were observed 6 and 10 h after the fifth injection of interleukin-1. Ten hours after the fifth injection of interleukin-1, diabetic blood glucose levels were observed together with a 50% reduction in plasma insulin concentration. Ultrastructural examination showed no signs of Betacell lysis. In conclusion, interleukin-1 has bimodal effects on glucose homeostasis in vivo, a slight lowering of the blood glucose followed by impaired glucose tolerance and later by diabetic blood glucose levels. Two hours after the last of five daily injections of interleukin-1 impaired glucose tolerance is primarily caused by a state of insulin resistance, whereas diabetic blood glucose levels are associated with inhibition of insulin secretion. Thus, interleukin-1 causes a diabetic state in normal animals, but it remains to be demonstrated that administration of interleukin-1 to normal animals leads to permanent diabetes due to Beta-cell destruction. [ABSTRACT FROM AUTHOR]