Effects of the glucagon-like peptide-1 receptor agonist liraglutide on systolic function in patients with coronary artery disease and type 2 diabetes: a randomized double-blind placebo-controlled crossover study.

BACKGROUND: Patients with type 2 diabetes (T2D) and coronary artery disease (CAD) have increased risk of cardiac dysfunction. The diabetic heart is characterized by increased fatty acid oxidation and reduced glucose uptake resulting in reduced cardiac efficiency. Glucagon-like peptide-1 (GLP-1) has shown to increase myocardial glucose uptake and to improve myocardial function. We examined the effect of the GLP-1 receptor agonist, liraglutide, on the systolic function of the left ventricle (LV) in patients with T2D and stable CAD. METHODS: In this placebo-controlled crossover study, 41 subjects with T2D and stable CAD were randomized to liraglutide or placebo and underwent dobutamine stress echocardiography (DSE) and exercise tolerance test at beginning and end of each intervention. The primary endpoint was changes in LV ejection fraction. Secondary endpoints were exercise capacity and other measures of systolic function: wall motion score index (WMSI), global longitudinal strain (GLS) and strain rate (GLSR). RESULTS: Liraglutide, when compared to placebo, did not improve LV ejection fraction at rest (+0.54 %; 95 % CI 2.38-3.45), at low stress (+0.03 %; 95 % CI 3.25-3.32), at peak stress (+1.12 %; 95 % CI 3.45-5.69), or at recovery (+4.06 %; 95 % CI 0.81-8.93). No significant changes in WMSI were observed at any stress levels. GLS and GLSR at rest did not improve. The maximal exercise capacity estimated by metabolic equivalents was not affected by liraglutide. CONCLUSION: In conclusion, liraglutide did not improve the systolic function of the left ventricle during DSE or the exercise capacity in patients with T2D and stable CAD. Clinical Trial Registration http://www.clinicaltrials.gov (unique identifier: NCT01595789).

IA-2 antibody-negative status predicts remission and recovery of C-peptide levels in type 1 diabetic patients treated with cyclosporin.

OBJECTIVE: The use of cyclosporin in recent-onset type 1 diabetes has demonstrated the potential for immune intervention in the treatment and prevention of the disease. However, a proportion of patients failed to respond to cyclosporin treatment. Indicators of resistance to immune intervention would be valuable for the most effective use of such therapies in disease prevention. The aim of this study was to determine whether presence of IA-2 antibodies is such a marker. RESEARCH DESIGN AND METHODS: IA-2 antibodies were determined by radioligand binding assay in sera from patients recruited into the Canadian-European cyclosporin trial. Insulin dose requirements and glucagon-stimulated C-peptide secretion were analyzed in patients grouped according to IA-2 antibody status at entry. RESULTS: Cyclosporin treatment had no significant effect on frequency of IA-2 antibodies during the 1 year of treatment. Cyclosporin caused significant reduction in insulin requirements and significant increases in C-peptide secretion mainly in patients negative for IA-2 antibodies. Analysis of GAD antibodies in combination with antibodies to IA-2 indicated that the group most resistant to cyclosporin were IA-2 antibody positive, GAD antibody negative. CONCLUSIONS: The results demonstrate that IA-2 antibody analysis is valuable in identifying individuals for whom immunosuppressive treatment would be most effective.

Increased urinary orosomucoid excretion is not related to impaired renal function in patients with type 2 diabetes.

OBJECTIVES: Increased urinary orosomucoid excretion rate (UOER) independently predicted cardiovascular mortality in patients with type 2 diabetes at 5-years of follow-up. To further explore UOER in relation to local renal physiological phenomena, we studied renal glomerular and tubular functions in patients with type 2 diabetes and normal or increased UOER. METHODS: We performed a cross-sectional study of 40 patients with type 2 diabetes (normal UOER, n=16; increased UOER, n=24) who displayed no signs of cardiovascular disease and 21 healthy control persons. The renal clearance values of [(51)Cr]ethylenediaminetetraacetic acid ([(51)Cr]EDTA), lithium, orosomucoid, albumin, and sodium were measured. RESULTS: Patients with type 2 diabetes had normal glomerular filtration rate (GFR) measured by [(51)Cr]EDTA clearance. The clearance value of orosomucoid was highly increased in patients with increased UOER. The clearance values of albumin were similar in patients with increased UOER and in healthy controls. Investigations of renal tubular function revealed normal and similar levels of lithium clearance and proximal and distal reabsorption of sodium and water. Serum values of orosomucoid were higher in patients with increased UOER than in healthy controls (P<.001), but were still within reference limits, suggesting chronic low-grade inflammation. UOER was associated with increasing values of orosomucoid clearance (P<.0001) independently of serum orosomucoid. CONCLUSIONS: Patients with type 2 diabetes and increased UOER had normal GFR and showed no signs of renal glomerular or tubular dysfunction. We therefore hypothesize that increased levels of UOER may be caused by local renal production of orosomucoid due to chronic low-grade inflammation.

[Diabetes passport--understanding and use among different ethnic groups of diabetes patients. Interviews with Turkish, Pakistani and Danish patients]. / Diabetespatienters forståelse for og vurdering af egen vandrejournal. Interview med tyrkiske, pakistanske og danske patienter.

INTRODUCTION: Diabetes passports for patients have been used for years in hospitals in our region. Since 2004 data have been printed from the electronic database DiabetesRASK and a new edition of the passport is given to patients at each visit. One of the objectives of the passport is to serve as a pedagogic tool. However, patients' understanding and use of the passport has never been studied. MATERIALS AND METHODS: Inclusion criteria for patients: type 2 diabetes, born in Turkey (T) or Pakistan (P), regular attendees at the outpatient clinics at Hvidovre Hospital or Amager Hospital and their personal diabetes data in the database DiabetesRASK. A comparable group of Danish diabetes patients was selected. All were invited to participate in a semi-structured interview. RESULTS: 14 T, 11 P and 10 D patients participated in the study. 53% T and 73% P had the ability to read in their own language while 15% T and 55% P were able to read in Danish. In the groups fewer than 25% had ever shown their passport to the GP. Between 0% and 36% of any of the given questions were understood or identified correctly by T patients. Similar figures for the P and D patients were 0-55% and 30-100%. CONCLUSION: It is demonstrated that the diabetes passport is not widely used by patients. Furthermore, we found poor understanding of information on the passport in general but with great individual variability. The poorest understanding was found among immigrants, which might be the result of language problems. However, Danish patients also had insufficient understanding of the information. We recommend that the diabetes passport be rewritten so that it is more easily understood by patients and that outpatient clinics also allocate more resources to the guidance of patients concerning the passport.