Volume 1, Number 1, May 2004

EDITORIALDiabetes and cardiology: the common soil comes of age
Peter J Grant

Diabetes Vasc Dis Res 2004;1:9.

POPULAR
TOPICREVIEWRAGE and its ligands: a lasting memory in diabetic complications?
Shi-Fang Yan, Ravichandran Ramasamy, Loredana G Bucciarelli, Thoralf Wendt, Larisse K Lee, Barry I Hudson, David M Stern, Evanthia Lalla, Shi Du Yan, Ling Ling Rong, Yoshifumi Naka, Ann Marie Schmidt

The complications of diabetes are myriad and represent a rising cause of morbidity and mortality, particularly in the Western world. The update of the Diabetes Control and Clinical Trials Group/Epidemiology of Diabetes Interventions and Complications Research Group (DCCT/EDIC) suggested that previous strict control of hyperglycaemia was associated with reduced carotid atherosclerosis compared to conventional treatment, even after levels of glycosylated haemoglobin between the two treatment groups became indistinguishable. These intriguing findings prompt the key question, why does the blood vessel ‘remember’?
This review focuses on the hypothesis that the ligand/RAGE axis contributes importantly to glycaemic ‘memory’. Studies in rodent models of diabetes suggest that blockade or genetic modification of RAGE suppress diabetes-associated progression of atherosclerosis, exaggerated neointimal expansion consequent to acute arterial injury, and cardiac dysfunction.
We propose that therapeutic RAGE blockade will intercept maladaptive diabetes-associated memory in the vessel wall and provide cardiovascular protection in diabetes.

Diabetes Vasc Dis Res 2004;1:10-20.

POPULAR
TOPICREVIEWAcute coronary syndromes and diabetes mellitus
Benjamin H Trichon, Matthew T Roe

Patients with diabetes mellitus who present with acute ST-segment elevation myocardial infarction or non-ST-segment elevation acute coronary syndromes have a higher risk of adverse outcomes than patients without diabetes, and appear to derive greater benefit from evidence-based therapies. However, patients with diabetes mellitus are less commonly treated with proven therapies, so renewed efforts are needed to improve the quality of care and outcomes for patients with diabetes mellitus who present with acute coronary syndromes.

Diabetes Vasc Dis Res 2004;1:23-32.

POPULAR
TOPICREVIEWInitial experience with GLP-1 treatment on metabolic control and myocardial function in patients with type 2 diabetes mellitus and heart failure
Inga Thrainsdottir, Klas Malmberg, Arne Olsson, Mark Gutniak, Lars Rydén

Congestive heart failure (CHF) is a serious disease with a poor prognosis. Diabetes is an independent risk factor for CHF, probably in part due to disturbances in myocardial metabolism. Glucagon-like peptide-1 (GLP-1) causes glucose-dependent secretion of insulin, improving glycaemic control. In turn, this may improve myocardial metabolism and myocardial function.
The aim of the present study was to assess the feasibility and safety of three days’ infusion of recombinant GLP-1 in an open observational study in six patients with type 2 diabetes and CHF. The study included assessment of myocardial function.
There were no major complications of the infusion, and all patients completed the study protocol. Some improvement was observed in glycaemic state, and there was an insignificant trend towards improved myocardial function.
It is concluded that GLP-1 deserves further evaluation in such patients.

Diabetes Vasc Dis Res 2004;1:40-3.

ORIGINAL PAPERCommon polymorphisms in the glyoxalase-1 gene and their association with pro-thrombotic factors
Christopher P Gale, T Simon Futers, Lucinda KM Summers

Advanced glycation endproducts (AGEs) form at an accelerated rate in diabetes and contribute to the development of macrovascular disease. Their precursors are detoxified by the glyoxalase system. Perturbations of the glyoxalase-1 gene may alter AGEs' interactions and affect pro-thrombotic factors.
We screened the glyoxalase-1 gene for mutations and measured pro-thrombotic markers in 537 subjects from 89 healthy probands. Common single nucleotide polymorphisms (SNPs) were identified at positions -7 (C to T) and 20203 (C to A) from the translation start site. These SNPs were in Hardy-Weinberg equilibrium (CC=105, CA=266, AA=148; p>0.05; CC=126, CT=279, TT=114; p>0.05, respectively) and in linkage disequilibrium (D=27%, p<0.01), with mutant allele frequencies of 48% and 52% respectively.
A significant association was found between SNPs at position 20203 and PAI-1 antigen concentrations and -7 and factor XIII A2B2 complex (p=0.001 and p=0.042). After Bonferroni correction a significant association remained between the SNP at 20203 and PAI-1 concentrations (p=0.005), and after adjustment for pedigree the association accounted for 1.3% of its heritability (p=0.04). No significant associations were found for SNP -7 T to C and factor VII activity, tPa concentrations, fibrinogen concentrations or factor XIII concentrations and SNP 20203 C to A and factor VII concentrations, PAI-1 concentrations, tPa concentrations or fibrinogen concentrations.
Common variants in the glyoxalase-1 gene are associated with some pro-thrombotic factors, account for part of their heritability in healthy pedigrees and may alter susceptibility to macrovascular complications.

Diabetes Vasc Dis Res 2004;1:34-39.

POPULAR
TOPICORIGINAL PAPERPioglitazone plus a sulphonylurea or metformin is associated with increased lipoprotein particle size in patients with type 2 diabetes
Alfonso Perez, Mehmood Khan, Todd Johnson, Mahinda Karunaratne

To determine the effect of pioglitazone plus metformin or a sulphonylurea on lipoprotein particle size and subclass distribution in patients with type 2 diabetes.
Methods: Lipid profiles were determined for blood samples from patients participating in two randomised, double-blind, 24-week studies of pioglitazone 30 mg or 45 mg daily plus either metformin or a sulphonylurea.
Results: Samples from 177 patients were evaluated; 96 of these patients received a sulphonylurea, and 81 received metformin. Pioglitazone combination treatment produced significant increases from baseline for average and peak low-density lipoprotein (LDL) particle size at weeks 12 and 24 (p<0.0001 for each; range 0.29–0.39 nm for average and 0.36–0.55 nm for peak particle size, respectively). Significant shifts in high-density lipoprotein (HDL) and LDL distribution showed an increase in large particles and a decrease in small particles. For pioglitazone plus metformin, significant increases in levels of apolipoprotein (Apo) AI, Apo AI/AII-containing HDL, and lipoprotein(a) also were noted, whereas Apo B levels decreased.
Conclusions: These observed changes are thought to affect the atherogenic profile positively. Therefore, pioglitazone combination treatment may lead to decreased cardiovascular risk in patients with type 2 diabetes.

Diabetes Vasc Dis Res 2004;1:44-50.

COMMENTGlycation, receptor-mediated cell activation and vascular complications of diabetes
Paul J Thornalley

Diabetes Vasc Dis Res 2004;1:21-22.

COMMENTTreatment of CAD in patients with diabetes – what do we really know?
Dr Roberto A Corpus

Diabetes Vasc Dis Res 2004;1:33.

LETTERFluctuations in glycaemia in clinical diabetes mellitus type 2 are not associated with carotid intima-media thickening
Katharina Karrei, Carsta Koehler, Markolf Hanefeld, Theodora Temelkova-Kurktschiev, Stefano Del Prato

Diabetes Vasc Dis Res 2004;1:51-52.