Volume 1, Number 2, October 2004

POPULAR
TOPICEDITORIALObesity, adipocytes and squirrels
Peter J Grant

Diabetes Vasc Dis Res 2004;1:67.

POPULAR
TOPICREVIEWThe metabolic syndrome: one step forward, two steps back
Sun H Kim, Gerald M Reaven

Individuals with insulin resistance are at increased risk of glucose intolerance, dyslipidaemia and essential hypertension. In 1988, it was proposed that this cluster of abnormalities associated with insulin resistance identifies individuals at increased risk for cardiovascular disease. Recently, in an effort to raise awareness of this problem, both the World Health Organisation (WHO) and the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program have suggested a set of clinical criteria to diagnose individuals with what they both refer to as the metabolic syndrome. Although using the same term, the two groups have different goals for creating this diagnosis and different criteria to identify individuals, which relate to their different institutional goals. This review critically evaluates the similarities and differences between the two groups’ concepts of the metabolic syndrome and questions the clinical utility of making the diagnosis with either set of definitions.

Diabetes Vasc Dis Res 2004;1:68-75.

POPULAR
TOPICREVIEWInsulin resistance and cardiovascular disease: the role of PPARγ activators beyond their anti-diabetic action
Daniel Walcher, Nikolaus Marx

Over the past few years it has been recognised that insulin resistance (IR) is an independent risk factor for major cardiovascular events. In addition, IR is associated with other factors such as hypertension, dyslipidaemia and endothelial dysfunction, and this cluster of metabolic disorders contributes to the cardiovascular risk of patients with IR. Given the increasing number of patients with IR, the modulation of their cardiovascular risk is a major task in diabetology and vascular medicine. This review will focus on the role of IR as a cardiovascular risk factor and on the potential of activators of the nuclear transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) to modulate these risk factors associated with IR.

Diabetes Vasc Dis Res 2004;1:76-81.

ORIGINAL PAPEREffects of low-dose continuous combined HRT on vascular function in women with type 2 diabetes
Andrew FB Kernohan, Angela Spiers, Naveed Sattar, Chris Hillier, Steve J Cleland, Michael Small, Mary-Ann Lumsden, John MC Connell, John R Petrie

Background: Improvement in vascular endothelial function is widely cited as a beneficial effect of hormone replacement therapy (HRT). Women with type 2 diabetes (T2DM) are at increased cardiovascular risk and have impaired endothelial function. Any benefits of HRT on endothelial function in this group are of particular interest.
Objectives: We assessed effects on vascular function of oral 17β oestradiol (1 mg) and norethisterone (0.5 mg) in postmenopausal women with T2DM.
Design: Double-blind, randomised, placebo-controlled trial. Assessments: Twenty-eight women had pulse wave velocity (PWV) and adhesion molecules VCAM-1 and ICAM-1 assessed before and after three months’ treatment. Twenty-four women also had gluteal fat biopsy for assessment of resistance vessel function (using wire myography).
Results: HRT did not affect PWV, VCAM-1, ICAM-1 or carbachol response. Effects of L-NAME and indomethacin on carbachol sensitivity were similar in both groups.
Conclusions<:/i> This HRT preparation had no detectable effect on these measures of endothelial function in women with T2DM.

Diabetes Vasc Dis Res 2004;1:82-88.

ORIGINAL PAPEREnhanced left ventricular systolic function early in type 2 diabetic mice: clinical implications
Jorge A Alvarez, Maricela Reyes, Daniel Escobedo, Gregory L Freeman, Mark E Steinhelper, Marc D Feldman

It is unclear whether the increase in availability of substrates for energy production in diabetes can lead to enhanced systolic function early in the disease, before the onset of structural changes to the myocardium. To examine this issue, BKS.Cg-m +/+ Lepr ^db (db/db) mice with type 2 diabetes and wild type controls had left ventricular pressure-volume relationships determined in situ. We demonstrated that the db/db mice, when compared to their wild type controls, generated greater left ventricular pressure and an enhancement of left ventricular systolic function based on enhanced power/EDV, positive dP/dt, preload recruitable stroke work, dP/dt – EDV relationship, and curvilinear end-systolic elastance. This enhancement in systolic function occurred despite the db/db mice having greater body weight, but similar preload (end-diastolic volume) and afterload (effective arterial elastance).
We postulate that the previously described enhancement in renal glomerular filtration rate seen early in type 2 diabetes may be in part due to enhanced left ventricular systolic function early in this disease.

Diabetes Vasc Dis Res 2004;1:89-94.