Volume 5, Number 1, March 2008

POPULAR
TOPICEDITORIALDiabetes mellitus and vascular disease: targeting cardiometabolic risk
Peter J Grant

Diabetes Vasc Dis Res 2008;5:7-8.

POPULAR
TOPICREVIEWThe importance of treating cardiometabolic risk factors in patients with type 2 diabetes
Anthony H Barnett

Cardiometabolic risk factors are the combined vascular and metabolic components of risk that may lead to a cardiovascular event. There are numerous such factors. Underlying the concept of cardiometabolic risk is an association with excess visceral fat, leading to the dysregulation of the adipokines, the signalling proteins derived from adipose tissue. Changes in the levels of the adipokines – tumour necrosis factor-a, cholesteryl ester transfer protein and adiponectin, for example – can lead to alterations in insulin sensitivity and high-density lipoprotein cholesterol metabolism. At present, specific cardiometabolic risk factors are commonly managed on an individual basis. We are now moving from the era of single risk factor intervention, however, to multiple risk factor intervention in people at high cardiovascular risk, with the additional possibility of using new drug classes to target the underlying cardiometabolic problems more effectively.

Diabetes Vasc Dis Res 2008;5:9-14.

POPULAR
TOPICREVIEWBlocking the renin-angiotensin-aldosterone system to prevent diabetes mellitus
Darren K McGuire, Jeffrey R Winterfield, Jason A Rytlewski, Ele Ferrannini

Type 2 diabetes mellitus (DM) is increasing around the world, and the public health impact of DM, driven largely by cardiovascular disease complications, underpins the importance of continued efforts toward primary prevention of DM. Only a few interventions have been shown to prevent DM, with none of them yet proven to improve cardiovascular risk commensurately. Accumulating evidence suggest that drugs that block the renin-angiotensin-aldosterone system (RAAS), many of which have proven cardiovascular disease (CVD) benefit, also have favourable effects on parameters of glucose metabolism and incident diabetes. Here we review the evidence accumulated to date from animal studies, clinical mechanistic studies and clinical trials regarding the effect of RAAS inhibition and incident DM.

Diabetes Vasc Dis Res 2008;5:59-66.

POPULAR
TOPICORIGINAL PAPERElevated serum ferritin concentrations in prediabetic subjects
Faranak Sharifi, N Mousavi Nasab, H Jazebi Zadeh

Background: Few data are available on the association of variables of the insulin resistance syndrome and serum ferritin, an indicator of body iron stores. We examined the relationship between serum ferritin levels and impaired fasting glucose, a pre-diabetes stage associated with insulin resistance, in this study.
Subjects & methods: One hundred and eighty seven people, including 91 subjects with impaired fasting glucose (IFG) and 96 healthy people who were well matched for age and sex, were enrolled. Body mass index (BMI) and blood pressure of the participants were measured and serum cholesterol, triglyceride, white blood cells (WBC) count, C-reactive protein (CRP) and ferritin were evaluated. All the data were analysed by t-test, χ2 test and analysis of variance.
Results: The IFG group had higher serum ferritin concentrations (85.5+6.6 µg/L vs. 49.4+3.7 µg/L, p=0.001). A positive correlation was found between fasting plasma glucose and serum ferritin (r=0.29, p=0.001). Using multiple regression analysis, we found an association between serum ferritin and blood pressure (0.15, p=0.01), FPG (0.29, p=0.001), triglyceride (0.08, p=0.01) and cholesterol (0.07, p=0.03). The odds ratio for the association of IFG in male subjects with a high serum ferritin level was 8.3 (95% CI: 1.2–11.9, p=0.01) and for females was 3.06 (95% CI: 0.58–15, p=0.1).
Conclusion: Based on the data from our study, aelevation in serum ferritin can be seen in pre-diabetes stage, before the occurrence of an overt diabetes mellitus.

Diabetes Vasc Dis Res 2008;5:15-18.

ORIGINAL PAPERAminoterminal pro-brain natriuretic peptide (NT-proBNP) and sleep-disordered breathing in morbidly obese females: a cross-sectional study
Juan Ybarra, Francesc Planas, Jose M Pou

Sleep-disordered breathing (SDB) is often encountered in morbid obesity (MO) in conjunction with insulin resistance (IR). Aminoterminal pro-brain natriuretic peptide (NT-proBNP) is a promising marker for left ventricular dysfunction (LVD) in MO. We sought to explore the factors that may influence the relationships of SDB and IR with NT-proBNP in MO women.
We performed a cross-sectional pilot study involving 110 asymptomatic MO (44.5+0.7 kg/m2) young women. SDB risk was assessed using a modified version of the Berlin Questionnaire (BQ). IR was assessed using the homeostasis model assessment (HOMA) index and adiponectin levels. LVD was assessed using NT-proBNP and echocardiograms.
In this study, NT-proBNP levels and LVD increased significantly along the BQ strata. Multiple regression analysis identified BQ and log-transformed HOMA as the independent variables predicting as much as 48.0% of the variability of logNT-proBNP.
In conclusion, NT-pro-BNP levels are independently predicted by SDB and IR in asymptomatic MO women. Larger prospective studies are warranted.

Diabetes Vasc Dis Res 2008;5:19-24.

ORIGINAL PAPERBeneficial effects of strategies for primary prevention of diabetes on cardiovascular risk factors: results of the Indian Diabetes Prevention Programme
Chamukuttan Snehalatha, Simon Mary, Vasant V Joshi, Ambady Ramachandran

In subjects with impaired glucose tolerance (IGT) who participated in the Indian Diabetes Prevention Programme (IDPP), abnormalities related to body mass index, waist circumference (WC), blood pressure (BP), lipid profile and electrocardiography were analysed (at baseline and third-year follow-up) in control, lifestyle modification (LSM), metformin (MET) and LSM + MET groups.
At baseline, elevated levels of low-density lipoprotein cholesterol (LDL-C) showed the highest (78.6%) and total cholesterol (TC) showed the lowest (42%) prevalence. At follow-up, prevalence of hypertension (BP > 130/> 85 mmHg) had increased significantly in all groups. Cardiovascular abnormalities were lower in intervention groups, with the lowest rates in the MET group (p=0.013 vs. control); the LDL–C level decreased in intervention groups.
In this programme, Asian Indian IGT subjects were observed to have a high prevalence of cardiovascular risk factors. LSM and MET had beneficial effects on the atherogenic phenotype of lipids but had no influence on blood pressure.

Diabetes Vasc Dis Res 2008;5:25-29.

ORIGINAL PAPERDetection and characterisation of microcirculatory abnormalities in the skin of diabetic patients with microvascular complications
Belinda A Brooks, Susan V Mclennan, Stephen M Twigg, Dennis K Yue

The aim of this study was to characterise microvascular blood flow in the skin and to compare it with biomarkers of endothelial dysfunction and tissue inflammation in patients with type 2 diabetes with (n=20) or without (n=20) microvascular complications and 20 control subjects. Microvascular function was measured by laser Doppler velocimetry in combination with iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP). Blood was collected for measurement of biomarkers including plasminogen activator inhibitor-1 (PAI-1), soluble intercellular adhesion molecule (sICAM), soluble vascular cell adhesion molecule (sVCAM) and high-sensitivity C-reactive protein (hsCRP).
Both ACh and SNP responses fall progressively with the development of diabetes and microvascular complications. For the total cohort, there was a significant overall correlation between ACh and SNP response (r=0.7, p<0.0001), and this relationship was particularly strong in those with microvascular complications. There was a trend towards higher hsCRP levels across the three groups, but no difference in other biomarkers.<
Abnormalities of microvascular blood flow are evident in diabetes and become more marked with the development of microvascular complications. This relationship was similar to that shown by the marker of inflammation (hsCRP), but stronger than that pertaining to biomarkers of endothelial function. As both ACh and SNP responses are attenuated, the disturbance is not characteristic of endothelial dysfunction alone.

Diabetes Vasc Dis Res 2008;5:30-35.

POPULAR
TOPICORIGINAL PAPERMetabolic syndrome in the Philippine general population: prevalence and risk for atherosclerotic cardiovascular disease and diabetes mellitus
Dante D Morales, Felix Eduardo R Punzalan, Elizabeth Paz-Pacheco, Rody G Sy, Charmaine A Duante For The National Nutrition And Health Survey (Nnhes): 2003 Group

The objectives of this study were to determine the prevalence of metabolic syndrome (MS) and its component risk factors among Filipinos using three sets of criteria and to evaluate the association between MS and atherosclerotic cardiovascular disease and diabetes mellitus. The study utilised a multi-staged cluster sampling design.
The prevalence of MS was found to be 11.9% by National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP III) criteria, 14.5% by International Diabetes Federation (IDF) criteria and 18.6% by NCEP/ATP III criteria modified by the American Heart Association/National Heart, Lung and Blood Institute (NCEP/ATP III-AHA/NHLBI) criteria. Low levels of high-density lipoprotein cholesterol (HDL-C) occurred in 60.2% of men and 80.9% of women. Abdominal obesity was noted in 17.7% of men and 35.1% of women. Blood pressure (BP) > 130/85 mmHg was seen in 33.3%, hypertriglyceridaemia in 20.6% and fasting blood sugar > 100 mg/dL (5.55 mmol/L) in 7.1%. Age-adjusted odds ratios showed that MS, by all three definitions, predisposed an individual to diabetes mellitus (DM) and stroke while MS by the IDF definition predisposed an individual to myocardial infarction (MI). Individuals with MS did not have a significant predisposition to angina and peripheral artery disease (PAD).
Thus, the metabolic syndrome is common in Filipinos, with low HDL-C as the most prevalent component. The metabolic syndrome predisposes to diabetes mellitus and stroke, with a tendency to MI using the IDF criteria.

Diabetes Vasc Dis Res 2008;5:36-43.

ORIGINAL PAPERCharacterisation of atherosclerotic lesions with scanning electron microscopy (SEM) of wet tissue
Yehuda Kamari, Hofit Cohen, Aviv Shaish, Rafael Bitzur, Arnon Afek, Shlomzion Shen, Anya Vainshtein, Dror Harats

Atherosclerotic cardiovascular disease (CVD) is the universal leading cause of mortality and a major cause of morbidity. Additionally, the global epidemic of diabetes is associated with considerable cardiovascular mortality risk due to accelerated premature atherosclerosis.
Development of effective therapies for atherosclerosis is dependent upon improved tools to assess atherosclerotic lesion progression in animal models. We present a novel technique that utilises scanning electron microscopy (SEM) for imaging wet biological specimens, thus enabling rapid and high-resolution imaging of atherosclerotic lesions. This wet SEM technique was used in an apoE-deficient mice model for morphological characterisation of early and advanced atherosclerotic lesions. Further demonstration of lipid-rich atherosclerotic lesions was carried out with osmium tetroxide staining for cholesterol. Gold immunolabelling of specific epitopes was applied in identification of the cellular and molecular components within the atherosclerotic lesions, namely foam cells, smooth muscle cells and collagen.
The wet SEM technique demonstrates an accurate and detailed structural evaluation of the pathological process of atherosclerosis. Understanding the mechanisms that precipitate the atherosclerotic process, utilising this novel technique, may assist in the development of innovative therapeutic interventions for CVD management and prevention in the general population and in those with diabetes.

Diabetes Vasc Dis Res 2008;5:44-47.

ORIGINAL PAPERDrinking modulates monocyte migration in healthy subjects: a randomised intervention study of water, ethanol, red wine and beer with or without alcohol
Armin Imhof, Roza Blagieva, Nikolaus Marx, Wolfgang Koenig

Moderate alcohol consumption is associated with reduced cardiovascular mortality compared to non-consumption of alcohol and heavy drinking. Experimental data suggest a direct effect of alcohol on atherosclerotic lesion development. We assessed the effect of consumption of moderate amounts of alcoholic and non-alcoholic beverages on monocyte migration, a crucial step in atherogenesis.
Forty-nine healthy men and women (aged 22–56 years) were enrolled in this randomised controlled trial. After wash-out, participants were assigned to either ethanol (concentration 12.5%), beer (5.6%) or red wine (12.5%) equivalent to 30 grams of ethanol per day (g/d) for men and 20 g/d for women, or to the same amount of de-alcoholised beer or red wine, or to water. Monocyte migration was evaluated ex vivo using a modified Boyden chamber.
Intake of ethanol or de-alcoholised red wine significantly reduced monocyte chemoattractant protein-1 (MCP-1)-induced monocyte migration by 58% (p<0.05; n=6) and 36% (p<0.05; n=7) and FMLP (N-formyl-methionyl-leucyl-phenylalanine)-induced migration by 41% (p<0.05) and 36% (p<0.05), respectively. MCP-1 receptor expression was not affected by these interventions, as shown by flow cytometry.
Short-term intervention with moderate amounts of ethanol and de-alcoholised red wine inhibits monocyte migration ex vivo. This might represent one mechanism by which alcoholic beverages lower cardiovascular risk.

Diabetes Vasc Dis Res 2008;5:48-53.

SHORT REPORTPatients with the metabolic syndrome and a disturbed cortisol balance display more microalbuminuria
Sarah F Janssen, Theodorus B Twickler, Christel Jublanc, Maarten J Cramer, Eric Bruckert

The objective of this study was to investigate whether patients with the metabolic syndrome (MetS) and an imbalance in cortisol metabolism express increased urinary albumin excretion compared to those patients with metabolic syndrome alone.
Seventy-four patients with MetS were evaluated using a low-dose dexamethasone suppression test (LDDST) to identify disturbed cortisol balance (cortisol levels > 50 nmol/L after LDDST). The level of albumin in the urine was also evaluated.
Disturbed cortisol balance was found in 8% of all evaluated patients with MetS. Microalbuminuria was present significantly more often (p<0.01) in those patients with MetS and an imbalance in cortisol metabolism compared with patients suffering MetS alone (urine albumin: 210 mg/L vs. 26 mg/L, respectively, p<0.01).
A substantial percentage of patients with MetS had inappropriate cortisol homeostasis. Of importance, excretion of urinary albumin was increased in these patients. This observation may indicate that this subgroup within the MetS population has a higher cardiovascular risk and possible increased endothelial dysfunction, with a subsequent need for stricter control to prevent cardiovascular morbidity and mortality.

Diabetes Vasc Dis Res 2008;5:54-58.