Volume 4, Number 4, December 2007

EDITORIALCombating childhood type 2 diabetes mellitus: it will take a village
Darren K McGuire, Kathleen L Wyne

Diabetes Vasc Dis Res 2007;4:283-284.

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TOPICREVIEWEpidemiology of paediatric metabolic syndrome and type 2 diabetes mellitus

The epidemic in childhood obesity is a driving force behind the increase in paediatric metabolic syndrome, a collection of abnormalities that is associated in adults with increased risk for cardiovascular disease and type 2 diabetes mellitus. Although there is no clear consensus about the paediatric definition for metabolic syndrome, the prevalence of this syndrome is clearly rising. Children with metabolic syndrome are at increased risk for metabolic syndrome in adulthood. A late consequence of metabolic syndrome is type 2 diabetes, which increasingly affects adolescents. The rise in metabolic syndrome and type 2 diabetes in children is almost sure to lead to an increase in associated complications in young adulthood, including early cardiovascular disease. This epidemic will bear fruit in forthcoming decades, putting further stress on the healthcare system and probably leading to increased morbidity and a shorter lifespan for future generations.

Diabetes Vasc Dis Res 2007;4:285-296.

REVIEWVascular disease in paediatric type 2 diabetes: the state of the art
T Brooks Vaughan, Fernando Ovalle, Elaine Moreland

Type 2 diabetes is an emerging problem in the paediatric population. Paediatricians and paediatric endocrinologists are struggling with how to best assess, predict and treat cardiovascular risk factors in these patients. There is a notable lack of consensus in how to proceed, even among experts in the field. There are very limited data from quality trials in established paediatric type 2 diabetes. We address the available information regarding traditional and non-traditional indices of cardiovascular risk, including examination findings, biochemical markers and non-invasive imaging modalities. We discuss the utility and pitfalls of applying knowledge gained in adult medicine to the paediatric population. Potential treatment strategies are reviewed, including the currently available pharmaceutical options, with the acknowledgement that there are few drugs formally approved in the paediatric population.

Diabetes Vasc Dis Res 2007;4:297-304.

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TOPICREVIEWPhysical activity for the prevention and management of youth-onset type 2 diabetes mellitus: focus on cardiovascular complications
Jonathan Mcgavock, Elizabeth Sellers, Heather Dean

With the growing prevalence of childhood obesity and type 2 diabetes mellitus (T2DM) in youth, the challenge of cardiovascular disease risk management has entered the paediatric realm, affecting specialists, family physicians and allied healthcare professionals alike. Currently, there is little evidence to support optimal strategies for management of T2DM in youth and the associated cardiovascular complications. Physical activity plays a powerful role in the prevention and management of T2DM and cardiovascular disease in adults. This review will focus on the role of physical activity for the prevention of T2DM in youth and its associated cardiovascular complications. The first part describes the prevalence of cardiovascular risk factors in this cohort. The second part focuses on the role of physical activity in the prevention and management of T2DM in youth. Collectively, the limited intervention and observation studies published to date suggest that daily targets of 60–90 minutes of physical activity and less than 60 minutes of screen time (i.e. time spent in front of a television, computer or video games) are required for the prevention and management of T2DM in youth. Large-scale intervention studies are needed to determine the most effective physical activity strategies for the prevention and management of T2DM in youth.

Diabetes Vasc Dis Res 2007;4:305-310.

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TOPICREVIEWTargeting obesity to reduce the risk for type 2 diabetes and other co-morbidities in African American youth: a review of the literature and recommendations for prevention
Chinyelu O Nwobu, Carolyn C Johnson

Over the last decade, the prevalence of obesity has continued to rise within the adolescent population of the US. Data show that African American youth are disproportionately affected by the obesity epidemic due to their higher risk for obesity-related co-morbidities, such as type 2 diabetes. Interventions that target risk factors for obesity at the individual, family and community levels are needed in order to prevent the onset of type 2 diabetes and related complications. This article provides an overview of the prevalence of obesity and type 2 diabetes in African American youth, the pathophysiology of the disease, and the behavioural risk factors that have contributed to its high prevalence within the African American adolescent population. Successful intervention strategies that target modifiable risk factors, such as diet and physical activity, will be identified. Finally, recommendations for programmes to prevent the onset of type 2 diabetes within the African American adolescent population are presented.

Diabetes Vasc Dis Res 2007;4:311-319.

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TOPICREVIEWAtherosclerosis in type 2 diabetes: a role for fibrate therapy?
George Steiner

Vascular complications associated with type 2 diabetes confer significant morbidity and mortality. Atherosclerosis develops much earlier and progresses more rapidly than in subjects without diabetes. The clustering of cardiovascular risk factors associated with type 2 diabetes is mainly responsible for accelerated atherosclerotic disease. While statins remain the primary lipid-modifying therapy, the pharmacological profile of the fibrates suggests potential as an alternative or additional treatment for reducing the risk of atherosclerotic vascular complications in type 2 diabetes.

Diabetes Vasc Dis Res 2007;4:368-374.

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TOPICORIGINAL PAPERImpact of metabolic syndrome definitions on prevalence estimates: a study in a Portuguese community
Ana-Cristina Santos, Henrique Barros

This study compared the prevalence of metabolic syndrome (MS) according to World Health Organization (WHO), National Cholesterol Education Program Third Adult Treatment Panel (NCEP-ATP III), International Diabetes Federation (IDF) and American Heart Association/ National Heart, Lung and Blood Institute (AHA/NHLBI) definitions, to evaluate how well the different classifications agreed. The study also compared their 10-year predicted risk of coronary heart disease (CHD) with the Framingham risk score (FRS).
Some 886 women and 547 men aged 18–92 years were included in the study. Demographic and personal medical history data were obtained at interview. Four operational definitions of MS were used (those of the WHO, NCEP-ATP III, AHA/NHLBI and IDF).
The prevalence of metabolic syndrome was found to be 26.4% (WHO criteria), 24.0% (NCEP-ATP III criteria), 41.9% (IDF criteria) and 37.2% (AHA/NHLBI criteria). According to the definition used, central obesity ranged from 41.9% to 75.1% and high blood pressure from 52.9% to 65.8%. Agreement between classifications ranged from 75.2% (κ=0.47) to 90.4% (κ=0.80) and was lower in males. The 10-year predicted risk of CHD by FRS was similar between the different definitions.
IDF and AHA/NHLBI definitions resulted in a higher prevalence of MS than the NCEP-ATP III or WHO definition. Overall, however, good agreement was found between definitions, and the predicted 10-year of CHD risk was similar.

Diabetes Vasc Dis Res 2007;4:320-327.

ORIGINAL PAPERLevels of adiponectin, C-reactive protein and interleukin-1 receptor antagonist are associated with the relative change in body mass index between childhood and adulthood
Juha Saltevo, Mauno Vanhala, Hannu Kautiainen, Markku Laakso

Obesity has been related to subclinical inflammation and decreased levels of adiponectin. We examined the relationship between inflammatory markers and adiponectin and the change in body mass index (BMI) between childhood and adulthood. Our study included 368 subjects (176 men and 192 women) from a population-based cohort whose weight and height had been recorded at the age of seven years. They participated in this study as adults (with a mean age of 46 years); levels of adiponectin, interleukin-1 receptor antagonist (IL-1 Ra) and high-sensitivity C-reactive protein (hs-CRP) were measured. The relative change of BMI from childhood to adulthood was significantly associated with levels of IL-1 Ra (men: r=0.27 [95% CI: 0.12 to 0.40] and women: 0.64 [0.55 to 0.72]), hs-CRP (r=0.15 and 0.52, respectively) and adiponectin (r=-0.13 and -0.29, respectively) in both genders.
Decreased levels of adiponectin and elevated levels of IL-1 Ra and hs-CRP at adulthood appear to be related to the change in BMI between childhood and adulthood.

Diabetes Vasc Dis Res 2007;4:328-331.

ORIGINAL PAPERDouble-edged relationship between adiposity and coronary artery calcification in type 1 diabetes
Baqiyyah Conway, Rachel G Miller, Tina Costacou, Linda Fried, Sheryl Kelsey, Rhobert W Evans, Daniel Edmundowicz, Trevor J Orchard

Coronary artery disease (CAD), a leading cause of death in type 1 diabetes (T1D), often occurs two or more decades earlier in this population compared to the population without diabetes. Although CAD generally increases with adiposity, this association is unclear in T1D. In this study, we examined associations of adiposity with coronary artery calcium (CAC) in 315 individuals with T1D.
Mean age and diabetes duration were 42 and 34 years, respectively, at study entry. CAC, visceral adiposity (VAT) and subcutaneous adiposity (SAT) were determined by electron beam tomography; and BMI and waist circumference (WC) were determined.
The presence of CAC was positively associated with VAT, SAT and BMI in men (p<0.05) and with all four adiposity measures in women (p<0.05) after adjustment for age and other traditional cardiovascular risk factors. However, after adjustment, the degree of CAC was not associated with any of the four adiposity measures, with the exception of SAT in women. Women in the lowest tertile of SAT had more CAC than those in the second tertile (p<0.016).
Adiposity was positively associated with the presence of CAC, but the relationship with its severity was either inverse or non-existent. This double-edged association emphasises the complex relationship between adiposity and cardiovascular risk in diabetes.

Diabetes Vasc Dis Res 2007;4:332-339.

ORIGINAL PAPEREffective cut-off values of waist circumference to detect the clustering of cardiovascular risk factors of metabolic syndrome in Japanese men and women
Jung Su Lee, Kiyoshi Kawakubo, Katsumi Mori, Akira Akabayashi

The purpose of this study was to determine effective cut-off values of waist circumference (WC) to detect the clustering of cardiovascular risk factors (CCRF) in a Japanese population. The subjects were 2,476 men and women who participated in a health examination in Tokyo. The CCRF was defined according to the International Diabetes Federation (IDF) and the Japanese Committee of the Criteria for Metabolic Syndrome (JCCMS). The effective (accurate and sensitive) values were tested using the receiver operating characteristics analysis. The accurate (maximised sensitivity plus specificity) values were 81 cm and 80 cm using the IDF and JCCMS criteria for men, and 82 cm for both criteria for women. From the ROC curve, 85 cm was identified as an effective value for men. Thus, the effective cut-off value of WC for the Japanese should be ~85 cm for men and ~82 cm for women.

Diabetes Vasc Dis Res 2007;4:340-345.

ORIGINAL PAPERAdmission glycaemia and outcome in patients with acute coronary syndrome
Damaris Müdespacher, Dragana Radovanovic, Edoardo Camenzind, Manfred Essig, Osmund Bertel, Paul Erne, Franz Robert Eberli, Felix Gutzwiller On Behalf Of The Amis Plus Investigators

Some studies of patients with acute myocardial infarction have reported that hyperglycaemia at admission may be associated with a worse outcome. This study sought to evaluate the association of blood glucose at admission with the outcome of unselected patients with acute coronary syndrome (ACS).
Using the Acute Myocardial Infarction and unstable angina in Switzerland (AMIS Plus) registry, ACS patients were stratified according to their blood glucose on admission: group 1: 2.80–6.99 mmol/L, group 2: 7.00–11.09 mmol/L and group 3: > 11.10 mmol/L. Odds ratios for in-hospital mortality were calculated using logistic regression models.
Of 2,786 patients, 73% were male and 21% were known to have diabetes. In-hospital mortality increased from 3% in group 1 to 7% in group 2 and to 15% in group 3. Higher glucose levels were associated with larger enzymatic infarct sizes (p<0.001) and had a weak negative correlation with angiographic or echographic left ventricular ejection fraction. High admission glycaemia in ACS patients remains a significant independent predictor of in-hospital mortality (adjusted OR 1.08; 95% confidence intervals [CI] 1.05–1.14, p<0.001) per mmol/L. The OR for in-hospital mortality was 1.04 (95% CI 0.99–1.1; p=0.140) per mmol/L for patients with diabetes but 1.21 (95% CI 112–1.30; p<0.001) per mmol/L for non-diabetic patients.
In conclusion, elevated glucose level in ACS patients on admission is a significant independent predictor of in-hospital mortality and is even more important for patients who do not have known diabetes.

Diabetes Vasc Dis Res 2007;4:346-352.

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TOPICORIGINAL PAPERThe European Perspective on Diabetes Prevention: development and Implementation of A European Guideline and training standards for diabetes prevention (IMAGE)
Peter EH Schwarz, Ulrike Gruhl, Stefan R Bornstein, Rüdiger Landgraf, Michael Hall, JaakKo Tuomilehto

The prevalence of type 2 diabetes has increased dramatically in Europe, particularly in younger people. Nevertheless, jointly developed prevention strategies are still lacking. The development and Implementation of A European Guideline and training standards for diabetes prevention (IMAGE) project was initiated by the Technical University Dresden in response to this major public health concern of the European Union.
Within the IMAGE project, four specific objectives will be developed and implemented into clinical practice: a) joint European guidelines; b) a European training curriculum for prevention managers; c) European standards for quality control of diabetes prevention programmes; and d) a European e-health training portal for prevention managers.
This three-year-project began in June 2007. At the time of writing, 32 institutions from 16 countries have become involved.
The development of competent guidelines and education programmes, as well as the establishment of quality standards for the primary prevention of type 2 diabetes, should significantly enhance the ability of healthcare professionals to respond swiftly to its drastic increase and its burden to society.

Diabetes Vasc Dis Res 2007;4:353-357.

ORIGINAL PAPERBeneficial effects of ramipril on myocardial diastolic function in patients with type 2 diabetes mellitus, normal LV systolic function and without coronary artery disease: a prospective study using tissue Doppler
Thorsten Siegmund, Petra-Maria Schumm-Draeger, Diethmar Antoni, Helene Von Bibra

Angiotensin-converting enzyme (ACE) inhibitors can improve cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM). Myocardial diastolic function (Ve) is a known marker of cardiovascular prognosis. It could potentially indicate the effects of preventive therapy if evaluated by tissue Doppler. We tested the hypothesis that treatment with the ACE inhibitor ramipril has beneficial effects on Ve. In this study, 16 subjects on insulin therapy (eight receiving 10 mg ramipril/day compared to eight matched controls who were not treated with an ACE inhibitor) were followed up for a period of nine months. Myocardial and vascular function were assessed by tissue Doppler and ultrasound.
In the ramipril group, Ve improved significantly after nine months of treatment (7.8+0.9 cm/s to 8.6+0.9 cm/s, p<0.04). Systolic blood pressure and intima media thickness (IMT) demonstrated a trend towards improvement. In controls, Ve remained unchanged and there was a trend towards deterioration in stiffness index beta (p<0.07).
In conclusion, the observed improvement of myocardial diastolic function with ramipril in patients with T2DM is an encouraging result. It might contribute to the overall improvement that has been observed with hard cardiovascular end points.

Diabetes Vasc Dis Res 2007;4:358-364.

ORIGINAL PAPERMicroalbuminuria and the metabolic syndrome in non-diabetic black Africans
Ikechi G Okpechi, Michael D Pascoe, Charles R Swanepoel, Brian L Rayner

It is recognised that the metabolic syndrome promotes the development of cardiovascular disease. Although several studies have shown a relationship between the metabolic syndrome and kidney disease, few of these have used non-diabetic subjects, especially in the African population.
This was a cross-sectional study of subjects of African origin, using the metabolic syndrome (MS) criteria of the National Cholesterol Education Program (NCEP) third Adult Treatment Panel (ATP III). Subjects with impaired fasting glucose, with two-hour glucose > 11.1 mmol/L after a glucose tolerance test, were excluded. Spot urine for albumin-to-creatinine ratio (ACR) was measured and the glomerular filtration rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) equation. Microalbuminuria was defined as ACR between 3–30 mg/mmol.
There was a significant decline in GFR and a significant increase in ACR with increasing number of MS traits. ACR increased four-fold between subjects with no MS traits and those with four or more traits. In subjects with the metabolic syndrome, there was a significant correlation between ACR and systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting glucose. Estimated GFR correlated significantly and inversely with body mass index (BMI) and serum leptin.
These observations raise major clinical and public health concerns for developing countries, where both the metabolic syndrome and kidney disease are being reported more and more frequently. The potential economic impact is huge.

Diabetes Vasc Dis Res 2007;4:3565-367.

LETTERWaist circumference in type 2 diabetes: is routine measurement helpful?
Jyothis T George, Jonathan C Thow, Paul E Jennings, Vijay Jayagopal,

Diabetes Vasc Dis Res 2007;4:375-376.