Pregnancy complications and maternal cardiovascular risk: opportunities for intervention and screening?

The link between defective nutrition of the fetus and vascular disease in later life is now well established. Naveed Sattar and Ian Greer report on the intriguing probability that complications in pregnancy also predispose mothers to later vascular and metabolic disease

Ethnicity-specific obesity cut-points in the development of Type 2 diabetes - a prospective study including three ethnic groups in the United Kingdom

Aims: Conventional definitions of obesity, e.g. body mass index (BMI) ≥ 30 kg/m2 or waist circumference cut-points of 102 cm (men) and 88 cm (women), may underestimate metabolic risk in non-Europeans. We prospectively identified equivalent ethnicity-specific obesity cut-points for the estimation of diabetes risk in British South Asians, African-Caribbeans and Europeans. Methods: We studied a population-based cohort from London, UK (1356 Europeans, 842 South Asians, 335 African-Caribbeans) who were aged 40–69 years at baseline (1988–1991), when they underwent anthropometry, fasting and post-load (75 g oral glucose tolerance test) blood tests. Incident Type 2 diabetes was identified from primary care records, participant recall and/or follow-up biochemistry. Ethnicity-specific obesity cut-points in association with diabetes incidence were estimated using negative binomial regression. Results: Diabetes incidence rates (per 1000 person years) at a median follow-up of 19 years were 20.8 (95% CI: 18.4, 23.6) and 12.0 (8.3, 17.2) in South Asian men and women, 16.5 (12.7, 21.4) and 17.5 (13.0, 23.7) in African-Caribbean men and women, and 7.4 (6.3, 8.7), and 7.2 (5.3, 9.8) in European men and women. For incidence rates equivalent to those at a BMI of 30 kg/m2 in European men and women, age- and sex-adjusted cut-points were: South Asians, 25.2 (23.4, 26.6) kg/m2; and African-Caribbeans, 27.2 (25.2, 28.6) kg/m2. For South Asian and African-Caribbean men, respectively, waist circumference cut-points of 90.4 (85.0, 94.5) and 90.6 (85.0, 94.5) cm were equivalent to a value of 102 cm in European men. Waist circumference cut-points of 84.0 (74.0, 90.0) cm in South Asian women and 81.2 (71.4, 87.4) cm in African-Caribbean women were equivalent to a value of 88 cm in European women. Conclusions: In prospective analyses, British South Asians and African-Caribbeans had equivalent diabetes incidence rates at substantially lower obesity levels than the conventional European cut-points

Association between grip strength and diabetes prevalence in black, South Asian, and white European ethnic groups: a cross-sectional study of 418,656 UK Biobank participants

Aims: To quantify the extent to which ethnic differences in muscular strength might account for the substantially higher prevalence of diabetes in black and South-Asian compared with white European adults. Methods: This cross-sectional study used baseline data from the UK Biobank study on 418 656 white European, black and South-Asian participants, aged 40–69 years, who had complete data on diabetes status and hand-grip strength. Associations between hand-grip strength and diabetes were assessed using logistic regression and were adjusted for potential confounding factors. Results: Lower grip strength was associated with higher prevalence of diabetes, independent of confounding factors, across all ethnicities in both men and women. Diabetes prevalence was approximately three- to fourfold higher in South-Asian and two- to threefold higher in black participants compared with white European participants across all levels of grip strength, but grip strength in South-Asian men and women was ~5–6 kg lower than in the other ethnic groups. Thus, the attributable risk for diabetes associated with low grip strength was substantially higher in South-Asian participants (3.9 and 4.2 cases per 100 men and women, respectively) than in white participants (2.0 and 0.6 cases per 100 men and women, respectively). Attributable risk associated with low grip strength was also high in black men (4.3 cases) but not in black women (0.4 cases). Conclusions: Low strength is associated with a disproportionately large number of diabetes cases in South-Asian men and women and in black men. Trials are needed to determine whether interventions to improve strength in these groups could help reduce ethnic inequalities in diabetes prevalence

Allopurinol use yields potentially beneficial effects on inflammatory indices in those with recent ischemic stroke: a randomized, double-blind, placebo-controlled trial

<p><b>Background and Purpose</b>: Elevated serum uric acid level is associated with poor outcome and increased risk of recurrent events after stroke. The xanthine oxidase inhibitor allopurinol lowers uric acid but also attenuates expression of inflammatory adhesion molecules in murine models, reduces oxidative stress in the vasculature, and improves endothelial function. We sought to investigate whether allopurinol alters expression of inflammatory markers after acute ischemic stroke.</p> <p><b>Methods</b>: We performed a randomized, double-blind, placebo-controlled trial to investigate the safety, tolerability, and effect of 6 weeks’ treatment with high- (300 mg once a day) or low- (100 mg once a day) dose allopurinol on levels of uric acid and circulating inflammatory markers after ischemic stroke.</p> <p><b>Results</b>: We enrolled 50 patients with acute ischemic stroke (17, 17, and 16 in the high, low, and placebo groups, respectively). Mean (±SD) age was 70 (±13) years. Groups had similar characteristics at baseline. There were no serious adverse events. Uric acid levels were significantly reduced at both 7 days and 6 weeks in the high-dose group (by 0.14 mmol/L at 6 weeks, P=0.002). Intercellular adhesion molecule-1 concentration (ng/mL) rose by 51.2 in the placebo group, rose slightly (by 10.6) in the low-dose allopurinol group, but fell in the high-dose group (by 2.6; difference between groups P=0.012, Kruskal-Wallis test).</p> <p><b>Conclusion</b>: Allopurinol treatment is well tolerated and attenuates the rise in intercellular adhesion molecule-1 levels seen after stroke. Uric acid levels were lowered with high doses. These findings support further evaluation of allopurinol as a preventive measure after stroke.</p&gt

Waist-to-height ratio and cardiometabolic risk factors in adolescence: findings from a prospective birth cohort

What is already known about this subject In adults, associations between body mass index (BMI), waist-to-height ratio (WHtR) and cardiometabolic outcomes are similar. In children and adolescents, results from cross-sectional studies examining the associations between BMI z scores, WHtR and cardiometabolic outcomes are conflicting and there is a paucity of prospective data.<p></p> What this study adds This is the first study to demonstrate the prospective association between WHtR in childhood and cardiometabolic outcomes in adolescent boys. WHtR is a simple calculation that can be used to identify children and adolescents for cardiometabolic risk without the need for reference growth charts. The WHtR cut-point of ≥0.5 was highly specific in identifying cardiometabolic risk co-occurrence but has poor sensitivity.<p></p> Objective To examine the associations between body mass index (BMI) and waist-to-height ratio (WHtR) measured in childhood and adolescence and cardiometabolic risk factors in adolescence.<p></p> Methods Secondary data analysis of the Avon Longitudinal Study of Parents and Children, a population based cohort. Data from 2858 adolescents aged 15.5 (standard deviation 0.4) years and 2710 of these participants as children aged 7–9 years were used in this analysis. Outcome measures were cardiometabolic risk factors, including triglycerides, low density lipoprotein cholesterol, high density lipoprotein cholesterol, insulin, glucose and blood pressure at 15 years of age.<p></p> Results Both BMI and WHtR measured at ages 7–9 years and at age 15 years were associated with cardiometabolic risk factors in adolescents. A WHtR ≥0.5 at 7–9 years increased the odds by 4.6 [95% confidence interval 2.6 to 8.1] for males and 1.6 [0.7 to 3.9] for females of having three or more cardiometabolic risk factors in adolescence. Cross-sectional analysis indicated that adolescents who had a WHtR ≥0.5, the odds ratio of having three or more cardiometabolic risk factors was 6.8 [4.4 to 10.6] for males and 3.8 [2.3 to 6.3] for females. The WHtR cut-point was highly specific in identifying cardiometabolic risk co-occurrence in male children and adolescents as well as female children (90 to 95%), but had poor sensitivity (17 to 53%). Similar associations were observed when BMI was used to define excess adiposity.<p></p> Conclusions WHtR is a simple alternative to age and sex adjusted BMI for assessing cardiometabolic risk in adolescents

Williams-Beuren syndrome: a rare presentation of aortic hypoplasia

William-Beuren syndrome (WBS) is a rare genetic disorder resulting from a micro-deletion of the elastin gene located on the long arm of chromosome 7 (7q11.23). Characterized by typical elfin facies, mental deficiency, overfriendly personality and occasionally infantile hypercalcemia together with various eye, teeth, cardiovascular, renal and skeletal abnormalities. Herein, we describe two cases of diffuse narrowing of the entire aorta, with associated pulmonary artery narrowing. To the best of our knowledge, these two cases of aortic hypoplasia associated with WBS are the first to be reported in the region

Ceramides: a new player in the inflammation-insulin resistance paradigm?

No abstract available

Differential effects of anti-B7-1 and anti-B7-2 monoclonal antibody treatment on the development of diabetes in the nonobese diabetic mouse.

Insulin-dependent diabetes mellitus (IDDM) is thought to be an immunologically mediated disease resulting in the complete destruction of the insulin-producing islets of Langerhans. It has become increasingly clear that autoreactive T cells play a major role in the development and progression of this disease. In this study, we examined the role of the CD28/B7 costimulation pathway in the development and progression of autoimmune diabetes in the nonobese diabetic (NOD) mouse model. Female NOD mice treated at the onset of insulitis (2-4 wk of age) with CTLA4Ig immunoglobulin (Ig) (a soluble CD28 antagonist) or a monoclonal antibody (mAb) specific for B7-2 (a CD28 ligand) did not develop diabetes. However, neither of these treatments altered the disease process when administered late, at > 10 wk of age. Histological examination of islets from the various treatment groups showed that while CTLA4Ig and anti-B7-2 mAb treatment blocked the development of diabetes, these reagents had little effect on the development or severity of insulitis. Together these results suggest that blockade of costimulatory signals by CTLA4Ig or anti-B7-2 acts early in disease development, after insulitis but before the onset of frank diabetes. NOD mice were also treated with mAbs to another CD28 ligand, B7-1. In contrast to the previous results, the anti-B7-1 treatment significantly accelerated the development of disease in female mice and, most interestingly, induced diabetes in normally resistant male mice. A combination of anti-B7-1 and anti-B7-2 mAbs also resulted in an accelerated onset of diabetes, similar to that observed with anti-B7-1 mAb treatment alone, suggesting that anti-B7-1 mAb's effect was dominant. Furthermore, treatment with anti-B7-1 mAbs resulted in a more rapid and severe infiltrate. Finally, T cells isolated from the pancreas of these anti-B7-1-treated animals exhibited a more activated phenotype than T cells isolated from any of the other treatment groups. These studies demonstrate that costimulatory signals play an important role in the autoimmune process, and that different members of the B7 family have distinct regulatory functions during the development of autoimmune diabetes