A multi-centered trial investigating gestational treatment with ursodeoxycholic acid compared to metformin to reduce effects of diabetes mellitus (GUARD): a randomized controlled trial protocol.

BACKGROUND: Each year in the UK, approximately 35,000 women develop gestational diabetes mellitus (GDM). The condition increases the risk of obstetric and neonatal complications for mother and child, including preeclampsia, preterm birth, and large for gestational age babies. Biochemical consequences include maternal hyperglycemia, neonatal hypoglycemia, and dyslipidemia. Metformin is the most commonly used firstline pharmacological treatment. However, there are concerns about its widespread use during pregnancy, due to its limited efficacy and potential safety concerns. Therefore, there is a need for additional therapies that improve both maternal-fetal glucose and lipid metabolism. Ursodeoxycholic acid (UDCA) is not currently used for treatment for GDM. However, it can improve glucose control in type 2 diabetes, and it improves fetal lipid profiles in gestational cholestasis. Consequentially, it is hypothesized that treatment with UDCA for women with GDM may improve both maternal metabolism and neonatal outcomes. The primary outcome of this trial is to assess the efficacy of UDCA compared with metformin to improve glucose levels in women with GDM. METHODS: The trial is a two-armed, open-label, multi-center, randomized controlled trial. Women are eligible if they have been diagnosed with GDM by an oral glucose tolerance test between 24 + 0 and 30 + 6 weeks' gestation, and if they require pharmacological intervention. In total, 158 pregnant women will be recruited across seven NHS Trusts in England and Wales. Women who consent will be recruited and randomized to either metformin or UDCA, which will be taken daily until the birth of their baby. Maternal and neonatal blood samples will be taken to evaluate the impact of the treatments on maternal glucose control, and maternal and neonatal lipid metabolism. Maternal and fetal outcomes will be evaluated, and acceptability of UDCA compared with metformin will be assessed. DISCUSSION: This trial has the potential to identify a potential new treatment for women with GDM. If successful, a future large multi-center trial will be designed to investigate where decisions can be personalized to identify which women will respond more effectively to UDCA than alternatives to improve maternal and baby outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04407650.

Elevated Blood Pressure and Associations with Sodium Intake Among Multiethnic Youth in Edmonton, Canada: Findings from WHY ACT NOW.

INTRODUCTION: This study examined the prevalence of pre-hypertension (PHT) and hypertension (HT) in urban youth, and assessed the effects of sodium intake and obesity on blood pressure (BP) by ethnicity. METHODS: A convenience sample of 557 multiethnic youth, aged 11-23 years, was recruited from 12 schools and institutions in Edmonton, Alberta, Canada. Participants were divided by self-identified ethnicity into four groups (Indigenous, African and Middle Eastern (AME), Asian, and European). RESULTS: Between October 2013 and March 2014, one-on-one interviews were conducted to collect data on demographics, physical activity, diet, and Body Mass Index (BMI). BP was obtained at two different times during the interview and measured a third time in cases of high variability. The standard deviation scores (SDS) of systolic BP (SBP) and diastolic BP (DBP) were used to estimate associations with sodium intake (per 1000 mg/day). Overall, 18.2% and 5.4% of the participants had PHT and HT, respectively. Indigenous and AME participants showed the highest rates of PHT (23.1%). Indigenous and European participants showed higher rates of HT (8.3% and 5.3%, respectively) than other ethnic groups (AME = 4.4%, Asian = 3.9%). There was a positive association between 1000 mg/day increase in sodium intake and SDS of SBP by 0.041 (95% CI 0.007-0.083; p = 0.04) among pre-hypertensive participants. Over 85% of participants exceeded the recommended dietary sodium intake. Mean BMI and dietary sodium intake were higher among pre-hypertensive participants (4219 mg/day) than normotensive (3475 mg/day). CONCLUSIONS: The prevalence of HT varied by ethnicity. High dietary sodium intake was of concern. There is a need for culturally-tailored, population-based interventions to reduce sodium intake.

Gene Variants at Loci Related to Blood Pressure Account for Variation in Response to Antihypertensive Drugs Between Black and White Individuals.

Selection of antihypertensive treatment according to self-defined ethnicity is recommended by some guidelines but might be better guided by individual genotype rather than ethnicity or race. We compared the extent to which variation in blood pressure response across different ethnicities may be explained by genetic factors: genetically defined ancestry and gene variants at loci known to be associated with blood pressure. We analyzed data from 5 trials in which genotyping had been performed (n=4696) and in which treatment responses to ß-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blocker, thiazide or thiazide-like diuretic and calcium channel blocker were available. Genetically defined ancestry for proportion of African ancestry was computed using the 1000 genomes population database as a reference. Differences in response to the thiazide diuretic hydrochlorothiazide, the ß-blockers atenolol and metoprolol, the angiotensin-converting enzyme inhibitor lisinopril, and the angiotensin receptor blocker candesartan were more closely associated to genetically defined ancestry than self-defined ethnicity in admixed subjects. A relatively small number of gene variants related to loci associated with drug-signaling pathways (KCNK3, SULT1C3, AMH, PDE3A, PLCE1, PRKAG2) with large effect size (-3.5 to +3.5 mm Hg difference in response per allele) and differing allele frequencies in black versus white individuals explained a large proportion of the difference in response to candesartan and hydrochlorothiazide between these groups. These findings suggest that a genomic precision medicine approach can be used to individualize antihypertensive treatment within and across populations without recourse to surrogates of genetic structure such as self-defined ethnicity.

Can arterial wave augmentation in young adults help account for variability of cardiovascular risk in different British ethnic groups?

OBJECTIVE: Traditional cardiovascular risk factors do not fully account for ethnic differences in cardiovascular disease. We tested if arterial function indices, particularly augmentation index (AIx), and their determinants from childhood could underlie such ethnic variability among young British adults in the 'DASH' longitudinal study. METHODS: DASH, at http://dash.sphsu.mrc.ac.uk/, includes representative samples of six main British ethnic groups. Pulse wave velocity (PWV) and AIx were recorded using the Arteriograph device at ages 21-23 years in a subsample (n = 666); psychosocial, anthropometric, and blood pressure (BP) measures were collected then and in two previous surveys at ages 11-13 years and 14-16 years. For n = 334, physical activity was measured over 5 days (ActivPal). RESULTS: Unadjusted values and regression models for PWVs were similar or lower in ethnic minority than in White UK young adults, whereas AIx was higher - Caribbean (14.9, 95% confidence interval 12.3-17.0%), West African (15.3, 12.9-17.7%), Indian (15.1, 13.0-17.2%), and Pakistani/Bangladeshi (15.7, 13.7-17.7%), compared with White UK (11.9, 10.2-13.6%). In multivariate models, adjusted for sex, central SBP, height, and heart rate, Indian and Pakistani/Bangladeshi young adults had higher AIx (ß = 3.35, 4.20, respectively, P < 0.01) than White UK with a similar trend for West Africans and Caribbeans but not statistically significant. Unlike PWV, physical activity, psychosocial or deprivation measures were not associated with AIx, with borderline associations from brachial BP but no other childhood variables. CONCLUSION: Early adult AIx, but not arterial stiffness, may be a useful tool for testing components of excess cardiovascular risk in some ethnic minority groups.

Do arterial stiffness and wave reflection underlie cardiovascular risk in ethnic minorities?

Increasing evidence indicates that remarkable differences in cardiovascular risk between ethnic groups cannot be fully explained by traditional risk factors such as hypertension, diabetes or dislipidemia measured in midlife. Therefore, the underlying pathophysiology leading to this "excess risk" in ethnic minority groups is still poorly understood, and one way to address this issue is to shift the focus from "risk" to examine target organs, particularly blood vessels and their arterial properties more directly. In fact, structural and functional changes of the vascular system may be identifiable at very early stages of life when traditional factors are not yet developed. Arterial stiffening, measured as aortic pulse wave velocity, and wave reflection parameters, especially augmentation index, seem to be an important pathophysiological mechanism for the development of cardiovascular disease and predict mortality independent of other risk factors. However, data regarding these arterial indices in ethnic minorities are relatively rare and the heterogeneity between populations, techniques and statistical methods make it difficult to fully understand their role.

Detecting depression in pregnancy: validation of EPDS in British Pakistani mothers.

Recent reports suggest that antenatal depression is as prevalent as postnatal depression. The Edinburgh Postnatal Depression Scale (EPDS) is the most widely used tool to detect postnatal depression, which can also detect depression during the antenatal period. Mothers of Pakistani origin have the highest birth rate in the UK. The validity of EPDS has not been assessed in this group. A prospective cohort of 714 women in their third trimester of pregnancy completed the EPDS while waiting for their antenatal visit. Women scoring 12 or more on the EPDS, and a random sample of low scores were assessed with the Schedule for Clinical Assessment in Neuropsychiatry to establish psychiatric diagnosis. A cut-off point of 8 showed the best discrimination with sensitivity = 89.6% and specificity 54.7%. Positive predictive value was 29.4 and negative predictive value was 96.2. The area under the curve (AUC) was 0.72 (0.66-0.78). When language is taken into account the area under the ROC curve for subjects who preferred the Urdu or Punjabi language is slightly higher at 0.79 than those who preferred English (0.61). We have not been able to find a single clear cut-off is a result of the AUCs not being particularly large, and confirms that the EPDS should only be used as a screen and not for diagnostic purposes. The larger AUC for the Urdu/Punjabi speakers than for the English speakers suggests that the EPDS is as good a screen for this group as for the indigenous English population.

Adherence to the USDA dietary recommendations for fruit and vegetable intake and risk of fatal stroke among ethnic groups: a prospective cohort study.

BACKGROUND: Stroke is the fourth leading cause of death in the U.S. and stroke mortality rates differ substantially by ethnic group. The impact of adherence to the USDA dietary guidelines on risk for fatal stroke among different ethnic groups has not previously been examined. METHODS: A prospective cohort design was used to examine associations between adherence with dietary recommendations for fruit and vegetable intake and risk for stroke mortality among 174,888 men and women representing five ethnic groups; African American, Native Hawaiian, Japanese American, Latino, and Caucasian. Dietary intake was assessed using a mailed quantitative food frequency questionnaire. Associations were examined using Cox proportional hazards models. RESULTS: There was no evidence that ethnicity modified associations between fruit and vegetable intake and stroke mortality. When data for different ethnicities were combined, a reduced risk for fatal stroke was observed among women who were adherent with the USDA dietary recommendations for vegetable intake, although this result did not reach statistical significance (RR = 0.84, 95% CI = 0.68-1.04). No associations were observed among men. CONCLUSIONS: The results of this study do not provide evidence that dietary intake of fruits and vegetables differentially impacts risk for stroke mortality among different ethnic groups.

The predictive ability of blood pressure in elderly trial patients.

OBJECTIVES: To assess the impact of the blood pressure (BP) profile on cardiovascular risk in the Medical Research Council (UK) elderly trial; investigate whether the effects of hypertensive drugs in reducing event rates are solely a product of systolic pressure reduction. METHODS: Using longitudinal BP data from 4396 hypertensive patients, the general trend over time was estimated using a first-stage multilevel model. We then investigated how BP acted alongside other BP-related covariates in a second-stage 'time-to-event' statistical model, assessing risk for stroke events and coronary heart disease (CHD). Differences in outcome prediction between diuretic, ß-blocker and placebo treatment arms were investigated. RESULTS: The ß-blocker arm experienced comparatively poor control of current SBP, episodic peaks and variability in BP levels. After adjusting for the mean level, variability in SBP over time was significant: risk ratio was 1.15 [95% confidence interval (CI): 1.01-1.31] across all patients for stroke events. The risk ratio for current SBP was 1.36 (95% CI: 1.16-1.58). Current DBP and variability in DBP also predicted stroke independently: risk ratios was 1.43 and 1.18, respectively. The risk factors exhibited weaker associations with CHD risk; only the highest measured value and variability in SBP showed a statistically significant association: risk ratios were 1.26 and 1.16, respectively. CONCLUSION: Individual risk characterization could be augmented with additional prognostic information, besides current SBP, including current diastolic pressure, temporal variability over and above general trends and historical measurements.

Cardiotrophin 1 is involved in cardiac, vascular, and renal fibrosis and dysfunction.

Cardiotrophin 1 (CT-1), a cytokine belonging to the interleukin 6 family, is increased in hypertension and in heart failure. We aimed to study the precise role of CT-1 on cardiac, vascular, and renal function; morphology; and remodeling in early stages without hypertension. CT-1 (20 µg/kg per day) or vehicle was administrated to Wistar rats for 6 weeks. Cardiac and vascular functions were analyzed in vivo using M-mode echocardiography, Doppler, and echo tracking device and ex vivo using a scanning acoustic microscopy method. Cardiovascular and renal histomorphology were measured by immunohistochemistry, RT-PCR, and Western blot. Kidney functional properties were assessed by serum creatinine and neutrophile gelatinase-associated lipocalin and microalbuminuria/creatininuria ratio. Without alterations in blood pressure levels, CT-1 treatment increased left ventricular volumes, reduced fractional shortening and ejection fraction, and induced myocardial dilatation and myocardial fibrosis. In the carotid artery of CT-1-treated rats, the circumferential wall stress-incremental elastic modulus curve was shifted leftward, and the acoustic speed of sound in the aorta was augmented, indicating increased arterial stiffness. Vascular media thickness, collagen, and fibronectin content were increased by CT-1 treatment. CT-1-treated rats presented unaltered serum creatinine concentrations but increased urinary and serum neutrophile gelatinase-associated lipocalin and microalbuminuria/creatininuria ratio. This paralleled a glomerular and tubulointerstitial fibrosis accompanied by renal epithelial-mesenchymal transition. CT-1 is a new potent fibrotic agent in heart, vessels, and kidney able to induce cardiovascular-renal dysfunction independent from blood pressure. Thus, CT-1 could be a new target simultaneously integrating alterations of heart, vessels, and kidney in early stages of heart failure.

Social stress and depression during pregnancy and in the postnatal period in British Pakistani mothers: a cohort study.

BACKGROUND: Depressive disorders are common and disabling among perinatal women. The rates are high in ethnic minority groups. The causes are not known in British Pakistani women. The aim of this study was to estimate the rates, correlates and maintaining factors of perinatal depression in a Pakistani sample in UK. The design used was a cross-sectional two phase population based survey with a prospective cohort study. METHODS: All women in 3rd trimester attending antenatal clinic were screened with the Edinburgh postnatal depression scale (EPDS). Women scoring 12 or more on EPDS and a random sample of low scorers were interviewed using the Schedules for Assessment in Neuropsychiatry (SCAN) and the Life Events and Difficulties schedule (LEDS). Social support was assessed with the Multidimensional Scale for Perceived Social Support (MSPSS). They were reassessed 6 months after the delivery using the same measures. RESULTS: The weighted prevalence of depression was 16.8%. Depressed mothers had more marked non health difficulties (housing, financial and marital). They had less social support and were socially isolated. Marked social isolation and marked non-health related difficulties were independent predictors of depression. Analyses of all the possible risk factors, comparing 26 persistent depressed with 27 depression resolved group showed significant differences in the MSPSS subscales between the two groups. LIMITATIONS: The study lacked inter-rater reliability testing between the individuals carrying out diagnostic interviews. The study sample did not accurately represent the general population and information about the origins of depression in this group of mothers was limited. CONCLUSION: Depression in British Pakistani mothers is associated with social isolation, poor social support and severe and persistent social difficulties. The findings will have implications in planning suitable services for this group.

Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a high-sensitivity assay.

OBJECTIVES: This paper sought to evaluate whether high sensitivity troponin (hs-cTnT) can immediately exclude acute myocardial infarction (AMI) at a novel 'rule out' cut-off. BACKGROUND: Subgroup analysis of recent evidence suggests that undetectable hs-cTnT may exclude AMI at presentation. METHODS: In a cohort study, we prospectively enrolled patients with chest pain, evaluating them with standard troponin T and testing for hs-cTnT (Roche Diagnostics, Basel, Switzerland) at presentation. The primary outcome was a diagnosis of AMI. We also followed up patients for adverse events within 6 months. After subsequent clinical implementation of hs-cTnT, we again evaluated whether initially undetectable hs-cTnT ruled out a subsequent rise. RESULTS: Of 703 patients in the cohort study, 130 (18.5%) had AMI, none of whom initially had undetectable hs-cTnT (sensitivity: 100.0%, 95% confidence interval [CI]: 95.1% to 100.0%, negative predictive value: 100.0%, 95% CI: 98.1% to 100.0%). This strategy would rule out AMI in 27.7% of patients, 2 (1.0%) of whom died or had AMI within 6 months (1 periprocedural AMI, 1 noncardiac death). We evaluated this approach in an additional 915 patients in clinical practice. Only 1 patient (0.6%) with initially undetectable hs-cTnT had subsequent elevation (to 17 ng/l), giving a sensitivity of 99.8% (95% CI: 99.1% to 100.0%) and a negative predictive value of 99.4% (95% CI: 96.6% to 100.0%). CONCLUSIONS: Undetectable hs-cTnT at presentation has very high negative predictive value, which may be considered to rule out AMI, identifying patients at low risk of adverse events. Pending further validation, this strategy may reduce the need for serial testing and empirical treatment, enabling earlier reassurance for patients and fewer unnecessary evaluations and hospital admissions.

Diagnosing pulmonary embolism: a comparison of clinical probability scores.

Pulmonary embolism (PE) is a major cause of community and in-hospital mortality. This study aimed to compare the performance of the British Thoracic Society (BTS) score to the Wells' score in diagnosing PE. Data from two separate prospective diagnostic PE studies were analysed. All patients underwent gold standard investigation to determine the presence or absence of PE, together with a 3-month follow-up. The posttest prevalence of PE was compared using both scores and the receiver operating characteristic (ROC) curves. Seven hundred and seventy-nine patients were consented and investigated for PE. In patients with pleuritic chest pain, respiratory rate <20 breaths/min and absence of dyspnoea, 4·0% [95% confidence interval (CI) 1·9-7·9%] had PE. The BTS score allocated 463/779 patients as low probability, compared to 565/779 according to the Wells' score. Both scores identified a low risk group in the Manchester Investigation of Pulmonary Embolism Diagnosis cohort, however the BTS low probability group in the Thromboembolism Assessment and Diagnosis study had a prevalence of 9·7% (95% CI 5·8-15·9%). For the BTS score, the areas under the ROC curves were 0·67 (95% CI 0·61-0·72) and 0·71 (95% CI 0·61-0·75). For the Wells' score these were 0·76 (95%CI 0·71-0·81) and 0·68 (95%CI 0·64-0·73). Given the lack of BTS validation studies to date, the Wells' score appears to be the safer assessment option.

Nutritional composition of commonly consumed composite dishes for Afro-Caribbeans (mainly Jamaicans) in the United Kingdom.

PRIMARY OBJECTIVE: To provide the calculated nutritional composition of 18 commonly consumed composite dishes among Afro-Caribbeans residing in the United Kingdom. METHODS AND PROCEDURES: Weighed recipes were collected in Afro-Caribbean households (mainly Jamaicans) in Manchester, UK. MAIN OUTCOMES AND RESULTS: A total of 30 weighed recipes were collected for a variety of 18 Afro-Caribbean composite dishes. Among them, fried dumpling, Ackee and saltfish, fried chicken and rice and peas were high in energy, providing 201-356 kcal/100 g. Fried fish, Ackee and saltfish, stewed fish, and fried chicken had a high fat content (between 11.5% and 25.9%). CONCLUSIONS: We have provided for the first time some data on the energy, macronutrient and micronutrient content per 100 g for 18 Afro-Caribbean foods. These recipe data provide essential information for accurately assessing dietary intake and for determining associations between diet and chronic diseases among this population.

Small vessel remodeling and impaired endothelial-dependent dilatation in subcutaneous resistance arteries from patients with acromegaly.

CONTEXT: Patients with acromegaly have increased morbidity and mortality, predominantly from cardiovascular disease. Hypertension and diabetes are more prevalent, and both cause small vessel remodeling and endothelial dysfunction. OBJECTIVE: To understand the structure and function of small arteries in acromegaly, sc blood vessels from gluteal fat biopsies were harvested from 18 patients with active disease (AD; age, 56 +/- 15 yr; 14 males), 23 patients in remission (CD; age, 55 +/- 12 yr; 15 males), and 20 healthy controls (age, 55 +/- 11 yr; 10 males) and examined in vitro using pressure myography. DESIGN: Contractile responses to cumulative noradrenaline concentrations were recorded and followed by dose-dependent dilator responses to acetylcholine. The acetylcholine protocol was repeated after incubation with a nitric oxide synthase inhibitor (N-nitro-L-arginine methyl ester) and cyclooxygenase inhibitor (indomethacin). After perfusion with Ca(2+)-free physiological saline solution, structural measurements were recorded at varying intraluminal pressures (3-180 mm Hg). RESULTS: Wall thickness and wall:lumen ratio were increased in AD, reduced with treatment but remained greater in CD than controls. Wall cross-sectional area was increased in AD vs. controls (P < 0.001), decreased with treatment (AD vs. CD, P < 0.001), but remained higher than controls (CD vs. controls, P = 0.015). Growth index was increased in AD (20%) compared to controls (CD, 9%). Contractility was similar in all groups. Endothelial-dependent dysfunction was evident in AD compared with CD (P < 0.001) and controls (P < 0.01). Dilation did not change after N-nitro-L-arginine methyl ester but was impaired after indomethacin incubation. CONCLUSION: Active acromegaly is associated with hypertrophic remodeling of the vascular wall and embarrassed endothelial function due to reduced nitric oxide and endothelium-derived hyperpolarizing factor bioavailability, both of which may contribute to the early mortality from cardiovascular disease.

Nutritional composition of commonly consumed composite dishes from the Central Province of Cameroon.

PRIMARY OBJECTIVE: To provide nutritional composition of 34 composite dishes commonly consumed in Cameroon, in order to enable dietary intake to be calculated from a Quantitative Food Frequency Questionnaire developed specifically for this population to determine associations between diet and diabetes. METHODS AND PROCEDURES: A total of 197 recipes were collected for 34 composite dishes. Multiple samples of each dish were collected from a range of 2-16 households in the villages of Evadoula and in the city of Yaounde. MAIN OUTCOMES AND RESULTS: The average nutritional composition for these composite dishes was calculated using the US Department of Agriculture National Nutrient Database. We provide the energy, macronutrient and micronutrient content of these foods. CONCLUSIONS: We provide, for the first time, the macronutrient and micronutrient content of 34 commonly consumed composite dishes in the Central Province of Cameroon. Such data are essential for calculating nutrient intake and determining associations between diet and diabetes and other chronic diseases. These data may also be used for nutrition interventions aimed at modifying commonly consumed composite dishes to improve dietary intake.

Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study.

BACKGROUND: Different blood pressure (BP)-lowering drugs could have different effects on central aortic pressures and thus cardiovascular outcome despite similar effects on brachial BP. The Conduit Artery Function Evaluation (CAFE) study, a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), examined the impact of 2 different BP lowering-regimens (atenolol+/-thiazide-based versus amlodipine+/-perindopril-based therapy) on derived central aortic pressures and hemodynamics. METHODS AND RESULTS: The CAFE study recruited 2199 patients in 5 ASCOT centers. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and hemodynamic indexes on repeated visits for up to 4 years. Most patients received combination therapy throughout the study. Despite similar brachial systolic BPs between treatment groups (Delta0.7 mm Hg; 95% CI, -0.4 to 1.7; P=0.2), there were substantial reductions in central aortic pressures with the amlodipine regimen (central aortic systolic BP, Delta4.3 mm Hg; 95% CI, 3.3 to 5.4; P<0.0001; central aortic pulse pressure, Delta3.0 mm Hg; 95% CI, 2.1 to 3.9; P<0.0001). Cox proportional-hazards modeling showed that central pulse pressure was significantly associated with a post hoc-defined composite outcome of total cardiovascular events/procedures and development of renal impairment in the CAFE cohort (unadjusted, P<0.0001; adjusted for baseline variables, P<0.05). CONCLUSIONS: BP-lowering drugs can have substantially different effects on central aortic pressures and hemodynamics despite a similar impact on brachial BP. Moreover, central aortic pulse pressure may be a determinant of clinical outcomes, and differences in central aortic pressures may be a potential mechanism to explain the different clinical outcomes between the 2 BP treatment arms in ASCOT.

Screening for insulin resistance in women with polycystic ovarian syndrome.

INTRODUCTION: Insulin resistance is implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). Insulin-sensitizing agents are increasingly used in the treatment of infertility and hirsutism in PCOS. However, not all women with PCOS are insulin-resistant. OBJECTIVE: To assess the degree of insulin resistance within a clinic population of women referred for treatment of oligomenorrhoea or infertility. DESIGN: We evaluated 25 consecutive PCOS outpatients referred for treatment of menstrual dysfunction/infertility and a matched control group. All underwent a standard oral glucose tolerance test (OGTT) with serial insulin measurements. Insulin sensitivity was calculated using homeostasis model assessment (HOMA). RESULTS: Five of the 25 clinic patients had abnormal glucose handling (two had previously unknown type 2 diabetes and three had impaired glucose tolerance). Fasting and 2-h insulin levels were significantly higher in the PCOS women. Mean HOMA-S (insulin sensitivity) was even lower for PCOS women with normal GTT status (mean (95% confidence interval): 0.53 (0.34-0.72)) than for controls (0.94 (0.84-1.04)) (F = 4.2, p < 0.001). HOMA-B (pancreatic beta-cell function) was nearly tripled for normal GTT status PCOS women at 273 (205-342) versus 105 (70-139) for controls (F = 6.8, p < 0.001). CONCLUSIONS: The results suggest a role for routine measurement of HOMA-S in identifying women with PCOS with insulin resistance with a view to targeting them with insulin-sensitizing agents.

Cardiovascular risk profiles in UK-born Caribbeans and Irish living in England and Wales.

Cardiovascular disease is the leading cause of morbidity and mortality among Caribbean and Irish origin people living in England and Wales. Yet mortality from coronary heart disease (CHD) of migrant Caribbeans is lower than the national average, while stroke mortality is higher. The Irish experience higher than average mortality from both diseases. Little is known about the health of the children of these migrants. The Health Survey for England (HSE) 1999 was used to investigate for the first time cardiovascular risk factors in UK-born Caribbeans aged 35-44 and Irish aged 35-44 and 45-54 years. Caribbean men were more likely to smoke but had higher mean HDL-cholesterol than men in the general population. Caribbean women had greater body mass indices and lower mean triglyceride levels. Irish men in both age groups smoked more than men in the general population, but in the younger group had lower diastolic blood pressure (BP). At age 35-44 only, Irish women were shorter than women in the general population. These findings were independent of differences in socio-economic position. Previously, Caribbean-born migrants to Britain had generally favourable lipid profiles in line with lower CHD rates, despite obesity and diabetes. The nationally representative but small-scale data presented here suggest that UK-born Caribbeans appear to be losing this more favourable lipid pattern and among men smoking rates are now higher compared with general population men, suggesting that an increase in CHD rates can be expected. Further research should examine how improved education and specific intervention programs could be used to reduce smoking among UK-born Irish and Caribbean men, and obesity among UK-born Caribbean women. The next HSE also needs to include adequate numbers of younger people of different ethnic origins to allow time trends in these anthropometric, behavioural and metabolic risk factors to be examined reliably and fully.

Nutrient intakes of an adult Pakistani, European and African-Caribbean community in inner city Britain.

OBJECTIVES: To report nutrient intakes for three different ethnic groups living in inner city Manchester and explore under-reporting in each group. DESIGN: Cross-sectional survey. All participants completed one of three food frequency questionnaires, specifically developed for each ethnic group, and took part in a larger international survey of risk factors for diabetes and hypertension. SETTING: Participants were drawn randomly from seven GP registers in inner city Manchester, UK. PARTICIPANTS: Men and women aged 25-79 years, 86 European, 246 African-Caribbean origin and 84 Pakistani origin participants were included in the analysis. RESULTS: Body mass index was highest in the Pakistani women, 30.2 kg m-2. European participants had the highest reported energy intakes (EIs) for men and women (10.9 and 9.6 MJ, respectively). Pakistani men and women had the highest percentage of energy from fat (36.7 and 36.6%, respectively). Iron intakes were low in the African-Caribbean group and calcium intakes were low in the Pakistani group. Under-reporting [assessed as EI : basal metabolic rate (BMR) ratio <1.2] appeared to be high and occurred across all ethnic groups, with those apparently under-reporting having higher BMIs in all groups. CONCLUSION: The data provide nutrient intake estimates in three different ethnic groups using a similar method. Limitations include under-reporting across all ethnic groups in a similar pattern with under-reporters having higher BMIs in all groups, as found elsewhere.

C-reactive protein and the insulin-like growth factor (IGF)-system in relation to risk of cardiovascular disease in different ethnic groups.

Inflammatory processes, marked in part by the acute phase reactant C-reactive protein (CRP) and insulin resistance are implicated in atherogenesis. Low insulin-like growth factor-I (IGF-I) and IGF binding protein-1 (IGFBP-1) concentrations are closely associated with insulin resistance. We examined CRP in ethnic groups with differing risk for cardiovascular disease and type 2 diabetes and its relationship with insulin sensitivity (Homeostasis model assessment (HOMA)-S) and the IGF system. European (n=155), Pakistani (n=108) and African-Caribbean (African Caribbean) (n=177) origin participants were randomly sampled from population registers. All underwent basic anthropometry, glucose tolerance testing and measurement of insulin sensitivity, CRP and other metabolic variables. CRP was significantly lower in African Caribbean men and women than in other ethnic groups. Across all groups CRP correlated negatively with (HOMA-S) (rho=-0.29, P<0.001). Regression analysis which included ethnicity and body mass index (BMI) showed that low HOMA-S (beta=-0.17, P<0.001) and low IGFBP-1 (beta=-0.14, P<0.001) were independently and inversely associated with CRP, but the effect was modified by obesity. In obese subjects insulin sensitivity was not associated with CRP. However, for the whole population, a 2.7 mg/l increase in CRP was associated with a 50% (95% confidence interval (CI) 10-210%) greater risk of WHO defined metabolic syndrome, independent of IGF-I (odds ratio (OR) 0.46 (95% CI 0.22-0.96)), IGFBP-1 (OR 0.58 (0.44-0.76)), female sex (OR 0.43 (0.22-0.84)), NEFA (OR 1.06 (1.03-1.09)) and Pakistani ethnicity. High CRP (as a measure of chronic subclinical inflammation), low IGF-I and low IGFBP-1 are independently associated with the presence of the metabolic syndrome and with insulin resistance. In obese subjects insulin sensitivity is not associated with changes in CRP whilst in non-obese subjects CRP independently contributes to variation in HOMA-S.