Eleanor M. Scott

Guidelines for osteoporosis in coeliac disease and inflammatory bowel disease

Osteoporotic fractures are a major public health problem. It has been estimated that in the USA the remaining lifetime fracture risk at the age of 50 years is 40% for white women and 13% for white men,1 the major fracture sites being spine, forearm and hip. This results in considerable morbidity and mortality and rising costs, including acute hospital care and long term care in the home or nursing home. The estimated total annual cost of osteoporotic fractures in England and Wales is £742 million (

Association between polymorphisms in the Clock gene, obesity and the metabolic syndrome in man.

464 million).2These costs are likely to increase as the population ages. ### 2.1 BONE MINERAL DENSITY Osteoporosis can be reliably detected by measurement of bone mineral density (BMD), which can be expressed as the number of SDs above or below either the mean BMD for young adults (T score) or the mean BMD for age matched controls (Z score). A BMD more than 2.5 SD below the mean for a young adult is generally taken to indicate osteoporosis.3 Stratification for fracture risk is possible using BMD. The risk increases roughly twofold for each SD decline in BMD below the population mean.4 5 This compares with a 1.5-fold increase in the risk of death from coronary artery disease with each SD increase in cholesterol concentrations or diastolic pressure. ### 2.2 RISK FACTORS FOR FRACTURE It is important to recognise that osteoporosis is but one of a number of factors predisposing to fracture, just as a raised cholesterol and diastolic pressure are each just one of many factors predisposing to coronary artery disease. Awareness of surroundings, mobility, and eyesight collectively contribute to a tendency to fall and all are likely to be important.6 Furthermore, bone strength is largely related to trabecular structure, certainly in the proximal femur, whereas BMD is a composite measurement of both cortical and trabecular bone.7 Although the …

Impact of Type 2 Diabetes Mellitus on Sympathetic Neural Mechanisms in Hypertension

Objective:Accumulating evidence raises the hypothesis that dysregulation of intrinsic clock mechanisms are involved in the development of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease. The aim of the present study was to investigate the relationship between three known common polymorphisms in the Clock gene and features of the metabolic syndrome in man.Methods:Genotype and haplotype analysis was carried out in a cohort of 537 individuals from 89 families characterized for inflammatory, atherothrombotic and metabolic risk associated with insulin resistance.Results:Heritability of the metabolic syndrome, defined according to International Diabetes Federation criteria, was 0.40. Haplotype analysis indicated three common haplotypes: CAT, TGT and CGC (rs4864548-rs3736544-rs1801260) with frequencies of 31, 33 and 28%, respectively. The CGC haplotype was less prevalent in subjects with the metabolic syndrome (P=0.0015) and was associated with lower waist circumference (P=0.007), lower hip circumference (P=0.023), lower body mass index (P=0.043) and lower leptin levels (P=0.028). The CAT haplotype was significantly associated with the presence of the metabolic syndrome (P=0.020).Conclusions:These findings suggest that the Clock gene CGC haplotype may be protective for the development of obesity and support the hypothesis that genetic variation in the Clock gene may play a role in the development of the metabolic syndrome, type 2 diabetes and cardiovascular disease.

Genetic and Environmental Determinants of Fibrin Structure and Function: Relevance to Clinical Disease

Background—Essential hypertension (EHT) is a major cardiovascular risk factor, and the additional presence of type 2 diabetes mellitus (DM2) increases this risk. However, although the sympathetic nerve hyperactivity of EHT is known to play a role in cardiovascular risk, the level of sympathetic nerve activity is known neither in DM2 nor in hypertensive type 2 diabetic patients (EHT+DM2). Therefore, we planned to quantify the vasoconstrictor sympathetic nerve activity in patients with EHT+DM2 and with DM2 relative to that in matched groups with EHT and normal blood pressure (NT). Methods and Results—In 68 closely matched subjects with EHT+DM2 (n=17), DM2 (n=17), EHT (n=17), and NT (n=17), we measured resting muscle sympathetic nerve activity as the mean frequency of multiunit bursts (MSNA) and of single units (s-MSNA) with defined vasoconstrictor properties. The s-MSNA in EHT+DM2 (97±3.8 impulses/100 beats) was greater (at least P <0.001) than in EHT (69±3.4 impulses/100 beats) and DM2 (78±4.1 impulses/100 beats), and all these were significantly greater (at least P <0.01) than in NT (53±3.3 impulses/100 beats) despite similar age and body mass index. The MSNA followed a similar trend. In addition, the level of insulin was also raised in EHT+DM2 (20.4±3.6 &mgr;U/mL) and DM2 (18.1±3.1 &mgr;U/mL; at least P <0.05) compared with HT or NT. Conclusions—Patients with EHT+DM2, EHT, or DM2 had central sympathetic hyperactivity, although plasma insulin levels were raised only in EHT+DM2 and DM2. The combination of EHT and DM2 resulted in the greatest sympathetic hyperactivity and level of plasma insulin, and this hyperactivity could constitute a mechanism for the increased risks of this condition.

Water ingestion increases sympathetic vasoconstrictor discharge in normal human subjects

The formation of a fibrin clot is one of the key events in atherothrombotic vascular disease. The structure of the fibrin clot and the genetic and environmental factors that modify it have effects on its biological function. Alterations in fibrin structure and function have implications for the clinical presentation of vascular disease. This review briefly describes the key features involved in the formation of a fibrin clot, its typical structure, and function. This is followed by a review of the current literature on genetic and environmental influences on fibrin structure/function and the relationship to clinical disease.

Hypertensive left ventricular hypertrophy: Relation to peripheral sympathetic drive

A marked pressor response to water drinking has been observed in patients with autonomic failure and in the elderly, and has been attributed to sympathetic vasoconstrictor activation, despite the absence of such a pressor response in healthy subjects with intact sympathetic mechanisms. We investigated whether water drinking in normal subjects affected peripheral sympathetic neural discharge and its effect on vascular resistance. In nine normal human subjects, we examined the effect of water ingestion on muscle sympathetic neural activity from the peroneal nerve, as multi-unit bursts (muscle sympathetic nerve activity; MSNA) and as single-unit impulses (s-MSNA) with vasoconstrictor function, and on calf vascular resistance for 120 min. In each subject, water ingestion caused increases in s-MSNA and MSNA which peaked at 30 min after ingestion; they increased respectively (mean+/-S.E.M.) from 42+/-4 to 58+/-5 impulses/100 beats (P<0.01) and from 36+/-4 to 51+/-5 bursts/100 beats (P<0.001). There were corresponding increases in calf vascular resistance and in plasma noradrenaline levels. A significant correlation occurred between all of these data. In conclusion, measurement of MSNA has provided direct evidence that water drinking in normal human subjects increases sympathetic nerve traffic, leading to peripheral vasoconstriction. This sympathetic activation was not accompanied by significant changes in arterial blood pressure.

Should obese women with polycystic ovary syndrome receive treatment for infertility

OBJECTIVES This study was designed to examine whether the occurrence of left ventricular hypertrophy (LVH) in moderate to severe essential hypertension (EHT) was associated with alteration in peripheral sympathetic drive. BACKGROUND In hypertension, LVH is an independent predictor of increased morbidity and mortality. The reported mechanisms leading to LVH remain unclear but include hemodynamic and humoral factors. The sympathetic nervous system may be important, particularly as catecholamines have been shown to have trophic properties. We tested the hypothesis that sympathetic activity measured using microneurography could be different in patients with hypertension depending on the presence of LVH. METHODS We examined 28 subjects with moderate to severe EHT (stages 2 to 3; Joint National Committee [JNC]-VI classification). Fourteen had echocardiographic evidence of LVH (EHT + LVH), while the other 14 subjects (EHT) did not. Subjects were matched in terms of age, body mass index and levels of arterial blood pressure. Peripheral muscle sympathetic nerve activity was measured from both multiunit bursts (MSNA) and single unit (s-MSNA) vasoconstrictor impulses via the peroneal nerve. RESULTS The mean frequency of s-MSNA and MSNA was greater in the EHT + LVH group than it was in the EHT group (mean +/- SEM; 75.9 +/- 6.9 impulses/100 beats vs. 52.1 +/- 2.9 impulses/100 beats, p < 0.001 and 64.2 +/- 5.7 bursts/100 beats vs. 48.9 +/- 2.8 bursts/100 beats, p < 0.05). CONCLUSIONS These results indicate that, in subjects with moderate to severe hypertension, the presence of LVH is associated with higher sympathetic discharge, evidenced by an increase in unitary firing frequency and also by fiber recruitment.

Does the school fruit and vegetable scheme improve children's diet? A non‐randomised controlled trial

Given the risks such women will face in pregnancy, they should lose weight first

Molecular clocks, type 2 diabetes and cardiovascular disease

Objective: Evaluation of the impact on diet of the school fruit and vegetable scheme (SFVS). Design: Non-randomised controlled trial. Setting: Infant and primary schools in the north of England. Participants: 3703 children aged four to six years (reception, year 1, and year 2). Intervention: One portion of fruit or vegetable provided per child on each school day between February and December 2004. Main outcome measures: Fruit and vegetables consumed and intake of nutrients. Results: The SFVS was associated with an increase in fruit intake across reception and year 1 pupils of 0.4 portions (95% confidence interval, 0.2 to 0.5) and 0.6 portions (0.4 to 0.9), respectively, at three months, which fell to 0.2 (0.1 to 0.4) and 0.3 (0.1 to 0.6) at seven months. In year 2 it was associated with an increase of 0.5 portions (0.2 to 0.7) of fruit at three months, which fell to baseline values at seven months when these children were no longer eligible for the scheme. Overall, at seven months there were no changes in vegetable consumption, no associations between the SFVS and energy, fat, or salt intake, and small changes in carotene and vitamin C intake. Conclusions: The SFVS promoted an increase in fruit intake after three months. At seven months the effect remained significant but reduced, and it returned to baseline in year 2 when pupils were no longer part of the scheme. There was a small impact on the intake of some nutrients across the children surveyed.

Closed-Loop Insulin Delivery during Pregnancy in Women with Type 1 Diabetes

The westernised world is in the midst of an epidemic of type 2 diabetes and associated cardiovascular disease. These closely interlinked conditions have a common pathophysiological basis underpinned by insulin resistance and the metabolic syndrome. Contemporary changes in environmental factors on a background of genetic susceptibility are thought to account for the increases seen. Life on earth is governed by the 24-hour environment of light and darkness cycling with the rotation of the earth. Numerous metabolic and physiological pathways are coordinated to this 24-hour cycle by an endogenous clock. Recent epidemiological evidence and animal data suggest that disturbance of circadian rhythms through genetic and environmental influences on the molecular clock is pivotal in the pathogenesis of obesity, type 2 diabetes and cardiovascular disease. This review describes current knowledge on the topic.