bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis and Testing of Electrorheological Bypass Dampers
Authors: Lindler Jason , Wereley Norman M.
Published: August 2008

We experimentally validate nonlinear quasi-steady electrorheological (ER) and magnetorheological (MR) damper models, using an idealized Bingham plastic shear flow mechanism, for the flow mode of damper operation. An electrorheological valve or bypass damper was designed, and fabricated using predominantly commercial off-the-shelf hydraulic components. Both the hydraulic cylinder and the bypass duct have cylindrical geometry, and damping forces are developed in the annular bypass via Poiseuille (flow mode) flow. Damper models assume parallel plate geometry. Three nondimensional groups are used for damper analysis, namely, the Bingham number, Bi, the nondimensional plug thickness, 6, and the area coefficient defined as the ratio of the piston head area, AP, to the cross-sectional area of the annular bypass, Ad. In the flow mode case, the damping coefficient, which is defined as the ratio of equivalent viscous damping of the Bingham plastic material, Ceq, to the Newtonian viscous damping, C, is a function only of the nondimensional plug thickness. The damper was tested using a mechanical damper dynamometer for sinusoidal stroke of 2 in., over a range of frequencies below 0.63 Hz. The damping coefficient vs. nondimensional plug thickness diagram was experimentally validated using these data over a range of damper shaft velocities or frequencies and applied electric fields. Because the behavior of ER and MR fluids are qualitatively similar, these ER damper modeling results can be extended to analysis of flow mode MR dampers.
Electromagnetic Stress Sensor for Bridge Cables and Prestressed Concrete Structures
Authors: Bouchilloux P. , Lhermet N. , Claeyssen F.
Published: August 2008

This paper presents the design, construction, and test results of an electromagnetic stress sensor. The sensor uses the reverse magnetostrictive effect found in high elastic limit steels such as those used in cables and in prestressed concrete. This effect is characterized by the variation in the steel's magnetic permeability as a function of its internal stress. Consequently, the internal stresses in these high elastic limit steels can be found by measuring their permeability. The permeability can be measured indirectly by measuring the inductance of a coil placed around or near the cable.

We designed a prototype of the sensor with a finite element program. We also used this program to optimize the sensing coil and the measurement frequency and to design the magnetic shielding around the sensor. We built and tested the prototype in our laboratory. We evaluated the precision, accuracy, linearity, and reliability of the sensor, and also the influence of external thermal and magnetic perturbations on the sensor measurements. This paper provides experimental data demonstrating that the prototype meets the desired performance criteria.

The major advantages of this sensor are its robustness and its ability to operate continuously for several decades, even in hostile environments. Also, this sensor can be either embedded in or added to the structure (e.g., bridge cables and nuclear plant concrete foundations), which makes the task of monitoring stresses easier and less expensive.
Colonic Adenoma With Squamous Metaplasia
Authors: Pantanowitz Liron
Published: August 2008

Squamous metaplasia arising within colon adenomas is a rare occurrence, with a 0.4% incidence noted predominantly in elderly males. A case of squamous metaplasia arising in a tubulovillous adenoma of the cecum, associated with adenocarcinoma, is described. Squamous metaplasia was immunoreactive for beta-catenin, but negative for cytokeratin 20, CDX2, p63, estrogen receptor, progesterone receptor, p16, and human papilloma virus. Squamous differentiation may serve as a precursor lesion for squamous neoplasia of the colorectum.
Multiple sclerosis: chemokine receptor expression on circulating lymphocytes in correlation with radiographic measures of tissue injury
Authors: Fox RJ , Kivisakk P , Fisher E , Tucky B , Lee JC , Rudick RA , Ransohoff RM
Published: August 2008

Background

Leukocytes expressing inflammatory chemokine receptors (CKRs), most consistently CCR2, CCR5, and CXCR3, have been identified in multiple sclerosis (MS) tissue lesions and provide attractive therapeutic targets. Our previous studies found large inter-individual differences in expression of these CKRs but stable levels over time within subjects. This observation suggests a CKR “set-point” within individuals, which might relate to inflammatory injury in MS. We evaluated the correlation between CKR levels and magnetic resonance imaging (MRI) measures of disease activity.

Methods

Fifty-five relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) patients were prospectively followed with annual CKR and MRI studies. Multiparameter flow cytometry was used to determine CCR2, CCR5, and CXCR3 expression on CD4 and CD8 cells. Simultaneous cranial MRIs were performed, and quantitative measures of T2, T1, and gadolinium lesions, brain parenchymal fraction (BPF), and whole brain and fractionated magnetization transfer ratio (MTR) were performed using automated software. Spearman’s rank correlations evaluated the relationship between CKR levels and MRI measures.

Results

Significant correlations were observed between CXCR3 expression on CD8 cells and measures of new (T1) and total (T1, T2) lesion volumes, lesion MTR, and BPF; higher levels of CXCR3 expression were correlated with greater injury on MRI (| r| = 0.27–0.42). In contrast, CD4 cell CKR expression was only minimally correlated with MRI measures.

Conclusions

Over 2 years, we observed significant correlations between the percent of CD8 cells expressing CXCR3 and MRI measures of MS inflammatory activity and tissue destruction. These observations are consistent with a pathogenic role for cytotoxic T cells in MS brain and have significant implications regarding T-cell targeted therapeutic strategies.
Outcome measures for trials of remyelinating agents in multiple sclerosis: retrospective longitudinal analysis of visual evoked potential latency
Authors: Niklas A , Sebraoui H , Heß E , Wagner A , Then Bergh F
Published: August 2008

Objective

Visual evoked potentials (VEP) may be suitable surrogate outcome measures in multiple sclerosis (MS) remyelination trials. The extent of spontaneous changes of subclinically delayed VEP is unknown, whereas VEP improve after acute optic neuritis (ON).

Methods

In all, 124 patients with three VEP recordings at least 3 months apart: 71 patients with MS who had never suffered clinical ON; 53 patients with ON (isolated ON or ON as an attack of MS at first recording). Latencies of P100 were analyzed by multivariate analysis of variance.

Results

Eyes of patients with MS had a mean P100 latency of 110.2 ms, worsening mildly over time ( n = 104 eyes, P = 0.022). MS patients' eyes with subclinical demyelination (delayed P100 latency at first recording >116 ms) showed no significant evidence of remyelination ( n = 24 eyes, P = 0.27). By contrast, in ON patients' affected eyes, mean P100 latency decreased ( P = 0.001), whereas unaffected eyes remained stable ( P = 0.26). Clinically non-affected eyes from both diagnostic groups with subclinically prolonged latencies remained stable ( n = 32: mean P100 at 124.8 ± 10.7, 123.5 ± 13.6, and 122.8 ± 13.1 ms; P = 0.57), whereas non-affected eyes with normal latency at baseline deteriorated slightly ( P = 0.001). A subgroup with more homogeneously defined follow-up periods confirmed this observation. Non-affected eyes selected for stability (difference <5 ms) between first and second recording deteriorated (normal baseline, n = 66 eyes, P = 0.013) or remained stable (prolonged baseline, n = 18 eyes, 95% confidence interval of change –5.42 to +6.89 ms, P = 0.805).

Conclusion

Prolonged P100 latencies in eyes never affected by clinical ON remain stable and thus can be used as surrogate outcome measure for remyelination trials.
Managing care of type 2 diabetes. Learnings from T2ARDIS*
Authors: Bottomley Julia M ,   T2ARDIS Steering Committee and UK Centres
Published: August 2008

The T2ARDIS* survey reported total resource use in the NHS and Social Services for people with type 2 diabetes.

Patients and methods Cross-sectional postal survey data were acquired from a random sample of people diagnosed with type 2 diabetes from population-wide diabetes registers. Aggregated resource use, implications for healthcare management, and costs in the NHS and Social Services were considered. The data were compared to resource data in the general population to determine the impact of developing diabetic complications, particularly vascular disease. Implications for services were also considered.

Results At a population level, on average one in four patients reported microvascular complications, one in 10 macrovascular complications and one in 14 reported both. Compared to the general population, people with type 2 diabetes were admitted to hospital more often and stayed longer as in-patients. This trend was similar for out-patient care. Across the whole cohort, more than 40% of the NHS cost was due to in-patient care. Diabetic complications increased costs in the NHS and Social Services, costs of insulin products and other drugs. The average annual spend on oral antidiabetic drugs accounted for only 2% of NHS costs for diabetes.

Conclusion Most of the costs of care for the person with type 2 diabetes are borne by the NHS and the hospital sector. T2ARDIS* has probably under-estimated costs of the co-morbidity of type 2 diabetes. Complications significantly increase costs across all sectors. Evidence indicates that preventing the vascular complications of diabetes could avoid or delay hospitalisations and disability. Targeting resources should optimise the use of available services.
The role of central fat accumulation in type 2 diabetes
Authors: Lean Mike EJ
Published: August 2008

This article examines the merits of body mass index (BMI), waist and hip measurements as indicators of total body fat and diabetes risk. Diabetes risk increases with obesity, with the accumulation of central fat being closely related with insulin resistance. This promotes other features of metabolic syndrome, including glucose intolerance, to increase vascular risk.
Human islet transplantation: expectation versus reality
Authors: Heald Karen , Jay Tessa , Downing Richard
Published: August 2008

Although experimental islet isolation and transplantation has continued for over 25 years, the results of human islet transplantation in patients with type 1 diabetes were disappointing until June 2000 when the University of Alberta, Edmonton, Canada reported 100% insulin independence in a cohort of seven patients. The study introduced several innovations now under evaluation worldwide. In the United Kingdom, an Islet Transplant Consortium has been established to co-ordinate clinical trials in several centres. The Canadian results have renewed hope of establishing islet transplantation as a treatment for diabetes while highlighting the need to identify plentiful sources of insulin secreting tissue and alternatives to current immunosuppressive therapies.
Scottish Intercollegiate Guidelines Network: management of diabetes (SIGN 55)
Authors: Campbell Ian W , Nairn Moray
Published: August 2008

In Scotland the St Vincent Declaration has been implemented via the Scottish Intercollegiate Guidelines Network (SIGN). Between 1996—1998, seven guidelines were published. SIGN 55 has revised and updated these previous guidelines and now includes a section on diet and lifestyle. SIGN 55 will be a key cornerstone of the Scottish Diabetes Framework.
Prospective evaluation of diabetic ischaemic heart disease by computed tomography: the PREDICT study
Authors: Elkeles Robert S , Flather Marcus , Feher Michael D , Godsland Ian , Richmond William , Humphries Stephen E , Rubens Michael B , Underwood S Richard
Published: August 2008

Coronary heart disease (CHD) is the main cause of morbidity and mortality in type 2 diabetic subjects. Electron beam computed tomography (EBCT) of the coronary arteries provides a non-invasive method of detecting and quantifying coronary calcification (coronary calcium score), which is known to be an early marker of coronary atheroma in non-diabetic subjects. 600 type 2 diabetic subjects aged between 50 and 70 years of either sex will undergo EBCT. They will be followed-up for a mean period of four years. Recruitment started in September 2000 and preliminary results are expected in 2004. The primary aim is to assess the predictive power of the coronary calcium score for coronary events specifically in type 2 diabetic subjects. Secondary aims are to assess the relationship between coronary calcium score in type 2 diabetes and conventional risk factors, with novel risk markers, plasma homocysteine and C-reactive protein, and with key genetic markers of CHD.
Insulin resistance, haemostatic factors and cardiovascular risk
Authors: Mills Joseph D , Grant Peter J
Published: August 2008

Increased insulin resistance, which is present in the majority of type 2 diabetics patients, is associated with other metabolic and pro-coagulant cardiovascular risk factors and may account for the accelerated atherosclerosis and increased thrombotic potential observed in these patients. In individuals with normoglycaemia or impaired glucose tolerance (IGT), hyperinsulinaemia (a marker of insulin resistance) is associated with a similar clustering of risk factors and is predictive of cardiovascular events. The origins of insulin resistance are not well understood but data from families, twins and extended pedigrees suggest significant genetic and environmental contributions. The clustering of atherogenic traits begins in childhood, carries through to adult life and may result from the multiple effects of individual genes (pleiotropy) and environmental influences. Important environmental determinants of insulin resistance may occur before birth and, in conjunction with subsequent diet and exercise habits which result in obesity, lead to increased insulin resistance and cardiovascular risk. Therefore, primary prevention should centre around lifestyle changes which increase insulin sensitivity, maintain normoglycaemia and ameliorate atherothrombotic risk factor clustering.
Has abciximab's ship come in?
Authors: Kalra Paul R
Published: August 2008

The ADMIRAL (Abciximab before Direct angioplasty and stenting in Myocardial Infarction Regarding Acute and Long-term follow-up) study is a multicentre, double-blind trial in 300 patients presenting with myocardial infarction. They were randomised to treatment with abciximab or placebo, followed by stenting. Abciximab treatment in diabetic and non-diabetic patients improved outcomes at 30 days and 6 months, with these improvements being related to a higher frequency of normal coronary blood flow at 24 hours and 6 months after intervention.
Review: Angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists in diabetic renal disease
Authors: Walker James D
Published: August 2008

In mortality terms diabetic nephropathy is the most important microvascular complication of diabetes. Even a small elevation in urinary albumin loss (microalbuminuria) is an independent predictor of end-stage renal failure (ESRF) and death. Detection, confirmation and treatment of diabetic nephropathy are mandatory aspects of diabetes care. Over the last decade a considerable body of evidence has built up suggesting that angiotensin-converting enzyme (ACE) inhibitors are superior to other antihypertensive agents in terms of both renal and overall vascular protection. More recently a number of important studies have reported the beneficial effects of angiotensin receptor antagonists (AIIA) in patients with type 2 diabetes at the stages of microalbuminuria and proteinuria. To date no large studies have directly compared ACE inhibitors with AIIA in patients with diabetic nephropathy. However, given the current state of knowledge, evidence-based therapeutic decisions are possible for individual patients with diabetic nephropathy.
Review: Which patients with diabetes should receive which antiplatelet agents?
Authors: Lowe Gordon
Published: August 2008

Patients with diabetes mellitus tend to have activated blood platelets, and increased circulating levels of co-factors (fibrinogen, von Willebrand factor) which promote platelet adhesion, aggregation and thrombosis. Systematic reviews of randomised controlled trials of antiplatelet agents show that antiplatelet agents reduce the risk of serious vascular events (myocardial infarction, stroke or death) by about one-quarter in patients with symptomatic vascular disease (secondary prevention), including those with diabetes. So, secondary prevention with an antiplatelet agent (aspirin, clopidogrel, or dipyridamole) should be considered in all diabetic patients with symptomatic vascular disease. Systematic reviews of randomised controlled trials of aspirin in primary prevention show a similar proportional reduction in coronary heart disease events, but not in stroke or death. The excess of adverse events for aspirin (haemorrhagic stroke, major gastrointestinal bleeds), which is unrelated to risk of cardiovascular disease, results in a lower risk: benefit ratio in primary prevention, and is also less cost-effective when aspirin is prescribed. Current SIGN guidelines recommend that aspirin be considered for primary prevention of coronary heart disease in diabetic or non-diabetic persons whose coronary risk is formally estimated to be ≥ 2% per year (in practice, over 80% of diabetic adults without symptomatic vascular disease). Discussions between clinicians and patients should address the potential benefits and harms of aspirin in primary prevention, as well as patient preferences. Further trials are required to identify subgroups in whom primary prevention is most beneficial.
Review: The management of tibial artery disease in diabetes
Authors: Torella Francesco , Ashleigh Ray J , Bolia Amman , Nasim Akhtar
Published: August 2008

Foot ulceration and gangrene are important causes of morbidity in diabetic patients. Healing of such lesions requires surgical debridement of the infected and necrotic tissue, and restoration of pulsatile blood flow to the foot. As occlusive atherosclerosis of the tibial arteries is particularly common in diabetic patients, infrapopliteal revascularisation is often required. This has traditionally been accomplished by transluminal angioplasty or surgical bypass, with moderately good results. More recently, subintimal angioplasty has been proposed as an alternative, minimally invasive treatment to recanalise long arterial occlusions, with promising patency rates even in small vessels. Advanced reconstructive techniques, including local or free tissue flaps can be used to accelerate healing of large foot wounds after successful revascularisation. Treatment of diabetic tibial artery disease is challenging and requires an aggressive multidisciplinary approach, with co-operation between diabetologists, interventional radiologists, vascular and plastic surgeons.
Review: Managing the diabetic patient with angina
Authors: Foo Kong , Timmis Adam D
Published: August 2008

Angina is common in the adult diabetic population. The symptoms of diabetic angina are commonly atypical, and often absent (silent ischaemia). Conventional anti-anginal drugs are effective in diabetic patients, but referral for angiography and consideration of percutaneous or surgical revascularisation is necessary if symptoms persist. Secondary prevention strategies are reviewed within the context of medical and surgical treatment options.
Impaired glucose tolerance and metformin: clinical and mechanistic aspects
Authors: Hermann Leif Sparre , Wiernsperger Nicolas
Published: August 2008

The Diabetes Prevention Program (DPP) showed that metformin reduced the incidence of diabetes in subjects with impaired glucose tolerance (IGT) who were at high risk of progression to type 2 diabetes. Metformin was not as efficient as intensive life style intervention, but had a clinically significant effect in obese individuals and in those with impaired fasting glucose (IFG). This review discusses the clinical implications and the mechanistic aspects of the effect of metformin in IGT and IFG. Acute actions of metformin on postprandial metabolism to improve hepatic glucose handling and improve the lipid profile could contribute to the lower incidence of diabetes. Longer term improvements in haemodynamic parameters and reduced oxidative stress are also implicated. Metformin offers a potential alternative or complement to lifestyle intervention for IGT, and deserves further evaluation in this respect.
Screening patients with ischaemic heart disease and hypertension for undiagnosed diabetes
Authors: Savage George , Ewing Peter , Kirkwood Helen , Cowie Katrina
Published: August 2008

Diabetes mellitus is an important condition with a significant morbidity and mortality. Up to 50% of people with diabetes may be as yet undiagnosed. Widespread population screening so far has had a low uptake and yield. This study is a cross-sectional survey screening for undiagnosed diabetes amongst patients with ischaemic heart disease (IHD) or hypertension, in a semi-rural practice in Scotland. The results produced a screening uptake of 83.7% and a yield of 3.48% for patients with IHD, and an uptake of 79.65% and a yield of 3% for hypertensive patients. To identify one new case of diabetes we had to screen 24 patients with IHD and 33 with hypertension. This was feasible within an organised review system for patients with these conditions with no additional resource implications. The study is limited by the lack of multi-ethnic mix, rural setting, relative affluence, and the existing organised chronic disease management plans in this practice. This may underestimate the yield if screening were to be extended to both groups nationally. More work is needed to see if such screening for diabetes is feasible and worthwhile on a national basis.
Comparison of the postprandial glucose and insulin profiles with nateglinide and gliclazide in type 2 diabetic patients
Authors: Schweizer Anja , Ball Michele , Owens David R , Cressier Floriane , Holmes David O , Brunel Patrick
Published: August 2008

Aim

The aim of this study was to compare glucose, insulin and proinsulin profiles during nateglinide and gliclazide treatment over an extended postprandial period.

Materials and methods

This double-blind crossover trial was conducted in 23 type 2 diabetic patients (mean HbA1C 6.6%; range 6.0—7.4%) who received, for one week each, nateglinide 120 mg t.i.d., gliclazide 80 mg b.i.d. and placebo, with a one week wash out period between treatments.

Results

The 2-hour postprandial glucose concentration was markedly lower with nateglinide than with gliclazide (5.83 vs. 7.21 mmol/L; p<0.05), as was the post-meal peak glucose elevation (8.63 vs. 9.72 mmol/L; p=0.085), which was associated with earlier, higher and shorter-lived insulin and proinsulin secretory responses. However, 0—7-hour AUCs during standardised meal test for glucose and insulin between the two drugs did not statistically differ. No symptomatic hypoglycaemic events occurred during the 7-hour test period.

Conclusion

Nateglinide was more effective than gliclazide in controlling postprandial hyperglycaemia and showed a faster effect on insulin and proinsulin secretion.
Review: Female sexual dysfunctions — the new models
Authors: Basson Rosemary
Published: August 2008

A new model of women's sexual response reflects their various motivations to be sexual and the fact that psychological and biological factors strongly influence their arousability. Examples of factors stemming from diabetes are included. To increase emotional intimacy with their partner, women will deliberately find or be receptive to sexual stimuli that can potentially be sexually arousing. Only later do they sense specifically sexual need to continue for the sake of sexual sensations, sexual tension and possible orgasmic release. A model of women's subjective sexual arousal reflects the ongoing modulation from her emotions and cognitions as well as highly variable genital feedback.
Pathophysiology of erectile dysfunction
Authors: Eardley Ian
Published: August 2008

New knowledge regarding the importance of vascular, endocrine, cellular, neural and psychological mechanisms in the pathophysiology of erectile dysfunction has led to changes in the theories of causation. Additionally several drugs can impair sexual function. These topics are reviewed herein.
Apomorphine SL in the treatment of erectile dysfunction
Authors: Kell Philip , Dean John , Ralph David
Published: August 2008

Men with erectile dysfunction (ED) have a high incidence of comorbid cardiovascular disease and diabetes. Additionally, some drugs used to treat cardiovascular disease have been implicated as contributors to ED. Sublingual (SL) apomorphine (Uprima®), a compound with D2-like dopamine receptor agonist effects, has a rapid onset of action, resulting in erectile response within 10 minutes of dosing in some patients (median onset of effect is 18—19 minutes). Apomorphine SL improves erectile function in men with mild-to-moderate ED and is well tolerated in patients with diabetes and/or cardiovascular disease.
Sildenafil citrate in the management of diabetic erectile dysfunction
Authors: Hackett Geoff
Published: August 2008

The efficacy and safety of sildenafil citrate (Viagra) in the treatment of erectile dysfunction (ED) in diabetic men have been investigated in randomised, placebo-controlled trials. In all trials and across all subgroups of patients, sildenafil was associated with improvements in erectile function compared with placebo and side-effects of treatment (mainly headache, flushing and dyspepsia) were mostly transient and mild-to-moderate. Sildenafil is, therefore, concluded to be an effective and well-tolerated treatment for ED in men with diabetes.
Schedule 11 — impact on treating erectile dysfunction
Authors: Hackett Geoff
Published: August 2008

Since 1998, NHS therapy for erectile dysfunction (ED) has only been available under schedule 11 regulations. This involves restriction to certain medical conditions and restrictions of the quantity of medications. A new category was introduced, namely a patient confirmed by a consultant as suffering from `severe distress'. Recent evidence suggests that ED is closely related to many important men's health issues and that restricting access to therapy in this way is both wasteful of resources and leading to missed healthcare opportunities. In the light of recent evidence, certain aspects of schedule 11 need to be reviewed.
The Diabetes Prevention Program: will it really change the way we manage glycaemia?
Authors: Slama Gérard
Published: August 2008

Intervention in the pre-diabetic state to prevent diabetes, its complications and cardiovascular death provides an enticing therapeutic target. Although no drug treatments are as yet indicated for this condition, recent clinical evidence may support active intervention strategies to prevent the conversion of impaired glucose tolerance (IGT) to type 2 diabetes in the future. This article briefly reviews the current position in this field and considers the implications of findings from the latest clinical trials in subjects with IGT.
A patient's perspective
Authors: Salt Neale
Published: August 2008

I was first diagnosed with insulin dependent diabetes at the age of 40. Following this diagnosis I began to gradually experience increasing problems with obtaining and maintaining erections. Although I knew something was wrong, I was embarrassed and thought the problem would just go away. It was a couple of years before I made the decision to go and see my doctor and was diagnosed as suffering from erectile dysfunction (ED) at the age of 42.
Diabetes and sexual function in older adults: results of an international survey
Authors: Nicolosi Alfredo , Glasser Dale B , Brock Gerald , Laumann Edward , Gingell Clive
Published: August 2008

The Global Study of Sexual Attitudes and Behaviors (GSSAB) is a contemporaneous survey of attitudes, behaviours, beliefs and satisfaction with relationships among men and women aged 40—80 years. Interviews were conducted with more than 26,000 subjects from 28 countries.

Data captured from the survey indicated that the majority of adults are sexually active into their later years and that sex remains an important part of their overall life. This paper will discuss comparisons between diabetic and non-diabetic participants. Overall, approximately 10% of subjects reported that they had diabetes mellitus. Fewer diabetic than non-diabetic subjects reported that they had had sexual intercourse in the last 12 months and among sexually active subjects, diabetic subjects tended to report lower levels of physical and emotional satisfaction in their relationship with their partner. Symptoms of sexual dysfunction were more common among diabetic men than non-diabetic men. However, fewer than 15% of subjects had discussed their sexual problems with a doctor.
Review: The pathogenesis of type 2 diabetes and cardiovascular disease
Authors: Marso Steven P
Published: August 2008

Type 2 diabetes mellitus is increasing in prevalence, and is a potent risk factor for the development of atherosclerotic vascular disease and increased risk of adverse cardiovascular events. Approximately 15—25% of patients presenting with ischaemic heart disease have a history of diabetes mellitus. This cohort of patients continues to be at heightened short and long-term risk. This review highlights the many proposed biological drivers that likely play a deterministic role in the cardiovascular outcome of patients with type 2 diabetes mellitus.
Type 2 diabetes and atherosclerotic cardiovascular disease: do they share common antecedents?
Authors: Krentz Andrew J
Published: August 2008

It has been suggested that the association between type 2 diabetes and atherosclerotic cardiovascular disease might result from a shared antecedent — the `common soil' hypothesis. The antecedent could provide a fundamental link between type 2 diabetes and atherosclerosis via the metabolic (or insulin resistance) syndrome. The relative contributions of genes, fetal nutrition and environmental factors to this syndrome remain unclear. Although most patients with type 2 diabetes have insulin resistance, it is uncertain whether the insulin resistance-hyperinsulinaemia complex directly promotes atherogenesis, and whether type 2 diabetes and atheroma are connected via a common mediator such as central obesity, vascular endothelial dysfunction, or disordered lipid metabolism. Insulin sensitivity and cardiovascular risk may be influenced by adipocytokines (e.g. leptin and adiponectin), by excess fatty acids liberated from visceral fat, and inflammatory processes. Disturbances of the neuro-endocrine system, possibly mediated via visceral obesity, are also under investigation. Other putative links between type 2 diabetes and atheroma include polymorphisms in the genes for tumour necrosis factor-α,insulin-like growth factor-1 promoter, and lamin A/C. Trials with certain cardioprotective agents including inhibitors of the renin-angiotensin-aldosterone system and statins can improve cardiovascular outcomes and protect against the development of type 2 diabetes, lending support to the common soil hypothesis.
Prevention of diabetes in cardiovascular studies: implications for the aetiology of type 2 diabetes
Authors: Mcdougall Claire , Fisher Miles
Published: August 2008

Recent studies have shown the importance of lifestyle measures in preventing or delaying the development of type 2 diabetes in people with impaired glucose tolerance (IGT). Lifestyle measures appear to be more beneficial than therapy with metformin, or acarbose, and the benefit is most likely to be mediated by reductions in insulin resistance. Several large, multi-centre cardiovascular studies have also been performed where the development of new diabetes has been a secondary end point, and some ACE inhibitors, angiotensin receptor antagonists, and statins also appear to prevent or delay the development of diabetes in at-risk patients. These may act by increasing insulin sensitivity, decreasing inflammatory markers, or by affecting other key components of the metabolic syndrome. This is being tested in ongoing studies in patients with IGT.
NICE guidelines: management of blood glucose in type 2 diabetes
Authors: Bailey Clifford J , Campbell Ian W
Published: August 2008

NICE work if you can achieve it: the latest guidelines for management of blood glucose in type 2 diabetes.
Optimising glycaemic control — the role of long-acting insulin analogues in basal insulin therapy
Authors: Owens David Raymond
Published: August 2008

Current insulin treatment regimens effectively combat post-prandial hyperglycaemia, but are unable to reinstate normal fasting plasma glucose concentrations. The advent of long-acting soluble insulin analogues, such as insulin glargine and insulin detemir, offers improved control of basal hyperglycaemia without increasing the risk of hypoglycaemia.
Review: Landmark developments in clinical cardiology over the last 50 years
Authors: Julian Desmond G
Published: August 2008

The practice of cardiology has been transformed over the last 50 years. In the 1950s, cardiologists were mainly concerned with rheumatic valve disease and congenital heart disease in the older child and adult. Today, the focus is almost exclusively on coronary heart disease. The changes are partly due to epidemiological factors but, to a large extent, they are due to a series of remarkable advances. These include diagnostic techniques, such as echocardiography and coronary arteriography, and both medical and surgical treatments. Most of these developments are the result of the work of innovative individuals.
Type 2 diabetes as an inflammatory disorder
Authors: Sattar Naveed , Perry Colin G , Petrie John R
Published: August 2008

Although considerable research has addressed the potential role of inflammatory mediators in the pathogenesis of coronary heart disease, the relevance of this pathway to the pathogenesis of type 2 diabetes has only recently attracted interest. Circulating levels of inflammatory mediators correlate with insulin resistance and are significantly elevated in groups at risk of type 2 diabetes. Several prospective studies indicate that C-reactive protein and white cell count, together with other acute phase markers, predict incident diabetes independently of established predictors. Measures known to prevent diabetes (weight loss, exercise and metformin) and those more recently suggested (statins, ACE inhibitors and thiazolidinediones) have all been shown to exhibit anti-inflammatory actions. Mechanisms linking inflammation to diabetes development are beginning to be unravelled. Emerging knowledge of inflammatory mediators may help to predict those at risk of type 2 diabetes, and further work in this area may lead to novel means of prevention and treatment.
Obesity in type 2 diabetes — local experience in a district general hospital
Authors: Richardson Tristan , Kerr David
Published: August 2008

Obesity, diabetes and glycaemic control are inter-linked. Weight gain is associated with worsening diabetic control and can be exacerbated by therapies aimed at controlling hyperglycaemia. Auditing our practice in a district general hospital, we have examined our diabetic population with regards to age and weight, HbA1C and body mass index (BMI), and for weight gain following conversion to insulin.
The ethics of auditing diabetes in primary care
Authors: Cosgrove Martin
Published: August 2008

The modern general practitioner is able to examine and audit his practice diabetes population in great detail because of extensive computerisation and Read-coding. The ability to compare one practice statistics with another brings with it added pressures to be seen to achieve certain standards. Whilst this is a laudable concept, it results in some ethical issues that have hitherto not been explored. In this article, Dr Martin Cosgrove explores some ethical aspects of audit in general practice and outlines three pitfalls for general practitioners when undertaking audit in preparation for external assessment.
Review: Autonomic neuropathy: a marker of cardiovascular risk
Authors: Kempler Peter
Published: August 2008

Cardiac autonomic neuropathy (CAN) represents a serious complication as it carries an approximately five-fold risk of mortality in patients with diabetes just as in those with chronic liver diseases. The high mortality rate may be related to silent myocardial infarction, cardiac arrhythmias, cardiovascular and cardiorespiratory instability and to other causes not yet explained. Resting tachycardia due to parasympathetic damage may represent one of the earliest signs. Typical findings referring to autonomic dysfunction may include exercise intolerance, orthostatic hypotension and cardiac dysfunction to rest or exercise. Severe autonomic neuropathy may be responsible for spontaneous respiratory arrest and unexplained sudden death. A relationship between the presence and/or severity of CAN and corrected QT interval prolongation is well documented. Better understanding of the prognostic importance of autonomic neuropathy followed the use of simple non-invasive cardiovascular reflex tests. These most commonly include heart rate variation in response to deep breathing, standing, the Valsalva maneouvre and blood pressure response to standing and sustained handgrip. Near normoglycaemia is now generally accepted as the primary approach to the prevention of diabetic neuropathy, but is not achievable in most patients. Our experience of the use of the antioxidant alpha-lipoic acid in the treatment of cardiac autonomic neuropathy is described.
Review: Peripheral arterial disease in diabetes: time for a co-ordinated approach to management
Authors: Krentz Andrew J , Mani Raj , Shearman Cliff P
Published: August 2008

Peripheral arterial disease (PAD) is a major manifestation of systemic atherosclerosis. A close association between PAD and diabetes mellitus has long been recognised. Substantial morbidity results from PAD-related intermittent claudication, ulceration and critical limb ischaemia, culminating for some patients in limb loss or death. While effective lifestyle and pharmacological treatments are available for intermittent claudication these approaches are widely underutilised. Surgical intervention is indicated in relatively few patients with stable intermittent claudication. However, the high risk of premature death from the consequences of generalised atherosclerosis, notably coronary heart disease, mandates identification and treatment of modifiable cardiovascular risk factors. Sub-optimal management of cardiovascular risk in patients with PAD may reflect disparate and poorly co-ordinated care. Among patients with diabetes, PAD poses additional dangers, arterial insufficiency being a major, and possibly underestimated, component of diabetic foot disease. The combination of PAD and diabetic neuropathy is common, particularly in the elderly, resulting in impaired infection control and delayed healing of foot ulcers. PAD may also cause ischaemic ulcers. The contribution of PAD to duration of hospitalisation and longer-term clinical outcomes remains uncertain. There appears to be scope for improving the efficiency of clinical care for patients with PAD. A co-ordinated multi-disciplinary approach is required to deliver optimal care to these patients. Modifiable cardiovascular risk factors should be identified and treated. Deficiencies in podiatry and related services in the UK need to be addressed.
The aetiology of neuropathy in experimental diabetes
Authors: Cameron Norman E
Published: August 2008

Most information on the aetiology of experimental diabetic neuropathy comes from studies on rodent models, particularly the streptozotocin-diabetic rat. The major factor that impairs small and large nerve fibre function is a decrease in nerve and ganglion perfusion. This leads to reduced conduction velocity, increased resistance to ischaemic conduction failure, blunted regenerative capacity, painful neuropathy, and autonomic nerve dysfunction. Hyperglycaemia, altered lipid metabolism and reduced insulin action combine to cause adverse metabolic effects on vasa nervorum, vascular endothelium being a notable target. The resultant reduced vasodilation and increased vasoconstriction causes endoneurial hypoxia. Oxidative stress is of primary importance, due to increased production of reactive oxygen species from a plethora of intra- and extracellular sources. Advanced glycation and carbonyl stress play a supporting role, as does essential fatty acid dysmetabolism. These mechanisms are associated with alterations in cell signalling mediated by protein kinases, nuclear factor Kappa B and poly (ADP-ribose) polymerase.
Review: Reconsidering the value of fibrates: lessons from the trials
Authors: Barter Philip
Published: August 2008

Therapy with both statins and fibrates reduces the risk of coronary events. In the fibrate studies the extent of reduction is disproportionately large in people with features of the metabolic syndrome such as overweight, elevated baseline levels of plasma triglyceride and low baseline high density lipoprotein-cholesterol (HDL-c). In such people, treatment with fibrates results in a 40—50% reduction in coronary heart disease events, much greater than predicted (from the human population studies) by the joint changes in concentrations of HDL-c or low density lipoprotein-cholesterol.
Dyslipidaemia in type 2 diabetes: epidemiology and biochemistry
Authors: Valabhji Jonathan , Elkeles Robert S
Published: August 2008

Lipid abnormalities in type 2 diabetes are characterised by high triglyceride concentrations, low high density lipoprotein-cholesterol concentrations, and normal total and low density lipoprotein-cholesterol (LDL-c) concentrations. LDL particles, however, are small and dense. Epidemiological evidence for these lipid abnormalities, and for the associations between lipid abnormalities and the increased risk of cardiovascular disease in type 2 diabetes, are presented. Most, of the lipid abnormalities in type 2 diabetes can be explained by reduced action of insulin at the tissue level. The biochemical and metabolic mechanisms underlying the lipid abnormalities are discussed.
ASCOT — lipid lowering arm
Authors: Kirby Mike
Published: August 2008

The Anglo-Scandinavian Cardiac Outcomes Lipid Lowering Arm (ASCOT-LLA) has recently been terminated early due to significant reductions in major cardiovascular events amongst patients taking atorvastatin. This article summarises the study and considers its implications for clinical practice.
Review: Implications from hypertension outcome trials for the management of patients with hypertension and diabetes
Authors: Brown Morris J
Published: August 2008

The UKPDS highlighted the importance of blood pressure control in patients with type 2 diabetes. In this review I draw on data from the INSIGHT and other recent outcome trials in hypertension which provide clear evidence that it is the achievement of good control of blood pressure, irrespective of the initial choice of drug, that is the major determinant of outcome. The INSIGHT trial provides hard evidence of how resistant to treatment patients with diabetes really are. In this review I offer a theoretical and practical solution in the form of a stepwise algorithm using multiple therapies.
Blood pressure measurement in diabetes: theory and practice
Authors: Petrie John R
Published: August 2008

Good blood pressure (BP) control is at least as important as blood glucose control in diabetes, and may be easier to achieve. BP measurement is currently undergoing considerable change, e.g. patient empowerment is being facilitated by self-monitoring of BP at home using affordable semi-automatic devices. This article discusses some of the common pitfalls from a personal perspective. Features of best practice for BP measurement are outlined and some practical suggestions for improvement in a diabetes setting are provided.
Comparing audits of cardiovascular risk in patients with diabetes in primary care
Authors: Kennedy Susan
Published: August 2008

Regular audit of clinical standards with appropriate audit standards encourages small but sustainable improvements in care. The National Service Framework for Diabetes in England and Wales, and the Clinical Standards Board for Scotland, have generated a great number of proposals for improvements in the delivery and documentation of cardiovascular disease prevention in diabetes. In the future, advances in information technology and managed clinical networks are proposed to facilitate improvement in diabetes care. This article describes how, over the last few years, some cardiovascular aspects of diabetes care, including blood pressure control and aspirin/statin prescription, have been monitored and improved in general practice in a deprived area.
Review: The management of acute myocardial infarction in patients with diabetes mellitus
Authors: Williams Ian L , Noronha Brian , Zaman Azfar G
Published: August 2008

Diabetic subjects are more likely to experience a myocardial infarction and have worse outcomes compared to non-diabetic subjects. The underlying pathophysiology of the atherosclerotic process is not significantly different in diabetic subjects, but the prothrombotic and procoagulant state with which diabetes is associated is thought to contribute to the higher incidence of and worse prognosis after myocardial infarction. Difficulties of re-establishing vessel patency by thrombolytic or mechanical means contribute to the high morbidity and mortality. The diffuse nature of arterial disease with accompanying metabolic derangement contribute to impaired compensatory mechanisms, increased infarct size and a disproportionately more substantial impairment of left ventricular function. The newer adjuvant antithrombotic and anticoagulant agents have particular roles in management therefore and careful modulation of glucose metabolism in the acute and follow-up phase of an infarct may favourably influence outcome.
Review: Insulin-like growth factor-related proteins and diabetic complications
Authors: Livingstone Callum , Ferns Gordon Aa
Published: August 2008

The insulin-like growth factor system and, in particular, insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-1 (IGFBP-1) are dysregulated in type 1 and type 2 diabetes. Serum IGF-I levels are low in both forms of diabetes, and this may be in part genetically determined. It is possible that the reduced serum levels of IGF-I are involved in the development of microvascular and macrovascular complications. Fasting serum IGFBP-1 levels are usually low in early type 2 diabetic patients with insulin resistance and hyperinsulinaemia but may be raised in patients with particularly poor glycaemic control and severe beta-cell failure. Treatment with IGF-I/binding protein complexes has been shown to improve glycaemic control in conjunction with insulin and may in future have a place in the treatment of diabetes, potentially to prevent diabetic complications. Serum IGFBP-1 determination may have utility in the assessment of cardiovascular risk and as an indicator for insulin resistance.