bluuebunny/crossref_metadata_2025 huggingface dataset:
The HOPE Study and MICRO-HOPE Substudy
Authors: Patel Vinod , Panja Srinivas , Venkataraman Asok
Published: August 2008

Background

ACE inhibitors have a special role in diabetes care. They have been proven to reduce urinary albumin excretion and reduce the rate of progression of diabetic nephropathy and retinopathy. 1-3 There is proven benefit post myocardial infarction, with a greater beneficial effect in patients with diabetes in comparison to those without. 4 The effect of ACE inhibitors in patients who have low ejection fractions or overt cardiac failure is well described.5 More recent studies indicate other benefits of ACE inhibitors such as improving dyslipidaemia and insulin sensitivity.

Cardiovascular disease is the commonest cause of mortality among patients with type 2 diabetes. A recent study reports the standardised mortality ratio to be considerably higher in people with diabetes with the vast majority of the excess due to cardiovascular disease (type 1 diabetes: women x 6.41, men x 2.94, type 2 diabetes: women x 1.6, men x 1.41).6 Patients with type 2 diabetes who have no evidence of previous coronary heart disease were found to be at the same risk of myocardial infarction and cardiovascular death as non-diabetic patients who had already suffered from a myocardial infarction.7

The diabetes subject cohort of the HOPE Study, (Heart Outcomes Prevention Evaluation Study), sought to investigate whether ACE inhibitor treatment with ramipril in high-risk patients with diabetes lowers the risk of cardiovascular events.8 Within this main study the MICRO-HOPE substudy investigated the effect of ACE inhibitor treatment with ramipril on microalbuminuria and diabetic retinopathy. 9 The aim of this article is to offer a clinical summary of the above studies and suggest recommendations for clinical practice.
Retinal perfusion pressure and pulse pressure: clinical parameters predicting progression to sight-threatening diabetic retinopathy
Authors: Patel Vinod , Sailesh Sankaranarayanan , Panja Srinivas , Kohner Eva
Published: August 2008

Background and aims his paper investigates the roles of retinal perfusion pressure and pulse pressure in progression to sight-threatening diabetic retinopathy. Retinal perfusion pressure is dependent upon the systemic blood pressure and the intra-ocular pressure. We have examined the hypothesis that the early deleterious effect of hypertension on the retinal circulation which leads to perfusion pressure damage is due to a unique relationship between the intra-ocular pressure and the systemic blood pressure. Clinically this is manifest as hypertensive retinopathy and diabetic retinopathy.

Materials and methods From a prospective database, data on all new patients with background diabetic retinopathy referred during a three year period (n=104) were analysed for progression to sight-threatening diabetic retinopathy.

Results Retinal perfusion pressure and pulse pressure were found to be the strongest predictors of progression to sight-threatening diabetic retinopathy (Chi Square linear trend statistic, relative risk ratios).

Progression to maculopathy by quartilesFor retinal perfusion pressure, the relative risk ratios increased from 1.00 in the first quartile (39.7—50.1 mmHg), to x 5.8 in the second quartile (50.2—56.1 mmHg), to x 6.4 in the third quartile (56.2—60.0 mmHg), to x 9.1 in the fourth quartile (60.1—75.3 mmHg) (p=0.012). For pulse pressure the values were x 1.00, x 4.0, x 4.5, x 6.0 respectively (p=0.021). For systolic pressure the values were x 1.00, x 3.4, x 5.5, x 5.5 respectively (p=0.026). Diastolic pressure was not significant.

Progression to proliferative retinopathy by quartilesFor retinal perfusion pressure, the relative risk ratios increased from 1.00 in the first quartile to x 2.9 in the second quartile, x 4.2 in the third quartile to x 4.1 in the fourth quartile (p=0.002). For pulse pressure the values were x 1.00, x 1.7, x 3.8, x 5.5 respectively (p=0.002). For systolic pressure the values were x 1.00, x 0.5, x 2.9, x 3.8 respectively (p=0.008). Diastolic pressure was not significant.

Conclusion Retinal perfusion pressure and the pulse pressure are important predictors of progression to sight-threatening diabetic retinopathy.
Monitoring antioxidant effects using methaemoglobin formation in diabetic erythrocytes †
Authors: Coleman Michael D , Tolley Helen L , Desai Amisha K
Published: August 2008

Deficiencies in the reducing power of diabetic erythrocytes can be studied using the sulphone metabolite, monoacetyl dapsone hydroxylamine (MADDS-NHOH) to generate methaemoglobin, which is a form of oxidative stress. The effects of three antioxidants, dyhydrolipoic acid (DHLA), lipoic acid and ascorbate were compared using this method in erythrocytes of type 1 diabetic patients. During 2-hour incubations, DHLA and lipoic acid significantly reduced MADDS-NHOH-mediated methaemoglobin formation to the same extent in diabetic and non-diabetic erythrocytes. In contrast, ascorbate markedly increased MADDS-NHOH-mediated methaemoglobin formation at all time points up to 2 hours for diabetic cells and 15—60 minutes in non-diabetic erythrocytes. Ascorbate abolished the deficiency in methaemoglobin sensitivity normally seen in diabetic erythrocytes compared with non-diabetic erythrocytes. During a 1-hour pre-incubation period, neither DHLA, lipoic acid nor ascorbate significantly altered total thiol concentrations. After a 2-hour incubation with MADDS-NHOH, thiol concentrations did not significantly change in the non-diabetic erythrocytes, but they fell significantly in the diabetic cells. Diabetic and non-diabetic erythrocytes pre-incubated with ascorbate, DHLA and lipoic acid showed no changes in thiol levels in the presence of MADDS-NHOH. In summary, ascorbate, DHLA and lipoic acid showed contrasting effects on methaemoglobin generation, although they each abolished the diabetic erythrocytic deficit in total thiol status caused by hydroxylamine-mediated methaemoglobin formation. This work provides evidence for the potential future use of antioxidant supplements in diabetic management.
Utilisation of minimum databases for effective diabetes care
Authors: Winocour Peter H
Published: August 2008

Effective diabetes care requires a functional information system that can be utilised in different healthcare settings. Such systems will enable focused individual patient care, and provide an opportunity to identify and meet needs within area health economies, address issues of quality of healthcare, and support research, education and audit. At present over 25% of secondary care services in the United Kingdom do not have any computerised diabetes database. This severely impairs efforts to identify the case load and provide integrated diabetes care across primary and secondary care, and to offer full coverage of screening schemes to detect diabetic retinopathy. The data included in any such system need to be structured and operate at different levels of complexity and detail. It should be feasible to enter and access data whilst maintaining patient confidentiality. Funding issues need to be addressed in the establishment and maintenance of databases if the ambitions of the National Service Framework (NSF) for Diabetes are to be realised.
The STORM report: implications for care
Authors: Campbell Ian W
Published: August 2008

Sibutramine is a newly available satiety-inducing agent which also increases energy expenditure. Its efficacy was evaluated with a two-year controlled study called STORM (Sibutramine Trial of Obesity Reduction and Maintenance). 605 obese subjects (BMI 30—45 kg/m2) were recruited, and 499 completed an initial six months of exercise, diet and sibutramine (10 mg/day) therapy. 93% achieved >5% weight loss. After a further 18 months of this treatment most subjects maintained 80% of their body weight loss whereas subjects receiving placebo tablets regained over 75% of their weight loss. The STORM trial suggests that sibutramine promotes weight loss and may assist weight control in obese subjects unable to maintain adequate dietary regimens, whereas efficacy of the pancreatic lipase inhibitor orlistat is dependent on dietary compliance.
The Scottish Intercollegiate Guidelines Network (SIGN)
Authors: Miller Juliet
Published: August 2008

The Scottish Intercollegiate Guidelines Network (SIGN) was established in 1993. It develops evidence-based clinical guidelines for the National Health Service in Scotland. The development of the guidelines includes systematic identification and critical evaluation of available evidence, and in the development of recommendations for changes in practice, representatives of all the relevant disciplines and professions are involved. To date 55 SIGN guidelines have been published; the most recent of which is the revised guidelines on the management of diabetes.
Effect of losartan on insulin sensitivity and serum lipids in hypertensive type 2 diabetic patients
Authors: Mulcahy Michael P , Ahmed Kahlid , Luzio Stephen , Owens David R , Lazarus John H
Published: August 2008

Background Insulin resistance and hypertension are common co-existing conditions. Antihypertensive agents have differing effects on insulin sensitivity (SI). We studied 11 mildly hypertensive insulin-resistant type 2 diabetic patients to observe any changes in SI, glucose effectiveness (SG), serum total cholesterol, serum triglycerides and blood pressure (BP) with the introduction of the angiotensin II inhibitor, losartan.

Methods To assess SI and SG, we used the frequently sampled, intravenous glucose tolerance test with minimal model analysis prior to and after three months treatment with losartan potassium 50—100 mg daily. BP was assessed using a Space Labs 24-hour BP recording device before, during and after treatment with losartan.

Results There were no significant differences in SI and SG pre-and post-treatment, however, there was a non-significant reduction in mean BP, total cholesterol and triglyceride concentrations.

Conclusion There were no adverse effects of losartan on SI or SG. The lower but non-significant serum total cholesterol and triglyceride concentrations warrant further study.
Review: Type 2 diabetes — implications for macrovascular mechanics and disease
Authors: Nicolaides Eleftherios , Jones Christopher Jh
Published: August 2008

Before macrovascular disease is established, type 2 diabetes is associated with structural and functional changes in large arteries that lead to increased stiffness, abnormal pulse wave travel and systolic hypertension. Structural changes result mainly from glycation of wall components. Functional changes originate in endothelial dysfunction. Increased arterial stiffness, or decreased arterial distensibility, increases pulse wave velocity and the amplitude of reflected waves, so that reflected waves arrive early and augment central systolic pressure. This promotes the development of left ventricular hypertrophy, an independent risk factor for cardiovascular mortality. One of the major mechanisms of arterial stiffening is endothelial dysfunction with reduced nitric oxide (NO)-mediated vasodilatation, the initial lesion in pre-atherosclerotic diabetes. To understand better the mechanisms of endothelial dysfunction will be vital if future therapeutic interventions are targeted to disease prevention. Protein glycation in poorly controlled diabetes is also damaging to blood vessels and must be limited by good diabetic control over the longer term.
Review: Overview of diabetic eye disease
Authors: Leese Graham P , Ellis John D
Published: August 2008

Visual impairment in diabetes is much more common than blindness, and causes major functional disability. Much of this could be avoided by early detection using comprehensive eye screening programmes. These would be most efficiently delivered by digital photography, and automated grading of normal images. Slit lamp examination would provide back-up for patients whose eyes are difficult to examine. It may be possible to extend screening intervals for patients with no baseline retinopathy. There is strong evidence that aggressive glycaemic and blood pressure control prevent development and progression of retinal disease. Laser treatment is less successful in preventing visual loss in maculopathy than in proliferative retinopathy. New drugs such as protein kinase-C inhibitors may become available to treat diabetic retinal disease.
Review: The epidemic of diabetic renal disease — the practical challenges for renal replacement programmes
Authors: Davies Simon J
Published: August 2008

Diabetic patients represent the largest group requiring renal replacement therapy in the developed nations, although take-on rates in the UK still lag behind other countries. As a group, diabetic patients present specific challenges to those providing renal replacement, including disproportionate late referral and under-recognition of renal insufficiency, multiple co-morbidity, and issues relating to choice of dialysis modality and when dialysis should be started. This review explores these issues and argues that it is by concentrating on the pre-dialysis phase of care that clinicians are most likely to achieve a more favourable clinical outcome. In addition to the benefits of good blood pressure and diabetic control, time is needed to inform and educate the patient prior to dialysis, and to evaluate co-morbidity if transplantation is to be considered. To achieve this, patients require nephrological supervision in the context of a well-resourced, multidisciplinary pre-dialysis programme, commencing a minimum of one year before starting renal replacement therapy.
Vascular disease and survival in patients with type 2 diabetes and nephropathy
Authors: Joss Nicola , Paterson Kenneth R , Deighan Christopher J , Simpson Keith , Boulton-Jones J Michael
Published: August 2008

Diabetic nephropathy in patients with type 2 diabetes is associated with progressive renal failure and accelerated cardiovascular disease. We performed a retrospective review of 126 patients who presented to a combined diabetic-renal clinic between 1989 and 1999. We analysed the prevalence of vascular disease, cardiovascular risk factors and the use of cardioprotective drugs. Patient survival was analysed and poor prognostic indicators were identified. At referral, 68% had documented vascular disease, mean blood pressure (BP) was 162/84 mmHg, HbA1C 8.2% and cholesterol 6.2 mmol/L. Significant improvements were achieved in BP and cholesterol. Median patient survival from time of referral was 61 months. Seventy-three percent of deaths were a consequence of vascular disease. Factors predicting death at referral were low haemoglobin, low creatinine clearance, high albumin: creatinine ratio, lack of use of aspirin and female sex. These data highlight the extent of vascular disease and poor survival in patients with type 2 diabetes and nephropathy. The importance of early cardioprotection is emphasised.
Pioglitazone reduces atherogenic dense low density lipoprotein (LDL) particles in patients with type 2 diabetes mellitus
Authors: Winkler Karl , Friedrich Isolde , Baumstark Manfred W , Wieland Heinrich , März Winfried
Published: August 2008

Aim The new oral antidiabetic agent pioglitazone improves insulin sensitivity and glycaemic control, lowers triglycerides and increases high density lipoprotein (HDL) cholesterol in type 2 diabetes. The effect of pioglitazone on low density lipoprotein (LDL) subfractions is investigated, herein.

Methods The effect of pioglitazone monotherapy (45 mg o.d. for six months) on LDL subfractions was observed in 30 patients with poorly controlled type 2 diabetes (HbA1C ≥ 7.5% and < 11.5% and triglycerides ≥ 150 mg/dL). The distribution of LDL subfractions was determined by equilibrium density gradient ultracentrifugation before and during treatment.

Results HbA1C (9.5% before and 7.4% on treatment, p<0.001), triglycerides (-135 mg/dL [-32.2%], p=0.002) and apo B in LDL-6 (the most dense LDL subfraction) decreased significantly. The mean diameter of LDL particles increased (19.5 nm before and 19.8 nm on treatment, p=0.005), while the mean LDL density decreased significantly (from 1.0394 kg/L to 1.0381 kg/L on treatment; p=0.033). HDL increased from 36.3 mg/dL to 44.2 mg/dL (+ 21.6%, p<0.001). Total cholesterol and LDL-cholesterol did not change significantly.

Conclusions The results confirm that pioglitazone improves glycaemic control in patients with type 2 diabetes. In addition, pioglitazone reduced the proportion of atherogenic dense LDL. The effects of pioglitazone on lipoprotein metabolism may translate into a reduced risk for atherosclerotic complications in type 2 diabetes.
Diabetes and embryonic stem cells: a guide to the ethical debate
Authors: Kirklin Deborah
Published: August 2008

Stem cell research, if successful, could provide a means of replacing damaged tissue in patients with diabetes. Controversially, the best stem cells for research and possible therapies seem to be those harvested from embryos, cloned or otherwise. As a result the morality of undertaking such research is hotly contested with vocal champions both for and against this work. To help clinicians and scientists reach their own conclusions about whether stem cell research using human embryos should be sanctioned or not, an impartial overview of the moral arguments offered by both sides is provided.
Review: The vascular system and erectile dysfunction in diabetes — the role of penile Doppler
Authors: Jones Robert WA , Gingell J Clive
Published: August 2008

Diabetes is associated with an increased risk of Dvasculogenic erectile dysfunction due to arterial occlusive disease and impaired vascular smooth muscle relaxation. Doppler ultrasound of the cavernosal artery offers a functional evaluation of penile haemodynamics, in particular the accurate assessment of arterial insufficiency. The current role of penile Doppler testing in the assessment of diabetic patients with erectile dysfunction is reviewed.
Erectile dysfunction in patients with diabetes mellitus — advances in treatment with phosphodiesterase type 5 inhibitors
Authors: Snow Kenneth J
Published: August 2008

Erectile dysfunction (ED) is a common complication of diabetes mellitus. In four independent, 12-week, randomised, placebo-controlled clinical trials that evaluated the pro-erectile properties of the selective phosphodiesterase type 5 (PDE-5) inhibitors, sildenafil (Viagra) (25—100 mg), tadalafil (10 and 20 mg) and vardenafil (10 and 20 mg) in men with ED secondary to diabetes mellitus, all the active drugs were significantly superior to placebo. In this difficult-to-treat population, the greatest difference from placebo for the overall responder rate of diabetic men reporting improved erections occurred with vardenafil 20 mg (72% vs. 13% for placebo).

All the PDE-5 inhibitors were generally well tolerated. There were fewer reports of visual disturbance with vardenafil or tadalafil than with sildenafil, which may be due to their greater selectivity for PDE-5 inhibition and less cross-reactivity with retinal PDE-6 inhibition.

The studies suggest there may be significant differences between the three drugs. However, only head-to-head studies will determine true differences in both efficacy and side effect profile.
The importance of assessing and treating sexual dysfunction in the cardiac patient
Authors: Martin Emma
Published: August 2008

In March 2001 the Male Cardiovascular Health Clinic was set up to assess and treat sexual dysfunction (which is primarily erectile dysfunction) in male cardiac patients. Emma Martin (Cardiac Sexual Advice Sister) and Dr Graham Jackson (Consultant Cardiologist) saw the need to offer care to cardiac patients and their partners for sexually related conditions that were otherwise going unnoticed and untreated. Emma Martin gives an account of her role, which has proved challenging and rewarding.
Team skills
Authors: Johnson David
Published: August 2008

David Johnson, a senior route check 747 Captain with British Airways, gives a personal account of team resource management. Captain Johnson's involvement with clinical governance began after an article he had written, describing similarities between aviation and medicine particularly in the area of team skills, attracted the attention of Professor Aidan Halligan and the NHS Clinical Governance Support Team. But why clinical governance and what has this to do with diabetes and vascular disease?
Review: Diabetes as a procoagulant condition
Authors: Kluft Cornelis , Jespersen Jorgen
Published: August 2008

Major known effects of the metabolic derangements of diabetes in haemostasis are induction of platelet-vascular activation by hyperglycaemia, the increase in fibrinogen, modification of fibrin substrate by glucose and hypofibrinolysis related to insulin resistance. The platelet effects are specifically expressed during high shear stress and may be relevant in particular for developing of micro-angiopathy. Hypofibrinolysis, increased fibrinogen and modifications of fibrin may aggravate microthrombosis and organ damage and contribute to precipitation of coronary and cerebral infarction. In addition to specific anti-diabetic medication to reduce the haemostatic effects, specific antiplatelet and profibrinolytic treatments may be relevant for reducing further the morbidity and mortality in diabetics for both micro- and macro-angiopathy.
Review: The genetics of macrovascular disease in diabetes
Authors: Iacoviello Licia , Ciccarone Elisabetta , Donati Maria Benedetta
Published: August 2008

Patients with diabetes mellitus show an increased risk of developing macrovascular disease. Although common cardiovascular risk factors are abnormally high in patients with type 2 diabetes compared to the general population, they cannot fully explain the high rate of vascular complications. Indeed the occurrence and the severity of such complications are highly heterogeneous even in patients with comparable levels of glycaemic control and similar prevalence of cardiovascular risk factors. Large-vessel atherosclerosis can precede the clinical manifestation of diabetes. This suggests that both atherosclerosis and type 2 diabetes may have common genetic and environmental antecedents. A large body of evidence supports the possible role of genetics in determining the expression of the ischaemic vascular phenotype in diabetic patients, mainly derived from studies in ethnic groups or in first-degree relatives of diabetic patients and from association studies with genetic polymorphisms. Unravelling the polygenic susceptibility factors for macrovascular complications of diabetes is difficult, since diabetes per se has multifactorial inheritance. Direct evidence is largely based on the candidate gene approach in case-control studies. Several systems provide candidate genes that could by themselves or by interacting with other factors, increase the risk of ischaemic vascular disease in diabetic patients mainly related to lipid metabolism, lipoprotein oxidation and haemostatic processes.
Sibutramine update
Authors: Day Caroline , Bailey Clifford J
Published: August 2008

The introduction of sibutramine has brought a new therapeutic option for the management of many overweight and obese patients. To date it has been used by more than eight million patients in over 70 countries. As part of a comprehensive programme that includes diet and lifestyle guidance, the additive effect of sibutramine (10 or 15 mg/day) facilitates patients to achieve and sustain greater weight loss. Overall weight loss is typically 5—10% of starting body weight, and this is almost entirely due to loss of excess adipose tissue. Commensurate with this level of weight loss, benefits have been noted in comorbidities such as insulin resistance, type 2 diabetes and dyslipidaemia. Sibutramine is a serotonin-noradrenaline (norepinephrine) re-uptake inhibitor which acts centrally to induce satiety and maintain thermogenic expenditure. The main side effects are increased heart rate and blood pressure which are generally small, but require frequent checks.
Insulin resistance syndrome in South Asians
Authors: Kain Kirti , Catto Andrew J
Published: August 2008

Although South Asians express increased features (conventional) of insulin resistance syndrome, these do not fully explain the increased mortality both from ischaemic heart disease and ischaemic stroke in South Asians compared to Whites. Thrombotic risk factors for vascular disease, as a part of insulin resistance syndrome in South Asians, are being investigated and are an important moiety. The management of the epidemic of ischaemic vascular disease in South Asians is a major global endeavour.
Review: The dark ages of diabetes
Authors: Tattersall Robert
Published: August 2008

At the time of Queen Elizabeth's coronation in 1953, diabetes was still relatively uncommon. In the young the situation was profoundly depressing. Those whose lives had been saved by insulin in the previous 30 years were now succumbing to blindness, kidney failure and heart attacks for which there was no treatment. Clinics were poorly organised, patchily distributed and, except in major cities, run by general physicians with no training in the management of chronic disease. Yet, in the five years after the coronation, the seeds of many future advances including the delineation of diabetic angiopathy, photocoagulation and diabetes specialist nurses were sown by pioneers whose work went largely unrecognised at the time.
Review: Fifty years of type 1 diabetes
Authors: Gale Edwin Am
Published: August 2008

Research is done by people. Type 1 diabetes was discovered because certain people were in certain places at the right time. Perhaps in a parallel universe someone else would have made the same observations or reached the same insights, but that is not what happened here. It has been my privilege to know many of the people concerned with the discovery, and this is my version of what they achieved.
Review: Fifty years of diabetes management in primary care
Authors: Kirby Mike
Published: August 2008

The incidence of diabetes has increased exponentially over the last 50 years, meaning that the management of diabetes solely by specialist healthcare professionals is no longer feasible. Since the 1970s, primary and community healthcare professionals have increasingly treated patients with diabetes. Advances in diabetes equipment and new treatments have further enabled patients to be treated more conveniently and this has enhanced their quality of life. There has also been an evolution in health service strategies for diabetes — notably growing acknowledgement of the benefits of intensive treatment for patients with type 2, as well as type 1 diabetes, and the now well-recognised importance of effective shared care programmes between primary and secondary healthcare professionals. Thus, the organisation and delivery of care for patients with diabetes has improved dramatically since 1952.
Review: Diabetic Association, BDA, Diabetes UK
Authors: Curnow Sue
Published: August 2008

Patient empowerment, knowledge and an integrated care team are the keys to successful chronic disease management. The Diabetic Association — now known as Diabetes UK — has always advocated patient-centred care and has provided a platform for the patient, the healthcare professional and scientist to meet. From the beginning of the Charity's history, patients and professionals have worked together to promote the present day Mission: `to improve the lives of people with diabetes and to work towards a future without diabetes'; and to set people free from the restrictions of diabetes, provide the highest quality care and information for all.
Do all diabetic patients need statins? A view from primary care
Authors: Ballinger Paul
Published: August 2008

A majority of type 2 diabetic patients now receive routine care from their General Practitioner. The biggest single cause of mortality amongst such patients is ischaemic heart disease; diabetes is now considered to be of equivalent risk to a previous myocardial infarction in non-diabetic individuals. Most type 2 diabetic patients have the insulin resistance syndrome, and accelerated atheromatous disease at the time of diagnosis. The current guidelines on lipid management fail to recognise the unique dyslipidaemia of diabetes, and tend to undertreat the disease. There is a powerful case for all type 2 diabetic patients to receive treatment with a statin at the time of diagnosis.
Diabetic neuropathy: achieving best practice
Authors: Tesfaye Solomon
Published: August 2008

Peripheral neuropathy is one of the commonest complications of diabetes and the commonest form of neuropathy in the developed world.1 Diabetic polyneuropathy encompasses several neuropathic syndromes, and the commonest presentation is chronic distal symmetrical neuropathy (DSP). DSP, often associated with autonomic neuropathy, has two clinical consequences: namely neuropathic pain and foot ulceration. Both often occur in the same individual, and cause severe curtailment of quality of life. The other, less common presentations of diabetic polyneuropathy include acute painful neuropathies, and focal neuropathies (amyotrophy, pressure palsies, truncal radiculopathies, mononeuropathies and mononeuritis multiplex).2 Table 1 shows a recent classification of diabetic polyneuropathy based upon the natural history of the various syndromes.3
Using insulin earlier in the treatment of type 2 diabetes
Authors: Gadsby Roger
Published: August 2008

Type 2 diabetes is a progressive disease. Initial management with diet and exercise is fundamental. However, even if concordance is good, many will go on to require oral agent therapy to control hyperglycaemia. Initial metformin monotherapy and then oral combination therapy may be required as the disease progresses. When combinations of oral agents are insufficient to achieve good glycaemic control insulin therapy will be required. Various combinations of insulin and oral agents can be used to reduce the complications of hypoglycaemia and weight gain associated with insulin treatment. Simple regimes, using once-daily long-acting insulin analogues combined with oral metformin would seem to offer the possibility of good glycaemic control with minimal weight gain and hypoglycaemia.
Cost-outcome benefits of fibrate therapy in type 2 diabetes
Authors: Feher Michael D , Langley-Hawthorne Clare E , Byrne Christopher D
Published: August 2008

To date there have been few studies focusing on economic assessments of fibrate therapy in the management of coronary heart disease (CHD), particularly in patients with type 2 diabetes. A cost-effectiveness model for an economic analysis was established by an assessment of `cost per CHD event avoided' for fibrate therapy. This model was derived from: i) data on CHD events in patients with and without diabetes from randomised controlled trials of lipid-lowering agents, ii) comparisons of fibrate and HMG CoA reductase inhibitor (statin) treatment compared to no treatment and iii) current UK-based drug and clinical event costs. Treatment benefits over a five-year period were calculated, and the sensitivity of the model to the individual variables tested. Fibrate therapy was substantially more cost-effective than statin therapy in patients with diabetes. Economic costings for fenofibrate, as the index fibrate commonly used in the UK, confirmed an annual cost of £2,642— £3,700 per CHD event avoided over a five-year assessment period. Cost-effectiveness ratios derived in the economic model demonstrated that fibrate therapy was equally effective as statin therapy, but at a 54% reduction in annual cost. Current and future CHD treatment guidelines should incorporate pharmacoeconomic data for fibrate as well as statin therapy.
Increased carotid intimal media thickness precedes albuminuria in South Indian type 2 diabetic subjects
Authors: Viswanathan Vijay , Snehalatha Chamukuttan , Mohan Rangamoorthy Suresh , Mamtha Nair Balakrishnan , Ramachandran Ambady
Published: August 2008

Introduction Intimal media thickness (IMT) of common carotid artery (CCA) is used as an index of atherosclerosis. IMT is increased in subjects with diabetes and also with diabetic nephropathy.

Aim The study was undertaken in South Indian type 2 diabetic patients with different degrees of albuminuria to see whether albuminuria worsened IMT.

Material and methods IMT was measured by ultrasonography in 273 diabetic subjects with normoalbuminuria (n=91), microalbuminuria (n=92), clinical proteinuria (Prot) (n=90) and in age-matched non-diabetic subjects (n=99). The diabetic subjects were older than the non-diabetic subjects hence IMT was age-adjusted using a linear regression formula.

Results Age-adjusted IMT value in diabetic subjects was significantly higher (0.88±0.3 mm) than in non-diabetic subjects (0.57±0.34 mm) (p<0.001). Mean IMT in normoalbuminuria (0.87±0.26 mm), microalbuminuria (0.90± 0.33 mm) and Prot (0.86±0.39 mm) patients were not significantly different from each other. Male gender, age, diabetes and total cholesterol were independently associated with IMT, while duration of diabetes, hypertension and HbA1C were not.

Conclusion Increased carotid IMT occurred in type 2 diabetes prior to the presence of albuminuria. Further deterioration in IMT did not occur with the presence of albuminuria.
Review: Lipids and stroke
Authors: Buckley Brendan M
Published: August 2008

Stroke is the third leading cause of death in adults. Although vascular disease is the prime contributor to its pathogenesis, dyslipidaemia is not unambiguously established as a risk factor for stroke in the same way that it is for coronary artery disease. Non-statin treatments of dyslipidaemia have not been shown clearly to help in preventing stroke. However, large clinical trials of treatment with statins over a number of years have demonstrated that these drugs decrease ischaemic stroke rates in persons at risk. Whether this reflects the efficacy of statins in lowering low density lipoprotein-cholesterol (LDL-c) concentrations alone or whether additional mechanisms may apply is not clear.
When and how to measure lipids and their role in CHD risk prediction
Authors: Richmond William
Published: August 2008

Accurate lipid and lipoprotein measurements, control of pre-analytical factors and consideration of biological variability are required for the reliable assessment of coronary heart disease (CHD) risk and the management of dyslipidaemia. Inclusion of high density lipoprotein-cholesterol, in addition to total cholesterol, in risk calculations is preferred to attain good sensitivity and specificity. Although the strong and independent association of triglyceride with CHD has been confirmed, its large biological variation limits its utility as a risk factor or primary treatment target. A fasting profile including triglyceride is essential however for consideration of genetic and secondary causes of dyslipidaemia and decisions on therapeutic intervention.
Pharmacological management of hyperlipidaemia
Authors: Evans Marc , Roberts Aled , Rees Alan
Published: August 2008

Coronary heart disease (CHD) is a major cause of morbidity and mortality. Recent evidence supports the benefits of intensive low density lipoprotein-cholesterol (LDL-c) reduc-of intensive low density lipoprotein-cholesterol (LDL-c) reduction on CHD risk with various ongoing end point trials addressing the issue of optimal cholesterol reduction. Statins reduce LDL-c, and have been shown to reduce CHD event rates in both primary and secondary prevention trials. The magnitude of this effect is not fully accounted for by LDL-c reduction alone and may relate to effects on other lipid parameters.

Fibrates represent the best treatment for raising high density lipoprotein-cholesterol (HDL-c) and a variety of agents, which specifically target HDL-c, are under development.

New therapies being developed to meet the challenge of intensive cholesterol lowering include rosuvastatin, a potent statin, producing reductions in LDL-c of up to 69% and ezetimibe, a selective cholesterol absorption inhibitor, producing reductions in LDL-c of up to 25%.

This review summarises the evidence regarding dyslipidaemia and vascular risk and how advances in lipid-lowering therapy may be important in future management of hyperlipidaemia.
DAIS: how it relates to other lipid intervention studies in diabetes
Authors: Steiner George
Published: August 2008

The Diabetes Atherosclerosis Intervention Study (DAIS) was a multicentre, double-blind, randomised, placebo controlled, angiographic trial of the effects of fenofibrate on lipoprotein abnormalities in people with type 2 diabetes. Fenofibrate improved the lipid profile and retarded the progression of coronary artery disease. DAIS and its implications are considered within the context of other major lipid studies.
Clinical trials of lipid-lowering medication in diabetes
Authors: Durrington Paul
Published: August 2008

Evidence that patients with type 2 diabetes can benefit from statin therapy is strong. Issues remain to be resolved about whether all patients with type 2 diabetes should receive statin treatment. For the present the National Institute for Clinical Excellence has recommended statin treatment in secondary prevention and in primary prevention when coronary heart disease (CHD) risk exceeds 15% over the next 10 years or lipid levels are high. Fibrates are a better first-line drug therapy when triglycerides exceed 10 mmol/L. Consideration should also be given to combining a fibrate with a statin in patients with CHD whose triglycerides exceed 2.3 mmol/L despite statin treatment, but this requires careful monitoring for myositis. Clinical guidelines are needed for the use of lipid-lowering medication in type 1 diabetes.
`Size is not everything`: the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT)
Authors: Mcinnes Gordon T
Published: August 2008

ALLHAT, the largest ever antihypertensiv e trial, compared cardiac outcomes in 42,418 high-risk individuals with mild-to-moderate hypertension, including 36% with diabetes, randomised to: 1) the thiazide-type diuretic, chlorthalidone; or 2) the ACE inhibitor, lisinopril; or 3) the calcium channel blocker, amlodipine. No differences between the groups were observed for the primary outcome coronary heart disease (CHD) but chlorthalidone was superior in preventing some cardiovascular disease events. Since diuretics are less expensive, it might be inferred that these drugs should be the preferred first-line antihypertensive therapy. However, the design and conduct of ALLHAT make interpretation of the results difficult. Despite its size, ALLHAT has few practical implications for management of hypertension.
Optimising treatment of hypertension to prevent cardiovascular complications in type 2 diabetes
Authors: Daly Caroline , Purcell Henry
Published: August 2008

Diabetes is associated with an increased risk of cardiovascular disease which is amplified in the presence of hypertension. Tight control of blood pressure (BP) reduces cardiovascular events in patients with type 2 diabetes. It has been suggested that drugs which interrupt the renin-angiotensin system (RAS) may be superior to other classes of antihypertensive agents. This review assesses the evidence for this suggestion, focusing on recently reported trials including ALLHAT, ANBP2, LIFE, and SCOPE. The evidence suggests that antihypertensive agents which interrupt the RAS offer benefits for diabetic patients with multiple cardiovascular risk factors.
Should BP targets be lower in diabetic patients with microalbuminuria or nephropathy? A systematic review of randomised controlled trials
Authors: Kaiser Thomas , Florack Christiane , Stephan Uta , Sawicki Peter T
Published: August 2008

Does antihypertensive treatment in normotensive patients with diabetic nephropathy alter the progression of kidney failure? We have evaluated studies of renal function which either assessed the effects of different therapeutic blood pressure (BP) goals, or the effects of antihypertensive therapy within the normotensive BP range. Need for renal replacement therapy was regarded as the most valid end point for assessment of deterioration of nephropathy, and change in the glomerular filtration rate (GFR) was regarded as a valid surrogate parameter. Five randomised controlled trials (RCTs) which included normotensive and hypertensive type 1 and type 2 diabetic patients have investigated the effect of lowering of BP within the normotensive range, or from hypertensive values to within the normotensive range. Albumin excretion in urine decreased in the groups randomised to lower BP values, but none of the trials demonstrated any beneficial effect of this intervention on the progression of kidney failure as assessed by the course of GFR. In conclusion, in diabetic patients with microalbuminuria or overt nephropathy, there is no evidence in the literature from RCTs for a beneficial effect of lowering BP within the normotensive range on the risk of kidney replacement therapy or on the loss of glomerular function.
Commentary: Should BP targets be lower in diabetic patients with microalbuminuria or nephropathy?
Authors: Walker James D
Published: August 2008

The authors in the preceding paper have answered a number of specific questions regarding the management of diabetic renal disease. Using a systematic review, they have concluded that although urinary albumin excretion decreases in patients randomised to lower blood pressure (BP) levels within the normotensive range (< 140/90 mmHg), no trials to-date have demonstrated a beneficial effect on glomerular filtration rate (GFR). Thus, the authors state that the available literature does not provide dat S a to support the assertion that BP-lowering within the normotensive range reduces the risk of renal replacement therapy. However, these findings require interpretation before they can influence clinical practice. The benefits of BP-lowering extend far beyond the glomerulus — a fact of crucial importance in terms of the macrovasculopathy so frequently seen inpatients with diabetic renal disease. Moreover, achieving BP levels within the normotensive range in these patients is in itself a success. The analysis provided by Kaiser et al. does suggest that, rather than lowering BP within the normotensive range, other therapeutic avenues may be more fruitfully explored to maximise health gain in this high-risk cohort.
Hypertension, diabetes and cardiovascular risk in ethnic minorities in the UK
Authors: Cappuccio Francesco P , Barbato Antonio , Kerry Sally M
Published: August 2008

Mortality from coronary heart disease (CHD), stroke and end-stage renal failure (ESRF) is high in South Asian (Indo-Asian) migrants in the UK. This is associated with a high prevalence of diabetes and hypertension.

Mortality from stroke and ESRF is also high in migrants to the UK of black African origin. However, CHD mortality is low in this group. This pattern of mortality is also associated with a high prevalence of hypertension and diabetes.

Conventional risk factors, such as cigarette smoking and hypercholesterolaemia, are less prevalent in ethnic minority populations in the UK and unlikely to explain the differences seen between groups, although each risk factor is likely to contribute to the variation in vascular disease within each group.
Metformin inhibits monocyte adhesion to endothelial cells and foam cell formation
Authors: Mamputu Jean-Claude , Wiernsperger Nicolas , Renier Geneviève
Published: August 2008

The United Kingdom Prospective Diabetes Study (UKPDS) found that metformin reduces macrovascular complications in type 2 diabetic patients. To investigate the mechanisms involved we examined the effect of metformin on monocyte adhesion to human endothelial cells (ECs) induced by advanced glycation end-products (AGE), and on monocyte differentiation into macrophages and foam cell formation. Treatment of human ECs with AGEs (100 µg/ml) for up to 12 hours significantly increased human monocyte adhesion. Pre-treatment of the cells with metformin (0.1—2.5 µg/ml) inhibited AGE-induced monocyte adhesion and expression of endothelial cell adhesion molecules. In culture, human monocytes spontaneously differentiated into macrophages, as indicated by phenotypic changes, and increased expression of lectin-like oxidised low-density lipoprotein (LDL) receptor and scavenger receptor type A. Incubation of these cells in the presence of metformin decreased expression of all of these parameters. Metformin also inhibited foam cell formation induced by minimally modified LDL. Overall, these results suggest new mechanisms by which metformin may reduce the risk of vascular complications in patients with type 2 diabetes.
Diagnosis of type 2 diabetes in primary care
Authors: Evans Philip H , Luthra Manjo , Powell Roy , Sweeney Kieran G , Gray Denis Pereira
Published: August 2008

Little is known about the impact of case-finding and protocol-driven screening at a practice level on the increasing prevalence of type 2 diabetes. This cross-sectional study investigated the diagnostic process in 154 patients with diabetes in a single practice with protocol-led screening for diabetes. A large proportion (87%) were diagnosed in primary care and of the 116 (86.6%) patients with type 2 diabetes the majority (58.6%) were also asymptomatic at the time of diagnosis. The commonest reason for screening was the presence of hypertension.
A survey of the number of medications taken by patients 70 years of age and over with diabetes
Authors: Cosgrove Martin
Published: August 2008

Diabetes is a condition where multiple risk factors must be controlled to prevent and treat vascular disease. Polypharmacy is therefore an inevitable consequence of treating diabetes, particularly for the older patient for whom the risk of a fatal vascular event is far greater. The older diabetes patient is also more likely to have coexistent conditions that need treating. This article describes the level of polypharmacy in patients with diabetes who are ≥ 70 years in one general practice. These patients were taking a mean of four cardio-diabetes medications (three for vascular disease/risk factors and one for diabetes). In addition to their cardio-diabetes medications, the average patient was also taking three medications for co-existent conditions.
Diabetes services in primary care: are we prepared for the diabetes NSF?
Authors: Buckley Martin G , Liversedge Stephen N , Dean John D
Published: August 2008

Aims

To conduct a survey examining issues relating to implementation of the diabetes NSF (National Service Framework) in primary care.

Methods

Fifty-two general practices were sent a questionnaire (14 questions) to investigate issues relating to implementation of the NSF for diabetes.

Results

A completed questionnaire was returned by 32 (≥ 60%) of practices. Of these, 30 (93.7%) had a practice register for diabetes, 18 (56.2%) had a screening policy for undiagnosed diabetes and 23 (71.9%) had specific diabetes clinics (SDC).

The practice nurse was at the front line of diabetes care, with the general practitioner, podiatrist and dietitian playing an increased role when patients had uncontrolled risk factors, or complications. In SDC lack of funding, specialist personnel and time were the main barriers to implementing the diabetes NSF.

In most practices holding SDC, patients with diabetes (65.2%) were not seen in the same clinics as patients with other cardiovascular risk problems, but without diabetes (34.8%). In those general practices not holding SDC, the majority reported they did not wish to develop these clinics (60%), due mainly to time restrictions. Only a minority (24%) of general practices referred patients with psychological problems, related to diabetes, to clinical psychology services.

Conclusion

Many general practices lack the necessary infrastructure to deliver comprehensive diabetes care and will struggle, without additional resources, to meet standards of care required, following NSF implementation.