bluuebunny/crossref_metadata_2025 huggingface dataset:
The Glasgow Chart — a simple method for calculation of cardiovascular risk in type 2 diabetes
Authors: Mcintyre Martin , Kerr Stuart , Kennon Brian , Small Michael
Published: August 2008

Aims Current guidelines for lipid lowering as primary prevention advocate a treatment threshold 10-year coronary heart disease (CHD) risk of ≥ 30%. There is a variety of methods of calculating CHD risk, of varying complexity, which incorporate different factors. We aimed to determine if different methods of CHD risk calculation give different results and if a simpler method of CHD risk calculation could be developed for type 2 diabetes.

Methods Using three recognised methods based on the Framingham equation, CHD risk was calculated for 200 consecutive patients with type 2 diabetes attending the clinic. A simple method of establishing those who should be treated with lipid-lowering agents was developed and sensitivity and specificity compared to the established method.

Results Using method 1, only 58 (29%) of the patients would be above the treatment threshold; 108 (54%) with method 2; and 140 (70%) with method 3 ( 2=68.3, p < 0.001). Using the Glasgow Chart, sensitivity and specificity would be 100% and 85% respectively if patients are identified with total cholesterol ≥ 5.0 mmol/L plus two of: 1) age ≥ 50 years; 2) blood pressure ≥ 140/80 mmHg; 3) microalbuminuria.

Conclusions It makes a significant difference which method is used to calculate CHD risk. Our simple method seems to be applicable to patients with type 2 diabetes, but requires confirmation in a larger population.
Review: Diabetes and assisted reproductive technology
Authors: Taylor Clare T
Published: August 2008

Patients with a range of medical disorders, including diabetes mellitus, are increasingly seeking access to assisted reproductive technology (ART). With appropriate patient selection, monitoring and counselling, these technologies may be applied successfully. Diabetes in the female is associated with disturbed ovarian function but strict metabolic control may encourage resumption of ovulation and allow ovarian stimulation for ART. Insulin metabolism appears intimately involved with ovarian function, through mechanisms encompassing the actions of insulin-like growth factors, but is not yet fully understood. Diabetes has minimal effects on spermatogenesis but may severely disrupt erectile and/or ejaculatory function; the techniques of epididymal sperm aspiration and intracytoplasmic sperm injection (ICSI) are particularly useful in such cases. Well-controlled diabetes is not associated with recurrent miscarriage but diabetes is a risk factor for pregnancy-induced hypertension and, poorly controlled, is associated with neonatal macrosomia. In reproduction, as in general health, good metabolic control is key to a successful outcome.
Review: Modern treatment of erectile dysfunction
Authors: Ali Waleed , Besarani Dler , Kirby Roger
Published: August 2008

Within the last two decades, major advances have been made in the development of effective treatments for erectile dysfunction. Oral therapy is now established as the mainstay of treatment and new treatments continue to emerge following the launch of sildenafil in 1998. We review here modern treatment strategies for erectile dysfunction.
Cardiovascular safety in erectile dysfunction treatment
Authors: Jackson Graham
Published: August 2008

Sexual activity does not increase stress to the heart compared to other daily physical activities. Simple guidelines exist for advice in the outpatient and inpatient setting. Erectile dysfunction (ED) is common in cardiac patients and should be routinely asked about. Treating ED is safe and effective if the patient is properly assessed and counselled.
Review: Epidemiology of diabetes — its history in the last 50 years
Authors: Zimmet Paul
Published: August 2008

The application of epidemiology to the study of diabetes mellitus has provided new insights into many aspects of this major public health problem including its natural history, prevalence, incidence, morbidity and mortality in diverse populations around the globe. The main impetus came from the late Kelly West's book `Epidemiology of Diabetes and its Vascular Lesions' published in 1978. In addition, World Health Organization and American Diabetes Association Expert Committees made astute recommendations on the classification and criteria for diabetes and associated categories of glucose intolerance as well as methodological issues for diabetes epidemiology studies in diverse populations. These studies have provided direction for research into the possible molecular defects and biochemical mechanisms underlying both type 1 and 2 diabetes as well as important information on the extrinsic (social, cultural and environmental) risk determinants.
Review: Type 2 diabetes: how far have we come?
Authors: Lebovitz Harold E
Published: August 2008

The last 50 years has witnessed the recognition of type 2 diabetes as a complex heterogeneous disease that results from an interaction between environmental factors and genetic predispositions. As its pathophysiology has been unfolded by the advances in clinical science, so its prevalence has increased dramatically, and it is now one of the major personal and public health problems worldwide. Therapeutic approaches to address insulin resistance and beta-cell dysfunction have intensified and diversified during the last decade, driven by indisputable evidence that the treatment goals include both glycaemic control and attention to all vascular risk factors. Advances in basic and clinical research over the last fifty years have culminated in sufficient strategies and pharmacological agents to start to achieve these goals. Equally as important, they have laid the foundation for what promise to be remarkable future developments.
Review: Thirty-seven years with diabetic retinopathy
Authors: Kohner Eva M
Published: August 2008

Diabetic retinopathy was rare 50 years ago. Since then it has become the commonest cause of visual loss in the working age population. Initially the only treatment available was pituitary ablation, and that only worked for some patients with proliferative retinopathy. In the 1970s laser treatment revolutionised the management of retinopathy. Improvements in the assessment and management of retinopathy stimulated research with controlled clinical trials. This has resulted in evidence-based recommendations for improvement in glucose and blood pressure control which has been shown to reduce the prevalence of retinopathy. Screening procedures are now available for most people with diabetes. New treatments under development, directed at the pathogenic mechanisms of retinopathy, offer hope that the laser will eventually be replaced by more effective and better tolerated treatment.
Review: Diabetes nursing: a personal perspective of the last 50 years
Authors: Mackinnon Mary
Published: August 2008

The last 50 years have embraced phenomenal advances in medicine and change in the delivery of healthcare. Nursing in general and diabetes nursing in particular have made and continue to make an important contribution to this evolutionary, even revolutionary process. The history and progress of nursing, the development of the role of specialist nurses and nurses in primary care, particularly practice nurses working with general practitioners, have made a difference in the continuing care of people with diabetes in the UK. Nurses working with their medical colleagues and other healthcare providers have many skills and talents to offer which need to be identified, valued and fostered. The art of nursing is encompassed in the support, care and education of people with diabetes.
Review: The management of stable angina in diabetes
Authors: Williams Ian L , Vazir Ali , Zaman Azfar G
Published: August 2008

Cardiovascular atherosclerosis is the commonest underlying cause of death in patients with diabetes mellitus. The development of atherosclerosis is often accelerated and the outcome is worse in diabetic than non-diabetic patients. This may relate to abnormalities of platelet function, coagulation, blood pressure and lipid metabolism that are characteristic of diabetes. Management of angina in diabetes should focus on reducing symptoms and prolonging life. In both of these areas there are issues specific to the diabetic patient. The role of percutaneous and surgical approaches to coronary disease in diabetic patients continues to evolve and optimal therapy remains unclear. Herein explores the clinical management of coronary artery disease in patients with diabetes. The pathophysiological basis of stable and unstable coronary syndromes is explained and the effect of diabetes on coronary disease and its subsequent management is discussed.
Review: Endothelial dysfunction and pre-symptomatic atherosclerosis in type 1 diabetes — pathogenesis and identification
Authors: Browne Duncan , Meeking Darryl , Shaw Kenneth , Cummings Michael
Published: August 2008

The vascular endothelium offers an attractive model for detecting functional abnormalities prior to structural changes in the vasculature. Demonstration of progression from endothelial dysfunction through to atherosclerosis is required. Measurements of forearm bloodflow, biochemical markers and biophysical assessments of the endothelium have been employed as research tools for investigating pre-symptomatic atherosclerosis.

However, studies examining endothelial function in type 1 diabetes have been sparse and conflicting. Differences in methodology and the study populations were potential confounding factors. Augmented vasodilatory prostanoids compensate for reduced nitric oxide bioavailability in determining endothelial function in type 1 diabetes. Hyperglycaemia appears to be the initiating event in type 1 diabetes which promotes a variety of biochemical events which are pathogenic to the endothelium.

Improved understanding of the endothelium may facilitate the development of novel diagnostic tools and interventions targeting the accelerated atherosclerosis associated with type 1 diabetes.
The problem of polypharmacy in type 2 diabetes
Authors: Emslie-Smith Alistair , Dowall Jon , Morris Andrew
Published: August 2008

Evidence of improvements in outcomes gained by aggressive treatment of hypertension, hyperglycaemia and Edyslipidaemia in type 2 diabetic patients has encouraged the setting of ambitious targets for risk factor control. The therapeutic regimens needed to achieve tight control results in polypharmacy for many patients. The recent DARTS Study demonstrated poor adherence to oral hypoglycaemic drug therapy, particularly in patients prescribed combination oral hypoglycaemic drug therapy, multiple daily dose regimens and co-medications. This suggests that simplifying drug regimens, minimising tablet-counts and the use of once-daily and modified-release preparations and of fixed-combination drug preparations may be important. With regard to taking medication an alliance is needed which allows greater mutual understanding and agreement between patient and doctor. This move towards `concordance' in care planning is also crucial to success.
Quality driven management of tablet-treated type 2 diabetes — potential increases in GP practice prescribing costs
Authors: Stott Peter
Published: August 2008

A prospective audit was undertaken to characterise Ametabolic control, risk-factor profiles and costs of pharmaceutical agents required to achieve quality target measures in 100 type 2 diabetic patients attending a diabetic clinic in UK general practice. Despite reasonable glycaemic control, the coronary risk of these patients was high due to age, diabetes and dyslipidaemia. It proved impossible to quantify coronary risk for many older patients exactly since existing scales do not apply to patients aged over 75 years. The extra cost of initiating new treatments to modify coronary heart disease (CHD) risk for an average patient with type 2 diabetes was estimated to be £400—£860 (average £633) per annum. The treatment costs of instituting treatment to achieve quality measures should be considered when new quality standards are introduced. Without this investment the long-term costs of managing the complications of diabetes will be much higher.
Failure to define the pathogenesis and treatment of human diabetic neuropathy
Authors: Malik Rayaz
Published: August 2008

The clinical manifestations, underlying pathology and aetiology of human diabetic neuropathy are varied and complex. Much data has been generated from preclinical models to provide a conceptual framework for the cause and treatment of human diabetic neuropathy. Despite this there remains much debate and controversy on the pathophysiology of the condition. Furthermore, many of the interventions reaching phase III clinical trials have failed to prove effective. To date we have no evidence-based and effective treatment(s) for human diabetic neuropathy.
Painful diabetic neuropathy — current understanding and management for the primary care team
Authors: Kirby Mike
Published: August 2008

Primary care has an increasing role in the diagnosis and treatment of painful diabetic neuropathy (PDN), and early accurate diagnosis and intervention can greatly improve the prognosis. With the incidence of diabetes predicted to increase dramatically, the number of patients with PDN is set to soar. PDN can have a serious impact on quality of life, leading to severe depression and even suicide. The evolution of a schematic approach to the diagnosis and treatment of PDN can offer new hope to many patients. This review focuses on PDN and current treatment strategies. Many leading pain clinics have adopted a multidisciplinary approach to the pharmacological and non-pharmacological management of PDN.
Review: Lipid lowering drugs, inflammation and cardiovascular disease
Authors: Schachter Michael
Published: August 2008

Inflammation is an integral part of atherosclerosis, both in its early phases and in acute coronary syndromes. Markers of inflammation, especially C-reactive protein (CRP) are increasingly recognised as predictors of cardiovascular events. At the same time, evidence is growing that the statins have anti-inflammatory properties which may at least in part be independent of their effect on lipids. Statins can rapidly lower levels of CRP and this may be paralleled by changes in cardiovascular risk which precede reductions in serum cholesterol levels. This therefore represents an additional rationale for the use of statins in cardiovascular disease prevention, both primary and secondary. It must be noted that the fibrates also possess anti-inflammatory activity, although by different mechanisms: this has not been explored to the same extent as is the case for the statins. Equally, the statins may ultimately be useful in other forms of chronic inflammatory disease.
Lack of association between early atherosclerotic carotid artery wall lesions and serum level of homocysteine
Authors: Rajala Ulla , Päivänsalo Markku , Laakso Mauri , Pelkonen Outi , Koskela Pentti , Suramo Ilkka , Keinänen-Kiukaanniemi Sirkka
Published: August 2008

The present study evaluated the possible association of high serum levels of homocysteine with ultrasonographic manifestations of carotid atherosclerosis in 65-year-old Finnish subjects drawn from a population-based cohort. Carotid ultrasonographic measurements were performed on 54 diabetic subjects, 97 subjects with impaired glucose tolerance and 57 normoglycaemic subjects. There were no statistically significant differences between the groups in the homocysteine levels. The median homocysteine level was higher in the subjects with a history of myocardial infarction (MI) (n=9) than in the subjects with no history of MI (14.8 [range 8.7—18.3] vs.12.3 [range 6.4—49.0] µmol/L, p=0.045). In the subjects without a history of MI or stroke, the maximal intima-media thickness (IMT) of the common carotid artery did not differ in the homocysteine quintiles. There was no association between the number of atheromatous plaques and the homocysteine level. In conclusion, although high levels of serum homocysteine were not associated with early atherosclerotic changes (i.e. increased carotid IMT or the number of plaques), high homocysteine concentrations were associated with advanced atherosclerosis (i.e. a history of MI).
Review: Hypertension in diabetes: a perspective from clinical pharmacology
Authors: Ross Sarah , Macleod Mary-Joan
Published: August 2008

The treatment of co-existing hypertension is vital to reduce morbidity and mortality from complications of diabetes. There is a vast array of evidence on the subject and the choice of antihypertensive medication is extensive. We have reviewed the evidence for blood pressure (BP) control in diabetes, and examined the evidence to support the use of each class of drug, concentrating on patients without nephropathy or microalbuminuria. Control of BP should be the overriding aim, and requires over time more than one drug in most patients. The weight of evidence suggests that BP-lowering per se is more important than the actual agent used.
Review: Homocysteine, endothelial dysfunction and oxidative stress in type 1 diabetes mellitus
Authors: Wotherspoon Fiona , Laight David W , Shaw Kenneth M , Cummings Michael H
Published: August 2008

Type 1 diabetes is associated with an increased risk of cardiovascular disease, which cannot be fully explained by traditional risk factors. Elevated plasma homocysteine is an independent risk factor for macrovascular disease in the general population. This review examines the evidence for hyperhomocysteinaemia in patients with type 1 diabetes and describes the mechanisms that may lead to increased macrovascular susceptibility.

While reports of plasma homocysteine levels in type 1 diabetes are inconsistent, increased plasma homocysteine levels have been found in subgroups of patients with microalbuminuria, nephropathy and macrovascular disease. Although a direct causal relationship between plasma homocysteine and atherosclerosis remains to be proven, potential mechanisms of vascular damage by homocysteine include endothelial dysfunction linked to increased oxidative stress. This could contribute to the association between hyperhomocysteinaemia and macrovascular disease in type 1 diabetes.
Auditing diabetes values in primary care
Authors: Cosgrove Martin , Hunter Jan
Published: August 2008

Auditing values in diabetes care can potentially give the wrong impression. Using a single value such as percentage of patients with a blood pressure ≥ 140/80 mmHg does not reflect what is happening in the practice as a whole. There is a risk that patients who will never achieve such targets will be viewed with less enthusiasm than they should by their primary care team members. This article describes a simple method of auditing diabetes values that includes all diabetes patients and is helpful when comparing year on year progress.
Effects of chronic treatment with glibenclamide and/or metformin on the resistance to ischaemia of isolated hearts from Zucker Diabetic Fatty rats (ZDF/GMI-fa/fa)
Authors: Lavanchy Nicole , Christe Georges , Cand Francine , Wiernsperger Nicolas , Verdetti Jean
Published: August 2008

The study was carried out to determine whether metformin (M) had any deleterious effect on the tolerance to ischaemia of the isolated diabetic rat when administered chronically in combination with glibenclamide (G). The male Zucker Diabetic Fatty (ZDF) rat served as a model of type 2 diabetes that resembles the human syndrome. Three groups of rats were treated for one month with M (100 mg/kg) or G (2 mg/kg) or G + M in their daily food. One group was untreated (C). Aortically perfused hearts were subjected to a 25-minute global low-flow ischaemia and a 30-minute reperfusion. Heart rate (HR), left ventricular developed pressure (LVDP), rate pressure product (RPP) and coronary flow (CF) were monitored.

When compared to C hearts, the hearts from G + M rats showed improvements in HR, LVDP and RPP at the end of reperfusion. Hearts from G and M rats exhibited no difference. Myocardial glycogen stores at the end of in the three other groups.

The study did not reveal any deleterious effect of the chronic G + M therapy on the functional recovery of the isolated diabetic heart submitted to ischaemia and reperfusion: indeed, an increase in residual contractile capacity was found.
Review: Helping the athlete with type 1 diabetes
Authors: Gallen Ian W
Published: August 2008

Exercise is a significant physiological challenge with markedly increased cardiac output, respiration and fuel mobilisation. Whilst the cardio-respiratory response to exercise is similar in type 1 diabetes to that seen in non-diabetic subjects, the response to mobilisation of fuel source to support exercise is impaired. This effect, when combined with the difficulties of nutrition and insulin therapy in type 1 diabetes may negatively impact on the performance of the athlete with diabetes. Hypoglycaemia both during and following exercise, is a significant risk. Furthermore, hyperglycaemia prior to and following some types of exercises can also be problematic. The effect on blood glucose of varying sports can be predicted, and therefore, pro-active adjustments of insulin therapy and nutrition can be made. This article outlines the important differences seen with exercise in type 1 diabetes and discusses appropriate strategies to normalise performance and reduce the risk of hypoglycaemia.
Continuous subcutaneous insulin infusion: short-term benefits apparent, long-term benefits speculative
Authors: Hammond Peter
Published: August 2008

Continuous subcutaneous insulin infusion (CSII) is increasingly used as a means of insulin delivery for those with type 1 diabetes, and has recently been endorsed by NICE for this purpose. CSII improves glycaemic control compared to other intensified insulin regimens, with a small decrease in HbA1C and mean blood glucose, and a larger reduction in glucose fluctuation. This improved control is not associated with an increased risk of hypoglycaemia and CSII probably results in significantly lower rates of severe hypoglycaemia. There is no evidence that those using CSII are at increased risk of diabetic ketoacidosis. CSII is uniquely associated with a small risk of application site infection. CSII has a positive impact on quality of life. There is much less evidence concerning the benefits of CSII in reducing microvascular or macrovascular complication rates. Small studies, mostly from the 1980s, show improvements in markers of early nephropathy, retinopathy progression and neuropathy, but the potential long-term impact of CSII has not been proven. Recently CSII has been used in the management of those Br J Diabetes Vasc Dis 2004;4:104—08 with type 2 diabetes but evidence is lacking with regard to the benefits of using it in this group.
A user perspective on Continuous Subcutaneous Insulin Infusion (CSII) therapy
Authors: Ford Melissa P
Published: August 2008

For this patient, clinical benefits of CSII are complemented by quality-of-life benefits. CSII allows her to eat, exercise, work, and socialise similarly to non-diabetic peers, mitigating psychosocial impacts of insulin dependence. Tailoring insulin dosage more precisely to meet insulin requirement has allowed her to pursue educational and personal goals while maintaining a healthy weight and an optimal HbA1C, without severe hypoglycaemia or diabetic ketoacidosis.
Needle-free insulin
Authors: Brown Harry
Published: August 2008

Needle-based delivery systems suit the vast majority of people with type 1 and type 2 diabetes who require insulin. However, a small group may be better suited to a needle-free delivery system. In the UK, GPs can now prescribe, on the NHS, such a needle-free delivery system — sometimes called a jet injector. These devices are not necessarily pain free but they have a well-established history and offer patients and their healthcare professionals a credible alternative to a needle-based insulin injection.
Initiating insulin in patients with type 2 diabetes within primary care
Authors: Kirby Mike
Published: August 2008

This article considers the challenge of initiating insulin therapy in people with type 2 diabetes in a primary care setting. Professor Mike Kirby discusses the changing interface of primary and secondary care roles and the influence of guidelines, goals and targets. Issues of patient concern and selection of insulin regimen are also addressed.
Review: Renal dysfunction as a marker of increased vascular risk
Authors: Andrews Peter
Published: August 2008

Minimisation of risk factors for the development of vascular disease has made a major contribution to the decline in vascular morbidity and mortality reported over the last decade. Recent evidence has highlighted that elevation of serum creatinine is a strong marker of increased vascular risk, with a predictive value as high as the development of diabetes. As serum creatinine is easily measured — albeit often misinterpreted — this provides another easily applied clinical tool for the stratification of cardiovascular risk and the targeting of preventative medicine in primary and secondary care.
Review: When should bariatric surgery be used in the treatment of type 2 diabetes?
Authors: Pinkney Jonathan , Kerrigan David
Published: August 2008

Non-randomised observational studies show that bariatric surgery has a highly beneficial impact on diabetes. Bariatric surgery leads to remission of bariatric surgery has a highly beneficial impact on Diabetes. Bariatric surgery leads to remission of diabetes in at least two thirds of patients, and reductions in drug therapy for many others. Those with more recent onset diabetes, fewer treatment requirements, and able to achieve most weight loss are more likely to achieve remission. Therefore, bariatric surgery is an attractive treatment option to consider for selected more severely obese patients with favourable characteristics. Although data on bariatric surgery in subjects with diabetes are provocative, all recent clinical studies have been uncontrolled or otherwise flawed. Moreover, bariatric surgery has yet to be compared either with medical treatment for weight loss, or against standard medical treatment for diabetes in any randomised controlled trial with diabetes-specific end points. There remains a need for long-term randomised controlled trials before bariatric surgery is used more widely as a first-line treatment for obese patients with type 2 diabetes.
Non-invasive imaging for coronary artery disease in diabetes
Authors: Tschoepe Diethelm , Burchert Wolfgang
Published: August 2008

Diabetic patients are at greater risk of cardiovascular disease than non-diabetic individuals, coronary artery disease (CAD) has a less favourable prognosis and is more likely to be silent in diabetic than in non-diabetic patients. Thus, screening is an integral component of risk-reduction strategies for such patients. The available non-invasive testing options include exercise tolerance testing (ETT), stress echocardiography, and stress myocardial perfusion imaging (MPI) with or without gated single-photon emission computed tomography (SPECT). Calcium scoring with electron beam computed tomography (EBCT) and magnetic resonance imaging (MRI) are promising techniques, requiring further validation. Stress MPI with gated SPECT enables assessment of myocardial ischaemia, viability, and function, and allows for risk stratification to improve clinical management in diabetic patients.
Screening for IGT and diabetes
Authors: Tringham Jennifer R , Davies Melanie J
Published: August 2008

Type 2 diabetes is increasingly common and a significant proportion of individuals are undiagnosed. Around 15—20% of the adult population have impaired glucose tolerance (IGT) or impaired fasting glycaemia (IFG) and are at an increased risk of subsequently developing diabetes.

There is a wealth of information regarding the practicalities of various methods of screening for diabetes, and to a lesser extent for IGT. For diabetes screening a targeted approach is preferred. A fasting plasma glucose (FPG) followed by an oral glucose tolerance test (OGTT) if FPG is between 5.5—6.9 mmol/L is recommended. In detecting pre-diabetes (IGT or IFG) risk factor questionnaires and risk scores are the preferred option but these require further evaluation.
Low-dose statins: useful and safe?
Authors: Schachter Mike
Published: August 2008

This article considers the raison d'être for the use of low-dose statins, their safety, efficacy and potential as non-prescription drugs. It is very much a personal contribution to a controversial area which has become very topical.
Avandamet
Authors: Kunhiraman Biju , Itoua-Nganongo William , Fonseca Vivian
Published: August 2008

Type 2 diabetes mellitus is characterised by multiple defects including decreased insulin mediated glucose disposal, higher endogenous glucose production mainly from liver and inadequate pancreatic secretion of insulin. Metformin and thiazolidinediones (TZDs) decrease insulin resistance by different mechanisms of action, and since both have the advantage of decreasing hyperglycaemia without increasing insulin secretion, they make an attractive option for combination. Metformin decreases hepatic glucose production and enhances peripheral glucose uptake while TZDs, by acting on peroxisome proliferator-activated receptor-gamma (PPARγ) receptors increase glucose uptake.

The combination has also been shown to improve glycaemic control, improve insulin sensitivity and improve beta-cell function. The availability of the two drugs in one pill has the potential to improve patientcompliance and decrease costs.
New prolonged-release metformin improves gastrointestinal tolerability
Authors: Davidson Jaime , Howlett Harry
Published: August 2008

Current guidelines for the management of type 2 diabetes recommend initiating pharmacological therapy with metformin, particularly in overweight patients, but gastrointestinal side-effects and a complex administration regimen sometimes present barriers to its use. A novel, prolonged-release metformin formulation (Glucophage® SR*), given once-daily in double-blind, randomised, placebo-controlled trials, was associated with fewer gastrointestinal side-effects, than immediate-release metformin. A retrospective review of 468 metformin-treated patients in the USA found better gastrointestinal tolerability with prolonged-release metformin in patients new to metformin, or switched from the immediate-release formulation. The efficacy of the two formulations was similar. The improved tolerability associated with prolonged-release metformin probably arises from the tablet design, which releases metformin into the upper intestine by diffusion from a dual hydrophilic polymer matrix (GelShield diffusion system). This provides slower, smoother and longer drug delivery, without an initial rapid rise in plasma metformin. This novel metformin formulation may simplify the delivery of metformin-based therapy.
Review: Newer antipsychotic agents, carbohydrate metabolism and cardiovascular risk
Authors: Akhtar Simeen , Kelly Ciara , Gallagher Andrew , Petrie John R
Published: August 2008

With widespread use of `atypical' antipsychotics for the treatment of psychiatric disorders, attention has focused on their association with obesity, diabetes and risk factors for cardiovascular disease. People with schizophrenia are more likely to develop diabetes than the general population, with antipsychotics appearing to add to this risk. The exact mechanism(s) by which antipsychotics cause hyperglycaemia, diabetic ketoacidosis and aggravation of pre-existing diabetes remain uncertain. Plausible mechanisms have been postulated for the promotion of obesity by these agents, with resultant insulin resistance and type 2 diabetes in some patients. Whatever the mechanism, careful consideration of potential risks and benefits is required in prescribing: people with schizophrenia are often exposed to antipsychotic agents in the long term and frequently have co-existing cardiovascular risk factors (smoking, poor diet, physical inactivity, social deprivation). Regular monitoring of body weight, blood glucose and serum lipids may help clinical management.
Review: New antiplatelet guidelines for managing peripheral arterial disease — what are the implications for diabetes?
Authors: Kirby Mike , Gardener Rebecca
Published: August 2008

Peripheral arterial disease (PAD) presents a major health problem in the UK and is often over looked because many patients are asymptomatic. The prevalence rises markedly in diabetes. Primary care has an important role in the identification and management of vascular disease and the prevention of secondary events. New guidelines underline the importance of antiplatelet agents.
Physician assistant — management perspective
Authors: Lamb Linda
Published: August 2008

In this article Linda Lamb, the PMS/Finance Manager of Tipton Care Organisation — original employers of the physician assistant (PA) pilot scheme, outlines the problems of general practitioner (GP) recruitment and highlights the personnel and economic rationale for introducing PAs to the UK health service
Review: Aldosterone — the future challenge in cardiovascular disease?
Authors: Connell John
Published: August 2008

Mineralocorticoid receptor activation plays a key role in cardiovascular disease and hypertension, which are particularly prevalent in diabetes mellitus; secondary hyperaldosteronism contributes to cardiac failure. Major intervention trials in heart failure have demonstrated unequivocal benefit from aldosterone receptor antagonism. Focused experimental studies in humans and in animal models of hypertension have shown that aldosterone blockade improves a number of pathogenic abnormalities including vascular endothelial dysfunction and altered baroreflex function, and prevents the development of cardiac hypertrophy and renal histological damage. Based on recent outcomes studies, the challenge is now to transfer the experimental evidence into clinical M practice.
Review: The evolution of insulin treatment in type 1 diabetes: the advent of analogues
Authors: Gallen Ian
Published: August 2008

Treating patients with type 1 diabetes to near-normal glycaemic levels significantly reduces the risk of microvascular complications and improves patient outcomes. Consequently, achieving and maintaining optimal glycaemic control is a key therapeutic aim and clear guidance regarding glycaemic targets now exists. The challenge is to achieve this level of control in routine clinical practice whilst minimising the treatment-related adverse events of hypoglycaemia and weight gain. The development of both rapid- and long-acting insulin analogues offers the potential to meet this challenge, with results from clinical trials indicating that analogue insulins have therapeutic benefits over older insulin preparations. However, it is important to see if these benefits can be repeated in non-clinical trial patient populations and, therefore, this article summarises the results from prospective audits of introducing insulin lispro and insulin glargine into routine clinical practice in patients with type 1 diabetes.
Erectile dysfunction and diabetes: a study in primary care
Authors: Lloyd Brendan , Williams Rhys , Huber Jörg
Published: August 2008

This study set out to determine whether there has been an increase in awareness of ED amongst men with diabetes following the introduction of oral therapy and whether there is an association between ED and QoL. Current perceptions of 157 men with diabetes were compared with the results of a 1997 survey. Those who reported ED (66/157) completed a questionnaire assessing the impact of ED on QoL. Patients are more aware of ED now than in 1997; more treatments are now offered in primary care. The results demonstrated a weak, but significant, association between awareness of therapy (represented by the number of treatments of which patients were aware) and QoL. Patients who were aware of treatments had a significantly worse QoL than those who were unaware.
A one-year retrospective audit of the DIGAMI protocol
Authors: Buch Harit N , Barton David M , Varughese George I , Hodgson Ellen , Scarpello John HB
Published: August 2008

Aim To assess the impact of post-MI diabetes-care upon changes in diabetes therapy and on cardiovascular risk factors.

Patients and methods Retrospective audit of case notes of patients with diabetes who were treated according to the DIGAMI protocol following an acute MI and who had completed at least one year of follow-up (n=86).

Results A majority of patients continued insulin therapy beyond the standard recommendation of three months (7%, 84%, 75% at 0, 3 and 12 months respectively) resulting in an increase in the number of patients attending hospital diabetes clinics (17%, 94% and 61%). A majority of patients belonged to DIGAMI low-risk group 1 (85%) which was the category of patients shown to have a significant survival benefit in the original DIGAMI cohort. At the end of one year an increased number of patients achieved targets for control of systolic BP (49, 59 and 77 at 0, 3 and 12 months), diastolic BP (44, 74 and 77%), TC (34, 73 and 80%) and HbA1C (24, 45 and 60%) (p<0.05 for all). Weight increased progressively (82 kg, 87 kg A and 88 kg, p<0.05). Percentage of smokers was reduced (31, 9 and 11, p<0.05).

Conclusion There was a significant rise in the number of patients receiving long-term insulin therapy, and attending secondary care follow-up. A significant and sustained increase was observed in achieving targets for HbA1C, BP and cholesterol.
The treatment of necrobiosis lipoidica
Authors: Tidman Michael J , Duncan Catriona
Published: August 2008

Necrobiosis lipoidica is an inflammatory disorder, associated with diabetes mellitus, for which the underlying pathological mechanism is unknown and for which there is no rational therapy. However, benefit has been reported from such different treatment regimens as drugs acting on the haemostatic mechanisms, corticosteroid therapy (topical, intralesional and systemic), enhancers of wound healing, surgery and immunomodulating therapies (including photochemotherapy). This is a review of these treatment options.
Effect of nateglinide and glimepiride in reducing postprandial hyperglycaemia in patients with type 2 diabetes mellitus
Authors: Abletshauser Claudia , Brunel Patrick , Usadel Klaus-Henning , Hanefeld Markolf
Published: August 2008

Aim — The purpose of this study was to compare the effect of nateglinide on two-hour post-meal glucose levels with that of glimepiride in patients with type 2 diabetes mellitus. Methods — Glucose and insulin levels were measured during 14-hour profiles (comprising three meal challenges) and intravenous glucose tolerance tests performed before and after five-weeks of treatment with nateglinide (120 mg, a.c.) or glimepiride (1 mg, o.d.) in a randomised, two-centre, double-blind, crossover study in 26 patients with type 2 diabetes and fasting initial glucose levels < 13.9 mmol/L. Results — Mean two-hour postprandial glucose levels were significantly lower during nateglinide treatment than during glimepiride treatment (9.46 vs. 10.00 mmol/L, respectively; p<0.05). The 14-hour incremental glucose area under the curve was -2.2 mmol•h/L during nateglinide treatment and +6.2 mmol•h/L during glimepiride treatment (p<0.01). Nateglinide improved both the early insulin response during meals and the acute insulin response during intravenous glucose tolerance tests, restoring the biphasic insulin secretion pattern. Both insulin secretagogues improved intravenous glucose tolerance relative to the pre-treatment period, but only nateglinide restored a biphasic insulin profile. Conclusions — By restoring a more physiological post-load insulin response, nateglinide is more effective than glimepiride in controlling postprandial glucose excursions.
NSF for Diabetes, update — year two
Authors: Day Caroline
Published: August 2008

To establish standards and improve the delivery of healthcare to people with diabetes in the UK, the Department of Health introduced a Diabetes National Service Framework (NSF). This article outlines progress on this initiative with particular attention to the recently published report covering implementation of the Diabetes NSF over the past two years.
Exercise, metformin and hypoglycaemia: a neglected entity
Authors: Omari Abdullah , Yue Dennis K , Twigg Stephen M
Published: August 2008

We describe a case of hypoglycaemia induced by exercise in a patient with type 2 diabetes taking metformin, who was not taking insulin or sulphonylurea medication. The hypoglycaemia resolved after the dosage of metformin was reduced, despite increased physical activity. A brief review of the literature identifying the frequency of and risk factors for hypoglycaemia during treatment with metformin is discussed.
Review: Vascular protective effects of peroxisome proliferator-activated receptor agonists
Authors: Cariou Bertrand , Fruchart Jean-Charles , Staels Bart
Published: August 2008

ardiovascular disease is significantly increased in patients with the metabolic syndrome and type 2 diabetes. A clustering of risk factors, including dyslipidaemia, insulin resistance, hypertension, inflammation and coagulation disorders are acting in concert to promote cardiovascular events in these patients. Peroxisome proliferator-activated receptors (PPARs) are transcription factors that influence vascular function by altering gene expression in vascular tissue and indirectly via effects on other tissues. Indeed, PPAR activation displays beneficial effects on glucose homeostasis and lipid metabolism, and also on endothelial function and vessel wall inflammation. Clinically used PPARα agonists, such as fibrates, and PPARγ agonists, such as insulin-sensitising thiazolidinediones, may consequently alter the process of atherosclerosis, especially in subjects with the metabolic syndrome and type 2 diabetes. The present review highlights emerging evidence for beneficial effects of PPAR α and PPARγ in the prevention and treatment of atherosclerosis in such high-risk patients.
Review: Development and therapeutic potential of incretin hormone analogues for type 2 diabetes
Authors: Green Brian D , Irwin Nigel , Gault Victor A , O'Harte Finbarr Pm , Flatt Peter R
Published: August 2008

The rising prevalence of type 2 diabetes and increasing burden of diabetic complications requires new approaches to diabetes therapy. An encouraging new approach for development of future anti-diabetic drugs is based on analogues of incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Both peptides reduce postprandial glucose by stimulating glucose-dependent insulin release and exert a number of other beneficial actions including trophic effects on the beta-cell. Efforts are currently focused on developing stable analogues of GLP-1 and GIP which are resistant to dipeptidylpeptidase IV mediated degradation and renal filtration. Thus, by increasing the half-life and potency of these incretins, they should become a new class of agents for the treatment of type 2 diabetes.
Auto-ophthalmoscopy: a novel way to practice retinal examination
Authors: Armour Roger H , Kirby Michael G
Published: August 2008

Proficiency at retinal examination takes a long time to acquire. The authors investigated auto-ophthalmoscopy — the examination of one's own retina — as a way of helping the student or practitioner. They report the first pilot study in the 145-year history of the method. Auto-ophthalmoscopy is best taught by demonstration and is best learnt under supervision. It takes practice, which is in itself useful in learning how to use a direct ophthalmoscope. Of 20 participants in the pilot study, 11 saw their retinae. One of the authors, who has type 2 diabetes, has seen and sketched his own micro-aneurysms.
The outcome of total hip arthroplasty in diabetes mellitus
Authors: Chan Peter Kh , Brenkel Ivan J , Aderinto Joseph
Published: August 2008

n analysis on prospective data on our hip database was carried out on all patients undergoing primary cemented unilateral total hip arthroplasty. There were 1,220 non-diabetic and 77 diabetic patients identified with at least three years follow-up. We found no significant difference with respect to age, sex and diagnosis between the two groups. Diabetic patients did have a significantly higher body mass index (BMI) and higher incidence of coronary artery disease. We found no increase in the rate of deep periprosthetic infection, superficial wound complications, dislocation, blood loss and deep vein thrombosis (DVT) between patients with and without diabetes even after adjusting for potential confounders. Diabetic patients had a longer length of stay (10.73 versus 9.56 days, p<0.05). Further analysis of the diabetic group showed no difference, with the same outcomes in patients between insulin-dependent and non-insulin dependent diabetic subsets. From this study we conclude that at the time of taking informed consent from patients undergoing total hip arthroplasty the only potential difference between those with and without diabetes is that the length of stay may be longer for patients with diabetes. Br J Diabetes Vasc Dis 2005;5:146—9
A prospective study to investigate the incidence of atherosclerotic vascular disease in patients with newly diagnosed type 2 diabetes mellitus
Authors: Doyle Arthur , Buchanan Linda M , Reith Shiela Bm , Bridges Allan
Published: August 2008

Type 2 diabetes is associated with premature cardiovascular disease (CVD). We examined the extent of vascular disease and modifiable risk factors in 50 sequential patients with type 2 diabetes, without a previous diagnosis of vascular disease, at their first presentation to a hospital diabetes clinic. Sixty-four per cent of patients were obese (BMI ≥ 30). Average HbA1C was 6.8% and mean total cholesterol was 5.74 mmol/L. Forty-seven per cent were hypertensive (systolic pressures ≥ 140) and 18% were current smokers.

Eighteen point four per cent of this population had ischaemic heart disease detectable by ECG and exercise ECG. Eighteen per cent had a reduced ankle: brachial pressure index and 49% had carotid atheroma by Doppler scanning.

These findings illustrate the case for aggressive primary vascular disease prevention strategies from the time of diagnosis in type 2 diabetes.
Review: Diabetic autonomic dysfunction: adverse effects on presentation, management and outcomes of acute coronary syndromes
Authors: Saha Mrin , Timmis Adam D
Published: August 2008

n acute coronary syndromes there is increasing speculation that autonomic dysfunction complicating diabetes may adversely affect outcomes. Mechanisms are unclear but the potential effects on the timing of plaque events, the mode of presentation, myocardial oxygen demand and arrhythmogenesis are discussed in this article.
Review: Managing cardiovascular risk in patients with diabetes
Authors: Donnelly Richard
Published: August 2008

The increasingly large number of patients with diabetes in the UK are at greatly increased risk of cardiovascular disease, including coronary heart disease and stroke, compared to the general population. Many diabetes patients exhibit metabolic syndrome and these additional risk factors, such as raised hypertension and cholesterol, multiply the overall risk. Reducing these risk factors to target levels is essential and requires a multifactorial approach. Lifestyle changes, tight glycaemic control, antiplatelet drugs (aspirin) and control of lipid levels, e.g. using statins, can all have significant beneficial effects. Blood pressure control is another vital aspect in reducing risk and a number of recent studies have provided evidence supporting the use of angiotensin-converting enzyme inhibitors as first-line treatment in patients with diabetes.