bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and management of hyperglycaemia in patients given thrombolysis for acute coronary syndromes
Authors: Baynes Kevin Cr , Mcintosh Colin , Feher Michael D
Published: August 2008

The prevalence of hyperglycaemia in patients given thrombolysis for suspected acute myocardial infarction has not been clearly established. This is a retrospective case-note study of 69 consecutive patients who received thrombolysis on admission to a coronary care unit over a 15-month period. Admission plasma glucose > 7.8 mmol/L was observed in 46%, whilst a random glucose > 11.0 mmol/L was recorded in 22% of the group. A history of type 2 diabetes was present in 19%; with a glucose > 11.0 mmol/L being recorded in 61% on admission. Intravenous insulin therapy was administered to 43% of those without a history of diabetes, but presentation hyperglycaemia in the diabetic range, whereas 88% of known diabetic patients were treated with insulin.

Hyperglycaemia/glucose intolerance, although commonly observed in patients thrombolysed for acute myocardial infarction, is not always managed with insulin therapy. There is a need for clear diabetes management protocols for all teams managing patients in coronary care units.
Initiating antiplatelet therapy in diabetes: a PCO view
Authors: Morrell Jonathan
Published: August 2008

Antiplatelet therapy has a role in the primary and secondary prevention of serious vascular events, especially in high-risk patients, including people with diabetes. This review considers the evidence and guideline recommendations for initiating antiplatelet therapy in people with diabetes with and without vascular disease. It concludes that, for diabetic patients with coronary heart disease, stroke or peripheral vascular disease, an antiplatelet agent (e.g. aspirin 75 mg per day or clopidogrel 75 mg per day) should be given routinely and continued in the long term. For diabetic patients with acute coronary syndromes, the addition of clopidogrel (75 mg daily) to usual therapy should be considered. For primary prevention, aspirin (75 mg) should be considered for all diabetic patients with well controlled hypertension and a ≥ 20% risk of developing coronary disease over 10 years.
Atherogenic dyslipidaemia in type 2 diabetes and metabolic syndrome: current and future treatment options
Authors: Bays Harold
Published: August 2008

Dyslipidaemia is a major risk factor for atherosclerotic coronary heart disease, which in turn is the commonest cause of mortality in type 2 diabetes. This highlights the importance of appropriate management of diabetic dyslipidaemia. Management is typically multifactorial and includes dietary recommendations, routine physical exercise, aggressive control of other lifestyle risk factors, and for many patients drug intervention. Future drug treatments will increasingly target not only mechanisms that might improve glucose and LDL cholesterol blood levels, but also improve other facets of diabetic dyslipidaemia, atherogenesis and vascular risk.
Nice timing for glitazones
Authors: Bailey Clifford J , Day Caroline , Krentz Andrew J
Published: August 2008

The National Institute for Clinical Excellence (NICE) recently revised its guidance on the use of thiazolidinediones (TZDs). Days later, the European Agency for the Evaluation of Medicinal Products (EMEA) announced licence changes for TZDs that supersede the NICE guidance. The EMEA has approved TZDs for monotherapy if metformin is contraindicated or not tolerated. This article summarises the latest changes surrounding the use of TZDs in the UK.
Review: The clinical evaluation of lower limb perfusion in diabetic foot disease
Authors: Williams Dean T , Price Patricia , Harding Keith G
Published: August 2008

Athorough clinical assessment and evaluation of foot perfusion is essential in managing diabetic foot disease. The treatment of macrovascular disease is key to reducing the high amputation rates seen in diabetic patients, particularly as small vessel dysfunction may make diabetic individuals more vulnerable to the effects of macrovascular, atherosclerotic disease. The clinical assessment remains paramount in the management of diabetic foot disease. The confounding effects of peripheral neuropathy on the symptoms and signs of lower limb arterial insufficiency can make assessment difficult. This article provides a resume of the clinical manifestation of lower limb ischaemia and neuropathy and the importance of accurate evaluation of the diabetic foot.
Review: Diabetic dyslipidaemia — the case for using statins
Authors: Gadsby Roger
Published: August 2008

Type 2 diabetes is associated with an increased risk of coronary heart disease (CHD). The association between CHD and abnormal plasma lipid levels has led current guidelines to recommend pharmacological modification of the lipid profile. Statins are particularly effective at reducing cholesterol levels, with additional benefits on other components of the lipid profile. Lipid-modifying therapy should be used routinely to reduce the risk of CHD in patients with type 2 diabetes.
The Alphabet strategy — a tool to achieve clinical trial standards in routine practice?
Authors: Jaiveer Pachaiappan , Saraswathy Jaiveer , Lee James D , Morrissey John , Patel Vinod
Published: August 2008

The Steno-2 study and UKPDS showed that targeted intensified intervention on modifiable cardiovascular risk factors in patients with type 2 diabetes reduces morbidity and mortality. The Alphabet POEM strategy (Practice Of Evidence-based Medicine) assessed the effect of systematic application of the Alphabet Strategy to care of patients with type 2 diabetes. In comparison to the Steno-2 intensive cohort, Alphabet POEM fared similarly with regard to diastolic blood pressure (BP), HbA1C, aspirin and angiotensin-converting enzyme (ACE) inhibitor use, but less well with respect to systolic BP, total cholesterol and use of statins. Alphabet POEM achieved better systolic and diastolic BP than UKPDS but glycaemic control was significantly worse. The standards achieved in the Steno-2 study and UKPDS are in principle, at least, partially achievable in a district general hospital in the UK, but fully achieving them in practice will probably need a radical restructuring, and greater provision of resources.
Are undiagnosed IGT/IFG and type 2 diabetes common in heart disease and hypertension?
Authors: Savage George , Ewing Peter , Kirkwood Helen , Carter Sarah
Published: August 2008

Diabetes mellitus causes significant morbidity and mortality, and up to 50% of people with diabetes may be as yet undiagnosed. Additionally impaired glucose tolerance (IGT) is known to increase vascular risk and the risk of developing diabetes.

The aim of this study was to look for IGT and/or impaired fasting glucose (IFG) and undiagnosed diabetes amongst patients with hypertension and patients with ischaemic heart disease (IHD) as part of an annual structured assessment.

In IHD patients the uptake was 83.45% with a yield of 2.47% for undiagnosed diabetes and 12.39% for IGT/IFG. In hypertensive patients the uptake was 75.84% with a yield of 2.01% for undiagnosed diabetes and 18.54% for IGT/IFG.

We concluded that looking for undiagnosed type 2 diabetes and patients with IGT/IFG in primary care may be worthwhile amongst patients with hypertension or IHD.
Primary prevention of type 2 diabetes in people of South Asian origin: potential roles of schools
Authors: Khunti Kamlesh , Davies Melanie
Published: August 2008

Children, like adults of South Asian origin are at increased risk of developing type 2 diabetes and other conditions associated with insulin resistance. The rising prevalence of excess body weight in children is of special concern as a promoter of insulin resistance. This article considers the evidence and need to develop and implement healthy lifestyle interventions in schools.
Review: Pharmacology of insulin
Authors: Ahmad Bushra
Published: August 2008

Diabetes is associated with microvascular and macrovascular complications leading to significant morbidity and mortality. Glycaemic control is important to prevent and delay the progression of these complications. An ideal insulin regimen in patients with diabetes would mirror the 24-hour insulin profile of a non-diabetic person and thereby prevent hyperglycaemia without inducing hypoglycaemia. This has, until recently, proved difficult to reproduce by regular subcutaneous insulin injections due to the inherent pharmacokinetic properties of the available insulins. Normoglycaemia was rarely achieved without hypoglycaemia compromising the quality of patients' lives. The advent of the new long- and short-acting insulin analogues are expected to both improve glycaemic control leading to a reduction in diabetes-related complications and reduce the incidence of hypoglycaemia thereby offering patients a better lifestyle.
Review: New approaches to insulin therapy in children and adolescents with type 1 diabetes
Authors: Acerini Carlo L , Deeb Asma
Published: August 2008

This article considers the problems associated with intensive glycaemic control in children and adolescents and how these may be circumvented. Use of insulin analogues, alternative insulin delivery methodologies and implementation of education programmes and other adjunctive strategies are discussed.
Review: Preventing diabetes in the obese: the XENDOS study and its context
Authors: Torgerson Jarl S
Published: August 2008

This article reviews the evidence, from both observational epidemiology and randomised clinical trials, that lifestyle modification as well as anti-diabetic drugs can reduce or delay the development of diabetes in overweight and obese patients with IGT. Particular consideration is given to the recently published XENDOS study which showed that the combination of orlistat and lifestyle changes over four years is safe and well tolerated, results in a weight loss of about six kg and reduces the risk of developing diabetes by 45% in obese IGT patients. Thus, addition of orlistat to lifestyle intervention has a greater diabetes-preventing effect than lifestyle modification alone.
Reclassifying insulins
Authors: Feher Michael D , Bailey Clifford J
Published: August 2008

Insulins have hitherto been distinguished as clear (short-acting) and cloudy (long-acting). However the introduction of glargine, which is a clear long-acting insulin, has prompted the need for reclassification. In view of the increasing emphasis on intensive insulin therapy using basal-bolus regimens, a new, simple, pragmatic classification is suggested in which insulins are categorised according to the timing and purpose of administration: basal (maintenance), bolus (meal) and biphasic (mixed).
Diabetic MRSA foot infection — role of linezolid therapy
Authors: Turner Joanna M , Hakeem Lukman M , Lockman K Ann , Bhattacharyya Diptendu N , Campbell Ian W
Published: August 2008

Diabetic foot ulceration is common and disabling, often leading to amputation of the leg. Foot ulcers commonly become infected and MRSA infection is becoming more prevalent. MRSA is becoming a major public health problem because of its associated high morbidity and mortality, due to difficulty in its eradication with conventional antibiotics. Although vancomycin is the present mainstay of treatment of MRSA infection, a recently introduced antibiotic, linezolid may have benefits. Linezolid can be given orally, obviating the need for i.v. monitoring and offering potential savings in hospital costs with earlier discharge because of its suitability for out-patient eradication of MRSA.
Review: Combination treatment with insulin and oral agents in type 2 diabetes mellitus
Authors: Burke John
Published: August 2008

The need to improve glycaemic control in type 2 diabetes has been reinforced by the United Kingdom Prospective Diabetes Study (UKPDS). Due to progressive deterioration of beta-cell function after diagnosis, oral hypoglycaemic agents often fail to maintain adequate glycaemic control after only a few years of treatment. This paper considers the treatment options available at this stage and reassures diabetologists that the combined use of insulin plus metformin with or without an added sulphonylurea is logical, is as effective as insulin alone, and provides superior weight regulation in many patients. A. combination of metformin with glargine insulin seems particularly effective and well tolerated. The long-term advantages of such treatments in terms of clinical outcomes have yet to be demonstrated in clinical trials.
Discovering diabetes: achieving target blood glucose control through a behavioural approach to insulin and food self-management
Authors: Brackenridge Betty , Swenson Kris
Published: August 2008

Dhysiological approaches to diabetes therapy can make excellent control possible while protecting patients' lifestyle choices. This paper describes a diabetes programme that employs a teaching method which promotes patient-centred values while pursuing optimal metabolic control. Discovery learning is an experience and inquiry-based method of instruction. It is used in the programme described herein to guide individuals with both type 1 and type 2 diabetes to make informed self-care decisions such as `writing their own diets', and adjusting insulin doses, if appropriate, based on their blood glucose results and experience.
Review: Ezetimibe — clinical and pharmacological profile
Authors: Rees Alan
Published: August 2008

The launch of ezetimibe, a novel cholesterol absorption inhibitor in 2003 may well herald the dawn of combination therapy in the management of dyslipidaemia. The recent identification of NPC 1L1 as the probable specific sterol permease involved in intestinal cholesterol absorption is an important breakthrough in the understanding of the mechanisms of cholesterol absorption. Combination of statin therapy with blockade of exogenous cholesterol absorption (the so called dual inhibition of cholesterol metabolism) is discussed together with the potential for tailoring therapy to the physiological profile of patients' cholesterol metabolism.
What are the clinical manifestations of cardiovascular disease in diabetes? Ten year analysis from a clinic based population
Authors: Stephens Jeffrey W , Humphries Steve E , Cooper Jacqueline A , Hurel Steven J
Published: August 2008

Aims

Cardiovascular disease may manifest as CHD, PVD and CbVD. Our aim was to explore these interactions and associated risk factors.

Methods

Patients were identified who attended clinic in 1990—1991 and remained under follow-up in 2000—2001. The latter were categorised by the presence/absence of manifest CHD, PVD and CbVD. Baseline clinic measurements (1990—1991) were studied in relation to CVD manifestations.

Results

Seven hundred and ninety-eight (CVD:358) patients were identified with follow-up. Of those with CVD: 51% had CHD, 14% PVD, and 9% CbVD exclusively. A further 17% had CHD+PVD, 4% CHD+CbVD, 2% PVD+CbVD, while 3% of patients had all three manifestations together. Increasing age, LDL-cholesterol and glucose were associated with increased risk of CHD, PVD and CbVD.

Conclusions

The majority of diabetic patients with CVD have $CHD (75%), and only 3% have a combination of CHD, PVD and CbVD.
Predictors of mortality in patients with peripheral vascular disease. A prospective follow-up study
Authors: Missouris Constantinos G , Kalaitzidis Rigas G , Kerry Sally M , Cappuccio Francesco P
Published: August 2008

Background

Peripheral vascular disease is associated with increased cardiovascular mortality and reduced life expectancy. The main causes of death are due to concomitant coronary heart and cerebrovascular disease.

Objective

To assess the long-term survival of patients with PVD and to investigate the impact of the presence of risk factors on mortality.

Design

Cohort study of patients with intermittent claudication and angiographically established PVD. Baseline investigations were performed in 1990—2; follow-up continued until 1999.

Setting

St George's Hospital in South London.

Patients

One hundred and ten consecutive patients (66 men and 44 women) referred electively for PVD and who underwent lower limb digital subtraction angiography.

Main outcome measures

Survival rates, all-cause mortality.

Results

Sixty-one patients (55.4%) died during the follow-up period (26 from cardiovascular causes). The overall five-year survival rate was 52% (95% C.I. 42—62). The survival rate was significantly lower in patients older than 70 years (38% [26—51]) compared to those 70 years or younger (69% [54—80])(p<0.05). The risk of all-cause mortality was almost two-fold in the older than younger age group (sex-adjusted hazards ratio 1.89 [1.08—3.10]). The presence of diabetes at the baseline was an important predictor of survival. After adjusting for age and sex diabetic patients had a hazards ratio of 1.79 (0.96—3.37) compared to non-diabetic patients for all-cause mortality. Further adjustment for hypertension, smoking and renal impairment did not attenuate the risk estimate. Hypertension, smoking and the presence of renal artery stenosis were associated with greater risk of all-cause mortality, although none of these estimates reached statistical significance.

Conclusions

Age and presence of diabetes are important independent prognostic factors for increased mortality in patients with peripheral vascular disease.
Weight gain and insulin therapy
Authors: Khan Rehman
Published: August 2008

Weight gain is common with insulin therapy in type 1 and type 2 diabetes. Excessive weight gain worsens glycaemic control and increases cardiovascular risk. It can also increase diabetic morbidity and mortality if it acts as a psychological barrier to initiation or intensification of insulin therapy, or affects compliance. Insulin-associated weight gain might result from conservation of previously excreted glucose, defensive `snacking' caused by fear or experience of hypoglycaemia, or the `unphysiological' pharmacokinetic profiles that follow sc insulin administration. Strategies to limit insulin-mediated weight gain include increasing insulin sensitivity through dietary modification, exercise or insulin sensitising drugs. Attempts to replace insulin using regimens that accurately mimic physiological norms should also enable insulin to be dosed with maximum efficiency. The novel analogue insulin, detemir, has not of the pharmacological mechanisms underlying this shown the usual propensity for weight gain. Elucidation of the pharmacological mechanisms property could further clarify mechanism linking insulin with weight regulation.
Obesity, diabetes and VLCDs
Authors: Bennett Peggy
Published: August 2008

Excess weight gain is an increasing burden on individuals, societies and healthcare providers. The role of very low calorie diets (VLCD) in the treatment of overweight and obese people with diabetes is considered within the framework of a partnership between healthcare providers, a commercial organisation and the patient.
The `polypill' to reduce cardiovascular risk: proof of concept
Authors: Patel Vinod , Pedersen Oluf , Morrissey John , Parving Hans-Henrik , Gæde Peter , Lee James Douglas
Published: August 2008

This article considers data from the Steno-2 multifactorial intervention study in type 2 diabetes to which are applied the United Kingdom Prospective Diabetes Study (UKPDS) risk engine. Mathematical analyses support the use of a `polypill' to reduce cardiovascular risk in type 2 diabetes. It is suggested that the Polypill should include a statin, antihypertensive agents and aspirin.
Physician assistant
Authors: Catanzaro Rachel
Published: August 2008

Rachel Catanzaro is the lead physician assistant in Rowley Regis and Tipton PCT. Herein she outlines the training and responsibilities of this pioneering role which has been introduced to the UK healt
Why have a physician assistant?
Authors: Walton Ian
Published: August 2008

he rationale for including a physician assistant (PA) in the care team is described herein. Dr Ian Walton is a general practitioner (GP) who has championed this pilot scheme for enhancing healthcare delivery in the West Midlands.
Review: PDE-5 inhibitors — a summary
Authors: Hood Stuart , Kirby Mike
Published: August 2008

The orally administered PDE-5 inhibitors have become first-line treatment for erectile dysfunction. Although the three currently available PDE-5 inhibitors have shown similar efficacy, tadalafil has a much longer half-life than sildenafil or vardenafil, and the pharmacokinetic profile of tadalafil is not affected by food. However, there is a more immediate response to dosing with sildenafil and vardenafil than tadalafil. As with all drugs, there will be individual variations in response and the physician's skill is in finding the right drug for the right patient.
Vitamin B12 status of patients treated with metformin: a cross-sectional cohort study
Authors: Sparre Hermann Leif , Nilsson BO , Wettre Staffan
Published: August 2008

Aim

To assess the vitamin B12 status of patients with type 2diabetes who had been receiving metformin treatment for at least one year.

Methods

Patients with type 2 diabetes attending a diabetes clinic were included in a cross-sectional cohort study. Patients exposed to metformin for more than one year (n=53) were compared with a non-exposed control group (n=31). Serum cobalamin and other variables reflecting vitamin B12 status were measured.

Results

Patients on metformin had lower cobalamin (289±137 vs. 395±162 pmol/L; p<0.01) and holotranscobalamin (76±49 vs. 97±41 pmol/L; p<0.05), and higher HCy (11.3+3.3 vs. 10.3±2.3 µmol/L; p<0.05); these changes were correlated. Eight metformin patients, but no controls, had holotranscobalamin below the normal range (p<0.05). Methylmalonic acid and folate were similar in both groups.

Conclusion Patients exposed to long-term metformin therapy had 26.7% lower cobalamin, 21.6% lower holotranscobalamin and 9.7% higher HCy serum concentrations than control subjects. Such changes indicate a potential risk for development of vitamin B12 deficiency. Our results highlight the necessity of checking B12 status during metformin therapy.
Intussusception as a gastrointestinal complication of diabetes: case report and literature review
Authors: Rajeswaran Chinnadorai , Dawson Alison , Bonney Glen , Oxynos Costas , Nicholson Virginia L , Gilbey Stephen George
Published: August 2008

This is the first reported case of intussusception in a patient with type 1 diabetes mellitus complicated by gastroparesis and autonomic neuropathy. Literature on the reported cases of intussusception in patients with diabetes, its aetiopathology and possible association with gastroparesis has been systematically reviewed following a Medline database search (1951 to June 2003) Intussusception should be considered in the differential diagnosis of gastrointestinal symptoms in diabetic patients presenting with hyperglycaemia.
VALUE, blood pressure and diabetes — what can we learn?
Authors: Jarvis Sarah C
Published: August 2008

With the introduction of the new GMS contract, GPs need to treat patients efficiently and effectively in order to achieve Quality and Outcomes Framework points. The VALUE trial has shown that aggressive treatment of hypertension minimises the risk of further cardiovascular outcomes. Dr Sarah Jarvis, a GP, notes that applying the results of this trial to clinical practice will help GPs reach their targets and protect hypertensive patients against further health risks such as new onset diabetes.
Review: Physical disability and the cumulative impact of diabetes in older adults
Authors: Gregg Edward W , Caspersen Carl J
Published: August 2008

he already high and increasing prevalence of diabetes among older adults will make ageing-related outcomes like physical disability an increasingly important complication of diabetes. Disability is a key indicator of both overall morbidity and the success of public health efforts to compress the period of morbidity in old age for the overall population. Many cross-sectional and longitudinal studies have now associated diabetes with increased risk of disabilities in mobility and in instrumental and basic activities of living. The explanation for higher disability among persons with diabetes appears to be multifactorial with neuropathy, peripheral arterial disease, coronary heart disease, depression, obesity, visual impairment, and physical inactivity the most prominent factors. These factors are common in persons with diabetes and exert strong effects on risk of disability. Several promising interventions exist, ranging from exercise programmes and identification and treatment of depression, to long-term prevention of disability through better management of glycaemia and risk factors for cardiovascular disease. Preliminary findings from the U.S. Diabetes Surveillance System suggest that, like the general population, prevalence of physical disability may also have declined among persons with diabetes during the last decade. Ultimately, preventing disability will likely depend on a combination of secondary and tertiary prevention along with, ideally, preventing diabetes in the first place.
Review: Diabetes and insulin therapy in older people
Authors: Hendra Timothy J
Published: August 2008

Concerns about hypoglycaemia, plus lack of evidence of benefit, contributed to underutilisation of insulin for older people with type 2 diabetes in the past. Following the UKPDS it is clear that many elderly patients treated with diet and oral antidiabetic agents will develop beta-cell failure and will be at risk of worsening glycaemic control with reduced well-being unless insulin is considered. Following diabetes diagnosis, the mainstay of treatment will be dietary control and exercise together with management of cardiovascular risk factors. When glycaemic control deteriorates oral agents will be needed. However, whereas in the past insulin was seen as a last resort for older type 2 patients there is support for considering its early use in selected older people with preserved cognitive function and poor glycaemic control, as well as for frail older people with weight loss and poor quality of life. The regimens of choice may include a combination of basal insulin with oral agents or twice-daily combinations of premixed short and intermediate acting insulin. The development of insulin analogues with their associated reduced risk of hypoglycaemia may also herald a new era of insulin treatment for older people.
Predictors of improved glycaemic control with rosiglitazone therapy in type 2 diabetic patients: a practical approach for the primary care physician
Authors: Miyazaki Yoshinori , De Filippis Elena , Bajaj Mandeep , Wajcberg Estela , Glass Leonard , Triplitt Curtis , Cersosimo Eugenio , Mandarino Lawrence J , Defronzo Ralph A
Published: August 2008

Objective — To determine predictors of improved glycaemic control in patients with type 2 diabetes mellitus during rosiglitazone therapy using basic clinical parameters that are readily available in daily clinical practice. Research design and methods — Thirty-seven type 2 diabetic patients (men/women = 18/19; age = 54±2years; diabetes duration = 6±1 years; diet-/sulphonylurea-treated = 24/13) received a 75 g oral glucose tolerance test (OGTT) and determination of body fat before and after rosiglitazone (8 mg/day) for 12 weeks. Results — After rosiglitazone therapy, there were decreases in HbA1C (8.6±0.2 to 7.2±0.2%, p<0.0001), fasting plasma glucose (FPG) (10.6±0.3 to 8.0±0.3 mmol/L [191±6 to 145±6 mg/dL], p<0.0001), fasting plasma insulin (FPI) (108±6 to 84±6 pmol/L [18±1 to 14±µU/ml], p<0.05), fasting free fatty acids (FFA) (760±39 to 611±33 µEq/l, p<0.05), mean plasma glucose (PG) — OGTT (16.2±0.39 to 12.7±0.33 mmol/L [291±7 to 230±6 mg/dL], p<0.001), and mean FFA-OGTT (604±27 to 445±23 µEq/l, p<0.01) despite increases in body weight (85±2 to 88±2 kg, p<0.01) and % fat mass (37.9±2.0 to 39.5±1.9%, p<0.01). The insulinogenic index (IGI) during 0—120 minutes OGTT (IGI0-120) increased following rosiglitazone (0.19±0.03 to 0.30±0.05, p<0.01). Two different insulin sensitivity indices, calculated from PG and plasma insulin (PI) during OGTT, increased significantly: composite index of whole body insulin sensitivity (ISIcomposite): 2.3±0.3 to 3.4±0.4, p<0.05; oral glucose insulin sensitivity (OGIS): 248±5 to 294±6 ml/m2.min, p<0.001. Using clinical and laboratory variables obtained in daily clinical practice (age, gender, diabetes duration, sulphonylurea treatment, body mass index (BMI), % fat mass, fasting plasma insulin/C-peptide/FFA/lipids, IGI0-30, IGI0-120, and ISIcomposite or OGIS), stepwise regression analysis demonstrated that % fat mass (standard coefficient (S.C.) = —0.49, p=0.001) and OGIS (S.C. = 0.31, p=0.02) or ISIcomp (S.C. = 0.31, p=0.03) are significant predictors of the decrease in HbA1C after rosiglitazone (adjusted R2 =0.33, p=0.0004). Conclusions — Rosiglitazone improves insulin resistance and glycaemic control in type 2 diabetes. Obesity (more body fat mass) and reduced insulin sensitivity prior to treatment are the best predictors of glycaemic response to thiazolidinedione therapy in type 2 diabetes.
Dobutamine stress echocardiography in diabetes
Authors: Sharma Rajan , Brecker Stephen J
Published: August 2008

Cardiovascular disease is the leading cause of death in patients with diabetes so prompt diagnosis and treatment of high-risk groups is essential. Dobutamine stress echocardiography is a safe, cheap and reliable method for coronary artery disease diagnosis and provides important long-term prognostic information. The diagnostic accuracy and prognostic predictive power of this technique have been validated by a number of studies on patients with and without diabetes. This article discusses the place of dobutamine stress echocardiography in current cardiology practice and, in particular, its role in the cardiovascular risk stratification of patients with diabetes.
Review: Defining the role of statins in diabetes
Authors: Tuomilehto Jaakko , Leiter Lawrence A
Published: August 2008

Diabetes increases cardiovascular risk, and is recognised as a cardiovascular disease equivalent. Effective reduction of cardiovascular risk factors in diabetes patients is therefore vital. Several landmark clinical trials, including the Heart Protection Study, showed that statins reduce cardiovascular risk, even in patients with pretreatment low-density lipoprotein cholesterol (LDL-C) below 3 mmol/L. The Collaborative Atorvastatin Diabetes Study demonstrated that statin therapy significantly reduces LDL-C and major coronary events in patients with type 2 diabetes. Several studies have assessed which statins are most effective at reducing LDL-C. In patients with diabetes, rosuvastatin 10 mg and atorvastatin 10 mg bring 94% and 79% of patients, respectively, to European LDL-C goals. The benefits of more effective lipid lowering using high-dose statin therapy are being investigated in trials such as Treating to New Targets. Furthermore, studies indicate that combining a fibrate or niacin with a statin may offer more comprehensive lipid control in diabetes patients.
Review: Clinical assessment of endothelial function — an update
Authors: Swampillai Janice , Doshi Sagar , Fraser Alan G , Goodfellow Jonathan , Jones Christopher Jh
Published: August 2008

Endothelial dysfunction precedes clinically detectable vascular disease, suggesting its early detection may allow the targeting of treatment to improve endothelial function and thus inhibit progression of disease.1,2 Although the evidence for a preventive strategy remains circumstantial, there is worldwide interest in the measurement of endothelial function in relation to risk factors and treatment of atherosclerotic vascular disease. Unfortunately, a widely applicable clinical measurement of endothelial function does not yet exist; those that are available remain tools for research. The ideal clinical test of endothelial function should be specific, sensitive and reproducible, as well as simple to perform, painless, and inexpensive. In this review we outline the relative merits and disadvantages of the techniques that are available.
Comparison of three different definitions for the metabolic syndrome in non-diabetic Europeans
Authors:   THE DECODE STUDY GROUP, Qiao Qing
Published: August 2008

Aim — To compare definitions for the metabolic syndrome given by the World Health Organization (WHO), the European Group for Study of Insulin Resistance (EGIR), and the National Cholesterol Education Program (NCEP). Study population — 4,190 men and 4,950 women from seven cross-sectional European studies. Results — The age-standardised prevalence of the metabolic syndrome by different definitions was 16.5—24.7% in men and 15.2—20.9% in women aged 30—77 years, and was lowest by the EGIR criteria. Subjects who met all three definitions accounted for only 31% of the men and 34% of the women who had the metabolic syndrome by any of the three definitions, whereas 37% of these men and 39% of these women met only one of the three. Subjects with the NCEP definition only were more obese, hypertensive and dyslipidaemic than those identified by other definitions. Conclusions — The prevalence of the metabolic syndrome is high in non-diabetic Europeans. The agreement between the three definitions in the identification of subjects with the metabolic syndrome is poor and the phenotypes of those identified differ.
Review: Insulin secretion: function and therapy of pancreatic beta-cells in diabetes
Authors: Rorsman Patrik
Published: August 2008

nsulin is secreted from the beta-cells of the pancreatic islets in response to an elevation of blood glucose concentration. This review describes a current view of the metabolic control of insulin secretion and the molecular mechanisms involved, including the role played by the beta-cell to ensure correct release of insulin as a result of electrical signals. It then considers what goes wrong in type 2 diabetes, a disease resulting from insufficient insulin secretion. It focuses on the influence of genetics exploring the theory of a genetic predisposition to type 2 diabetes, as well as the roles played by age and obesity. Finally, the mode of action of the hypoglycaemic sulphonylureas is discussed and the potential implications for the beta-cell associated with a sulphonylurea-based therapy.
Pioglitazone — an oral antidiabetic agent and metabolic syndrome modulator. Can theory translate into practice?
Authors: Campbell Ian W
Published: August 2008

The metabolic syndrome, associated with insulin resistance, is a cluster of cardiovascular risk factors which results in premature morbidity and mortality from atherosclerotic vascular disease. Pioglitazone, a peroxisome-proliferator-activated receptor gamma (PPARγ) agonist, is an insulin sensitiser with the ability to address key features of the metabolic syndrome: glucose intolerance including type 2 diabetes, hypertension, dyslipidaemia, the pro-coagulant state, endothelial dysfunction, inflammation and atherosclerosis. The greatest potential benefit of pioglitazone is to influence atherogenesis itself through its pleiotrophic effects on vascular risk factors. This has been tested by the PROactive study, results of which are published in September 2005.
The incretin mimetic, exenatide: a novel treatment option for type 2 diabetes
Authors: Schnabel Catherine A
Published: August 2008

Exenatide, (BYETTA TM), is the first in a new class of agents termed incretin mimetics, which replicate several glucoregulatory effects of the endogenous incretin hormone, glucagon-like peptide-1 (GLP-1). Currently approved (April 2005) in the United States as an injectable adjunct to metformin and/or sulphonylurea therapy, exenatide improves glycaemic control through multiple mechanisms of action including: enhancement of glucose-dependent insulin secretion, restoration of first-phase insulin response, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying and reduction in food intake. Subcutaneous exenatide injected twice-daily before morning and evening meals shows immediate and sustained effects on both postprandial and fasting glucose concentrations and is accompanied by reductions in body weight. Since the actions of exenatide on insulin and glucagon secretion are glucose dependent, the risk of hypoglycaemia is minimised except when exenatide is used in conjunction with agents that induce hypoglycaemia, such as sulphonylureas. Mild-to-moderate nausea is the most common side effect, which can be reduced with dose titration upon initiation of therapy. The incretin mimetic, exenatide, is a novel therapeutic option to improve glycaemic control with potential weight reduction in patients with type 2 diabetes suboptimally controlled with metformin or a sulphonylurea.
Review: Diabetes mellitus in South African Indians
Authors: Seedat Yackoob K
Published: August 2008

Diabetes mellitus is common in the South Asian population residing in the Indian diaspora. Cardiovascular disease is a major cause of death in the Indians of South Africa. This study reviews the epidemiology and clinical pattern of diabetes mellitus in the South African Indian population from the available published literature. The concept of insulin resistance in the Indian population group appears to be interesting and has a novel approach towards explaining the high risk of cardiovascular disease. Dietary factors and physical inactivity could contribute to diabete mellitus.
Intima-media thickness and atherosclerotic plaques in popliteal, tibial, brachial and radial arteries in 65-year-old Finns with diabetes
Authors: Rajala Ulla , Päivänsalo Markku , Laakso Mauri , Suramo Ilkka , Keinänen-Kiukaanniemi Sirkka
Published: August 2008

The aim of the present study was to examine the intima-media thickness (IMT) and the number of atherosclerotic plaques in the medium-sized arteries of the lower and upper limbs in 65-year-old Finns (45 diabetic subjects, 65 subjects with impaired glucose tolerance [IGT] and 38 normoglycaemic [NGT] subjects). The maximal IMT of radial arteries was higher in subjects with diabetes (0.41 mm±0.07) than in those with IGT (0.36 mm±0.06) or NGT (0.35 mm±0.07) (p<0.001), but in popliteal, tibial and brachial arteries there were no significant differences between the groups. A large proportion of the study population had plaques in their lower limb arteries and some subjects had a very high number of plaques. The proportion of subjects with diabetes in the highest quintile of the number (≥ 79) of tibial plaques was 47%, while the corresponding number was 26% among those with a lower number of plaques (p=0.030). The occurrence of plaques in brachial and radial arteries was low. Diabetic subjects tended to have radial plaques more often than subjects with IGT and NGT.
Review: Treatment of lipids to reduce cardiovascular risk among people with the metabolic syndrome or type 2 diabetes
Authors: Wild Sarah H , Byrne Christopher D
Published: August 2008

he metabolic syndrome is present in approximately 20% of general populations in developed countries and in approximately 80% of people with type 2 diabetes. High triglyceride levels, low high-density cholesterol levels and central obesity are three of the five features of the metabolic syndrome and contribute to the increased risk of cardiovascular disease (CVD) among people with the metabolic syndrome. Lifestyle interventions and treatment with statins reduce risk of CVD but absolute risk of cardiovascular events among high-risk populations remains high. This article reviews the options for treating the atherogenic dyslipidaemia associated with the metabolic syndrome.
Review: Blood pressure reduction in the metabolic syndrome and type 2 diabetes: current concepts
Authors: Schachter Michael
Published: August 2008

ypertension very frequently co-exists with type 2 diabetes and with the metabolic syndrome, though any links regarding underlying pathophysiology remain controversial. However, there is no doubt that the combination greatly increases cardiovascular and renal disease risks. At the same time there is extensive evidence that blood pressure (BP) lowering is a highly effective means of reducing these risks. Current guidelines and other advice emphasise that both the threshold for intervention and the target for BP lowering are below those for the general hypertensive population, at about 130/80 mmHg, but even less in the presence of nephropathy. Blockade of the renin-angiotensin system is considered highly desirable, preferably using angiotensin receptor blockers. Combination drug therapy is almost always needed, and the ABCD rule is helpful as a guide in this respect. The combination of beta blockers and thiazides should usually be avoided, especially in the metabolic syndrome, as it may promote the emergence of overt diabetes. But ultimately the key consideration should be the BP achieved rather than the means required to achieve it.
Review: Aspirin and diabetes
Authors: Raghavan Rajeev P , Laight David W , Shaw Kenneth M , Cummings Michael H
Published: August 2008

Type 2 diabetes accounts for a large proportion of cardiovascular disease within the UK. Inflammation is increasingly seen as a core process (even touted as a causative factor) connecting the metabolic syndrome and cardiovascular disease. Inflammatory markers, adhesion molecules, transcription regulators such as PPAR-gamma and NF-kappa B are being recognised as key elements of the underlying pathological process. In particular the links between oxidative stress, metabolic syndrome components and a pro-inflammatory milieu are becoming increasingly recognised.

Salicylates have been used extensively for more than a hundred years but remain the subject of much research and scientific debate. Mechanisms of aspirin action, such as effects on endothelial function, oxidative stress, hyperglycaemia, inflammation, and mechanisms of aspirin resistance are being elucidated. With the advent of COX-2 selective inhibitors, the importance of the cyclo-oxygenase (COX-1 & COX-2 enzymes) pathways and the implications of more selective COX manipulation are being re-evaluated. There is no universal consensus on the use and dose of aspirin in diabetes. This review focuses upon the impact that aspirin may have to ameliorate the pathophysiology of diabetes and CVD.
Review: Comparing cardiovascular outcomes in diabetes studies
Authors: Mccallum Roland W , Fisher Miles
Published: August 2008

iabetes can be considered as a cardiovascular disease leading to the premature death of patients. The increase in cardiovascular risk has been extensively investigated and is associated with a cluster of adverse factors. The effects of various treatments used to affect the pathogenesis of the atherosclerotic process have been investigated in many large trials. A number of issues make the interpretation and comparison of these trials complicated, and in particular the use of a single primary end point such as mortality has been replaced with composite end points. The effects of risk factors and interventions on coronary heart disease (CHD) risk has been converted to cardiovascular disease (CVD) risk for understandable reasons, but this makes the interpretation and comparison of results even more complex. This review provides a critical analysis of outcome studies, highlighting differences in design, end points, patient inclusion and definitions in recent cardiovascular diabetology trials, and examines the potential pitfalls in making unjustified comparisons. Br J Diabetes Vasc Dis 2006; 6:111—18
Review: Sulphonylureas and cardiovascular risk: facts and controversies
Authors: Valensi Paul , Slama Gérard
Published: August 2008

Cardiovascular complications are the principal cause of death in type 2 diabetes. The importance of glycaemic control in preventing cardiovascular complications has been demonstrated. However, some oral antidiabetic agents and especially some sulphonylureas (SU) have been accused of having a deleterious effect on cardiovascular risk. A retrospective analysis of the administrative database of Saskatchewan Health for 5,795 subjects, identified by their first-ever dispensation for an oral antidiabetic agent, suggests that a higher exposure to SUs was associated with increased mortality. Nevertheless, the effects of SUs on cardiac ATP-sensitive potassium channels in experimental studies vary between agents and studies, so that the clinical relevance of this phenomenon is unclear. Moreover, 11 years of follow-up of patients randomised to glibenclamide or chlorpropamide in the United Kingdom Prospective Diabetes Study demonstrated no adverse effects on a range of cardiovascular end points. Despite SU structural differences and differences in binding to cardiac SU receptors, the clinical evidence base does not support the selection of one sulphonylurea over another on the basis of ischaemic preconditioning, possibly because ischaemic preconditioning may be blunted or absent in diabetes. The main objective remains the prevention or delay of diabetic complications through improvement of glycaemic control together with other cardiovascular risk factors.
The role of metformin and pioglitazone in early combination treatment of type 2 diabetes mellitus
Authors: Campbell Ian W
Published: August 2008

Metformin will celebrate 50 years of clinical use in 2007. Pioglitazone was introduced into clinical practice in 1999. Both metformin and pioglitazone have positive effects on components of the metabolic syndrome, namely: insulin resistance, hyperinsulinaemia, visceral obesity, hyperglycaemia, dyslipidaemia and hypertension and risk factors involved in endothelial dysfunction, inflammation and atherosclerosis. Improvements in cardiovascular outcomes have been demonstrated in patients at high risk of macrovascular events with pioglitazone (PROactive) and in overweight patients with metformin (UKPDS 34). Pioglitazone may also help to sustain beta-cell function. Introduction of combination therapy using two differently acting oral antidiabetic agents at the time of diagnosis or early thereafter is becoming increasingly common in order to reach glycaemic targets (e.g. HbA1C ≤7.0%). The combination of metformin and pioglitazone in an early stage of type 2 diabetes enables greater likelihood that these targets can be with insulin secretagogues. attained without the risk of hypoglycaemia associated with insulin secretagogues
Review: Non-alcoholic fatty liver disease: natural history, pathogenesis and treatment
Authors: Mcavoy Norma C , Ferguson James W , Campbell Ian W , Hayes Peter C
Published: August 2008

Non-alcoholic fatty liver disease (NAFLD) is the term used to describe the alcohol-like liver injury that occurs in the absence of alcohol abuse. It embraces a range of histological abnormalities including simple steatosis or fatty liver, non-alcoholic steatohepatitis (NASH) and NAFLD induced cirrhosis. The predominant risk factor for NAFLD appears to be insulin resistance. Simple steatosis and NASH are generally asymptomatic and it is only the development of cirrhosis that has clinical consequence. At present, therapy in NAFLD concentrates on managing risk factors but in the future clinical trials may provide robust evidence for the use of insulin sensitising agents and other potential therapies.