Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study.

SLCO1B1 gene variants are associated with severe statin-induced myopathy. We examined whether these variants are also associated with general statin intolerance in a large population of patients with type 2 diabetes receiving statins as part of routine clinical care. A total of 4,196 individuals were genotyped for rs4149056 (Val174Ala) and rs2306283 (Asp130Asn).

The misclassification of facial expressions in generalised social phobia.

The aim of this study was to investigate facial expression recognition (FER) accuracy in social phobia and in particular to explore how facial expressions of emotion were misclassified. We hypothesised that compared with healthy controls, subjects with social phobia would be no less accurate in their identification of facial emotions (as reported in previous studies) but that they would misclassify facial expressions as expressing threatening emotions (anger, fear or disgust). Thirty individuals with social phobia and twenty-seven healthy controls completed a FER task which featured six basic emotions morphed using computer techniques between 0 percent (neutral) and 100 percent intensity (full emotion).

The use of metformin in type 1 diabetes: a systematic review of efficacy.

Aims/hypothesis: As adding metformin to insulin therapy has been advocated in type 1 diabetes, we conducted a systematic review of published clinical trials and clinical trial databases to assess the effects on HbA(1c), weight, insulin-dose requirement and adverse effects.

Methods: We constructed evidence tables and fitted a fixed-effects model (inverse variance method) in order to assess heterogeneity between studies and give a crude measure of each overall treatment effect.

Results: Of 197 studies identified, nine involved randomisation with informed consent of patients with type 1 diabetes to metformin (vs placebo or comparator) in either a parallel or crossover design for at least 1 week.

Use of insulin glargine and cancer incidence in Scotland: a study from the Scottish Diabetes Research Network Epidemiology Group.

Aims/hypothesis: The aim of the present study was to examine whether patients with diabetes in Scotland using insulin glargine have a greater cancer risk than patients using other types of insulin.

Methods: We used a nationwide diabetes clinical database that covers the majority of the Scottish population with diagnosed diabetes, and examined patients with diabetes who were exposed to any insulin therapy between 1 January 2002 and 31 December 2005. Among these we defined a fixed cohort based on exposure during a 4 month period in 2003 (n = 36,254, in whom 715 cases of cancer occurred) and a cohort of new insulin users across the period (n = 12,852 in whom 381 cancers occurred).

Effects of atorvastatin on kidney outcomes and cardiovascular disease in patients with diabetes: an analysis from the Collaborative Atorvastatin Diabetes Study (CARDS).

Background: We examined whether atorvastatin affects diabetic kidney disease and whether the effect of atorvastatin on cardiovascular disease (CVD) varies by kidney status in patients with diabetes.

Study Design: The Collaborative Atorvastatin Diabetes Study (CARDS) randomized placebo-controlled trial.

Setting & Participants: Patients with type 2 diabetes and no prior CVD (n = 2,838).

Targets of statin therapy: LDL cholesterol, non-HDL cholesterol, and apolipoprotein B in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS).

Background: LDL can vary considerably in its cholesterol content; thus, lowering LDL cholesterol (LDLC) as a goal of statin treatment implies the existence of considerable variation in the extent to which statin treatment removes circulating LDL particles. This consideration is particularly applicable in diabetes mellitus, in which LDL is frequently depleted of cholesterol.

Methods: Type 2 diabetes patients randomly allocated to 10 mg/day atorvastatin (n = 1154) or to placebo (n = 1196) for 1 year were studied to compare spontaneous and statin-induced apolipoprotein B (apo B) concentrations (a measure of LDL particle concentration) at LDLC and non-HDL cholesterol (non-HDLC) concentrations proposed as statin targets in type 2 diabetes.

Apolipoproteins, cardiovascular risk and statin response in type 2 diabetes: the Collaborative Atorvastatin Diabetes Study (CARDS).

Aims/hypothesis: Controversy surrounds whether the ratio of apolipoprotein B (ApoB) to apolipoprotein A-I (ApoA-I) is the best lipoprotein discriminator of CHD risk in non-diabetic populations, but the issue has never been investigated in type 2 diabetes.

Methods: In 2,627 participants without known vascular disease in the Collaborative Atorvastatin Diabetes Study, ApoB, ApoA-I, LDL-cholesterol (LDLC) and HDL-cholesterol (HDLC) were assayed at baseline.

Results: There were 108 CHD and 59 stroke endpoints over 3.

The safety and tolerability of atorvastatin 10 mg in the Collaborative Atorvastatin Diabetes Study (CARDS).

The objective of this study was to evaluate the safety and tolerability of atorvastatin 10 mg compared with placebo in 2,838 patients with type 2 diabetes and no history of coronary heart disease who were enrolled in the Collaborative Atorvastatin Diabetes Study (CARDS) and followed for 3.9 years. The percentages of patients experiencing treatment-associated adverse events (AEs), serious AEs and discontinuations due to AEs in the atorvastatin (n=1,428) and placebo (n=1,410) groups were 23.

A genetic link between type 2 diabetes and prostate cancer.

Epidemiological studies suggest that men with type 2 diabetes are less likely than non-diabetic men to develop prostate cancer. The cause of this association is not known. Recent genetic studies have highlighted a potential genetic link between the two diseases.

Risk of myocardial infarction in men and women with type 2 diabetes in the UK: a cohort study using the General Practice Research Database.

Aims/hypothesis: Our primary aim was to establish reliable and generalisable estimates of the risk of myocardial infarction (MI) for men and women with type 2 diabetes in the UK compared with people without diabetes. Our secondary aim was to investigate how the MI risk associated with diabetes differs between men and women.

Methods: A cohort study using the General Practice Research Database (1992-1999) was carried out, selecting 40,727 patients with type 2 diabetes and 194,913 age and sex-matched patients without diabetes.

Antibodies to periodontal pathogens and coronary artery calcification in type 1 diabetic and nondiabetic subjects.

Background And Objective: The aim of this study was to examine whether serum immunoglobulin G (IgG) levels to Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans are higher in type 1 diabetic patients than in controls and are associated with coronary artery calcification, a measure of atherosclerosis.

Material And Methods: One-hundred and ninety nine type 1 diabetic patients (mean age 38 +/- 4 years) and 201 age- and gender-matched nondiabetic subjects had coronary artery calcification, as measured by electron beam computed tomography. Serum IgG levels to P.

Lipid goals in metabolic syndrome and diabetes.

There is considerable disparity between the major clinical guidelines on lipid targets in diabetes and metabolic syndrome. Over the past few years, several trials have reported results that contribute to the evidence base for such lipid targets. The Treat to New Targets study data provide support for the efficacy and safety of using high-dose statin therapy for reducing low-density lipoprotein cholesterol (LDL-C) to at least 2 mmol/L in patients with diabetes and established cardiovascular disease (CVD).

Evaluation of autologous chondrocyte transplantation via a collagen membrane in equine articular defects: results at 12 and 18 months.

Objective: To evaluate a technique of autologous chondrocyte implantation (ACI) similar to the other techniques using cell-seeded resorbable collagen membranes in large articular defects.

Methods: Autologous cartilage was harvested arthroscopically from the lateral trochlear ridge of the femur in fifteen 3-year-old horses. After culture and expansion of chondrocytes the newly created ACI construct (autologous chondrocytes cultured expanded, seeded on a collagen membrane, porcine small intestine submucosa) was implanted into 15mm defects on the medial trochlear ridge of the femur in the opposite femoropatellar joint.

Stroke prediction and stroke prevention with atorvastatin in the Collaborative Atorvastatin Diabetes Study (CARDS).

Aims: Patients with Type 2 diabetes have an elevated risk of stroke. The role of lipid levels and diabetes-specific factors in risk prediction of stroke is unclear, and estimates of efficacy of lipid-lowering therapy vary between trials. We examined predictors of stroke and the effect of atorvastatin on specific stroke subtypes in Type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS) [a trial of 2838 participants with mean low-density lipoprotein cholesterol < 4.

Cost-effectiveness of primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes: results from the Collaborative Atorvastatin Diabetes Study (CARDS).

Aims/hypothesis: We estimated the cost-effectiveness of atorvastatin treatment in the primary prevention of cardiovascular disease in patients with type 2 diabetes using data from the Collaborative Atorvastatin Diabetes Study (CARDS).

Subjects And Methods: A total of 2,838 patients, who were aged 40 to 75 years and had type 2 diabetes without a documented history of cardiovascular disease and without elevated LDL-cholesterol, were recruited from 32 centres in the UK and Ireland and randomly allocated to atorvastatin 10 mg daily (n = 1,428) or placebo (n = 1,410). These subjects were followed-up for a median period of 3.

Risk of stroke in people with type 2 diabetes in the UK: a study using the General Practice Research Database.

Aims/hypothesis: Risk estimates for stroke in patients with diabetes vary. We sought to obtain reliable risk estimates for stroke and the association with diabetes, comorbidity and lifestyle in a large cohort of type 2 diabetic patients in the UK.

Materials And Methods: Using the General Practice Research Database, we identified all patients who had type 2 diabetes and were aged 35 to 89 years on 1 January 1992.

Analysis of efficacy and safety in patients aged 65-75 years at randomization: Collaborative Atorvastatin Diabetes Study (CARDS).

Objective: Rates of cardiovascular disease are highest in the elderly. Lipid-lowering statin therapy reduces the proportional risk as effectively in older patients as in younger individuals; however, limited data are available for elderly patients with type 2 diabetes. We conducted a post hoc analysis to compare the efficacy and safety of atorvastatin among 1,129 patients aged 65-75 years at randomization with 1,709 younger patients in the Collaborative Atorvastatin Diabetes Study (CARDS).

Mortality in people with type 2 diabetes in the UK.

Aims: Under-reporting of diabetes on death certificates contributes to the unreliable estimates of mortality as a result of diabetes. The influence of obesity on mortality in Type 2 diabetes is not well documented. We aimed to study mortality from diabetes and the influence of obesity on mortality in Type 2 diabetes in a large cohort selected from the General Practice Research Database (GPRD).

High risk of cardiovascular disease in patients with type 1 diabetes in the U.K.: a cohort study using the general practice research database.

Objective: To estimate the absolute and relative risk of cardiovascular disease (CVD) in patients with type 1 diabetes in the U.K.

Research Design And Methods: Subjects with type 1 diabetes (n = 7,479) and five age- and sex-matched subjects without diabetes (n = 38,116) and free of CVD at baseline were selected from the General Practice Research Database (GPRD), a large primary care database representative of the U.

Insight into the nature of the CRP-coronary event association using Mendelian randomization.

Background: It is unclear wheather the association between C-reactive protein (CRP) and incident coronary events is free from bias and confounding. Individuals homozygous for a +1444C>T polymorphism in the CRP gene have higher circulating concentrations of CRP. Since the distribution of this polymorphism occurs at random during gamete formation, its association with coronary events should not be biased or confounded.

Coronary heart disease in women: why the disproportionate risk?

Women with diabetes experience much greater relative risks of coronary heart disease (CHD) compared with the nondiabetic population than do men with diabetes. In type 2 diabetes, much of the greater elevation in risk in women is explained by a more adverse pattern of known CHD risk factors. In type 1 diabetes the picture is less clear, but current evidence suggests that a cardioprotective lipid profile is found in type 1 diabetic men, thus reducing the effect of diabetes on CHD, but that in women this is not the case.

All-cause mortality rates in patients with type 1 diabetes mellitus compared with a non-diabetic population from the UK general practice research database, 1992-1999.

Aims/hypothesis: We compiled up to date estimates of the absolute and relative risk of all-cause mortality in patients with type 1 diabetes in the UK.

Materials And Methods: We selected patients with type 1 diabetes (n=7,713), and for each of these diabetic subjects five age- and sex-matched control subjects without diabetes (n=38,518) from the General Practice Research Database (GPRD). Baseline was 1 January 1992; subjects were followed until 1999.

Treatment of lipid disorders in patients with diabetes.

The use of lipid-lowering drugs in diabetes is aimed primarily at reducing the large cardiovascular disease (CVD) risk burden experienced by this group of patients. Statin therapy has been shown to be highly efficacious in reducing CVD risk, both in those with and without prior CVD. Therefore, statins are the first-line lipid-lowering therapy in patients with diabetes.