Diabetes Mellitus Subgroup Research Articles

Association between prior aspirin use and optical coherence tomography findings in type II diabetes mellitus patients presenting with first acute coronary events

Aims: Aspirin has been shown to be beneficial in the primary prevention, secondary prevention, and treatment of acute coronary syndromes (ACS). However, it is less clear whether prior aspirin therapy affects lesion morphology in ACS. The aim of the present study is to investigate the association between prior aspirin use and the culprit lesion morphology examined by optical coherence tomography (OCT) in patients with the first ACS event. We further performed subgroup analysis on the basis of the presence or the absence of type 2 diabetes mellitus (DM). Methods and results: We studied 250 patients with the first ACS event who had identifiable 250 native de novo culprit lesions suitable for percutaneous coronary intervention (PCI) and OCT examinations. All patients underwent OCT examinations before PCI. Clinical and OCT findings were compared between the two groups divided on the basis of prior aspirin use (ASA; n= 27: 11%, non-ASA; n = 223: 89%), and then, in diabetic (n=75, 30%) and non-diabetic patients (n=175, 70%) for the subset analysis. TCFA was defined as lipid-rich plaque (one or more quadrants) with fibrous cap thickness < 70μm. There were no significant differences in the clinical presentations between ASA and non-ASA groups. Frequency of coronary occlusion at initial angiogram was also similar in both groups (ASA: 30% vs non-ASA: 24%, P = 0.64). In DM subgroup analysis, 7 (9%) patients were ASA group and 68 (91%) were non-ASA group, whereas 20 (11%) patients were ASA group and 155 (89%) were non-ASA group in non-DM subgroup. In OCT analysis, the presence of thrombi (ASA: 41% vs. non-ASA: 70%, P < 0.01) was significantly less frequent in ASA group, whereas frequency of TCFA (ASA: 48% vs. non-ASA: 60%, P = 0.30), plaque rupture (ASA: 26% vs. non-ASA: 42%, P = 0.15), thinnest cap thickness (ASA: median: 60 μm [IQR: 50-105] vs. non-ASA: 60 μm [50-80], P = 0.71), and lipid quadrants (ASA: median: 3 [IQR: 2-4] vs. non-ASA: 3 [3-4], P = 0.87) were not statistically significant between the two groups. In non-diabetic patients, presence of thrombi was significantly greater in non-ASA group (ASA: 30% vs. non-ASA: 71%, P <0.01), whereas no significant difference in the frequency of the presence of thrombi was observed in diabetic patients (ASA: 71% vs. non-ASA: 68%, P =1.00). No other differences in OCT findings were detected between diabetic and non-diabetic patients. Conclusions: Prior aspirin use before the first ACS event was associated with the frequency of OCT-derived thrombus detection in the culprit lesions, although this effect was observed only in non-diabetic patients.

Rate and predictors of blood pressure control in a federal qualified health center in Michigan: a huge concern?

Hypertension (HTN) is particularly burdensome in low-income groups. Federal-qualified health centers (FQHCs) provide care for low-income and medically underserved populations. To assess the rates and predictors of blood pressure (BP) control in an FQHC in Michigan, a retrospective analysis of all patients with HTN, coronary artery disease, and/or diabetes mellitus (DM) seen between January 2006 and December 2008 was conducted. Of 212 patients identified, 154 had a history of HTN and 122 had DM. BP control was achieved in 38.2% of the entire cohort and in 31.1% of patients with DM. The mean age was lower in patients with controlled BP in both the total population (P=.05) and the DM subgroup (P=.02). A logistic regression model found only female sex (odds ratio, 2.27; P=.02) to be associated with BP control and a trend towards an association of age with uncontrolled BP (odds ratio, 0.97; P=.06). BP control in nondiabetics was 47.8% vs 31.1% in diabetic patients (P=.02). We found that patients who attended the FQHC had a lower rate of BP control compared with the national average. Our study revealed a male sex disparity and significantly lower rate of BP control among DM patients.

Diabetes is associated with lower global cognitive function in schizophrenia

BackgroundCo-morbidity of schizophrenia (SZ) and metabolic problems such as diabetes mellitus (DM) has been suggested by many studies. Nonetheless, it is still debated whether DM affects cognitive dysfunction associated with SZ and how much treatment for DM is beneficial for cognitive functions in SZ. We addressed these questions by re-assessing the cognitive dataset from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study. MethodsWe identified 1289 SZ patients in which scores for several cognitive domains of verbal memory, vigilance, processing speed, reasoning, and working memory together with the composite score and metabolic characteristics (body mass index, dyslipidemia, hypertension, and DM) were available at baseline of the trial. We performed multiple linear regression analyses to assess the impact of DM on cognitive performance of SZ patients, controlling for a number of other confounding factors including obesity, hypertension, and dyslipidemia. We also conducted analyses of covariance to compare cognitive performance among SZ patients without DM and diabetic SZ sub-groups based on anti-diabetic drugs they were receiving at baseline of the trial. ResultsCo-morbid DM with SZ predicted worse overall cognitive performance and lower scores for three cognitive domains (vigilance, processing speed, and reasoning), but none of the other metabolic factors (i.e., obesity, hypertension and dyslipidemia) correlated with cognitive function in SZ. Furthermore, SZ patients with untreated DM showed poorer overall cognitive performance and a significantly lower score in the domain of vigilance compared with SZ patients without DM. ConclusionOur data suggest that DM negatively affects the overall cognitive function of SZ patients.

Effects of renin-angiotensin system inhibitors on coronary in-stent restenosis: a meta-analysis of randomised controlled trials

BackgroundRAS inhibitors have been proved to antiproliferative effect on neointimal hyperplasia so as to prevent in-stent restenosis (ISR) in animal models. However whether RAS inhibitors could prevent ISR in human...

Impact of Myocardial Acceleration during Isovolumic Contraction in Evaluating Subclinical Right Ventricular Systolic Dysfunction in Type 2 Diabetes Mellitus Patients

In diabetes mellitus (DM) patients, left ventricular dysfunction is widely evaluated and established by conventional diagnostic methods, whereas right ventricular (RV) function is not as sufficiently evaluated. The aim of this study is to assess the preclinical effects of DM on RV function by using novel Tissue Doppler Imaging (TDI)-derived indices. The study included 96 patients with type II DM [60 with DM only and 36 patients with coexisting DM and hypertension (DMHT)] and 40 healthy controls. Conventional parameters and TDI-derived systolic velocities of tricuspid annulus [isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IVV), peak systolic velocity during ejection period (Sa), RV Tei index] were measured. TDI-derived RV IVA was significantly lower in both DM and DMHT patients compared to controls indicating subclinical impairment in RV systolic function in the study patients (P = 0,0001). However RV IVA was similar in DM and DMHT subgroup supporting RV systolic impairment in DM was independent from HT. In correlation analysis, RV IVA was significantly correlated with the existence of diabetic nephropathy (r =-0,38; P = 0,003), retinopathy (r =-0,35; P = 0,006), insulin resistance (r =-0,52; P = 0,0001). Diabetes is associated with subclinical RV systolic dysfunction, regardless of coexisting hypertension. Tissue Doppler-derived IVA; is a novel, non-invasive parameter which may be used in early detection of RV systolic dysfunction in patients with DM.

Stroke: Highlights of Selected Articles

Executive functions are cognitive processes essential for controlling goal-oriented behavior and responding to new and novel situations. Executive function includes the processes of planning, initiation, organization, inhibition, problem solving, self-monitoring, and error correction. It has been estimated that ≈75% of stroke survivors experience impaired executive function (executive dysfunction), resulting in reduced capacity to regain independence in activities of daily living, particularly when new movement strategies are necessary to compensate for limb weakness. A variety of cognitive rehabilitation interventions are implemented within clinical practice in an attempt to improve executive function and, consequently, independence with activities of daily living.1 To determine the effects of cognitive rehabilitation on executive dysfunction for adults with stroke or other nonprogressive acquired brain injuries. We searched: …

Comparative Study of Atherosclerotic Parameters in Mongolian and Japanese Patients with Hypertension and Diabetes Mellitus

Cardiovascular disease is becoming increasingly more problematic in Mongolia. The cardioankle vascular index (CAVI) and circulating C-reactive protein (CRP) are new atherosclerosis-related parameters, but no comparative studies of atherosclerotic parameters including CAVI and CRP are available between Mongolian and Japanese populations, such as disease populations of hypertension (HT) and diabetes mellitus (DM). Our study objective was to examine atherosclerotic profiles in HT and DM patients in both countries. From a hospital-based population, 156 Mongolian outpatients with HT and DM (men: 46%, mean age: 57.1 years) and 156 age- and sex-matched Japanese outpatients with HT and DM (men: 46%, age: 57.7) were recruited. Body mass index (BMI), heart rate (HR), blood pressure (BP), pulse pressure (PP), ankle-brachial index (ABI), ultrasonographic carotid intima-media thickness (IMT), blood total cholesterol (T-Cho), glucose, insulin and homeostasis model assessment of insulin resistance (HOMA-IR) were measured, in addition to CAVI and CRP. The levels of BMI, HR, BP, PP, insulin and IMT were significantly higher and T-Cho and glucose were significantly lower in the Mongolian patients in comparison to the Japanese patients. Particularly, the levels of CAVI (mean+/-SD) (8.1+/-1.1 vs. 8.8+/-1.2) and CRP(median[interquartile range])(0.05[0.03-0.12]vs. 0.19[0.09-0.42]mg/dL)were significantly higher in Mongolian than Japanese patients. These significant differences remained unchanged, even after taking into account multiple variables, including BP and HOMA-IR. In addition, except for CAVI in the subgroup of DM, generally similar trends regarding atherosclerotic parameters were seen in the subgroup by sex and disease (HT, DM and HT plus DM). These findings suggest that Mongolian patients with HT and DM may be at higher risk for cardiovascular disease than Japanese patients.

Nifedipine Intake Increases the Risk for Periodontal Destruction in Subjects With Type 2 Diabetes Mellitus

This study investigated the possible association of nifedipine (NIF) intake and diabetes mellitus (DM) with periodontal destruction. A group of Chinese subjects (N = 1,083, age: 63 +/- 8.7 years) were screened. Three hundred fifty-eight non-smokers with hypertension were selected for the study and were grouped based on DM status as non-DM and DM groups, DM(-) and DM(+) respectively. NIF(+) and NIF(-) indicated NIF intake or not. The groups were further divided: NIF(-)/DM(-) (n = 135); NIF(+)/DM(-) (n = 108); NIF(-)/DM(+) (n = 64); and NIF(+)/DM(+) (n = 51). The periodontal conditions in anterior teeth were assessed using plaque index, sulcus bleeding index, clinical attachment loss (AL), probing depth (PD), and the number of missing teeth. Using analysis of covariance, NIF intake was associated with mean PD and extent of PD > or =4 mm in the non-DM and DM groups. The subjects in the NIF(+)/DM(+) subgroup showed greater mean AL and percentage of sites with AL > or =5 mm and AL > or =7 mm than those in NIF(-)/DM(+) subgroup, whereas no significant difference existed between subjects in NIF(-)/DM(-) and NIF(+)/DM(-) subgroups. The NIF(+)/DM(+) subgroup exhibited a greater percentage of sites with AL > or =5 mm (35.5%) compared to the other three subgroups (24.7% for NIF[-]/DM[-], P = 0.004; 25.0% for NIF[+]/DM[-], P = 0.007; and 25.2% for NIF[-]/DM[+], P = 0.016). Logistic regression analysis showed that the NIF(+)/DM(+) subgroup had a significantly higher risk for having >10% of sites with AL > or =5 mm compared to the NIF(-)/DM(-) subgroup (odds ratio [OR] = 2.9; 95% confidence interval [CI]: 1.2 to 7.4; P = 0.022), the NIF(+)/DM(-) subgroup (OR = 3.1; 95% CI: 1.2 to 8.1; P = 0.020), and the NIF(-)/DM(+) subgroup (OR = 5.1; CI: 1.8 to 14.3; P = 0.002). NIF intake may increase the risk for periodontal destruction in patients with type 2 DM.

Easily obtainable clinical features increase the diagnostic accuracy for latent autoimmune diabetes in adults: An evidence-based report

Latent autoimmune diabetes in adults (LADA) represents a subgroup of diabetes mellitus. LADA is characterised by adult-onset diabetes and circulating autoimmune antibodies. LADA patients may need a different therapeutic approach than the usual type 2 diabetes mellitus. When LADA is inadequately diagnosed as type 2 diabetes mellitus, LADA patients will mistakenly be exposed to a high dose of oral glucose lowering drugs and their possible side effects. To assess which clinical features predict the presence or absence of LADA in patients older than 25 years presenting with hyperglycemia. A structured Medline and Embase search was conducted. Titles and abstracts were screened using predetermined selection criteria. Critical appraisal was based on standardized validity criteria for diagnostic research. One-hundred and eighty-four papers were retrieved of which after assessment of relevance and validity 2 studies remained for further analysis. One study reported a probability of LADA of 0.99 with one or two out of the following five clinical features: age at onset <50 years; acute symptoms; BMI<25 kg/m(2); a history of autoimmune disease; a family history positive for diabetes mellitus. The other study reported a probability of LADA of zero with none of the following clinical features and of 0.32 with one out of three: fasting blood glucose> or =15 mmol/l and/or HbA(1c)> or =10%; 10% reduction in body weight in the previous 3 months; BMI<25 kg/m(2). Further testing for LADA by measurement of autoimmune antibodies appears to be unnecessary in the absence of a specific set of clinical features. Before initiating therapy applying the above criteria may help to separate LADA from usual type 2 diabetes.

Effects of valsartan, mycophenolate mofetil and their combined application on TRAIL and nuclear factor-kappaB expression in the kidneys of diabetic rats

To evaluate the expression of TNF-related apoptosis inducing ligand (TRAIL) and nuclear factor (NF)-kappaB in the kidney tissues of diabetic rats and the effects of valsartan, mycophenolate mofetil (MMF), and their combined application on the renal TRAIL and NF-kappaB expression. Eighty uninephrectomized male Wistar rats were randomly divided into 2 groups: normal control (NC) group (n = 28), undergoing intraperitoneal injection of citric acid buffer, and diabetes mellitus (DM) group, undergoing intraperitoneal injection of streptozotocin (STZ) to establish DM models. The 52 DM rats were randomly divided into 7 equal subgroups: DM without treatment for 4 weeks (DM4), DM without treatment for 8 weeks (DM8) DM without treatment for 12 weeks (DM12) , and DM without treatment for 16 weeks (DM16), valsartan treatment (DM + V), MMF treatment (DM + M), and combined treatment (DM + V + M). The treatment subgroups were treated for 8 weeks immediately after the diabetic models ere established. Twenty-four hour urine was collected to measure the amount of protein 4, 8, 12, and 16 weeks after the induction of DM respectively. The rats were sacrificed. Blood samples were collected from the abdominal aorta to detect the blood urea nitrogen (BUN), serum creatinine (sCr), albumin, and glucose. The kidneys were taken out. Hypertrophy index (left kidney weight/body weight) was determined. Quantitative real time RT-PCR was performed to detect the expression of TRAIL and NF-kappaB mRNA. Immunohistochemistry was used to detect the protein expression of TRAIL and NF-kappaB. 1) The 24 h urine protein levels and hypertrophy indexes of all DM subgroups were significantly higher than those of the NC groups (all P <0.05). 24 h urine protein and hypertrophy index increased gradually and peaked in the l2th week; blood albumin gradually decreased since the 8th week(P <0.01), and BUN and sCr began to decrease only since the 16th week (both P <0.01). Compared with the DM 8 subgroup, the hypertrophy index and 24 h urine protein of the different treatment subgroups, especially the DM + V + M subgroup, were significantly lower (all P <0.05). 2) Quantitative real time RT-PCR showed that compared with the NC group, the TRAIL expression levels of the DM subgroups were significantly lower before the 12th week after induction of DM model (all P < 0.01), and then significantly higher in the 16th week (all P < 0.01). The TRAIL expression of the treatment groups, especially that of the DM + M subgroup, were significantly higher than that of the DM8 group (all P <0.05). Compared with the NC group, the NF-kappaB expression levels of the DM subgroups were significantly higher time-dependently (all P <0.01). Compared with the DM8 group, the NF-kappaB expression levels of the treatment subgroups, especially that of the DM + V + M subgroup were significantly lower (all P <0.05). 3) The expression of TRAIL was mainly located in the convoluted tubule of kidney, and no TRAIL protein expression was detected in the glomeruli or renal vasculature. The levels of NF-kappaB protein expression, shown in glomeruli and convoluted tubules, of all DM subgroups were all higher than that of the NC group. The NF-kappaB protein expression level of the DM + V + M subgroup was significantly lower. The number of NF-kappaB positive cells was significantly related to the mononuclear macrophage infiltration , kidney function, and structural lesion. An important monitoring factor in the autoimmune system, TRAIL closely participates in the pathogenesis of diabetic nephropathy, possibly controlled by NF-kappaB. In the early stage combination of valsartan and MMF may upregulate the expression of TRAIL, thus protecting the kidney function.

The islet autoantibody titres: their clinical relevance in latent autoimmune diabetes in adults (LADA) and the classification of diabetes mellitus

Latent autoimmune diabetes in the adult (LADA) is a slowly progressive form of autoimmune diabetes, characterized by diabetes-associated autoantibody positivity. A recent hypothesis proposes that LADA consists of a heterogeneous population, wherein several subgroups can be identified based on their autoimmune status. A systematic review of the literature was carried out to appraise whether the clinical characteristics of LADA patients correlate with the titre and numbers of diabetes-associated autoantibodies. We found that the simultaneous presence of multiple autoantibodies and/or a high-titre anti-glutamic acid decarboxylase (GAD)--compared with single and low-titre autoantibody--is associated with an early age of onset, low fasting C-peptide values as a marker of reduced pancreatic B-cell function, a high predictive value for future insulin requirement, the presence of other autoimmune disorders, a low prevalence of markers of the metabolic syndrome including high body mass index, hypertension and dyslipidaemia, and a high prevalence of the genotype known to increase the risk of Type 1 diabetes. We propose a more continuous classification of diabetes mellitus, based on the finding that the clinical characteristics gradually change from classic Type 1 diabetes to LADA and finally to Type 2 diabetes. Future studies should focus on determining optimal cut-off points of anti-GAD for differentiating clinically relevant diabetes mellitus subgroups.

Cardiovascular Risk Factors and Venous Thromboembolism

The concept that venous thromboembolism (VTE) and atherosclerosis are 2 completely distinct entities has recently been challenged because patients with VTE have more asymptomatic atherosclerosis and more cardiovascular events than control subjects. We performed a meta-analysis to assess the association between cardiovascular risk factors and VTE. Medline and EMBASE databases were searched to identify studies that evaluated the prevalence of major cardiovascular risk factors in VTE patients and control subjects. Studies were selected using a priori defined criteria, and each study was reviewed by 2 authors who abstracted data on study characteristics, study quality, and outcomes. Odds ratios or weighted means and 95% confidence intervals (CIs) were then calculated and pooled using a random-effects model. Statistical heterogeneity was evaluated through the use of chi2 and I2 statistics. Twenty-one case-control and cohort studies with a total of 63 552 patients met the inclusion criteria. Compared with control subjects, the risk of VTE was 2.33 for obesity (95% CI, 1.68 to 3.24), 1.51 for hypertension (95% CI, 1.23 to 1.85), 1.42 for diabetes mellitus (95% CI, 1.12 to 1.77), 1.18 for smoking (95% CI, 0.95 to 1.46), and 1.16 for hypercholesterolemia (95% CI, 0.67 to 2.02). Weighted mean high-density lipoprotein cholesterol levels were significantly lower in VTE patients, whereas no difference was observed for total and low-density lipoprotein cholesterol levels. Significant heterogeneity among studies was present in all subgroups except for the diabetes mellitus subgroup. Higher-quality studies were more homogeneous, and significant associations remained unchanged. Cardiovascular risk factors are associated with VTE. This association is clinically relevant with respect to individual screening, risk factor modification, and primary and secondary prevention of VTE. Prospective studies should further investigate the underlying mechanisms of this relationship.

Posterior capsule opacification after combined cataract surgery and vitrectomy

To compare the degree of posterior capsule opacification (PCO) after combined cataract surgery and vitrectomy and after cataract surgery alone in age-matched control patients and in patients with and without diabetes mellitus (DM). Sugita Eye Hospital, Nagoya, Japan. In a prospective study, patients were divided into 2 groups: those having cataract surgery alone (cataract group) and those having combined cataract and vitrectomy surgery (combined group). The 2 groups were further divided into patients without DM (non-DM subgroup) and patients with DM (DM subgroup). The PCO rates were determined 3, 6, and 12 months after surgery using the POCO system. In the cataract group, the non-DM subgroup and the DM subgroup each comprised 42 eyes of 42 patients. In the combined group, the non-DM subgroup comprised 26 eyes of 26 patients and the DM subgroup, 23 eyes of 23 patients. In the cataract group, the PCO rate in the DM subgroup was significantly higher than in the non-DM subgroup at every postoperative examination (P<.05). In the non-DM subgroup, the PCO rate was significantly higher at every postoperative examination in patients having combined surgery than in patients having cataract surgery alone (P<.05). In the combined group, the PCO rate did not differ significantly between the non-DM subgroup and the DM subgroup. Even patients without DM must be carefully monitored for PCO development after combined surgery.

Learning from large cardiovascular clinical trials: Classical cardiovascular risk factors

The number of cardiovascular risk factors significantly influences age adjusted cardiovascular death rates according to the data of the MRFIT Trial. Up to 60% of patients with Type 2 diabetes have concomitant hypertension. In the HOT (Hypertension Optimal Treatment) Study lowering of blood pressure was particularly beneficial in the subgroup of diabetes mellitus: there was a 51% reduction in major cardiovascular events in target group ≤80 mmHg, compared with target group ≤90 mmHg ( p = 0.005). Analysis of the diabetic patient group in the CAPPP (The CAPtopril Prevention Project) showed that captopril was superior for preventing cardiovascular events in hypertensive patients with diabetes. In the diabetic cohort of the LIFE Study losartan was more effective than athenolol in reducing cardiovascular morbidity and mortality as well as mortality from all causes in patients with hypertension, diabetes and left ventricular hypertrophy. In the Heart Protection Study 5963 people with diabetes were studied. For the first occurrence of any major vascular events among diabetic participants, there was a 22% reduction in the event rate simvastatin-allocated versus placebo allocated patients ( p < 0.0001). DAIS (Diabetes Atherosclerosis Intervention Study) data suggest that treatment with fenofibrate reduces the angiographic progression of coronary artery disease in patients with Type 2 diabetes. According to results on multifactorial intervention in patients with Type 2 diabetes (the STENO-2 study) the overall cardiovascular risk reduction was 53%. In conclusion, management of cardiovascular risk factors should be considered as the cornerstone of diabetes care.

Increased risk for cardiovascular outcomes and effect of cholesterol-lowering pravastatin therapy in patients with diabetes mellitus in the pravastatin anti-atherosclerosis trial in the elderly (PATE)

Background: The Pravastatin Anti-atherosclerosis Trial in the Elderly (PATE) was the first large-scale, prospective clinical trial to show that cholesterol-lowering therapy with pravastatin is effective in reducing the risk for cardiovascular events (CVEs) in elderly (aged ≥60 years) patients with hypercholesterolemia. PATE also included a subgroup of patients with diabetes mellitus (DM). Objective: The aim of this post hoc analysis was to assess the effects of lon-gtermpravastatin therapy on cardiovascular outcomes in the subgroup of patients with DM compared with a subgroup without it. Methods: PATE was conducted at 50 hospitals, universities, and clinics acrossJapan. Patients were randomly allocated to 1 of 2 treatment groups: low-dose pravastatin (5 mg PO QD; L group) or standard-lose pravastatin (in Japan, 10 mg PO QD; S group). Treatment was given for 3 to 5 years. Serum cholesterol levels were measured and the prevalence of CVEs was determined. The primary end point of the study was the S:L risk ratio for fatal or nonfatal CVEs. The secondary end point was the effect of diabetic patients' glycemic control on CVEs. Results: A total of 665 patients (527 women, 138 men; mean [SD] age, 72.8[5.7] years) were followed up for a mean of 3.9 years (range, 3–5 years). Among these, 199 patients had DM; 104 patients with DM were allocated to the L group and 95 to the S group. Four hundred sixty-six patients did not have DM (L group, 230 patients; S group, 236 patients). Overall, between 3 months and 3 years after the initiation of treatment, patients in the L group (mean dose, 4.5 mg/d) experienced reductions from baseline total cholesterol level of 11% to 13%. Those in the S group (mean dose, 8.3 mg/d) experienced reductions from baseline of 15% to 17%. Decreases in low-density lipoprotein cholesterol (LDL-C) levels were 17% to 20% and 23% to 26% in the L and S groups, respectively. Statistically similar reductions were noted between patients with DM and those without it in response to either dose. The DM subgroup experienced 32 CVEs (L group, 17; S group, 15) compared with 39 CVEs (L group, 25; S group, 14) in the subgroup without DM. The S:L CVE risk ratio (primary end point) was 0.94 (95% Cl, 0.46–1.92) in patients with DM and 0.54 (95% Cl, 0.28–1.05) in those without DM; the differences between the treatment groups were not statistically significant. The risk for CVEs in patients with DM whose glycosylated hemoglobin concentrations were <8.0% and ≥8.0% were, respectively, 1.87-fold (95% Cl, 1.09–3.20; P = 0.02) and 3.79-fold (95% Cl, 1.92–7.48; P < 0.01) higher than that in patients without DM. Conclusions: In this post hoc analysis of the effects of long-term cholesterol-loweringtherapy (low- and standard-dose pravastatin) on cardiovascular outcomes in elderly patients with DM, dose had no effect on the risk for CVEs in these patients as it did in those without DM. Poorer glycemic control in patients with DM was related to a higher risk for CVEs. The lack of pravastatin efficacy found in the subgroup with DM may have been attributable to the small differences in LDL-C levels found between the 2 treatment groups and/or the small sample size of the study.

Effects of ezetimibe added to on-going statin therapy on the lipid profile of hypercholesterolemic patients with diabetes mellitus or metabolic syndrome

SUMMARYObjective: To conduct a post-hoc assessment of the lipid-modifying effects of adding the cholesterol absorption inhibitor, ezetimibe, to on-going statin therapy in patients with diabetes mellitus (DM) or metabolic syndrome (MetS).Research design and methods: This was a post-hoc analysis of data from a randomized, double-blind, placebo-controlled trial designed to evaluate the low-density lipoprotein cholesterol (LDL-C)-lowering efficacy and safety of adding ezetimibe 10 mg/day versus placebo to ongoing, open-label statin treatment for 8 weeks in hypercholesterolemic patients. Qualifying LDL-C levels and target LDL-C goals were based on National Cholesterol Education Program risk categories. The DM subgroup were patients who entered the study with a prior diagnosis of DM. Patients were classified as having MetS if they met 3 or more of the following criteria at baseline: triglycerides (TG) ≥ 150 mg/dL (1.69 mmol/L); high-density lipoprotein cholesterol (HDL-C) < 40 mg/dL (1.04 mmol/L) for men or < 50 mg/dL (1.29 mmol/L) for women; fasting serum glucose (FSG) ≥ 110 mg/dL (≥ 6.1 mmol/L); a diagnosis of hypertension or taking hypertension medication or blood pressure ≥ 130/ ≥ 85 mmHg; waist circumference > 88 cm (women) or > 102 cm (men). DM patients were excluded from the MetS subgroup analysis.Main outcome measures: The objectives were to assess the effects of treatment on plasma concentrations of LDL-C and other lipid variables, and on the percentage of patients achieving LDL-C target levels at the end of the study.Results: Of 769 patients enrolled in the original study, there were 191 (24.8%) with DM and 195 (25.4%) with MetS. Regardless of subgroup, ezetimibe + statin was significantly more effective than statin alone at lowering plasma levels of LDL-C, non-HDL-C, total cholesterol, apolipoprotein B, and triglycerides (between-group p < 0.001 for all). For all lipid parameters, the relative treatment effects were generally consistent regardless of DM or MetS status. Significantly more ezetimibe than placebo patients in all subgroups achieved prespecified LDL-C goals ( p < 0.001 for all), and although more patients in the DM and MetS groups, respectively, achieved the goal compared with their non-DM and non-MetS counterparts [83.6% (DM) versus 67.2 (non-DM) and 71.8% (MetS) versus 65.6% (non-MetS)], these differences were not significant after adjusting for differences in baseline LDL-C levels. Ezetimibe was well-tolerated and had a favorable safety profile in all subgroups.Conclusions: The co-administration of ezetimibe with statins, a therapeutic regimen that inhibits both the absorption and synthesis of cholesterol, offers a well-tolerated and efficacious treatment to lower LDL-C in patients with DM and MetS.

Plasminogen Activator Inhibitor Type-1 (PAI-1) Levels Are Decreased in NIDDM Patients treated with Insulin

We examined 25 non-insulin-dependent diabetes mellitus (NIDDM) patients treated with sulfonylurea (SU) regi mens, 14 NIDDM patients with 8-12 weeks long-acting insulin (INS) treatment and 15 age-matched normoinsulinemic healthy controls. Plasminogen activator inhibitor-1 (PAI-1) levels were significantly increased in NIDDM patients treated by SU agents (median 58.9, range 14-217 ng/ml) compared to patients with insulin therapy (median 20.7, 4-53 ng/ml) and normal controls (median 10.8, 4-52 ng/ml) (p &lt; 0.001). Non-insulin- dependent diabetes mellitus subgroups were not different in other hemostatic (von Willebrand factor, thrombomodulin, tis sue factor pathway inhibitor, platelet factor-4 levels) and meta bolic (C-peptide, triglycerides) parameters and PAI-1 levels did not correlate with these hemostatic and metabolic parameters. This finding suggests that insulin application itself may cause decreased PAI-1 levels, probably by influence on intracellular calcium. This hypothesis requires further research. Key Words: PAI-1—Insulin treatment—Non—insulin—dependent diabetes mellitus.

Cephalic phase of pancreatic polypeptide release: a valid test of autonomic neuropathy in diabetics?

We investigated pancreatic polypeptide (PP) release by chew and spit sham feeding as a test of autonomic function in 33 patients with diabetes mellitus (DM) and 24 age-matched healthy controls. Plasma samples were taken at nine 5-min time intervals, and PP plasma levels were determined by radioimmunoassay. Autonomic neuropathy (AN) was diagnosed and staged according to four standardized tests of cardiovascular autonomic function. The integrated PP response during sham feeding was decreased in DM patients (1067 ± 397 vs. 2670 ± 394 pg/ml/30 min; P < 0.05). The maximum increase of PP plasma levels was significantly different between the DM subgroups with AN (36 ± 19 pg/ml; n = 13) and without AN (132 ± 36 pg/ml; n = 20) but varied widely in healthy controls (219 ± 29 pg/ml; range 20–460 pg/ml). A cutoff of maximum PP increase < 20 pg/ml (specificity 100%) resulted in only 46% sensitivity, while a cutoff < 160 pg/ml (sensitivity 100%) yielded 38% specificity for diagnosis of AN. The diagnostic value of the PP test for identifying individual patients against the variable reference range is therefore limited. Maximum PP increase < 20 pg/ml indicates AN, while maximum PP increase > 160 pg/ml excludes AN in diabetic patients.