Low 25-Hydroxyvitamin D and Risk of Type 2 Diabetes: A Prospective Cohort Study and Metaanalysis Shoaib Afzal1, Stig E.

Bojesen, and Brge G. Nordestgaard.

ABSTRACT: BACKGROUND: Vitamin D deficiency has been implicated in decreased insulin secretion and increased insulin resistance, hallmarks of type 2 diabetes mellitus. We tested the hypothesis that low plasma 25-hydroxyvitamin D [25(OH)D] is associated with increased risk of type 2 diabetes in the general population. METHODS: We measured 25(OH)D in 9841 participants from the general population, of whom 810 developed type 2 diabetes during 29 years of follow-up. Analyses were adjusted for sex, age, smoking status, body mass index, income, physical activity, HDL cholesterol, and calendar month of blood draw. RESULTS: Lower 25(OH)D concentrations, by clinical categories or seasonally adjusted quartiles, were associated with higher cumulative incidence of type 2 diabetes (trend, P = 2107 and P = 41010). Multivariable adjusted hazard ratios of type 2 diabetes were 1.22 (95% CI 0.851.74) for 25(OH)D <5 vs 20 g/L and 1.35 (1.09 1.66) for lowest vs highest quartile. Also, the multivariable adjusted hazard ratio of type 2 diabetes for a 50% lower concentration of 25(OH)D was 1.12 (1.03 1.21); the corresponding hazard ratio for those 58 years old was 1.26 (1.151.41). Finally, in a metaanalysis of 16 studies, the odds ratio for type 2 diabetes was 1.50 (1.33 1.70) for the bottom vs top quartile of 25(OH)D. CONCLUSIONS: We observed an association of low plasma 25(OH)D with increased risk of type 2 diabetes. This finding was substantiated in a metaanalysis.

Received for publication July 12, 2012. Accepted for publication October 31, 2012 2012 The American Association for Clinical Chemistry

Prognostic Utility of Secretory Phospholipase A2 in Patients with Stable Coronary Artery Disease

Michelle L. O'Donoghue, Ziad Mallat, David A. Morrow, Joelle Benessiano, Sarah Sloan, Torbjrn Omland, Scott D. Solomon, Eugene Braunwald, Alain Tedgui, and Marc S. Sabatine.

ABSTRACT:

BACKGROUND: Secretory phospholipase A2 (sPLA2) may contribute to atherogenesis. To date, few prospective studies have examined the utility of sPLA 2 for risk stratification in coronary artery disease (CAD). The phospholipase A2 enzymes are members of a large family that hydrolyze the sn-2 ester of glycerophospholipids to release free fatty acids and lysophospholipids. The secretory phospholipase A2 (sPLA2)7 family consists of 10 isoenzymes that are involved in a variety of biological processes that include hydrolysis of phospholipids, release of arachidonic acid, and eicosanoid generation (1). sPLA2 enzymes are distinct from lipoprotein-associated phospholipase A2 (Lp-PLA2), another biomarker that has been extensively studied for risk stratification and is now being evaluated as a potential therapeutic target (2). Growing evidence suggests that sPLA2 may play a causal role in the development of atherosclerosis. sPLA2-X has been shown to promote macrophage foam cell formation in murine models (3), and upregulated sPLA2-IIA or sPLA2-V expression has been shown to increase atherosclerotic lesion size in transgenic mice (4, 5). Additionally, genetic deletion of sPLA2-V or direct inhibition of sPLA2 activity has been shown to reduce atherosclerotic lesion progression in animals (5,,7). To date, a small number of studies have evaluated the utility of sPLA 2 for risk stratification in primary prevention populations and in patients with acute coronary syndrome (ACS) (1). However, the prognostic utility of sPLA2 activity has not been well established in a large population of patients with stable coronary artery disease (CAD). Determination of this association is particularly relevant given the interest in sPLA2 as a possible therapeutic target for helping to delay the progression of atherosclerosis (8). Furthermore, the relative prognostic utility of sPLA2 compared with other wellestablished markers of risk, including those measured using new high-sensitivity assays, remains unknown. We hypothesized that sPLA2 activity would provide incremental information for risk stratification beyond established clinical risk factors and biomarkers in a large cohort of subjects with stable CAD.

METHODS: We measured plasma sPLA2 activity at baseline in 3708 subjects in the PEACE randomized trial of trandolapril vs placebo in stable CAD. Median follow-up was 4.8 years. We used Cox regression to adjust for demographics, clinical risk factors, apolipoprotein B, apolipoprotein A1, and medications.

RESULTS: After multivariable adjustment, sPLA2 was associated with an increased risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio Q4:Q1 1.55, 95% CI 1.132.14) and cardiovascular death or heart failure (1.91, 1.203.03). In further multivariable assessment, increased activity levels of sPLA2 were associated with the risk of cardiovascular death, myocardial infarction, or stroke (adjusted hazard ratio 1.47, 95% CI 1.062.04), independent of lipoprotein-associated phospholipase A2 mass and C-reactive protein, and modestly improved the area under the curve (AUC) beyond established clinical risk factors (AUC 0.6680.675, P = 0.01). sPLA2, N-terminal pro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T all were independently associated with cardiovascular death or heart failure, and each improved risk discrimination (P = 0.02, P < 0.001, P < 0.001, respectively). CONCLUSIONS: sPLA2 activity provides independent prognostic information beyond established risk markers in patients with stable CAD. These data are encouraging for studies designed to evaluate the role of sPLA2 as a therapeutic target. Received for publication March 31, 2011. Accepted for publication June 29, 2011. 2011 The American Association for Clinical Chemistry

Determination of Antimicrobial Resistance Pattern and Production of ExtendedSpectrum -Lactamases amongst Esche-richia coli and Klebsiella pneumoniae from Clinical Isolates Anand Kalaskar, Kandi Vramana ABSTRACT: Background: The prevalence of antibiotic resistance among extended-spectrum lactamase (ESBL) producing Escherichia coliand Klebsiella pneumoniae has been increased markedly in recent years. The present study was done to know the prevalence of ESBL production among isolates of E. coli and K. pneumoniae and to study the susceptibility pattern of isolates against different antibiotics. Methods: Extended-spectrum -lactamase producing E. coli and K. pneumoniae were isolated from various samples obtained from outdoor and indoor patients of the Prathima Institute of medical sciences, Andhra Pradesh, India. They were tested for ESBL production by double disc synergy test and resistance to various antibiotics like fluoroquinolones, cephalosporins, aminoglycosides and -lactamase inhibitor combinations and susceptibility to carbapenems were determined by Kirby-Bauer disc diffusion method. Results: A total of 94 ESBL producing isolates were obtained. Of them 60 were E. coli and 34 K. pneumoniae. They were obtained from urine, sputum, pus, wound swabs blood & tracheal aspirates. Urine (38.29%) was the main source of ESBL-producing isolates from all patients, followed by sputum (34.04%). About 37.23% of these isolates were collected from medical wards and 27.65% were collected from outdoor. All isolates were susceptible to imipenem. The resistance to cephalosporins (1-4 generations) was almost 100%. Resistance to Aztreonam, Ampicillin and Co-amoxyclav was also 100%. A high degree of resistance was observed to other antibiotics. Conclusion: The highest prevalence of resistance to ESBL in E. coli and K. pneumonia is associated with a multitude of infections in hospitalized patients with a significant longer duration of hospital stay, increased morbidity and greater hospital charges. Advanced drug resistance surveillance and molecular characteristics of ESBL isolates is necessary to guide the proper and judicious antibiotic use.