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Pomona, CA, United States

Phung O.J.,Western University of Health Sciences | Phung O.J.,Western Diabetes Institute | Schwartzman E.,Western University of Health Sciences | Schwartzman E.,Western Diabetes Institute | And 3 more authors.
Diabetic Medicine

Aims: Sulphonylurea use has been linked with increased cardiovascular disease risk; however, previous studies have been inconsistent. Type 2 diabetes independently increases risk for cardiovascular disease, so understanding the link between longer-term use of anti-diabetic medications and cardiovascular disease has important clinical implications. Methods: Literature search in MEDLINE and CENTRAL was conducted throughout December 2011 for clinical and observational studies that reported the association between sulphonylurea and cardiovascular disease events. Ratios (relative risk, odds ratios or hazard ratios) adjusted for potential confounders (concomitant medications, baseline cardiovascular risk, diabetes severity) were pooled using a random-effects model to yield relative risks and associated 95% confidence intervals. Results: This meta-analysis included 33 studies (n = 1,325,446 patients), followed for a range of 0.46-10.4 years. In all studies, compared with other oral diabetes drugs, sulphonylurea use was associated with a significantly increased risk of cardiovascular death (relative risk 1.27, 95% confidence interval 1.18-1.34, n = 27 comparisons) and composite cardiovascular event (including myocardial infarction, stroke, cardiovascular-related hospitalization or cardiovascular death) (relative risk 1.10, 95% confidence interval 1.04-1.16, n = 43 comparisons). In studies comparing sulphonylurea vs. metformin, these relative risks were 1.26 (95% confidence interval 1.17-1.35, n = 17 comparisons) and 1.18 (95%confidence interval 1.13-1.24, n = 16 comparisons), respectively. Conclusions: Results suggest that sulphonylurea use may elevate the risk of cardiovascular disease among patients with diabetes. This meta-analysis expands the pool of studies evaluating cardiovascular mortality compared with prior observations while using adjusted estimates, and assessing an additional outcome of a composite cardiovascular event. This finding warrants consideration in clinical practice when other treatment options may be available. © 2013 Diabetes UK. Source

Allen R.W.,Western University of Health Sciences | Schwartzman E.,Western University of Health Sciences | Schwartzman E.,Western Diabetes Institute | Baker W.L.,University of Connecticut | And 3 more authors.
Annals of Family Medicine

Purpose Cinnamon has been studied in randomized controlled trials (RCTs) for its glycemic-lowering effects, but studies have been small and show conflicting results. A prior meta-analysis did not show significant results, but several RCTs have been published since then. We conducted an updated systematic review and meta-analysis of RCTs evaluating cinnamon's effect on glycemia and lipid levels. Methods: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched through February 2012. Included RCTs evaluated cinnamon compared with control in patients with type 2 diabetes and reported at least one of the following: glycated hemoglobin (A1c), fasting plasma glucose, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), or triglycerides. Weighted mean differences (with 95% confidence intervals) for endpoints were calculated using random-effects models. Results: In a meta-analysis of 10 RCTs (n = 543 patients), cinnamon doses of 120 mg/d to 6 g/d for 4 to 18 weeks reduced levels of fasting plasma glucose (-24.59 mg/dL; 95% CI, -40.52 to -8.67 mg/dL), total cholesterol (-15.60 mg/ dL; 95% CI, -29.76 to -1.44 mg/dL), LDL-C (-9.42 mg/dL; 95% CI, -17.21 to -1.63 mg/dL), and triglycerides (-29.59 mg/dL; 95% CI, -48.27 to -10.91 mg/ dL). Cinnamon also increased levels of HDL-C (1.66 mg/dL; 95% CI, 1.09 to 2.24 mg/dL). No significant effect on hemoglobin A1c levels (-0.16%; 95%, CI -0.39% to 0.02%) was seen. High degrees of heterogeneity were present for all analyses except HDL-C (I2 ranging from 66.5% to 94.72%). Conclusions: The consumption of cinnamon is associated with a statistically significant decrease in levels of fasting plasma glucose, total cholesterol, LDL-C, and triglyceride levels, and an increase in HDL-C levels; however, no significant effect on hemoglobin A1c was found. The high degree of heterogeneity may limit the ability to apply these results to patient care, because the preferred dose and duration of therapy are unclear. Source

Lagman M.,Western University of Health Sciences | Ly J.,Western University of Health Sciences | Saing T.,Western University of Health Sciences | Singh M.K.,Western University of Health Sciences | And 6 more authors.

Tuberculosis (TB) remains an eminent global burden with one third of the world's population latently infected with Mycobacterium tuberculosis (M. tb). Individuals with compromised immune systems are especially vulnerable to M. tb infection. In fact, individuals with Type 2 Diabetes Mellitus (T2DM) are two to three times more susceptible to TB than those without T2DM. In this study, we report that individuals with T2DM have lower levels of glutathione (GSH) due to compromised levels of GSH synthesis and metabolism enzymes. Transforming growth factor beta (TGF-β), a cytokine that is known to decrease the expression of the catalytic subunit of glutamine-cysteine ligase (GCLC) was found in increased levels in the plasma samples from individuals with T2DM, explaining the possible underlying mechanism that is responsible for decreased levels of GSH in individuals with T2DM. Moreover, increased levels of pro-inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-17 (IL-17) were observed in plasma samples isolated from individuals with T2DM. Increased levels of IL-6 and IL-17 was accompanied by enhanced production of free radicals further indicating an alternative mechanism for the decreased levels of GSH in individuals with T2DM. Augmenting the levels of GSH in macrophages isolated from individuals with T2DM resulted in improved control of M. tb infection. Furthermore, cytokines that are responsible for controlling M. tb infection at the cellular and granuloma level such as tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), interleukin-2 (IL-2), interferon-gamma (IFN-γ), and interleukin-12 (IL-12), were found to be compromised in plasma samples isolated from individuals with T2DM. On the other hand, interleukin-10 (IL-10), an immunosuppressive cytokine was increased in plasma samples isolated from individuals with T2DM. Overall, these findings suggest that lower levels of GSH in individuals with T2DM lead to their increased susceptibility to M. tb infection. © 2015 Lagman et al. Source

Ly J.,Western University of Health Sciences | Lagman M.,Western University of Health Sciences | Saing T.,Western University of Health Sciences | Singh M.K.,Western University of Health Sciences | And 8 more authors.
Journal of Interferon and Cytokine Research

Cytokines are signaling biomolecules that serve as key regulators of our immune system. CD4+ T-cells can be grouped into 2 major categories based on their cytokine profile: T-helper 1 (TH1) subset and T-helper 2 (TH2) subset. Protective immunity against HIV infection requires TH1-directed CD4 T-cell responses, mediated by cytokines, such as interleukin-1β (IL-1β), IL-12, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). Cytokines released by the TH1 subset of CD4 T-cells are considered important for mediating effective immune responses against intracellular pathogens such as Mycobacterium tuberculosis (M. tb). Oxidative stress and redox imbalance that occur during HIV infection often lead to inappropriate immune responses. Glutathione (GSH) is an antioxidant present in nearly all cells and is recognized for its function in maintaining redox homeostasis. Our laboratory previously reported that individuals with HIV infection have lower levels of GSH. In this study, we report a link between lower levels of GSH and dysregulation of TH1- and TH2-associated cytokines in the plasma samples of HIV-positive subjects. Furthermore, we demonstrate that supplementing individuals with HIV infection for 13 weeks with liposomal GSH (lGSH) resulted in a significant increase in the levels of TH1 cytokines, IL-1β, IL-12, IFN-γ, and TNF-α. lGSH supplementation in individuals with HIV infection also resulted in a substantial decrease in the levels of free radicals and immunosuppressive cytokines, IL-10 and TGF-β, relative to those in a placebo-controlled cohort. Finally, we determined the effects of lGSH supplementation in improving the functions of immune cells to control M. tb infection by conducting in vitro assays using peripheral blood mononuclear cells collected from HIV-positive individuals at post-GSH supplementation. Our studies establish a correlation between low levels of GSH and increased susceptibility to M. tb infection through TH2-directed response, which may be relieved with lGSH supplementation enhancing the TH1 response. © Copyright 2015, Mary Ann Liebert, Inc. Source

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