Impact of mulberry leaf extract on type 2 diabetes (Mul-DM): A randomized, placebo-controlled pilot study.

AIMS: Mulberry leaves have been used anecdotally in Asia to treat many disease states, including glucose abnormalities. Animal and human studies illustrate potential benefit of mulberry leaf extract (MLE) in type 2 diabetes mellitus (DM2). The purpose of this study is to evaluate the glycemic and safety effects of MLE in patients with DM2. MATERIALS & METHODS: This randomized, double-blind, placebo-controlled pilot study evaluated MLE (1000mg standardized) versus matching placebo given three times daily with meals. Patients (n=24) were included if they had DM2 on single or combination oral therapy with a stable hemoglobin A1C (A1C). A 2-week placebo run-in (baseline) was followed by initiation of randomized medication for 3 months. Primary endpoints were change in A1C and self-monitoring blood glucoses (SMBG). Safety was also evaluated. RESULTS: Of 24 patients enrolled, 17 patients completed the study. Post-prandial SMBG was significantly decreased at 3 months in the MLE group versus baseline (16.1%; p<0.05). This improvement in post-prandial SMBG persisted when compared to placebo (18.2%; p<0.05). A1C decreased from 7.30% at baseline to 6.94% in the MLE group but did not reach statistical significance (p=0.079). There was no difference in A1C between MLE and placebo. A significant 15% increase occurred in serum creatinine when the MLE group was compared to baseline or placebo (p<0.05 for both). There was no significant effect on weight, fasting SMBG, blood pressure, hypoglycemia, or other safety evaluation markers. CONCLUSIONS: These results suggest that mulberry leaf extract may be a useful complementary mealtime glucose option for patients with DM2. ClinicalTrials.gov Identifier NCT00795704.

Impact of vitamin D status on statin-induced myopathy.

INTRODUCTION: There is a multitude of evidence supporting the benefit of statin use in cardiovascular disease; however, statin-induced myopathy is a major reason for statin discontinuation and non-adherence. Vitamin D deficiency has been independently associated with muscle weakness and severe myopathy, and may be a confounder for statin-induced myopathies. Since there is no consensus on a treatment course of action for statin-induced myopathy, investigation into potential confounders to elucidate the dynamics of statin-induced myopathy is warranted. METHODS: A retrospective chart review was conducted on 105 patients in a cardiometabolic clinic with a vitamin D drawn from December 2006 to April 2008. Patients exposed to statins were divided into two groups: (1) patients with low vitamin D (<32 ng/mL) [n = 52] and (2) patients with a sufficient vitamin D level (⩾32 ng/mL) [n = 32]. Data were compared via t-tests or Fisher's Exact, as appropriate. RESULTS: There were 41 statin-specific myopathies amongst the 24 statin-intolerant patients. Low vitamin D was significantly associated with statin-induced myopathy (p = 0.048). Following prescription vitamin D supplementation, statin tolerance rates were significantly higher in patients with a baseline vitamin D ⩽20 ng/mL than those with a baseline vitamin D >20 ng/mL (90% vs 33%; p = 0.036). CONCLUSION: Vitamin D status may be considered a modifiable risk factor for muscle-related adverse effects of statins, and supplementation of vitamin D (particularly when ⩽20 ng/mL) may improve statin tolerance.

Pterostilbene on metabolic parameters: a randomized, double-blind, and placebo-controlled trial.

Introduction. The purpose of this trial was to evaluate the effect of pterostilbene on metabolic parameters. Methods. A prospective, randomized, double-blind, and placebo-controlled study that enrolled 80 patients with a total cholesterol ≥200 mg/dL and/or LDL ≥ 100 mg/dL. Subjects were divided into four groups: (1) pterostilbene 125 mg twice daily; (2) pterostilbene 50 mg twice daily; (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily; (4) matching placebo twice daily for 6-8 weeks. Endpoints included lipids, blood pressure, and weight. Linear mixed models were used to examine and compare changes in parameters over time. Models were adjusted for age, gender, and race. Results. LDL increased with pterostilbene monotherapy (17.1 mg/dL; P = 0.001) which was not seen with GE combination (P = 0.47). Presence of a baseline cholesterol medication appeared to attenuate LDL effects. Both systolic (-7.8 mmHg; P < 0.01) and diastolic blood pressure (-7.3 mmHg; P < 0.001) were reduced with high dose pterostilbene. Patients not on cholesterol medication (n = 51) exhibited minor weight loss with pterostilbene (-0.62 kg/m(2); P = 0.012). Conclusion. Pterostilbene increases LDL and reduces blood pressure in adults. This trial is registered with Clinicaltrials.gov NCT01267227.

Analysis of safety from a human clinical trial with pterostilbene.

Objectives. The purpose of this trial was to evaluate the safety of long-term pterostilbene administration in humans. Methodology. The trial was a prospective, randomized, double-blind placebo-controlled intervention trial enrolling patients with hypercholesterolemia (defined as a baseline total cholesterol ≥200 mg/dL and/or baseline low-density lipoprotein cholesterol ≥100 mg/dL). Eighty subjects were divided equally into one of four groups: (1) pterostilbene 125 mg twice daily, (2) pterostilbene 50 mg twice daily, (3) pterostilbene 50 mg + grape extract (GE) 100 mg twice daily, and (4) matching placebo twice daily for 6-8 weeks. Safety markers included biochemical and subjective measures. Linear mixed models were used to estimate primary safety measure treatment effects. Results. The majority of patients completed the trial (91.3%). The average age was 54 years. The majority of patients were females (71%) and Caucasians (70%). There were no adverse drug reactions (ADRs) on hepatic, renal, or glucose markers based on biochemical analysis. There were no statistically significant self-reported or major ADRs. Conclusion. Pterostilbene is generally safe for use in humans up to 250 mg/day.

Implementation of a pharmacist-led, multidisciplinary diabetes management team.

PURPOSE: The development, implementation, and evaluation of a pharmacist-led, multidisciplinary diabetes management team (DMT) at a 564-bed medical center in Jackson, Mississippi, are described. SUMMARY: The overwhelming prevalence of diabetes in Mississippi has a major impact on the state's health care system. Mississippi Baptist Health Systems (MBHS) developed a consultation-driven DMT in November 2008. The DMT embraced the multidisciplinary approach by uniting pharmacists, physicians, and other health care providers to optimize the care of patients with diabetes. The DMT initially focused on patients undergoing coronary artery bypass graft (CABG) surgery but also manages patients with a variety of causes of hyperglycemia. To evaluate the success of the DMT, postoperative serum blood glucose levels were collected from January 2008 through December 2010 for patients undergoing CABG at MBHS before and after the implementation of the DMT. The primary outcome was the number of patients with serum blood glucose concentrations exceeding 200 mg/dL. Secondary outcomes measured included the rates of sternal surgical-site infection and the frequency of hypoglycemia. CONCLUSION: Implementation of a pharmacist-led, multidisciplinary DMT helped to achieve intensive glycemic control in CABG patients and decrease the rate of infection.

Systematic review and meta-analysis of immunosuppressant therapy clinical trials in membranous lupus nephritis.

PURPOSE: We performed a systematic review and meta-analysis to compare response rates (complete remission plus partial remission) for nonsteroid immunosuppressant therapy to steroid-only immunosuppressant therapy in patients with membranous lupus nephritis. METHODS: A literature review was conducted from June 25, 2010 by querying PubMed, MEDLINE, and EMBASE databases. Inclusion criteria were trials containing remission data on patients with confirmed pure class V (Va and Vb) membranous lupus nephritis. The primary analysis evaluates response rates for regimens that contain at least one nonsteroid immunosuppressant therapy and steroid-only immunosuppressant therapy. A proportion meta-analysis using a DerSimonian-Laird random-effects model was performed. Data are reported as pooled proportions in percentages with 95% confidence intervals. Significant heterogeneity and/or bias were compensated for by trial exclusion. RESULTS: Twenty-four studies met inclusion criteria for meta-analysis, which yielded 34 groups of patients' data. Upon meta-analysis, the response rate for nonsteroid immunosuppressant therapy is higher than for steroids alone (81% [74%-87%] vs 60% [39%-79%]), even when compensating for significant heterogeneity and bias (76% [71%-81%] versus 60% [39%-79%]). CONCLUSION: Nonsteroid immunosuppressant therapies in combination with steroids seem to be more effective than steroids alone for inducing partial or complete remission in patients with membranous lupus nephritis who have nephrotic proteinuria at baseline. This trial was not able to analyze adverse events, flares, relapses, or patient survival because of underreporting.

Impact of sitagliptin on markers of beta-cell function: a meta-analysis.

BACKGROUND: Progressive beta-cell dysfunction and beta-cell failure are fundamental pathogenic consequences of type 2 diabetes. Dipeptidyl peptidase-IV inhibitors may exhibit improvement on preclinical measures of both beta-cell function, homeostasis model assessment of beta-cell (HOMA-beta) index, and beta-cell dysfunction, proinsulin/insulin ratio (PI/IR), correlating to beta-cell survival. RESEARCH DESIGN AND METHODS: A systematic literature search through July 2008 was conducted to extract a consensus of randomized, controlled trials of sitagliptin therapy on measures of beta-cell function. A random-effects model meta-analysis evaluated effects on HOMA-beta and PI/IR versus placebo. Several subgroup analyses, including active control, were conducted. Studies were included if they met the following criteria: (1) randomized trials on sitagliptin; (2) placebo or active control; and (3) data reported on HOMA-beta or PI/IR. RESULTS: A total of 11 trials (n = 3039) reported effects on HOMA-beta and 8 trials (n = 2325) on PI/IR versus placebo. Four trials (n = 1425) were included in the active control subgroup analysis. Sitagliptin significantly improved HOMA-beta index by 12.03% [95% confidence interval (CI), 9.45-14.60] versus placebo. Sitagliptin also significantly decreased PI/IR -0.06 (95% CI, -0.08 to -0.04). Sitagliptin was inferior to active control for HOMA-beta index [5.64% (95% CI, 0.38-10.90)], but not different in terms of PI/IR [0.01 (95% CI, -0.04 to 0.06)]. CONCLUSIONS: Despite significant improvement in HOMA-beta index and PI/IR from placebo, there does not seem to be a benefit of dipeptidyl peptidase-IV inhibitors over other agents with respect to beta-cell function/activity. Long-term prevention of beta-cell dysfunction cannot be ruled out.