Jennifer R McDuffie

The effect of a low-carbohydrate, ketogenic diet versus a low-glycemic index diet on glycemic control in type 2 diabetes mellitus.

ObjectiveDietary carbohydrate is the major determinant of postprandial glucose levels, and several clinical studies have shown that low-carbohydrate diets improve glycemic control. In this study, we tested the hypothesis that a diet lower in carbohydrate would lead to greater improvement in glycemic control over a 24-week period in patients with obesity and type 2 diabetes mellitus.Research design and methodsEighty-four community volunteers with obesity and type 2 diabetes were randomized to either a low-carbohydrate, ketogenic diet (<20 g of carbohydrate daily; LCKD) or a low-glycemic, reduced-calorie diet (500 kcal/day deficit from weight maintenance diet; LGID). Both groups received group meetings, nutritional supplementation, and an exercise recommendation. The main outcome was glycemic control, measured by hemoglobin A1c.ResultsForty-nine (58.3%) participants completed the study. Both interventions led to improvements in hemoglobin A1c, fasting glucose, fasting insulin, and weight loss. The LCKD group had greater improvements in hemoglobin A1c (-1.5% vs. -0.5%, p = 0.03), body weight (-11.1 kg vs. -6.9 kg, p = 0.008), and high density lipoprotein cholesterol (+5.6 mg/dL vs. 0 mg/dL, p < 0.001) compared to the LGID group. Diabetes medications were reduced or eliminated in 95.2% of LCKD vs. 62% of LGID participants (p < 0.01).ConclusionDietary modification led to improvements in glycemic control and medication reduction/elimination in motivated volunteers with type 2 diabetes. The diet lower in carbohydrate led to greater improvements in glycemic control, and more frequent medication reduction/elimination than the low glycemic index diet. Lifestyle modification using low carbohydrate interventions is effective for improving and reversing type 2 diabetes.

Comparative Effectiveness of Warfarin and New Oral Anticoagulants for the Management of Atrial Fibrillation and Venous Thromboembolism: A Systematic Review

BACKGROUND New oral anticoagulants (NOACs), including direct thrombin inhibitors (DTIs) and factor Xa (FXa) inhibitors, are emerging alternatives for prophylaxis and treatment of atrial fibrillation (AF) and venous thromboembolism (VTE). PURPOSE To compare the benefits and harms of NOACs versus warfarin for AF and VTE. DATA SOURCES MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews from January 2001 through July 2012; U.S. Food and Drug Administration (FDA) database for adverse event reports. STUDY SELECTION English-language, randomized, controlled trials (RCTs) comparing NOACs with warfarin for management of AF or VTE and observational studies and FDA reports on adverse effects. DATA EXTRACTION Two independent reviewers abstracted data and rated study quality and strength of evidence. DATA SYNTHESIS Six good-quality RCTs compared NOACs (2 DTI studies, 4 FXa inhibitor studies) with warfarin. In AF, NOACs decreased all-cause mortality (risk ratio [RR], 0.88 [95% CI, 0.82 to 0.96]); in VTE, NOACs did not differ for mortality or VTE outcomes. Across indications, adverse effects of NOACs compared with warfarin were fatal bleeding (RR, 0.60 [CI, 0.46 to 0.77]), major bleeding (RR, 0.80 [CI, 0.63 to 1.01]), gastrointestinal bleeding (RR, 1.30 [CI, 0.97 to 1.73]), and discontinuation due to adverse events (RR, 1.23 [CI, 1.05 to 1.44]). Subgroup analyses suggest a higher risk for myocardial infarction with DTIs than with FXa inhibitors. Bleeding risk for NOACs may be increased in persons older than 75 years or those receiving warfarin who have good control. LIMITATION There were no head-to-head comparisons of NOACs and limited data on harms. CONCLUSION New oral anticoagulants are a viable option for patients receiving long-term anticoagulation. Treatment benefits compared with warfarin are small and vary depending on the control achieved by warfarin treatment. PRIMARY FUNDING SOURCE Department of Veterans Affairs.

Effects of Metformin on Body Weight and Body Composition in Obese Insulin-Resistant Children A Randomized Clinical Trial

OBJECTIVE Metformin can decrease adiposity and ameliorate obesity-related comorbid conditions, including abnormalities in glucose homeostasis in adolescents, but there are few data evaluating the efficacy of metformin among younger children. Our objective was to determine whether metformin treatment causes weight loss and improves obesity-related comorbidities in obese children, who are insulin-resistant. RESEARCH DESIGN AND METHODS This study was a randomized double-blind placebo-controlled trial consisting of 100 severely obese (mean BMI 34.6 ± 6.6 kg/m2) insulin-resistant children aged 6–12 years, randomized to 1,000 mg metformin (n = 53) or placebo (n = 47) twice daily for 6 months, followed by open-label metformin treatment for 6 months. All children and their parents participated in a monthly dietitian-administered weight-reduction program. RESULTS Eighty-five percent completed the 6-month randomized phase. Children prescribed metformin had significantly greater decreases in BMI (difference −1.09 kg/m2, CI −1.87 to −0.31, P = 0.006), body weight (difference −3.38 kg, CI −5.2 to −1.57, P < 0.001), BMI Z score (difference between metformin and placebo groups −0.07, CI −0.12 to −0.01, P = 0.02), and fat mass (difference −1.40 kg, CI −2.74 to −0.06, P = 0.04). Fasting plasma glucose (P = 0.007) and homeostasis model assessment (HOMA) insulin resistance index (P = 0.006) also improved more in metformin-treated children than in placebo-treated children. Gastrointestinal symptoms were significantly more prevalent in metformin-treated children, which limited maximal tolerated dosage in 17%. During the 6-month open-label phase, children treated previously with placebo decreased their BMI Z score; those treated continuously with metformin did not significantly change BMI Z score further. CONCLUSIONS Metformin had modest but favorable effects on body weight, body composition, and glucose homeostasis in obese insulin-resistant children participating in a low-intensity weight-reduction program.

Estimation of Body Fatness by Air Displacement Plethysmography in African American and White Children

The purpose of this study was to determine the ability of air displacement plethysmography (ADP) to estimate body fatness in prepubertal and early pubertal African American and white children. One hundred nineteen nonoverweight and overweight boys (N = 56) and girls (N = 63), age (mean ± SD) 9.8 ± 1.7 y, body mass index 25.9 ± 7.6 kg/m2 (range, 14.2–47.0 kg/m2), and mean percent body fat (%BF) by dual-energy x-ray absorptiometry (DXA) 39.2 ± 11.7% (range, 12.2–57.5%), were studied. %BF by ADP was compared with DXA %BF estimates and with body fat by several field methods: skinfold thicknesses using the Slaughter et al. equations (Hum Biol 60: 709–723, 1988), bioelectrical impedance analysis (BIA) using the Houtkooper et al. equation (J Appl Physiol 72: 366–373, 1992), and a predictive equation using skinfold thicknesses, BIA, and weight (Goran et al.: Am J Clin Nutr 63: 299–305, 1996). All methods used to estimate %BF were significantly correlated with DXA (all p < 0.0001), with r2 ranging from 0.85 (skinfold measurements) to 0.95 (ADP). ADP using the Siri equation underestimated %BF by −1.9% (p < 0.001); the Bland-Altman limits of agreement (defined as ±2 SD) were ±7.4%. %BF by ADP-Siri underestimated %BF by DXA by 3.0% for girls (p < 0.001) and by 0.6% for boys (NS). Agreement between body fat estimation by ADP and DXA did not vary with age, race, or pubertal stage. Application of the age-adjusted Lohman model to ADP significantly increased the magnitude of the underestimation to −6.9% (p < 0.0001). Prediction of %BF by the Slaughter skinfold thickness equation showed no significant mean bias for the overall data, but significantly underestimated %BF in girls (−3.7%) while overestimating %BF in boys (+2.4%) with wide limits of agreement (±17.7%, p < 0.01 versus ADP). %BF by the Houtkooper BIA equation or Goran model underestimated %BF to a significantly greater degree than ADP (Houtkooper, −8.1%; Goran, −10.1%; both p < 0.0001 versus DXA or ADP). Determination of %BF from ADP using the Siri model slightly underestimates %BF as determined by DXA in girls, but appears to be superior to existing field methods both in accuracy and limits of agreement. Because of the ease with which it can be performed, ADP may prove useful for investigations of adiposity in children.

A Randomized Trial of a Low-Carbohydrate Diet vs Orlistat Plus a Low-Fat Diet for Weight Loss

BACKGROUND Two potent weight loss therapies, a low-carbohydrate, ketogenic diet (LCKD) and orlistat therapy combined with a low-fat diet (O + LFD), are available to the public but, to our knowledge, have never been compared. METHODS Overweight or obese outpatients (n = 146) from the Department of Veterans Affairs primary care clinics in Durham, North Carolina, were randomized to either LCKD instruction (initially, <20 g of carbohydrate daily) or orlistat therapy, 120 mg orally 3 times daily, plus low-fat diet instruction (<30% energy from fat, 500-1000 kcal/d deficit) delivered at group meetings over 48 weeks. Main outcome measures were body weight, blood pressure, fasting serum lipid, and glycemic parameters. RESULTS The mean age was 52 years and mean body mass index was 39.3 (calculated as weight in kilograms divided by height in meters squared); 72% were men, 55% were black, and 32% had type 2 diabetes mellitus. Of the study participants, 57 of the LCKD group (79%) and 65 of the O + LFD group (88%) completed measurements at 48 weeks. Weight loss was similar for the LCKD (expected mean change, -9.5%) and the O + LFD (-8.5%) (P = .60 for comparison) groups. The LCKD had a more beneficial impact than O + LFD on systolic (-5.9 vs 1.5 mm Hg) and diastolic (-4.5 vs 0.4 mm Hg) blood pressures (P < .001 for both comparisons). High-density lipoprotein cholesterol and triglyceride levels improved similarly within both groups. Low-density lipoprotein cholesterol levels improved within the O + LFD group only, whereas glucose, insulin, and hemoglobin A(1c) levels improved within the LCKD group only; comparisons between groups, however, were not statistically significant. CONCLUSION In a sample of medical outpatients, an LCKD led to similar improvements as O + LFD for weight, serum lipid, and glycemic parameters and was more effective for lowering blood pressure. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00108524.

Efficacy of orlistat as an adjunct to behavioral treatment in overweight African American and Caucasian adolescents with obesity-related co-morbid conditions.

This pilot study compared the efficacy of orlistat as an adjunctive treatment for obesity between African American and Caucasian adolescents. Twenty obese adolescents with obesity-related co-morbid conditions underwent measurements of body composition, glucose homeostasis by frequently sampled intravenous glucose tolerance test (FSIGT), and fasting lipids before and after 6 months treatment with orlistat 120 mg tid in conjunction with a comprehensive behavioral program. Weight (p < 0.05), BMI (p < 0.001), total cholesterol (p < 0.001), LDL cholesterol (p < 0.001), fasting insulin (p < 0.02) and fasting glucose (p < 0.003) were lower after treatment. Insulin sensitivity, measured during the FSIGT, improved significantly (p < 0.02), as did fasting indices such as the homeostasis model assessment for insulin resistance (p < 0.01). African American subjects exhibited significantly less improvement in weight (p < 0.05), BMI (p < 0.01), waist circumference (p = 0.03), and insulin sensitivity (p = 0.05). Improvements in cholesterol were not significantly different between African Americans and Caucasians. We conclude that Caucasians lost more weight and had greater improvements in insulin sensitivity than African Americans, but both exhibited improvements in plasma lipids. The true benefit of orlistat treatment over a comprehensive behavioral program remains to be determined in placebo-controlled trials.

Smoking Cessation Interventions for Patients with Depression: A Systematic Review and Meta-analysis

OBJECTIVESWe conducted a systematic literature review of smoking cessation interventions for patients with histories of depressive disorders or current significant depressive symptoms. We examined the comparative effectiveness of smoking cessation strategies on abstinence rates, differential effects of cessation strategies by depression status (i.e., history positive vs. current depression), and differential effects by gender.DATA SOURCESPeer-reviewed literature in MEDLINE, Embase, PsycINFO, and Cochrane Library.Study eligibility criteria, participants, and interventionsRandomized controlled trials or secondary analysis of RCT data comparing two or more smoking cessation interventions or intervention to control, and reporting cessation outcomes in adults with depression.STUDY APPRAISAL AND SYNTHESIS METHODSTwo trained researchers screened articles for inclusion. When possible, we estimated pooled risk ratios with 95% confidence intervals by using a random effects model with the Mantel–Haenszel method. We synthesized other studies qualitatively. We classified each intervention as antidepressants, nicotine replacement therapy (NRT), brief smoking cessation counseling, smoking cessation behavioral counseling, or behavioral mood management.RESULTSWe identified 16 unique RCTs, of which, only three trials recruited participants with current depression. Meta-analysis demonstrated a small, positive effect of adding behavioral mood management (RR = 1.41, 95% CI 1.01–1.96). All included antidepressant trials showed small, positive effects, but risk ratio summary was not significant (RR = 1.31, 95% CI 0.73–2.34). Three NRT trials demonstrated small, positive effects on smoking cessation rates. We found insufficient evidence to examine gender and depression status moderator effects.LIMITATIONSFew RCTs exist that test smoking cessation interventions among adults with depression. To make meaningful comparisons, we created broad intervention categories that contained heterogeneity.CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGSFew trials enrolled smokers with current depression. Most of data identified were from subgroup analyses of patients history-positive for depression. However, several promising interventions exist. Healthcare providers should consider encouraging their patients with significant depressive symptoms or depression histories to seek smoking cessation services that include NRT and behavioral mood management.

Computer-assisted self-interviewing: a multimedia approach to dietary assessment

Currently available dietary assessment tools have limited ability to obtain valid data within the resource constraints of large-scale studies. Many obstacles to gathering data can be overcome with computer-assisted self-interviewing (CASI). Computers can conduct personalized, in-depth interviews without interviewers; provide standardized data collection with appropriate levels of probing; automate data entry; encourage subjects to review and correct inconsistent data; and ensure that responses are complete. Interactive multimedia tools can motivate subjects and improve participation. Visual and aural cues may stimulate recall and improve data quality. CASI is appropriate for use in populations in which literacy is low and in multiple ethnic groups. A prototype CASI diet-history program was developed for use in the United States. The diet-history approach was selected to improve cognitive support and capture information on usual diet. Scripts were based on recorded interviews with dietitians and interviewers from the National Health and Nutrition Examination Survey. At the end of the interview, participants are given information on how their reported nutrient intakes compare with current recommendations for their age and sex. The prototype was tested in focus groups of mixed age, sex, ethnicity, and education, with encouraging results. The development of multimedia-based dietary assessment tools seems a logical next step in improving dietary assessment methods.

Longitudinal Adherence to Fecal Occult Blood Testing Impacts Colorectal Cancer Screening Quality

OBJECTIVES:Existing cross-sectional quality measures for colorectal cancer (CRC) screening do not assess longitudinal adherence and thus may overestimate the quality of care. Our goal was to evaluate the adherence to repeated yearly fecal occult blood tests (FOBTs) in order to better understand the extent to which longitudinal adherence may impact screening quality.METHODS:This was a retrospective cohort analysis of 1,122,645 patients aged 50–75 years seen at any of the 136 Department of Veterans Affairs medical centers across the United States in 2000 and followed through 2005. The primary outcome was receipt of adequate CRC screening as defined by receipt of FOBTs in at least 4 out of 5 years or receipt of any number of FOBTs in addition to at least one colonoscopy, flexible sigmoidoscopy, or double-contrast barium enema. In a predefined subset of patients receiving exclusively FOBT, adherence with repeated testing was determined over the 5-year study period.RESULTS:Only 41.1% of men and 43.6% of women received adequate screening. Of the 384,527 men who received exclusively FOBT, 42.1% received a single FOBT, 26.0% received 2 tests, 17.8% received 3 tests, and only 14.1% were documented to have received at least 4 tests during the study period. Among the 10,469 female veterans receiving FOBT alone, rates were similar with only 13.7% completing at least 4 FOBTs in the 5-year study period.CONCLUSIONS:Adherence to repeated FOBT is low, suggesting that cross-sectional measurements of quality may overestimate the programmatic success of CRC screening.

Brief psychotherapy for depression: a systematic review and meta-analysis

Objective: Because evidence-based psychotherapies of 12 to 20 sessions can be perceived as too lengthy and time intensive for the treatment of depression in primary care, a number of studies have examined abbreviated psychotherapy protocols. The purpose of this study was to conduct a systematic review and meta-analysis to determine the efficacy of brief psychotherapy (i.e., < 8 sessions) for depression. Methods: We used combined literature searches in PubMed, EMBASE, PsycINFO, and an Internet-accessible database of clinical trials of psychotherapy to conduct two systematic searches: one for existing systematic reviews and another for randomized controlled trials (RCTs). Included studies examined evidence-based psychotherapy(s) of eight or fewer sessions, focused on adults with depression, contained an acceptable control condition, were published in English, and used validated measures of depressive symptoms. Results: We retained 2 systematic reviews and 15 RCTs evaluating cognitive behavioral therapy, problem-solving therapy, and mindfulness-based cognitive therapy. The systematic reviews found brief psychotherapies to be more efficacious than control, with effect sizes ranging from −0.33 to −0.25. Our meta-analysis found six to eight sessions of cognitive behavioral therapy to be more efficacious than control (ES −0.42, 95% CI −0.74 to −0.10, I2 = 56%). A sensitivity analysis controlled for statistical heterogeneity but showed smaller treatment effects (ES −0.24, 95% CI −0.42 to −0.06, I2 = 0%). Conclusions: Depression can be efficaciously treated with six to eight sessions of psychotherapy, particularly cognitive behavioral therapy and problem-solving therapy. Access to non-pharmacologic treatments for depression could be improved by training healthcare providers to deliver brief psychotherapies.