Caroline Kaercher Kramer

Standards of Medical Care in Diabetes--2008: response to Hirsch, Inzucchi, and Kirkman.

The American Diabetes Association (ADA) has released a Standards of Medical Care in Diabetes Position Statement for 2008 (1). In this document, it is stated that aspirin therapy should be used as a primary prevention strategy in diabetic patients at increased cardiovascular (CV) risk, including those who are >40 years old or have additional risk factors. The recommendation is based on evidence graded “A,” which is defined by the ADA as “evidence from well-conducted, randomized controlled trials that are adequately powered or compelling nonexperimental evidence.” As this indication seemed very …

Are Metabolically Healthy Overweight and Obesity Benign Conditions?A Systematic Review and Meta-analysis

BACKGROUND Recent interest has focused on a unique subgroup of overweight and obese individuals who have normal metabolic features despite increased adiposity. Normal-weight individuals with adverse metabolic status have also been described. However, it remains unclear whether metabolic phenotype modifies the morbidity and mortality associated with higher body mass index (BMI). PURPOSE To determine the effect of metabolic status on all-cause mortality and cardiovascular events in normal-weight, overweight, and obese persons. DATA SOURCES Studies were identified from electronic databases. STUDY SELECTION Included studies evaluated all-cause mortality or cardiovascular events (or both) and clinical characteristics of 6 patient groups defined by BMI category (normal weight/overweight/obesity) and metabolic status (healthy/unhealthy), as defined by the presence or absence of components of the metabolic syndrome by Adult Treatment Panel III or International Diabetes Federation criteria. DATA EXTRACTION Two independent reviewers extracted the data. Metabolically healthy people of normal weight made up the reference group. DATA SYNTHESIS Eight studies (n = 61 386; 3988 events) evaluated participants for all-cause mortality and/or cardiovascular events. Metabolically healthy obese individuals (relative risk [RR], 1.24; 95% CI, 1.02 to 1.55) had increased risk for events compared with metabolically healthy normal-weight individuals when only studies with 10 or more years of follow-up were considered. All metabolically unhealthy groups had a similarly elevated risk: normal weight (RR, 3.14; CI, 2.36 to 3.93), overweight (RR, 2.70; CI, 2.08 to 3.30), and obese (RR, 2.65; CI, 2.18 to 3.12). LIMITATION Duration of exposure to the metabolic-BMI phenotypes was not described in the studies and could partially affect the estimates. CONCLUSION Compared with metabolically healthy normal-weight individuals, obese persons are at increased risk for adverse long-term outcomes even in the absence of metabolic abnormalities, suggesting that there is no healthy pattern of increased weight. PRIMARY FUNDING SOURCE Intramural funds from the Leadership Sinai Centre for Diabetes.

A1C and Diabetes Diagnosis: The Rancho Bernardo Study

OBJECTIVE To examine the sensitivity and specificity of A1C as a diagnostic test for type 2 diabetes in older adults. RESEARCH DESIGN AND METHODS Cross-sectional study of community-dwelling adults without known diabetes who had an oral glucose tolerance test and A1C measured on the same day. RESULTS Mean age of the 2,107 participants was 69.4 ± 11.1 years; 43% were men. Based on the American Diabetes Association (ADA) criteria, 198 had previously undiagnosed type 2 diabetes. The sensitivity/specificity of A1C cut point of 6.5% was 44/79%. Results were similar in age- and sex-stratified analyses. Given the A1C cut point of 6.5%, 85% of participants were classified as nondiabetic by ADA criteria. CONCLUSIONS The limited sensitivity of the A1C test may result in delayed diagnosis of type 2 diabetes, while the strict use of ADA criteria may fail to identify a high proportion of individuals with diabetes by A1C ≥6.5% or retinopathy.

Effect of Antihyperglycemic Agents Added to Metformin and a Sulfonylurea on Glycemic Control and Weight Gain in Type 2 Diabetes: A Network Meta-analysis

BACKGROUND Few studies have examined the effect of adding a third antihyperglycemic drug when blood glucose control is not achieved by using metformin and a sulfonylurea. PURPOSE To compare the efficacy of add-on antihyperglycemic drugs in patients with type 2 diabetes that is not controlled with metformin and a sulfonylurea. DATA SOURCES MEDLINE, EMBASE, Cochrane Library, LILACS, and ClinicalTrials.gov electronic databases. STUDY SELECTION Randomized trials at least 24 weeks in duration. Studies evaluated the effects of adding a third antihyperglycemic drug to treatment of adults aged 18 years or older with type 2 diabetes and a hemoglobin A(1c) (HbA(1c)) level greater than 7.0% who were already receiving a combination of metformin and a sulfonylurea. DATA EXTRACTION Primary end points were change in HbA(1c) level, change in weight, and frequency of severe hypoglycemia. DATA SYNTHESIS Eighteen trials involving 4535 participants that lasted a mean of 31.3 weeks (24 to 52 weeks) were included. Compared with placebo, drug classes did not differ in effect on HbA(1c) level (reduction ranging from -0.70% [95% credible interval {CrI}, -1.33% to -0.08%] for acarbose to -1.08% [CrI, -1.41% to -0.77%] for insulin). Weight increase was seen with insulins (2.84 kg [CrI, 1.76 to 3.90 kg]) and thiazolidinediones (4.25 kg [CrI, 2.76 to 5.66 kg]), and weight loss was seen with glucagon-like peptide-1 agonists (-1.63 kg [CrI, -2.71 to -0.60 kg]). Insulins caused twice the absolute number of severe hypoglycemic episodes than noninsulin antihyperglycemic agents. LIMITATIONS Most of the trials were short term, and trial quality varied. With so few trials relative to antihyperglycemic agents, investigators relied on indirect comparisons, which increased the uncertainty of the findings and conclusions. CONCLUSION There is no clear difference in benefit between drug classes when adding a third agent to treatment of patients with type 2 diabetes who are already receiving metformin and a sulfonylurea. The most appropriate option should depend on each patients clinical characteristics. PRIMARY FUNDING SOURCE Conselho Nacional de Desenvolvimento Científico e Tecnológico and Coordenacăo de Aperfeicoamento de Pessoal de Nível Superior.

Diabetic Retinopathy Predicts All-Cause Mortality and Cardiovascular Events in Both Type 1 and 2 Diabetes: Meta-analysis of observational studies

OBJECTIVE The prognostic significance of diabetic retinopathy (DR) for death and cardiovascular (CV) outcomes is debated. We investigated the association of DR with all-cause mortality and CV events in patients with diabetes by a systematic review and meta-analysis. RESEARCH DESIGN AND METHODS The electronic databases Medline and Embase were searched for cohort studies that evaluated DR in type 2 or type 1 diabetic patients and reported total mortality and/or fatal and nonfatal CV events, including myocardial infarction, angina pectoris, coronary artery bypass graft, ischemic changes on a conventional 12-lead electrocardiogram, transient ischemic attack, nonfatal stroke, or lower leg amputation. Data extraction was performed by two reviewers independently. Pooled effect estimates were obtained by using random-effects meta-analysis. RESULTS The analysis included 20 studies that fulfilled the inclusion criteria, providing data from 19,234 patients. In patients with type 2 diabetes (n = 14,896), the presence of any degree of DR increased the chance for all-cause mortality and/or CV events by 2.34 (95% CI 1.96–2.80) compared with patients without DR. In patients with type 1 diabetes (n = 4,438), the corresponding odds ratio was 4.10 (1.50–11.18). These associations remained after adjusting for traditional CV risk factors. DR was also predictive of all-cause mortality in type 2 diabetes (odds ratio 2.41 [1.87–3.10]) and type 1 diabetes (3.65 [1.05–12.66]). CONCLUSIONS The presence of DR was associated with an increased risk of all-cause mortality and CV events in both type 2 and type 1 diabetic patients.

Serum uric acid levels improve prediction of incident type 2 diabetes in individuals with impaired fasting glucose: the Rancho Bernardo Study.

OBJECTIVE To determine whether serum uric acid predicts incident type 2 diabetes by glucose tolerance status in older community-dwelling adults. RESEARCH DESIGN AND METHODS Participants without diabetes at baseline were evaluated for incident type 2 diabetes 13 years later. Baseline glucose tolerance status was defined as normoglycemia, impaired fasting glucose, and impaired postchallenge glucose tolerance. RESULTS A total of 566 participants were included (mean age 63.3 ± 8.6 years; 41% men). Regression models adjusted for age, sex, BMI, diuretic use, and estimated glomerular filtration rate showed that for each 1 mg/dl increment in uric acid levels, incident type 2 diabetes risk increased by ∼60%. When analyses were stratified by glucose status, uric acid levels independently predicted incident type 2 diabetes among participants who had impaired fasting glucose (odds ratio 1.75, 95% CI 1.1–2.9, P = 0.02). CONCLUSIONS Uric acid may be a useful predictor of type 2 diabetes in older adults with impaired fasting glucose.

Thyroid Ultrasound Features and Risk of Carcinoma: A Systematic Review and Meta-Analysis of Observational Studies

Background: Thyroid nodules are a common finding in the general population, and their detection is increasing with the widespread use of ultrasound (US). Thyroid cancer is found in 5–15% of cases depending on sex, age, and exposure to other risk factors. Some US parameters have been associated with increased risk of malignancy. However, no characteristic seems sufficiently reliable in isolation to diagnose malignancy. The objective of this meta-analysis was to evaluate the diagnostic performance of US features for thyroid malignancy in patients with unselected thyroid nodules and nodules with indeterminate fine-needle aspiration (FNA) cytology. Methods: Electronic databases were reviewed for studies published prior to July 2012 that evaluated US features of thyroid nodules and reported postoperative histopathologic diagnosis. A manual search of references of review and key articles, and previous meta-analyses was also performed. A separate meta-analysis was performed including only nodules with indeterminate cytology. Analyzed features were solid structure, hypoechogenicity, irregular margins, absence of halo, microcalcifications, central vascularization, solitary nodule, heterogeneity, taller than wide shape, and absence of elasticity. Results: Fifty-two observational studies (12,786 nodules) were included. Nine studies included nodules with indeterminate cytology as a separate category, comprising 1851 nodules. In unselected nodules, all US features were significantly associated with malignancy with an odds ratio varying from 1.78 to 35.7, and microcalcifications, irregular margins, and a taller than wide shape had high specificities (Sp; 87.8%, 83.1%, 96.6%) and positive likelihood ratios (LHR; 3.26, 2.99, 8.07). Absence of elasticity was the single feature with the best diagnostic performance (sensitivity 87.9%, Sp 86.2%, and positive LHR 6.39). The presence of central vascularization was the most specific US feature in nodules with indeterminate cytology (Sp 96% and positive LHR 2.13). Conclusions: US features in isolation do not provide reliable information to select nodules that should have a FNA performed. A combination of US characteristics with higher likelihood ratios and consequently with higher post-test probabilities of malignancy—microcalcifications, or a taller than wide shape, or irregular margins, or absence of elasticity—will probably identify nodules with an increased risk for malignancy. Further studies are required to standardize elastography techniques and evaluate outcomes, especially in nodules with an indeterminate cytology.

Fiber intake and glycemic control in patients with type 2 diabetes mellitus: a systematic review with meta-analysis of randomized controlled trials

This systematic review with meta-analysis of randomized controlled trials (RCT) aimed to analyze the effect of fiber intake on glycemic control in patients with type 2 diabetes. Databases were searched up to November 2012 using the following medical subject headings: diabetes, fiber, and randomized controlled trial. Absolute changes in glycated hemoglobin and fasting plasma glucose were reported as differences between baseline and end-of-study measures. Pooled estimates were obtained using random-effects models. Of the 22,046 articles initially identified, 11 (13 comparisons; range of duration, 8-24 weeks) fulfilled the inclusion criteria, providing data from 605 patients. High-fiber diets, including diets with foods rich in fiber (up to 42.5 g/day; four studies) or supplements containing soluble fiber (up to 15.0 g/day; nine studies), reduced absolute values of glycated hemoglobin by 0.55% (95% CI -0.96 to -0.13) and fasting plasma glucose by 9.97 mg/dL (95% CI -18.16 to -1.78). In conclusion, increased fiber intake improved glycemic control, indicating it should be considered as an adjunctive tool in the treatment of patients with type 2 diabetes.

Efficacy and safety of topiramate on weight loss: a meta-analysis of randomized controlled trials

Topiramate was associated with weight loss in clinical trials. We summarize the evidence on the efficacy and safety of topiramate in the treatment of overweight/obesity. The databases Medline, Embase, and Cochrane were searched. Randomized controlled studies with at least 16 weeks of duration that report the effect of topiramate on weight loss and adverse events were eligible for inclusion. Ten studies were included (3320 individuals). Patients treated with topiramate lost an average of 5.34 kg (95% confidence interval [95%CI]−6.12 to −4.56) of additional weight as compared with placebo. According to meta‐regression analysis, treatment duration and dosage were associated with the efficacy of topiramate treatment. Evaluating trials using topiramate 96–200 mg day−1, the weight loss was higher in trials with >28 weeks of duration (−6.58 kg [95%CI −7.48 to −5.68]) than in trials with ≤28 weeks (−4.11 kg [95%CI −4.92 to −3.30]). Data of 6620 individuals were available for adverse events evaluation and those more frequently observed were paraesthesia, taste impairment and psychomotor disturbances. The odds ratio for adverse events leading to topiramate withdrawal was 1.94 (95%CI 1.64–2.29) compared with the control group. In conclusion, topiramate might be a useful adjunctive therapeutic tool in the treatment of obesity as long as proper warnings about side effects are considered.

A Prospective Study of Abdominal Obesity and Coronary Artery Calcium Progression in Older Adults

OBJECTIVE Little is known about obesity measurements and coronary artery calcium (CAC) progression in older adults. We examined the sex-specific association between measures of body size and fat distribution with CAC progression. SUBJECTS AND METHODS Participants were 156 men and 182 women (mean age 67 yr) without known heart disease who had electron-beam computed tomography for CAC at baseline and again 4.5 yr later. Obesity assessments were weight, height, body mass index, waist and hip circumference, waist to hip ratio, waist to height ratio, sc and visceral adipose tissue (SAT, VAT), and SAT to VAT ratio based on abdominal electron-beam computed tomography. CAC progression was defined as categorical (square root increased on total CAC volume score > or = 2.5 mm(3)) and continuous variables. RESULTS During the follow-up, 55% of men and 38.5% of women had CAC progression. Increased waist to hip ratio (> or = 0.9 for men, > or = 0.85 for women) and waist to height ratio (> or = 0.55 for men, > or = 0.54 for women) were positively and independently associated with CAC progression [median (interquartile range)] [60.8 (145) vs. 10.8 (56) mm(3), P = 0.002 and 50 (153) vs. 22(84) mm(3), P = 0.03, respectively]. In women but not men, an increased waist circumference (> 88 cm) independently predicted CAC progression (odds ratio 3.0 95% confidence interval 1.03-8.0, P = 0.04), whereas VAT to SAT ratio predicted CAC progression in men but not women (odds ratio 2.8 95% confidence interval 1.01-7.8, P = 0.04). CONCLUSION In this study of older adults without known heart disease, abdominal obesity was an independent predictor of CAC progression. These results point to the importance of using clinical measurements of abdominal obesity to identify individuals at increased risk for atherosclerosis.