Increased Glucose Uptake in Visceral Versus Subcutaneous Adipose Tissue Revealed by PET Imaging Thomas Christen, Yuri Sheikine, Viviane Z. Rocha, Shelley Hurwitz, Allison B. Goldfine, Marcelo Di ...Carli, Peter Libby Visceral adipose tissue (VAT) burden correlates better with cardiovascular risk than does subcutaneous adipose tissue (SAT) burden. In diet-induced obese mice, the stromal vascular cell (SVC) fraction of VAT exhibited higher glucose uptake than that from SAT. Moreover, glucose uptake was stimulated to a greater extent by TNF-alpha and IL-1beta in SVC from VAT compared with SAT. In humans, VAT exhibited higher fluorodeoxyglucose positron emission tomography (FDG-PET) uptake compared with SAT independent of age, sex, body mass index, comorbidities, and medications. The use of FDG-PET as a research tool could provide noninvasive mechanistic insights into the metabolic variables of adipose tissue in vivo.
Abstract Objective Higher hemoglobin A1c (HbA1c ) is associated with lower cognitive function in type 2 diabetes. To determine whether associations persist at lower levels of dysglycemia in patients ...who have established cardiovascular disease, cognitive performance was assessed in the Targeting INflammation Using SALsalate in CardioVascular Disease (TINSAL-CVD) trial. Methods The age-adjusted relationships between HbA1c and cognitive performance measured by the Mini-Mental State Examination, Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Trail Making Test, and Categorical Verbal Fluency were assessed in 226 men with metabolic syndrome and established stable coronary artery disease. Results Of the participants, 61.5% had normoglycemia, 20.8% had impaired fasting glucose, and 17.7% had type 2 diabetes. HbA1c was associated with cognitive function tests of Digit Symbol Substitution Test, Rey Auditory Verbal Learning Test, Trail Making Test, and Categorical Verbal Fluency (all P < .02), but not the Mini-Mental State Examination. In an age-adjusted model, a 1% (11 mmol/mol) higher HbA1c value was associated with a 5.9 lower Digit Symbol Substitution Test score (95% confidence interval CI, −9.58 to −2.21; P < .0001); a 2.44 lower Rey Auditory Verbal Learning Test score (95% CI, −4.00 to −0.87; P < .0001); a 15.6 higher Trail Making Test score (95% CI, 5.73 to 25.6; P < .0001); and a 3.71 lower Categorical Verbal Fluency score (95% CI, −6.41 to −1.01; P < .02). In a multivariate model adjusting for age, education, and cardiovascular covariates, HbA1c remained associated with cognitive function tests of Rey Auditory Verbal Learning Test ( R 2 = 0.27, P < .0001), Trail Making Test ( R 2 = 0.18, P < .0001), and Categorical Verbal Fluency ( R 2 = 0.20, P < .0001), although association with the Digit Symbol Substitution Test was reduced. Conclusions Higher HbA1c is associated with lower cognitive function performance scores across multiple domain tests in men with metabolic syndrome and coronary artery disease. Future studies may demonstrate whether glucose lowering within the normative range improves cognitive health.
This report highlights a roundtable discussion that occurred during the annual meeting of the International Diabetes Federation (IDF) in November 2009, in Montreal, Quebec, Canada. Participants ...included Bernard Zinman, MD, Michael A. Nauck, MD, PhD, Jorge Plutzky, MD, and Allison B. Goldfine, MD. The roundtable was chaired by Vivian A. Fonseca, MD. Among the topics discussed were the burden of type 2 diabetes mellitus and the importance of "appropriate therapy," which includes not only managing glycemia but also the management of concomitant risk factors such as hypertension and dyslipidemia. The discussants also identified issues that remain to be resolved, such as determining the nature of first-line therapy (e.g., should initial dual-agent therapy be encouraged?) and agreeing upon the most appropriate agent to be combined with metformin, which is the current standard of care. Among the new treatments discussed for type 2 diabetes were the analogues of the incretin hormones glucagonlike peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), namely, the GLP-1 receptor agonists-as well as the inhibitors of dipeptidyl peptidase-4 (DPP-4), the enzyme that regulates the bioactivity of the endogenous incretin hormones. These agents have some interesting advantages; not only do they effectively lower glucose, but they also have demonstrated beneficial metabolic and cardiovascular effects. Particularly with respect to the GIP and GLP-1, weight loss, blood pressure reductions, and beta-cell function improvements have been observed in clinical trials. What remains to be determined, by means of additional clinical experience and perhaps additional head-to-head trials, are the long-term benefits of GLP-1 receptor agonists and DPP-4 inhibitors and the sorts of roles these 2 classes of agents may play in the type 2 diabetes therapeutic continuum.
Abstract Purpose To compare effects of Roux-en-Y gastric bypass versus a multi-disciplinary, group-based medical diabetes and weight management program on physical fitness and behaviors. Methods ...Physical behavior and fitness was assessed in participants of the study Surgery or Lifestyle With Intensive Medical Management in the Treatment of Type 2 Diabetes(SLIMM-T2D)(NCT01073020), a randomized parallel-group trial conducted at a U.S. academic hospital and diabetes clinic with 18-24-month follow-up. Thirty-eight type 2 diabetes patients with hemoglobin A1c above 6.5% and BMI 30-42 kg/m2 were randomized to Roux-en-Y gastric bypass or medical program. A six-minute-walk-test to evaluate fitness, self-reported physical activity, standardized physical surveys, and cardiometabolic risk assessment were performed at baseline and after intervention. Results Both groups similarly improved six-minute-walk-test distance, with greater improvements in oxygen saturation and reduced heart rate following surgery. Self-reported physical activity improved similarly at 18-24-months following interventions, although exercise increased gradually following surgery, whereas early substantial increases in medical group were not fully sustained. Self-reported total and physical health were similar by Short Form-36, but improved more in the Impact of Weight on Quality of Life survey following surgery. Improvement in cardiovascular risk scores, HbA1c , and BMI were greater after surgery. Conclusion In this small, randomized study, both interventions led to therapeutic lifestyle changes and improved objective and self-reported physical fitness. Greater improvements in heart rate, oxygen saturation, and perceived impact of weight on health were seen following surgery, which could be attributable to greater weight loss. Clinical importance of these improvements with greater weight loss warrants further investigation.
Abstract Objectives This study sought to evaluate differential effects of visceral fat (VF) and subcutaneous fat and their effects on metabolic syndrome (MetS) risk across body mass index (BMI) ...categories. Background The regional distribution of adipose tissue is an emerging risk factor for cardiometabolic disease, although serial changes in fat distribution have not been extensively investigated. VF and its alterations over time may be a better marker for risk than BMI in normal weight and overweight or obese individuals. Methods We studied 1,511 individuals in the MESA (Multi-Ethnic Study of Atherosclerosis) with adiposity assessment by computed tomography (CT). A total of 253 participants without MetS at initial scan underwent repeat CT (median interval 3.3 years). We used discrete Cox regression with net reclassification to investigate whether baseline and changes in VF area are associated with MetS. Results Higher VF was associated with cardiometabolic risk and coronary artery calcification, regardless of BMI. After adjustment, VF was more strongly associated with incident MetS than subcutaneous fat regardless of weight, with a 28% greater MetS hazard per 100 cm2 /m VF area and significant net reclassification (net reclassification index: 0.44, 95% confidence interval CI: 0.29 to 0.60) over clinical risk. In individuals with serial imaging, initial VF (hazard ratio: 1.24 per 100 cm2 /m, 95% CI: 1.08 to 1.44 per 100 cm2 /m, p = 0.003) and change in VF (hazard ratio: 1.05 per 5% change, 95% CI: 1.01 to 1.08 per 5% change, p = 0.02) were associated with MetS after adjustment. Changes in subcutaneous fat were not associated with incident MetS after adjustment for clinical risk and VF area. Conclusions VF is modestly associated with BMI. However, across BMI, a single measure of and longitudinal change in VF predict MetS, even accounting for weight changes. Visceral adiposity is essential to assessing cardiometabolic risk, regardless of age, race, or BMI, and may serve as a marker and target of therapy in cardiometabolic disease.
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