Translational Research Institute for Metabolism and Diabetes

Orlando, FL, United States

Translational Research Institute for Metabolism and Diabetes

Orlando, FL, United States

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Johannsen N.M.,Pennington Biomedical Research Center | Johannsen N.M.,Louisiana State University | Sparks L.M.,Translational Research Institute for Metabolism and Diabetes | Zhang Z.,Pennington Biomedical Research Center | And 4 more authors.
PLoS ONE | Year: 2013

Aims:To assess the determinants of exercise training-induced improvements in glucose control (HbA1C) including changes in serum total adiponectin and FFA concentrations, and skeletal muscle peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) protein content.Methods:A sub-cohort (n = 35; 48% men; 74% Caucasian) from the HART-D study undertaking muscle biopsies before and after 9 months of aerobic (AT), resistance (RT), or combination training (ATRT).Results:Changes in HbA1C were associated with changes in adiponectin (r = -0.45, P = 0.007). Participants diagnosed with type 2 diabetes for a longer duration had the largest increase in PGC-1α (r = 0.44, P = 0.008). Statistical modeling examining changes in HbA1C suggested that male sex (P = 0.05), non-Caucasian ethnicity (P = 0.02), duration of type 2 diabetes (r = 0.40; P<0.002) and changes in FFA (r = 0.36; P<0.004), adiponectin (r = -0.26; P<0.03), and PGC-1α (r = -0.28; P = 0.02) explain ∼65% of the variability in the changes in HbA1C.Conclusions:Decreases in HbA1C after 9 months of exercise were associated with shorter duration of diabetes, lowering of serum FFA concentrations, increasing serum adiponectin concentrations and increasing skeletal muscle PGC-1α protein expression.Trial Registration:ClinicalTrials.gov NCT00458133. © 2013 Johannsen et al.


Hall K.D.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | Chen K.Y.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | Guo J.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | Lam Y.Y.,Pennington Biomedical Research Center | And 7 more authors.
American Journal of Clinical Nutrition | Year: 2016

The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive suppression of energy expenditure (EE). Therefore, isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE, increased fat oxidation, and loss of body fat. In contrast, a more conventional view that "a calorie is a calorie" predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat. Objective: We investigated whether an isocaloric low-carbohydrate ketogenic diet (KD) is associated with changes in EE, respiratory quotient (RQ), and body composition. Design: Seventeen overweight or obese men were admitted to metabolic wards, where they consumed a high-carbohydrate baseline diet (BD) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein. Subjects spent 2 consecutive days each week residing in metabolic chambers to measure changes in EE (EEchamber), sleeping EE (SEE), and RQ. Body composition changes were measured by dualenergy X-ray absorptiometry. Average EE during the final 2 wk of the BD and KD periods was measured by doubly labeled water (EEDLW). Results: Subjects lost weight and body fat throughout the study corresponding to an overall negative energy balance of ∼ 300 kcal/d. Compared with BD, the KD coincided with increased EEchamber (57 ± 13 kcal/d, P = 0.0004) and SEE (89 ± 14 kcal/d, P > 0.0001) and decreased RQ (-0.111 ± 0.003, P > 0.0001). EEDLW increased by 151 ± 63 kcal/d (P = 0.03). Body fat loss slowed during the KD and coincided with increased protein utilization and loss of fat-free mass. Conclusion: The isocaloric KD was not accompanied by increased body fat loss but was associated with relatively small increases in EE that were near the limits of detection with the use of state-ofthe-art technology. © 2016 American Society for Nutrition.


Toro-Ramos T.,St Lukes Roosevelt Hospital | Toro-Ramos T.,Columbia University | Goodpaster B.H.,University of Pittsburgh | Goodpaster B.H.,Translational Research Institute for Metabolism and Diabetes | And 10 more authors.
Obesity | Year: 2015

Objective To assess changes in total (TAT), subcutaneous (SAT), visceral (VAT), and intermuscular (IMAT) adipose tissue by whole-body MRI before surgery and at 12 months and 24 months post-surgery in a subset of participants of the Longitudinal Assessment of Bariatric Surgery-2. Methods From 0 to 12 months, n-=-20 females and 3 males; from 12 to 24 months, n-=-42 females and 7 males. Paired t-tests and GLM repeated measures examined changes in TAT, SAT, VAT, and IMAT at 12 and 24 months, with sex and age as covariates. Results Changes from 0 to 12 months included weight (-41.9-±-12.1 kg; -36%), TAT (-33.5-±-9.6 kg; -56%), SAT (-29.2-±-8.2 kg; -55%), VAT (-3.3-±-1.6 kg; -73%), and IMAT (-0.99-±-0.68 kg; -50%), all P-<-0.001. In females, from 12 to 24 months, despite relative weight stability (-1.8-±-6.5 kg, -2%; P-=-0.085), VAT (-0.5-±-0.7 kg; -30%; P-<-0.001) and IMAT (-0.2-±-0.4 kg; -14%; P-=-0.012) decreased further. In males, from 12 to 24 months, weight increased (5.1-±-5.2 kg; 6%; P-=-0.04) with no significant changes in TAT or sub-depots. Conclusions Bariatric surgery continues to induce favorable changes in body composition, i.e., persistent adipose tissue loss at 24 months in the absence of further significant weight loss. © 2014 The Obesity Society.


Qi Q.,Harvard University | Bray G.A.,Harvard University | Bray G.A.,Louisiana State University | Smith S.R.,Translational Research Institute for Metabolism and Diabetes | And 3 more authors.
Circulation | Year: 2011

Background Common genetic variants in the insulin receptor substrate 1 (IRS1) gene have been recently associated with insulin resistance and hyperinsulinemia. We examined whether the best-associated variant modifies the long-term changes in insulin resistance and body weight in response to weight-loss diets in Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. Methods and Results-We genotyped IRS1 rs2943641 in 738 overweight adults (61% were women) who were randomly assigned to 1 of 4 diets varying in macronutrient contents for 2 years. We assessed the progress in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and weight loss by genotypes. At 6 months, participants with the risk-conferring CC genotype had greater decreases in insulin (P=0.009), HOMA-IR (P=0.015), and weight loss (P=0.018) than those without this genotype in the highest-carbohydrate diet group whereas an opposite genotype effect on changes in insulin and HOMA-IR (P≤ 0.05) was observed in participants assigned to the lowest-carbohydrate diet group. No significant differences were observed across genotypes in the other 2 diet groups. The tests for genotype by intervention interactions were all significant (P&l; 0.05). At 2 years, the genotype effect on changes in insulin and HOMA-IR remained significant in the highest-carbohydrate diet group (P< 0.05). The highest carbohydrate diet led to a greater improvement of insulin and HOMA-IR (P for genotype-time interaction ≤ 0.009) in participants with the CC genotype than those without this genotype across 2-year intervention. Conclusions-Individuals with the IRS1 rs2943641 CC genotype might obtain more benefits in weight loss and improvement of insulin resistance than those without this genotype by choosing a high-carbohydrate and low-fat diet. © 2011 American Heart Association, Inc.


Tussing-Humphreys L.,Louisiana State University | Frayn K.N.,University of Oxford | Smith S.R.,Translational Research Institute for Metabolism and Diabetes | Westerman M.,Intrinsic Lifesciences, Llc | And 4 more authors.
TheScientificWorldJournal | Year: 2011

Hepcidin is the main regulator of systemic iron homeostasis and is primarily produced by the liver but is also expressed, at the mRNA-level, in periphery tissues including the subcutaneous and visceral adipose tissue. Obesity is associated with elevated hepcidin concentrations and iron depletion suggesting that the exaggerated fat mass in obesity could contribute significantly to circulating hepcidin levels consequently altering iron homeostasis. The objective of this study was to determine if abdominal subcutaneous adipose tissue (AbScAT) releases hepcidin in vivo and if release is modified by obesity. Arterio-venous differences in concentrations of hepcidin were measured across AbScAT in 9 obese and 9 lean adults. Overall (n=18), mean plasma hepcidin concentrations were significantly higher in arterialized compared to AbScAT venous samples [mean difference (arterialized-AbScAT venous plasma hepcidin) = 4.9±9.6 ng/mL, P=0.04 ]. Net regional release was not calculated because mean venous plasma hepcidin concentrations were lower than mean arterialized concentrations indicating no net release. Significant correlations between AbScAT venous and arterialized plasma hepcidin concentrations with anthropometric variables were not observed. Findings from this vein drainage study suggest there is no net release of hepcidin from the AbScAT depot and thereby no ability to signal systemically, even in obesity. Copyright © 2011 Lisa Tussing-Humphreys et al.


Grosicki G.J.,Ball State University | Standley R.A.,Translational Research Institute for Metabolism and Diabetes | Murach K.A.,Ball State University | Raue U.,Ball State University | And 8 more authors.
Journal of Applied Physiology | Year: 2016

We examined single muscle fiber contractile function of the oldest-old (3F/2M, 89 ± 1 yr old) enrolled in The Health, Aging, and Body Composition Study (The Health ABC Study). Vastus lateralis muscle biopsies were obtained and single muscle fiber function was determined (n = 105) prior to myosin heavy chain (MHC) isoform identification with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cross-sectional area of MHC I muscle fibers (5,576 ± 333 μm2; n = 58) was 21% larger (P < 0.05) than MHC IIa fibers (4,518 ± 386 μm2; n = 47). Normalized power (an indicator of muscle fiber quality incorporating size, strength, and speed) of MHC I and IIa muscle fibers was 2.3 ± 0.1 and 17.4 ± 0.8 W/l, respectively. Compared with previous research from our lab using identical procedures, MHC I normalized power was 28% higher than healthy 20 yr olds and similar to younger octogenarians (∼80 yr old). Normalized power of MHC IIa fibers was 63% greater than 20 yr olds and 39% greater than younger octogenarians. These comparative data suggest that power output per unit size (i.e., muscle quality) of remaining muscle fibers improves with age, a phenomenon more pronounced in MHC IIa fibers. Age-related single muscle fiber quality improvements may be a compensatory mechanism to help offset decrements in whole muscle function. © 2016 the American Physiological Society.


Vijgen G.H.E.J.,Maastricht University | Sparks L.M.,Maastricht University | Sparks L.M.,Translational Research Institute for Metabolism and Diabetes | Bouvy N.D.,Maastricht University | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Since the discovery of functional brown adipose tissue (BAT) in adult humans, there has been a renewed interest in the physiology of human BAT. Imaging studies from our laboratory and others have shown increased glucose uptake in adipose tissue regions assumed to be BAT in humans. We have also shown that human BAT from the supraclavicular (SCV) region is positive for uncoupling protein-1. To date, however, the oxidative capacity of this adipose tissue (AT) depot has not been characterized in humans. Objective: We hypothesize that oxidative capacity is increased in the AT of the SCV region known to contain human BAT. Design: This was an observational prospective cohort study. Setting: The study was conducted at a referral center. Patients: Participants were 13 patients for whom thyroid gland surgery was indicated. Main Outcome Measure: Basal cellular oxygen consumption in human AT biopsy samples from the SCV region, known to be [18F]fluorodeoxyglucose positron emission tomography-computed tomography-positive, was compared with the cellular oxygen consumption in subcutaneous white adipose tissue (WAT) from the same region of the same subject. Results: We show for the first time that AT from the human BAT region displays increased oxygen consumption (P < .05), on average 300% higher, than subcutaneous WAT of the same individual. The contribution of the proton leak to maximal respiration increased with age in the WAT but not in the AT from the BAT region. Conclusions: These results suggest that human adipose tissue from the BAT region can be distinguished from subcutaneous WAT by a higher basal oxidative capacity. Additional studies are warranted to further elucidate the metabolic and bioenergetic characteristics of this AT depot in humans. Copyright © 2013 by The Endocrine Society.


PubMed | U.S. National Institute on Aging, Ball State University, Sticht Center on Aging, Translational Research Institute for Metabolism and Diabetes and 2 more.
Type: Journal Article | Journal: Journal of applied physiology (Bethesda, Md. : 1985) | Year: 2016

We examined single muscle fiber contractile function of the oldest-old (3F/2M, 89 1 yr old) enrolled in The Health, Aging, and Body Composition Study (The Health ABC Study). Vastus lateralis muscle biopsies were obtained and single muscle fiber function was determined (n = 105) prior to myosin heavy chain (MHC) isoform identification with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cross-sectional area of MHC I muscle fibers (5,576 333 m


Santanasto A.J.,University of Pittsburgh | Coen P.M.,University of Pittsburgh | Coen P.M.,Translational Research Institute for Metabolism and Diabetes | Glynn N.W.,University of Pittsburgh | And 8 more authors.
Experimental Gerontology | Year: 2016

Background: Age related declines in walking performance may be partly attributable to skeletal muscle mitochondrial dysfunction as mitochondria produce over 90% of ATP needed for movement and the capacity for oxidative phosphorylation decreases with age. Methods: Participants were from two studies: an ancillary to the Lifestyle Interventions and Independence for Elders (LIFE) Study (n = 33), which recruited lower functioning participants (Short Physical Performance Battery [SPPB], 7.8 ± 1.2), and the Study of Energy and Aging-Pilot (SEA, n = 29), which enrolled higher functioning (SPPB, 10.8 ± 1.4). Physical activity was measured objectively using the Actigraph accelerometer (LIFE) and SenseWear Pro armband (SEA). Phosphocreatine recovery following muscle contraction of the quadriceps was measured using 31P magnetic resonance spectroscopy and ATPmax (mM ATP/s) was calculated. Walking performance was defined as time (s) to walk 400 m at a usual-pace. The cross-sectional association between mitochondrial function and walking performance was assessed using multivariable linear regression. Results: Participants were 77.6 ± 5.3 years, 64.2% female and 67.2% white. ATPmax was similar in LIFE vs. SEA (0.52 ± 0.14 vs. 0.55 ± 0.14, p = 0.31), despite different function and activity levels (1.6 ± 2.2 vs.77.4 ± 73.3 min of moderate activity/day, p < 0.01). Higher ATPmax was related to faster walk-time in SEA (r2 = 0.19, p = 0.02,); but not the LIFE (r2 < 0.01, p = 0.74) cohort. Conclusions: Mitochondrial function was associated with walking performance in higher functioning, active older adults, but not lower functioning, sedentary older adults. © 2016.


Pratley R.E.,Florida Hospital Diabetes Institute | Pratley R.E.,Translational Research Institute for Metabolism and Diabetes | Pratley R.E.,Sanford Burnham Institute for Medical Research
Clinical Interventions in Aging | Year: 2014

Older people have the highest prevalence of type 2 diabetes mellitus (T2DM) of any age group and are thus frequent users of glucose-lowering agents. Because individuals 65 years or older are underrepresented in clinical studies, there is a lack of information regarding the efficacy and safety of available treatments in this population. Additionally, a high prevalence of comorbidities, polypharmacy, and frailty can make treatment of T2DM in this population challenging. Safety is an important consideration when choosing a treatment for older individuals. Renal impairment is quite common in older patients with T2DM and can contribute to hypoglycemia. Hypoglycemia can lead to serious consequences, such as falls and fractures, and cognitive changes. As such, hemoglobin A1c treatment targets, typically <7% in the general population, are less stringent in older people, with the goal being an individualized target that balances efficacy and safety. Many glucose-lowering agents can cause adverse events detrimental to older individuals, such as hypoglycemia (insulin, sulfonylureas), weight gain (sulfonylureas, thiazolidinediones), gastrointestinal events (metformin), and fractures (thiazolidinediones), and are contraindicated or require dose adjustments in those with renal impairment (most oral/injectable agents). Orally administered dipeptidyl peptidase (DPP)-4 inhibitors have a low risk of hypoglycemia and are generally well tolerated. Linagliptin is the only DPP-4 inhibitor excreted through nonrenal pathways and therefore does not require any dose adjustment in older patients with kidney disease. This paper reviews the findings of a recent study by Barnett et al assessing the efficacy and safety of the DPP-4 inhibitor linagliptin in patients with T2DM aged 70 years or older, which concluded that linagliptin may be a useful glucose-lowering option for older patients with T2DM. © 2014 Pratley.

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