Silvia Vallova

Effects of carnosine supplementation on glucose metabolism: Pilot clinical trial

Carnosine is a naturally present dipeptide in humans and an over‐the counter food additive. Evidence from animal studies supports the role for carnosine in the prevention and treatment of diabetes and cardiovascular disease, yet there is limited human data. This study investigated whether carnosine supplementation in individuals with overweight or obesity improves diabetes and cardiovascular risk factors.

A carnosine intervention study in overweight human volunteers: bioavailability and reactive carbonyl species sequestering effect.

Carnosine is a natural dipeptide able to react with reactive carbonyl species, which have been recently associated with the onset and progression of several human diseases. Herein, we report an intervention study in overweight individuals. Carnosine (2 g/day) was orally administered for twelve weeks in order to evaluate its bioavailability and metabolic fate. Two carnosine adducts were detected in the urine samples of all subjects. Such adducts are generated from a reaction with acrolein, which is one of the most toxic and reactive compounds among reactive carbonyl species. However, neither carnosine nor adducts have been detected in plasma. Urinary excretion of adducts and carnosine showed a positive correlation although a high variability of individual response to carnosine supplementation was observed. Interestingly, treated subjects showed a significant decrease in the percentage of excreted adducts in reduced form, accompanied by a significant increase of the urinary excretion of both carnosine and carnosine-acrolein adducts. Altogether, data suggest that acrolein is entrapped in vivo by carnosine although the response to its supplementation is possibly influenced by individual diversities in terms of carnosine dietary intake, metabolism and basal production of reactive carbonyl species.

Muscle Histidine-Containing Dipeptides Are Elevated by Glucose Intolerance in Both Rodents and Men

Objective Muscle carnosine and its methylated form anserine are histidine-containing dipeptides. Both dipeptides have the ability to quench reactive carbonyl species and previous studies have shown that endogenous tissue levels are decreased in chronic diseases, such as diabetes. Design and Methods Rodent study: Skeletal muscles of rats and mice were collected from 4 different diet-intervention studies, aiming to induce various degrees of glucose intolerance: 45% high-fat feeding (male rats), 60% high-fat feeding (male rats), cafeteria feeding (male rats), 70% high-fat feeding (female mice). Body weight, glucose-tolerance and muscle histidine-containing dipeptides were assessed. Human study: Muscle biopsies were taken from m. vastus lateralis in 35 males (9 lean, 8 obese, 9 prediabetic and 9 newly diagnosed type 2 diabetic patients) and muscle carnosine and gene expression of muscle fiber type markers were measured. Results Diet interventions in rodents (cafeteria and 70% high-fat feeding) induced increases in body weight, glucose intolerance and levels of histidine-containing dipeptides in muscle. In humans, obese, prediabetic and diabetic men had increased muscle carnosine content compared to the lean (+21% (p>0.1), +30% (p<0.05) and +39% (p<0.05), respectively). The gene expression of fast-oxidative type 2A myosin heavy chain was increased in the prediabetic (1.8-fold, p<0.05) and tended to increase in the diabetic men (1.6-fold, p = 0.07), compared to healthy lean subjects. Conclusion Muscle histidine-containing dipeptides increases with progressive glucose intolerance, in male individuals (cross-sectional). In addition, high-fat diet-induced glucose intolerance was associated with increased muscle histidine-containing dipeptides in female mice (interventional). Increased muscle carnosine content might reflect fiber type composition and/or act as a compensatory mechanism aimed at preventing cell damage in states of impaired glucose tolerance.

Combined aerobic-strength exercise improves cognitive functions in patients with mild cognitive impairment

important given the trend toward earlier and more accurate diagnosis of dementia and the emphasis on providing person-centered care. SHARE’s approach involves discussions led by a SHARE counselor with both “SHARE partners”. This approach has shown great promise in previous trials for improving a variety of outcomes for both individuals. Moreover, SHARE has been found to be feasible and acceptable to early-stage families: persons who have early-stage dementia are often fully aware of the meaning of their diagnosis and able to communicate care choices and preferences. This presentation will describe the SHARE Program and report on the results of its randomized controlled trial with 130 care dyads (e.g., improved carer symptoms of depression, lessened relationship strain, and increased service use). Discussion will focus on the utility of a dyadic approach, future directions for the SHARE program, and the implications for enhancing the shortand longterm well-being of both care partners.

Aerobic-strength exercise improves metabolism and clinical state in Parkinson's disease patients

Regular exercise ameliorates motor symptoms in Parkinson’s disease (PD). Here, we aimed to provide evidence that exercise brings additional benefits to the whole-body metabolism and skeletal muscle molecular and functional characteristics, which might help to explain exercise-induced improvements in the clinical state. 3-months supervised endurance/strength training was performed in early/mid-stage PD patients and age/gender-matched individuals (n = 11/11). The effects of exercise on resting energy expenditure (REE), glucose metabolism, adiposity, and muscle energy metabolism (31P-MRS) were evaluated and compared to non-exercising PD patients. Two muscle biopsies were taken to determine intervention-induced changes in fiber type, mitochondrial content, and expression of genes related to muscle energy metabolism, as well as proliferative and regenerative capacity. Exercise improved the clinical disability score (MDS-UPDRS), bradykinesia, balance, walking speed, REE, and glucose metabolism and increased muscle expression of energy sensors (AMPK). However, the exercise-induced increase in muscle mass/strength, mitochondrial content, type II fiber size, and postexercise phosphocreatine (PCr) recovery (31P-MRS) were found only in controls. Nevertheless, MDS-UPDRS was associated with muscle AMPK and mechano-growth factor (MGF) expression. Improvements in fasting glycemia were positively associated with muscle function and the expression of Sirt1 and Cox7a1, and the parameters of fitness/strength were positively associated with the expression of MyHC2, MyHC7, and MGF. Moreover, reduced bradykinesia was associated with better muscle metabolism (maximal oxidative capacity and postexercise PCr recovery; 31P-MRS). Exercise training improved the clinical state in early/mid-stage Parkinson’s disease patients, including motor functions and whole-body metabolism. Although the adaptive response to exercise in PD was different from that of controls, exercise-induced improvements in the PD clinical state were associated with specific adaptive changes in muscle functional, metabolic, and molecular characteristics. Clinical Trial Registration www.ClinicalTrials.gov, identifier NCT02253732.

A LINK BETWEEN COGNITIVE FUNCTION AND PHYSICAL ACTIVITY: THE IMPACT OF AEROBIC-STRENGTH EXERCISE IN SENIORS WITH MILD COGNITIVE IMPAIRMENT AND/OR IMPAIRED GLUCOSE METABOLISM

was similar between the experimental (n1⁄430, 68%), and control conditions (n1⁄427, 67.5%), but participants in the experimental condition were more likely to return for subsequent evaluations (T11⁄4100%, T21⁄493%) than participants in the control condition (T11⁄480%, T21⁄472%). Across training conditions, global cognition improved following the intervention, t(74)1⁄44.7, p<0.001, with improvements maintained at follow-up, t(73)1⁄43.9, p<0.001. Conclusions:Tailored and adaptive, as well as more generic CCT improved overall cognitive function in older diabetic adults, both in the short term and in the long-term. This suggests that in T2D elderly, cognitive activity in general may have long-term benefits for cognition. The lack of effect on disease management is consistent with prior investigations where no transfer of skills to other domains have been found. Evaluation of secondary outcomes, including specific cognitive domains and self-efficacy, is underway.

EFFECTS OF ENDURANCE-STRENGTH TRAINING ON MOTOR FUNCTIONS, COGNITION AND GLUCOSE METABOLISM IN PATIENTS WITH PARKINSON'S DISEASE

P2-021 EFFECTS OF ENDURANCE-STRENGTH TRAINING ON MOTOR FUNCTIONS, COGNITION AND GLUCOSE METABOLISM IN PATIENTS WITH PARKINSON’S DISEASE Jozef Ukropec, Patrik Krumpolec, Lucia Slobodova, Veronika Tirpakova, Matej Vajda, Eva Heckova, Rouyun Ma, Radka Klepochova, Igor Straka, Silvia Vallova, Stanislav Sutovsky, Zuzana Kosutzka, Chia-Liang Tsai, Ming-Chyi Pai, Peter Turcani, Ulrike Dydak, Wolfgang Bogner, Martin Krssak, Peter Valkovic, Milan Sedliak, Barbara Ukropcova, Institute of Experimental Endocrinology Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia; Institute of Experimental Endocrinology, Biomedical Research Center, SAS, Bratislava, Slovakia; Faculty of Medicine, Comenius University, Bratislava, Slovakia; Slovak Medical University, Institute of Sports Medicine, Bratislava, Slovakia; Faculty of Physical Education and Sports, Comenius University, Bratislava, Slovakia; Internal Medicine III, Medical University of Vienna, Vienna, Austria; School of Health Sciences, Purdue University, West Lafayette, IN, USA; Medical University Vienna, Vienna, Austria; Faculty of Medicine, Comenius University & University Hospital Bratislava, Bratislava, Slovakia; Institute of Physical Education, Health and Leisure Studies, National Cheng Kung University, Tainan, Taiwan; National Cheng Kung University Hospital, Tainan, Taiwan; School of Health Sciences, Purdue University, West Lafayette, IN, USA; Medical University of Vienna, Vienna, Austria; Institute of Experimental Endocrinology, Biomedical Research Center, SAS, Bratislava, Slovakia. Contact e-mail: jozef.ukropec@savba.sk

EFFECTS OF AEROBIC-STRENGTH TRAINING ON SELECTED MOLECULAR TARGETS IN CEREBROSPINAL FLUID OF SENIORS WITH MILD COGNITIVE IMPAIRMENT

Background:Cerebrospinal fluid (CSF) levels of total tau protein (hTau), phosphorylated tau (pTau181P), and amyloid-beta of 42 amino acids (Ab1-42) are established biomarkers for the diagnosis of Alzheimer’s disease (AD), but the discriminatory power for differential dementia diagnosis remains suboptimal. Also, current laboratory measures of CSF pTau181P are thought to underestimate the total levels of phosphorylated tau. The goal of this study is to investigate if the non-phosphorylated tau fraction (pTau rel) would improve the diagnostic performance of the routine AD biomarker panel for differential dementia diagnosis. Methods:The study population consisted of clinically diagnosed AD patients (n1⁄445), definite frontotemporal lobar degeneration (FTLD) patients (n1⁄445), definite Creutzfeldt-Jakob disease (CJD) patients (n1⁄420) and cognitively healthy controls (n1⁄420). CSF levels of Ab1-42, hTau, pTau181P and pTau rel were determined with commercially available single-analyte ELISA kits (INNOTEST b-Amyloid(142), INNOTEST hTau-Ag and INNOTEST Phospho-Tau(181P) from Fujirebio Europe, Belgium; pTAU rel ELISA Kit from AJ Roboscreen, IBL International GmbH, Germany). Receiver operating characteristic (ROC) curve analyses were used to obtain area under the curve (AUC) values. AUC values were compared using DeLong tests. Results:Diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. To evaluate the diagnostic power of pTau rel in the routine AD biomarker panel, the single (routine) marker with the highest AUC value was compared with that of pTau rel. Additionally, the (routine) biomarker ratio with the highest AUC value was compared with its equivalent using pTau rel. An overview of the results is listed in Table 1. Conclusions: The diagnostic performance of pTau rel for differential dementia diagnosis (comparing AD, FTLD, CJD patients and healthy controls) is not better than the diagnostic performance of the routine AD CSF biomarkers.