Objective
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.
Methods
In a double‐blind randomized pilot trial in nondiabetic individuals with overweight and obesity (age 43 ± 8 years; body mass index 31 ± 4 kg/m2), 15 individuals were randomly assigned to 2 g carnosine daily and 15 individuals to placebo for 12 weeks. Insulin sensitivity and secretion, glucose tolerance (oral glucose tolerance test), blood pressure, plasma lipid profile, skeletal muscle (1H‐MRS), and urinary carnosine levels were measured.
Results
Carnosine concentrations increased in urine after supplementation (P < 0.05). An increase in fasting insulin and insulin resistance was hampered in individuals receiving carnosine compared to placebo, and this remained significant after adjustment for age, sex, and change in body weight (P = 0.02, P = 0.04, respectively). Two‐hour glucose and insulin were both lower after carnosine supplementation compared to placebo in individuals with impaired glucose tolerance (P < 0.05).
Conclusions
These pilot intervention data suggest that carnosine supplementation may be an effective strategy for prevention of type 2 diabetes.
Context:
Heterozygous inactivating mutations of the calcium-sensing receptor (CaSR) gene cause alterations in calcium metabolism familial hypocalciuric hypercalcemia (FHH). In addition, ...calcium-sensing receptor is expressed in the myocardium and endocrine cells including pancreatic islets, enteroendocrine cells, and adipose tissue.
Objective:
To discern whether FHH is associated with cardiometabolic alterations of clinical significance, endocrine responses to systemic calcium stimulation and oral glucose tolerance tests were performed. Ectopic lipid deposition and heart function were assessed using magnetic resonance spectroscopy/imaging.
Participants:
Eight FHH patients and nine controls matched for anthropometric characteristics (age 45 ± 18 y; body mass index 29 ± 4 vs 29 ± 6 kg/m2) were studied to determine cardiac function, ectopic and visceral lipid content, and insulin sensitivity and secretion.
Results:
Insulin sensitivity (clamp-like index: 4.5 ± 0.6 vs 4.3 ± 0.4 mg/kg · min), basal (insulin secretion rate: 266 ± 33 vs 218 ± 25 pmol/min), and glucose-stimulated β-cell function (adaptation index: 180.2 ± 12.2 vs 176.2 ± 17.4) as well as calcium-stimulated insulin secretion were comparable between FHH and controls, respectively. Ectopic lipid content in liver 3.75% (1.4%; 34%) vs 4.18% (0.9%; 28%), soleus muscle (1.07% ± 0.38% vs 1.02% ± 0.56 %), and myocardium (0.39% ± 0.3% vs 0.32% ± 0.1 %), visceral and sc adipose tissue distribution (0.51 ± 0.16 vs 0.47 ± 0.17) as well as heart function (ejection fraction: 71.5% ± 8% vs 72.8% ± 8 %; E to A ratio: 1.4% ± 0.6% vs 1.3% ± 0.7%) were not different between the groups.
Conclusion:
Despite comprehensive cardiometabolic phenotyping, no alterations in myocardial function, lipid distribution, or glucose metabolism were observed in FHH. Thus, FHH might reflect a laboratory finding without any relevant cardiometabolic alterations.
To date, no direct scientific evidence has been found linking tissue changes in multiple sclerosis (MS) patients, such as demyelination, axonal destruction or gliosis, with either steady progression ...and/or stepwise accumulation of focal CNS lesions. Tissue changes such as reduction of the retinal nerve fiber layer (RNFL) and the total macular volume (TMV), or brain- and spinal cord atrophy indicates an irreversible stage of tissue destruction. Whether these changes are found in all MS patients, and if there is a correlation with clinical disease state, remains controversial. The objective of our study was to determine, whether there was any correlation between the RNFL or TMV of patients with MS, and: (1) the lesion load along the visual pathways, (2) the ratios and absolute concentrations of metabolites in the normal-appearing white matter (NAWM), (3) standard brain atrophy indices, (4) disease activity or (5) disease duration.
28 MS patients (RRMS, n = 23; secondary progressive MS (SPMS), n = 5) with moderately-high disease activity or long disease course were included in the study. We utilised: (1) magnetic resonance imaging (MRI) and (2) -spectroscopy (MRS), both operating at 3 Tesla, and (3) high-resolution spectral domain-OCT with locked reference images and eye tracking mode) to undertake the study.
There was no consistency in the pattern of CNS metabolites, brain atrophy indices and the RNFL/TMV between individuals, which ranged from normal to markedly-reduced levels. Furthermore, there was no strict correlation between CNS metabolites, lesions along the visual pathways, atrophy indices, RNFL, TMV, disease duration or disability.
Based on the findings of this study, we recommend that the concept of 'clinico-radiologico paradox' in multiple sclerosis be extended to CROP-'clinico-radiologico-ophthalmological paradox'. Furthermore, OCT data of MS patients should be interpreted with caution.
Abstract Phosphorous (31 P) magnetization transfer (MT) experiments enable the non-invasive investigation of human muscle metabolism in various physiological and pathological conditions. The purpose ...of our study was to investigate the feasibility of time-resolved MT, and to compare the results of MT experiments at 3 T and 7 T. Six healthy volunteers were examined on a 3 T and a 7 T MR scanner using the same setup and identical measurement protocols. In the calf muscle of all volunteers, four separate MT experiments (each ∼10 min duration) were performed in one session. The forward rate constant of the ATP synthesis reaction ( kATP ) and creatine kinase reaction ( kCK ), as well as corresponding metabolic fluxes ( FATP , FCK ), were estimated. A comparison of these exchange parameters, apparent T1 s, data quality, quantification precision, and reproducibility was performed. The data quality and reproducibility of the same MT experiments at 7 T was significantly higher (i.e., kATP 2.7 times higher and kCK 3.4 times higher) than at 3 T ( p < 0.05). The values for kATP ( p = 0.35) and kCK ( p = 0.09) at both field strengths were indistinguishable. Even a single MT experiment at 7 T provided better data quality than did a 4 times-longer MT experiment at 3 T. The minimal time-resolution to reliably quantify both FATP and FCK at 7 T was ∼6 min. Our results show that MT experiments at 7 T can be at least 4 times faster than 3 T MT experiments and still provide significantly better quantification. This enables time-resolved MT experiments for the observation of slow metabolic changes in the human calf muscle at 7 T.
Abstract Chronic cerebral hypoperfusion and aging can be related to vascular dementia manifested by the decline in cognitive abilities and memory impairment. The identification of specific biomarkers ...of vascular disorder in early stages is important for the development of neuroprotective agents. In the present study, a three-vessel occlusion (3-VO) rat model of vascular dementia in the middle-aged rat brain was used to investigate the effect of global cerebral hypoperfusion. A multimodal study was performed using magnetic resonance spectroscopy, MR-microimaging, histology and behavioral tests. Our measurements showed a signal alteration in T2-weighted MR images, the elevation of T2 relaxation times and histologically proven neural cell death in the hippocampal area, as well as mild changes in concentration of proton and phosphorus metabolites. These changes were accompanied by mild behavioral alterations in the open field and slightly decreased habituation. The analysis of the effects of vascular pathology on cognitive functions and neurodegeneration can contribute to the development of new treatment strategies for early stages of neurodegeneration.
Objective. The objective of the present study is to investigate the relationship of cardiac fat depots with disturbances of the carbohydrate metabolism in women with PCOS. Methods. An oral glucose ...tolerance test (OGTT) was realized, and metabolic parameters were collected in 48 women with PCOS and in 20 controls. Intramyocardial fat (MYCL) and pericardial fat (PERI) were measured using 1H-magnetic resonance spectroscopy and imaging. Results. Only in PCOS women, PERI was positively and independently related to parameters of glucose metabolism (HbA1c: p=0.001, fasting plasma glucose: p<0.001, stimulated glucose at 30 and 60 minutes in the OGTT). Thus, the disposition index, insulin sensitivity, and adiponectin also declined with the increase of PERI in women with PCOS; however, these results were not independent of BMI and age. In addition, PERI was positively related to atherogenic lipid profiles, BMI, waist circumference, CRP, and liver fat in women with PCOS. A negative relation of PERI with triglycerides and a positive relation with BMI and waist circumference could be observed in the controls. No relationship of MYCL with diabetes-specific parameters could be found in the study population. Conclusion. PERI is related to metabolic disturbances in women with PCOS, but not in metabolically healthy lean subjects. This clinical trial was registered at ClinicalTrials.gov and has the registration number NCT03204461.
PDF
