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Purpose: Scarce information on the prevalence and characteristics of olfactory disfunction (OD) in type 2 diabetic (T2D) patients are available. The aims of this study were (1) to assess the olfactory function in T2D patients and to compare it with a control group of individuals without T2D, and (2) to evaluate the differences in OD within T2D patients according to the presence of diabetic complications., Methods: A group of 39 T2D patients and a control group of 39 healthy individuals were enrolled. Each subject underwent an evaluation of the olfactory performance using the Sniffing Olfactory Screening Test (SOST) and completed a questionnaire assessing the subjective perception of olfaction. According to the presence of diabetic complications, the group of T2D patients was divided into two subgroups. Non-parametric tests and regression analysis were used for statistical analysis., Results: No differences in the subjective perception of olfaction were demonstrated among T2D patients (with and without complications) and controls. A significant difference for the SOST score was demonstrated among the different groups. In particular, OD was more frequent in T2D patients than in controls. In addition, OD was far more frequent in T2D patients with complications. Regression analysis did not demonstrate any significant association between OD and clinical/demographic characteristics of T2D patients., Conclusion: T2D patients were more frequently affected by OD. The subgroup analysis suggested a possible relationship between OD and diabetic complications since patients with T2D diabetic complications demonstrated lower olfactory abilities than controls subjects and T2D patients without diabetic complications., (© 2021. The Author(s).)

Purpose: Aims of the present study were to investigate a wide array of psychological symptoms through validated psychometric tests, before and after 5 weeks of deep Transcranial Magnetic Stimulation (dTMS) in individuals with obesity, and to identify possible relationships with neuroendocrine parameters., Methods: Forty-five patients with obesity (33 F, 12 M; age 48.8 ± 9.9 years; body wt 97.6 ± 14.2 Kg; BMI 36.2 ± 4.2) were randomized into two groups: 26 received high frequency (HF) dTMS and 19 Sham stimulation for 5 weeks. At baseline and after the 5-week treatment, all patients underwent the following psychometric evaluations: Food Cravings Questionnaire-Trait (FCQ-T) and its subscales, Barratt Impulsiveness Scale-11 (BIS-11), State and Trait Anxiety Inventory (STAI-y1 and STAI-y2), and Beck Depression Inventory (BDI). Hormonal and neuroendocrine markers were assessed at the first and last dTMS session., Results: By adjusting for baseline variables and treatment arms, a significant decrease in body wt and BMI was found in HF group, both with univariate (p = 0.019) and multivariate analyses (p = 0.012). Impulsivity significantly decreased in HF group, both with univariate (p = 0.031) and multivariate analyses (p = 0.011). A positive association between the impulsivity score change and the leptin level variation (p = 0.031) was found., Conclusion: The decrease of impulsivity together with the BMI reduction in individuals with obesity, treated with real stimulation, suggests that impulsivity may be a risk factor for obesity. Treatment with dTMS revealed to be effective in reducing both BMI and impulsivity by enhancing inhibitory capacity of Pre-Frontal Cortex (PFC), and modulating neuroendocrine system, especially leptin., (© 2021. The Author(s).)

Purpose: In obesity, metabolic and voluntary factors regulate appetite, and a dysregulation of the reward pathway was demonstrated in all addiction disorders. Deep transcranial magnetic stimulation (dTMS) is already used to modulate cerebral dopamine activation in neuro-psychiatric diseases. We presently assess the acute effect of high frequency (HF) and low frequency (LF) dTMS on the modulation of the main neuropeptides and neurotransmitters involved in the reward pathway in obese subjects., Methods: This study was designed as a double-blind, sham-controlled, randomized clinical trial. Thirty-three obese patients (9 males, 24 females, age 48.1 ± 10.6, BMI 36.4 ± 4.7) were enrolled in the study. All patients were studied during a single dTMS session and blood aliquots were drawn before and after a single dTMS session. Metabolic and neuro-endocrine parameters were evaluated before and after: (1) 18 Hz dTMS (HF, 13 patients); (2) 1 Hz dTMS (LF, 10 patients); (3) Sham treatment (Sham, 10 patients)., Results: No statistically significant variations in metabolic parameters, systolic and diastolic blood pressure, and heart rate were shown acutely. HF showed a significant increase of β-endorphin compared to other groups (p = 0.048); a significant increase of ghrelin in LF (p = 0.041) was also demonstrated., Conclusions: A single session of HF dTMS treatment determines in obese subjects an acute increase of β-endorphin level, indicating an activation of the reward pathway. The present findings constitute proof of principle for a potential application of this methodology in obesity treatment.

Physical activity, together with diet and pharmacological therapy, represents one of the three cornerstones in type 2 diabetes mellitus treatment and care. The therapeutic appeal of regular physical activity stems from: (i) its non-pharmacological nature; (ii) its beneficial effects on the metabolic risk factors associated with diabetes complications; (iii) its low costs. Evidence accumulated in the last years suggests that aerobic training-endurance training-constitutes a safe modality of intervention, achievable, and effective in diabetes treatment, whenever it is not limited by comorbidities. Aerobic training exerts insulin-mimetic effects and has been shown to lower mortality risk too. Anaerobic, intense physical activity, such as that of strength or power sports disciplines, is not univocally recognized as safe and simple to realize, however, it is important in stimulating energy and glucose metabolism. According to recent evidence, high-intensity training may be prescribed even in the face of cardiovascular diseases, peripheral vascular disease, or osteoarthritis. Some studies have shown resistance training to be more efficient than aerobic exercise in improving glycemic control. This review explores the most up-to-date indications emerging from literature in support of the beneficial effects of strength stimulation and resistance training in patients with type 2 diabetes without complications.

An increase of visceral fat affects human bone health causing fragility, mechanical strength reduction, and increased propensity to fractures because of impaired bone matrix microstructure and aberrant bone cell function. Adult Danio rerio (zebrafish) represents a powerful model to study both metabolic diseases and bone metabolism. The aim of this study was to generate an obese adult zebrafish by high-fat diet and evaluate metabolic and bone tissue effects. Fish blood glucose and insulin levels were found to be altered in high-fat diet fish revealing a failure in β-cells insulin production. Blood analysis of adipokines revealed significant alterations in adiponectin and leptin levels that are common in human and other obesity animal models. Advanced glycation end products (AGEs), derived from hyperglycemia condition, were found to be altered too. All these alterations were associated with an impaired bone metabolism. The scales of high-fat diet fish shown bone resorption lacunae associated with an intense osteoclastic tartrate-resistant acid phosphatase (TRAP) activity, whereas alkaline phosphatase (ALP) decreased. These data suggest that an imbalance of fat metabolism alters energy metabolism generating an osteoporosis-like phenotype in adult zebrafish scales. The zebrafish obesity model can contribute to elucidate in vivo the molecular mechanisms of metabolic changes in human obese patients.

Purpose: Bone marrow fat is a functionally distinct adipose tissue that may contribute to systemic metabolism. This study aimed at evaluating a possible association between bone marrow fat and insulin sensitivity indices., Methods: Fifty obese (n = 23) and non-obese (n = 27) premenopausal women underwent proton magnetic resonance spectroscopy to measure vertebral bone marrow fat content and unsaturation index at L4 level. Abdominal visceral, subcutaneous fat, and epicardial fat were also measured using magnetic resonance imaging. Bone mineral density was measured by dual-energy X-ray absorptiometry. Body composition was assessed by bioelectrical impedance analysis. Fasting serum glucose, insulin, lipids, adiponectin were measured; the insulin resistance index HOMA (HOMA-IR) was calculated., Results: Bone marrow fat content and unsaturation index were similar in obese and non-obese women (38.5 ± 0.1 vs. 38.6 ± 0.1%, p = 0.994; 0.162 ± 0.065 vs. 0.175 ± 0.048, p = 0.473, respectively). Bone marrow fat content negatively correlated with insulin and HOMA-IR (r = -0.342, r = -0.352, respectively, p = 0.01) and positively with high density lipoprotein cholesterol (r = 0.270, p = 0.043). From a multivariate regression model including lnHOMA-IR as a dependent variable and visceral, subcutaneous, epicardial fat, and bone marrow fat as independent variables, lnHOMA-IR was significantly associated with bone marrow fat (β = -0.008 ± 0.004, p = 0.04) and subcutaneous fat (β = 0.003 ± 0.001, p = 0.04). Bone marrow fat, among the other adipose depots, was a significant predictor of circulating adiponectin (β = 0.147 ± 0.060, p = 0.021). Bone marrow fat unsaturation index negatively correlated with visceral fat (r = -0.316, p = 0.026)., Conclusions: There is a relationship between bone marrow fat content and insulin sensitivity in obese and non-obese premenopausal women, possibly mediated by adiponectin secretion. Visceral fat does not seem to regulate bone marrow fat content while it may affect bone marrow fat composition.

Purpose: The purpose of this study is to investigate Ranolazine action on skeletal muscle differentiation and mitochondrial oxidative phenomena. Ranolazine, an antianginal drug, which acts blocking the late INaL current, was shown to lower hemoglobin A1c in patients with diabetes. In the present study, we hypothesized an action of Ranolazine on skeletal muscle cells regeneration and oxidative process, leading to a reduction of insulin resistance., Methods: 10 μM Ranolazine was added to C2C12 murine myoblastic cells during proliferation, differentiation and newly formed myotubes., Results: Ranolazine promoted the development of a specific myogenic phenotype: increasing the expression of myogenic regulator factors and inhibiting cell cycle progression factor (p21). Ranolazine stimulated calcium signaling (calmodulin-dependent kinases) and reduced reactive oxygen species levels. Furthermore, Ranolazine maintained mitochondrial homeostasis. During the differentiation phase, Ranolazine promoted myotubes formation. Ranolazine did not modify kinases involved in skeletal muscle differentiation and glucose uptake (extracellular signal-regulated kinases 1/2 and AKT pathways), but activated calcium signaling pathways. During proliferation, Ranolazine did not modify the number of mitochondria while decreasing osteopontin protein levels. Lastly, neo-formed myotubes treated with Ranolazine showed typical hypertrophic phenotype., Conclusion: In conclusion, our results indicate that Ranolazine stimulates myogenesis and reduces a pro-oxidant inflammation/oxidative condition, activating a calcium signaling pathway. These newly described mechanisms may partially explain the glucose lowering effect of the drug.

Skeletal muscle regeneration and hypertrophy are important adaptive responses to both physical activity and pathological stimuli. This research was performed to investigate DNA demethylation action on the late phase of muscle differentiation and early stage of hypertrophy. The epigenetic process involved in myogenesis was studied with the DNA-demethylating agent 5-azacytidine (AZA). We induced muscle differentiation in C2C12 mouse myoblasts in the presence of 5 μM AZA and growth or differentiation medium for 48, 72, and 96 h. To study a potential AZA hypertrophic effect, we stimulated 72 h differentiated myotubes with AZA for 24 h. Unstimulated cells were used as control. By western blot and immunofluorescence analysis, we examined AZA action on myogenic regulatory factors expression, hypertrophic signaling pathway and myotube morphology. During differentiation, protein levels of myogenic markers, Myf6 and Myosin Heavy Chain (MyHC), were higher in AZA stimulated cells compared to control. Myostatin and p21 analysis revealed morphological changes which reflect a tendency to hypertrophy in myotubes. In AZA stimulated neo formed myotubes, we observed that IGF-I pathway, kinases p70 S6, 4E-BP1, and ERK1/2 were activated. Furthermore, AZA treatment increased MyHC protein content in stimulated neo myotubes. Our work demonstrates that DNA demethylation could plays an important role in promoting the late phase of myogenesis, activating endocellular pathways involved in protein increment and stimulating the hypertrophic process.