[Show abstract][Hide abstract] ABSTRACT: The nonobese diabetic (NOD) mouse represents a well-established experimental model analogous to human type 1 diabetes mellitus (T1D) as it is characterized by progressive autoimmune destruction of pancreatic
-cells. Experiments were designed to investigate the impact of moderate-intensity training on T1D immunomodulation and inflammation. Under a chronic exercise regime, NOD mice were trained on a treadmill for 12 weeks (12 m/min for 30 min, 5 d/wk) while age-matched, control animals were left untrained. Prior to and upon completion of the training period, fed plasma glucose and immunological soluble factors were monitored. Both groups showed deteriorated glycemic profiles throughout the study although trained mice tended to be more compensated than controls after 10 weeks of training. An exercise-induced weight loss was detected in the trained mice with respect to the controls from week 6. After 12 weeks, IL-6 and MIP-1
were decreased in the trained animals compared to their baseline values and versus controls, although not significantly. Morphometric analysis of pancreata revealed the presence of larger infiltrates along with decreased
-cells areas in the control mice compared to trained mice. Exercise may exert positive immunomodulation of systemic functions with respect to both T1D and inflammation, but only in a stringent therapeutic window.
Journal of Diabetes Research 09/2015; 2015(5):737586. DOI:10.1155/2015/737586 · 2.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diabetes mellitus is a metabolic disease possible to treat via several different therapeutic approaches. Since the advent of insulin in 1922, type 1 diabetes mellitus has become a chronic treatable disease. Nonetheless, type 1 diabetes mellitus can be a devastating disease when the macro- and microangiopathic complications take place after several years of illness. Starting from the eighties, pancreas/islet transplantation has become a potential innovative treatment of diabetes mellitus. The major advantage of pancreas/islet transplantation is the restoration of c-peptide cosecretion along with insulin; the major disadvantage is the need to administer immunosuppressive drugs which are diabetogenic themselves. Islet transplantation is the progenitor of more recent forms of cellular and stem cell therapies which will be reviewed herein. Cellular therapies for diabetes mellitus are still an experimental procedure. Herein we present the actual current achievements and an outlook of close future possible advancements in the area of cellular transplantation for the cure of diabetes mellitus.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess the exercise intensity during a ski marathon race by monitoring the heart rate (HR) of a well-trained male amateur skier taking part in La Sgambeda 2012 (42 km long). The race consisted of a preliminary short lap of 3.5 km and two almost identical laps of 19 and 19.5 km, respectively. The subject’s resting and maximal heart rates (HRrest and HRmax) were 60 and 180 beats/min, respectively. During the race, HR and altitude were recorded every 1 s using a HR monitor with GPS system. To describe the exercise intensity profile, three reference HRs were selected. The reference HRs were calculated from the “Karvonen formula” by multiplying the HR reserve (HRR; HRR = HRmax−HRrest) by the factors 0.5, 0.7, 0.9 and adding these values to HRrest. The HR profile was classified into four levels of exercise intensity. The skier performed the race in 1 h 55 min 40 s, with an HRmean of 160 beats/min (89 % of HRmax and 83 % of HRR). Nearly the entire race (96.6 %) was perform
Sport Sciences for Health 01/2014; 11(1):1-4. DOI:10.1007/s11332-014-0187-8
[Show abstract][Hide abstract] ABSTRACT: THERE IS AN INCREASING INTEREST IN DEVELOPING LOW-INTENSITY RESISTANCE TRAINING METHODS TO REDUCE BOTH THE MECHANICAL STRESS ON JOINTS IN INDIVIDUALS FROM DIFFERENT AGE GROUPS AND THE RISK OF INJURIES IN ATHLETES. BLOOD FLOW RESTRICTION RESISTANCE TRAINING (BFRRT) HAS BEEN SHOWN TO BE AN EFFECTIVE METHOD FOR IMPROVING MUSCULAR FUNCTION, USING LOW AND MODERATE LOAD INTENSITY. THEREFORE, THE PURPOSE OF THE PRESENT ARTICLE IS TO HIGHLIGHT THE MAIN METABOLIC AND NEUROMUSCULAR ADAPTATIONS TO BFRRT AND TO SUGGEST AN ALTERNATIVE IMPLEMENTATION OF BFRRT THROUGH THE MODULATION OF THE VELOCITY OF THE MUSCLE CONTRACTION.
[Show abstract][Hide abstract] ABSTRACT: Heat dissipation during sport exercise is an important physiological mechanism that may influence athletic performance. Our aim was to test the hypothesis that differences exist in the dynamics of exercise-associated skin temperature changes between trained and untrained subjects. We investigated thermoregulation of a local muscle area (muscle-tendon unit) involved in a localized steady-load exercise (standing heels raise) using infrared thermography. Seven trained female subjects and seven untrained female controls were studied. Each subject performed standing heels raise exercise for 2 min. Thermal images were recorded prior to exercise (1 min), during exercise (2 min), and after exercise (7 min). The analysis of thermal images provided the skin temperature time course, which was characterized by a set of descriptive parameters. Two-way ANOVA for repeated measures detected a significant interaction (p = 0.03) between group and time, thus indicating that athletic subjects increased their skin temperature differently with respect to untrained subjects. This was confirmed by comparing the parameters describing the speed of rise of skin temperature. It was found that trained subjects responded to exercise more quickly than untrained controls (p < 0.05). In conclusion, physical training improves the ability to rapidly elevate skin temperature in response to a localized exercise in female subjects.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Several studies report martial arts as a good model for investigating neuroendocrine responses to competitive fighting. However, little is known on the metabolic responses elicited by elite athletes during fighting. In particular, the metabolic picture in elite athletes of martial arts is little known. AIM: In the present study, our aim was to investigate the acute effects of a session of karate practice on the glucose-insulin system. SUBJECTS AND METHODS: Ten healthy individuals (6M/4F; BMI: 22.1 ± 0.7 kg/m(2); 21.9 ± 1.1 years, mean ± SE) who practice karate in national or international competitions were enrolled. All participants completed two experimental trials in a randomised-crossover fashion. A basal blood sample was collected from each athlete to assess plasma glucose, insulin, cortisol, testosterone and catecholamines, before karate training session. In two separate days, another blood sample was collected from each participants after 3 min of real fighting (kumite) and 3 min of ritualized simulation of combat (kata). RESULTS: In both trials, plasma glucose resulted to be higher at the end the of performance compared to the basal (p < 0.001 after kumite and p < 0.02 after kata). In contrast, insulin was similar in the basal and after physical activity in the two trials. Catecholamines were higher after kata and kumite sessions with respect to the basal values (p < 0.04) and, in particular, epinephrine post-kumite values were much greater than those measured after kata. CONCLUSIONS: Our results indicate that unlike performances of karate (kumite and kata) elicit different plasma glucose increases. In particular, we found that glucose and epinephrine concentrations increased more after kumite than after kata.
Sport Sciences for Health 12/2012; 8(2-3):81-85. DOI:10.1007/s11332-012-0132-7
[Show abstract][Hide abstract] ABSTRACT: Adult growth hormone deficiency (GHD) has detrimental effects on metabolic profile, leading to an increased cardiovascular mortality and morbidity. Above all, disturbance in postprandial triglyceride metabolism is of major concern because of the crucial role of triglyceride-rich lipoproteins in atherogenesis. The majority of previous studies on GH replacement have shown favourable changes in the fasting lipid profile. Aim of this study is to investigate whether this beneficial effect is exerted also on postprandial triglyceride (TG) metabolism.
We challenged nine GHD patients with a standardized fat loading meal at baseline and after 6 months of GH replacement therapy. Nine healthy control subjects were similarly tested under baseline conditions. Blood samples were obtained before and up to 8 h after fat loading for serum lipid analysis.
We found that GHD patients with fasting TG level in the normal range (1·29 ± 0·31 mm) had a delayed postprandial TG clearance compared to healthy controls (triglyceride level at 8 h, 3·82 ± 0·83 vs 1 ± 0·06 mm P < 0·01), and the postprandial hypertriglyceridaemia was not corrected by 6 months of GH therapy.
This study has shown for the first time that GHD adult patients have a higher postprandial triglyceridaemia compared to healthy controls when challenged by a standardized fat load and that this atherogenic feature is not normalized by short-term GH treatment despite a decrease in visceral fat mass described during the replacement therapy.
[Show abstract][Hide abstract] ABSTRACT: Several simple measures of graft function after islet transplantation have been proposed but a comparative evaluation is lacking. Here, we compared the performance of five indices of β-cell function: β-score, transplant estimated function (TEF), homeostasis model assessment (HOMA) 2-B%, C-peptide/glucose ratio, and Secretory Units of Islets in Transplantation (SUIT).
Two cohorts of transplanted patients were analyzed. Cohort 1 consisted of 14 recipients with type 1 diabetes of islet transplantation whereas cohort 2 consisted of 21 recipients with type 1 diabetes of cultured islet cell graft. The five surrogate indices were compared against the first- and second-phase insulin response to arginine in cohort 1, and against the C-peptide response to a hyperglycemic clamp in cohort 2.
We found that the performances of the five surrogate indices were close one to each other in cohort 1. The correlation coefficients ranged 0.62 to 0.67 and 0.62 to 0.68 against the first- and second-phase insulin response to arginine, respectively. In cohort 2, we found that the β-score, TEF, C-peptide/glucose ratio, and SUIT were reasonably well correlated with the clamp response (correlation coefficients were in the range 0.71-0.81), whereas HOMA2-B% showed a modest performance (r=0.54). HOMA2-B% could not be evaluated in one patient whose fasting glucose concentration level was below the lower bound indicated by the HOMA calculator (3 mmol/L). SUIT could not be evaluated in three patients whose fasting glucose concentration was below the glucose threshold of the SUIT formula (3.43 mmol/L).
In summary, no single index outperformed the others. Nevertheless, when the benefit to cost ratio is considered, TEF stands out for its good performance at a very low cost.
[Show abstract][Hide abstract] ABSTRACT: Physical exercise induces adaptive changes leading to a muscle phenotype with enhanced performance. We first investigated whether genetic polymorphisms altering enzymes involved in DNA methylation, probably responsible of DNA methylation deficiency, are present in athletes' DNA. We determined the polymorphic variants C667T/A1298C of 5,10-methylenetetrahydrofolate reductase (MTHFR), A2756G of methionine synthase (MTR), A66G of methionine synthase reductase (MTRR), G742A of betaine:homocysteine methyltransferase (BHMT), and 68-bp ins of cystathionine β-synthase (CBS) genes in 77 athletes and 54 control subjects. The frequency of MTHFR (AC), MTR (AG), and MTRR (AG) heterozygous genotypes was found statistically different in the athletes compared with the control group (P=0.0001, P=0.018, and P=0.0001), suggesting a reduced DNA methylating capacity. We therefore assessed whether DNA hypomethylation might increase the expression of myogenic proteins expressed during early (Myf-5 and MyoD), intermediate (Myf-6), and late-phase (MHC) of myogenesis in a cellular model of hypomethylated or unhypomethylated C2C12 myoblasts. Myogenic proteins are largely induced in hypomethylated cells [fold change (FC)=Myf-5: 1.21, 1.35; MyoD: 0.9, 1.47; Myf-6: 1.39, 1.66; MHC: 1.35, 3.10 in GMA, DMA, respectively] compared with the control groups (FC=Myf-5: 1.0, 1.38; MyoD: 1.0, 1.14; Myf-6: 1.0, 1.44; MHC: 1.0, 2.20 in GM, DM, respectively). Diameters and length of hypomethylated myotubes were greater then their respective controls. Our findings suggest that DNA hypomethylation due to lesser efficiency of polymorphic MTHFR, MS, and MSR enzymes induces the activation of factors determining proliferation and differentiation of myoblasts promoting muscle growth and increase of muscle mass.
[Show abstract][Hide abstract] ABSTRACT: The last decade has seen much debate on ghrelin as a potential target for treating obesity. Despite a close connection between snack food intake and obesity, snacking is controversially reviewed as a good habit in a healthy nutritional regimen. The aim of the study was to evaluate whether a different nutrient composition influences postprandial ghrelin levels and glucose increments induced by 6 isoglucidic snack food. 20 healthy individuals (10 M/10 F; BMI 23.1 ± 0.5; age 33 ± 0.67 years, mean and SE) from H San Raffaele Scientific Institute and Milan University were enrolled. The subjects underwent OGTT (50 g) and 6 isoglucidic test-meal loads to assess the ghrelin circulating levels and the area under glycemic curves induced by 6 commercial snacks. 3 h after hazelnut chocolate intake, ghrelin was significantly lower than with wafer chocolate intake (p<0.002). As a response to all snacks, the glycemic curves were not different even though hazelnut chocolate showed the lowest glycemic curve. Moreover, snack fat content was found to be inversely correlated to 3-h plasma ghrelin levels (p<0.0001; R (2)=0.77) and positively associated with satiety scores (p<0.02; R (2)=0.28). Also energy load was inversely correlated to 3-h plasma ghrelin (p<0.0001; R (2)=0.73). Our results indicate that snack food administered in equivalent glucidic loads elicits postprandial ghrelin suppression and satiety ratings in different ways. Further studies are needed to elucidate the role of ghrelin as hunger-hormone in the regulation of energy balance.
Hormone and Metabolic Research 02/2011; 43(2):135-40. DOI:10.1055/s-0030-1269900 · 2.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Regular physical exercise exerts positive effects, prolonging survival and improving quality of life of HIV-1-infected patients.
A 3-month supervised endurance training program in subjects with AIDS-related lipodystrophy and type 2 diabetes mellitus improved
aerobic capacity, pancreatic beta-cell function and immune profile, with a reduction in the proinflammatory cytokines monocyte
chemotactic protein-1 and tumor necrosis factor-alpha. Appropriate physical exercise combined with specific pharmacological
and dietetic therapies could prevent the development of secondary metabolic and cardiovascular disorders.
Key wordsHIV-lipodistrophy-Insulin sensitivity-Exercise training-Inflammation
Sport Sciences for Health 08/2010; 6(1):23-26. DOI:10.1007/s11332-010-0092-8
[Show abstract][Hide abstract] ABSTRACT: Il termine omeostasi — coniato intorno al 1930 dal fisiologo americano Walter Bradford Cannon e divulgato nel suo libro The Wisdom of the Body — designa l’attitudine degli esseri viventi a mantenere entro ristretti margini di variazione i valori di grandezze fisiologiche
(ad esempio, la temperatura, l’equilibrio acido-base, la glicemia). Cannon sviluppò il concetto di omeostasi partendo dall’idea
di Claude Bernard del milieu interieur, ossia di un ambiente interno all’organismo la cui costanza è essenziale per il mantenimento della vita. Attorno al 1935, Rudolph Schoenheimer affinò questa intuizione dal punto di vista teorico formulando il concetto di stato dinamico dei costituenti corporei. L’idea portante è che la concentrazione di una sostanza nell’organismo è funzione di tre processi che avvengono in esso
simultaneamente: produzione, distribuzione, utilizzazione. Il continuo rinnovamento dei livelli circolanti della sostanza
nell’organismo è chiamato turnover. Schoenheimer fu un pioniere nell’uso di isotopi radioattivi e stabili per studiare il
turnover di proteine e lipidi nell’animale ed esercitò una straordinaria influenza sulle successive generazioni di biochimici.
[Show abstract][Hide abstract] ABSTRACT: The use of pediatric donors can increase the number of donors available for pancreas transplantation.
The aim of this study was to verify if pancreas transplantation from pediatric donors is as effective as transplantation from adult donors to restore metabolic control in type 1 diabetic patients.
From 2000 to April 2009 we performed 17 pancreas transplantations from pediatric donors: 9 simultaneous kidney-pancreas (SPK), 6 pancreas transplantation alone (PTA), and 2 pancreas after kidney (PAK). All subjects received whole organs with enteric diversion of exocrine secretions; 11 underwent systemic and 6 underwent portal venous graft drainage. The immunosuppressive therapy was as follows: prednisone, mycophenolate mofetil, anti-thymocyte globulin (ATG), and cyclosporine or tacrolimus. The pediatric donor population had a mean age of 15.3 years (range, 12-17), a mean weight of 60.1 kg (range, 42-75), and a mean body mass index (BMI) of 21 (range, 17.9-23.4).
After 9 years the overall patient survival rate was 94.12%, whereas the graft survival rate was 63.35%. Normal glucose and insulin levels were maintained either fasting or during oral glucose tolerance test (OGTT). The group of recipients of pediatric organs was compared with patients receiving organs from adult donors (n = 125); the mean glucose values were lower in the pediatric group, whereas insulin production was higher in the adult patients. Early venous thrombosis was 17.6% in the pediatric group and 20% in adult recipients (Fisher exact test, P = not significant [NS]).
Pediatric donors restored insulin independence in adult diabetic recipients, representing a valid source of organs for pancreas transplantation.
[Show abstract][Hide abstract] ABSTRACT: The classical minimal model (MM) index of insulin sensitivity, S(I), does not account for how fast or slow insulin action takes place. In a recent work, we proposed a new dynamic insulin sensitivity index, S(I)(D), which is able to take into account the dynamics of insulin action as well. The new index is a function of two MM parameters, namely S(I) and p(2), the latter parameter governing the speed of rise and decay of insulin action. We have previously shown that in normal glucose tolerant subjects S(I)(D) provides a more comprehensive picture of insulin action on glucose metabolism than S(I). The aim of this study is to show that resorting to S(I)(D) rather S(I) is even more appropriate when studying diabetic patients who have a low and slow insulin action. We analyzed insulin-modified intravenous glucose tolerance test studies performed in 10 diabetic subjects and mixed meal glucose tolerance test studies exploiting the triple tracer technique in 14 diabetic subjects. We derived both S(I) and S(I)(D) resorting to Bayesian and Fisherian identification strategies. The results show that S(I)(D) is estimated more precisely than S(I) when using the Bayesian approach. In addition, the less labor-intensive Fisherian approach can still be used to obtain reliable point estimates of S(I)(D) but not of S(I). These results suggest that S(I)(D) yields a comprehensive, precise, and cost-effective assessment of insulin sensitivity in subjects with impaired insulin action like impaired glucose tolerant subjects or diabetic patients.
[Show abstract][Hide abstract] ABSTRACT: Studies have pointed to insulin resistance as a pathogenic factor in fatty liver. Although pancreatic B-cell function is believed to be involved, its role is unclear. This study was undertaken to test whether fasting C-peptide, an index of fasting B-cell function, was related to intra-hepatic fat (IHF) content in non-diabetic humans.
We assessed, retrospectively, fasting plasma C-peptide concentration in 31 patients with fatty liver and 62 individuals without fatty liver. The IHF content was measured by proton magnetic resonance spectroscopy ((1)H-MRS), while insulin sensitivity was estimated based on fasting plasma glucose and insulin with the homestasis model assessment (HOMA) 2 method.
Age, sex and body mass index (BMI) were not different between groups. Patients with fatty liver had higher fasting insulin (P < 0.01), C-peptide (P < 0.005) and lower insulin sensitivity (HOMA2-%S). Fasting insulin alone explained 14% of the IHF content variability (P < 0.001); inclusion of fasting C-peptide in multivariate regression explained up to 32% (P < 0.001). A subgroup analysis was performed by matching 1 : 1 for HOMA2-%S. These data were analysed by conditional logistic regression which showed that, when HOMA2-%S was matched between groups, fasting C-peptide remained the only significant predictor of fatty liver.
Non-diabetic individuals with fatty liver are characterized by increased fasting plasma C-peptide concentration, irrespective of their insulin resistant state.
Diabetic Medicine 09/2009; 26(9):847-54. DOI:10.1111/j.1464-5491.2009.02785.x · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Clinical studies on the effect of growth hormone (GH) on thyroid function in patients with GH deficiency are contradictory. Further, the majority of published observations are limited to the first 6-12 months of GH replacement therapy. The aim of our study was to estimate the incidence of clinically relevant hypothyroidism in a cohort of patients with adult GH deficiency (AGHD) during long-term therapy with recombinant human GH (rhGH).
The study was designed as a retrospective collection of data on thyroid function in 49 AGHD patients of whom 44 (90%) had multiple hormone deficiency. Thirty-seven patients (76%) were on stable levothyroxine (LT4) replacement therapy (HYPO), and 12 (24%) were euthyroid (EUT). Therapy with rhGH was started at a dose of 3.5 microg/kg body weight and adjusted according to insulin-like growth factor-I (IGF-I) levels. At baseline, 6 months, 12 months, and yearly thereafter we measured free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone, and IGF-I. Study outcome was fT4 level below the normal range (9 pmol/L), irrespectively of fT3 or thyroid-stimulating hormone levels.
During a follow-up of 115 patient-years, mean fT4 level decreased significantly, although remaining within the normal range (p = 0.0242; month 48 vs. baseline). The largest decrease was between baseline and month 6, when fT4 decreased of 1.43 pmol/L (95% confidence interval, 0.33-2.53) per 1 unit (microg/kg body weight) increase in rhGH dose. The incidence of hypothyroidism was 1.2 (HYPO group) and 6.7 (EUT group) events per 100 patient-years.
We confirm that in patients with AGHD, rhGH therapy is associated with a small, although significant, decrement of fT4 in the first 6 months of replacement therapy. However, the incidence of hypothyroidism is low. Monitoring of thyroid function during rhGH therapy is advisable, particularly in the first year of therapy when the largest decrease in fT4 occurs.
Thyroid: official journal of the American Thyroid Association 12/2008; 18(12):1249-54. DOI:10.1089/thy.2008.0266 · 4.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In obese patients, the diet-induced weight loss markedly improves glucose tolerance with an increase in insulin sensitivity and a partial reduction of insulin secretion. The association with metformin treatment might potentiate the effect of diet alone.
From patients admitted to our Nutritional Division for diet programme, we selected obese, non-diabetic, uncomplicated patients with age 18-65 years and body mass index 35-50 kg/m(2) and studied the effects of a 6-month pharmacological treatment with either metformin (850 mg twice daily) or rosiglitazone (4 mg twice daily) on possible changes in body weight, fat mass, glucose and lipids metabolism.
A significant weight loss and reduction of fat mass was demonstrated with metformin (-9.7 +/- 1.8 kg and -6.6 +/- 1.1 kg) and also with rosiglitazone (-11.0 +/- 1.9 kg and -7.2 +/- 1.8 kg), without fluid retention in either treatment group. Rosiglitazone administration induced a significant decrease in glucose concentration (4.7 +/- 0.1 vs. 4.4 +/- 0.1 mmol/l, p < 0.005) and insulin-circulating level (13.6 +/- 1.5 vs. 8.0 +/- 0.,7 microU/ml, p < 0.005), an increase in insulin sensitivity as measured by homeostatic model assessment (HOMA) of insulin sensitivity (68.9 +/- 8.8 vs. 109.9 +/- 10.3, p < 0.005) with a concomitant decrease in beta-cell function as measured by HOMA of beta-cell function (163.2 +/- 16.1 vs. 127.4 +/- 8.4, p < 0.005). In contrast, metformin did not produce any significant effect on blood glucose concentration, insulin level and HOMA2 indexes. No adverse events were registered with pharmacological treatments.
Our study shows that in severely obese, non-diabetic, hyperinsulinaemic patients undergoing a nutritional programme, rosiglitazone is more effective than metformin in producing favourable changes in fasting-based indexes of glucose metabolism, with a reduction of both insulin resistance and hyperinsulinaemia. In spite of previous studies reporting rosiglitazone-induced body weight gain, in our study the joint treatment with diet and rosiglitazone was accompanied by weight loss and fat mass reduction.