[Effect of guar on plasma lipids and on the biological activity of insulin in patients with type 2 diabetes mellitus]. / Effetto del guar sui lipidi plasmatici e sulla attività biologica dell'insulina nei pazienti con diabete tipo 2.

10 patients with type 2 diabetes mellitus, in stable weight and diet therapy, followed a 2 months nutritional supplementation with guar, 15 g/day. Their previous nutritional and pharmacological therapy was not modified throughout the study. No changes occurred in body weight or major parameters of metabolic control. However, a significant fall occurred in fasting plasma, total and LDL cholesterol, and apolipoprotein B concentrations. Insulin sensitivity, measured by the "steady state plasma glucose", obtained after a 150 min glucose-insulin-somatostatin infusion, improved in all patients but two. A significant correlation was observed between steady state plasma glucose variations, the glycosylated haemoglobin A1c (r = 0.70; p less than 0.005), total (r = 0.77; p less than 0.001), and LDL cholesterol (r = 0.69; p less than 0.005) and apolipoprotein B concentrations (r = 0.75; p less than 0.005).

In vitro gene and chromosome characterization of expanded bone marrow mesenchymal stem cells for musculo-skeletal applications.

OBJECTIVE: A number of studies have shown the role of expanded Bone Marrow-derived Mesenchymal Stem Cells in the repair and regeneration of musculo-skeletal tissues. The current European regulations define in vitro expanded cells for clinical purposes as substantially manipulated and include them in the class of Advanced-Therapy Medicinal Products to be manufactured in compliance with current Good Manufacturing Practice. Among the characteristics that such cells should display, genomic stability has recently become a major safety concern. The aim of this study is to perform a chromosomal and genetic characterization of Bone Marrow-derived Mesenchymal Stem Cells expanded in compliance with Good Manufacturing Practice for a potential clinical use in orthopaedics. MATERIALS AND METHODS: Mesenchymal Stem Cells, isolated from bone marrow, were expanded for six weeks in compliance with current Good Manufacturing Practice. DNA profiling analyses were applied to test cross-contamination absence. Genomic stability was evaluated by means of karyotyping, sequencing of TP53, p21/CDKN1A and MDM2 genes and the expression analysis of c-MYC and H-RAS oncogenes, p21/CDKN1A, TP53, p16/CDKN2A, RB1 and p27/CDKN1B tumor suppressor genes and hTERT gene. RESULTS: The DNA profiling analysis showed a unique genetic profile for each Mesenchymal Stem Cell culture, indicating the absence of cross-contamination. Karyotyping evidentiated some chromosomal abnormalities within the 10% limit set by the Cell Products Working Party review, except for one patient. In all cases, the molecular biology analyses did not revealed DNA point mutations, acquisition or changes in gene expression. hTERT levels were undetectable. CONCLUSIONS: Cultured Mesenchymal Stem Cells do not seem to be prone to malignant transformation. In fact, although some chromosomal aberrations were found, molecular biology analyses demonstrated that the expansion phase did not induce the acquisition of de novo genetic changes.

Estimation of B-cell function by the urinary excretion rate of C-peptide in diabetic patients: comparison with C-peptide response to glucagon and to a mixed meal.

This study examined the relationship between the C-peptide response to intravenous glucagon and mixed meal stimulation and the 24 h urinary excretion rate of C-peptide and its urinary excretion during the glucagon test in nine control subjects, eighteen Type 1 (insulin-dependent) and twenty-two Type 2 (non-insulin-dependent) diabetic patients. Compared to controls (61.0 +/- 7.1 micrograms), the 24-h urine excretion rate of C-peptide was 8.2 +/- 3.1 micrograms (p less than 0.001) in Type 1 and 89.8 +/- 12.9 micrograms (p = NS) in Type 2 diabetic patients. C-peptide urinary excretion rate during the glucagon test was 6.92 +/- 1.11 micrograms, 0.42 +/- 0.10 microgram (p less than 0.001) and 6.47 +/- 1.13 micrograms (p = NS) respectively. Fasting serum C-peptide values were 1.53 +/- 0.16 ng/ml in controls, 0.42 +/- 0.09 ng/ml in Type 1 (p less than 0.0001) and 2.08 +/- 0.22 ng/ml in Type 2 diabetics (p = NS); C-peptide areas under the curve after glucagon stimulation were, respectively, 241.6 +/- 20.3 ng/ml, 29.2 +/- 5.9 ng/ml (p less than 0.0001) and 170.9 +/- 17.9 ng/ml (p less than 0.03) and after the meal test they were 204.7 +/- 15.6, 68.7 +/- 19.8 ng/ml (p less than 0.0001) and 265.5 +/- 32.9 ng/ml (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of 'physiological' doses of triiodothyronine replacement on the hormonal and metabolic adaptation to short-term semistarvation and to low-calorie diet in obese patients.

In four groups of obese patients matched for Body Mass Index (BMI), we studied the effects of different 3-week semi-starvation treatments followed by an 8-week hypocaloric (1008 kcal, protein 20%, carbohydrate 40%) diet with or without low doses of T3 therapy. Dietary intake (formula diet) in the semi-starvation period was 480 kcal, with 66 g protein (P) and 51 g carbohydrate (CHO) in groups I and III and with 33 g P and 84 g CHO in groups II and IV. Moreover, groups III and IV were given low doses (20 micrograms twice a day) of T3 while groups I and II received a placebo. During semi-starvation periods, a similar fall in BMI values was found in all groups, while during the low-calorie diet, T3-treated patients showed the greater BMI reduction. During semi-starvation, nitrogen balance was significantly more negative in low-protein than in high-protein-treated groups; differences between T3-treated (III and IV) and control (I and II) groups were not significant over this relatively short treatment period. No differences in 24 h urinary 3-methylhistidine or alanine excretion were evident between the four groups. During the entire period of study, daily urine creatinine excretion did not change in any group. In conclusion, in our study low-dose T3 therapy was seen to favour weight loss during low-calorie diet although negative effects on protein metabolism were not excluded, particularly when relatively small amounts of protein were administered.

Clinical application of the 24-H urinary C-peptide excretion rate and its relationship to metabolic control in diabetics.

In this study, we evaluated in normal subjects, insulin-dependent (IDD) and non-insulin-dependent (NIDD) diabetics, the diurnal urinary C-peptide excretion rate (CPR-U) and its relationship to serum C-peptide concentration and glucose:C-peptide molar ratio, and to the common parameters of metabolic control. The CPR-U (and CPR-U/g creatinine) were significantly lower in IDD and higher in NIDD compared to control subjects. Moreover, a good and significant correlation with serum C-peptide concentrations and the glucose:C-peptide ratio in diabetic subjects as well as in controls and diabetics considered together was found. A slight but significant correlation was present in diabetic subjects between CPR-U and body mass index (r = 0.45), 24-h glycosuria (r = 0.36), HbA1 levels (r = 0.31), post-prandial glucose concentrations (r = 0.26) and per cent glucose variation after each meal (r = 0.34). No differences were found in CPR-U and the degree of metabolic control between obese and non-obese NIDD. In conclusion, CPR-U may be a useful and simple method of defining the secretory activity of the B-cell. Metabolic control in diabetics is slightly correlated to the degree of B-cell function as evaluated by the diurnal excretion rate of C-peptide in urine.

Relationships between iodothyronine peripheral metabolism and ketone bodies during hypocaloric dietary manipulations.

Relationships between iodothyronine and metabolic substrate metabolism during undernutrition were evaluated in four normal subjects who fasted for 48h (Group I) and in four groups (II to V) of obese patients who underwent selective dietary manipulations: 360 calories [carbohydrate (CHO) 40 g/day]; 800 calories containing respectively 19 g/day - ketogenic - (K) and 112 g/day - non ketogenic - (NK) of CHO; and a step-diet programme (during which total calories were progressively reduced from 2500 to 500). Serum T3 levels decreased significantly and constantly during fasting, 360 and 800 K studies, and transiently during the 800 NK diet. During the step-diet programme, a significant fall was found only when 1250 K or less were given. Conversely, serum reverse T3 rose significantly and constantly during 360 and 800 K diets, while a transient increase was found during the 800 NK diet. During the step-diet programme reverse T3 rose only when 750 calories were given. Ketogenesis developed in all studies but one (800 NK), and in the step-diet programme significantly below the 1000 calorie step. Other substrate modifications in each study were also evaluated. Serum T3 levels showed a significant correlation with ketone bodies (KB) in all the ketogenic studies, while no correlation was found in non ketogenic study (800 NK). During the step-diet programme ketone bodies and iodothyronine modifications appeared to be related to the amount of calories. Based on these results, we suggest a relationship between the dietary-induced modifications of iodothyronine metabolism and the development of ketogenesis.

Effect of dietary carbohydrates during hypocaloric treatment of obesity on peripheral thyroid hormone metabolism.

The effect of different hypocaloric carbohydrate (CHO) intakes was evaluated in 8 groups of obese patients in order to assess the role of the CHO and the other dietary sources in modulating the peripheral thyroid hormone metabolism. These changes were independent of those of bw. Serum T3 concentrations appear to be more easily affected than those of reverse T3 by dietary manipulation and CHO content of the diet. A fall in T3 levels during the entire period of study with respect to the basal levels occurred only when the CHO of the diet was 120 g/day or less, independent of caloric intake (360, 645 or 1200 calories). Moreover, reverse T3 concentrations were found increased during the entire period of study when total CHO were very low (40 to 50 g/day) while they demonstrated only a transient increase when CHO were at least 105 g/day (with 645 or more total calories). Indeed, our data indicate that a threshold may exist in dietary CHO, independent of caloric intake, below which modifications occur in thyroid hormone concentrations. From these results it appears that the CHO content of the diet is more important than non-CHO sources in modulating peripheral thyroid hormone metabolism and that the influence of total calories is perhaps as pronounced as that of CHO when a "permissive" amount of CHO is ingested.