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F Meschi

Publications and source records attributed to F Meschi.

At least 19 recordsLinked to original sources
PubMed1998

Parameters associated with residual insulin secretion during the first year of disease in children and adolescents with Type 1 diabetes mellitus.

Factors associated with residual insulin secretion and spontaneous remission in Type 1 diabetic patients are important in the evaluation of treatment aimed at modifying the natural history of Type 1 DM. We investigated the effect of parameters at onset on residual beta cell function in 215 Type 1 DM children and adolescents. Blood gas analysis, HLA, GAD and IA-2 antibodies before the start of insulin treatment were recorded for each patient. Residual C-peptide secretion was assessed by the glucagon test, and parameters of metabolic control (HbA1c and insulin dose U kg(-1) day(-1)) were examined at disease onset and after 3, 6, and 12 months. Residual C-peptide secretion throughout the first year of disease was significantly reduced in patients with disease onset before age 5. Multiple regression analysis showed that low pH at onset showed a significant and independent association with reduced C-peptide at 3 months (p = 0.02) and that the detection of GAD antibodies had a significant independent association with decreased C-peptide secretion at 6 months of follow-up (p = 0.02). Insulin requirement was higher in the youngest patients group and in patients with GAD antibodies. Spontaneous insulin remission (HbA1c <6% and insulin <0.3 U kg(-1) day(-1)) occurred in 22/192 (11%) patients at 3 months of follow-up, in 15/190 (8%) patients at 6 months and in 8/169 (5%) patient at 12 months. Remission was more prevalent in older patients (p = 0.01) and in patients without detectable GAD antibodies: (14/64 vs 8/128, p = 0.001). Sex, IA-2 antibodies and HLA DR were not independently associated with C-peptide secretion, insulin requirement or remission in the first year of Type 1 DM. This study confirms the association of young age, severe acidosis at disease onset, and GAD antibodies with decreased residual beta-cell function and spontaneous remission during the first year of insulin treatment. These factors should be considered in trials evaluating therapies to retain beta-cell function and induce remission at and after disease onset.

Adolescent↗
PubMed1998

Residual beta-cell function and spontaneous clinical remission in type 1 diabetes mellitus: the role of puberty.

To investigate the role of puberty on spontaneous clinical remission and on secretion of residual C-peptide during the first year of type 1 diabetes mellitus, we studied 77 pre-pubertal, 39 pubertal and 41 post-pubertal type 1 diabetic patients. Spontaneous partial clinical remission (HbA1c within the normal range and insulin dose less than 0.3 U x kg(-1) body weight x day(-1) lasting for at least 10 days) decreased with duration of diabetes: months 3 vs 6 vs 12, respectively 13 vs 7 vs 4% (P<0.025). Remission was higher in post-pubertal than pubertal and prepubertal patients: month 6 respectively 20 vs 5 vs 1% (P<0.001). Secretion of C-peptide was significantly lower in pre-pubertal than the other two groups of patients. Basal and stimulated C-peptide secretion were higher in patients in clinical remission than in those who were not: basal value 0.4 (0.26-0.53) vs 0.28 (0.14-0.4) nmol/l (P<0.05); stimulated value 0.63 (0.5-0.95) vs 0.56 (0.31-0.74) nmol/l (P<0.05). Spontaneous remission is less frequent in children and adolescent patients than in adult post-pubertal patients, but different mechanisms may be involved. Low residual insulin secretion seems implicated in children meanwhile low insulin sensitivity could be more important in pubertal patients.

Adolescent↗
PubMed1998

Autoimmune responses to the beta cell autoantigen, insulin, and the INS VNTR-IDDM2 locus.

Type 1 diabetes is associated with autoimmunity to insulin. Genetic susceptibility to type 1 diabetes is polygenic and includes the INS VNTR-IDDM2 locus which may regulate the expression of insulin in pancreas and thymus. In order to determine whether insulin autoimmunity could be attributed to a genetic susceptibility conferred by the INS VNTR-IDDM2 locus, peripheral blood T cell proliferation to human insulin and insulin autoantibodies (IAA) was measured in patients with new onset type 1 diabetes and control subjects. IAA were detected in 21 of 53 patients and in none of 25 control subjects, while T cell responses were low (stimulation index range 0.4-7.2) and similar in both groups. Both antibody and T cell responses were higher in younger subjects and IAA were more prevalent in patients with the HLA-DR4 allele. No relationship was observed between humoral and cellular responses to insulin. No association was found between the INS VNTR-IDDM2-susceptible allele and insulin autoimmunity. Increased T cell responses and IAA were found in patients with either the diabetes-susceptible or the diabetes-protective INS VNTR-IDDM2 locus genotypes, and increased T cell responses were also found in control subjects with either susceptible or protective INS VNTR-IDDM2 locus genotypes. This study confirms that primary T cell proliferative responses to insulin are low and detectable also in control subjects. The detection of T cell proliferation and autoantibodies to insulin in subjects with and without the protective INS VNTR-IDDM2 locus genotypes does not support the hypothesis of an allele-specific capacity for tolerance induction which could determine a susceptibility to develop autoimmunity against the insulin protein and subsequently diabetes.

Adolescent↗
PubMed1998

Growth changes in children and adolescents with short-term diabetes.

OBJECTIVE: Height and weight changes during the first 3 years of diabetes were prospectively followed in 152 diabetic children and adolescents. RESEARCH DESIGN AND METHODS: The study sample consisted of 152 Caucasian diabetic patients (84 boys; 68 girls) followed from diabetes onset in the Paediatric Diabetes Unit and 80 Caucasian normal subjects (49 boys; 31 girls) assessed in the Outpatient General Paediatric Clinic of the same hospital for routine examination and not affected by problems that might influence growth. Diabetic patients and control subjects were consecutively enrolled in the study between 1989 and 1992; diabetic patients with positive markers for celiac disease (positive antiendomysial antibodies) and thyroid disease (positive antimicrosomial antibodies) or any other chronic disease were not considered in the study. Mean age of diabetic patients (8.9 +/- 4.1 years) and control subjects (8.5 +/- 4.2 years) at recruitment in the study was similar. RESULTS: At onset of diabetes, the mean height expressed as the height standard deviation score (HSDS) was significantly greater than the expected values (P < 0.0001) and was independent of sex and pubertal stage. During the first 3 years of diabetes, HSDS decreased significantly (F = 6.9; P < 0.001). Meanwhile, growth velocity as standard deviation score (SDS) decreased significantly between the 1st and 2nd year (-0.12 +/- 2.1; -0.76 +/- 2.6, respectively; P < 0.05), but it was similar between the 2nd and 3rd year of diabetes. Weight expressed as SDS increased significantly during the first 2 years of diabetes but not thereafter. Height changes during the study period were independent from pubertal stage and sex. Metabolic control and insulin requirement, in our series, were not clearly related to height and weight changes. CONCLUSIONS: Diabetic patients at onset of diabetes are taller than age- and sex-matched nondiabetic subjects. During the first years of the disease, linear growth decreases independently of metabolic control and weight changes.

Adolescent↗
PubMed1998

Two-step islet autoantibody screening for risk assessment of type 1 diabetes in relatives.

OBJECTIVE: To examine the performance of islet cell antibodies (ICAs) and antibodies to glutamate decarboxylase (GADA), IA-2 (IA-2 antibody [IA-2A]), and insulin (insulin autoantibody [IAA]), alone and in combination, in assessing type 1 diabetes risk within type 1 diabetic families to identify a practical and effective screening strategy for predicting type 1 diabetes in relatives. RESEARCH DESIGN AND METHODS: ICA, GADA, IA-2A, and IAA were determined in 806 first-degree relatives participating in a prospective type 1 diabetes family study (median follow-up 6.17 years, range 0.6-8.3). The conferred risk of developing type 1 diabetes within 6 years was evaluated by Kaplan-Meier for each antibody marker, used alone or in combination. RESULTS: ICAs were detected in 3%, GADA in 5.1%, IA-2A in 2.5%, and IAA in 3.7% of relatives; > or =1 antibody markers were detected in 10.7% of relatives and > or =2 were detected in 1.9% of relatives. The risk of type 1 diabetes at 6 years was 1.5% in relatives with only 1 marker and 24.8% in relatives with > or =2 markers. As a practical and effective strategy for type 1 diabetes risk assessment in relatives, this study indicates a first-step screening based on GADA and IA-2A measurement--which identified 6.5% of relatives, including all who developed the disease, with a 6-year type 1 diabetes risk of 9.0%--followed by a second step based on ICA and IAA measurement in relatives with either GADA or IA-2A, which identified a total of 1.9% of all relatives as having > or =2 markers, and a 6-year risk of 24.8%, including 6 of 7 who developed type 1 diabetes. CONCLUSIONS: A two-step antibody screening, based first on GADA and IA-2A and then on ICA and IAA measurements in identified individuals, is likely to be a practical, sensitive, and effective strategy for predicting type 1 diabetes in first-degree relatives.

Adult↗
PubMed1997

Bone modeling indexes at onset and during the first year of follow-Up in insulin-dependent diabetic children.

Osteopenia has been described as a complication of insulin-dependent diabetes mellitus (IDDM). We measured bone modeling indexes during the first year of IDDM. At each time point the values obtained from diabetic children have been compared with those of control subjects. We selected 27 prepubertal children with IDDM (6.35 +/- 2.16 years). We also enrolled 30 healthy prepubertal children of comparable age (5.85 +/- 3.05 years). Height, height standard deviation scores, glycated haemoglobin (HbA1C), basal c-peptide concentrations, insulin dose, serum concentrations of procollagen type I C-terminal propeptide (PICP), and collagen type I C-terminal telopeptide (ICTP) were measured at onset of IDDM and at 3, 6 and 12 months. ICTP was in the normal range at onset of IDDM and decreased during the follow-up to reach a significant difference compared to controls after 3, 6 and 12 months of insulin treatment (P < 0.04). PICP concentrations increased significantly at 3 months (P = 0.05) compared to onset. At 3 and 12 months PICP values were significantly higher than those of control children (P = 0.04). Correlations were found between PICP concentrations and HbA1C and c-peptide at onset of diabetes (r = -0.45 and r = 0.47, respectively). Bone formation at onset of IDDM is not impaired; the introduction of insulin therapy, together with the achievement of a good metabolic control, determines an increase of bone matrix formation coupled with a decrease of bone resorption, that determines a positive balance of bone modeling.

Adolescent↗
PubMed1997

Frequency and correlates of severe hypoglycaemia in children and adolescents with diabetes mellitus.

UNLABELLED: Frequency and correlates of severe hypoglycaemia have been retrospectively analysed in a cohort of diabetic children and adolescents with median (range) age 14.5 (3.2-25.5) years followed from the onset of the disease by the same diabetic clinic. During the years 1992-1994, 53 of the 187 patients reported 74 hypoglycaemic episodes: the average frequency of hypoglycaemia during the 3 years surveyed was 14.9 episodes/ 100 patients per year. Frequency of hypoglycaemia decreased significantly with age (chi 2 = 24.1; P < 0.0001) and was independent of duration of diabetes. Glycosylated haemoglobin and insulin dose were similar in patients with and without hypoglycaemia, matched for age and duration of diabetes. One out of two hypoglycaemic episodes occurred during sleep and no explanation was available for 50% of episodes. CONCLUSION: In this study severe hypoglycaemia was more frequent in young children than in adolescents and was independent of metabolic control and insulin dose.

Adolescent↗
PubMed1996

Urinary growth hormone excretion in children and adolescents with insulin-dependent diabetes mellitus.

Urinary growth hormone (uGH) excretion was evaluated in 96 type-1 insulin-dependent diabetic patients and 37 age-matched healthy subjects. The growth hormone concentration was measured by a solid-phase immunoradiometric assay on 3 consecutive overnight urine collections. uGH excretion was comparable between diabetic patients and healthy subjects: 10.9 (0.1-34.8) vs. 9.1 (2.6-34.5) pg/min. In both groups uGH excretion was lower in prepubertal than in pubescent or pubertal individuals (diabetic patients, H = 29.7, p = 0.001; healthy subjects, H = 10.4, p = 0.006). In diabetic patients uGH excretion was related to beta 2-microglobulin excretion (r = 0.308; p = 0.005) and to urinary albumin excretion (r = 0.230; p = 0.02) but it was independent of HbA1c and overnight glycemic values. The coefficient of variation of uGH excretion was higher in diabetic patients with respect to healthy subjects: 50 (3-141) vs. 28(3-100)% (p = 0.002). Among diabetic patients it was greater in prepubertal than in pubescent or pubertal patients (H = 13.7; p = 0.002); in contrast, it was independent of pubertal stage in healthy individuals (H = 2.4; NS). The coefficient of variation of uGH was not related to HbA1c, the duration of diabetes, the coefficient of variation of urinary albumin excretion and the coefficient of variation of beta 2-microglobulin excretion. In conclusion uGH excretion is comparable among diabetic patients and healthy subjects, but its day-to-day fluctuation is greater in the former than in the latter group. Renal function but not metabolic control can influence uGH excretion. The day-to-day fluctuation in uGH excretion is independent of metabolic control and renal function.

Adolescent↗
PubMed1996

[Metabolic control in insulin dependent diabetic adolescent during a trial by computerized graphic meter for the assessment of glycemia].

Insulin-dependent diabetes mellitus is associated to important micro and macro vascular complications. A good metabolic control can reduce the risk of complications. Aim of the study was to evaluate the metabolic control in adolescent diabetic patients using an educational system with graphic visualisation of capillary glycaemia. 40 (22 males, 18 females) insulin-dependent diabetic patients (age: 16.9 +/- 3.5 yrs; duration of diabetes: 6.7 +/- 4.6 yrs) were divided in two groups matched for age, sex, duration of diabetes and metabolic control. Patients of group 1 used One Touch II Video for three months. One Touch II Video is an educational program for diabetes mellitus linked to a meter for glycaemia assessment. Patients of group 2 were used as control group. All data were expressed as a mean +/- SD and were analysed by parametric t-Student test. In group 1 HbA1c at the end of the study was significantly reduced compared to the initial value: 8.58 +/- 1.65% vs 7.9 +/- 1.0% (p < 0.05). In group 2 HbA1c at end of the study was no different from the initial value. At short term One Touch II Video could be a useful instrument to improve metabolic control in insulin-dependent diabetic adolescents.

Adolescent↗
PubMed1995

Prevalence and correlates of obesity in insulin dependent diabetic patients.

The prevalence of obesity, according to sex and pubertal stage, and the correlations between obesity and metabolic data were investigated in 286 diabetic patients (164 boys, 122 girls) with mean (SD) age 15.3 (3.2) years and mean (SD) duration of diabetes 7.5 (4.1) years. Prevalence of obesity according to the body mass index (BMI) criteria was 6.3%. Girls were more often obese than boys but the prevalence approached statistical significance only for the BMI criteria, at 9.8% v 3.7% (chi 2 = 3.5; p = 0.06); obesity was independent of pubertal stage. Distribution of BMI values of diabetic girls was skewed towards the high centiles of the INSERM tables: < 25th centile, 8.6%; 25th-50th centile, 17.3%; 50th-75th centile, 25.9%; > 75th centile, 48.2% (chi 2 = 19.17, p < 0.0005). BMI values of diabetic boys were homogeneously distributed. Age, duration of diabetes, insulin requirement, daily number of insulin injections, and metabolic control (HbA1c) were comparable in obese and non-obese diabetic patients. Moreover metabolic control and insulin requirements were comparable between diabetic patients with BMI above and below the 50th centile of the INSERM tables after matching for sex. In conclusion the prevalence of obesity in diabetic children and adolescents is quite similar to the prevalence reported in their non-diabetic peers. Obesity and BMI excess correlate with female gender but are independent of insulin requirement and metabolic control.

Adolescent↗
PubMed1995

In vivo metabolic effects of insulin-like growth factor-I not mediated through the insulin receptor.

Patients with mutations affecting insulin receptor function may maintain some degree of metabolic control. The hypothesis has been put forth that in these patients, fuels may be metabolized through pathways (i.e. receptor activation) that become relevant in such abnormal conditions. The aim of our study was to evaluate the metabolic effects of insulin-like growth factor-I (IGF-I) in a 19-yr-old patient with homozygous mutation of the insulin receptor alpha-subunit. Her metabolic and hormonal features were marked hyperglycemia (11-33 mmol/L) and hyperinsulinemia (1000-2000 pmol/L); normal free fatty acids and lactate; low IGF-I; glycerol, alanine, and pyruvate below the normal range; and elevated beta-hydroxybutyrate. Unlike diabetic ketoacidosis, no triglyceride or protein breakdown was present, suggesting a compensatory mechanism, possibly sustained by the insulin concentration acting on IGF-I receptors. Subcutaneous administration of IGF-I (40, 80, and 120 micrograms/kg), although not affecting plasma glucose, resulted in a rapid decrease in free fatty acids and prevented the rise of beta-hydroxybutyrate levels compared to placebo. Therefore, IGF-I can exert direct metabolic effects in vivo, probably through activation of its own receptor, even at a concentration not affecting blood glucose levels. Furthermore, these findings are consistent with the hypothesis that IGF-I receptors may be activated by high insulin levels, providing lipid and protein regulation in patients with nonfunctional insulin receptors.

Adult↗
PubMed1994

Disseminated intravascular coagulation and severe peripheral neuropathy complicating ketoacidosis in a newly diagnosed diabetic child.

Disseminated intravascular coagulation is a very rare complication of diabetic ketoacidosis. Central nervous system palsy but not peripheral neuropathy has been reported in these patients. On the other hand, signs of peripheral neuropathy may also be present at the onset of diabetes, but they are usually reversible within a few days after correction of the metabolic derangement. We describe an unusual case of mononeuritis multiplex syndrome still present after 2 months of follow-up in a child with diabetic ketoacidosis complicated by disseminated intravascular coagulation at the onset of insulin-dependent diabetes. These neurological impairments may be consistent with functional neural lesions due to vasa nervorum thrombosis and prolonged ischaemia.

Blood Pressure↗
PubMed1994

Post-exercise albuminuria does not predict microalbuminuria in type 1 diabetic patients.

To investigate whether post-exercise urinary albumin excretion in Type 1 diabetic children and adolescents may prospectively predict the development of microalbuminuria, we have assessed post-exercise urinary albumin excretion before and after 6.2 +/- 1.7 years of follow-up in 66 diabetic children and adolescents. Post-exercise urinary albumin excretion rose significantly above the pre-exercise values in diabetic patients by 2.7 (-3.8 to 84.2) micrograms min-1 (p < 0.001) and in a group of 9 healthy individuals by 3.9 (-0.7 to 13.7) micrograms min-1 (p < 0.02) without significant differences between groups. Post-exercise albuminuria was greater in postpubertal than prepubertal 9.8 vs 4.3 micrograms min-1 (p < 0.03) and pubertal 9.8 vs 6.0 micrograms min-1 (p < 0.02) patients; post-exercise changes in urinary albumin excretion were also positively related to glycated haemoglobin (r = 0.293; p < 0.05). Eight out of 66 patients developed microalbuminuria at follow-up. Urinary albumin excretion at follow-up was comparable between patients with normal and abnormal post-exercise urinary albumin excretion; moreover post-exercise urinary albumin excretion was within the normal range in 5 out of 8 patients with microalbuminuria at follow-up. In conclusion post-exercise albuminuria does not seem to be a useful predictor of the onset of microalbuminuria in Type 1 diabetic children and adolescents.

Adolescent↗
PubMed1993

Decrease of glomerular hyperfiltration in short-term diabetic adolescents without microalbuminuria.

OBJECTIVE: This study has been designed to follow prospectively the GFR and UAE of young patients with short-term IDDM and normal UAE. RESEARCH DESIGN AND METHODS: The study population consisted of 19 patients with glomerular hyperfiltration and 19 patients with normal GFR, matched for duration of diabetes and age. GFR has been assessed by radioisotopic tracer and UAE by RIA at the beginning of the study and after 30.5 +/- 10.4 mo of follow-up. RESULTS: GFR decreased in the two groups btt delta GFR of patients with glomerular hyperfiltration was greater than delta GFR of patients with normal GFR (0.83 +/- 0.55 vs. 0.28 +/- 0.63 ml.min-1.mo-1; P < 0.01). UAE, BP, and prevalence of microalbuminuria were comparable between the two groups at follow-up. Rate of fall of GFR was positively correlated with initial GFR (r = 0.59, P < 0.001) but not with initial UAE, BP, or changes in HbA1C, UAE, BP, or pubertal development during follow-up. CONCLUSIONS: Investigation of kidney function in children and adolescents with IDDM over a 3-yr follow-up period shows that glomerular hyperfiltration is characterized by a greater decline in GFR without an increased rate of appearance of microalbuminuria, than in patients with normal GFR.

Adolescent↗
PubMed1992

HLA-antigens in Italian type 1 diabetic patients: role of DR3/DR4 antigens and breast feeding in the onset of the disease.

HLA-A, B, C, DR and DQ typing was performed in 381 Italian insulin-dependent diabetic patients and in 905 normal Italian subjects. The diabetic patients had significantly higher frequencies of HLA-Cw7, B8, B18, DR3, DR4, DQw2 and DQw3 and significantly lower frequencies of HLA-B17, Bw51, DR2, DR7 and DRw11. The frequency of heterozygosity for HLA-DR3/DR4 was significantly higher in patients who developed the disease in the first 2 years of life and DR3+/DR4-, DQw2 and DQw3 alleles were higher in those aged less than 14 years at onset. The HLA-DR4 allele was associated with onset of diabetes in autumn and HLA-B18 with onset in Autumn-winter. Diabetic children who were breast fed had a later onset of insulin-dependent diabetes mellitus than those who were bottle fed but these differences were independent of HLA typing (11.8 +/- 0.72 years vs 9.23 +/- 0.42 years; mean +/- SEM). We conclude that: (1) in general, HLA distribution in Italian insulin-dependent diabetic patients reflects previous data reported in other European and North American populations; (2) HLA-DR3 and DR4 are strongly associated with insulin-dependent diabetes in Italy as well, and these alleles seem to predispose to an earlier onset of the disease; and (3) breast feeding may delay the onset of the disease.

Age Factors↗