Biomedical subjects
Publications and source records attributed to M Vanelli.
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Clinical characteristics and metabolic control in a large cohort of children with Type 1 diabetes (T1DM) were evaluated. Fifty-three Italian centers for childhood diabetes collected blood samples and clinical records from 3560 consecutive eligible patients aged 1.6-17.10 yr with disease duration >12 months. HbA1c determinations were centralized in a Diabetes Control and Complications Trial-controlled laboratory. HbA1c grand mean was 8.87 +/- 1.77%. Thirty-two percent of the patients had HbA1c values <8.0%. Puberty and disease duration were the main determinants of increase in HbA1c levels (<0.001). HbA1c values were inversely correlated to the frequency of blood glucose monitoring (p<0.001). Among the total population, 53.7% of the patients had 4 or more injections per day, 37.8% three injections, 7.4% < or =2 injections and only 1.1% was on pumps. Daily number of injections increased with age (p<0.001). Hypoglycemia episodes were reported in 17.6% patient-years and diabetic ketoacidosis (DKA) in 1.0% of children, more frequently in those with HbA1c >8.8% (p<0.02). Two thirds of Italian children with T1DM have HbA1c>8% despite regionalized centers, multidisciplinary team approach, free access to appropriate diabetes care, education, frequent blood glucose monitoring and multiple insulin injections.
AIMS: To test for anti-CD38 autoimmunity in children with newly-diagnosed type 1 diabetes mellitus (DM1). METHODS: Serum anti-CD38 autoantibodies were detected by Western blot in 270 children (130 girls, 140 boys, mean age 8 +/- 4 years) with newly-diagnosed DM1 and 179 gender- and age-matched non-diabetic children. In 126 diabetic children, another blood sample was obtained 15 +/- 4 months after the diagnosis. RESULTS: Anti-CD38 autoantibody titers at least 3 SD above the mean value for the control group were found in 4.4% of children with DM1 vs 0.6% of controls (chi2 = 5.8, p <0.016). No statistical differences were observed between anti-CD38 positive and negative patients in terms of phenotype. At follow-up, of six diabetic children who were positive for anti-CD38 antibodies, two were new cases. A positive correlation was found between the antibody titer of diabetic sera at diagnosis and follow up (r = 0.46, p <0.0001). CONCLUSION: An autoimmune reaction against CD38, a protein expressed in human islets, is associated with newly-diagnosed DM1. In children with DM1, CD38 autoimmunity increases with time and persists.
This paper reports an 8-yr retrospective study on the effects of an uninterrupted procedure of transition of 73 adolescents with Type 1 diabetes from the Paediatric to the Adult Clinic held in the same hospital. Interviewed patients had a mean age of 21.0+/-0.95 yr at transition. Patients were satisfied with the information received before transition (100%), and appreciated being introduced to the adult physician prior to being transferred (92%), and having found their paediatrician during the first visit at the Adult Clinic (100%). Consensus for transition was attained after 2-4 consultations in 66.6% of patients. Seventy-nine percent of patients considered 20 yr of age as an appropriate age to be transferred. Patients confirmed to have found at the Adult Clinic: privacy (85%), confidentiality (95%), short waiting times (78%), informal atmosphere (100%), and the same consultant (100%). Only 3% of patients tried to go back to the Paediatric Clinic but they were discouraged. Clinic attendance rate ranged between 92 and 100%. We consider that the key factors for a successful process of transition from a Paediatric to an Adult Clinic are: age at transfer around 20 yr, smooth movement within the same hospital, consensus of patients and their parents, prior personal contact with the adult physician, paediatrician attendance at the first visit at the adult service and his unambiguous role against all attempts to go back to the paediatric service and, finally, the availability of the same physician at out-patient clinic visits.
OBJECTIVE: To trace growth charts for height, weight and body mass index (BMI) that apply to the whole Italian population. Different charts were drawn for central-north and south Italy since children in central-north regions are known to be taller and leaner. DESIGN: Cross-sectional study. SETTING: A sample of schoolchildren covering 16 of the 20 Italian regions, with data collected between 1994 and 2000. SUBJECTS: A total of 27 421 girls and 27 374 boys, aged 6-20 y. METHODS: Height and weight were measured using portable Harpenden stadiometers and properly calibrated scales, respectively. SIEDP references are presented both as centiles and as LMS curves for the calculation of standard deviation scores. According to International Obesity Task Force, SIEDP charts for BMI include the limits for overweight and obesity, ie the centiles having, at 18 y of age, the value of 25 and 30 kg/m(2), respectively. RESULTS: The comparison between SIEDP and Tanner et al's charts for height, still in use among most Italian paediatricians, shows that before puberty Italian children are 2-4 cm taller than their English peers. Because of these differences, Tanner's charts fail to detect, when applied to Italian children, 50-90% of short children aged 6-11 y, ie with stature below the 3rd centile of their reference population. Rolland-Cachera et al's centiles for BMI are lower than those of SIEDP standards, mainly during adolescence (up to 6.6 kg/m(2) for the 97th centile), and apply poorly to Italian children. The prevalence of overweight is 27 (boys) and 19% (girls) in south Italy vs 17 (boys) and 10% (girls) in central-north Italy. CONCLUSIONS: These references intend to supply Italian paediatricians with a tool that avoids the use of outdated or inadequate charts, and thus should be suitable for monitoring their patients' growth. SPONSORSHIP: Italian Society for Pediatric Endocrinology and Diabetes (SIEDP).
In the last two years we discovered that three of our patients with type 1 diabetes mellitus (0.8%) suffered an unexpected worsening in their glycemic control due to a reduction of their insulin dosage in favour of some "alternative" diabetes treatments using herbs, vitamins, fantastic diets and trace elements prescribed by non-medical practitioners. The first patient, a 6.6 year old boy, was admitted to hospital because of a severe ketoacidosis with first degree coma as a result of his parents having reduced his insulin dosage by 77% and replacing the insulin with an ayurvedic herbal preparation (Bardana Actium Lapp). The second patient, a 10.4 year old boy, was admitted to hospital after his teachers noticed that he appeared tired, thinner and polyuric. During hospital admission for mild ketoacidosis the mother, reluctant at first, finally confessed that her son was under the care of a "clinical ecologist". Having identified several food allergies this "clinical ecologist" had placed the child on a spartan diet of bread, water and salt, and had reduced his insulin dosage by 68%. The third patient, a 21 year old male, upon transfer to the Adult Diabetic Center, reported that he had been under the care of a pranotherapist for several years. The pranotherapist had prescribed a cellular nutrition preparation (called "Madonna drops"), a meditation program and also a 50% reduction in his insulin dosage. During this period his HbAlc values had increased from 6.4% to 12%. Current orthodox diabetes treatments are considered unsatisfactory by many people and it is thus not surprising that they search for "miracle" cures. It is important, however, that hospital staff do not ridicule the patients or their parents for trying these alternative therapies. Nevertheless, it would be useful for staff to discuss in advance these "therapies" with patients, highlighting their ineffectiveness and strongly discouraging cures that call for a reduction or elimination of the insulin treatment.
This study examined whether patients who received prescriptions for conventional and atypical antipsychotics in routine outpatient care continued medication therapy. Prescription refill records of more than 25,000 patients from a national retail pharmacy chain were surveyed during a full eight-month period. At the start of the ninth month, 48 percent of the patients taking conventional agents were continuing therapy. The overall rate for those taking atypical agents was 44 percent; however, the rate for those taking clozapine was 71 percent. Atypical agents, despite their improved side effect profile, were not associated with higher rates of continued treatment. A highly supervised medication administration process, frequent patient-provider contact, and favorable patient selection may help explain the higher rate among patients taking clozapine.
The hormonal regulation of the ob gene and leptin secretion in humans is still unclear. To investigate the interactions among leptin, cortisol, and GH, we analyzed and time-cross-correlated their spontaneous 24-h secretion in 12 short normal prepubertal children of both sexes (6 females and 6 males). Time-cross-correlation analyses demonstrated that leptin and cortisol were correlated in both a negative and positive fashion. The negative correlation, with cortisol leading leptin by 4 and 3 h for boys and girls, respectively, might reflect the stimulatory effect of CRH on the sympathetic system, which inhibits leptin secretion; the positive correlation, with leptin leading cortisol by 6 and 5 h for boys and girls, respectively, might reflect a direct effect of leptin on CRH secretion in the hypophyseal portal system. Time-cross-correlation analyses also showed a strong positive correlation between GH and leptin concentrations, with GH leading leptin by 5 and 2 h for boys and girls, respectively, suggesting a possible direct leptin-releasing effect of GH on adipocytes. We conclude that cross-correlation analyses of 24-h hormone secretions under baseline physiological conditions suggest that the hypothalamic-pituitary-adrenal axis might have a prevailing inhibitory effect on leptin secretion, whereas leptin might exert a positive effect on the hypothalamic-pituitary-adrenal axis. The relation between GH and leptin could be a direct one and characterized prevalently by a positive effect of GH on leptin secretion. Further investigations using different experimental systems are needed to ascertain the validity of these mathematically educed conclusions.
OBJECTIVE: It is unclear whether the demands of good metabolic control or the consequences of poor control have a greater influence on quality of life (QOL) for adolescents with diabetes. This study aimed to assess these relations in a large international cohort of adolescents with diabetes and their families. RESEARCH DESIGN AND METHODS: The study involved 2,101 adolescents, aged 10-18 years, from 21 centers in 17 countries in Europe, Japan, and North America. Clinical and demographic data were collected from March through August 1998. HbA(1c) was analyzed centrally (normal range 4.4-6.3%; mean 5.4%). Adolescent QOL was assessed by a previously developed Diabetes Quality of Life (DQOL) questionnaire for adolescents, measuring the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. Parents and health professionals assessed family burden using newly constructed questionnaires. RESULTS: Mean HbA(1c) was 8.7% (range 4.8-17.4). Lower HbA(1c) was associated with lower impact (P < 0.0001), fewer worries (P < 0.05), greater satisfaction (P < 0.0001), and better health perception (P < 0.0001) for adolescents. Girls showed increased worries (P < 0.01), less satisfaction, and poorer health perception (P < 0.01) earlier than boys. Parent and health professional perceptions of burden decreased with age of adolescent (P < 0.0001). Patients from ethnic minorities had poorer scores for impact (P < 0.0001), worries (P < 0.05), and health perception (P < 0.01). There was no correlation between adolescent and parent or between adolescent and professional scores. CONCLUSIONS: In a multiple regression model, lower HbA(1c) was significantly associated with better adolescent-rated QOL on all four subscales and with lower perceived family burden as assessed by parents and health professionals.
OBJECTIVE: Twenty-one international pediatric diabetes centers from 17 countries investigated the effect of simple feedback about the grand mean HbA(1c) level of all centers and the average value of each center on changes in metabolic control, rate of severe hypoglycemia, and insulin therapy over a 3-year period. RESEARCH DESIGN AND METHODS: Clinical data collection and determination of HbA(1c) levels were conducted at a central location in 1995 (n = 2,780, age 0-18 years) and 1998 (n = 2,101, age 11-18 years). RESULTS: Striking differences in average HbA(1c) concentrations were found among centers; these differences remained after adjustment for the significant confounders of sex, age, and diabetes duration. They were apparent even in patients with short diabetes duration and remained stable 3 years later (mean adjusted HbA(1c) level: 8.62 +/- 0.03 vs. 8.67 +/- 0.04 [1995 vs. 1998, respectively]). Three centers had improved significantly, four centers had deteriorated significantly in their overall adjusted HbA(1c) levels, and 14 centers had not changed in glycemic control. During the observation period, there were increases in the adjusted insulin dose by 0.076 U/kg, the adjusted number of injections by 0.23 injections per day, and the adjusted BMI by 0.95 kg/m(2). The 1995 versus 1998 difference in glycemic control for the seven centers could not be explained by prevailing insulin regimens or rates of hypoglycemia. CONCLUSIONS: This study reveals significant outcome differences among large international pediatric diabetes centers. Feedback and comparison of HbA(1c) levels led to an intensification of insulin therapy in most centers, but improved glycemic control in only a few.
The aim of this study was to evaluate serum advanced glycation end products (S-AGEs) in a group of adolescents and young adults with type 1 (insulin-dependent) diabetes mellitus and with diabetic microvascular complications (nephropathy or retinopathy). Fifty-two patients were included in the study (age range 14.2-28.8 years, onset of diabetes before the age of 12 years, duration of diabetes longer than 7 years); 45 patients without diabetic angiopathy and 63 healthy controls were also selected. S-AGEs were significantly increased in patients with diabetic angiopathy compared with controls (19.9+/-3.8 vs. 11.8+/-2.8 U/ml, P<0.001). Higher S-AGE levels were found in patients with severe diabetic nephropathy and retinopathy. When the albumin excretion rate (AER) was >100 microg/min per 1.73 m2, S-AGE levels were 23.1+/-2.4 U/ml; when the AER was 50-100 microg/min per 1.73 m2 levels were 19.8+/-1.9 U/ml, and for an AER of 20-50 microg/min per 1.73 m2 the corresponding value was 16.1+/-2.1 U/ml (P<0.005). Patients with proliferative retinopathy had S-AGE levels of 22.2+/-2.6 U/ml, those with preproliferative retinopathy 20.7+/-2.2 U/ml, and background retinopathy 17.6+/-1.9 U/ml (P<0.01). A significant correlation was found between levels of glycosylated hemoglobin (HbA1c) and S-AGE (r=0.43, P<0.01). S-AGE concentrations are markedly increased in type 1 diabetic adolescents and young adults with diabetic nephropathy and retinopathy. The severity of diabetic angiopathy is related to the serum levels of AGEs.
OBJECTIVE: To assess plasma homocysteine levels in adolescents and young adults with type 1 (insulin-dependent) diabetes with and without microvascular complications. STUDY DESIGN: Homocysteine levels were measured during fasting and after methionine loading in plasma of 61 patients with onset of diabetes before the age of 12 years and duration of disease longer than 7 years. They had an albumin excretion rate (AER) between 20 and 200 microg/min in 2 of 3 overnight urine collections in a period of 6 months and/or retinopathy. Patients with persistent microalbuminuria were divided into 2 groups: subjects with AER of 20 to 70 microg/min and patients with AER of 70 to 200 microg/min. Adolescents (n = 54) without signs of diabetic retinopathy or nephropathy and matched control subjects (n = 63) were also studied. RESULTS: Homocysteine concentrations before and after methionine load were higher in adolescents with diabetic complications than in healthy subjects (fasting values: 12. 4 +/- 7.9 micromol/L vs 7.8 +/- 4.2 micromol/L; P <.01; after methionine load: 28.1 +/- 13.2 micromol/L vs 16.6 +/- 7.3 micromol/L; P <.005). Values of 11.9 micromol/L or higher were considered to constitute fasting hyperhomocysteinemia. The increase of homocysteine concentrations was particularly evident in young diabetic patients with AER >70 microg/min (fasting values: 14.7 +/- 5.6 micromol/L; after methionine load: 34.2 +/- 12.6 micromol/L) and in patients with proliferative retinopathy (fasting values: 15.1 +/- 5.0 micromol/L; after methionine load: 36.8 +/- 12.5 micromol/L). CONCLUSIONS: Increased plasma homocysteine concentrations may contribute to increased morbidity and death from cardiovascular disease in adolescents and young adults with diabetic retinopathy and nephropathy.
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Diabetic Nephropathy is one of the microvascular complications associated with type 1 diabetes mellitus with a major portion of the excess morbidity and mortality. In order to avoid or at least delay its onset we should detect a very small amount of proteins in the urine (between 15-20 and 200 micrograms/min.) that is a strong predictor of those likely to progress to overt nephropathy. This detection can be obtained evaluating an overnight sample of urine and suggest preventives interventions. such as intensive diabetes management and angiotensin converting enzyme inhibition (ACEi). Furthermore, associated risk factors should be prevented or treated (hypertension, retinopathy, hyperlipidemia and smoking).
Neonatal diabetes (ND) is a rare condition of hyperglycaemia which occurs, generally, within the first month of life, requires insulin therapy and lasts more than two weeks. The pathogenesis is uncertain and the different clinical variants are heterogeneous; both a "permanent" and a "transient" form of ND exist. We report the clinical history of three neonates (A.L., A.B. and V.I.) in which a tout-court diagnosis of ND was done; the follow-up allowed us to reevaluate the initial diagnoses and suppose different ethiopathogenic mechanisms. Clinical observations, insulin requirement and biochemical data obtained during the years of follow-up allowed to distinguish three different situations: a "permanent" ND (A.L.), a "transient-recurrent" ND (A.B.), and a Maturity Onset Diabetes of the Young (MODY) (V.I.).
OBJECTIVE: To shorten the period of carbohydrate intolerance preceding the diagnosis of IDDM in children. RESEARCH DESIGN AND METHODS: The incidence of diabetic ketoacidosis (DKA) was studied in newly diagnosed diabetic children aged 6-14 years, in the area of Parma, Italy, 8 years after an information program on DKA was introduced to teachers, students, parents, and pediatricians. Information was provided by displaying a poster with a few practical messages in 177 primary and secondary public schools. The pediatricians working in the same area were given equipment for the measurement of both glycosuria and blood glucose levels, as well as cards listing guidelines for the early diagnosis of diabetes, to be given to patients. A toll-free number was also provided. Clinical and laboratory features of 24 young diabetic patients diagnosed in the Parma area (group 1) were compared with those of 30 patients coming from two nearby areas in which no campaign for the prevention of DKA had been carried out (group 2). RESULTS: From 1 January 1991 to 31 December 1997, DKA was diagnosed in 3 children from group 1 (12.5%) and in 25 children from group 2 (83.0%) (chi 2 = 26.8; P = 0.0001). The three cases of DKA in group 1 were observed in 1991 (n = 1) and in 1992 (n = 2). No patients from the Parma area who had DKA were admitted to our unit after 1992. The duration of symptoms before diagnosis was 5.0 +/- 6.0 and 28.0 +/- 10.0 days (P < 0.0001), in groups 1 and 2, respectively, Metabolic derangements were less severe in patients of group 1 than in those of group 2. Hospitalization for the treatment of overt diabetes and for the teaching of self-management of the disease lasted 5.4 +/- 1.2 days in group 1 and 13.3 +/- 2.4 days in group 2 (P = 0.002). The total cost of the 8-year campaign was $23,470. CONCLUSIONS: The prevention program for DKA in diabetic children aged 6-14 years, carried out in the Parma area during the last 8 years, was successful. Thanks to this program, cumulative frequency of DKA in new-onset IDDM decreased from 78% during 1987-1991 to 12.5% during 1991-1997. None of the newly diagnosed diabetic children aged 6-14 years and from the Parma area were ever admitted to the hospital for DKA after 1992.
OBJECTIVE: To evaluate whether erythrocyte sodium-lithium countertransport (Na+/Li+ CT) activity may identify adolescents and young adults with childhood-onset of type 1 diabetes to be at greater risk to develop persistent microalbuminuria and incipient diabetic nephropathy. RESEARCH DESIGN AND METHODS: In January 1989, Na+/Li+ CT was measured in 170 normoalbuminuric diabetic adolescents and young adults (age 12-23 years; onset of diabetes before age 18 years; duration of diabetes longer than 7 years). Participants were clinically examined at baseline and biennially thereafter. Na+/Li+ CT activity was measured every 2 years during the 8-year follow-up period. Na+/Li+ CT activity was measured also in parents of diabetic offspring. RESULTS: Over 8 years, 18 (10 male, 8 female) out of 170 patients (10.5%) developed persistent microalbuminuria; no patient developed overt nephropathy. The risk of developing microalbuminuria was higher in children with increased Na+/Li+ CT (using 300 mumol.1 erythrocytes-1.h-1 as the arbitrary cutoff point) (group 1) compared with those with normal Na+/Li+ CT at the beginning of the study (group 2) (18.98 vs. 3.29%, P < 0.01; sensitivity 96.7%; specificity 57.9%). Sex did not influence predictive value, sensitivity, or specificity. Na+/Li+ CT was not significantly correlated with HbA1c or duration of type 1 diabetes. The percentage of offspring with both parents having Na+/Li+ CT activity above the median values was significantly higher in patients in group 1 than in group 2. The odds ratio for the occurrence of microalbuminuria after adjustment for confounding variables (albumin excretion rate [AER], sex, HbA1c, mean blood pressure, cholesterol, triglycerides) in type 1 diabetic adolescents with elevated baseline erythrocyte Na+/Li+ CT was 4.5 (95% CI of 2.1-11.4). CONCLUSIONS: These results confirm those of previous studies and suggest that Na+/Li+ CT may be one of the predictors and risk factors for incipient diabetic nephropathy in adolescents and young adults with onset of diabetes during childhood. Persistently increased Na+/Li+ CT activity may help to identify normotensive, normoalbuminuric patients with type 1 diabetes who are predisposed to develop microalbuminuria and incipient diabetic nephropathy.
Insulin regimens and metabolic control in children and adolescents with Type 1 diabetes mellitus were evaluated in a cross-sectional, non-population-based investigation, involving 22 paediatric departments, from 18 countries in Europe, Japan, and North America. Blood samples and information were collected from 2873 children from March to August 1995. HbA1c was determined once and analysed centrally (normal range 4.4-6.3%, mean 5.4%). Year of birth, sex, duration of diabetes, height, body weight, number of daily insulin injections, types and doses of insulin were recorded. Average HbA1c in children under 11 years was 8.3 +/- 1.3% (mean +/- SD) compared with 8.9 +/- 1.8% in those aged 12-18 years. The average insulin dose per kg body weight was almost constant (0.65 U kg(-1) 24 h(-1)) in children aged 2-9 years for both sexes, but there was a sharp increase during the pubertal years, particularly in girls. The increase in BMI of children with diabetes was much faster during adolescence compared to healthy children, especially in females. Sixty per cent of the children (n = 1707) used two daily insulin injections while 37% (n = 1071) used three or more. Of those on two or three injections daily, 37% used pre-mixed insulins, either alone or in combination with short- and intermediate-acting insulin. Pre-adolescent children on pre-mixed insulin showed similar HbA1c levels to those on a combination of short- and long-acting insulins, whereas in adolescents significantly better HbA1c values were achieved with individual combinations. Very young children were treated with a higher proportion of long-acting insulin. Among adolescent boys, lower HbA1c was related to use of more short-acting insulin. This association was not found in girls. We conclude that numerous insulin injection regimens are currently used in paediatric diabetes centres around the world, with an increasing tendency towards intensive diabetes management, particularly in older adolescents. Nevertheless, the goal of near normoglycaemia is achieved in only a few.