Role of the C1858T polymorphism of protein tyrosine phosphatase non-receptor type 22 (PTPN22) in children and adolescents with type 1 diabetes.

In recent years, increasing interest has been devoted to the susceptibility gene polymorphisms in type 1 diabetes (T1D) as well as in other autoimmune diseases. Among these, a nucleotide polymorphism of the gene encoding for the protein tyrosine phosphatase non-receptor type 22 (PTPN22) has been associated with T1D in several studies. The aim of this study is to define the frequency of the C1858T polymorphism in the PTPN22 gene in a cohort of 113 Caucasian patients (58 males and 55 females) with T1D, and to assess a possible correlation with a group of clinically relevant variables: age at onset, gender, diabetes-related autoantibodies, residual ß-cell function and daily insulin requirement (IR) 6 months after diagnosis. Using a PCR-RFLP approach, we evidenced a 17.7% frequency of the PTPN22 C1858T polymorphism in diabetic patients, higher than the frequency showed in the general population. A statistically significant correlation between this polymorphism and higher levels of C-peptide at diagnosis and lower IR at 6 months from diagnosis was observed (P=0.001 and P=0.04). Moreover, 1858T variant carriers were more frequently positive for glutamic acid decarboxylase (GAD) autoantibodies at diagnosis than wild-type subjects (P=0.19). On the other hand, no significant difference regarding age at onset, gender distribution, insulinoma-associated 2 molecule (IA2) and islet cell antibodies (ICA) positivity was found. These findings, if adequately confirmed in the future and extended to larger samples, may characterize a subset of T1D patients with a defined genetic pattern, who may be eligible for trials aimed to preserve residual ß-cell function in the coming years.

Insulin pump failures in Italian children with Type 1 diabetes: retrospective 1-year cohort study.

AIMS: Insulin pump failure and/or malfunction requiring replacement have not been thoroughly investigated. This study evaluated pump replacement in children and adolescents with Type 1 diabetes using insulin pump therapy. METHODS: Data were collected for all participants younger than 19 years, starting insulin pump therapy before 31 December 2013. For each child, age, disease duration, date of insulin pump therapy initiation, insulin pump model, failure/malfunction/replacement yes/no and reason were considered for the year 2013. RESULTS: Data were returned by 40 of 43 paediatric centres belonging to the Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology. In total, 1574 of 11 311 (13.9%) children and adolescents with Type 1 diabetes were using an insulin pump: 29.2% Animas VIBE™ , 9.4% Medtronic MiniMed 715/515™ , 34.3% Medtronic MiniMed VEO™ , 24.3% Accu-Check Spirit Combo™ and 2.8% other models. In 2013, 0.165 insulin pump replacements per patient-year (11.8% due to pump failure/malfunction and 4.7% due to accidental damage) were recorded. Animas VIBE™ (22.1%) and Medtronic MiniMed VEO™ (17.7%) were the most replaced. CONCLUSIONS: In a large cohort of Italian children and adolescents with Type 1 diabetes, insulin pump failure/malfunction and consequent replacement are aligned with rates previously reported and higher in more sophisticated pump models.

Bone maturity and thyroidal status at birth: role of the ultrasonographic evaluation of the distal femoral epiphysis.

PURPOSE: Thyroidal hormones are important for bone development, and ultrasonographic (US) evaluation of the distal femoral epiphysis (DFE) has recently been suggested as a new method for the assessment of skeletal maturity in infants. A delayed bone maturation, expressed by a smaller or absent DFE nucleus (in terms of DFE surface area, sum of the epiphyseal diameters, or DFE height and acetabular size), has been largely demonstrated in diagnosed hypothyroid infants, while no data analyze the role and meaning of the DFE dimensions (in terms of volume) in newborn before knowledge of the congenital neonatal screening results. The aims of the present study were to ultrasonographically evaluate the volume of DFE in newborns, and to determine whether it has any predictive role for the thyroidal status at birth. MATERIALS AND METHODS: 238 newborns (M/F: 121 /117) were evaluated. The gestational age, body weight and length at birth were registered. Neonatal screening for congenital hypothyroidism (CH), based on TSH levels on blood spot, was performed in all on the 3 rd day of life. The DFE volume was ultrasonographically evaluated, taking into account the three diameters of the DFE nucleus, within 48 hours of birth. RESULTS: No newborn was found to have CH on neonatal screening. The DFE volume ranged between 0.00 cm and 0.61 cm (mean 0.14 ± 0.10 cm, median 0.13 cm). The DFE volume did not differ between males and females, while it was significantly greater in at term babies than in preterm babies. No differences in TSH values at screening were noted among the groups. The DFE volume was significantly related to gestational age, birth weight and length. A significant relationship was found between the DFE volume and TSH concentrations at screening. CONCLUSION: US evaluation of DFE volume provides a simple method for assessing bone maturity at birth, which is related to gestational age, body weight and length at birth. Nonetheless, it has any predictive role for thyroidal status at birth, being not related to TSH levels on neonatal screening for CH.

Molecular characterization of 6 unrelated Italian patients with 5alpha-reductase type 2 deficiency.

Steroid 5alpha-reductase (5alphaR) deficiency (OMIM number #264600) is a rare 46,XY disorder of sex differentiation caused by mutations in the 5alphaR type 2 gene (SRD5A2) resulting in dihydrotestosterone deficiency during fetal development. We report on the analysis of the SRD5A2 gene in 6 unrelated 46,XY Italian patients with external genitalia morphology ranging from predominantly female to nearly completely male. Three subjects were seen and assessed at birth, 1 patient was referred to us before puberty, and 2 at postpubertal age. Six different causative mutations (5 missense and 1 nonsense) and a rare polymorphism were identified. Four patients presented homozygous single-base substitutions. These SRD5A2 mutations were located in exon 2 (variant Cys133Gly), exon 4 (Gly196Ser and Ala207Asp) and exon 5 (Tyr235Phe). A fifth subject was a compound heterozygote who carried a nonsense mutation in exon 1 (Trp53X) and a second SRD5A2 alteration in exon 5 (Tyr235Phe). The final patient presented a mutation in only 1 allele (Gly34Trp) together with the Ala49Thr variant. The molecular characterization of these patients made it possible to identify novel mutations and to confirm, before gender assignment or any surgical approach, the suspected 5alphaR deficiency in 2 newborns, 1 of whom had inconclusive hormonal data. 5alphaR deficiency in subjects without parental consanguinity and the presence of compound heterozygotic patients suggest that SRD5A2 mutations carrier frequency may be higher than previously thought.

Increased circulating nitric oxide in young patients with type 1 diabetes and persistent microalbuminuria: relation to glomerular hyperfiltration.

Hyperglycemia has been causally linked to vascular and glomerular dysfunction by a variety of biochemical mechanisms, including a glucose-dependent abnormality in nitric oxide (NO) production and action. NO is a candidate for mediating hyperfiltration and the increased vascular permeability induced by diabetes. Serum nitrite and nitrate (NO2-+ NO3-) concentrations were assessed as an index of NO production in 30 adolescents and young adults with type 1 diabetes, 15 with and 15 without microalbuminuria (albumin excretion rate [AER] between 20 and 200 microg/min), compared with a well-balanced group of healthy control subjects. In all subjects, glomerular filtration rate (GFR) was determined by radionuclide imaging. Our study showed that NO2- + NO3- serum content and GFR values were significantly higher in microalbuminuric diabetic patients than in the other 2 groups. GFR was significantly and positively related to AER levels (r2 = 0.75, P < 0.0001), whereas NO2- + NO3- serum content was independently associated with both AER and GFR values (beta = 2.086, P = 0.05, beta = 1.273, P = 0.0085, respectively), suggesting a strong link between circulating NO, glomerular hyperfiltration, and microalbuminuria in young type 1 diabetic patients with early nephropathy. Interestingly, mean HbA1c, serum concentration was significantly higher in microalbuminuric than in normoalbuminuric diabetic subjects (P < 0.05) and was independently associated with AER values, suggesting a role for chronic hyperglycemia in the genesis of diabetic nephropathy. Moreover, HbA1c serum concentration was significantly and positively related to NO2 + NO3 serum content (r2 = 0.45, P = 0.0063) and GFR values (r2 = 0.57, P = 0.0011), suggesting that chronic hyperglycemia may act through a mechanism that involves increased NO generation and/or action. In conclusion, we suggest that in young type 1 diabetic patients with early nephropathy, chronic hyperglycemia is associated with an increased NO biosynthesis and action that contributes to generating glomerular hyperfiltration and persistent microalbuminuria.

Relationship between reduced BCL-2 expression in circulating mononuclear cells and early nephropathy in type 1 diabetes.

Microalbuminuria is the earliest clinical evidence of diabetic nephropathy, but the mechanisms linking hyperglycemia and kidney complications are not clear. The aim of this study was to evaluate whether enhanced oxidative stress in patients with microalbuminuria can contribute to diabetic nephropathy development through downregulation of the antiapoptotic gene Bcl-2 that promotes in turn a pro-inflammatory status. We studied 30 patients with type 1 diabetes (15 with and 15 without microalbuminuria) compared to 15 matched healthy controls. Plasma oxidant status, and expression of Bcl-2, activated NF-kB, inducible Nitric Oxide synthase (iNOS), and monocyte chemoattractant protein (MCP)-1 in circulating monocytes were evaluated at baseline and after 8-week oral vitamin E treatment (600 mg b.i.d.). Bcl-2 expression was significantly reduced in microalbuminuric diabetic patients as a consequence of increased oxidant burden secondary to persistent hyperglycemia. Bcl-2 down-regulation was associated with enhanced expression of NF-kB, iNOS and MCP-1, and showed a strong correlation with the albumin excretion rate. Low Bcl-2 expression and high inflammatory status were normalized by vitamin E both in vivo and in vitro. Our study showed that Bcl-2 down-regulation in diabetic patients with poor glycemic control results in the activation of the NF-kB pathway leading to the development of nephropathy. Vitamin E might provide a novel form of therapy for prevention of nephropathy in diabetic patients in which an acceptable glycemic control is difficult to achieve despite insulin therapy.

HLA DR/DQ alleles and risk of type I diabetes in childhood: a population-based case-control study.

The objective was to evaluate HLA DR/DQ alleles and their risk factor for type 1 diabetes in the Abruzzo region (central Italy). Sixty incident cases from the Abruzzo region were studied together with 120 unrelated control subjects living in the same administrative areas. The relative risk of diabetes associated with the alleles under study was calculated by deriving the odds ratio (OR) maximum likelihood estimates and their 95% confidence intervals (CI) by the exponentiation of the logistic regression beta-parameter. The combination DRB1*03/DQA1*0501/DQB1*0201 was found in 20.0% of patients and 7.1% of the control subjects, conferring an OR of 4.04 and a CI of 1.97-8.49. The combination DRB1*04/DQA1*0301/DQB1*0302 was found in 23.3% of diabetic patients and 6.7% of controls, giving an OR of 5.69 and a CI of 2.77-12.05. DRB1*11/DQA1*0505/DQB1*0301 and DQA1*0505/DQB1*0301 were negatively associated with type 1 diabetes (OR=0.27, CI 0.11-0.57; OR=0.07, CI 0.02-0.19). The DQA1 genotype at risk was found to be DQA1*0301/DQA1*0501: OR=23.80, CI 2.97-190.89, as it occurred with the highest frequency in the patient group. The DQB1 genotype at risk was found to be DQB1*0201/DQB1*0302, which occurred in 13.3% of patients but in only 1.1% of the control group (OR=29.75, CI 5.36-549.25). Our results shed further light on the risk of development of this disease during a specific time period in an area where the overall incidence of type 1 diabetes is known.

Controlled study in diabetic children comparing insulin-dosage adjustment by manual and computer algorithms.

A controlled trial of a new microprocessor device for insulin-dosage adjustment was undertaken in two matched groups of a priori well-controlled diabetic children. A prospective study design with three equal 8-wk periods was used. In the first period, both groups used manual methods for insulin-dosage adjustment after manual criteria. In the second period, one group of children adjusted insulin dosage by computer algorithms, whereas the other continued to use manual methods. In the third period, both groups again adjusted insulin by traditional methods. Mean premeal glycemia and glycosylated hemoglobin levels did not change in either group throughout the study. During the second period, episodes of hypoglycemia were more frequent in children without the computer than in those who used the device. In keeping with the latter outcome, the group that used the microprocessor device was given less insulin in the second period than the first (0.88 +/- 0.02 vs. 0.94 +/- 0.02 U.kg-1.day-1, P less than 0.0001) and in comparison to the control group of patients who concurrently were given an increased insulin dose in the second period compared with the first. This study showed that insulin treatment through specific computer-mediated dosage-adjusting algorithms was safe and minimized hypoglycemia by effectively accommodating seasonally changing insulin requirements. We recommend the device to help diabetic children and their families in the care of insulin-dependent diabetes.

Increased Na+/Li+ countertransport activity may help to identify type 1 diabetic adolescents and young adults at risk for developing persistent microalbuminuria.

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.

Increased vascular endothelial growth factor serum concentrations may help to identify patients with onset of type 1 diabetes during childhood at risk for developing persistent microalbuminuria.

This study was designed to evaluate whether vascular endothelial growth factor serum concentrations may identify adolescents with onset of type 1 diabetes during childhood at greater risk to develop persistent microalbuminuria and incipient diabetic nephropathy. In January 1989, vascular endothelial growth factor serum levels were measured in 101 normoalbuminuric diabetic children and adolescents (aged 7-14.9 yr; onset of diabetes before age 18 yr; duration of diabetes >7 yr). Participants were clinically examined at baseline and annually thereafter. Vascular endothelial growth factor serum concentrations were measured every year during the 8-yr follow-up period. Over 8 yr, 11 of 101 patients (10.9%) developed persistent microalbuminuria; no patient developed overt nephropathy. The risk of developing microalbuminuria was higher in children with increased vascular endothelial growth factor serum levels (using 160 pg/ml as the arbitrary cut-off point; group 1) compared with those with normal vascular endothelial growth factor serum levels at the beginning of the study (group 2; 19.2 vs. 2.0%; P < 0.01; sensitivity, 90.9%; specificity, 53.3%). The odds ratio for the occurrence of microalbuminuria after adjustment for confounding variables (albumin excretion rate, sex, hemoglobin A(1c), mean blood pressure, cholesterol, and triglycerides) in type 1 diabetic adolescents with elevated vascular endothelial growth factor serum levels was 4.1 (95% confidence interval, 2.0-10.9). These results suggest that vascular endothelial growth factor serum concentrations may be one of the predictors and risk factors for microalbuminuria and incipient diabetic nephropathy in adolescents and young adults with onset of diabetes during childhood. Persistently increased vascular endothelial growth factor serum levels may help to identify normotensive, normoalbuminuric patients with type 1 diabetes who are predisposed to develop persistent microalbuminuria later in life.

Incidence of insulin-dependent diabetes mellitus (0-14 years) in the Abruzzo Region, Italy, 1990-1995: results from a population-based register.

OBJECTIVE: To provide incidence data of insulin dependent diabetes mellitus (IDDM) in the Abruzzo Region, Italy in 0-14 year-old children and contribute to a better understanding of IDDM geographical variability throughout Italy. SUBJECTS AND METHODS: All incident cases younger than 15 years first diagnosed with IDDM according to the WHO criteria between 1 January 1990 and 31 December 1995 and resident in the Abruzzo Region were recorded. The primary sources were divisions of pediatrics, endocrinology or medicine, diabetic centers for adult patients and the Regional Pediatric Diabetology Centre. Secondary independent sources included registered prescriptions for insulin in local district units of the National Health System and the regional IDDM association for children. RESULTS: During the six years, 117 new cases of IDDM in the age-group 0-14 were identified, with an overall standardized incidence rate of 9.34/100,000/year (95% C.I. 7.76-10.95). The crude incidence rate was highest in the 10-14 year age-group (10.64, 95% C.I. 7.66-13.62). Teramo province showed the highest standardized incidence rate, 10.30/100,000/year (95% C.I. 6.58-14.02); it is noteworthy that the IDDM rate in Teramo (15.40/100,000/year) was the highest in peninsular Italy in 1994. Abruzzo Region shows significantly higher rates than other central Italian regions. No significant difference in rates between males and females was observed. Seasonality was not observed from incidence data. CONCLUSIONS: We report the highest incidence rate for IDDM in children in the Italian mainland in the years 1990-95. Our findings confirm the need for epidemiological research to provide more information about the distribution of genetic markers and the etiologic role of environmental factors in Italian regions.

Metabolic control in children and adolescents with diabetes: experience of two Italian Regional Centers.

A survey on glycemic control in 201 diabetic children and adolescents, aged 0-18 years, was performed in two Italian Centers for Childhood Diabetes (Chieti and Parma). Mean HbA1c was 7.8+/-1.4 (range 4.8-13.3%; median 7.6%). With progression of diabetes duration, deterioration of glycemic control was observed (r=0.20; p< 0.002), more evident in girls than in boys, with peaks at 14 (8.9+/-2.0 vs 6.9+/-1.7%; p<0.05) and 16 years (9.5+/-1.4% vs 8.1+/-1.1; p<0.02). No differences were found in BMI values in boys or girls, or for insulin doses which were increased significantly in both sexes according to age (r= 0.33, p<0.04). The number of insulin injections did not influence glycemic control. Only one severe hypoglycemic episode was reported during the period of observation. This study demonstrates that modern management, continuous education and patient and family empowerment are effective in attaining excellent glycemic control without increasing the risk of hypoglycemia.

Health-related quality of life and treatment preferences in adolescents with type 1 diabetes. The VIPKIDS study.

A multi-centre, observational, cross-sectional study was carried out to determine whether the health-related quality of life (HRQOL) of adolescents with type 1 diabetes is affected by different insulin treatment systems, and which features of HRQOL are impacted by the respective insulin treatment. The study regarded 577 adolescents, aged 10-17 years, with type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) (n = 306) or multiple daily injections (MDI) (n = 271). The Insulin Delivery System Rating Questionnaire was validated in Italian and was self-completed by the subjects during a routine visit to the centres. Subjects were compared following the domains of the questionnaire. Good HRQOL was seen in subjects treated with either MDI or CSII. Significant differences were not found in the domains for general diabetes, including diabetes worries, social burden and psychological well-being. Multiple quantile regression analysis showed that CSII confers significant advantages in terms of HRQOL with improvements in treatment satisfaction, perceived clinical efficacy and reduction in treatment interference with daily activities. This favourable impact was more evident in subjects reporting lower HRQOL scores, suggesting that CSII may be especially useful for individuals perceiving a poor HRQOL. Analysis of the domains indicated that CSII was associated with a higher HRQOL than MDI. Life-course HRQOL evaluation using a standardised questionnaire can ensure better chronic disease management. This is particularly important when providing individualised care for adolescents, as they become increasingly responsible for managing their diabetes.

Early diagnosis of 5alpha-reductase deficiency in newborns.

5Alpha-reductase-2 deficiency is a rare autosomal recessive form of 46,XY disorders of sex differentiation (DSD), caused by mutations in the steroid 5alpha-reductase type 2 gene (SRD5A2), presenting at birth with variable degrees of undervirilization. We report on three Italian newborns with 46,XY DSD in whom the evaluation of testosterone, dihydrotestosterone, testosterone/dihydrotestosterone (T/DHT) ratio and molecular analysis of the 5alpha-reductase type 2 gene was made in their first month of life. Baseline T/DHT ratio suggested 5alpha-reductase-2 deficiency; the diagnosis was confirmed by molecular genetics (homozygous mutation in exon 4 [G196S], heterozygous mutation in exon 1 and 5 [W35X/Y235F], heterozygous mutation plus polymorphism in exon 1 [G34W/A49T]). Proper investigation permitted early reassignment to male sex in two babies, assigned to female sex just after birth. In infancy, the T/DHT ratio, assessed by suitable assay methods and evaluated by age-appropriate reference values, seems to be able to select newborns affected by 5alpha-reductase-2 deficiency. Molecular analysis of the SRD5A2 gene should be warranted in newborns with abnormal ratio before sex assignment.

Enhanced soluble CD40 ligand contributes to endothelial cell dysfunction in vitro and monocyte activation in patients with diabetes mellitus: effect of improved metabolic control.

AIMS/HYPOTHESIS: Inflammation plays a pathogenic role in the development of accelerated atherosclerosis in diabetes. Soluble CD40 ligand (sCD40L) is enhanced in diabetes; however, the molecular mechanisms linking sCD40L to accelerated atherosclerosis in diabetes are still unclear. We tested the hypothesis that sCD40L may be involved in the vascular complications in diabetes and exerts its effect by triggering inflammatory reactions on mononuclear and endothelial cells (ECs). METHODS: We studied 70 patients, 40 with type 2 and 30 with type 1 diabetes, with a history or physical examination negative for cardiovascular disease, and 40 non-diabetic and 30 healthy subjects, matched with the type 2 and type 1 diabetic patients, respectively. Plasma and serum sCD40L, and plasma soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, E-selectin and monocyte chemo-attractant protein-1 (MCP-1) were measured. Adhesion molecules and MCP-1 release, the ability to repair an injury in ECs, and O2- generation in monocytes were analysed in vitro after stimulation with serum from patients or controls. RESULTS: Type 2 and type 1 diabetic patients had significantly higher sCD40L levels than controls. Furthermore, high sCD40L was associated with in vitro adhesion molecules and MCP-1 release, impaired migration in ECs and enhanced O2- generation in monocytes. Improved metabolic control was associated with a reduction of plasma sCD40L by 37.5% in 12 type 1 diabetic patients. Furthermore, elevated sCD40L in diabetic patients was significantly correlated with HbA1c levels. CONCLUSIONS/INTERPRETATION: Upregulation of sCD40L as a consequence of persistent hyperglycaemia in diabetic patients results in EC activation and monocyte recruitment to the arterial wall, possibly contributing to accelerated atherosclerosis development in diabetes.

Plasma renin and aldosterone in youngsters with insulin-dependent diabetes mellitus.

We studied plasma renin activity (PRA) and aldosterone in three groups of subjects. Group 1 consisted of seven Type I diabetics with microalbuminuria (greater than 25 micrograms/min), age 12.0-19.5 yr (mean +/- SD: 15.4 +/- 2.2), duration of disease 6.5-10.1 yr (7.9 +/- 1.9), HbA1c 9.6-16.0% (12.6 +/- 2.9). Group 2 consisted of seven sex and age-matched diabetics, duration of disease 3.7-9.0 yr (6.0 +/- 2.3), HbA1c less than 8%, microalbuminuria less than 10 micrograms/min, and microangiopathy-free. Group 3 consisted of seven healthy subjects. After overnight recumbency the PRA in group 1 patients was significantly higher than that for group 2 (3.926 +/- 4.54 ng/ml/h vs. 1.416 +/- 0.44; p less than 0.05) or for group 3 (3.926 +/- 4.54 vs. 1.11 +/- 0.82; p less than 0.007). After physical exercise the group 1 PRA value (10.199 +/- 9.62) was higher than in either group 2 (2.821 +/- 1.77; p less than 0.005) or group 3 (1.61 +/- 0.803; p less than 0.0006). Poor metabolic control and the presence of microalbuminuria can play a role in perturbations of the Renin-Angiotensin system. The presence of microalbuminuria can be an important indicator of mildly impaired renal function and may influence PRA production.

Effects of ketoacidosis and puberty on basal and TRH-stimulated thyroid hormones and TSH in children with diabetes mellitus.

Basal and TRH-stimulated thyroid hormones and TSH were evaluated in two groups of prepubertal and pubertal diabetics: group B - 45 children without ketoacidosis; group C - 16 children with ketoacidosis. The diabetic patients showed no signs of diabetic microangiopathy. Fifty-three healthy subjects served as controls (group A). T4, T3, FT4 and FT3 serum levels were reduced in diabetics, particularly in ketotic ones; T4 and T3 values were lower in pubertal than in prepubertal non-ketotic diabetics and in pubertal than in prepubertal controls, while no significant difference was observed between pubertal and prepubertal ketotic patients. Moreover, no difference in rT3 serum concentrations was found between group A, B and C, but non-ketotic and ketotic pubertals showed a significant rT3 reduction if compared with non-ketotic and ketotic prepubertals and with healthy pubertals. TBG was lower in group B and group C diabetics than in controls. After TRH stimulus, T3 levels showed a significant increase both in controls and in non-ketotic diabetics, while no variation was observed in ketotic children; furthermore, at 120 minutes T3 values were lower in diabetic than in healthy children, particularly in ketotic ones. Basal TSH serum concentrations were reduced in ketotic diabetics, while no difference was found between nonketotic and control subjects. After TRH stimulus, TSH peak was higher in pubertal non-ketotic diabetics than in pubertal controls, while no difference was found between prepubertal and pubertal diabetics, both in non-ketotic and in ketotic status.(ABSTRACT TRUNCATED AT 250 WORDS)