Effect of insulin with concurrent amino acid infusion on protein metabolism in rapidly growing pubertal children with type 1 diabetes

Insulin treatment of prepubertal children with insulin-dependent diabetes improves body protein balance by decreasing the rate of protein degradation without stimulating protein synthesis. However, insulin also causes hypoaminoacidemia, so the inability of insulin to stimulate protein synthesis may have been limited by substrate availability. We investigated the ability of insulin to stimulate protein synthesis in growing pubertal children who were given sufficient amino acids to counter insulin-induced hypoaminoacidemia. Protein metabolism in six pubertal children with type 1 diabetes was assessed from leucine kinetics during a primed, 6-h infusion of L-[1-(13)C]leucine. The children were studied in the postabsorptive state during a basal (insulin withdrawn) period and during the infusion of 0.83 mU * kg(-1) * min(-1) human regular insulin. Amino acids and glucose were given with insulin to prevent hypoaminoacidemia and hypoglycemia. Net leucine balance was significantly higher with insulin than in the basal state, the result of decreased protein degradation but also decreased protein synthesis. The data suggest that insulin alone does not increase protein synthesis in pubertal children with type 1 diabetes.     

Transition from multiple daily injections to continuous subcutaneous insulin infusion in type 1 diabetes mellitus

OBJECTIVE: To review our experience with insulin dosing during the conversion from multiple daily injections to continuous subcutaneous insulin infusion (CSII) for children and adolescents with type 1 diabetes mellitus. STUDY DESIGN: The charts of 65 children who started CSII from January 1998 to April 2000 were reviewed. Data regarding insulin dose and hemoglobin A1c levels were collected from the prepump visit and first (at 1 to 2 months) and second (at 3 to 6 months) visits after being placed on pump therapy. RESULTS: Pubertal patients had a decrease in total insulin dose taking CSII; prepubertal patients had little change (-18 +/- 3.5% vs -1.7 +/- 5%, P =.01). On CSII, the basal insulin dose comprised 40% to 45% of total insulin in both prepubertal and pubertal patients. Maximal basal rate in prepubertal patients occurred from 9 PM to 12 AM and in pubertal patients from 3 AM to 9 AM and from 9 PM to 12 AM. CONCLUSION: Guidelines established for CSII dosing in adults do not necessarily apply to children. The total daily insulin dose needs to be decreased in pubertal patients but may remain unchanged in prepubertal patients. The basal rate comprises 40% to 45% of the total daily insulin dose, and the timing of maximum basal rates is likely to occur in the late evening hours in prepubertal children.     

Insulin resistance of puberty in African-American children: lack of a compensatory increase in insulin secretion

Type 2 diabetes has been increasing in children, mostly affecting minority populations at around the age of puberty. Despite a multitude of studies demonstrating pubertal insulin resistance/hyperinsulinemia in white children, data are almost non-existent in African-American children. The aim of the present study was to investigate the impact of puberty on glucose metabolism, insulin sensitivity and secretion in African-American children. Twenty prepubertal and 16 pubertal African-American subjects participated. All underwent a 3-h hyperinsulinemic (40 mU/m(2)/min) euglycemic clamp to determine insulin-stimulated glucose disposal, and a 2-h hyperglycemic (12.5 mmol/L) clamp to assess first- and second-phase insulin secretion. Body composition was assessed by dual energy X-ray absorptiometry (DEXA) and visceral and subcutaneous abdominal adiposity with computed tomography (CT) scan at L4-L5. Total glucose disposal, glucose oxidation and non-oxidative glucose disposal were significantly lower in the pubertal group compared with the prepubertal one (53.8 +/- 3.9 vs. 72.2 +/- 5.0 micromol/kg/min, p = 0.009; 23.3 +/- 1.1 vs. 31.6 +/- 1.7 micromol/kg/min, p = 0.001; and 30.0 +/- 3.3 vs. 40.5 +/- 3.9 micromol/kg/min, p = 0.049, respectively). Insulin sensitivity was approximately 30% lower in the adolescents compared with the prepubertal children. However, first- and second-phase insulin secretions were not different between the two groups (971.4 +/- 180.6 vs. 1044.0 +/- 191.4 pmol/L and 999.6 +/- 159.6 vs. 955.8 +/- 142.2 pmol/L, respectively). In conclusion, despite approximately 30% lower insulin sensitivity in African-American adolescents compared with prepubertal children, insulin secretion is not higher. This is in contrast to published findings in white children in whom insulin secretion is higher during puberty. These racial differences in physiologic adaptation to puberty could play a role in the higher prevalence of type 2 diabetes in African-American children at the time of puberty.     

Bone maturation in 1788 children and adolescents with diabetes mellitus type 1

Diabetes mellitus type 1 might interfere with pubertal development. Particularly, long-term metabolic control and intensity of insulin treatment have been reported to contribute to a delay in pubertal onset. Data on somatic development in diabetic children are conflicting; therefore we studied bone age in 1788 children from Germany and Austria with type 1 diabetes. Bone age was retarded by -0.27 +/- 1.1 years in the whole group, but particularly in the adolescents at the end of puberty (>16 years; -0.76 +/- 1.29y). Bone age delay was more pronounced in boys, and in children with long-term median HbAlc levels of 7.5 - 9.0%. No associations were found with current HbAlc levels or the intensity of insulin treatment. Bone age determinations in diabetic children should only be performed when clinical signs of impaired somatic development are present. In addition, the potential influence of diabetes on bone development needs to be considered in the interpretation of carpograms.     

Initial insulin therapy in children and adolescents with type 1 diabetes mellitus

Weitzel D, Pfeffer U, Dost A, Herbst A, Knerr I, Holl R. Initial insulin therapy in children and adolescents with type 1 diabetes mellitus. Objective: The aim of the study was to define parameters that influence the initial insulin dosage in young subjects with type 1 diabetes regarding the amount of daily insulin, the ratios of basal and prandial insulin, and the insulin/carbohydrate ratios. Study design: We used a computer‐based registry (with prospectively collected data) in Germany and Austria, a software for the management and data documentation of diabetic patients (DPV), to analyze the initial insulin therapy in 2247 children with newly diagnosed type 1 diabetes to identify factors that influence diabetes therapy within the first 10 d. Results: For both genders, glucosylated hemoglobin A1c (HbA1c), blood pH at diabetes onset, and pubertal status are the major factors determining the initial insulin dosage calculated as the amount of daily insulin per kilogram body weight (kg), the basal and prandial insulin dose per kilogram, and day and the insulin/carbohydrate ratios for meals. The frequency of hypoglycemia correlated with increasing quotient of applied to calculated insulin dosage. Conclusion: The predictive factors of insulin requirement may exert beneficial effects on the assessment and adjustment of insulin therapy in young diabetic subjects at disease onset. On the basis of a multiple, linear regression, we suggest a formula to calculate the initial insulin therapy.     

Prevalence and clinical features of type 1.5 diabetes mellitus in children

AIM: To classify children with diabetes mellitus as type 1, 1.5 or 2, based on strict criteria, and then compare their features and treatment. METHODS: In this retrospective study, all children with diabetes mellitus in our clinic with antibody status available (n = 120) were reclassified as type 1, 1.5 or type 2 based on status of antibodies to the pancreas and presence of obesity and/or acanthosis nigricans, and their features compared. RESULTS: Sixty-four percent of type 2 patients were reclassified as type 1.5. Type 1.5 patients had significantly lower BMI SDS, blood pressure and acanthosis nigricans than type 2 patients. They had a higher insulin requirement (0.82 +/- 0.44 U/kg/day) than type 1 (0.72 +/- 0.35 U/kg/day) or type 2 (0.28 +/- 0.3 U/kg/day) patients. Total cholesterol, HDL-cholesterol, ALT and AST significantly worsened from type 1 to 1.5 to type 2 patients. CONCLUSIONS: Type 1.5 diabetes mellitus should be considered among obese adolescents presenting as type 2, as their clinical course is more aggressive and insulin requirement higher.     

Leucine kinetics during simultaneously administered insulin and dexamethasone in preterm infants with severe lung disease

The objective of this study was to determine whether insulin administration would prevent the well-documented catabolic effect of dexamethasone given to preterm infants with chronic lung disease. We studied leucine metabolism in 11 very-low-birth-weight infants before dexamethasone treatment and on d 2, 4, and 7 thereafter. During the first 4 d of dexamethasone, insulin was administered i.v. at a dose of 0.5 (n = 7) or 1.0 (n = 5) IU/kg/d. Leucine turnover was not significantly different between d 0 (337 +/- 41.3 micromol leucine/kg/h), d 2 (288 +/- 27.2 micromol leucine/kg/h), d 4 (302 +/- 22.1 micromol leucine/kg/h), and d 7 (321 +/- 21.2 micromol leucine/kg/h), and neither was leucine breakdown (272 +/- 21.9 micromol leucine/kg/h on d 0, 225 +/- 21.5 micromol leucine/kg/h on d 2, 231 +/- 21 micromol leucine/kg/h on d 4, and 242 +/- 17.6 micromol leucine/kg/h on d 7). Weight gain rates were significantly lower during the first week of dexamethasone treatment compared with the week before treatment or the second and third week. We conclude that during insulin and corticosteroid administration in very-low-birth-weight infants, no changes were observed in leucine kinetics in contrast to previous studies. The decrease in weight gain was not reversed.     

Pubertal changes in serum leptin levels in adolescents with type 1 diabetes mellitus: a controlled longitudinal study

The mechanism of the pubertal delay seen in some adolescents with type 1 diabetes mellitus is not entirely clear. Since leptin has been implicated as a neuroendocrine modulator of puberty, we measured serum leptin levels longitudinally in 24 post-'honeymoon' patients with diabetes mellitus (M/F = 15/9) with a mean (+/- SD) age of 10.5 +/- 0.9 years and 26 controls (M/F = 15/11) with a mean age of 10.0 +/- 1.1 years. Physical examinations; serum leptin, IGF-I, IGFBP-3 and IGFBP-1 levels; and bone age X-rays were performed annually for up to 48 months. Glycosylated hemoglobin (HbA1c) was measured 2-4 times a year in patients with diabetes mellitus. Serum leptin levels strongly correlated with the body mass index z-scores (BMI-Z) in both controls (r = 0.666, p <0.00001) and diabetic patients (r = 0.577, p <0.00001). Girls had increased serum leptin levels for a given BMI compared to boys (p <0.005). There were no significant differences in serum leptin levels of patients with diabetes mellitus compared to controls, nor were differences seen when the groups were stratified by age, Tanner stage, or gender. There were also no significant correlations between serum leptin levels and degree of metabolic control (i.e. HbA1c) or insulin dose standardized for body weight. Although there was no significant diabetes-related or metabolic control-related delay in bone age z-score or pubertal development, there was a significant negative correlation between HbA1c and growth velocity z-score, indicating that children with poor diabetes control had modest but significant slowing of growth. It is concluded that neither pubertal development nor serum leptin levels are significantly altered in adolescents with diabetes mellitus managed with standard therapy. The potential role of leptin in initiation of pubertal development is not easily demonstrable in observational studies.     

Insulin resistance in newly diagnosed type 1 diabetic children and adolescents

The aim of this study was to estimate insulin resistance in newly diagnosed type 1 diabetic children and adolescents and to analyse the correlation between insulin secretion and impaired insulin action. 37 patients with type 1 diabetes mellitus aged 12.9 +/- 3 years were included in the study. Duration of diabetes was 6 months. Euglycemic-hyperinsulinemic clamp was performed to estimate insulin resistance. Glucose disposal rate was calculated as index M - mg/kg/min. Insulin secretion was measured by glucagon test. The serum level of cholesterol, HDL-Ch, triglycerides and HbA1 was examined. The height, weight, skinfold, waist and hip circumference were measured. Body mass index and waist/hip ratio were calculated. In children and adolescents with type1 diabetes mellitus insulin resistance of various degree was observed. The glucose disposal rate (M index) was 3.2 - 11.8 mg/kg/min., mean 7.08 +/- 2.5 mg/kg/min. The insulin resistance depended on patients' age (r= - 0.3, p<0.05,) and the stage of puberty. There was no difference in insulin secretion in insulin-resistant and insulin-sensitive subjects. The insulin resistance was related to BMI (r=-0.33; p=0.04), and with skinfold thickness (r=-0.59; p=0.001). In insulin-sensitive children the insulin dose was lower (0.45: 0.67; p<0.02). No influence of insulin resistance on metabolic control was observed. Insulin resistance is observed in newly diagnosed type 1 diabetic children and adolescents. No relationship between insulin secretion and impaired insulin action was found. Insulin resistance was greater during III Tanner stage of puberty and in obese children.     

Leucine kinetics during feeding in normal newborns

To examine how leucine and protein metabolism is affected by feeding, leucine kinetics were determined in 11 normal term newborns during feeding using a prime constant tracer infusion of 1-13C leucine combined with respiratory calorimetry. Fed newborns were compared with previously studied fasting newborns. Feeding and fasting newborns had similar rates of leucine oxidation (34 +/- 3 mumol/kg/h versus 31 +/- 4 mumol/kg/h) and leucine release from existing protein (156 +/- 16 mumol/kg/h versus 164 +/- 8 mumol/kg/h). In contrast, nonoxidative disposal rates of leucine (a reflection of protein synthesis) were significantly greater in feeding newborns (170 +/- 13 mumol/kg/h versus 129 +/- 9 mumol/kg/h). A significant positive correlation between birth weight and leucine flux was demonstrated in both feeding and fasting newborns. These results suggest that 1) newborns may accomplish protein accretion primarily by increases in protein synthesis rather than suppression of protein breakdown; 2) an estimate can be made of the minimal leucine intake required to replace irreversible leucine oxidative losses (816 mumol/kg/d, 107 mg/kg/d); and 3) the positive correlation between birth weight and leucine flux in both feeding and fasting newborns may be a result of differences in previous protein and energy supplies.     

Improved diabetes control by using ''close adjustment algorithms''

BACKGROUND: Intensive insulin therapy increases the frequency of severe hypoglycemia despite markedly improved glycemic control in patients with type 1 diabetes mellitus. To determine the optimal dose of insulin, the authors designed algorithms based on self-monitored blood glucose levels. METHODS: Each dose of insulin was composed of two components: a basal dose determined on the basis of blood glucose levels over the previous two days and an additional dose determined on the basis of blood glucose level just before insulin injection. The patients were instructed to adjust each dose according to the algorithms. The authors investigated the effects of using algorithms on glycemic control, anthropometric data, body composition, and lipid profile in seven females with type 1 diabetes 12-20 years old. RESULTS: After 3 months, the daily dose of insulin increased significantly from 0.93 +/- 0.18 to 1.16 +/- 0.26 units/kg of body weight, and haemoglobin A(1C) decreased significantly from 8.27 +/- 1.33 to 6.50 +/- 0.64%. Severe hypoglycemia, however, did not occur. Body mass index increased significantly from 21.7 +/- 2.7 to 22.7 +/- 2.9 kg/m(2) with no increase in the percentage of body fat. All lipid-profile data showed a decreasing trend. CONCLUSIONS: Algorithms developed on the basis of self-monitored blood glucose levels are useful in determining the optimal dose of insulin and can improve glycemic control and lipid metabolism.     

Decreased lumbar spine bone mass and low bone turnover in children and adolescents with insulin dependent diabetes mellitus followed longitudinally

The effects of insulin dependent diabetes mellitus (IDDM) on bone metabolism are still not well defined. We evaluated total bone mineral content (TBMC) and bone mineral density (BMD) at the lumbar spine and femoral neck using dual X-ray absorptiometry in 26 IDDM children (15 M, 11 F) with a mean chronological age of 12.1+/-3.1 yr (range 7.1-14.2 yr). Duration of diabetes was 4.3+/-2.9 yr, with a mean glycosylated hemoglobin of 9.2+/-0.4%. BMD and TBMC standard deviation scores (Z-scores) were determined by comparing our results to controls matched for age, sex and pubertal status. BMD and bone formation and resorption markers were determined at the beginning of the study and after one year of follow up. Mean lumbar spine Z-score was -1.06+/-0.2, with negative values in 24 of 26 children (92.6%); 14/26 patients (53.8%) had a lumbar spine Z-score >1.0 SD below the mean. Mean lumbar spine Z-score remained unchanged after one year of follow up (-1.02+/-0.3). No significant differences were obtained in femoral neck BMD or TBMC between groups. No correlation was observed between lumbar spine BMD Z-scores and duration of IDDM or degree of diabetes control, as assessed by the mean glycosylated hemoglobin. Daily urinary calcium excretion was elevated in our patients initially and after one year of follow up; however, no correlation was obtained between lumbar spine BMD and 24 h urinary calcium excretion. Carboxy-terminal propeptide of type 1 collagen values and levels of urinary cross-linked N-telopeptides of type 1 collagen in the diabetic children were significantly lower than those of the matched controls. Osteoblastic activity as assessed by serum osteocalcin and by the carboxy-terminal propeptide of type I collagen and bone resorption as measured by cross-linked N-telopeptides of type 1 collagen did not correlate with the lumbar spine Z-scores. When IDDM patients were subdivided into males and females and into children with more than or less than 2 yr duration of diabetes since diagnosis, no differences between groups were found. These results suggest that insulin dependent diabetes in children is associated with low bone turnover resulting in a deficit in bone mass which may be manifested as osteopenia in the growing bone. This defect is already present in trabecular bone early on in the disease and seems not to be related to glycemic control.     

Response of circulating ghrelin levels to insulin therapy in children with newly diagnosed type 1 diabetes mellitus

Ghrelin is secreted primarily by the stomach, although other tissues such as the pancreas synthesize a minor proportion. The discovery of a new cell type that produces ghrelin in the human pancreas and that this organ expresses GHS-R opens new perspectives in the understanding of the control of glucose metabolism. We have studied 22 children with newly diagnosed type 1 diabetes mellitus at four different points: at diagnosis before insulin therapy, after 48-60 h of insulin therapy, and after 1 and 4 mo of insulin treatment. At each point circulating levels of ghrelin, leptin, IGF-I, IGF binding protein (IGFBP)-1, IGFBP-2, IGFBP-3, and glucose were determined. Ghrelin levels were significantly decreased at diagnosis (573 +/- 68 pg/mL, p < 0.01) compared with controls (867 +/- 38 pg/mL) and remained decreased after insulin therapy (d 2: 595 +/- 68 pg/mL; 1 mo: 590 +/- 61 pg/mL; 4 mo: 538 +/- 67 pg/mL) with no differences before or after insulin treatment. There was a negative correlation between ghrelin levels and body mass index at all of the study points, whereas a negative correlation between ghrelin and glucose concentrations was only observed after insulin therapy. No correlation between ghrelin and HbA1c was found at any point. A positive correlation between ghrelin and IGFBP-1 was found after insulin therapy, but no correlation with other members of the IGF system or leptin was found. In conclusion, these data could indicate a possible link between glucose concentrations and ghrelin; hence, the persisting low ghrelin levels in diabetic children may suggest a defensive mechanism against hyperglycemia.     

The effect of 3 years of recombinant growth hormone therapy on glucose metabolism in short Chinese children with beta-thalassemia major

Growth retardation and diabetes mellitus are common in children and adolescents with beta-thalassemia major despite hypertransfusion regimen and iron chelation therapy. The purpose of this study was to investigate the effects of growth hormone (GH) treatment on glucose metabolism in children with beta-thalassemia major. GH therapy for 3 years improved the height SD scores of eight short prepubertal Chinese children with beta-thalassemia major from -2.15 +/- 0.90 to -1.14 +/- 0.78 (paired t-test, p = 0.01) without excessive advancement in bone age (ABA/CA = 0.95 +/- 0.27). There was no deleterious effect on glucose metabolism with no change in fasting blood sugar, serum fructosamine, fasting and stimulated insulin to intravenous glucose infusion (sum of 1+3 min insulin, In 1+3'; incremental insulin 0-10 min area above fasting concentrations, deltaInAUC0-10'; ratio of incremental 0-10 min insulin area above fasting concentrations over glucose area above fasting concentrations, delta0-10'AUCIn/G; ratio of incremental 0-10 min insulin over peak glucose above basal 0-10 min, delta0-10'InAUC/deltaGPeak), and glucose disappearance coefficient (Kg). Short term GH therapy improves the height of children with beta-thalassemia major but the effect of treatment on final height still needs to be determined.     

Management of hyperglycemia in minority children with type 2 diabetes mellitus

This paper discusses management of hyperglycemia in minority children with type 2 diabetes mellitus (DM). Over the past several years the incidence of type 2 DM in minority children and adolescents has markedly increased. Intensive management of children with type 2 DM includes exercise, diet, insulin therapy, oral drug (metformin) therapy, and combination insulin-oral drug therapy. The results of a study of the efficacy of treatment modalities in 35 African-American children are presented. In the study, the patients were divided into two groups, one treated with diet or metformin therapy (20 children) and the other with insulin or a combination of insulin and metformin (15 children). All of the children in the study were negative for antibodies to glutamic acid decarboxylase. Plasma glucose and serum C-peptide concentrations were measured at 0, 30, 60, 90, and 120 min after ingestion of a liquid meal (Sustacal) (7 ml/kg with a maximum of 360 ml). The increase of C-peptide (ACP) in response to the mixed meal was calculated by peak minus fasting C-peptide. ACP was significantly higher in those children treated with diet/metformin than in those treated with insulin/insulin and metformin combination therapy (4.6 +/- 1.9 vs 21 +/- 1.6, p <0.01). Mean HbA1c at one-year follow up was lower for the diet/metformin patients than in the insulin/insulin and metformin group (7.0 +/- 2.8 vs 11.4 +/- 3.7, p <0.01). Our results indicate that in children with type 2 DM, there is more severe pancreatic beta-cell dysfunction in the group of children requiring insulin therapy.     

Insulin detemir is characterized by a more reproducible pharmacokinetic profile than insulin glargine in children and adolescents with type 1 diabetes: results from a randomized, double-blind, controlled trial

Insulin detemir (detemir) has previously been shown to be associated with lower within-subject variability compared with other basal insulin preparations in adults with type 1 diabetes mellitus (T1DM). This randomized, double-blind, crossover trial compared the within-subject variability of detemir and insulin glargine (glargine) in pharmacokinetic properties in children and adolescents with T1DM. The trial enrolled 32 children and adolescents (19 girls and 13 boys; mean +/- SD: age 13 +/- 2.5 yr and T1DM duration 6.3 +/- 3.0 yr) with a hemoglobin A1c (HbA1c) of 7.9 +/- 1.0%. Participants were randomized to a specific treatment sequence in which a dose of 0.4 U/kg of detemir and glargine was injected subcutaneously 24 h apart at each of two dosing visits. Insulin concentrations were measured at frequent intervals for a period of 16-h post-dosing. Detemir showed statistically significantly less within-subject variability compared with glargine with a 3.1-fold and 2.9-fold lower coefficient of variation (CV, %) for the area under the concentration-time curve [AUC((0-16) (h))] and the maximum concentration (C(max)), respectively. Separate analyses demonstrated a 2.5-fold and 2.9-fold lower CV (%) with detemir in children (8-12 yr) and a 4-fold and 3.8-fold lower CV (%) with detemir in adolescents (13-17 yr). No safety concerns were raised during the trial. In conclusion, within-subject variability in pharmacokinetic properties was significantly lower for detemir than for glargine in children and adolescents with T1DM. This indicates a less variable absorption with detemir, which is expected to be associated with a more predictable therapeutic effect also in this population.     

Ghrelin, IGF-I and IGFBP-3 levels in children with type 1 diabetes mellitus

There is a strong relationship between ghrelin, insulin, glucose and IGF-I/IGFBP-3 metabolism. This aim of this study was to investigate ghrelin level, and its relationship with IGF-I and IGFBP-3 levels in children with type 1 diabetes mellitus (DM1). Twenty-seven children with DM1 and 25 healthy controls were investigated. Ghrelin levels were similar, and IGF-I and IGFBP-3 levels were lower, in prepubertal and pubertal patients compared to controls. In the patient group, ghrelin levels were negatively correlated with chronological age, height, weight, pubertal status and IGF-I, but had no correlation with fasting glucose, HbA1c, insulin dose, duration of insulin therapy, and IGFBP-3 levels. Similar ghrelin levels in patients compared to controls may suggest that ghrelin levels remain unchanged in children with DM1, or that altered ghrelin levels at diagnosis recover as a consequence of insulin therapy. The lack of correlation of serum ghrelin levels with fasting plasma glucose, HbA1c and insulin dose suggests that ghrelin level is not affected by these parameters. Decreased IGF-I level and its negative correlation with ghrelin are compatible with previous findings.     

Prevalence of type 2 diabetes mellitus and impaired glucose tolerance in obese Argentinean children and adolescents

The aim of this study was to evaluate the prevalence of type 2 diabetes mellitus (DM2) and impaired glucose tolerance (IGT) in obese children and adolescents and to examine insulin resistance and insulin secretion. We studied 427 asymptomatic obese patients. DM2 and IGT were diagnosed by an oral glucose tolerance test. Insulin resistance and P-cell function were assessed by using homeostasis model assessment (HOMA), insulin/glucose index (I/GI), fasting insulin and insulin sensitivity index (ISI-composite). Thirty patients showed IGT (7%) and seven had DM2 (1.6%). The mean age was 10.7 +/- 3.5 years, the diabetic group being significantly older than the normal group (p < 0.01). The mean body mass index was 30 +/- 5.3 kg/m2 without significant differences between groups. beta-Cell function declined significantly in the patients with IGT and DM2, and insulin resistance increased significantly. Given the rather high prevalence of glucose metabolism impairment, children with obesity should undergo glucose tolerance testing for appropriate therapeutic intervention.     

Characterization of alterations in carbohydrate metabolism in children with Prader-Willi syndrome

OBJECTIVE: To study carbohydrate metabolism and insulin sensitivity and secretion in children and adolescents with Prader-Willi syndrome (PWS) compared with multifactorial obesity (MO) controls. PATIENTS AND METHODS: Seventy-five patients with PWS and 395 controls with MO were studied by oral glucose tolerance test. Insulin resistance (IR) and beta-cell function were assessed by homeostasis model assessment (HOMA), insulin glucose index, fasting insulin and insulin sensitivity index. RESULTS: The incidence of diabetes mellitus was 0% in PWS and 1.5% in MO, while carbohydrate intolerance was 9.3% in the former group and 7.6% in the latter (NS); basal insulin level (12 +/- 8.2 vs 22.3 +/- 25 mU/ml) and HOMA-IR (2.47 +/- 1.6 vs 4.18 +/- 5.05) were lower in PWS (p = 0.004 and 0.04, respectively), whereas HOMA beta-cell index was lower in PWS than in MO (59 +/- 42 vs 102 +/- 119, p = 0.03). ISI Composite was higher in PWS compared to MO (6 +/- 5.7 vs 4.18 +/- 5.05, p = 0.04). CONCLUSION: Patients with PWS presented lower insulin resistance and a dissociation between beta-cell secretion and the degree of obesity.     

The influence of physical activity on ghrelin and IGF‐1/IGFBP‐3 levels in children and adolescents with type 1 diabetes mellitus

Huber J, Fröhlich‐Reiterer EE, Sudi K, Suppan E, Weinhandl G, Jasser‐Nitsche H, Aigner R, Borkenstein MH. The influence of physical activity on ghrelin and IGF‐1/IGFBP‐3 levels in children and adolescents with type 1 diabetes mellitus. Objectives: The aim of the study was to determine the influence of regular physical activity on ghrelin and IGF‐1/IGFBP‐3 levels during a diabetes camp. Methods: Twenty‐eight children and adolescents (14 boys; mean age 12.1 yr) with type 1 diabetes mellitus (T1DM, mean duration of diabetes 4.8 yr) attending a 2‐wk diabetes camp that features increased regular physical activities have been studied. Serum levels of ghrelin (total and acylated), growth hormone (GH), insulin‐like growth factor‐1 (IGF‐1), insulin‐like growth factor‐bindng protein‐3 (IGFBP‐3) and insulin were measured in fasting state on day 1 and day 14. Improvement of metabolic control was documented by haemoglobin A1c (HbA1c). Glucose levels and insulin doses were determined daily. Results: Mean insulin dosage decreased from 0.87 to 0.78 U/kg/d, mean HbA1c levels decreased from 8.6 to 8.3%, but the changes were not statistical. There was a significant decline in total ghrelin. IGFBP‐3 and IGF‐1 decreased also significantly. Total basal ghrelin was inversely related to the change in IGFBP‐3. Conclusions: We hypothesize an association between ghrelin and metabolic control in T1DM. Higher ghrelin levels might be associated with poor metabolic control. The dynamic of IGFBP‐3 levels appears to be under the influence of basal ghrelin concentrations in T1DM.