Euthyroid sick syndrome in type I diabetes mellitus in children and adolescents

We studied concentrations of thyroid hormones (T3, T4, FT4, rT3, TBG and TSH) in 62 type I diabetic children and adolescents. The patients were classified into group A (n = 27, good control, HbA1c less than 10%), group B (n = 19, poor control, HbA1c greater than 10%) and group C (n = 16, diabetic ketoacidosis, pH less than 7.1 and HCO3 less than 15 mmol/L. All patients were treated with two daily injections of purified monocomponent insulins. Thirty healthy subjects of the same age served as control group. Patients in group B and C had significantly lower T3 and higher rT3 levels (p less than 0.001) compared to the matched controls (1.5 vs 2.2; 0.9 vs 2.2; 0.58 vs 0.3 and 0.6 vs 0.3 nmol/L). Serum TBG levels were significantly lower (p less than 0.01) in the group A (19.5 +/- 4.3 mg/L), group B (20.3 +/- 3.3) and group C (18.0 +/- 3.4) compared with control group (24.2 +/- 3.1). There was significantly negative correlation between T3 and HbA1c in group B (r = 0.546; p less than 0.02). The results of this study confirm that euthyroid sick syndrome does exist in type I diabetic children and adolescents with poor metabolic control and ketoacidosis. The inverse relationship between T3 and HbA1c percentage (low T3 and high HbA1c) points to the poor diabetic control.     

Varying role of vitamin D deficiency in the etiology of rickets in young children vs. adolescents in northern India

The relative importance of calcium vs. vitamin D deficiency in the etiology of nutritional rickets in the tropics may be different in children compared with adolescents. We studied calcium intake, sun exposure, serum alkaline phosphatase, and 25 hydroxyvitamin D in 24 children and 16 adolescents with rickets/osteomalacia. The values were compared with those obtained in control subjects (34 children and 19 adolescents). We found that young children with rickets had lower calcium intake compared with controls (285 +/- 113 vs. 404 +/- 149 mg/day, p < 0.01), but similar sun exposure (55 +/- 28 vs. 56 +/- 23 min x m2/day) and 25 hydroxyvitamin D (49 +/- 38 vs. 61 +/- 36 nmol/l). Sixteen of 24 children with rickets had 25 hydroxyvitamin D above the rachitic range (> 25 nmol/l), in contrast to one of 16 adolescents. Adolescent patients had low calcium intake vs. controls (305 +/- 196 vs. 762 +/- 183 mg, p < 0.001), and lower sunshine exposure (16 +/- 15 vs. 27 +/- 17 min x m2/day, p < 0.01) and serum 25 hydroxyvitamin D (12.6 +/- 7.1 vs. 46 +/- 45.4 nmol/l, p < 0.001). The odds ratio for developing rickets with a daily calcium intake below 300 mg was 4.8 (95 per cent CI, 1.9 - 12.4, p = 0.001). Subjects with rickets were randomized to receive 1 g calcium daily, with or without vitamin D. Children showed complete healing in 3 months, whether they received calcium alone or with vitamin D. Adolescents showed no response to calcium alone, but had complete healing with calcium and vitamin D in 3-9 months (mean 5.3 months). Thus deficient calcium intake is universal among children and adolescents with rickets/osteomalacia. Inadequate sun exposure and vitamin D deficiency are important in the etiology of adolescent osteomalacia.     

Improved folate status in children and adolescents during voluntary fortification of food with folate

OBJECTIVE: To assess longitudinal changes in folate status in South Australian children and adolescents during fortification of food with folic acid. METHODS: Sixty-nine children and adolescents (age 12.8 +/- 2.3 years), 47 with diabetes and 22 healthy controls, had their folate status assessed at the beginning of 1999 and again after a mean 1.1 +/- 0.23 years. Intake of folate at baseline was assessed with a quantitative food frequency questionnaire. RESULTS: Baseline red cell folate (mean +/- standard deviation (SD)) was 756 +/- 294.5 nmol/L and remained constant at follow up at 736 +/- 299 nmol/L (P = 0.55) in the whole group. Serum folate increased from 24.4 +/- 6.3 nmol/L to 27.2 +/- 8.8 nmol/L (P = 0.002). Children with diabetes showed a significant increase in serum folate (from 26.3 +/- 5.7-30.1 +/- 7.9, P < 0.001) and stable red cell folate (835.8 +/- 278.6 and 808.6 +/- 296.7, P = 0.51) between baseline and the second samples, while controls showed stable serum (20.4 +/- 5.7 and 21.1 +/- 7.7, P = 0.7) and red cell folate (586.6 +/- 255.9 and 579.8 +/- 240.1, P = 0.92). A third sample collected in 17 subjects after a further 9 +/- 1.3 months showed a further increase in serum and red cell folate. Mean folate intake at baseline was 301 +/- 129 micro g/day, below the mean recommended for prevention of neural tube defects. CONCLUSIONS: Voluntary fortification of food with folate is associated with improved folate status in South Australian children and adolescents, but may not be sufficient at current levels to provide maximal protection against neural tube defects at a population level.     

Children with coeliac disease and insulin dependent diabetes mellitus--growth, diabetes control and dietary intake

We aimed to assess the growth, diabetes control, dietary intake and compliance with a gluten-free diet in children with insulin dependent diabetes mellitus (IDDM) and coeliac disease in a major paediatric and adolescent diabetes clinic. Children with IDDM and biopsy-proven coeliac disease aged <18 years were included and compared with IDDM controls matched for age, sex and duration of diabetes. Twenty patients with coeliac disease and IDDM participated (15 female, age 7.4-17.3 yr), with two matched IDDM controls for each (age 6.9-17.4 yr). The prevalence of coeliac disease in this diabetes clinic population was 2.6%. All patients completed a 3 day food record (3DFR) and a 7 day food frequency questionnaire (FFQ) to assess dietary intake and gluten-free compliance. Diabetes control measured by HbA1c was not different between groups or compared to the overall clinic population (8.48 +/- 0.98% for coeliac patients vs 8.87 +/- 1.46 for IDDM controls vs 8.60 +/- 1.30 for overall clinic population aged 5.0-17.9 yr). Height, weight and BMI standard deviation scores were not different between coeliac patients and IDDM controls. No clinically significant differences were found in intake of energy, macronutrients or micronutrients. The proportion of energy intake from carbohydrate, protein and fat was within recommended ranges, except for a higher saturated fat intake. Only 30% of coeliac patients complied with a strict gluten-free diet, but growth parameters were unaffected by dietary compliance. Thus, we found that children and adolescents with coexisting IDDM and coeliac disease have normal growth, equivalent diabetes control and no differences in energy or nutrient intake compared to matched IDDM controls in our clinic population.     

Early changes of some serum proteins and metals in diabetic children

Serum concentrations of prealbumin, albumin, orosomucoid, magnesium, zinc and calcium were studied in 30 children with newly diagnosed IDDM aged 3-15 years, during the first two years of the disease, and in 44 healthy control children. On admission serum prealbumin was significantly lower in IDDM children (149 +/- 48 mg/l) (M +/- SD) than in healthy controls (194 +/- 39 mg/l) (p less than 0.001). During the two years follow-up prealbumin increased significantly, but did not reach the level of healthy controls. Serum albumin was slightly increased at diagnosis (p less than 0.01), but later decreased significantly (p less than 0.01). Orosomucoid concentrations did not differ between diabetics and controls. Serum magnesium was initially within the reference interval but later decreased, and after 2 years of IDDM it was highly significantly reduced (p less than 0.001). Serum zinc was significantly reduced in IDDM children at diagnosis (p less than 0.001), but was within the reference interval after one and 2 years. Serum calcium was increased in the IDDM group at diagnosis (p less than 0.01), but later normalized. It is concluded that in early IDDM there is a decrease in serum prealbumin and albumin, and serum magnesium decreases progressively, while serum zinc is only transiently reduced.     

Nitrites in induced sputum as a simple and cheap non-invasive marker of airway inflammation for asthmatic schoolchildren.

To determine if there are differences in the nitric oxide metabolites (nitrites) in sputum of patients with persistent asthma and healthy schoolchildren, we performed a case-control study in a tertiary care hospital in Arequipa, Perú. Nitrites in induced sputum samples were measured using the Griess assay in 30 persistent asthmatics (mean age of 10.1 yr) and 30 controls (mean age of 11.9 yr). The mean +/- s.d. of nitrites among asthmatics was significantly higher than the controls (16.30 +/- 8.6 vs. 10.25 +/- 4.68 nmol/ml, respectively, p = 0.001). Moreover, the nitrite level in the sputum in children with severe persistent asthma was higher than in the level found in the moderate and mild asthmatics (32.83 +/- 9.48 vs. 18.10 +/- 1.96 vs. 11.84 +/- 4.73 nmol/ml, respectively, p < 0.01 for linear trend). This study showed for the first time in children that asthmatics have significantly higher levels of nitrites in induced sputum than healthy controls and that the level of nitrite correlates with the severity of the asthma. Nitrite levels in sputum, a simple and cheap, non-invasive method, may be a good alternative to measure the severity of inflammation in asthmatic children.     

Cerebrospinal fluid soluble L-selectin (sCD62L) in meningoencephalitis

The leucocyte adhesion molecule L-selectin (CD62L) is rapidly cleaved off proteolytically after cell activation, generating soluble L-selectin (sCD62L) molecules. sCD62L concentrations were determined in 185 cerebrospinal fluid (CSF) samples obtained from children aged 1 month to 17 years. In 36 CSF samples of children with meningoencephalitis, sCD62L was significantly higher (median 209 fmol/ml) than in samples of children with other febrile diseases (n = 67, median 50 fmol/ml) or non-febrile disorders (n = 82, median 44 fmol/ml). There was a positive correlation between CSF protein and CSF sCD62L (rS = 0.68), suggesting that a disturbed blood-brain barrier contributes to raised sCD62L concentrations in the CSF. However, the CSF sCD62L/protein ratio of children with meningoencephalitis was significantly higher than in children with other febrile diseases or non-febrile disorders, indicating that sCD62L concentrations in children with meningoencephalitis were higher than expected from plasma leakage alone. It is concluded that both an impaired blood-brain barrier and the generation of sCD62L by infiltrating leucocytes contribute to raised CSF sCD62L concentrations in children with meningoencephalitis.     

Cerebrospinal fluid soluble L-selectin (sCD62L) in meningoencephalitis.

The leucocyte adhesion molecule L-selectin (CD62L) is rapidly cleaved off proteolytically after cell activation, generating soluble L-selectin (sCD62L) molecules. sCD62L concentrations were determined in 185 cerebrospinal fluid (CSF) samples obtained from children aged 1 month to 17 years. In 36 CSF samples of children with meningoencephalitis, sCD62L was significantly higher (median 209 fmol/ml) than in samples of children with other febrile diseases (n = 67, median 50 fmol/ml) or non-febrile disorders (n = 82, median 44 fmol/ml). There was a positive correlation between CSF protein and CSF sCD62L (rS = 0.68), suggesting that a disturbed blood-brain barrier contributes to raised sCD62L concentrations in the CSF. However, the CSF sCD62L/protein ratio of children with meningoencephalitis was significantly higher than in children with other febrile diseases or non-febrile disorders, indicating that sCD62L concentrations in children with meningoencephalitis were higher than expected from plasma leakage alone. It is concluded that both an impaired blood-brain barrier and the generation of sCD62L by infiltrating leucocytes contribute to raised CSF sCD62L concentrations in children with meningoencephalitis.     

No evidence for a major beta-cell dysfunction in young adults born with intra-uterine growth retardation

The association between low birth weight and the later development of type 2 diabetes is well established. It has been hypothesized that in utero undernutrition may affect pancreatic beta-cell development, leading to an impaired beta-cell function in adulthood. We have previously demonstrated that intrauterine growth retardation (IUGR) is associated with insulin-resistance early in adulthood. The aim of this study was to test whether IUGR would affect beta-cell function in young adults. Twelve 25-yr-old insulin-resistant subjects with IUGR were matched for age gender and body mass index (BMI) to 13 controls. All of them had normal glucose tolerance. Mean fasting plasma glucose did not significantly differ between the group with IUGR and the control group (97 +/- 7 vs. 98 +/- 4 mg/dL; p = 0.83). Blood glucose was maintained at 124.8 +/- 6.5 vs. 126.2 +/- 7.5 mg/dL above the basal glycemia in the IUGR and control groups (p = 0.64) throughout the hyperglycemic clamp. Serum insulin concentrations did not significantly differ between the group with IUGR and the control group either during the first (0-10 min) phase (311 +/- 252 vs. 248 +/- 184 pmol/L, p = 0.85) or during the second (80-100 min) phase (575 +/- 284 vs. 559 +/- 413 pmol/L, p = 0.72). C-peptide concentrations were similar in both groups during the two phases (2.35 +/- 1.44 vs. 2.59 +/- 1.10 nmol/L, p = 0.39 and 4.86 +/- 1.36 vs. 4.96 +/- 1.41 nmol/L, p = 0.91). In conclusion, our data do not argue in favor of an impairment of beta-cell function at 25 yr of age as a consequence of in utero undernutrition, but rather suggest that insulin resistance might be the primary defect responsible for the development of metabolic disorders associated with IUGR in adulthood.     

Accelerated pubertal development in patients with shunted hydrocephalus

OBJECTIVE: To evaluate pubertal development and peripheral concentrations of gonadotrophins and sex hormones in children with shunted hydrocephalus compared with healthy controls. STUDY DESIGN: 114 patients (52 females, 62 males) and 73 healthy controls (35 females, 38 males) aged 5 to 20 years were analysed for stage of puberty, age at menarche, testicular volume, basal serum follicle stimulating hormone (FSH), luteinising hormone (LH), sex hormone binding globulin (SHBG), testosterone and oestradiol concentrations, and free androgen index. RESULTS: Male gonadal and male and female pubic hair development occurred significantly earlier in the patients than in the controls. The mean age at menarche was significantly lower in the female patients than in their controls (11.7 v 13.2 years; p < 0.001), and lower than it had been for their mothers (v 13.1 years; p < 0.001). Relative testicular volume was higher in the male patients than in their controls (1.2 standard deviation score (SDS) v 0.2 SDS; p < 0.001). The prepubertal patients had higher basal LH (0.13 U/l v 0.08 U/l; p < 0.001) and SHBG (132.3 nmol/l v 109.1 nmol/l; p < 0.01) than the controls. Both the prepubertal and pubertal females had significantly higher basal FSH than their controls (1.57 U/l v 1.03 U/l; p < 0.05, and 4.0 U/l v 2.9 U/l; p < 0.01, respectively). CONCLUSIONS: Hydrocephalic children experience accelerated pubertal maturation, reflected in a younger age at menarche in females and an increased testicular volume in males. This may be because of enhanced gonadotrophin secretion, possibly resulting from unphysiological variations in intracranial pressure.     

Spontaneous and provoked growth hormone (GH) secretion and insulin-like growth factor I (IGF-I) concentration in patients with beta thalassaemia and delayed growth

Growth retardation in children with thalassaemia major is multifactorial. We studied the growth hormone (GH) response to provocation by clonidine and glucagon, measured the circulating concentrations of insulin, insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP3), and ferritin, and evaluated the spontaneous nocturnal (12 h) GH secretion in prepubertal patients with thalassaemia and age-matched children with constitutional short stature (CSS) (height SDS < -2, but normal GH response to provocation). The anatomy of the hypothalamic pituitary area was studied in patients with abnormal GH secretion using MRI scanning. Children with thalassaemia had significantly lower peak GH response to provocation by clonidine and glucagon (8.8 +/- 2.3 micrograms/l and 8.2 +/- 3.1 micrograms/l respectively) than did controls (17.6 +/- 2.7 micrograms/l and 15.7 +/- 3.7 micrograms/l respectively). They had significantly decreased circulating concentrations of IGF-I and IGFBP3 (68.5 +/- 19 ng/ml and 1.22 +/- 0.27 mg/l respectively) compared to controls (153 +/- 42 ng/ml and 2.16 +/- 0.37 mg/l respectively). Seven of the thalassaemic children had a GH peak response of < 7 micrograms/l after provocation. Those with a normal GH response after provocation also had significantly lower IGF-I and IGFBP3 concentrations than controls. Analysis of their spontaneous nocturnal GH secretion revealed lower mean (2.9 +/- 1.77 micrograms/l) and integrated (2.53 +/- 1.6 micrograms/l) concentrations compared to controls (4.9 +/- 0.29 micrograms/l and 5.6 +/- 0.52 micrograms/l respectively). Five of them had mean nocturnal GH concentration < 2 micrograms/l and four had maximum nocturnal peak below 10 micrograms/l. These data denoted defective spontaneous GH secretion in some of these patients. MRI studies revealed complete empty sella (n = 2), marked diminution of the pituitary size (n = 4), thinning of the pituitary stalk (n = 3) with its posterior displacement (n = 2), and evidence of iron deposition in the pituitary gland and midbrain (n = 7) in those patients with defective GH secretion (n = 9). Serum ferritin concentration was correlated significantly with the circulating IGF-I (r = -0.47, p < 0.01) and IGFBP3 (r = -0.43, p < 0.01) concentrations. These data prove a high prevalence of defective GH secretion in thalassaemic children associated with structural abnormality of their pituitary gland.     

Effects of a protein-rich diet during convalescence from shigellosis on catch-up growth, serum proteins, and insulin-like growth factor-I.

Shigellosis in children can cause growth retardation, worsening of malnutrition, and hypoproteinemia. To assess the effects of ingestion of a protein-rich diet during convalescence, 22 children aged 2 to 4 y with culture-proven shigellosis were randomly assigned after 5 d of antibiotic treatment to 21-d feeding regimens of either a 150 kcal/kg/d high-protein diet with 15% of calories as protein or an isocaloric control diet with 6% of calories as protein. At the start and end of dietary treatment, weight, height, mid-arm circumference, skinfold thickness, serum protein concentrations, and serum IGF-I were measured. Means of weight gain and increases in mid-arm circumference were greater in children fed high-protein diets than those fed control diets (1.23 versus 0.76 kg; 1.40 versus 0.96 cm; p < 0.05). Mean increase in height in children fed high-protein diets (0.83 cm) was not significantly greater than with control diets (0.74 cm). Mean increases in serum concentrations of total protein, prealbumin, and retinol-binding protein were greater in the high-protein group than in controls (p < 0.05). Mean serum concentrations of IGF-I were low in both groups before treatment [4.2 +/- 2.6 nmol/L (31.9 +/- 19.6 ng/mL) in controls; 3.1 +/- 3.4 nmol/L (24.0 +/- 26.3 ng/mL) in the high-protein group] but increased more in the high-protein group [39.0 +/- 16.2 nmol/L (298 +/- 124 ng/mL)] than in the control group [16.7 +/- 9.2 nmol/L (128 +/- 70 ng/mL), p < 0.01].(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma homocysteine levels in children and adolescents with type 1 diabetes

OBJECTIVE: Hyperhomocysteinemia has been established as a risk factor for cardiovascular disease. The objective was to investigate total plasma homocysteine concentrations in children and adolescents with type 1 diabetes and a control group. METHOD: Twenty-seven children with type 1 diabetes and 27 subjects of an age- and sex-matched control group were recruited. Fasting samples were collected for plasma total homocysteine, serum vitamin B12, folate, and creatinine. RESULTS: Fasting total homocysteine concentrations showed no difference between patients and controls (5.6 +/- 2.9 micromol/L vs 5.7 +/- 2.2 micromol/L; p greater than 0.05). The diabetic patients had significantly higher serum folate than the healthy controls (11.4 +/- 3.3 ng/mL vs 9.4 +/- 4.1 ng/mL; P = 0.02 and higher serum B12 than the control group (282.8 +/- 119 pg/mL vs 228.5 +/- 50.9 pg/mL; P = 0.03). Total plasma homocysteine concentration correlated with age (r = 0.44, P = 0.02), weight (r = 0.56, P = 0.002), body mass index (r = 0.57, P = 0.002), folate (r = -0.48, P = 0.01), and creatinine (r = 0.41, P = 0.03) in diabetic patients. In stepwise multivariate regression model for diabetics, the independent correlates for total plasma homocysteine concentration was folate (P = 0.002). CONCLUSION: We concluded that fasting plasma total homocysteine concentrations were within normal limits in children and adolescents with type 1 diabetes who were without any clinical evidence of microvascular and macrovascular complications.     

Reference values for the concentrations of triiodothyronine, thyroxine and thyrotropin in the blood serum of euthyroid children. Method: luminescence-enhanced enzyme immunoassay

Concentrations of triiodothyronine, thyroxine and thyrotropin were determined using the luminescence enhanced enzyme immunoassay method in blood serum of 343 (male = 197, female = 146) euthyroid children. Beyond the newborn age no significant difference was found for the thyrotropin concentration. Compilation of the values resulted in a physiological thyrotropin concentration of 1.73 +/- 0.81 (1s) microU/ml for infants, children and juveniles. In opposition to these results the thyroxine and triiodothyronine concentration showed an age-specific dependence. The thyroxine and triiodothyronine concentrations (means +/- 1s) decreased continuously from the infant age (TT4: 182.1 +/- 37.7 ng/ml, 234.9 +/- 48.6 nmol/l, TT3: 1.77 +/- 0.57 ng/ml, 2.73 +/- 0.88 nmol/l) to the juvenile age (TT4: 77.9 +/- 14.3 ng/ml, 100.5 +/- 18.4 nmol/l, TT3: 1.25 +/- 0.31 ng/ml, 1.93 +/- 0.48 nmol/l). The luminescence enhanced enzyme immunoassay technique is suitable for use in the routine thyroid laboratory.     

Alpha fetoprotein levels in neonatal hyperbilirubinaemia

Serum alpha fetoprotein (AFP) levels were studied in 15 neonatally hyperbilirubinaemic children and 15 controls matched for sex and gestational age. All children were born between 38 and 40 weeks of gestation. During the first seven weeks of postnatal life hyperbilirubinaemic children had serum AFP concentrations over twice as high as controls. At the age of 5-7 days the mean (+/- S.E.M.) serum AFP values were 52.4 +/- 5.8 mg/l for hyperbilirubinaemic children and 24.8 +/- 4.3 mg/l for controls (p less than 0.001). At 20-25 days of age they were 7.28 +/- 1.10 and 2.75 +/- 0.45 mg/l, respectively (p less than 0.001), and at 40-49 days 1.39 +/- 0.21 and 0.46 +/- 0.07 mg/l (p less than 0.001). However, no correlation was found between serum bilirubin and AFP concentrations in hyperbilirubinaemic children.     

Accelerated pubertal development in patients with shunted hydrocephalus.

OBJECTIVE: To evaluate pubertal development and peripheral concentrations of gonadotrophins and sex hormones in children with shunted hydrocephalus compared with healthy controls. STUDY DESIGN: 114 patients (52 females, 62 males) and 73 healthy controls (35 females, 38 males) aged 5 to 20 years were analysed for stage of puberty, age at menarche, testicular volume, basal serum follicle stimulating hormone (FSH), luteinising hormone (LH), sex hormone binding globulin (SHBG), testosterone and oestradiol concentrations, and free androgen index. RESULTS: Male gonadal and male and female pubic hair development occurred significantly earlier in the patients than in the controls. The mean age at menarche was significantly lower in the female patients than in their controls (11.7 v 13.2 years; p < 0.001), and lower than it had been for their mothers (v 13.1 years; p < 0.001). Relative testicular volume was higher in the male patients than in their controls (1.2 standard deviation score (SDS) v 0.2 SDS; p < 0.001). The prepubertal patients had higher basal LH (0.13 U/l v 0.08 U/l; p < 0.001) and SHBG (132.3 nmol/l v 109.1 nmol/l; p < 0.01) than the controls. Both the prepubertal and pubertal females had significantly higher basal FSH than their controls (1.57 U/l v 1.03 U/l; p < 0.05, and 4.0 U/l v 2.9 U/l; p < 0.01, respectively). CONCLUSIONS: Hydrocephalic children experience accelerated pubertal maturation, reflected in a younger age at menarche in females and an increased testicular volume in males. This may be because of enhanced gonadotrophin secretion, possibly resulting from unphysiological variations in intracranial pressure.     

Persisting glomerular hyperfiltration in short-term diabetic children without microalbuminuria

The renal function in a group of diabetic children (n=29;age;4-17 yr; IDDM duration: 1,5-13 yr) was studied with a 3 year interval. At the first evaluation glomerular filtration rate (GFR) as assessed by inulin clearance was significantly increased compared to control values (167 +/- 32 vs. 124 +/- 18 ml/min/1.73 m2; pl less than 0.01). Eighteen out of 29 children exhibited a glomerular hyperfiltration (GFR greater than 160). Three years later mean GFR was identical (169 +/- 25 ml/min/1.73 m2) and 16 children were hyperfiltrating. Among them, 11 have had a persisting glomerular hyperfiltration over the 3-year period. Renal plasma flow (RPF) was positively correlated to GFR (r=0.7; p less than 0.01) and remained elevated at both evaluations (794 +/- 163 and 812 +/- 157 ml/min/1.73 m2, p greater than 0.01 vs, control values). When the children were separated into 3 groups according to IDDM duration no significant differences were observed in the results for GFR and RPF, Mean urinary albumin excretion was comparable at the 3-year interval, and not significantly different from the control values (5.2 +/- 3.7 and 8.2 +/- 6.6 respectively vs. 8.65 +/- 4 microgram/min). None of the children demonstrated a persistent microalbuminuria. This study reveals a high proportion of diabetic children with a persisting glomerular hyperfiltration, without any other symptom of incipiens nephropathy, If elevated GFR plays an important role in the development of diabetic nephropathy, this study emphasizes the value of regular evaluation of renal function in diabetic children.     

Type 2 diabetes mellitus in African-American adolescents: impaired beta-cell function in the face of severe insulin resistance

We have previously demonstrated abnormalities in insulin secretion in adolescents with type 2 diabetes mellitus (DM2) in response to the mixed meal test and to glucagon. In order to further assess beta-cell function in DM2, we measured insulin and C-peptide responses to oral glucose in adolescents with DM2 in comparison to non-diabetic obese and lean adolescents. We studied 20 patients with DM2, 25 obese adolescents with matching body mass index (BMI) (33.8 +/- 1.4 vs 34.3 +/- 1.0 kg/m2), and 12 non-obese control adolescents (BMI 22.6 +/- 0.6 kg/m2). Mean age, sex and sexual maturation did not differ between the three groups. All adolescents with DM2 had negative islet cell antibodies (ICA); five patients were on diet and 15 on insulin treatment. Fasting lipid profiles were determined in all participants. Plasma glucose and serum C-peptide and insulin levels were measured at 0, 30, 60, 90, and 120 min after an oral glucose load. The C-peptide increment (deltaCP) was calculated as peak minus fasting C-peptide. Area under the curve (AUC) was estimated using the trapezoid method. Insulin resistance was estimated using the HOMA model (HOMA-IR). The first phase of insulin secretion (PH1) was computed using a previously published formula. Serum triglyceride levels were significantly higher in the patients with DM2 compared to the non-obese controls (1.4 +/- 0.1 vs 0.9 +/- 0.1 mmol/l; p = 0.02). Plasma glucose AUC was greater in the patients with DM2 compared to the obese and non-obese control groups (1,660 +/- 130 vs 717 +/- 17 vs 647 +/- 14 mmol/l x min; p < 0.0001). ACP was lower in adolescents with DM2 than in obese and non-obese adolescents (761 +/- 132 vs 1,721 +/- 165 vs 1,225 +/- 165 pmol/l; p < 0.001). Insulin AUC was lower in the patients with DM2 compared to obese controls (888 +/- 206 vs 1,606 +/- 166 pmol/l x h; p = 0.009), but comparable to that of the non-obese controls (888 +/- 206 vs 852 +/- 222 pmol/l x h; p = 0.9). Insulin AUC was also higher in the obese than in the non-obese group (p = 0.05). PH1 was significantly higher in the obese group compared to the patients with DM2 as well as to the non-obese controls (2,614 +/- 2,47.9 vs 929.6 +/- 403.5 vs 1,946 +/- 300.6 pmol/l, respectively; p = 0.001). PH1 was also higher in the non-obese controls than in the patients with DM2 (p = 0.05). HOMA-IR was three-fold higher in the patients with DM2 than in the BMI-matched obese group, and five-fold higher than in the lean controls (14.3 +/- 1.2 vs 5.4 +/- 0.8 vs 2.9 +/- 0.4; p = 0.0002). Adolescents with DM2 have dyslipidemia, a significant cardiovascular risk factor. Decreased beta-cell function is characteristic of adolescents with DM2 in the presence of severe insulin resistance.     

Postprandial hyperlipidemia after a fat loading test in minority adolescents with type 2 diabetes mellitus and obesity

The continuing increase in the incidence of type 2 diabetes mellitus (DM2) and obesity in children and adolescents is attributable to excessive caloric intake. Abnormal lipid metabolism in the postprandial state leads to long exposure of the vasculature to hyperlipidemia. Most children and adolescents with DM2 are obese, and many have fasting hypertriglyceridemia. Clustering of hyperlipidemia, DM2 and obesity increases the risk for cardiovascular disease. We therefore studied lipids, insulin, C-peptide, and glucose in response to an oral fat load simulating the fat content of a high-fat, fast-food meal in 12 type 2 diabetic obese, 15 non-diabetic obese, and 12 non-diabetic non-obese (control) adolescents (aged 10-19 yr; 87% African-Americans). All three groups were age-, sex-, and sexual maturation-matched. Mean body mass indices were similar in the diabetes and obese groups (32.7 +/- 1.1 vs 35.8 +/- 1.6 kg/m2). All patients with DM2 had fasting C-peptide > 0.2 nmol/l (0.7 ng/ml) and negative diabetes-associated autoantibodies. Serum total cholesterol, triglyceride, high- and low-density lipoprotein cholesterol, insulin, C-peptide, and plasma glucose levels were measured at 0, 2, 4, and 6 h after the fat load. The area under the curve (AUC) was calculated by trapezoidal estimation. Triglyceride AUC was significantly greater in the diabetes group than in the other two groups (15.7 +/- 2.9 vs 9.2 +/- 0.7 and 7.5 +/- 0.7 mmol x h/l [1389 +/- 258 vs 819 +/- 60 and 663 +/- 62 mg x h/dl]; p < 0.02 and <0.004, respectively), as were insulin, C-peptide, and glucose AUCs. Incremental triglyceride response (delta triglyceride = peak - fasting) in the diabetes group was significantly higher than that in the control group (2.1 +/- 0.7 vs 0.8 +/- 0.1 mmol/l 189.7 +/- 58.4 vs 71.2 +/- 11.1 mg/dl]; p < 0.04). Insulin resistance was estimated using the homeostasis model assessment (HOMA), which was greater in the diabetes group than in the obese and control groups (14.4 +/- 2.8 vs 5.2 +/- 0.8 and 3.2 +/- 0.4; p < 0.001 and < 0.0001, respectively). The diabetes group was divided into subgroups of high and normal fasting triglycerides on the basis of triglyceride levels above and below the 95th percentile. The delta triglyceride in the subgroup with high fasting triglycerides was substantially greater than in the subgroup with normal fasting triglycerides (3.4 +/- 1.1 vs 0.8 +/- 0.2 mmol/l [305.2 +/- 96.8 vs 74.2 +/- 18.0 mg/dl]; p < 0.001). Total cholesterol and triglyceride AUCs were much greater in the high vs normal fasting triglycerides subgroup (33.0 +/- 2.9 vs 24.2 +/- 1.9 and 23.6 +/- 3.5 vs 7.8 +/- 0.6 mmol x h/l [1274 +/- 113 vs 934 +/- 72 and 2085 +/- 309 vs 692 +/- 49 mg x h/dl]; p < 0.02 and <0.0001, respectively), as were insulin and C-peptide AUCs. HOMA was greater in the high vs normal fasting triglycerides subgroup (20.8 +/- 4.0 vs 8.0 +/- 1.6; p < 0.0001). In addition to elevated plasma glucose levels, there were no significant differences in either insulin or lipid parameters among the diabetes subgroup with normal fasting triglycerides, the obese group, and controls. Our data suggest that postprandial hyperlipidemia in response to a fat loading test is present in adolescents with DM2 who already have fasting hypertriglyceridemia. The degree of insulin resistance as an underlying abnormality--not DM per se--determines the degree of postprandial lipemia.     

The effects of smoking in pregnancy on factors influencing fetal growth

AIM: To evaluate the influence of maternal smoking during pregnancy on factors influencing fetal growth. METHODS: Thirty newborns of smoking mothers were prospectively compared with 60 newborns of non-smoking mothers. Pre-albumin, albumin, triglycerides, glucose, insulin, insulin-like growth factor I, IGF binding protein 3, pH, lactic acid, erythropoietin and hemoglobin concentrations were measured in umbilical cord blood. RESULTS: Infants of smoking mothers had a significantly lower birth weight (3418 +/- 533 vs. 3863 +/- 503 g; p < 0.001), length (50.5 +/- 2,6 vs. 52.3 +/- 1.9 cm; p < 0.001) and head circumference (34.6 +/- 1.8 vs. 35.8 +/- 1.1 cm; p < 0.001) than controls. They also had significantly lower insulin (3.2 (2.0-4.9) vs. 5.8 (4.6-7.1) mU/L; p = 0.008), insulin-like growth factor I (54.4 +/- 32.5 vs. 93.8 +/- 54.5 microg/L; p = 0.001) and IGF binding protein 3 (1664 +/- 432 vs. 1943 +/- 421 microg/L; p = 0.01) concentrations, than controls. Infants of smoking mothers also had significantly higher hemoglobin (167 +/- 14 vs. 157 +/- 13 g/L; p = 0.002) and erythropoietin (42.3 (25.1-72.4) vs. 26.3 (21.9-30.9) U/L; p = 0.03) than controls, but not pH or lactate concentrations. There was no significant difference in pre-albumin, albumin, triglycerides and glucose concentrations. CONCLUSIONS: Smoking during pregnancy causes symmetrical fetal growth impairment, possibly due to decreased oxygen transport to the fetus and decreased concentrations of fetal insulin, insulin-like growth factor I and IGF binding protein 3.