Search

Aims To characterize autonomic nervous system function by means ofthe heart rate and blood pressure responses to various stimuli in relationto pubertal maturation in patients with Type 1 diabetes mellitus (DM). Methods One hundred out of 138 eligible patients at the Out-patient Diabetes Clinicand 100 healthy control subjects were examined in terms of cardiovascularparameters at rest, during deep breathing and when standing. Heartrate variabil-ity was analysed with time domain,frequency domain and fractal dimension parameters. Tanner pubertalstaging was performed before the examinations. Results The time domain parameters of heart rate variability at restor during standing did not significantly differ between the patientsand controls in total or at pubertal stages. In the spectral analysis ofheart rate variability the very low frequency band was decreasedin the patients during standing (P = 0.023).The increase in the very low frequency (P = 0.013)and low frequency (P = 0.031) spectralpowers upon changing from a supine position to standing was attenuatedin the patients in total, while no significant differences wereobserved within the Tanner pubertal stages between patients and controls.Heart rate variability during deep breathing was decreased in the patientswith distal polyneuropathy (P = 0.006). Conclusions Although cardiovascular integrity is in the main well preserved inadolescent patients with Type 1 DM, these patients are prone toattenuated autonomic nervous system reactivity. Diabet. Med. 19, 932–938 (2002)

OBJECTIVE: To evaluate the interaction between serum free insulin, insulin-like binding protein (IGFBP)-1 and leptin concentrations during puberty in insulin-dependent diabetes mellitus (IDDM). DESIGN: Adolescent patients with IDDM (n=101, age >9 years, duration >2 years) from the Outpatient Clinic of the Department of Pediatrics at Oulu University Hospital, and non-diabetic controls, were recruited to the study. Free insulin, IGFBP-1, leptin and insulin antibody concentrations were measured from a fasting serum sample. RESULTS: Free insulin concentrations were lower in the patients than in the controls (4.3+/-2.3 mU/l compared with 6.5+/-3.1 mU/l, P

BACKGROUND The objective of this study was to assess the impact of pubertal maturation on urinary albumin excretion rate (AER) and persistent microalbuminuria, and to identify possible factors affecting urinary AER in adolescents with Type 1 diabetes. METHODS One hundred patients aged 9.1-19.0 years with a duration of diabetes of >2 years out of 138 eligible adolescents with Type 1 diabetes from an outpatient diabetes clinic participated in the study, together with 100 healthy controls. A timed overnight urine sample was collected in the hospital, where all the adolescents stayed for 22-24 h, and microalbuminuria was confirmed with at least one consecutive positive sample (AER 20-200 microg/min). RESULTS The prevalence of persistent microalbuminuria was 6%. All the patients affected were girls: one prepubertal (T I), one in late puberty (T IV) and three postpubertal (T V). These patients had significantly higher HbA(1c) levels than did the normoalbuminuric girls with Type 1 diabetes. Neither duration of diabetes nor age differed significantly between the two groups. AER increased more conspicuously with pubertal maturation in the boys with Type 1 diabetes than in the control boys, while the girls with diabetes had significantly higher body mass index (BMI) and serum total and LDL cholesterol than did the control girls. HbA(1c) was independently associated with AER in a multiple regression model. Diastolic blood pressure (BP) was elevated in both girls and boys with Type 1 diabetes as compared with healthy adolescents, while no difference was observed between the patients with microalbuminuria and normoalbuminuria. CONCLUSIONS Persistent microalbuminuria was mainly observed in late puberty and after puberty among adolescents with Type 1 diabetes. Female sex and poor metabolic control predispose such adolescents to this condition during pubertal maturation.

Collagen prolyl 4-hydroxylases (C-P4Hs) have a critical role in collagen synthesis, since 4-hydroxyproline residues are necessary for folding of the triple-helical molecules. Vertebrate C-P4Hs are alpha(2)beta(2) tetramers in which the beta subunit is identical to protein-disulfide isomerase (PDI). Three isoforms of the catalytic alpha subunit, PHY-1, PHY-2, and PHY-3, have been characterized from Caenorhabditis elegans, PHY-1 and PHY-2 being responsible for the hydroxylation of cuticle collagens, whereas PHY-3 is predicted to be involved in collagen synthesis in early embryos. We have characterized transcripts of two additional C. elegans alpha subunit-like genes, Y43F8B.4 and C14E2.4. Three transcripts were generated from Y43F8B.4, and a polypeptide encoded by one of them, named PHY-4.1, assembled into active (PHY-4.1)(2)/(PDI-2)(2) tetramers and PHY-4.1/PDI-2 dimers when coexpressed with C. elegans PDI-2 in insect cells. The C14E2.4 transcript was found to have a frameshift leading to the absence of codons for two residues critical for P4H catalytic activity. Thus, C. elegans has altogether four functional C-P4H alpha subunits, PHY-1, PHY-2, PHY-3, and PHY-4.1. The tetramers and dimers containing recombinant PHY-4.1 had a distinct substrate specificity from the other C-P4Hs in that they hydroxylated poly(l-proline) and certain other proline-rich peptides, including ones that are expressed in the pharynx, in addition to collagen-like peptides. These data and the observed restricted expression of the phy-4.1 transcript and PHY-4.1 polypeptide in the pharyngeal gland cells and the excretory duct suggest that in addition to collagens, PHY-4.1 may hydroxylate additional proline-rich proteins in vivo.

The collagen prolyl 4-hydroxylases (EC ) play a critical role in the synthesis of all collagens. The enzymes from all vertebrate species studied are alpha(2)beta(2) tetramers, in which the beta subunit is identical to protein disulfide isomerase (PDI). Two isoforms of the catalytic alpha subunit, PHY-1 and PHY-2, have previously been characterized from Caenorhabditis elegans. We report here on the cloning and characterization of a third C. elegans alpha subunit isoform, PHY-3. It is much shorter than the previously characterized vertebrate and C. elegans alpha subunits and shows 23-30% amino acid sequence identity to PHY-1 and PHY-2 within the catalytic C-terminal region. Recombinant PHY-3 coexpressed in insect cells with a C. elegans PDI isoform that does not associate with PHY-1 was found to be an active prolyl 4-hydroxylase. The phy-3 gene consists of five exons, and its expression pattern differs distinctly from the hypodermally expressed phy-1 and phy-2 in that it is expressed in embryos, late larval stages, and adult nematodes, expression in the latter being restricted to the spermatheca. Nematodes homozygous for a phy-3 deletion are phenotypically of the wild type and fertile, but the 4-hydroxyproline content of phy-3(-/-) early embryos was reduced by about 90%. PHY-3 is thus likely to be involved in the synthesis of collagens in early embryos, probably of those in the egg shell.

OBJECTIVE—To evaluate the impact of puberty on peripheral nerve function in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS—Of 138 eligible patients with type 1 diabetes, 100 patients (age >9 years and diabetes duration >2 years) attending an outpatient diabetes clinic and 100 age- and sex-matched healthy control subjects took part in this cross-sectional study. Peripheral motor and sensory nerve conduction tests, cardiovascular reflex tests on the autonomic nervous system, and measurements of vibration-perception threshold (VPT) were performed. RESULTS—Nerve conduction velocity (NCV) in the distal motor and sensory nerves, the motor nerve distal latency, and the sensory nerve action potential (SNAP) amplitude were impaired in the adolescent patients with type 1 diabetes. The deterioration in motor NCV, H-reflex latency, and SNAP amplitude became more conspicuous in late puberty and postpuberty and was related to poor metabolic control. A total of 10 patients had distal diabetic polyneuropathy (DP) neurophysiologically, and these patients had significantly lower heart-rate variation in the deep breathing test than the other patients. Three of the patients with DP had peripheral neurological signs or symptoms. A slight difference in the VPT between the patients and control subjects was observed after puberty. CONCLUSIONS—Increasing subclinical motor nerve impairment can be detected during late puberty and after puberty, and sensory NCV and SNAP amplitude are reduced in adolescents with type 1 diabetes. Poor metabolic control during puberty appears to induce deteriorating peripheral neural function in young patients with type 1 diabetes.