PLasma C-peptide and insulin in neonates, infants, and children.
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Blood Glucose↗
Biomedical subjects
M Knip
Publications and source records attributed to M Knip.
Presence of TRF immunoreactivity in marginal islet cells in rat pancreas.
Isolated rat pancreatic islet extracts were submitted to reverse phase high pressure chromatography (HPLC) and assayed for thyrotrophin releasing factor (TRF), glucagon and insulin in radioimmunoassays (RIA). Our anti-TRF serum was prepared by immunizing rabbits with TRF conjugated to bovine thyroglobulin (bTG) by bisdiazobenzidine. Anti-glucagon and antiinsulin were from a commercial source (Novo, Denmark). The concentrations of TRF, glucagon and insulin were 0.05 +/- 0.02, 0.06 +/- 0.02 and 1.0 +/- 0.2 pmol/islet, respectively. Formalin-fixed pancreatic sections were stained for TRF, glucagon and insulin by peroxidase, antiperoxidase (PAP) complex method. When the adjacent sections were stained for glucagon or insulin, it was observed that TRF and glucagon-specific peroxidase reactions were confined to the marginal islet cells, but insulin reactions to the central cells. The TRF-specific peroxidase reaction was clearly reduced when the anti-TRF serum was unchanged when the antiserum was pre-incubated with synthetic TRF. The present HPLC results suggest that the islets contained TRF. Immunocytochemical studies show that the TRF-immunoreactive material, either synthesized or bound, is localized in the marginal islet cells.
Animals↗
Metabolic characteristics and urine albumin excretion rate in relation to pubertal maturation in Type 1 diabetes.
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.
Adolescent↗
Intranasally administered insulin intended for prevention of type 1 diabetes--a safety study in healthy adults.
BACKGROUND: Intranasally applied insulin is one of the antigen-specific therapies currently tested in clinical type 1 diabetes prevention trials, for example, in the Type 1 Diabetes Prediction and Prevention Study (DIPP). The possibility that the therapy may cause hypoglycaemia or local irritation and the poorly known immunological safety of mucosal application of the antigen in healthy subjects prompted this study. METHODS: We used a randomised, placebo-controlled, double-blinded crossover study design with 3-week treatment periods to study the effects of once-daily intranasal application of human short-acting insulin without absorption-enhancing adjuvants in 20 non-diabetic adults. The selected 60 IU dose of insulin was equivalent to the weight-based dose used for the DIPP children. We investigated self-monitored blood glucose concentrations, nasal insulin effects and induction of diabetes-associated autoantibodies. RESULTS: The two treatment periods showed no differences in blood glucose concentrations or in the frequency of blood glucose values higher than 3.0 mmol/L. Of the eight measured hypoglycaemic values, only one, which occurred during placebo therapy, was associated with symptoms. Rhinoscopy revealed no nasal irritation, and mucociliary clearance, nasal airway patency and nasal airflow resistance were not affected by the insulin therapy. Eleven subjects complained of transient nasal stinging or unpleasant odour and one subject reduced the dose because of nasal irritation. The treatment did not induce production of any of the four diabetes-associated autoantibodies. CONCLUSIONS: Short-term use of intranasal insulin without absorption enhancers was predominantly well tolerated, the risk of hypoglycaemia was minimal and no objective nasal adverse effects were detected.
Administration, Intranasal↗
Genetic screening for individuals at high risk for type 1 diabetes in the general population using HLA Class II alleles as disease markers. A comparison between three European populations with variable rates of disease incidence.
BACKGROUND: To develop screening strategies for identification of individuals at increased genetic risk for type 1 diabetes in three populations with variable disease incidence rates and distinct ethnic origin. METHODS: A stepwise HLA DQB1-DQA1-DRB1-based screening approach was evaluated. Patients with childhood-onset type 1 diabetes were recruited from Finland (n = 1739), Hungary (n = 149), and Greece (n = 119). Consecutive newborns (2568 from Finland and 1047 from Greece) or healthy schoolchildren (n = 177 from Hungary) served as controls. RESULTS: The DQB1*02/0302 genotype conferred the highest disease risk in all populations. The DQB1*02/y (y not equal DQB1*0301,*0302,*0602,*0603, *0604) genotypes were more common and conferred a higher disease risk in the Greek population (OR 4.9) compared to the Finns (OR 1.2). DQB1*0302/x (x not equal DQB1*02, *0301, *0602, *0603, *0604) genotypes were, in contrast, more prevalent among Finnish cases (32.7%) as compared to Hungarians (18.1%) or Greeks (13.5%). The protective DQB1*0602 or *0603 positive genotypes were most common in the Finns, while DQB1*0301 was more common in Hungarians and Greeks. In all groups, DQA1 and DRB1*04 typing considerably increased the sensitivity of the DQB1-based screening. The different high-risk genotype combinations present in about 10% of the background population had a diagnostic sensitivity of 60% in Finland and 80% in Hungary and Greece. CONCLUSIONS: HLA DR-DQ-based screening is a feasible tool for the identification of individuals at increased genetic risk for type 1 diabetes in populations with diverse genetic background. The risk markers should, however, be individually selected for the target population since the screening efficiency of various markers is highly dependent on the ethnic group studied.
Biomarkers↗
Remission phase, endogenous insulin secretion and metabolic control in diabetic children.
The occurrence and duration of clinical remission were analyzed in 173 diabetic children. One hundred and twelve (65%) children experienced a remission, which was complete in only five (3%) cases. Duration varied from one month to three years, the mean being 8.5 months. Boys showed a more frequent and longer remission phase (p less than 0.01) than girls. Children with a negative remission history were younger (p less than 0.05) at the onset of diabetes than children having remission periods. Duration of remission correlated positively with age at onset (rs = 0.19; p less than 0.01) and the non-fasting serum C-peptide concentration (rs = 0.31; p less than 0.001). There was a negative correlation between duration of remission and daily insulin dose (r = -0.23; p less than 0.005). We found no correlation between duration of remission and duration of diabetes or hemoglobin A1 (HbA1) concentrations beyond the remission period. Serum C-peptide concentrations correlated negatively with HbA1 levels (rs = -0.23; p less than 0.001) indicating that residual B-cell function favors good metabolic control. There was a negative correlation between HbA1 concentration and duration of diabetes (r= -0.30; p less than 0.001). Clinical remission of long duration is associated with persisting endogenous insulin secretion, and reduced daily insulin requirement, but its favorable effect on metabolic control beyond the remission period is questionable.
Adolescent↗
Reduced bone mineral density in long-term survivors of childhood acute lymphoblastic leukemia.
PURPOSE: Osteoporosis and pathologic fractures are occasionally found in patients with childhood acute lymphoblastic leukemia (ALL). This study was performed to determine the degree of possible osteopenia in long-term survivors of childhood ALL. PATIENTS AND METHODS: Lumbar spine (L2-L4) and femoral neck bone mineral densities (BMDs) (g/cm2) were measured in 29 survivors (aged 12 to 30 years, median 17) of childhood ALL 2 to 20 (median 8) years after discontinuation of chemotherapy. These results were compared with those from 273 healthy controls and expressed as a percentage of the age- and sex-matched control values (mean +/- standard deviation). RESULTS: Lumbar and femoral BMDs were significantly reduced in survivors of childhood ALL. Particularly, male gender (lumbar: 91.7 +/- 10.4%, p = 0.008; femoral: 91.9 +/- 11.3%, p = 0.005) and a history of cranial irradiation (lumbar: 93.0 +/- 8.9%, p = 0.005; femoral: 94.4 +/- 13.3%, p = 0.03) were associated with low lumbar and femoral BMDs. CONCLUSIONS: The detected deficit in bone density in survivors of childhood ALL may predispose these patients to osteoporotic fractures later in adulthood. A follow-up of BMD in survivors of childhood ALL should facilitate the identification of patients who would require specific therapeutic interventions to prevent further decrease of their skeletal mass and preserve their BMD.
Absorptiometry, Photon↗
Glutamic acid decarboxylase and islet cell antibodies in healthy Estonian children.
The prevalence of antibodies to the 65 kDa isoform of glutamic acid decarboxylase (GADA) was compared with that of islet cell antibodies (ICA) in 614 non-diabetic Estonian children (314 males) aged 3-18 years representing the general population. GADA were analyzed with a radioligand assay, and ICA with a standard immunofluorescence method with a detection limit of 2.5 Juvenile Diabetes Foundation (JDF) units. Fourteen subjects (2.3%, 95% confidence interval [CI] 1.1-3.5%) tested positive for GADA (median level 10.8 relative units [RU], range 7.7-154.2 RU), while 10 (1.6%, CI 0.6-2.6%) had ICA (median levels 34 JDF units, range 3-97 JDF units). Five subjects (0.8%, CI 0.1-1.5%; p = 0.03 vs GADA and 0.15 vs ICA) were double positive. The individual with the second highest GADA level (129.3 RU) and the highest ICA level (97 JDF units) presented with type 1 diabetes 4 months later. A follow-up sample was obtained approximately 3-4 years after the first sampling in 14 subjects initially positive for ICA and/or GADA. Four of the nine initially ICA-positive children remained positive, but their levels decreased from a median of 42 to 18 JDF units (p = 0.06). Only two of the nine retested subjects initially positive for GADA remained positive in the second sample. These observations suggest that the prevalence of GADA in non-diabetic children is of the same magnitude as that of ICA. Combined positivity for both GADA and ICA is less prevalent than single antibody specificities, indicating that double autoantibody positivity may have a higher predictive value for future type 1 diabetes in the general population than either antibody separately. The evanescent character of diabetes-associated autoantibodies in a proportion of the unaffected children implies that more subjects may experience self-restricted beta-cell damage than the number progressing to actual disease.
Adolescent↗
Effect of once-a-week training program on physical fitness and metabolic control in children with IDDM.
To examine whether a physical activity program could improve physical fitness and glycemic control, 32 children and adolescents with insulin-dependent diabetes mellitus (IDDM) were examined before the program and 3 mo later. Fifty percent of the subjects (n = 16) participated in the training for 1 h/wk (exercise group), whereas the remaining subjects were engaged in nonphysical activities for an equal amount of time (nonexercise group). Age of the subjects ranged from 8.2 to 16.9 yr, (mean 11.9 yr), with mean duration of diabetes 0.6-13.1 yr (5.2 yr). During the 3-mo program peak oxygen consumption (VO2) rose from 40.0 to 43.8 ml.min-1.m-2 (P less than .01) in the exercise group but only by 1.3 ml.min-1.m-2 in the nonexercise group (NS). Metabolic control did not improve in either group, with glycosylated hemoglobin level rising from 9.8 to 10.5% (P less than .01) in the exercise group and from 9.4 to 9.7% (NS) in the control group. When subjects were stratified according to their participation, metabolic control was significantly better among diabetic subjects participating frequently (greater than or equal to 11 of 13 sessions) than among those participating infrequently (less than 11 of 13 sessions), regardless of the type of activity. It was concluded that a training program of 1 h/wk for 3 mo does improve physical fitness but not the metabolic control of diabetes. On the other hand, glycemic control appears to be best among diabetic subjects who are motivated to participate in any kind of program related to the treatment of their disease.
Adolescent↗