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Biomedical subjects

J Ludvigsson

Publications and source records attributed to J Ludvigsson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Determination of mRNA expression for IFN-gamma and IL-4 in lymphocytes from children with IDDM by RT-PCR technique.

Insulin-dependent diabetes mellitus (IDDM) is characterized by infiltration of T-lymphocytes in the islets of Langerhans. Antigens are presented to Th-lymphocytes which can be divided into Th1- and Th2-lymphocytes, producing interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) respectively. The aim of our study was to determine the messenger-RNA (mRNA) for these cytokines by RT-PCR in antigen-stimulated lymphocytes from children with newly diagnosed IDDM. The expression of mRNA for IL-4, and to a lesser degree IFN-gamma, is increased in lymphocytes stimulated with tetanus toxoid (TT). Loss of activity after freezing and thawing could be compensated for, by increased amplification, while the use of EDTA or sodium heparin in the blood samples did not influence the results. In a pilot application, the lymphocytes from children with newly diagnosed IDDM were stimulated with a peptide of glutamic acid decarboxylase (GAD) (a.a. 247-279) known to have a similar aminoacid sequence as the Coxsackie B virus (a.a. 32-47). Increased IFN-gamma mRNA could be seen in two out of four children, whereas IL-4 showed a less pronounced mRNA expression. No increased mRNA expression for IFN-gamma and IL-4 could be seen in healthy HLA-matched controls. Further studies are needed to confirm whether increased IFN-gamma mRNA in Th1-like lymphocytes stimulated with this specific GAD-peptide play a role in the cell-mediated immune response seen in children early after the onset of IDDM.

Adolescent↗
PubMed1998

Exhaled isoprene and acetone in newborn infants and in children with diabetes mellitus.

A new analytical method gas chromatography combined with UV spectrophotometry was used to measure isoprene and acetone in expired breath collected from four different groups of children: 1) healthy newborn babies, 2) healthy preschool children, 3) healthy school children, and 4) diabetic children in different metabolic states. Both isoprene and acetone could readily be determined in one single analysis of a 250-mL air sample. Newborn babies during the first postnatal week had undetectable or very low levels of isoprene in their expired air irrespective of catabolic or anabolic state. Breath isoprene increased with age, and healthy school children had higher levels than did healthy preschool children. No significant differences in breath isoprene were found between healthy and diabetic children. Breath acetone was found to correlate with metabolic state both in newborn babies and in diabetic children. These findings illustrate the potential use of a new technique for breath analysis in children with metabolic disturbances.

Acetone↗
PubMed1998

Hypoglycaemia during intensified insulin therapy of children and adolescents.

Good metabolic control prevents or at least postpones late vascular complications, but several studies indicate that such good metabolic control cannot be reached without simultaneous increase in the incidence of severe hypoglycaemia. We have been able to reduce late complications through multiple insulin therapy adjusted on the basis of active self control combined with active psychosocial support and education. A prospective regular registration of all hypoglycaemic incidents in about 130 diabetic children and adolescents shows that in spite of reasonably good HbA1c values (mean and median 6.9%, corresponding to 7.9% with the DCCT method), we have less incidence of severe hypoglycaemia (13-17 per 100 patient years) than reported in other recent studies (20-25 per 100 patient years). We saw no correlation between HbA1c and severe hypoglycaemia, but most hypoglycaemia was caused by mistake or reasons not related to degree of metabolic control. Our conclusion is that there is no inevitable relation-ship between low HbA1c and hypoglycaemia. Instead hypoglycaemia should be prevented parallel to and in the same way as we try to reach good metabolic control.

Adolescent↗
PubMed1997

Prevalence of diabetic retinopathy in children and adolescents with IDDM. A population-based multicentre study.

Vision-threatening diabetic retinopathy can be prevented if it is diagnosed before becoming too advanced. Since diabetic retinopathy has been reported to occur only rarely before the end of pubertal development, children and adolescents are seldom included in screening programmes. We invited 780 children and adolescents with insulin-dependent diabetes mellitus diagnosed before the age of 15.0 years (disease duration of < 12 years) and who were older than 9.0 years at the time of examination from eight regions of Sweden. Retinal examination was performed with stereoscopic fundus photograph. The photograph were rated according to a modified Airlie House classification. The dropouts (223/780, 28.6%) were significantly older and with a longer duration of diabetes than the examined children (p < 0.001 and 0.001, respectively). Photographs from 557 patients aged (median [interquartile range]:14.6 [12.4-17.0]) years and with a diabetes duration of 8.0 (5.5-9.9) years were evaluated. Retinopathy was demonstrated in 81 patients (14.5%):66 with background retinopathy, 2 with microaneurysms and hard exudates, 12 with preproliferative retinopathy, 1 with proliferative retinopathy. Preproliferative retinopathy was diagnosed in a 12.8-year-old girl in pubertal stage 3 and an 11.8-year-old boy in pubertal stage 2, and proliferative retinopathy was found in a 21.5-year-old girl. Retinopathy was demonstrated in 6% and 18% of patients in pubertal stages 1 and 5, respectively. The overall prevalence of retinopathy in this population may even be higher since the dropouts were older and had a longer duration of diabetes. Since background and preproliferative retinopathy were found in children before puberty, we recommend including children and adolescents in screening programmes for diabetic retinopathy from the age of 10 years.

Adolescent↗
PubMed1997

No acute effect of high blood glucose on nerve conduction in adolescents with IDDM.

The aim of the present study was to evaluate the acute effect of high blood glucose on the motor and sensory nerve conduction in adolescents with IDDM. Four patients, 15-18 years old, with a history of diabetes from 5 to 9 years underwent repeated studies of the conduction properties in the median, peroneal, and sural nerves within a 10-day period. Capillary blood glucose was drawn immediately before and after each examination. Repeated measurements in each patient revealed only a small variation in the values of ten nerve conduction parameters despite of large differences in the blood glucose level. A multiple regression analysis of the data from all patients in a total of 20 measurements gave P-values between 0.18 and 0.96, i.e. there was no correlation between any of the ten studied conduction parameters and the prevailing blood glucose level. This supports the view that nerve dysfunction is a consequence of long-term poor metabolic control (HbA1c) and not dependent on the acute effect of hyperglycemia in adolescents with IDDM.

Action Potentials↗
PubMed1997

Autoantibodies in relation to residual insulin secretion in children with IDDM.

To elucidate whether autoantibodies can be used to predict the intensity of autoimmune beta-cell destruction, we determined both C-peptide and autoantibodies (islet cell antibodies (ICA), insulin autoantibodies (IAA), islet cell surface antibodies (ICSA) and antibodies to glutamic acid decarboxylase (GADA)). In 89 diabetic children and adolescents at diagnosis at the age of 1.2-16.6 years (mean +/- S.D., 9.0 +/- 4.5). Only 12/89 (14%) had no autoantibodies at diagnosis, while 2 patients (2%) had all 4 autoantibodies. There was a positive correlation between GADA and ICA (P < 0.01). At diagnosis 70% of the patients had GADA, most common in patients above the age of 8 years at diagnosis (P < 0.001), and with higher GAD-index in girls (P < 0.05). ICA was detected in 63%, most common in the older age groups (P = 0.04). ICSA seen in 22% of the patients as well as IAA (detected in 32%) were most common < 8 years of age (P = 0.06, P = 0.08, respectively). Children with autoantibodies had similar C-peptide levels through the follow up period as children of the same sex and age without antibodies, except for patients with ICSA alone or in combination with other autoantibodies who tended to have higher C-peptide levels. We conclude that not even combinations of autoantibodies can be used to predict beta-cell destruction in IDDM patients.

Adolescent↗
PubMed1997

Unchanged insulin absorption after 4 days' use of subcutaneous indwelling catheters for insulin injections.

OBJECTIVE: Since 1985, we have used indwelling catheters (Insuflon, Maersk Medical, Lynge, Denmark; Chronimed, Minnetonka, MN) to lessen pain when injecting insulin. However, some patients experience a rise in blood glucose after using indwelling catheters for a few days. We therefore studied the absorption of 125I-labeled insulin when using indwelling catheters. RESEARCH DESIGN AND METHODS: Five men and five women participated (age 18-25 years, C-peptide negative, HbA1c 9.0 +/- 1.0% [mean +/- SD, DCA-2000 method], diabetes duration 5-21 [median 9.5] years). After thyroid blockage with potassium iodide, we injected 5IU of 125I-labeled short-acting insulin subcutaneously in the abdomen ("ordinary injection") and 5 IU on the contralateral side through an indwelling catheter ("catheter injection"). The injection/insertion area was free of lipohyper- and lipohypotrophies. Disappearance rate was measured for 180 min with a gamma camera. The patients injected all premeal injections of short-acting insulin through the same indwelling catheter in the following 4 days. The investigation procedure was repeated day 3 and 5. RESULTS: We found no statistically or clinically (95% CI) significant difference in residual activity of 125I-insulin after 60 min or in time for 50% of the injected depot to disappear (T-50%) among catheter injections on day 1, 3, and 5; ordinary injections on days 1, 3, and 5; or catheter and ordinary injections on days 1, 3, and 5, respectively. HbA1c correlated both to T-50% (r = 0.73, P = 0.016) and residual activity of 125I-insulin after 60 min (r = 0.69, P = 0.028), indicating that patients with a slower absorption will have a less ideal metabolic control when using premeal bolus injections. CONCLUSIONS: We conclude that using indwelling subcutaneous catheters for insulin injections for up to 4 days does not affect the absorption of short-acting insulin.

Absorption↗
PubMed1997

Severe hypoglycemia in children with IDDM. A prospective population study, 1992-1994.

OBJECTIVE: Is an increased incidence of severe hypoglycemia an unavoidable effect of improved metabolic control? And, if so, to what extent? RESEARCH DESIGN AND METHODS: In 1992-1994, severe hypoglycemia was prospectively registered in our intensively treated IDDM population, 146 children 1-18 years of age with > 90% of the patients on > or = 4 insulin injections per day. The two categories, "severe hypoglycemia with unconsciousness" (U hypoglycemia) and "severe hypoglycemia without unconsciousness but needing the assistance of another person" (NU hypoglycemia), were analyzed in relation to yearly mean HbAlc levels, insulin doses and proportion of short-acting insulin, age at onset, duration of diabetes, age, sex, and weight-to-height ratio. RESULTS: Yearly mean HbAlc levels improved from 8.1 +/- 1.6% in 1992 to 6.9 +/- 1.3% in 1994. The yearly incidence of U hypoglycemia was 0.15-0.19 events per patient-year, seen in 10-16% of patients, showing no significant increase from 1992-1994. For NU hypoglycemia, slightly increasing figures from 1.01 to 1.26 events per patient-year, seen in 27-38% of patients yearly, were reported. There was no significant correlation between severe (U or NU) hypoglycemia and HbAlc, but still an association was seen in certain calculations. In multiple regression analysis, U hypoglycemia was not related to any factor, but the square root of the rate of NU hypoglycemia was related to lower HbAlc levels (P = 0.0003), higher insulin doses (IU.kg-1.24 h-1) (P = 0.0024), and a lower proportion of short-acting insulin out of the total daily insulin dose (P = 0.031). CONCLUSIONS: Multiple-dose insulin therapy with rather low yearly mean HbAlc values causes a slight increase of NU hypoglycemia but no increase of U hypoglycemia in our population of children with IDDM. Near physiological HbAlc levels may be achieved without any pronounced risk of increasing the incidence of severe hypoglycemia when multiple-injection insulin therapy is combined with adequate self-control based on psychosocial support and active education.

Adolescent↗
PubMed1996

Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes.

Immunoprecipitating IgG autoantibodies to glutamic acid decarboxylase, GAD65, and/or a tyrosine phosphatase, IA2, are present in the majority of individuals experiencing pancreatic beta cell destruction and development of type 1 diabetes. Here we identify a third islet cell autoantigen, a novel 38-kD protein, which is specifically immunoprecipitated with sera from a subset of prediabetic individuals and newly diagnosed type 1 diabetic patients. The 38-kD autoantigen, named glima 38, is an amphiphilic membrane glycoprotein, specifically expressed in islet and neuronal cell lines, and thus shares the neuroendocrine expression patterns of GAD65 and IA2. Removal of N-linked carbohydrates results in a protein of 22,000 Mr. Glima 38 autoantibodies were detected in 16/86 (19%) of newly diagnosed patients, including three very young children, who had a rapid onset of disease, and in 6/44 (14%) of prediabetic individuals up to several years before clinical onset. The cumulative incidence of GAD65 and glima 38 antibodies in these two groups was 83 and 80%, respectively, and the cumulative incidence of GAD65, glima 38, and IA2 antibodies in the same groups was 91 and 84%, respectively. GAD65, IA2, and glima 38 represent three distinct targets of immunoprecipitating IgG autoantibodies associated with beta cell destruction and type 1 diabetes.

Adolescent↗
PubMed1996

Relations between age, metabolic control, disease adjustment and psychological aspects in insulin-dependent diabetes mellitus.

The relations between age, metabolic control, disease adjustment, and psychological factors in boys and girls with recently diagnosed insulin-dependent diabetes mellitus (IDDM) were studied. Older girls had significant higher postremission glycosylated haemoglobin A (Hb AIc) levels (p = 0.008). Girls with more hospitalizations had a lower developmental level (p = 0.05), and had significantly more problems in the behavioural rating (p = 0.05). Boys with more hospitalizations had a more external locus of control (p = 0.01), more difficulties with disease adjustment, more emotional problems, and were also clinically assessed as having more behavioural problems. Boys showing more difficulties in psychological adjustment to the disease also had higher postremission Hb AIc levels (p = 0.02). Although Swedish children with IDDM of short disease duration do not differ from healthy children in important psychological aspects, older girls and a small group of problematic younger boys are at risk of developing metabolic imbalance after a short disease duration.

Adolescent↗
PubMed1996

Psychological reactions at the onset of insulin-dependent diabetes mellitus in children and later adjustment and metabolic control.

The initial psychological reactions at the onset of insulin-dependent diabetes mellitus (IDDM) in a population-based sample of 76 children were studied with staff observations and a self-report questionnaire for children 12 years of age and more. Younger children reacted with more anger and less distress than the older children. High initial self-reported distress was associated with poorer subjective psychological IDDM adjustment at a follow-up 10 months later for the older children. The children's initial reactions as well as later adjustment were intimately associated with maternal initial reactions in the total group. The metabolic control, estimated as the mean level of the major fraction of glycosylated haemoglobin (Hb AIc) during the first 2 years, was poorer in the adolescent group. Initial anxiety over injections and protest but low general distress in mothers and children were associated with better metabolic control.

Adaptation, Psychological↗
PubMed1996

Islet cell surface antibodies are more common in patients and relatives in areas and during seasons with high incidence of insulin-dependent diabetes mellitus.

Although existence of islet cell antibodies (ICA) is regarded as secondary to beta cell death, islet cell surface antibodies (ICSA) might play a role in the disease process. We have collected information from nine European clinics to determine whether ICSA are more common in diabetic children or their relatives in geographical areas or time periods of high incidence of insulin-dependent diabetes mellitus (IDDM). In Finland and Sweden ("North group") with a high incidence of IDDM during childhood, 36% of the patients were positive or weakly positive for ICSA at diagnosis compared with 24% in France (p = 0.1), 11% in Berlin-Vienna (p < 0.01), and 14% in Italy (p < 0.01). This difference was seen in all age groups but was most pronounced in the youngest (0-4 y). This geographical difference was also seen among family members of whom 46% were positive or weakly positive in the North group, 25% in France (p < 0.001), 21% in Berlin-Vienna (p < 0.001), and 16% in Italy (p < 0.001). Of several analyzed antibodies (ICA, gastric parietal cell, thyroglobulin, and thyroid microsomal), only ICSA showed simultaneous positivity in all family members (r = 0.32, p < 0.01). ICSA were most common in family members of patients with short (< 8 d) duration of symptoms (p < 0.05) and showed a similar seasonality, both in patients and relatives, as the incidence of IDDM. We conclude that the geographical difference in incidence of childhood IDDM in Europe may be associated to similar geographical differences in occurrence of ICSA both in newly diagnosed diabetic children and in their relatives. Simultaneous existence of ICSA in both patients and family members and a similar seasonality for ICSA and incidence of IDDM suggest that ICSA may reflect an ongoing disease process.

Autoantibodies↗
PubMed1996

Glycemic control and prognosis in type I diabetic patients with microalbuminuria.

OBJECTIVE: To investigate the course of microalbuminuria during the 1980s in type I diabetes patients. RESEARCH DESIGN AND METHODS: This was a 10-year follow-up of 109 patients in whom type I diabetes was diagnosed between 1961 and 1980 before 15 years of age and who were initially investigated between 1977 and 1983 after a diabetes duration of > or = 3 years. Microalbuminuria was defined as an albumin excretion rate (AER) of 20-200 micrograms/min in two of three consecutive urine samples. RESULTS: At the initial investigation, 81 patients had normal AER, 27 had microalbuminuria, and 1 had macroalbuminuria. Between 1989 and 1992, 99 (91%) patients were reinvestigated. Only 5 (19%) of the initially microalbuminuric patients developed macroproteinuria during the 10-year follow-up period, and in 15 (58%) patients, AER decreased to normal. Three (4%) of the normoalbuminuric patients developed microalbuminuria but none macroproteinuria. The initially microalbuminuric patients, in whom AER normalized, improved their glycemic control from 1980-1983 to 1989-1991 (mean +/- SE HbA1c 7.5 +/- 0.2 to 6.6 +/- 0.3%; P = 0.01). CONCLUSIONS: In the majority of patients with microalbuminuria in whom it is possible to obtain good glycemic control, microalbuminuria will disappear and the risk of developing nephropathy will be markedly reduced.

Adolescent↗