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Biomedical subjects

J Ludvigsson

Publications and source records attributed to J Ludvigsson.

At least 55 records · Page 3Linked to original sources
PubMed2001

Seasonal variation of birth month and breastfeeding in children with diabetes mellitus.

OBJECTIVE: As breastfeeding is suggested to protect against diabetes mellitus we decided to investigate whether the seasonal variation of month of birth of diabetic children, with more diabetes in children born in summer, can be explained to some extent by a seasonal variation of exclusive breastfeeding. PATIENTS: A population-based group of 297 children who had been diagnosed with diabetes mellitus before the age of 15 years was compared with 792 matched healthy subjects. RESULTS: There was no difference in duration of breast-feeding between children who later got diabetes and the controls. Children (both diabetics and controls) born during the summer were exclusively breastfed for a mean period of 2.2 months. Corresponding figures for children born during winter were 2.8 months (p<0.04), spring 2.5 months (n.s.) and autumn 2.7 months (p<0.05). Seasonality was most pronounced in children who developed diabetes between the ages of 10 and 15 years. CONCLUSION: These results indicate that children born during the summer, who have increased risk of developing diabetes mellitus, have also been exclusively breastfed for a shorter time.

Adolescent↗
PubMed2001

Intensive insulin treatment in diabetic children.

Intensification of insulin therapy which maintains long-term near-normoglycaemia (HbA1c<7.0%) strongly protects against onset and/or progression of diabetic microangiopathy in Type 1 diabetes mellitus of adults. Similar intensification of insulin therapy is needed in diabetic children as well, in order to prevent complications a few years after diabetes onset, ie very often in young age. Provided adequate psychosocial support and education are available, children should be treated with multiple daily injections of insulin or, when necessary, with continuous subcutaneous insulin infusion, along with blood glucose monitoring. Insulin regimens may differ from child to child and vary from day to day in the same child, depending on lifestyle and considering all the available insulin preparations. These include the short-acting insulin (both human regular and short-acting insulin analogues), the intermediate-acting insulin (NPH and Lente), as well as the new long-acting insulin analogue glargine. The latter seems a promising candidate to substitute of basal insulin. The concern that intensified insulin therapy increases the risk of hypoglycaemia, as indicated by the Diabetes Control and Complications Trial (DCCT), is no longer tenable. On the contrary, a physiological, flexible insulin regimen better than a fixed insulin regimen, usually the twice daily split-mixed regimen, protects against the risk of hypoglycaemia in relation to food ingestion, physical exercise and sleep. Thus, appropriate education should be delivered at diabetes onset to the child and parents in order to start the strategy of intensified insulin therapy as early as possible.

Blood Glucose↗
PubMed2000

Th1-like dominance in high-risk first-degree relatives of type I diabetic patients.

AIMS/HYPOTHESIS: The humoral part of the immune system, including autoantibodies, is known to predict manifest Type I (insulin-dependent) diabetes mellitus in first-degree relatives but the cell-mediated immune process preceding the manifest disease still is not known. The aim of this investigation was to estimate the immunological balance of Th-like lymphocytes (Th1/Th2) in high-risk first-degree relatives of Type I diabetic children. METHODS: Peripheral blood mononuclear cells (PBMC) from 21 healthy high-risk first-degree relatives (ICA > or = 20) were examined and compared with the response seen in PBMC from children with newly diagnosed Type I diabetes and healthy control subjects of similar age, sex and HLA-type. Expression of interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) mRNA were determined by RT-PCR and as protein by ELISPOT after stimulation with specific epitopes of GAD65 (a.a. 247-279, 509-528, 524-543), bovine serum albumin, the ABBOS peptide (a.a. 152-169) and insulin. RESULTS: High-risk relatives had a high ratio of IFN-gamma:IL-4 compared with both diabetic children (p = 0.0005) and healthy control subjects (p = 0.004). Production of IFN-gamma seen in high-risk relatives was negatively correlated to production of GADA (r = -0.44, p = 0.05). The high concentration of IFN-gamma from high-risk relatives, decreased after stimulation with peptides of GAD65, the ABBOS peptide, BSA and insulin. Increased secretion of IL-4 was observed after stimulation with two peptides of GAD65 (a.a. 509-528 and 524-543), the ABBOS peptide and insulin. CONCLUSION/INTERPRETATION: Overwhelming production of IFN-gamma seen in peripheral blood mononuclear cells from high-risk first-degree relatives of children with Type I diabetes suggests a Th1-like immune deviation in the prediabetic phase.

Adolescent↗
PubMed2000

The ABBOS-peptide from bovine serum albumin causes an IFN-gamma and IL-4 mRNA response in lymphocytes from children with recent onset of type 1 diabetes.

The ABBOS-peptide from bovine serum albumin (BSA) in cow's milk has been suggested to initiate the autoimmune process against the beta-cells leading to type 1 diabetes. The aim of this study was to elucidate if the ABBOS-peptide is a possible trigger of type I diabetes. The cytokines IL-4 and IFN-gamma were determined at the level of transcription as mRNA in lymphocytes, stimulated with the ABBOS-peptide. Sixteen children with newly diagnosed type 1 diabetes were compared with 10 healthy controls matched for the diabetes associated HLA-type DR3/4. Antibodies to bovine serum albumin (BSA), insulin antibodies (IA), and antibodies against islet cells (ICA) were determined, as well as serum C-peptide. Increased mRNA expression for IFN-gamma and/or IL-4 could be observed in lymphocytes from 13/16 children with recent onset of diabetes after in vitro stimulation with the ABBOS-peptide. Low expression of IFN-gamma mRNA was associated with high secretion of C-peptide, whereas a positive relationship could be observed between expression of IL-4 mRNA and insulin antibodies. Expression of IFN-gamma and/or IL-4 mRNA was also detected in lymphocytes from 6/10 healthy controls. ABBOS may have a role as a reactive epitope in the upregulation of the autoimmune process against the beta-cells but ABBOS does not seem to cause any specific Th1 response. An increased mRNA expression could also be seen in lymphocytes from healthy controls. Thus, the ABBOS-peptide might just cause or reflect an unspecific immune activity.

Adolescent↗
PubMed2000

Thinner needles do not influence injection pain, insulin leakage or bleeding in children and adolescents with type 1 diabetes.

AIMS: To investigate pain, leakage and bleeding when injecting insulin with different diameters of needles. METHODS: Sixty children and adolescents aged 9-21 yrs participated in study A and 40 aged 8-20 yrs in study B. Both were double-blind and randomized. In study A, we evaluated the pain when injecting with three needles [Novo 27G/13 mm (N27), B-D MicroFine IV 28G/13 mm (B28), NovoFine 28G/12 mm (N28)] and in study B, with three needles [NovoFine 28G/12 mm (N28), B-D MicroFine+ 29G/13 mm (B29), NovoFine 30G/8 mm (N30)] and one placebo injection (no needle mounted). Abdominal and thigh injections were given in a 45 degrees angle with a lifted two-finger skinfold on two different visits, scoring pain on a 10-cm visual analog scale (VAS), and in study B faces were added to the scale. RESULTS: The median VAS scores in study A were 1.2 cm (N27), 1.2 cm (B28) and 1.0 cm (N28) for abdominal injections, and 1.2 cm (N27), 0.7 cm (B28) and 1.1 cm (N28) (n.s.) for thigh injections. The median VAS scores in study B were 2.5 cm (N28), 2.3 cm (B29) and 2.8 cm (N30) (n.s.) for abdominal injections, and 2.0 cm (N28), 1.5 cm (B29) and 1.9 cm (N30) (n.s.) for thigh injections. The overall median score of placebo injections was 0.1 cm (p=0.0001). Bleedings were less common with the B29 needle (35.5%) than with the N28 needle (48.1%) (p=0.028) but with no difference compared to the N30 needle (39.2%). Leakage of insulin was found in 14% of abdominal and 25% of thigh injections (p=0.0001) with no difference between the needles. VAS scores were higher in study B which may be explained by the facial VAS scale increasing the range of answers. CONCLUSIONS: We found no difference in injection pain, preference, bleeding or insulin leakage between the needles. Decreasing the needle diameter from 0.4 to 0.3 mm (27-30G) does not seem to decrease pain perception in this age group.

Clinical Trial↗
PubMed2000

Seasonal variation of HbA1c in intensive treatment of children with type 1 diabetes.

OBJECTIVE: The aim of this study was to measure whether there is a seasonal variation in glycosylated haemoglobin concentrations and insulin dose used in the intensive treatment of children with type 1 diabetes, and whether such variation is related to severe hypoglycaemia. PATIENTS: A geographic population of 114 intensively treated type 1 diabetic patients < 19 years of age, mean 12.7 (SD 4.3) years, with diabetes onset before 1995, were studied in a cohort 1995-96. METHODS: HbA1c, insulin doses and severe hypoglycaemia were registered at regular visits scheduled quarterly, but not standardised in time. Seasonal mean values were calculated for HbA1c and insulin dose. RESULTS: Lower HbA1c was seen in spring and summer, and higher in autumn and winter (p=0.023). Patients reporting severe hypoglycaemia had a seasonal variation in HbA1c (p=0.019) and a tendency to seasonal variation in insulin dose, while patients not reporting severe hypoglycaemia did not vary in HbA1c or insulin dose. CONCLUSIONS: Self-control and adjustment of insulin doses to seasonal change need to be improved also in intensively treated children, with regard to the risk for worsened metabolic control after the summer and increased severe hypoglycaemia in spring and early summer. The findings have important implications for design of short-term studies of metabolic control.

Adolescent↗
PubMed2000

The renin-angiotensin-aldosterone system is suppressed in adults with Type 1 diabetes.

Poor glycaemic control and high blood pressure are two important risk factors for the development of retinopathy and nephropathy in Type 1 diabetes. The renin-angiotensin-aldosterone system (RAAS) may be involved in this process, since treatment with angiotensin-converting enzyme (ACE) inhibitors postpones the development of these complications. We investigated whether plasma renin activity (PRA), plasma angiotensin II (Ang II) and atrial natriuretic peptide (ANP) differed in Type 1 diabetic patients compared with healthy controls. We recruited 80 patients with Type 1 diabetes of more than 10 years' duration and 75 age-matched controls. We found that PRA and Ang II concentrations were significantly lower in patients than in the controls. The levels of ANP, on the other hand, were higher in patients than in controls. PRA correlated negatively to the mean value of HbA(1c) during the previous five years. PRA and Ang II were significantly lower in patients with mean HbA(1c) >8.4% compared with those with mean HbA(1c) <7.2%. In summary, we found patients with Type 1 diabetes to have RAAS suppression and increased ANP levels, suggesting a state of fluid retention.

Adult↗
PubMed1999

Osteopontin is an autoantigen of the somatostatin cells in human islets: identification by screening random peptide libraries with sera of patients with insulin-dependent diabetes mellitus.

Random peptide libraries (RPLs) screening with IDDM sera has identified 5 disease-specific 'mimotopes' displayed on phage (phagotopes). We characterised one phagotope (CH1p), by raising a rabbit antibody against the peptide insert on phage, which was employed in immunohistochemistry, Western blotting and cDNA libraries screening. The CH1p mimotope was detected in somatostatin cells of human islets and experimentally raised anti-osteopontin antibodies or human sera positive for the phagotope, detected a similar subpopulation of islet cells. The screening of cDNA library identified a clone corresponding to human osteopontin. In summary, RPLs proved to be successful in the identification of a novel islet-related autoantigen (osteopontin), whose significance in disease remains to be established.

Animals↗
PubMed1999

Adverse events in intensively treated children and adolescents with type 1 diabetes.

The main objective of this study was to examine the relation between adverse events and degree of metabolic control and multiple-dose treatment. A total of 139 children, aged between 1 and 18 y, prospectively registered severe hypoglycaemia with or without unconsciousness, as well as hospitalized ketoacidosis, during 1994-95. Treatment from onset was multiple-dose insulin (> 95% > or = 4 doses) combined with intense training and psychosocial support. Median HbA1c was 6.9% (ref. 3.6-5.4%). The incidence of severe hypoglycaemia with unconsciousness was 0.17 events per patient-year, having decreased from the 1970s to the 1990s, parallel to a change from 1-2 to > or = 4 doses per day. There was no correlation or association to the year mean HbA1c for severe hypoglycaemia. Severe hypoglycaemic episodes in 1995 correlated to severe hypoglycaemic episodes in 1994 (r=0.38; p<0.0001). Severe hypoglycaemia with unconsciousness increased during the spring season, and according to case records the assumed causes were mainly mistakes with insulin, food and exercise. Ketoacidosis was rare: 0.015 episodes per patient-year. We conclude that multiple-dose insulin therapy from the very onset of diabetes, combined with adequate self-control, active problem-based training and psycho-social support, may limit severe hypoglycaemia and ketoacidosis. Strategies aimed at minimizing severe hypoglycaemia without compromising metabolic control need to be evaluated.

Adolescent↗
PubMed1999

Month of birth and risk of developing insulin dependent diabetes in south east Sweden.

Environmental factors very early in life may be important for later development of insulin dependent diabetes. Because several of these factors, such as infections, vary with season, we predicted a difference in birth pattern compared with the general population among children who develop diabetes. In a population based study we analysed all 1248 children from seven paediatric departments in the south east part of Sweden to evaluate whether there is such a relation. There was a significant difference in birth pattern in patients with diabetes compared with the general population. Children who developed diabetes at the age of 10-15 years accounted for most of this difference. Boys had a more pronounced difference in birth pattern than girls. Children diagnosed with diabetes during years of high incidence, as well as children with an infection before diagnosis of diabetes, showed a significantly different birth pattern compared with the background population. These results indicate that there is a difference in birth pattern in children who develop diabetes compared with the background population. This supports the theory that environmental factors early in life play a role in the development of diabetes many years later.

Adolescent↗
PubMed1999

Previous exposure to measles, mumps, and rubella--but not vaccination during adolescence--correlates to the prevalence of pancreatic and thyroid autoantibodies.

OBJECTIVE: This study was designed to determine whether a relationship exists between previous exposure to measles, mumps, and rubella (MMR) by natural infection or vaccination or by new immunization with MMR vaccine, and either the presence or levels of autoantibodies against thyroid cell and pancreatic beta-cell antigens. METHODS: Antibodies against MMR and autoantibodies against thyroglobulin, thyroid peroxidase, pancreas islet cells (ICA), islet cell surface, glutamic acid decarboxylase 65k autoantibodies, and insulin were studied before, and 3 months after, vaccination with combined MMR vaccine in 386 school children between 11 and 13 years of age. RESULTS: The vaccination changed neither the prevalence nor the level of autoantibodies. Children with rubella antibodies before vaccination had higher levels of ICA than did the rubella seronegative children. In contrast, thyroid autoantibody levels and prevalence were lower in children with antibodies against measles, mumps, or both before vaccination than in children without those antibodies. CONCLUSIONS: Previous natural infection or vaccination against measles, mumps, or both seemed to have an inhibitory effect on the development of thyroid autoantibodies. In contrast, children with previous exposure to rubella had higher levels of ICA. No evidence was found that MMR vaccination during adolescence may trigger autoimmunity.

Adolescent↗
PubMed1998

Autonomic function in children with type 1 diabetes mellitus.

We investigated autonomic function in 58 children and young adults with Type 1 diabetes mellitus (aged 7-22 years, duration from 3 to 18, 8.6 +/- 3.4 years) and in 74 healthy controls (6-21 years) using power spectral analysis of blood pressure and heart rate in addition to conventional standard autonomic function tests: deep breathing, the Valsalva manoeuvre, and a standing test. None of the diabetic patients were symptomatic. Reproducibility of the tests was assessed by determining the coefficient of variation in 9 controls (7.8-37.7%). Thirteen per cent of the subjects had difficulty in adequately performing the Valsalva manoeuvre. After adjustment for age, sex, body mass index, and respiratory frequency, results of the Valsalva manoeuvre and deep breathing were not different between patients and controls and there was no significant postural reduction in systolic blood pressure (> or = 20 mmHg) in the patients. Heart rate variation in the supine position during natural breathing was low in patients, although power spectral analysis of heart rate variation did not show a significant decrease in the power density in the high and the low frequency in patients compared to healthy controls. Beat-to-beat blood pressure fluctuation was significantly lower in patients and correlated with metabolic control (mean annual haemoglobin A1c), but not with disease duration and was abnormal in 7 diabetic children (12%). In contrast, tests of vagal activity were not impaired in the patients in this age range. We concluded that vagal involvement in Type 1 diabetic patients determined by spectral analysis of R-R intervals in addition to conventional tests is uncommon, but that beat-to-beat blood pressure variation was more likely to be affected.

Adolescent↗
PubMed1998

Unchanged incidence of severe retinopathy in a population of Type 1 diabetic patients with marked reduction of nephropathy.

The incidence of nephropathy in Type 1 diabetes mellitus has declined during the past decade, probably as a result of improved glycaemic control. We wanted to investigate whether the incidence of severe retinopathy has changed during the same time period and to evaluate the importance of glycaemic control in relation to the development of severe retinopathy and nephropathy. All 213 patients in whom Type 1 diabetes mellitus was diagnosed before the age of 15 years between 1961 and 1980 in a district in southeastern Sweden were studied. Ninety-two per cent of the patients were followed from the onset of diabetes to 1991 or to death. The cumulative incidence of severe retinopathy was not significantly different between the patients with diabetes onset 1961-65, 1966-70, 1971-75, and 1976-80. The risk of developing severe retinopathy or nephropathy was higher in patients with very poor glycaemic control (HbA1c > or = 8.4%) vs patients with poor control (HbA1c > or = 7.2 < 8.4%; p < 0.001). Patients with poor control had an increased risk of developing severe retinopathy vs patients with good control (HbA1c < 7.2%; p < 0.008) but there was no difference in the risk of nephropathy. No patients with good control developed nephropathy and only one patient developed severe retinopathy during 25 years of diabetes.

Adolescent↗
PubMed1998

Low dose linomide in Type I juvenile diabetes of recent onset: a randomised placebo-controlled double blind trial.

The quinoline-3-carboxamide, linomide, protects non-obese diabetic mice from diabetes. The effects of linomide on insulin needs and beta cell function were studied in recent juvenile Type I diabetes in a double-blind trial. Patients with recent onset diabetes were randomly assigned to treatment with a fixed dose of 2.5 mg linomide (42 patients) or placebo (21 patients) for 1 year, in addition to insulin and diet. Glycated haemoglobin was 10-15% lower at 9 months (p = 0.003) and 12 months (p < 0.05) in the linomide group. The insulin dose was 32-40% smaller in the linomide group at 3 (p < 0.03), 6 (p < 0.02), 9 (p < 0.001) and 12 months (p = 0.01). Insulin doses correlated negatively with C peptide values (p = 0.001-0.002). The trend for higher C peptide values in the linomide group did not reach significance. In a post hoc subgroup analysis performed in 40 patients (25 from the linomide group and 15 from the placebo group) who still had detectable residual beta cell function at entry, linomide was associated with 45-59% higher C peptide value at 6 months (p < 0.05), 9 months (p < 0.05) and 12 months (p < 0.05). The main adverse effects of linomide were mild transitory anaemia (45 vs 10% in the linomide and placebo groups), thrombocytopenia (24 vs 10%), and mild joint discomfort (45 vs 5%) with no clinical signs. In conclusion, low-dose linomide reduced the insulin needs in patients with juvenile Type I diabetes of recent onset and improved beta cell function in patients who still had detectable beta cell function at entry. These results support further clinical and experimental studies to define the effects of linomide in Type I diabetes provided the safety of linomide is reliably established.

Adjuvants, Immunologic↗
PubMed1998

Peptide from glutamic acid decarboxylase similar to coxsackie B virus stimulates IFN-gamma mRNA expression in Th1-like lymphocytes from children with recent-onset insulin-dependent diabetes mellitus.

At the clinical onset of insulin-dependent diabetes mellitus (type 1 diabetes), inflammation within the pancreatic islets of Langerhans causes insulitis. CD4+ or Th-lymphocytes will be activated after stimulation resulting in interferon-gamma (IFN-gamma) production by Th1-like lymphocytes and/or interleukin-4 (IL-4) secretion from Th2-like lymphocytes. The antigens responsible for this activation are unknown, but studies have suggested glutamic acid decarboxylase (GAD) to be a possible candidate. One peptide from this enzyme (amino acid 247-279) with a similar amino acid sequence to coxsackie B virus may cause lymphocyte proliferation in diabetic patients. In this study we have shown that this peptide activates Th1-like lymphocytes which produce increased amounts of IFN-gamma mRNA, but seldom mRNA for IL-4. Lymphocytes from healthy HLA-matched controls (DR3/4) did not respond with an upregulated mRNA expression for these cytokines when stimulated by the GAD-peptide (P<0.05). A low or absent expression of IFN-gamma mRNA was significantly correlated to a high fasting C-peptide at 3 months' duration (P<0.05). In conclusion, we suggest that GAD65 is involved in the development of type 1 diabetes and that the Th1-response may play a role in the destruction of beta cells.

Adolescent↗
PubMed1998

Islet cell surface antibodies (ICSA) do bind to human pancreas: computerised, quantitative determination of ICSA using both pre- and postembedding immunocolloidal techniques.

Islet cell surface antibodies (ICSA) have been demonstrated significantly more often in serum of patients with IDDM and their relatives than in healthy controls, but some investigators have been unable to show binding to human islets. It has therefore been suggested that ICSA is an artefact. We have localised and quantified ICSA binding to different specimens, including human pancreas. ICSA-positive and ICSA-negative patients' serum, determined by a RIA-method, were incubated with ultrathin sections of rat insulinoma (RIN5AH) cells, stained with Goat-anti-human IgG conjugated with 10 nm gold particles. Sections were viewed in transmission electron microscopy (Mag. 30,000 x) and image analyses was used to calculate immunolabelling. To test cell specificity we used (RIN5AH-cells, rat tumour cells producing growth hormone (GH3), normal human pancreas, human insulinoma, and mice liver). Sections showed good morphology. ICSA-positive sera, with or without islet cell antibodies (ICA) gave always higher immunocolloidal labelling then ICSA-negative sera on RIN5AH sections. Thus, the colloidal gold technique could confirm the ICSA results determined with RIA. Immunolabelling was pronounced on normal human pancreas and human insulinoma cells, but none was found on GH3-cells or mice liver cells. ICSA is not an artefact but do exist and bind to human islet cells and therefore maybe can be used as a marker for IDDM immunity.

Animals↗