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Biomedical subjects

J Ludvigsson

Publications and source records attributed to J Ludvigsson.

At least 19 recordsLinked to original sources
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

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↗
PubMed1995

Subclinical nerve dysfunction in children and adolescents with IDDM.

The purpose of this study was to investigate whether young insulin-dependent diabetic patients still develop peripheral nerve dysfunction when using modern multiple insulin injection therapy and to elucidate if this correlated with various disease parameters. Seventy-five patients, 7 to 20 years old with a duration of diabetes of more than 3 years, and 128 age-matched healthy control subjects underwent bilateral studies of median, peroneal, and sural nerves. Presence of diabetes lowered motor conduction velocity (p < 0.0001), sensory conduction velocity (p < 0.0001) and sensory nerve action potential (p < 0.05) in all examined nerves. The mean change in conduction velocity induced by diabetes was -4.8 m/s in the peroneal nerve, -3.3 m/s in the median motor nerve, -2.6 m/s in the sural nerve and -2.4 m/s in the median sensory nerve. Fifty-seven percent of the patients had abnormal conduction (values outside 95% predictive interval) which was seen most often in the motor nerves, especially in the peroneal nerve (41%) followed by the median nerve (24%). In multiple regression analysis, long-term poor metabolic control and increased body length correlated with nerve dysfunction identified in most examined parameters. Three patients had signs or symptoms suggestive of neuropathy. It is concluded that despite modern multiple insulin injection therapy, with reasonably good metabolic control, nerve dysfunction is still common in children and adolescents with insulin-dependent diabetes mellitus. Risk factors are increased height and long-term poor metabolic control.

Adolescent↗
PubMed1995

Normal values of nerve conduction in children and adolescents.

Healthy children and adolescents (n = 128) ranging in age from 6 to 20 years and in height from 114 to 193 cm underwent studies of median, peroneal and sural nerves bilaterally, including nerve conduction velocity, amplitude and motor distal latencies. Arms and legs were heated in all subjects to obtain skin temperatures around 34 degrees C. Both motor and sensory nerve conduction velocities were found to correlate more with height than with age. There was a strong negative correlation between height and peroneal conduction velocity (r = -0.40, P < 0.0001). On the contrary, a positive correlation was found between height and both median sensory (r = 0.30, P < 0.0001) and motor (r = 0.22, P < 0.001) conduction velocities. Skin temperature, even near 34 degrees C, had a strong effect on conduction velocity and motor distal latencies. It is concluded that consideration of height and temperature will improve the diagnostic safety of nerve conduction measurements in children and young adults.

Action Potentials↗
PubMed1995

Adult cancer risks among the mothers of children with cancer.

We investigated cancer risk among mothers of 2365 children who were diagnosed with cancer between 1973 and 1989 in Sweden. From the date of birth of the child until 31 December 1989, 38 cases of cancer were diagnosed among the mothers. The expected number of cases, according to national rates, was 30.9. Cancer of the thyroid was the only site showing a significantly increased risk among the mothers (observed = 6, expected = 1.2, P < 0.01), but two cases were medullary cancer associated with an inheritable syndrome, and inherited by their children.

Adult↗
PubMed1995

Psychological stress and the onset of IDDM in children.

OBJECTIVE: The purpose of the study was to determine whether psychosocial stress during different life periods could be a risk factor in the etiology/pathogenesis of insulin-dependent diabetes mellitus (IDDM) in children. RESEARCH DESIGN AND METHODS: In a population-based sample of 67 case patients 0-14 years of age and 61 matched healthy control subjects, life events during the entire lifespan before the onset of IDDM were recorded as well as measures of child behavior before onset, social support, and family function. RESULTS: Negative life events occurring during the first 2 years of life, life events with difficult adaptation, child behavioral deviances, and a more chaotic family function were more common in the case group. A stepwise logistic regression indicated that negative life events in the first 2 years increased the risk of IDDM and that premorbid child behavior as well as dysfunctional hierarchical family pattern affect the risk. CONCLUSIONS: Stress early in life may increase the risk for IDDM, presumably by affecting the autoimmune process. To confirm these results, it is necessary to make a truly prospective study.

Case-Control Studies↗
PubMed1995

T cell proliferative responses to glutamic acid decarboxylase-65 in IDDM are negatively associated with HLA DR3/4.

Based on studies in spontaneously non-obese diabetic (NOD) mice, it has been suggested that the Mr 65,000 isoform of glutamic acid decarboxylase (GAD65) is of major importance in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). In humans, antibodies to GAD65 are present before and at onset of the disease and in vitro T cell reactivity to GAD has also been reported. To further characterize the T cell recognition of GAD65, we incubated peripheral blood mononuclear cells from 45 newly diagnosed IDDM patients with purified recombinant human islet GAD65 and correlated the proliferative response with HLA DR haplotype and the presence of GAD65 autoantibodies. Fifty healthy individuals were studied as controls. Of the patients, 49% showed proliferative responses to GAD65 in contrast to only 4% of the controls. T cell proliferation to GAD65 was significantly more frequent in patients not being HLA DR3/4 heterozygous (19/29, 66%) as compared to HLA DR3/4 heterozygous patients (3/16, 19%) (p < 0.01). The difference was most pronounced in females with 64% (9/14) of the HLA non-DR3/4 patients being positive compared to none (0/6) of the HLA DR3/4 patients (p < 0.05). The overall frequency of GAD65 autoantibodies was 71% (32/45) with a similar distribution between patients with HLA DR3/4 (10/16, 63%) and HLA non-DR 3/4 (22/29, 76%). There was no correlation between levels of the T and B cell responses to GAD65 (r = 0.24). In conclusion, we find a proliferative T cell response to GAD65 in approximately 50% of recent onset IDDM patients and unexpectedly find the majority of responders to be HLA non-DR 3/4 heterozygous patients. No difference was observed in B cell responsiveness between the two HLA groups.

Adolescent↗
PubMed1994

Islet cell antibodies (ICA), insulin autoantibodies (IAA), islet cell surface antibodies (ICSA) and C-peptide in 1031 school children in a population with a high background incidence of IDDM.

Islet cell antibodies (ICA), insulin autoantibodies (IAA) and islet cell surface antibodies (ICSA) together with C-peptide were determined in 1031 healthy schoolchildren to evaluate the frequency of autoimmune reactions towards endocrine pancreas and its relation to insulin secretion in non-diabetic children. The prevalence of ICA (levels > 6 JDF units) was 1.4% (14/1012) while 44 children (4.3%) were ICSA-positive and 40 (4%) had IAA. Girls had higher titres of ICSA than boys. Young children (7-8 years) more often had IAA than 12-13-year-old children who, however, had ICA three times more often than the young children. There were no clear associations between the different antibodies. Of the children, 2.4% had very low post-prandial serum C-peptide values (< or = 0.25 nmol/l). Serum C-peptide was higher in girls than in boys (P < 0.001) and in older children than in younger (P < 0.001). Girls with low levels of ICA had high C-peptide values, while girls with high ICA titers had low C-peptide values, the latter perhaps indicating partial beta cell loss. IAA and ICSA were not related to C-peptide values but both positive ICSA and high C-peptide values were most common in the autumn (P < 0.02 and P < 0.0001, respectively). One of the ICA-positive children developed diabetes in 1991, 4 years after the blood sample was taken. Since after 5 years only one of the children has developed IDDM, it can be concluded autoimmune reactions towards endocrine pancreas and insulin may occur in many children without the development of manifest diabetes. Those with high ICA titers may have lost so many beta cells that their insulin secretion is affected, which in some cases might lead to diabetes many years later.

Adolescent↗
PubMed1994

Declining incidence of nephropathy in insulin-dependent diabetes mellitus.

BACKGROUND: The high relative mortality among patients with insulin-dependent diabetes mellitus results mainly from diabetic nephropathy. The cumulative incidence of nephropathy of 25 to 30 percent among patients who had had diabetes for 25 years remained stable from 1950 to the early 1980s. In a population study, we assessed recent trends in the incidence of diabetic nephropathy. METHODS: We studied all 213 patients in whom insulin-dependent diabetes mellitus was diagnosed before the age of 15 years between 1961 and 1980 in a district in southeastern Sweden. Ninety-two percent of the patients were followed from the onset of diabetes to 1991 or to death. Patients with persistent albuminuria (positive Albustix test) were considered to have diabetic nephropathy. Glycosylated hemoglobin was measured periodically in all patients, beginning in 1980. RESULTS: The cumulative incidence of persistent albuminuria after 25 years of diabetes decreased from 30.0 percent among the patients in whom diabetes developed in the period 1961 to 1965 to 8.9 percent among those in whom it developed from 1966 to 1970 (P = 0.01). After 20 years of diabetes, the cumulative incidence decreased from 28.0 percent among the patients in whom diabetes developed from 1961 to 1965 to 5.8 percent among those in whom it developed from 1971 to 1975 (P = 0.01). Persistent albuminuria has not yet developed in any patient in whom diabetes was diagnosed in the period 1976 to 1980. The average glycosylated hemoglobin value decreased from 7.4 percent in the period 1980 to 1985 to 7.0 percent from 1986 to 1991 (P < 0.001). The mean glycosylated hemoglobin value was higher in the patients with persistent albuminuria than the patients with no albuminuria (8.1 percent vs. 7.1 percent, P < 0.001). CONCLUSIONS: During the past decade the cumulative incidence of diabetic nephropathy, as manifested by persistent albuminuria, among patients who have had diabetes for 25 years has decreased substantially, probably as a result of improved glycemic control.

Adolescent↗
PubMed1994

A high weight gain early in life is associated with an increased risk of type 1 (insulin-dependent) diabetes mellitus.

Growth during the first years of life in relation to type of feeding in infancy was retrospectively studied in an unselected population-based group of 297 children who had been diagnosed with Type 1 (insulin-dependent) diabetes mellitus before the age of 15 years (probands) and 792 individually-matched referent subjects. Reliable data were collected from child welfare clinics. Probands weighed slightly less at birth but their weight gain at 6, 9, 18 and 30 months of age was significantly greater (p < 0.02) than that of referent children. The weight gain of children who had never been breast-fed was more marked than that of breast-fed children; this was found for both probands and referent children. But also among exclusively breast-fed children (> 2 months), probands gained significantly more in weight from birth up to 18 and 30 months of age than exclusively breast-fed referent children. Early weight gain appears to be a risk factor for development of Type 1 diabetes. The lower weight gain in breast-fed compared to non-breast-fed children may explain the protective effect of breast feeding against Type 1 diabetes observed in several studies.

Adolescent↗
PubMed1994

Indications for a more aggressive disease process in newly diagnosed insulin-dependent diabetic children in northern than in southern Europe.

Finland and Sweden have the highest incidence of insulin-dependent diabetes in children in the world, about 3-4 times that of countries in the Mediterranean area, with the exception of Sardinia. We have collected information from several European clinics and from Pittsburgh, USA, in order to find out whether this difference incidence is associated with corresponding differences of the disease pattern. Patients in Finland or Sweden ('North') and Pittsburgh were younger (< 10 years old) at diagnosis compared with those in the other clinics in Europe (P < 0.05 versus P < 0.02). In the North, boys were in excess (58%) in contrast to France (40%) and Pittsburgh (46%). Patients in the North had a shorter duration of symptoms (< 8 days; P < 0.001) and higher blood glucose (> 20 mmol/l; P < 0.05) than those attending the other European clinics. Irrespective of age, there were more ICA-positive patients in the North (94%) than in Berlin-Vienna (67%; P < 0.01) or in France (70%; P < 0.01). There was a tendency for non-diabetic parents and siblings in the North to have lower C-peptide values (< 0.26 pmol/ml) at the time of diagnosis of the proband and to be ICA-positive more often than relatives in the other European clinics. The seasonal variation of diagnosis showed no obvious geographical differences, with recorded diagnosis always lowest during the summer. We conclude that certain factors seem to cause not only a high incidence of diabetes in children in Finland and Sweden but perhaps also a more aggressive early disease process.

Adolescent↗
PubMed1994

Acute myeloid leukemia (AML-M1) with multiple trisomies and t(8;21)(q22;q22).

Cytogenetic analysis of an acute myeloid leukemia (AML-M1) showed the karyotype 53,XY, +6, +8,t(8;21)(q22;q22), +9, +10, +13, +19, +21. Only one AML with a massively hyperdiploid karyotype (> 50 chromosomes) and t(8;21) has been published before. A comparison of the two cases reveals similarities both with regard to the morphologic subtype (M1) and to which chromosomes were trisomic (+6, +8, +13, +19, and +21 were found in both cases). We surmise that the t(8;21) was the primary chromosomal abnormality and that the set of multiple trisomies occurred secondarily; this pattern of clonal evolution may have favored a more immature leukemic phenotype in these two cases than is regularly seen in t(8;21)-associated leukemias.

Child↗
PubMed1994

Space-time clustering in insulin-dependent diabetes mellitus (IDDM) in south-east Sweden.

Using the method developed by Knox, space-time clustering was analysed in all 584 cases of insulin-dependent diabetes mellitus (IDDM) diagnosed between 1977-1990 and below the age of 16 from four paediatric departments in south-east Sweden. The catchment areas of these clinics form a contiguous geographical area of 26,445 km2 with a total of 165,784 children aged 0-15 years. The annual incidence for the study period was 25.2 per 100,000 children aged 0-15 years with a statistically significant incidence variation between the years; highest incidence in 1983 (39.2) and lowest in 1977 and 1989 (18.9 and 20.7 respectively). In the analysis, 30 different combinations of critical cutoff values were used to define closeness in space and time of pairs of cases. Statistically significant results were seen for several combinations with the highest significance obtained for the cutoff values of 15 km and 7 months, respectively. This space-time clustering tended to be specially pronounced during the period with the highest incidence of IDDM, 1981-1985. Our results indicate that space-time clustering exists in IDDM. These findings may support the hypothesis that infectious agents (possibly viral) give rise to a portion of IDDM.

Adolescent↗
PubMed1994

Metabolic control is not altered when using indwelling catheters for insulin injections.

OBJECTIVE: To determine if the use of indwelling catheters for insulin injections affects the long- and short-term metabolic control of insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: Sixteen children and adolescents 9-20 years of age were included in a randomized 10-week crossover study using indwelling catheters (Insuflon, Pharma-Plast, Lynge, Denmark; CHRONIMED, Minnetonka, Minnesota) for insulin injections. Their diabetes duration was 7.5 +/- 3.3 years (range 2-14), and they used multiple injection therapy with 4-5 doses/day. C-peptide was < or = 0.15 nM fasting and < or = 0.30 nM postprandial. RESULTS: We found no significant difference between those with and without Insuflon in degree of metabolic control reflected by HbA1c (with Insuflon, 7.3 +/- 2.6%; without, 7.1 +/- 2.2%), 24-h profiles of blood glucose and free insulin, 24-h samples of glucosuria, or ketonuria. Weight, insulin doses per kilogram per 24 h, and insulin antibodies were all the same in the two groups. CONCLUSIONS: The long- and short-term metabolic control of IDDM was not altered by the use of indwelling catheters for insulin injections. Insuflon can be offered as an alternative to patients with IDDM who find regular injections uncomfortable.

Adolescent↗