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Biomedical subjects

G Dahlquist

Publications and source records attributed to G Dahlquist.

At least 37 records · Page 2Linked to original sources
PubMed2000

Infections and risk of Type I (insulin-dependent) diabetes mellitus in Lithuanian children.

AIMS/HYPOTHESIS: The role of infections in the aetiology of Type I diabetes is controversial. Certain enteroviral infections might be involved in triggering the beta-cell destruction but insufficient exposure to early infections might increase the risk. We studied how the number of infections experienced during several periods from birth to onset influence diabetes risk. METHODS: The study group came from the five largest Lithuanian cities: 124 patients, selected from the 0-14 years-of-age childhood diabetes register and 372 population-based control subjects matched with them for age group and sex. Information about infections and duration of breastfeeding was collected from health care booklets, other data from a mailed questionnaire, returned by 94.4% of patients and 72.6 % of control subjects. RESULTS: One or more infections experienced during the first half year of life tended to reduce diabetes risk. Crude odds ratios (95% confidence intervals) in the 0-14, 0-4 and 5-14 years-of-age groups were 0.66 (0.42-1.04), 1.06 (0.48-2.36) and 0.52 (0.30-0.90) respectively. Adjustment for the duration of breastfeeding, number of people in the household, duration of mother's education and birth order of the index child made little difference. Odds ratios (95 % confidence intervals) in the 0-14, 0-4 and 5-14 years-of-age groups were 0.60 (0.37-0.98), 0.94 (0.40-2.20) and 0.47 (0.26-0.87), respectively. The number of infections recorded during the last pre-onset year or from birth to onset did not influence diabetes risk. CONCLUSION/INTERPRETATION: Exposure to infections early in life could decrease diabetes risk, particularly for children diagnosed after the age of 4 years.

Adolescent↗
PubMed2000

Increased 24 h mean insulin-like growth factor binding protein-3 proteolytic activity in pubertal type 1 diabetic boys.

Hyperglycaemia and increased variability of blood glucose in pubertal children with type 1 diabetes may be related to increased growth hormone (GH) secretion and insulin resistance. The role of changes in insulin-like growth factor-I (IGF-I) bioavailability for the glycaemic control in these patients has not been completely elucidated. In particular, the possible role of increased IGF binding protein-3 (IGFBP-3) proteolysis reported in other insulin resistant states awaits further characterization. The aims of this study were to assess if hyperglycaemia in children with type 1 diabetes was associated with changes in free dissociable IGF-I (fdIGF-I) and IGF binding protein-3 protease activity (IGFBP-3-PA) and if increased insulin resistance during puberty was associated with changes in IGFBP-3-PA in healthy and diabetic children. In diabetic boys in the period of maximal linear growth (Tanner stage 3, n = 5), the mean level and the variability of IGFBP-3-PA, determined every second hour throughout 24 h, were significantly higher both compared to postpubertal diabetic boys (n = 6; P = 0.003 and P = 0.001, respectively), and to age matched healthy boys (n = 4; P = 0.006 and P < 0.001 respectively). This activation of IGFBP-3-PA was most prominent during the day time. The mean 24 h blood glucose level (determined hourly) was the only parameter studied that significantly predicted the changes in mean 24 h IGFBP-3-PA in the diabetes group. The mean 24 h concentrations of fdIGF-I were decreased in the diabetic boys compared to the healthy controls but statistical significance was only achieved in Tanner Stage 5 (p = 0.03). We speculate that the elevated levels of IGFBP-3-PA in Tanner 3 diabetic boys are related to deteriorated glucose homeostasis and that it may be a compensatory mechanism to attenuate the decrease in fdIGF-I in order to partly restore insulin sensitivity and glycemic control.

Adolescent↗
PubMed2000

Analysis of 20 years of prospective registration of childhood onset diabetes time trends and birth cohort effects. Swedish Childhood Diabetes Study Group.

UNLABELLED: The Swedish Childhood Diabetes Registry has been recording all cases of childhood onset diabetes nationwide, with a high level of ascertainment, since 1 July 1977. The present report describes and analyses the 8358 childhood onset cases occurring between 1 January 1978 and 31 December 1997. The mean annual incidence was 26.4/100,000 children per year (1978: 21.1 and 1997: 31.9). There was a significant log-linear increase over time, with a mean annual increase of 1.7%. The steepest mean increase was seen among the young onset cases (2.5%) and the steepest yearly increase (6.3%) was seen in this age group during the last 10-y period. A shift towards a younger age at onset was clearly indicated, as the age at onset was less during the last compared with the first 10-y period of observation. The increase over time was similar between the sexes and during winter and summer. When analysing the six full birth cohorts covered, we found no clear-cut shift in the trend. Birth cohorts (1978-82) up to 5 y of onset showed a time variability but no clear trend over time. Ecological analyses associating cumulative incidence by birth cohort to breastfeeding frequency showed no significant association. A statistically significant log-linear association was found to the official estimate of gross domestic product adjusted for similar price levels (p = 0.002). CONCLUSION: The incidence of childhood onset diabetes is rapidly increasing in Sweden, with a shift towards the younger age groups but with no trend in birth cohorts. Precipitating rather than initiating environmental risk factors are suggested, and the correlation to gross domestic product may suggest risk factors associated with wealth-such as a high growth rate, a known risk factor for childhood diabetes.

Adolescent↗
PubMed2000

Insulin-like growth factor binding protein-1 as glucose regulator in adolescent boys with type 1 diabetes.

UNLABELLED: The aim of the present study was to investigate whether the diurnal variability of B-Glucose is dependent on GH, IGF-I and IGFBP-1 levels, apart from insulin, and if there is any difference between Tanner stages 3 and 5. Five boys in Tanner stage 3 and 6 boys in stage 5 with type 1 diabetes were included. Blood was continuously collected from a cubital vein for 24 h. S-Insulin, S-GH, S-IGF-I and S-IGFBP-1 were analysed. B-Glucose was analysed hourly at bedside. One week before and 1 wk after the 24-h study period the participants performed self-monitoring of blood glucose (SMBG) during normal physiologic conditions. In the 24-h profile of B-Glucose, insulin, IGFBP-1 and GH, we found a significant positive correlation between B-Glucose and log IGFBP-1 (r = 0.5, p = 0.005) and an inverse correlation to insulin (r = -0.5, p = 0.004) but no correlation to logGH (r = -0.04, p = 0.831). In multiple regression analysis, B-Glucose was still significantly correlated to log IGFBP-1, when adjusting for insulin and GH, in Tanner stage 5. We found a difference between Tanner stages 3 and 5 in the variability of B-Glucose over a longer period during normal daily activity (p = 0.02), but not over the 24-h study period. CONCLUSION: We have demonstrated in type 1 diabetes adolescent boys a relationship between simultaneously measured blood-glucose and IGFBP-1 levels independent of the insulin and GH levels, suggesting that the free fraction of IGF-I influences the glucose metabolism.

Adolescent↗
PubMed2000

The length of the CTLA-4 microsatellite (AT)N-repeat affects the risk for type 1 diabetes. Diabetes Incidence in Sweden Study Group.

CTLA-4 is important to down-regulating T cell responses and has been implicated in type 1 (insulin dependent) diabetes mellitus in both linkage and association studies. The aim of our study was to relate the polymorphic (AT)n microsatellite in the 3' untranslated sequence of the CTLA-4 gene to diabetes risk. We studied 616 consecutively diagnosed 0-34 year-old Swedish patients and 502 matched controls by PCR-based genotyping fo determine the length of the 3'-end (AT)n repeat region of the CTLA-4 gene and categorizing alleles as predominantly monomorphic short (S) or highly polymorphic (in length) long (L) alleles. The odds of type 1 diabetes of subjects with the L/L genotype was estimated to be 1.84 times that of subjects with the S/S genotype (95% CI 1.44-2.73, p=0.002). Further analysis of the long alleles, partitioned into intermediate (I) length and very long (VL) alleles, suggested that L alleles act recessively in conferring diabetes risk (p=0.0009). This study suggests that the 3'-end (AT)n repeat region of the CTLA-4 gene represents a recessive risk factor for type 1 diabetes.

Abatacept↗
PubMed1999

Handling of scientific dishonesty in the Nordic countries. National Committees on Scientific Dishonesty in the Nordic Countries.

Despite a widely recognised need, most countries still have no coherent system to deal with scientific misconduct. Committees have been established by the national medical research councils in Denmark (1992), Norway (1994), and Sweden (1997), and by the Ministry of Education in Finland (1994), to deal with scientific misconduct--ie, to initiate preventive measures, to investigate alleged cases, or both. Each committee includes both scientifically and legally qualified members. The employing institutions are responsible for possible sanctions or punishments. So far, 47 cases have been accepted for investigation, the majority (25) being Danish. Disputed authorship was the most frequent reason for investigation. Junior researchers made complaints in only three of the investigated cases. Investigations have been completed in 37 cases; in nine cases, dishonesty was revealed--two of them were related to the same researchers. Cooperation between the four Nordic committees has shown close agreement on specific issues and cases, despite minor differences in definitions, organisation, and procedures.

Advisory Committees↗
PubMed1999

Effect of angiotensin converting enzyme inhibitor or beta blocker on glomerular structural changes in young microalbuminuric patients with Type I (insulin-dependent) diabetes mellitus.

AIMS/HYPOTHESIS: To investigate the influence of angiotensin converting enzyme inhibitors and beta blockers on the progression of early diabetic glomerulopathy. METHODS: Thirteen patients with Type I (insulin-dependent) diabetes mellitus (mean age 18.8 years) with microalbuminuria 31 (19-160) microg/min were randomised to treatment with enalapril (group 1, n = 7) or metoprolol (group 2, n = 6). Renal biopsies were taken before and after 38 (36-48) months of treatment. Albumin excretion rate, blood pressure and HbA1c were measured every third month. A reference group without antihypertensive treatment (group 3, n = 9), with similar age, diabetes duration and degree of microalbuminuria as group 1 and 2, had baseline and follow-up renal biopsies taken previously with an interval of 26-34 months, analysed at the same laboratory. Glomerular structures were measured by stereological methods. RESULTS: Measurements of basement membrane thickness, mesangial and matrix volume fractions were similar among groups at baseline. Structural variables were only increased in group 3 at follow-up. Delta values in basement membrane thickness and diabetic glomerulopathy index per 24 months were lower in group 1 and 2 than in group 3 (p < 0.05). Microalbuminuria returned to normal in group 1 and 2 only. Decreased albumin excretion rate tended to inversely correlate with increased basement membrane thickness (p = 0.08) and diabetic glomerulopathy index (p = 0.05). Mean HbA1c was similar between groups. Mean diastolic blood pressure was lower in group 1 and 2 than in group 3 (p < 0.01). Mean HbA1c and mean diastolic blood pressure correlated to changes in basement membrane thickness, mesangial volume fraction and diabetic glomerulopathy index (p < 0.05). CONCLUSION/INTERPRETATION: Contrary to findings in the group without antihypertensive treatment, no progression of glomerulopathy was seen in those treated with enalapril or metoprolol.

Adolescent↗
PubMed1999

Complex interaction between HLA DR and DQ in conferring risk for childhood type 1 diabetes.

Type 1 (insulin-dependent) diabetes mellitus is associated with HLA DR and DQ factors, but the primary risk alleles are difficult to identify because recombination events are rare in the DQ-DR region. The risk of HLA genotypes for type 1 diabetes was therefore studied in more than 420 incident new onset, population-based type 1 diabetes children and 340 age, sex and geographically matched controls from Sweden. A stepwise approach was used to analyse risk by relative and absolute risks, stratification analysis and the predispositional allele test. The strongest relative and absolute risks were observed for DQB1*02-DQA1*0501/DQB1*0302-DQA1*0301 heterozygotes (AR 1/46, P < 0.001) or the simultaneous presence of both DRB1*03 and DQB1*0302 (AR 1/52, P < 0.001). Stratification analysis showed that DQB1*0302 was more frequent among DRB1*04 patients than DRB1*04 controls (P < 0.001), while DRB1*03 was more frequent among both DQA1*0501 (P < 0.001) and DQB1*02 (P < 0.001) patients than respective controls. The predispositional allele test indicated that DRB1*03 (P < 0.001) would be the predominant risk factor on the DRB1*03-DQA1*0501-DQB1*02 haplotype. In contrast, although DQB1*0302 (P < 0.001) would be the predominant risk factor on the DRB1*04-DQA1*0301-DQB1*0302 haplotype, the predispositional allele test also showed that DRB1*0401, but no other DRB1*04 subtype, had an additive risk to that of DQB1*0302 (P < 0.002). It is concluded that the association between type 1 diabetes and HLA is due to a complex interaction between DR and DQ since (1) DRB1*03 was more strongly associated with the disease than DQA1*0501-DQB1*02 and (2) DRB1*0401 had an additive effect to DQB1*0302. The data from this population-based investigation suggest an independent role of DR in the risk of developing type 1 diabetes, perhaps by providing diseases-promoting transcomplementation molecules.

Adolescent↗
PubMed1999

Seasonal variation in the incidence of Type 1 diabetes mellitus during 1983 to 1992 in the countries around the Baltic Sea.

AIM: To examine seasonal patterns of incidence of Type 1 diabetes mellitus incidence in children aged 0-14 years in Finland, Sweden, Estonia, Latvia and Lithuania during 1983-1992 (1987-1992 for Finland). METHODS: The study used a method that models incidence data using combinations of sine waves to model seasonal variation around a possible linear trend. RESULTS: In Finland, a significant pattern was found for combined sexes and age groups 0-9 and 10-14 years. A significant pattern was also confirmed for 10-14 year-old boys. In Sweden, the best model with significant pattern was found separately for boys and girls and age groups 0-9 and 10-14 years, however, a significant pattern was confirmed for older girls only. A seasonal pattern in older boys in Finland and girls in Sweden was characterized by two cycles with decreased incidence in June and November-December. The pattern among younger children (0-9 or 5-9 years) had one cycle with a decreased incidence in May-June. In Estonia, a significant pattern was found for the age group 0-14 years and combined sexes. No significant seasonal patterns were found in Latvia and Lithuania. CONCLUSIONS: The seasonal pattern with two cycles among older children and one cycle only among younger children may indicate different triggers of Type 1 diabetes mellitus for different age groups.

Adolescent↗
PubMed1999

Potentials and pitfalls in neonatal screening for type 1 diabetes.

Childhood-onset diabetes is increasing all over the western world. Only 20-30% of monozygotic twin pairs are concordant for the disease. So far, more than 20 different risk genes have been identified on different chromosomes. The dominating risk genes differ with different age at onset and also in different populations. Thus, the aetiology of the disease is complex, with interactions between different risk genes and environmental risk factors. Several pathogenetic models have been proposed, most of which include autoimmune destruction mechanisms. Screening for genetic markers for diseases with such complex aetiology encounters pitfalls due to the low predictive value of each single marker in the general population. To overcome such problems combinations of markers and decision-tree analysis are necessary. The identification of several immune markers for the disease has provided potential for screening for secondary prevention. When increasing the number of markers to increase the predictive value, sensitivity will be lost. A Swedish population-based study found the best combined positive predictive value in the general population to be 20%, whereas the sensitivity was only 34%. Type 1 diabetes still needs more precise risk markers in addition to a very safe prevention strategy before neonatal screening programmes may be instituted.

Diabetes Mellitus, Type 1↗
PubMed1998

Association between autoantibody markers and subtypes of DR4 and DR4-DQ in Swedish children with insulin-dependent diabetes reveals closer association of tyrosine pyrophosphatase autoimmunity with DR4 than DQ8.

HLA DQA1*0301-DQB1*0302 (DQ8) and DQA1*0501-DQB1*0201 (DQ2) are positively and DQA1*0102-DQB1*0602 (DQ6) negatively associated with IDDM. In DQA1*0301-DQB1*0302 (DQ8)-positive patients, susceptibility is also mediated by DRB1*0401. The aim of the study was to determine the association between HLA-DR4 and DQ and the presence of GAD65, ICA512, and insulin autoantibodies as well as ICA in 425 Swedish children with IDDM and 367 controls in the age group of 0-15 years. We found that ICA512 autoantibodies were associated primarily with DRB1*0401 and not with DQA1*0301-DQB1*0302 (DQ8). No such hierarchy could be demonstrated for insulin autoantibodies, which were associated with both DQA1*0301-DQB1*0302 (DQ8) and DRB1*0401. GAD65 autoantibodies, known to be closely associated with DQA1*0501-DQB1*0201 (DQ2)-DRB1*0301 haplotype, also showed no preferential association with DQA1*0301-DQB1*0302 (DQ8) versus DRB1*04. These results suggest that the immune response to different beta-cell autoantigens may be mediated via HLA class II molecules from different loci. Design of the antigen-specific immuno-intervention trials should take into account these HLA-DR and DQ subtype associations.

Adolescent↗
PubMed1998

The aetiology of type 1 diabetes: an epidemiological perspective.

Type 1 diabetes is increasing rapidly in many parts of the Western world, most evidently in Scandinavia. A low concordance rate of insulin-dependent diabetes mellitus among monozygotic twins clearly indicates that genetic risk factors may be necessary, but are not sufficient for the disease to occur. The strongest genetic risk markers are located in the HLA region of chromosome 6, but these DNA specificities differ in different populations. Risk genes are indicated in other chromosomes of the human genome, suggesting a complex interaction between genes and environment as the cause of the disease. The pathogenesis of the disease is proposed to be autoimmune in nature and environmental risk factors may either initiate autoimmunity or accelerate an already ongoing beta-cell destruction. Risk factors disclosed by epidemiological studies that may accelerate the pathogenetic process are: a cold environment, a high growth rate, infections and stressful life events. Risk factors that may initiate the autoimmune process include early exposure to cow's milk proteins, nitrosamines or early foetal events such as blood group incompatibility or foetal viral infections. In conclusion, population-based epidemiological studies have helped to confirm proposed aetiological models that have arisen from experimental research. These epidemiological studies have also introduced important new findings that may reveal the complex aetiology of the disease and advance understanding closer to the ultimate goal of primary prevention.

Animals↗
PubMed1998

Familial and perinatal risk factors for micro- and macroalbuminuria in young IDDM patients.

It has been suggested that hereditary risk for hypertension and cardiovascular disease (CVD) as well as intrauterine growth may be involved in the pathogenesis of diabetic nephropathy. In the present study, we investigated the influence of familial and perinatal risk factors on the occurrence of micro- and macroalbuminuria in young IDDM patients. A cohort of 1,150 young patients with > or =5 years' duration of IDDM was screened for microalbuminuria. Data on family history of hypertension, CVD, IDDM, and NIDDM; perinatal factors such as birth weight, gestational age, and duration of breastfeeding; and maternal education, smoking, hypertension, and proteinuria during pregnancy were collected. We identified 75 patients with an albumin excretion rate > or =15 microg/min in more than two overnight urinary samples and compared them in a nested case-control study with three normoalbuminuric control subjects per patient from the same cohort, matched for diabetes duration. Perinatal factors were analyzed in all patients born at term (+/- 2 weeks), 59 of the 75 patients and 155 of the 225 control subjects. In univariate analysis, hypertension in parents (odds ratio [OR] 4.21), CVD in parents and grandparents (OR 1.26), maternal smoking during pregnancy (OR 3.21), and a low level of maternal education (OR 2.33) were significantly associated with the development of micro- and macroalbuminuria. When adjusted for other familial and perinatal factors, current mean blood pressure, HbA1c, smoking, BMI, sex, age, and postpubertal diabetes duration, using logistic regression analyses, only parental hypertension in all patients and maternal smoking during pregnancy and low level of maternal education in full-term patients were independent risk factors. When patients with poor glycemic control were analyzed separately, familial CVD, poor metabolic control, parental hypertension, maternal smoking during pregnancy, and level of maternal education were independent risk factors, with the adjusted OR markedly increased, compared with the matched subgroup with better HbA1c. In conclusion, familial hypertension and CVD, maternal smoking during pregnancy, and low level of maternal education may independently increase the risk for incipient nephropathy in full-term offspring who later develop IDDM. Current poor glycemic control seemed to increase the effect of these risk factors.

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

Analysis of critical residues of HLA-DQ6 molecules in insulin-dependent diabetes mellitus.

Among DQ6 molecules, DQA1*0102-DQB1*0602 is negatively associated with insulin-dependent diabetes mellitus (IDDM), but DQA1*0102-DQB1*0604 shows a neutral to positive association in Swedish children with IDDM. The aim of this study was to identify critical DQB1 residues that may account for the differences in IDDM association observed for these two DQ6 molecules. HLA-DQ genotyping in 425 IDDM patients and 367 matched controls showed DQ6 (B1*0602) in 1% of patients and 25% of controls (odds ratio (OR) 0.02). DQ6 (B1*0604) alone was neutral (9% of patients and 10% of controls) but in combination with DQ8, was positively associated (5% of patients, 1% of controls, OR 9.49). In both these DQ6 molecules the alpha-chain is the same but the beta-chain differs at positions 9, 30, 57, 70, 86 and 87. DQB1*0602 has F9, Y30, D57, G70, A86 and F87, whereas DQB1*0604 has Y9, H30, V57, R70, G86 and Y87. Three-dimensional models of the two DQ6 molecules, based on crystal coordinates of the homologous DR1 molecule, suggest that residue 57 beta will likely play a critical role in peptide-binding selectivity, whereas residue 70 beta is probably is major contact site for the T-cell receptor. The effects of these specific polymorphic substitutions in DQ molecules on peptide binding and T-cell receptor recognition may be significant in IDDM susceptibility.

Adolescent↗
PubMed1997

Early neonatal events and the disease incidence in nonobese diabetic mice.

Epidemiologic studies have shown that perinatal events are associated with an increased risk for type 1 (insulin-dependent) diabetes in childhood. We used nonobese diabetic mice to examine whether neonatal separation from the mother with or without phototherapy would affect the incidence of diabetes in this genetically susceptible mouse model. The newborn pups were taken from their mothers for two 4-h periods during each of five successive days. One group of animals was just taken from their mothers and were left lying in daylight in the cage, whereas another group was exposed to identical light as used for treatment of neonatal jaundice in infants. Treatment resulted in a 30% death rate. For animals surviving more than 3 mo the incidence of diabetes was significantly higher in both treatment groups compared with control animals, allowed to stay with their mother. The odds ratio for treatment versus control, stratifying for sex, was 3.42 (95% confidence interval, 1.57-7.74). Histologic insulitis did not differ between treated and untreated animals when examined either at clinical diabetes onset or at 8 mo of age. Blood glucose values at 8 mo of age (in animals without clinical diabetes) did not differ between-treated and untreated animals. It is concluded that neonatal separation of the nonobese diabetic mice from their mothers will lead to a significantly increased risk for diabetes. This increase in risk seems to be associated with the induction of metabolic alterations leading to increased peripheral insulin need rather than with an increased rate of beta cell destruction.

Animals↗