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G Dahlquist

Publications and source records attributed to G Dahlquist.

At least 19 recordsLinked to original sources
PubMed1992

[New discoveries on the etiology of type 1 diabetes--an example of molecular epidemiology].

During the past decade the incidence of type 1 diabetes has been on the increase in Sweden, as it has in many other Western countries. The paper consists in a review of new hypothesis as to the pathogenesis of disease, resulting from findings in intensive molecular, genetic, immunological and epidemiological studies. Reversal of the rising trend in the incidence of type 1 diabetes is dependent upon further detailed elucidation of the molecular biology of the genetic and immunological markers of the disease, and their predictive value in population based studies. The currently identified risk factors, which may be initiators or promoters of diabetes pathogenesis, also need to be further elucidated, for which purpose a molecular epidemiological strategy is recommended, as it has already been found to be a successful approach in studies of type 1 diabetes.

Autoimmunity↗
PubMed1992

Maternal-child blood group incompatibility and other perinatal events increase the risk for early-onset type 1 (insulin-dependent) diabetes mellitus.

The nationwide Swedish Childhood Diabetes Registry, which ascertains 99% of recent-onset Type 1 (insulin-dependent) diabetic children (0-14 years) in Sweden, was linked with the Swedish Medical Birth Registry. A matched case-control study was carried out analysing about 20 perinatal variables concerning mother and child. A total of 2757 infants who became diabetic during the period 1978-1988 were analysed. For each case infant three control children were randomly selected from among all infants born in the same year and at the same delivery unit as the case infant. The following statistically significant risk factors were identified for Type 1 diabetes with an onset before 15 years of age: maternal diabetes (OR = 3.90), maternal age above 35 (OR = 1.36), maternal non-smoking (OR = 1.54), pre-eclamptic toxaemia (OR = 1.19), caesarian section (OR = 1.32), and maternal-child blood group incompatibility (OR = 1.61). When the analysis was restricted to Type 1 diabetes with an onset before the age of 5 years, most odds ratios were increased - for blood group incompatibility OR = 3.86 (95% confidence interval 1.54-9.65). Icterus without blood group incompatibility was not a significant risk factor. When each risk factor was analysed after standardization for all other risk factors, the odds ratios remained significantly increased. Scrutiny of medical records for cases and control children with a diagnosis of blood group incompatibility verified the diagnosis in close to 90% of children. The more severe cases needing phototherapy and/or blood transfusion were found to have a greater risk than milder cases.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗
PubMed1992

A high linear growth is associated with an increased risk of childhood diabetes mellitus.

Insulin release and growth are intimately connected. The aim of the present study was to investigate height and weight in diabetic children from birth to onset of Type 1 (insulin-dependent) diabetes mellitus compared to that in referent children. Data on height and weight were collected from mailed questionnaires and from growth records obtained from the child health clinics and schools in 337 recent-onset diabetic children, 0-14 years old, and from 517 age-, sex-, and geographically matched referent children. A total of 9002 paired height and weight observations were collected. The anthropometric development of the children was expressed as standard deviation scores using the National Center for Health Statistics/Centers for Disease Control (NCHS/CDC) growth reference material. On the average, the diabetic children were consistently taller than the referent children, a finding more pronounced among the boys. The diabetic boys were significantly taller from 7 to 1 years before the clinical onset of the disease, regardless of age at onset. A similar tendency was found for the girls. When mean height from 5 to 1 years before onset was used as a possible risk factor for diabetes, a linearly increasing trend in the odds ratio was found for diabetes in boys (odds ratio = 1.0; 1.57; 2.46 for height standard deviation score values less than 0; 0-1 and greater than 1, respectively; p = 0.002 for trend). A similar, but statistically not significant, tendency was found for girls (odds ratio = 1.0; 1.44; 1.43). As regards height increment from birth similar trends in odds ratios were found.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

An increased level of antibodies to beta-lactoglobulin is a risk determinant for early-onset type 1 (insulin-dependent) diabetes mellitus independent of islet cell antibodies and early introduction of cow's milk.

Using a case-control design we have studied whether antibodies to cow's milk proteins are risk determinants for childhood-onset Type 1 (insulin-dependent) diabetes mellitus independent of early exposure to cow's milk formula and islet cell antibodies. Sera from 116 recent-onset diabetic children and 112 age- and sex-matched control children were analysed for cow's milk protein IgA, IgG and IgM antibodies, beta-lactoglobulin IgA and IgM antibodies and islet cell antibodies. The titres were compared to questionnaire data on duration of breast-feeding and introduction of formula feeding. Most antibody levels tended to be increased among diabetic compared to control children. This was statistically significant for cow's milk protein IgA antibodies (p less than 0.001) and beta-lactoglobulin IgA antibodies (p less than 0.01) as well as for islet cell antibody-positivity which was found among 92% of the diabetic and 3% of control children. The differences in cow's milk protein antibodies as well as beta-lactoglobulin antibodies were more pronounced among children with an early onset of Type 1 diabetes. Breast-feeding duration was significantly inversely related to the log of beta-lactoglobulin IgG (r = -0.16, p = 0.04) and the log of cow's milk protein IgA antibodies (r = -0.17, p less than 0.001). A positive correlation was found between formula feeding and the logarithm of beta-lactoglobulin IgG antibodies (r = 0.22, p = 0.01) and the log of cow's milk protein IgA antibodies (r = 0.16, p = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Predictive value of islet cell and insulin autoantibodies for type 1 (insulin-dependent) diabetes mellitus in a population-based study of newly-diagnosed diabetic and matched control children.

Most studies evaluating immune markers for prediction of Type 1 (insulin-dependent) diabetes mellitus have focused on first degree relatives, although only 10% of newly-diagnosed patients have an affected first degree relative. The Swedish Childhood Diabetes Register identifies 99% of all diabetic children at diagnosis. In this population-based study, islet cell antibodies and insulin autoantibodies in 0-14-year-old Swedish consecutively-diagnosed patients and control subjects were analysed to define their sensitivity and specificity. Over 16 months (1986-1987), 515 Swedish children developed diabetes. Plasma samples were obtained from 494 (96%) patients, and 420 matched control children. Among patients, the frequency of islet cell antibodies was 84% (415 of 494), insulin autoantibodies 43% (145 of 334); 40% (135 of 334) were positive for both and 88% (294 of 334) were positive for one or both. Among control children, 3% (14 of 420) had islet cell antibodies, 1% (4 of 390) insulin autoantibodies, and 4% (16 of 390) had either autoantibody marker. The predictive value of finding a patient with the disease was only 7% since 4% of the control children were antibody-positive and the cumulative incidence rate up to 15 years of age is 0.38%. None of the autoantibody-positive (n = 21) or negative control children developed diabetes during 3 to 5 years of follow-up. Longitudinal investigations of islet cell or insulin-autoantibody-positive healthy children are necessary to accurately determine the conversion rate from marker positivity to disease onset.

Adolescent↗
PubMed1992

Increased glomerular filtration rate as a predictor of diabetic nephropathy--an 8-year prospective study.

The objective was to study the natural history and the predictive value of glomerular filtration rate, albumin excretion rate, blood pressure, and hemoglobin A1c for diabetic nephropathy. A cohort of 75 type-1 diabetic adolescents with a diabetes duration of 8 years was studied. Thirty-one females, 33 males, mean age 16.9 +/- 0.3 (SEM) participated in the follow-up study. Glomerular filtration rate, albumin excretion rate, blood pressure, and hemoglobin A1c were measured every second year during 8 years to determine the predictive value of glomerular filtration rate for future nephropathy. Initial differences and patterns of changes in glomerular filtration rate, albumin excretion rate, and hemoglobin A1c were examined in patients who did (group 1) and did not (group 2) develop incipient or overt nephropathy. Five of 64 patients developed overt nephropathy. They had an initial glomerular filtration rate of greater than 125 ml/min/1.73 m2. Fifteen of 53 initially normoalbuminuric patients developed incipient and three of 53 overt nephropathy. Age, age at onset, diabetes duration, initial albumin excretion rate, initial blood pressure, and hemoglobin A1c were similar in groups 1 and 2. Glomerular filtration rate was initially higher in group 1 than in group 2 (P = 0.01). The positive predictive value for combined incipient and overt nephropathy of an initial glomerular filtration rate greater than 125 ml/min was 53%. The negative predictive value of glomerular filtration rate less than 125 ml/min was 95%. In initially normoalbuminuric patients multiple regression revealed initial glomerular filtration rate as the only significant independent predictor for nephropathy when also corrected for hemoglobin A1c (P = 0.04).(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1992

Risk of developing insulin-dependent diabetes mellitus (IDDM) before 35 years of age: indications of climatological determinants for age at onset.

This study analyses data from two nationwide prospective diabetes registries now covering about 3400 cases from 19 million person-years of follow-up in the age group 0-34 years. The risk of developing insulin-dependent diabetes mellitus (IDDM) per 100,000 individuals before 15 years was 386 (95% confidence intervals (CI): 362-410) for boys and 391 (95% CI: 367-415) for girls and by 35 years 701 (95% CI: 671-731) for men and 562 (95% CI: 534-690) for women. The incidence rate showed a maximum for both boys and girls in early puberty. After pubertal years a sharp increase in the male to female incidence ratio of IDDM was notable. At 10-14 years it was 0.94, at 15-19 years 1.59 and at 20-24 years 2.08. A Cox regression model was used to analyse the effects on age at onset of sex, population density and climatological factors as measured by north-south area of residence and season at onset. The effect of sex was confirmed (P less than 0.001). A significant effect (P = 0.004) of season was shown when the four seasons were classified according to a four stage scale related to mean temperature. When dividing Sweden into 11 regions according to north-south gradient (Latitude 55 degrees, 56 degrees, 57 degrees, ..., 65 degrees) a significant effect (P = 0.038) was also found. However, no effects of population density or living near the coast versus in the interior were found. It is concluded that a large proportion of the young are at risk of developing this chronic disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

The Swedish childhood diabetes study: indications of severe psychological stress as a risk factor for type 1 (insulin-dependent) diabetes mellitus in childhood.

This study is part of a nationwide case-referent study. All recent-onset Type 1 (insulin-dependent) diabetic children aged 0-14 years in Sweden were invited to participate. Referent subjects matched for age-, sex- and geographical distribution were selected. In all, 338 patients and 528 referent subjects took part. Life events during the last year prior to clinical onset of Type 1 diabetes were recorded on a questionnaire. The total frequency of life events did not differ between diabetic and referent children. However, qualitatively the life events reported by diabetic children revealed a tendency to increased severity. Events related specifically to actual or threatened losses within the family--events that may affect children differently in different age groups--were reported with a significantly higher frequency by diabetic patients than by referent subjects, aged 5-9 years. The relative risk that such events in fact comprise a risk factor for Type 1 diabetes was 1.82 (95% confidence limits 1.09, 3.03). The relative risk was significantly increased even when standardized for possible confounding factors such as age, sex and indices of social status of the family. We conclude that stressful life events, related to actual or threatened losses within the family, occurring in the vulnerable age group of 5-9 years, are associated with the onset of childhood Type 1 diabetes. Such stressful events may in fact be a risk factor for the disease.

Adolescent↗
PubMed1991

The Swedish Childhood Diabetes Study--a multivariate analysis of risk determinants for diabetes in different age groups.

In a nationwide incident case-referent study stepwise univariate analysis has revealed several risk determinants for childhood diabetes mellitus. In a multivariate analysis we have determined the set of risk determinants that would independently predict childhood Type 1 (insulin-dependent) diabetes. Possible interactions between the risk determinants and differences in risk profiles with different ages at onset were also examined. Reported familial insulin-treated and non-insulin-treated diabetes were significant risk factors in all age groups, as was also a low frequency of milk intake. The frequency of infections and a high intake of foods rich in nitrosamine tended to interact (OR 11.8, p = 0.053) indicating a synergistic effect. A Cox regression analysis revealed that stressful life events during the last year was the only variable that tended to affect the age at onset (p = 0.055). This indicated that psychological stress may rather precipitate than induce Type 1 diabetes. A short breast-feeding duration (OR = 3.81), and an increased body height (OR = 3.82) contributed significantly to the predictive model in only the youngest age group (0-4 years). An increased frequency of infections in the year preceding onset (OR = 2.15) and no vaccination against measles (OR = 3.33) contributed significantly to the model only in the age group 5-9 years. Various nutrients had different impacts on the risk of developing Type 1 diabetes in different age groups. It is concluded that in the genetically susceptible child, risk factors which are associated with eating habits, frequency of infections, vaccination status, growth pattern and severe psychological stress affect the risk of developing diabetes independently of each other.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1991

The Swedish childhood diabetes study. Vaccinations and infections as risk determinants for diabetes in childhood.

In a nationwide incident case referent study we have evaluated vaccinations, early and recent infections and the use of medicines as possible risk determinants for Type 1 (insulin-dependent) diabetes mellitus in childhood. A total of 339 recently onset diabetic and 528 referent children, age 0-14 years, were included. Information about infections was collected from a mailed questionnaire and about vaccinations from childhood health care centres and schools. When vaccinations were considered as possible risk factors for diabetes, a significant decrease in relative risk estimated as odds ratio (OR) was noted for measles vaccination (OR = 0.69; 95% confidence limits 0.48-0.98). For vaccination against tuberculosis, smallpox, tetanus, whooping cough, rubella and mumps no significant effect on OR for diabetes was found. The odds ratios for Type 1 diabetes for children exposed to 0.1-2 or over 2 infections during the last year before diagnosis of diabetes revealed a linear increase (OR = 1.0, 1.96 and 2.55 for 0, 1-2 and over 2 infections, respectively). The trend was still significant when standardized for possible confounders such as age and sex of the children, maternal age and education and intake of antibiotics and analgetics. In conclusion, a protective effect of measles vaccination for Type 1 diabetes in childhood is indicated as well as a possible causal relationship between the onset of the disease and the total load of recent infections.

Adolescent↗
PubMed1991

The Swedish Childhood Diabetes Study: a seven-fold decrease in short-term mortality?

Since 1 July 1977 all Swedish children aged 0-14 years with newly diagnosed Type 1 diabetes have been recorded on a central register. Out of 3228 patients registered up to 31 December 1985, 10 children (seven boys) had died during this time period. The overall mortality was 0.75 per 1000 patient-years. When compared with the general population the standardized mortality ratio (SMR) for both sexes was 2.09 (95% confidence limits 1.14-3.83). When analysed separately for sex, the higher mortality remained significant for males only (SMR = 2.61, 1.28-5.32). Five deaths were most probably due to diabetes and the remaining five were due to accidents, other diseases and, in one case, not identifiable with certainty. In comparison with previous studies there was a very low mortality in young-onset diabetic patients. However, short-term mortality is still significantly raised even in a country with a good economic and educational patient status and easy access to free hospital care.

Accidents↗
PubMed1991

Urinary C-peptide excretion in obese and anorectic children.

To assess the total insulin secretion in children in different nutritional states we have analysed the 24 h urinary C-peptide excretion in 32 obese children (16 boys and 16 girls) 8-15 years of age as well as in 7 girls with anorexia nervosa 11-16 years of age. Obese children had a median urinary C-peptide excretion rate of 0.27 nmol/kg/24 h, which was not different from that of a group of normal-weight children. In the group of anorectic girls, on the other hand, the median value 0.47 nmol/kg/24 h was significantly (p less than 0.05) higher than for normal-weight girls of the same age (median = 0.26 nmol/kg/24 h). These results indicate that in obese children insulin secretion, measured as the 24 h urinary C-peptide excretion per kg body weight, is the same as in normal-weight children. Total insulin secretion is consequently increased. In anorexia nervosa, on the other hand, the higher C-peptide excretion per kg body weight compared with normal-weight children, indicates that insulin secretion is increased in relation to body weight.

Adolescent↗
PubMed1990

The Swedish childhood diabetes study. An analysis of the temporal variation in diabetes incidence 1978-1987.

The Swedish Childhood Diabetes Register combines continuous prospective reporting on incident cases and regular retrospective review of hospital records in all paediatric departments in the country and has, from 1978 to 1987, compiled 3838 cases. A validity test using an independent source has revealed a degree of ascertainment of 100%. When fitting a linear regression model to the natural logarithm of the yearly incidence rates, a significant increase over time was found for girls and for both sexes combined. To analyse the time trend with respect to age, sex, calendar year and birth cohort and their interactions, Poisson regression modelling was used. There was a significant age effect and interaction between age and sex. When these age and sex effects were taken into account a significant increase over time was found. Calendar period had a significant effect when adjusted for cohort effects whereas cohort did not add significantly to the explanation of the variance. There was no significant interaction between sex and calendar period indicating similar time variations for both sexes. The temporal variability was also apparently similar among different age groups. The observed increase of childhood insulin-dependent diabetes mellitus (IDDM) affecting both sexes and all age groups, strongly supports the importance of environmental factors in the aetiology of IDDM.

Adolescent↗
PubMed1990

Insulin sensitivity and glucose-induced insulin response changes during adolescence.

Recently we reported that insulin resistance and glucose induced insulin release are inversely correlated to age in young healthy siblings of diabetic patients. To confirm this pattern of change with age, the subjects were reexamined after two years. The study was limited to the age groups with the lowest insulin sensitivity, i.e. 14.0-15.9 years for females and 16.0-17.9 years for males. All five girls and four of five boys showed an increased insulin sensitivity as measured by the somatostatin-insulin-glucose infusion test (p = 0.02). All subjects showed a decrease in fasting levels of insulin-like growth factor 1 (IGF-1) (p less than 0.01) during the observation period. All except one showed an increase in the levels of dehydroepiandrosterone sulphate (DHEA-S) (p less than 0.01). These data confirm that insulin sensitivity increases in the late teenage period. The parallelism to the changes of IGF-1 indicate that the pubertal changes in insulin sensitivity may partly be caused by growth hormone. Our data contradict the hypothesis that the low insulin sensitivity of puberty is due to the increased levels of DHEA-S.

Adolescent↗
PubMed1989

The Swedish childhood diabetes study--results from a nine year case register and a one year case-referent study indicating that type 1 (insulin-dependent) diabetes mellitus is associated with both type 2 (non-insulin-dependent) diabetes mellitus and autoimmune disorders.

From July 1, 1977 to July 1, 1986, 3,503 incident cases of Type 1 (insulin-dependent) diabetes mellitus were registered in the Swedish childhood diabetes study. Using data from this register and from a case-referent study, including all incident Type 1 diabetic children in Sweden during one year and, for each patient, two referent children matched according to age, sex and county, we have studied the associations between Type 1 diabetes and familial Type 1 and Type 2 (non-insulin-dependent) diabetes, thyroid, adrenal, allergic, rheumatic, heart and bowel disease. The mean annual incidence per 100,000 during the nine year period was 25.1 for boys and 23.5 for girls. In 8.5% of the patients, one parent had Type 1 diabetes, 73% of whom were fathers. Fifty-six of the patients (1.7%) had a parent with Type 2 diabetes. The prevalence of parental Type 1 diabetes tended to be higher in patients with younger age at onset; whereas, the opposite was found for patients with parental Type 2 diabetes. In the case-referent study, the age-adjusted odds ratio for Type 1 diabetes when a first and/or second degree relative had Type 1 diabetes was 5.5 (95% confidence limits 4.0-7.7), and in accordance with the findings of the case register, the odds ratio tended to be highest in patients with the youngest age at onset. Season at onset of the patients was not associated with parental Type 1 diabetes. The odds ratio for Type 1 diabetes was significantly increased 3.3 (95% confidence limits: 2.3-4.6) when Type 2 diabetes was reported in relatives (three generations).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

The Swedish childhood diabetes study--social and perinatal determinants for diabetes in childhood.

Using the Swedish childhood diabetes register, a nationwide, case-referent study was performed from September 1, 1985 to August 31, 1986. Based on the information from a mailed questionnaire sent to all incident diabetic children and for each diabetic child - two referent children matched according to age, sex, and county, we have analysed perinatal events and aspects of the social environment as possible risk factors for Type 1 (insulin-dependent) diabetes in childhood. A significantly larger proportion of the mothers of the diabetic children were older than 40 years compared to those of the referent children (33% and 24%, p = 0.01 respectively). A smaller percentage of mothers of the diabetic children had a high educational level compared to mothers of referent children (10% and 15%, p = 0.03 respectively) and 39% of the fathers of the diabetic children were manual workers compared to 31% of the fathers of referent children (p = 0.03). Perinatal events did not differ between diabetic and referent children. In children 0-6 years, the duration of breast-feeding was significantly shorter in diabetic children than among referent children (median duration for diabetic children 5 months compared to 6 months for referent children p = 0.03). When considering the presence of Type 1 diabetes among relatives, maternal age over 40 years, low educational level of the mother, and the father being a manual worker as risk factors, the presence of 1 to 4 of any of these risk factors increased the relative risk for Type 1 diabetes cumulatively from 1.2-7.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Child↗
PubMed1989

The Swedish childhood diabetes study III: IgM against coxsackie B viruses in newly diagnosed type 1 (insulin-dependent) diabetic children--no evidence of increased antibody frequency.

Sera from essentially all Swedish children aged 0-14 years with Type 1 (insulin-dependent) diabetes mellitus with onset during an autumn period (October-December 1985) and a late spring period (May-June 1986) were selected. In all, 98 patients were analysed for IgM antibodies against coxsackie B virus serotypes 1 through 5 by a mu-antibody capture radio immunoassay technique. Sera from 94 referent children matched for age, sex and residential area, collected during the same period, were also analysed. During the autumn period, 10 out of 67 (15%) diabetic children were IgM positive while 14 out of 75 (19%) of the healthy referent children demonstrated positivity. During the late spring period only one out of 31 (3%) children with diabetes and two out of 19 (10%) referent children were IgM positive. In the diabetic patients, five were coxsackie B2 positive while coxsackie B1, 3, 4 and 5 were represented by one to three patients each. Eight referent children were coxsackie B4 positive, six were B3 positive and two B2 positive, while no referent children were positive against coxsackie B1 and 5. During these two periods in late 1985 and early 1986 these data demonstrate no evidence of increased antibody frequency against coxsackie B virus 1 through 5 at the onset of childhood diabetes in Sweden.

Adolescent↗