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Biomedical subjects

O O Andersen

Publications and source records attributed to O O Andersen.

At least 19 recordsLinked to original sources

[Markers for risk of IDDM in children of Danish patients with IDDM. A population-based, historical prospective study].

To assess the offspring IDDM recurrence risk in a Danish population-based study and to investigate parental and offspring related biological variables that might influence this risk, we identified 2726 IDDM probands and their 2826 offspring from a background population of 1.725 million people (33% of the Danish population). Proband current age was 20-60 years and age at IDDM onset was 30 years or less. Offspring data were obtained by a questionnaire. The cumulative IDDM risk up to age 30 years was found significantly decreased in maternal offspring compared to paternal offspring (2.3 +/- 0.6% and 5.7 +/- 0.9%, RR = 2.40, 95% CI 1.30-4.47; Mantel Cox: p = 0.004) only if parents were diagnosed with IDDM before offspring birth. However, due to a low number of diabetic offspring of probands diagnosed with IDDM after offspring birth, this observation need to be confirmed in a larger population. Using the Cox proportional hazards model we found that among several biological variables tested separately on offspring of male and female probands, all diagnosed with IDDM before pregnancy, paternal age at IDDM onset was the only statistically significant predictor of IDDM risk in offspring. Our findings may be important for counselling families in which one parent has IDDM.

Adolescent↗

Predictors of IDDM recurrence risk in offspring of Danish IDDM patients. Danish IDDM Epidemiology and Genetics Group.

It has previously been observed that offspring of mothers with insulin-dependent diabetes mellitus (IDDM) have a lower risk of IDDM than offspring of IDDM affected fathers. To assess the offspring IDDM recurrence risk in a Danish population-based study and to investigate parental and offspring-related biological variables that might influence this risk, we identified 2726 IDDM probands and their 2826 offspring from a background population of 1.725 million people (33% of the Danish population). Current age of probands was 20-65 years and their age at IDDM onset was 30 years or less. Sixty-nine offspring (2.4%) were affected with IDDM. The sex difference in the parental-offspring IDDM transmission rate was confirmed. The cumulative IDDM risk up to age 30 years was found to be significantly decreased in maternal offspring compared to paternal offspring (2.3 +/- 0.6 and 5.7 +/- 0.9 %, RR = 2.40, 95% CI 1.30-4.47; p = 0.004) only if parents were diagnosed with IDDM before birth of the offspring. However, due to the low number of diabetic offspring of probands diagnosed with IDDM after offspring birth, this observation needs to be confirmed in a larger population. In a subpopulation of the 2380 offspring, whose parents were all diagnosed with IDDM before offspring birth, the recurrence risk was significantly increased in offspring of male probands diagnosed up to age 17 years compared to offspring of fathers diagnosed at older ages (8.5 +/- 1.8 and 3.6 +/- 1.0%; RR = 2.27, 95% CI 1.21-4.25; p = 0.006). No such relation was found in maternal offspring. Using the Cox proportional hazards model on this offspring subpopulation we found that paternal age at IDDM onset was the only statistically significant predictor of IDDM recurrence risk. Our findings may be important for counselling families in which one parent has IDDM.

Adult↗

Kinetics of insulin disappearance from plasma in cortisone-treated normal subjects.

The effect of glucocorticoid excess on insulin disappearance from plasma was examined in eight normal men during cortisone treatment (50 mg orally twice daily for 4 d) and in the absence of any medication (control) in random order. Constant infusion of insulin (1-5 mU/kg/min) was used to achieve different levels of steady state plasma insulin concentrations; normoglycaemia was preserved by a glucose clamp technique. The experimentally determined data were compared using a previously validated model of saturation kinetics. The amount of glucose required to maintain normoglycaemia during the insulin infusions was significantly less in the cortisone study than in the control study, while the parameter estimates for the kinetics of insulin disappearance from plasma were unaffected by cortisone. Thus, insulin action and insulin kinetics in the steady state are dissociated in normal subjects rendered insulin resistant by short-term cortisone treatment.

Adult↗

Kinetic models for insulin disappearance from plasma in type I diabetic patients.

We have tested whether our previous finding in normal subjects that the disappearance of insulin from plasma obeys saturation kinetics alone also applies to type I diabetic patients. In six long-term diabetic patients steady state plasma insulin concentrations resulting from constant insulin infusion at different rates were compared with the predictions of three models for the kinetics of insulin in plasma. The models allowed the existence of non-saturable (first order equation) or saturable (Michaëlis-Menten equation) mechanisms, or both. The minimal acceptable model included saturation kinetics alone in four subjects and first order kinetics alone in two subjects. The clearance of insulin in diabetic patients, calculated from the best fitting model, was 18.0 (median, range 10.0-23.7) ml X kg-1 X min.-1 versus 25.0 (18.6-47.1) ml X kg-1 X min.-1 in six normal subjects (2p = 0.008). Insulin thus disappears from plasma at a lower rate in diabetic patients than in normal subjects at physiological plasma concentrations.

Adult↗

Incidence of insulin-dependent diabetes mellitus (0--29 years at onset) in Denmark.

Incidence data from Denmark on the insulin-dependent diabetes mellitus in the age group 0--29 years have been collected in two different geographical areas (West and South Jutland plus Copenhagen and North Zealand). An incidence of 13.3 per 100,000 per year (range 12.5--13.6) was registered (N = 792). No difference was found between the two areas. The male incidence exceeded the female incidence by 25.4 per cent. The age distribution showed rising values until a peak in the early puberty with a decline until a rather constant level after puberty. From year to year a seasonal variation of onset was demonstrable with maximum in the winter and minimum in the summer for males only. Ascertainment was found to be between 87.7 and 98.6 per cent and the annual number of new insulin-dependent diabetics in Denmark in the age group 0--29 years can be calculated to 310-350.

Adolescent↗

Incidence, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus in Denmark.

The incidence, sex, seasonal and geographical patterns of juvenile-onset insulin-dependent diabetes mellitus (j.i.d.m.) were studied retrospectively on one third of the Danish population 1970-1974. The j.i.d.m. incidence remained fairly constant during the study period, the average being 13.2 per 100000 per year. The total number of boys exceeded the number of girls by 27%. A marked peak of incidence was found at 12-14 years, earlier for females than for males. A seasonal variation in onset (diagnosis) of j.i.d.m. was observed with the lowest number of new cases in May-July. The j.i.d.m. incidence seemed to show socioeconomic differences, being highest in those parts of the survey area with lower status.

Adolescent↗

Glucose tolerance and insulin secretion in hyperthyroidism.

To evaluate the glucose tolerance and insulin secretion in hyperthyroidism patients were examined in the toxic state and after they had been made euthyroid. Fasting values: In 42 untreated patients the glucose- and insulin concentrations in serum were significantly elevated. In 24 treated patients the glucose concentrations became normal, while the insulin concentrations remained elevated. Oral-glucose-tolerance test: In 20 untreated patients the glucose- and insulin responses were significantly increased. In 8 treated patients the glucose response became normal, while the insulin response remained unchanged. Intravenous-glucose-tolerance test: In 28 untreated patients the K-values were significantly decreased and the insulin response increased. In 23 treated patients the K-values rose significantly, but the insulin response remained unchanged. Intravenous-tolbutamide test: In 41 untreated patients the glucose concentration decreased significantly compared with the controls, and the insulin responses were significantly increased. In 23 treated patients the glucose concentrations decreased even more, while the insulin response remained unchanged. The results indicate enhanced sensitivity or an increase in the mass of beta-cells in hyperthyroidism. The glucose tolerance tests point to an increased peripheral insulin resistance. The normalized glucose tolerance and still enhanced insulin secretion during treatment support the assumption, that hyperthyroidism causes an increase in the beta-cell mass.

Administration, Oral↗

Morphology of experimental, organ-specific insulitis of the mouse pancreas.

The morphologic and metabolic effect of a single intracutaneous injection of homologous endocrine pancreas in Freund's complete adjuvant (CFA) was studied in 100 mice and compared with control groups which had been (1) immunized with murine insulin in CFA, (2) injected with CFA alone, or had (3) received no treatment. There were no differences between the control groups as regards the morphology of the pancreatic islets, and the glucose tolerance was normal. Mice immunized with islet homogenate exhibited morphological changes in the form of degranulation and cytoplasmic disintegration. These changes involved B-cells as well as A2-cells and were present from 7 to 18 days after the immunization. A significant reduction in glucose tolerance was observed 14 days after the immunization. Another characteristic finding in the islets from the immunized mice was the extra-vascular presence of mononuclear, agranular cells which on the basis of their morphological criteria appeared to represent lymphocytes.

Animals↗

Anti-insulin-antibodies and late diabetic complications.

Two hundred and seventy-four insulin-dependent juvenile diabetics were examined. One hundred and sixty-six patients were without late diabetic complications, while 108 patients had one or more complications. At the time of the investigation patients with and without complications were found to have the same insulin requirement. Retrospectively it was observed, that after treatment for 10 years the insulin requirement was significantly higher among patients who had developed complications after treatment for 19 years as compared to patients who after 19 years of treatment had not developed complications. One hundred and eighty-four patients, of which 110 were without and 74 with late diabetic omplications were examined for anti-insulin-antibodies. Patients with complications, especially those with early onset of proliferative retinopathy or nephropathy had a slightly although insignificantly elevated plasma insulin-binding capacity. The frequency of high titres was significantly greater among patients with complications as compared to the frequency in patients without complications. The observations support the assumption, that insulin-anti-insulin-antibody complexes may aggravate the vascular complications.

Adolescent↗

Clinical significance of anti-insulin-antibodies.

Treatment of diabetic patients with common available insulin preparations in most cases results in formation of immuno-globulins called anti-insulin-antibodies. During the last 10-15 years it has been established, that these immuno-globulins, especially IgE, may be responsible for allergical manifestations. Moreover it has been established, that immuno-globulins, especially IgM, may be responsible for insulin resistance in many cases. It is concluded, that anti-insulin-antibodies also are important for the insulin requirement in non-resistant diabetics. The investigations could not reveal any significance of anti-insulin-antibodies for the degree of regulation. The remission period has been defined, 45 per cent of patients examined fulfilled the criteria for remission. The investigations support the assumption, that anti-insulin-antibodies may shorten the remission period, probably due to neutralizing effect upon the endogenous insulin supply. Finally our findings are in accordance with the view, that insulin-anti-insulin-antibody complexes might deteriorate late diabetic vascular complications.

Adolescent↗