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Biomedical subjects

O Søvik

Publications and source records attributed to O Søvik.

At least 19 recordsLinked to original sources
PubMed2005

Preserved insulin response to tolbutamide in hepatocyte nuclear factor-1alpha mutation carriers.

AIMS: Diabetic subjects with mutations in the gene encoding hepatocyte nuclear factor (HNF)-1alpha (MODY3) are prone to develop hypoglycaemia at low doses of glibenclamide, interpreted as sulphonylurea hypersensitivity. The present study was undertaken to compare the plasma insulin responses to glucose and tolbutamide in HNF-1alpha mutation carriers with those of healthy control subjects. METHODS: Seven mutation carriers; three normoglycaemic, two with impaired glucose tolerance, and two with newly detected diabetes, underwent an oral glucose tolerance test and a tolbutamide-modified intravenous glucose tolerance test with measurements of plasma insulin. Twenty-two healthy subjects served as controls. RESULTS: The plasma insulin response to intravenous glucose was reduced in the HNF-1alpha mutation carriers compared to the control subjects, with an area under the curve (median (interquartile range)) of 812 min pmol/l (421, 1647) and 1933 min pmol/l (1521, 2908), respectively (P = 0.03). In striking contrast, the plasma insulin response to tolbutamide was preserved, with an area under the curve of 2109 min pmol/l (1126, 3172) and 2250 min pmol/l (1614, 3276) in the mutation carriers and control subjects, respectively. CONCLUSIONS: HNF-1alpha mutation carriers are characterized by preserved tolbutamide-induced insulin secretion. Compared to healthy subjects, our MODY3 individuals did not show any increased serum insulin response to tolbutamide, suggesting that HNF-1alpha mutation carriers are not characterized by sulphonylurea hypersensitivity.

Adult↗
PubMed2005

Diagnostic screening of NEUROD1 (MODY6) in subjects with MODY or gestational diabetes mellitus.

AIMS: Diagnostic screening of NEUROD1 in patients with maturity-onset diabetes of the young (MODY) without mutations in the known MODY-genes (MODYX) and in subjects diagnosed with gestational diabetes mellitus. METHODS: Direct sequencing of NEUROD1 was performed in (i) 73 probands with clinical MODY without mutations in hepatocyte nuclear factor (HNF)-4alpha (MODY1), glucokinase (MODY2) and hepatocyte nuclear factor (HNF)-1alpha (MODY3), and (ii) 51 subjects diagnosed with gestational diabetes. Control material consisted of 105 anonymous blood donors. RESULTS: Mean age at diagnosis of diabetes was 22 and 30 years in the MODYX patients and gestational diabetes mellitus subjects, respectively. Mean fasting blood glucose (9.6 +/- 4.3 vs. 5.7 +/- 1.0 mml/l) as well as glycosylated haemoglobin (8.2 +/- 2.4 vs. 6.0 +/- 0.6%) were higher in the MODYX patients than subjects with gestational diabetes. NEUROD1 mutations were not detected in our two study groups. Three previously reported polymorphisms were found: Ala45Thr, Pro197His and IVS1 -32 nt C>T. The amino acid substitution serine to cysteine in codon 29 (designated Ser29Cys) was detected in one out of 105 control subjects. As the control material consisted of anonymous blood donors, we were prevented from investigation of possible co-segregation between the sequence variant Ser29Cys and diabetes mellitus. CONCLUSIONS: As we found no NEUROD1 mutations, diagnostic screening for this gene is not warranted in Norwegian MODYX patients. Our study also suggests that NEUROD1 is not a candidate gene in gestational diabetes mellitus (GDM). The sequence variant Ser29Cys was identified in one anonymous DNA sample, but we were prevented from studying possible co-segregation with diabetes mellitus.

Adult↗
PubMed2005

Evaluation of a programme of group visits and computer-assisted consultations in the treatment of adolescents with Type 1 diabetes.

AIM: To examine the effects of group visits and computer-assisted consultations on quality of life and glycaemic control in adolescents with Type 1 diabetes. METHODS: A total of 116 adolescents, aged 11-17 years, and their parents were randomly assigned to an intervention (n = 62) or a control group (n = 54). The intervention group was invited to a 15-month programme comprising group visits and computer-assisted consultations. The control group was offered traditional out-patient consultations. Outcomes included changes in HbA(1c) and the adolescents' assessment of generic and disease-specific health-related quality of life measured by the Child Health Questionnaire (CHQ-CF87) and the Diabetes Quality of Life Questionnaire (DQOL), respectively. RESULTS: One hundred and one adolescents (55/46) agreed to participate, mean age 14.2 years (sd 1.5), mean diabetes duration 6.5 years (sd 3.6, range 1-16 years), mean HbA(1c) 9.3% (sd 1.4, range 6.1-12.8%). Eighty-three (72%) completed the questionnaires at follow-up (intervention/control 45/38). There were significant age by randomization group interactions for diabetes-related impact (P = 0.018), diabetes-related worries (P = 0.004), mental health (P = 0.046) and general behaviour (P = 0.029), implying that the intervention was effective in older adolescents (above 13-14 years). No significant effects on mean HbA(1c) were identified. CONCLUSIONS: Group visits and computer-assisted consultations had beneficial effects on health-related quality of life in older adolescents, the role of this intervention being questionable in younger adolescents.

Adolescent↗
PubMed2003

Measuring self-reported, health-related, quality of life in adolescents with type 1 diabetes using both generic and disease-specific instruments.

AIMS: To describe perceived functional health and well-being and diabetes-related impact, worry and satisfaction with life in relation to demographic and clinical variables in a population of adolescents with type 1 diabetes. To compare perceived functional health and well-being between adolescents with diabetes and a group of healthy controls and to analyse the relationship between generic functional health and well-being and diabetes-related impact, worry and satisfaction with life. METHODS: A total of 130 adolescents were invited to complete the Child Health Questionnaire (CHQ-CF87) and the Diabetes Quality of Life (DQOL) questionnaire modified for youths. A total of 115 (88.5%) subjects participated in the study; mean age 14.5 y (SD 1.86), mean duration of diabetes 6.99 y (SD 3.77, range 1-16 y), mean HbA1c 9.3% (SD 1.62, range 6.2-14.0%). Forty-eight percent of the subjects were girls. RESULTS: When compared with healthy adolescents, subjects with diabetes reported a significantly lower degree of general health. The CHQ-CF87 scales showed that higher age in adolescents with diabetes was associated with lower scores for mental health (p < 0.001), self-esteem (p < 0.001), behaviour (p = 0.004) and general health (p < 0.001). Findings from the DQOL questionnaire showed that older adolescents were more worried (p < 0.001), perceived a greater impact of diabetes on daily life (p = 0.008) and lower diabetes-related life satisfaction (p < 0.001). The scores for girls were lower than those for boys in assessment of mental health (p < 0.001), self-esteem (p = 0.004) and family cohesion (p = 0.002). Girls also reported a greater impact of diabetes (p = 0.028), more worries (p = 0.001) and less satisfaction with life (p = 0.006) than boys. Neither HbA1c, nor other clinical variables could sufficiently explain the variations in DQOL or CHQ-CF87. CONCLUSIONS: Health-related quality of life varied significantly by age and gender, but less so by HbA1c and other clinical variables. Adolescents with diabetes reported a significantly lower degree of general health than that reported by healthy controls. The CHQ-CF87 is a valuable supplement to DQOL, allowing for comparisons with the general population.

Adolescent↗
PubMed2002

The genetic abnormality in the beta cell determines the response to an oral glucose load.

AIMS/HYPOTHESIS: We assessed how the role of genes genetic causation in causing maturity-onset diabetes of the young (MODY) alters the response to an oral glucose tolerance test (OGTT). METHODS: We studied OGTT in 362 MODY subjects, from seven European centres; 245 had glucokinase gene mutations and 117 had Hepatocyte Nuclear Factor -1 alpha ( HNF-1alpha) gene mutations. RESULTS: BMI and age were similar in the genetically defined groups. Fasting plasma glucose (FPG) was less than 5.5 mmol/l in 2 % glucokinase subjects and 46 % HNF-1 alpha subjects ( p < 0.0001). Glucokinase subjects had a higher FPG than HNF-1 alpha subjects ([means +/- SD] 6.8 +/- 0.8 vs 6.0 +/- 1.9 mmol/l, p < 0.0001), a lower 2-h value (8.9 +/- 2.3 vs 11.2 +/- 5.2 mmol/l, p < 0.0001) and a lower OGTT increment (2-h - fasting) (2.1 +/- 2.3 vs 5.2 +/- 3.9 mmol/l, p < 0.0001). The relative proportions classified as diabetic depended on whether fasting (38 % vs 22 %, glucokinase vs HNF-1 alpha) or 2-h values (19 % vs 44 %) were used. Fasting and 2-h glucose values were not correlated in the glucokinase subjects ( r = -0.047, p = 0.65) but were strongly correlated in HNF-1 alpha subjects ( r = 0.8, p < 0.001). Insulin concentrations were higher in the glucokinase subjects throughout the OGTT. CONCLUSION/INTERPRETATION: The genetic cause of the beta-cell defect results in clear differences in both the fasting glucose and the response to an oral glucose load and this can help diagnostic genetic testing in MODY. OGTT results reflect not only the degree of hyperglycaemia but also the underlying cause.

Adult↗
PubMed2001

[Surgical treatment of vaginal agenesia].

BACKGROUND: Vaginal agenesia appears among 1 in 5,000-10,000 newborn girls, i.e. 3-6 patients per year in Norway. MATERIAL AND METHODS: From 1975 to 1998, 14 women (mean age 20 years) were operated for vaginal agenesia by McIndoe's method at Haukeland University Hospital. Twelve patients were examined 13 years later by questionnaire, gynaecological examination, ultrasound examination of the urinary tract, and blood and urinary test concerning kidney function and diabetes mellitus. RESULTS: Five patients had been re-operated within nine months because of contracture. In all patients (except one), the constructed vagina had good elasticity, width and depth. The donor area at the medial thigh was unaesthetic in four patients. No abnormalities were found in the urinary tract by ultrasound. One patients had a familial syndrome with Müllerian aplasia, progressive renal disease and mild diabetes mellitus. All patients found the operation important, despite memories of a painful postoperative period. INTERPRETATION: This study shows functional and psychological satisfactory results of construction of vagina in women with vaginal agenesia.

Adolescent↗
PubMed2001

Maternal and paternal age at delivery, birth order, and risk of childhood onset type 1 diabetes: population based cohort study.

OBJECTIVE: To estimate the associations of maternal and paternal age at delivery and of birth order with the risk of childhood onset type 1 diabetes. DESIGN: Cohort study by record linkage of the medical birth registry and the national childhood diabetes registry in Norway. SETTING: Norway. SUBJECTS: All live births in Norway between 1974 and 1998 (1.4 million people) were followed for a maximum of 15 years, contributing 8.2 million person years of observation during 1989-98. 1824 cases of type 1 diabetes diagnosed between 1989 and 1998 were identified. MAIN OUTCOME MEASURES: Incidence of type 1 diabetes. RESULTS: There was no association between maternal age at delivery and type 1 diabetes among firstborn children, but among fourth born children there was a 43.2% increase in incidence of diabetes for each five year increase in maternal age (95% confidence interval 6.4% to 92.6%). Each increase in birth order was associated with a 17.9% reduction in incidence (3.2% to 30.4%) when maternal age was 20-24 years, but the association was weaker when maternal age was 30 years or more. Paternal age was not associated with type 1 diabetes after maternal age was adjusted for. CONCLUSIONS: Intrauterine factors and early life environment may influence the risk of type 1 diabetes. The relation of maternal age and birth order to risk of type 1 diabetes is complex.

Adult↗
PubMed2001

Birth weight and childhood onset type 1 diabetes: population based cohort study.

OBJECTIVE: To assess the associations between birth weight or gestational age and risk of type 1 diabetes. DESIGN: Population based cohort study by record linkage of the medical birth registry and the National Childhood Diabetes Registry. SETTING: Two national registries in Norway. PARTICIPANTS: All live births in Norway between 1974 and 1998 (1 382 602 individuals) contributed a maximum of 15 years of observation, a total of 8 184 994 person years of observation in the period 1989 to 1998. 1824 children with type 1 diabetes were diagnosed between 1989 and 1998. MAIN OUTCOME MEASURES: Estimates of rate ratios with 95% confidence intervals for type 1 diabetes from Poisson regression analyses. RESULTS: The incidence rate of type 1 diabetes increased almost linearly with birth weight. The rate ratio for children with birth weights 4500 g or more compared with those with birth weights less than 2000 g was 2.21 (95% confidence interval 1.24 to 3.94), test for trend P=0.0001. There was no significant association between gestational age and type 1 diabetes. The results persisted after adjustment for maternal diabetes and other potential confounders. CONCLUSION: There is a relatively weak but significant association between birth weight and increased risk of type 1 diabetes consistent over a wide range of birth weights.

Adolescent↗
PubMed2001

[Generalized edema following insulin treatment of newly diagnosed diabetes mellitus].

BACKGROUND: Generalised oedema after introducing insulin therapy is an infrequent complication, usually appearing when large doses are used in underweight patients. The pathophysiology is unclear. MATERIALS AND METHODS: Two patients from two different hospitals are presented by case histories. A limited literature search was performed. RESULTS: Patient 1. A 13-year-old girl was admitted with polyuria and polydipsia and a weight loss of 15 kg over six months. She had ankle oedema, dry scaling skin, weight 31.6 kg (2 kg below 2.5th centile), marked hyperglycaemia (60 mmol/l), and ketonuria without acidosis. After one day with insulin infusion she was treated with subcutaneous injections, reaching after a few days a dose of 2 U/kg/day. She gradually developed generalised oedema and gained 20 kg over two weeks. From day 8 after admission she was treated with furosemide and from day 16 also with ephedrine. S-albumin reached a nadir of 25 g/l. The oedema gradually disappeared. The patient was discharged after one month, weighing 42 kg, and with a daily insulin dose of 88 U. Patient 2. A 14-year-old girl presented with decreased vision over a period of six months. She felt otherwise healthy and had no weight loss. Bilateral cataract and hyperglycaemia (20.7 mmol/l) were detected. There were normal serum electrolytes and no acidosis. After administration of insulin (increased up to 1.5 U/kg/day) she gradually developed generalised oedema, gaining 8.5 kg over nine days. S-albumin fell from 36 g/l to 28 g/l. She was treated with furosemide and the oedema gradually disappeared in the course of one month. None of the patients had proteinuria, liver failure or hyperaldosteronism, but both experienced transient and unexplained muscle pain and neuralgic pain in the legs. INTERPRETATIONS: One of the cases with newly diagnosed diabetes and generalised oedema presented here, supports suggestions in the literature of an association between marked weight loss and large insulin doses. However, as shown by the other case presented, this association is not obligate.

Adolescent↗
PubMed2001

[Diagnosis and treatment of congenital hyperinsulinism--to Paris at any price?].

BACKGROUND: Persistent hyperinsulinaemic hypoglycaemia of infancy (PHHI) is a hyperfunctional disorder of pancreatic insulin-producing cells with hypertrophic beta-cells present either focally or diffusely. With an estimated frequency of 1:50,000 live births, Norway will on average have one case per year. It is clearly difficult to maintain expertise in diagnostics and treatment with such a low incidence. MATERIAL AND METHODS: We report three Norwegian patients with PHHI who were successfully treated at Hôpital des Enfants Malades in Paris. RESULTS: Two patients were shown to have focal hyperinsulinism treated with partial pancreas resection. After follow-up of three and a half and two years respectively, these patients have normal glucose tolerance and exocrine pancreatic function. One patient with diffuse hyperinsulinism was operated with subtotal (90%) pancreatectomy. At 2.5-years follow-up this patient has slight glucose intolerance whereas her fasting blood glucose is low normal. The exocrine pancreatic function is normal. INTERPRETATION: Patients with PHHI should be referred to a centre where the possibility of focal hyperinsulinism can be thoroughly explored.

Child↗
PubMed2001

Persistent differences among centers over 3 years in glycemic control and hypoglycemia in a study of 3,805 children and adolescents with type 1 diabetes from the Hvidøre Study Group.

OBJECTIVE: Twenty-one international pediatric diabetes centers from 17 countries investigated the effect of simple feedback about the grand mean HbA(1c) level of all centers and the average value of each center on changes in metabolic control, rate of severe hypoglycemia, and insulin therapy over a 3-year period. RESEARCH DESIGN AND METHODS: Clinical data collection and determination of HbA(1c) levels were conducted at a central location in 1995 (n = 2,780, age 0-18 years) and 1998 (n = 2,101, age 11-18 years). RESULTS: Striking differences in average HbA(1c) concentrations were found among centers; these differences remained after adjustment for the significant confounders of sex, age, and diabetes duration. They were apparent even in patients with short diabetes duration and remained stable 3 years later (mean adjusted HbA(1c) level: 8.62 +/- 0.03 vs. 8.67 +/- 0.04 [1995 vs. 1998, respectively]). Three centers had improved significantly, four centers had deteriorated significantly in their overall adjusted HbA(1c) levels, and 14 centers had not changed in glycemic control. During the observation period, there were increases in the adjusted insulin dose by 0.076 U/kg, the adjusted number of injections by 0.23 injections per day, and the adjusted BMI by 0.95 kg/m(2). The 1995 versus 1998 difference in glycemic control for the seven centers could not be explained by prevailing insulin regimens or rates of hypoglycemia. CONCLUSIONS: This study reveals significant outcome differences among large international pediatric diabetes centers. Feedback and comparison of HbA(1c) levels led to an intensification of insulin therapy in most centers, but improved glycemic control in only a few.

Adolescent↗
PubMed2000

MODY associated with two novel hepatocyte nuclear factor-1alpha loss-of-function mutations (P112L and Q466X).

Maturity-onset diabetes of the young (MODY) is an autosomal dominant form of diabetes characterized by early onset of pancreatic dysfunction. MODY type 3 is caused by mutations in the hepatocyte nuclear factor (HNF)-1alpha. During a screening of Norwegian patients with suspected MODY we identified two novel HNF-1alpha mutations, P112L and Q466X. The molecular mechanisms underlying the disease were studied by analyzing the DNA binding properties, transcriptional activation, and subcellular localization of HNF-1alpha P112L and Q466X compared to wild type HNF-1alpha. P112L had reduced ability to bind an HNF1 consensus sequence and to activate transcription. Q466X did not differ from wild type HNF-1alpha in DNA binding activity. Transactivation, however, was markedly reduced. When both mutants were coexpressed with wild type HNF-1alpha in HeLa cells, transcriptional activity appeared unaffected, suggesting that a dominant-negative mechanism was not present. Immunolocalization experiments showed that P112L HNF-1alpha was correctly targeted to nuclei in HeLa cells. In contrast, some Q466X HNF-1alpha protein was retained in the cytoplasm, which indicated that the mechanism for nuclear localization was disturbed. Thus, the HNF-1alpha mutations P112L and Q466X both seem to impair pancreatic beta-cell function by loss-of-function mechanisms; P112L by reduced DNA binding and reduced ability to transactivate, and Q466X by reduced transactivation and incomplete nuclear targeting.

DNA↗
PubMed2000

[Genetic and immunologic risks for development of type 1 diabetes--experiences from an intervention trial].

BACKGROUND: Type 1 diabetes is a common multi-factorial disease. Recently, promising attempts have been made at preventing the disease in individuals at risk. We present our experiences as participants in an international multicentre intervention trial, the European Nicotinamide Diabetes Intervention Trial (ENDIT). The aim is to prevent prediabetic individuals from becoming overtly diabetic by the use of nicotinamide. MATERIAL AND METHODS: First degree relatives of type 1 diabetes children attending paediatric clinics in Norway were recruited. The level of islet cell antibodies (ICA) was determined. Individuals with ICA titer above 20 Juvenile Diabetes Foundation Units (JDFU) were allocated to treatment with nicotinamide or placebo in a double-blind design. In the Norwegian patients in the trial HLA-DQ genotypes were also determined. RESULTS: 56 individuals had ICA > 20 JDFU; 36 agreed to participate in the trial. Assessment of genetic and immunological risk did not seem to emotionally upset the majority of participants; so far, no serious adverse events have been observed. The final results of this trial are expected in year 2003. INTERPRETATION: Prevention of type 1 diabetes may be feasible in the future.

Adult↗