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Biomedical subjects

K Dahl-Jørgensen

Publications and source records attributed to K Dahl-Jørgensen.

At least 19 recordsLinked to original sources
PubMed2006

Children and adolescents with type 1 diabetes eat a more atherosclerosis-prone diet than healthy control subjects.

AIMS/HYPOTHESIS: We evaluated how well the diet of Norwegian children and adolescents with type 1 diabetes fulfils the Nordic and European dietary recommendations, focusing on parameters affecting prevention of atherosclerosis. We also compared the diet of this patient group with that of healthy same-age control subjects. MATERIALS AND METHODS: A total of 177 children and adolescents with type 1 diabetes (9-10-year-olds, 12-13-year-olds) and 1,809 healthy same-age control subjects recorded their food intake for 4 days in precoded food diaries. RESULTS: In children and adolescents with type 1 diabetes the percentage of energy (E%) from fat (33-35 E%) and saturated fat (14-15 E%) was higher than recommended for that group. Furthermore their intake of fibre was lower (16-19 g/day) than current recommendations. There were no differences in energy intake between diabetic subjects and healthy control subjects. Percentage of energy from fat (mean difference: 3.4 E%, p < 0.001) and saturated fat (mean difference: 1.0 E%, p < 0.001) was significantly higher among diabetic subjects than control subjects. Intake of fruits and vegetables was low (210 g/day) compared with recommendations, both in the diabetic and control subjects. CONCLUSIONS/INTERPRETATION: Diabetic children and adolescents had a high intake of energy from saturated fat and low intake of fibre, fruits and vegetables, which could increase the risk of development of atherosclerosis. This study supports the idea that nutritional guidance in the treatment of children and adolescents with type 1 diabetes should be more focused, especially with regard to intake of fibre, fruits and vegetables and to quality and quantity of fat intake.

Adolescent↗
PubMed2005

Atherosclerosis in childhood and adolescent type 1 diabetes: early disease, early treatment?

Autopsy studies have shown that atherosclerosis begins in adolescence in otherwise healthy individuals, and imaging techniques have shown that atherosclerosis develops earlier and is more prevalent in children with diabetes than in age-matched healthy controls. Cardiovascular disease has now overtaken diabetic nephropathy as the leading cause of premature mortality in young adults with diabetes, and the emphasis on disease prevention has accordingly shifted to a younger age group. The majority of children and adolescents with diabetes have suboptimal blood glucose control, and this contributes to accelerated arterial disease in this age group. Other conventional risk factors for coronary heart disease also need to be considered and treated aggressively. Effective early prevention of cardiovascular disease will involve lifestyle modification and full implementation of existing treatment guidelines, and large-scale prospective studies will be needed to establish the risks and benefits of early pharmacological intervention in children and adolescents.

Adolescent↗
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↗
PubMed1999

The predisposition to type 1 diabetes linked to the human leukocyte antigen complex includes at least one non-class II gene.

The human leukocyte antigen (HLA) complex, encompassing 3.5 Mb of DNA from the centromeric HLA-DPB2 locus to the telomeric HLA-F locus on chromosome 6p21, encodes a major part of the genetic predisposition to develop type 1 diabetes, designated "IDDM1." A primary role for allelic variation of the class II HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci has been established. However, studies of animals and humans have indicated that other, unmapped, major histocompatibility complex (MHC)-linked genes are participating in IDDM1. The strong linkage disequilibrium between genes in this complex makes mapping a difficult task. In the present paper, we report on the approach we have devised to circumvent the confounding effects of disequilibrium between class II alleles and alleles at other MHC loci. We have scanned 12 Mb of the MHC and flanking chromosome regions with microsatellite polymorphisms and analyzed the transmission of these marker alleles to diabetic probands from parents who were homozygous for the alleles of the HLA-DRB1, HLA-DQA1, and HLA-DQB1 genes. Our analysis, using three independent family sets, suggests the presence of an additional type I diabetes gene (or genes). This approach is useful for the analysis of other loci linked to common diseases, to verify if a candidate polymorphism can explain all of the association of a region or if the association is due to two or more loci in linkage disequilibrium with each other.

Alleles↗
PubMed1999

Modern insulin therapy in children and adolescents.

Clear evidence exists that near-normal blood glucose control will prevent serious late diabetic complications. This review summarizes the targets for blood glucose control and discusses why insulin replacement therapy is so complicated in children and adolescents. It is important that diabetes treatment teams have excellent knowledge of insulin preparations, insulin pharmacokinetics and action profiles and the limitations and pitfalls of therapy. This is necessary to be able to optimize and individualize treatment. A detailed summary of different insulin regimens is given and discussed to help treatment teams choose a suitable regimen for the individual patient. The use of home blood glucose measurement is necessary to reach the targets of treatment. If economic resources are limited, alternative strategies are suggested. In wealthy countries the lifestyle of adolescents demands great flexibility and a suggestion for systematic training to increase flexibility in daily life is presented.

Adolescent↗
PubMed1998

Diabetic microangiopathy.

Microvascular complications of diabetes include retinopathy, nephropathy and neuropathy. The first signs of these complications may develop in children and adolescents, particularly if insulin treatment has been inadequate. The mechanisms by which diabetic microangiopathy develop are not known, but probably include genetic influences. Several biochemical changes may interact, one important change being increased protein glycation. Important functional changes are increased organ blood flow, increased vascular permeability, abnormal blood viscosity and abnormal platelet and endothelial function. The structural hallmark of diabetic microangiopathy is the thickening of the capillary basement membrane. These changes may lead to occlusive angiopathy and to tissue hypoxia and damage. Screening for microangiopathy should start in children and adolescents after 5-y duration of the disease and 10y of age. The screening should include retinal examination through a dilated pupil or fundus photography, urinary albumin excretion rate, blood pressure measurement and neurological examination. Several intervention trials have shown that near normoglycaemia may reduce the risk of microangiopathy. There is a curvilinear association between the risk of development and progression of microangiopathy and mean blood glucose. Therefore, optimal insulin treatment is important in children and adolescents.

Adolescent↗
PubMed1998

Biochemical markers of diabetic microangiopathy. Past, present and future.

The first signs of diabetic microvascular complications in the eyes and kidney, and early signs of neuropathy, may develop in children and adolescents. The development and progression of such complications are clearly related to blood glucose control. The mechanisms by which microangiopathy develops are not exactly known, and there are no excellent biochemical markers with high predictive value for future microangiopathy. The best available markers today are HbA1c and the urinary albumin excretion. New biochemical markers related to advanced glycation end products (AGEs), and recently possible genetic markers, have been described. The predictive value of single markers and the combination of such markers has to be tested in long term clinical studies.

Adolescent↗
PubMed1998

The advanced glycation end product Nepsilon-(carboxymethyl)lysine is increased in serum from children and adolescents with type 1 diabetes.

OBJECTIVE: To investigate whether children and adolescents with type 1 diabetes have increased serum levels of the glycoxidation product Nepsilon-(carboxymethyl)lysine (CML) at an early stage of the disease. RESEARCH DESIGN AND METHODS: The serum levels of CML in 38 patients with type 1 diabetes aged 14+/-3.2 (mean+/-SD) years were compared with those in 26 control subjects aged 16+/-1.7 years. The mean duration of diabetes was 5+/-4.7 years, ranging from 0.5 to 15 years. The mean levels of HbA1c were 10.3+/-2.5% in the patient group. The serum levels of CML were measured using a monoclonal anti-CML antibody in a fluoremetric immunoassay. Serum protein levels of advanced glycation end products (AGEs) were assayed using a polyclonal antibody from rabbit immunized with AGE-RNase (pAGE). RESULTS: The serum levels of CML and pAGE were significantly increased in the patient group versus the control group: 1.08 (0.45-2.97) U/ml CML (median 10-90 percentiles) vs. 0.70 (0.36-1.79) U/ml CML, P < 0.03, and 6.6 (5.1-9.9) U/ml pAGE vs. 5.5 (3.7-8.2) U/ml AGEs, P < 0.01. A significant relationship between CML and pAGE was found in the IDDM group, r = 0.76, P < 0.001. The CML levels were not associated with the HbAlc levels (n = 23, r = -0.02, NS), cholesterol levels (n = 21, r = 0.07, NS), age, sex, or diabetes duration. CONCLUSIONS: Serum levels of CML are increased in patients with type 1 diabetes. This increase precedes the development of micro- and macrovascular complications.

Adolescent↗
PubMed1997

HLA associations in insulin-dependent diabetes mellitus: no independent association to particular DP genes.

Genes in the HLA complex are associated with susceptibility to develop insulin-dependent diabetes mellitus (IDDM). Several studies, from different populations, have demonstrated strong associations between particular DR and DQ alleles and disease susceptibility or protection. Whether also particular DP alleles may independently contribute is more controversial. Some studies have found a greater frequency of DPB1*0301 among IDDM patients compared to controls, apparently independently of linkage disequilibrium with high risk DR and DQ alleles. To address this question in an ethnically homogeneous population (Norwegian), we have DPA1 and DPB1 genotyped 237 IDDM patients and 287 DRB1-DQA1-DQB1 matched controls, carrying high risk DR3/4 or DR4/4 genotypes. We were unable to detect any significant independent associations between DP alleles and IDDM susceptibility or protection in this population. Thus, our results do not support previous reports on an independent association between some DP alleles and susceptibility to develop IDDM.

Alleles↗
PubMed1997

HLA-encoded genetic predisposition in IDDM: DR4 subtypes may be associated with different degrees of protection.

Recent studies have shown that the risk conferred by the high-risk DQA1*03-DQB1*0302 (DQ8) haplotype is modified by the DRB1*04 allele that is also carried by this haplotype. However, many of these studies suffer from lack of sufficient numbers of DQ-matched control subjects, which are necessary because there is a strong linkage disequilibrium between genes in the HLA complex. In the present study, using a large material of IDDM patients and DQ-matched control subjects, we have addressed the contribution of DR4 subtypes to IDDM susceptibility. Our data, together with recent data from others, clearly demonstrate that some DR4-DQ8 haplotypes are associated with disease susceptibility, while others are associated with protection, depending on the DRB1*04 allele carried by the same haplotype. In particular, our data demonstrate that DRB1*0401 confers a higher risk than DRB1*0404. Based on combined available data on the genetic susceptibility encoded by various DR4-DQ8 haplotypes and the amino acid composition of the involved DRbeta*04 chains as well as the ligand motifs for these DR4 subtypes, we have developed a unifying hypothesis explaining the different risks associated with different DR4-DQ8 haplotypes. We suggest that disease susceptibility is mainly conferred by DQ8 while DR4 subtypes confer different degrees of protection. Some DR4 subtypes (i.e., DRB1*0405, 0402, and 0401) confer little or no protection, while others (i.e., DRB1*0404, 0403, and 0406) cause an increasing degree of protection, possibly by binding a common protective peptide. Features of a protective peptide that fit such a model are briefly discussed.

Adolescent↗
PubMed1997

No independent associations of LMP2 and LMP7 polymorphisms with susceptibility to develop IDDM.

Results from a recent study suggested that polymorphisms within the HLA class II genes LMP2 and LMP7 were associated with the susceptibility for developing IDDM, and that this association could not be explained by linkage disequilibrium to HLA-DR or -DQ genes. We typed 285 IDDM patients and 337 HLA-DRB1-DQA1-DQB1 genotypically matched control subjects from an ethnically homogeneous population for both the G/T polymorphism in intron 6 of the LMP7 gene and the Arg-His polymorphism in the LMP2 gene. In addition, we typed IDDM families in which at least one parent was homozygous for a DRB1-DQA1-DQB1 haplotype and performed a transmission/disequilibrium test of these LMP polymorphisms. Our data suggest that none of these LMP2 or LMP7 polymorphisms are independently associated with IDDM susceptibility, in contrast to what has been previously reported by others. Further, our results suggest that one partial explanation for the previously reported independent association between IDDM and these LMP polymorphisms may have been that patients and control subjects were not matched for DRB1*04 subtypes. Our results emphasize the need for a complete matching for DRB1, DQA1, and DQB1 alleles between patients and control subjects when attempting to detect independent effects of other polymorphisms in the HLA complex on IDDM susceptibility or protection.

Cysteine Endopeptidases↗
PubMed1997

Increased serum levels of advanced glycation end products (AGEs) in children and adolescents with IDDM.

OBJECTIVE: To investigate whether the serum levels of advanced glycation end products (AGEs) are increased in IDDM children and adolescents and to study the effect of puberty on serum levels of AGEs (S-AGEs). RESEARCH DESIGN AND METHODS: A total of 68 children and adolescent IDDM patients (age, 13.3 +/- 4.0 years; duration of diabetes, 5.0 +/- 3.6 years; HbA1c, 8.2 +/- 2.0%; Tanner stage [public hair], 1 vs. 2-5, 24/42) recruited from the pediatric outpatient clinic at Aker University Hospital were compared with 25 healthy nondiabetic control subjects. S-AGEs were measured by a fluoremetric immunoassay. RESULTS: S-AGEs were significantly elevated in the diabetic group when compared with the control group (14.4 +/- 3.5 vs. 11.7 +/- 3.0 U/ml, P < 0.002). A significant correlation (r = 0.26, P < 0.04) was found between S-AGEs and HbA1c in the diabetic group but not in the control group. No significant correlation was found between S-AGEs and the duration of diabetes in the diabetic group or S-AGEs and blood glucose concentration or age in either group. We found no difference between S-AGEs in boys and girls and in prepubertal and pubertal diabetic or control subjects. CONCLUSIONS: S-AGEs are increased in young patients with diabetes before puberty. Since AGEs are linked to the pathogenesis of vascular complications, this observation suggests that the pathological processes leading to diabetic late complications start even before puberty.

Adolescent↗
PubMed1995

Urinary excretion of retinol-binding protein in healthy children and adolescents.

Retinol-binding protein (RBP) is a marker of tubular reabsorption in the kidneys. The aim of our study was to investigate urinary RBP excretion in healthy children to obtain reference values related to age and pubertal stage. Overnight samples from 143 subjects (73 girls, 70 boys) aged 10-18 years were investigated. RBP was quantified by a solid-phase sandwich enzyme immunoassay. Both the RBP excretion rate and the RBP/creatinine ratio (RBP/Cr) showed a skewed distribution. The medians and the 5th-95th percentiles were 38 ng/min (15-127) and 9 micrograms/mmol (4-23), respectively. The RBP excretion rate and RBP/Cr ratio were similar in both sexes, and linear multiple regression analysis showed no association with age or pubertal stage, although a weak relationship (r = 0.27) was found between RBP excretion rate and age in boys and RBP/Cr ratio and age (r = -0.28) in girls by simple correlation analysis. The correlation between RBP excretion rate and RBP/Cr ratio was 0.76; the RBP excretion rate and RBP/Cr ratio measured on 2 consecutive days, showed a correlation coefficient of 0.84 and 0.88, respectively. We conclude that overnight RBP excretion in children over 10 years shows a low day-to-day variation and, in practical terms, is independent of age, gender and pubertal stage.

Adolescent↗
PubMed1994

The effect of 8 years of strict glycaemic control on peripheral nerve function in IDDM patients: the Oslo Study.

We have investigated the effect of long-term strict glycaemic control on peripheral and autonomic nerve function in 45 IDDM patients (age 18-42 years, diabetes duration 7-23 years) without clinical signs of neuropathy or other neurological disease. They were randomly assigned to treatment either with continuous insulin infusion, multiple injections (4-6 times daily), or conventional treatment (twice daily) for 4 years and followed prospectively for 8 years. Motor and sensory nerve conduction velocities were measured at the start and after 8 years. Autonomic nerve function tests were performed only once, after 8 years. A significant reduction of nerve conduction velocity was observed during 8 years in patients with mean HbA1 more than 10% (n = 12, group mean 10.9%, range 10.1-13.2%) compared to patients with HbA1 less than 10% (n = 33, group mean 9.0%, range 7.5-9.9%). Change of motor nerve conduction velocity in the peroneal nerve was: -4.8 +/- 4.9 (SD) vs -2.2 +/- 5.3 m/s (p < 0.01). Change of motor nerve conduction velocity in the posterior tibial nerve was: -6.8 +/- 5.7 vs- 3.9 +/- 5.1 m/s (p < 0.05). No significant changes were observed in the ulnar nerve. Change of sensoric nerve conduction velocity in the sural nerve was: -8.9 +/- 8.0 vs -4.6 +/- 5.3 m/s (p < 0.05). Multiple regression analysis showed that a change in HbA1 of 1% resulted in a 1.3 m/s change in nerve conduction velocity during 8 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy.

We investigated in a randomized, prospective study the influence of improved blood glucose control during 2-3 years in young insulin-dependent diabetic (IDDM) patients with microalbuminuria, which is indicative of early nephropathy. Patients were randomized either to intensive treatment by continuous subcutaneous insulin infusion (CSII) (n = 9) or CT (n = 9). Kidney biopsies were taken at baseline and after 26-34 months. End points were structural changes in the glomeruli. Sensitive, quantitative, morphometric methods were used. The blood glucose control improved significantly (p = 0.01) during the study in the CSII-group as glycated haemoglobin (HbA1c) fell from 10.1% ([95% CI] 8.9-11.3) to 8.6% (7.9-9.2), but not in the CT-group, 10.1% (8.3-11.9) vs 9.7% (8.7-10.8). Mean HbA1c during the study period was significantly lower in the CSII-group than in the CT-group, 8.7% (8.1-9.3) vs 9.9% (8.5-11.3), p = 0.04. Basement membrane thickness (BMT) increased in both groups, most (CT vs CSII, p = 0.03) in the CT-group: 140 nm (50-230) vs CSII: 56 nm (27-86). In the CT-group only an increase was seen in matrix/mesangial volume fraction (p = 0.006) and matrix star volume (p = 0.04). Furthermore, a positive correlation between mean HbA1c during the study and change from baseline in BMT (r = 0.70, p = 0.001) and matrix/glomerular volume fraction (r = 0.33, p = 0.09, NS) was demonstrated. Albumin excretion rate correlated significantly to BMT and most of the matrix parameters.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Impaired contrast sensitivity in adolescents and young type 1 (insulin-dependent) diabetic patients with microalbuminuria.

We compared neurosensorial visual function by psychophysical tests (macular recovery time and contrast sensitivity) in two well matched groups of young Type 1 (insulin-dependent) diabetic patients with micro- and normoalbuminuria, respectively. The patients had normal visual acuity (> or = 1.0) and either no retinopathy or non-proliferative retinopathy. Thirty patients with microalbuminuria (albumin excretion > or = 15 micrograms/min in a least two out of three timed overnight urine samples) were matched (age, diabetes duration, mean one-year HbA1c, gender) with normoalbuminuric (n = 27) patients. Retinopathy (50 degree colour fundus photography) was assessed by counting microaneurysms and hemorrhages as 'red spots'. Contrast sensitivity was examined for the spatial frequencies of 1.5, 3, 6, 12 and 18 cycles per degree (cpd). Macular recovery time (nyctometry) refers to the time-related (2 min) ability of the retina to regain visual acuity following exposure to bright light (photostress). Contrast sensitivity score was reduced in patients with microalbuminuria compared to those without; 18 cpd (mean and 95% confidence intervals): [4.2 (3.8-4.7) vs 5.0 (4.6-5.4), p = 0.03]. Macular recovery performance was not significantly reduced: [21.0 arbitrary units (17.5-24.6) vs 26.0 (22.6-30.7), p = 0.12]. We conclude that impaired contrast sensitivity independent of background retinopathy is shown in a group of young Type 1 (insulin-dependent) diabetic patients with low-grade microalbuminuria compared to a group of patients with normoalbuminuria.

Adolescent↗