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Biomedical subjects

H B Mortensen

Publications and source records attributed to H B Mortensen.

At least 19 recordsLinked to original sources
PubMed2006

IRS1, KCNJ11, PPARgamma2 and HNF-1alpha: do amino acid polymorphisms in these candidate genes support a shared aetiology between type 1 and type 2 diabetes?

AIMS: Type 1 diabetes mellitus (T1DM) is a chronic disorder primarily triggered by environmental and immunological factors in genetically susceptible individuals. Despite the fact that there are indications of common aetiological features of T1DM and type 2 diabetes (T2DM), variation in genes involved in insulin secretion and insulin signalling has to a large extent been ignored as potential modifiers in the pathogenesis of T1DM. Recent studies suggest, however, that proven T2DM susceptibility gene variants may be involved in the pathogenesis of T1DM. The objective of this study was to estimate the impact of four selected amino acid polymorphisms -IRS-1 Gly972Arg, Kir6.2 Glu23Lys, HNF-1alpha Ala98Val and PPARgamma2 Pro12Ala in a Danish population of T1DM families. METHODS: All variants were genotyped in 490 simplex- and multiplex-T1DM families applying polymerase chain reaction-restriction fragment length polymorphism, and results were evaluated by means of a transmission disequilibrium test (TDT) analysis. RESULTS: TDT analysis revealed that the Arg972 IRS-1, the Lys23 Kir6.2 and the Val98 HNF-1alpha variants were transmitted from heterozygous parents to affected probands at frequencies of 49.1%, 47.0% and 54.1%, respectively (p > 0.05 for all). This was similar to the rate of transmission to unaffected siblings. The transmission rate of the Ala12 PPARgamma2 variant to affected probands was 46.5% (p > 0.05) which differed significantly from the transmission to unaffected offspring (p = 0.024). A combined analysis of the present and published pertinent data of 1691 transmissions showed a significantly decreased transmission of the PPARgamma2 Ala12 allele to affected probands (p = 0.0045). CONCLUSIONS: The Pro12Ala variant of PPARgamma2 is associated with T1DM, the minor Ala allele conferring a reduced risk. This same finding has been reported in patients with T2DM.

Adolescent↗
PubMed2005

Impact of IDDM2 on disease pathogenesis and progression in children with newly diagnosed type 1 diabetes: reduced insulin antibody titres and preserved beta cell function.

AIMS/HYPOTHESIS: The insulin-dependent diabetes mellitus 2 gene (IDDM2) is a type 1 diabetes susceptibility locus contributed to by the variable number of tandem repeats (VNTR) upstream of the insulin gene (INS). We investigated the association between INS VNTR class III alleles (-23HphIA/T) and both insulin antibody presentation and residual beta cell function during the first year after diagnosis in 257 children with type 1 diabetes. MATERIALS AND METHODS: To estimate C-peptide levels and autoantibody presentation, patients underwent a meal-stimulated C-peptide test 1, 6, and 12 months after diagnosis. The insulin -23HphIA/T variant was used as a marker of class III alleles and genotyped by PCR-RFLP. RESULTS: The insulin antibody titres at 1 and 6 months were significantly lower in the class III/III and class I/III genotype groups than in the class I/I genotype group (p = 0.01). Class III alleles were also associated with residual beta cell function 12 months after diagnosis and independently of age, sex, BMI, insulin antibody titres, and HLA-risk genotype group (p = 0.03). The C-peptide level was twice as high among class III/III genotypes as in class I/I and class I/III genotypes (319 vs 131 and 166 pmol/l, p=0.01). Furthermore, the class III/III genotype had a 1.1% reduction in HbA(1)c after adjustment for insulin dose (p = 0.04). CONCLUSIONS/INTERPRETATION: These findings suggest a direct connection in vivo between INS VNTR class III alleles, a decreased humoral immune response to insulin, and preservation of beta cell function in recent-onset type 1 diabetes.

C-Peptide↗
PubMed2005

Half of clinically defined maturity-onset diabetes of the young patients in Denmark do not have mutations in HNF4A, GCK, and TCF1.

AIMS/HYPOTHESIS: Maturity-onset diabetes of the young (MODY) is a genetically heterogeneous monogenic form of diabetes characterized by an autosomal dominant inheritance, an early clinical onset, and a primary defect in beta-cell function. The aims of the present study were to examine the prevalence and nature of mutations in the three common MODY genes, HNF4A, GCK, and TCF1, in Danish patients with a clinical diagnosis of MODY and to describe metabolic differences in probands with and without mutations in HNF4A, GCK, and TCF1. METHODS: Seventy-eight unrelated subjects of Danish Caucasian origin (29 men, 49 women) and their 351 family members were examined. The promotor and coding regions including intron-exon boundaries of HNF4A, GCK, and TCF1 were examined by denaturing HPLC and/or direct sequencing. RESULTS: We identified 29 different mutations in 38 MODY families. Fifteen of the mutations were novel. The variants segregated with diabetes within the families, and none of the variants were found in 100 normal Danish chromosomes. Our findings suggest a relative prevalence of 3% of MODY1 (two different mutations in two families), 10% of MODY2 (seven in eight), and 36% of MODY3 (21 in 28) among Danish kindred clinically diagnosed as MODY. No significant differences in biochemical and anthropometric measurements were observed at baseline examinations. CONCLUSIONS: Forty-nine percent of the families carried mutations in the three examined MODY genes. Our findings highlight that unidentified MODY genes may play a central role for diabetes characterized by autosomal dominant transmission. Furthermore, baseline measurements of various anthropometric and biochemical variables are not appropriate markers of MODYX.

Adolescent↗
PubMed2005

Factors associated with glycaemic outcome of childhood diabetes care in Denmark.

AIMS: To study how structure and process of care is associated with outcome assessed by HbA(1c). METHODS: Data for this cross-sectional study originated from the nationwide Danish Registry for Childhood Diabetes and two questionnaires. One questionnaire was sent to all children under 16 years of age with Type 1 diabetes in the year 2000 (N = 1087, response rate 80%). Another questionnaire was sent to the 19 centres in Denmark treating these children (response rate 100%). Simultaneously the children were asked to take a blood sample for central HbA(1c) analysis. Linear mixed models were used for analysis of associations between structure and process indicators and HbA(1c). Age, diabetes duration, sex, ethnicity, family structure and parents' occupational status were included as patient factors possibly affecting HbA(1c). RESULTS: More visits to the outpatient clinic and higher insulin dosage were significantly associated with higher HbA(1c) (P = 0.002 and P = 0.0001, respectively). Increased frequency of blood glucose monitoring (BGM/week) and completed nephropathy screening were significantly associated with lower HbA(1c) value (estimates -0.008 and -0.49, P = 0.02, respectively). The structure indicators were not associated with HbA(1c), but telephone hot-line was positively associated with the process indicator BGM (estimate 4.02, P = 0.04). Children without Danish parents performed BGM significantly less frequently (-7.11, P = 0.0005) and had higher HbA(1c) (0.41, P = 0.06). CONCLUSIONS: Most process indicators were significantly associated with HbA(1c), indicating relevant action of staff on glucose regulation. The structure indicators were not associated with outcome, necessitating more detailed studies on the influence of staffing resources, treatment strategies and targets in childhood diabetes management.

Adolescent↗
PubMed2003

Quality of diabetes management in children and adolescents in Denmark.

AIM: To describe the management of children and adolescents with Type 1 diabetes mellitus in Denmark. METHODS: Quality indicators with standards of childhood diabetes management were chosen based on international and national guidelines. Data originated from the nation-wide Danish Registry for Childhood Diabetes and two questionnaires: one questionnaire was sent to all children with diabetes (response rate 78%, n=1335) and the other was sent to the 19 centres in Denmark treating these children (response rate 100%). Simultaneously, the children were asked to take a blood sample for central HbA1c-analysis (normal range 4.3-5.8, mean 5.1%). RESULTS: Most children were managed at centres which complied with the standards for the process indicators for good diabetes management, but not with the standards for most structure and outcome indicators. Only one third of the children reached the treatment target for HbA1c. Their mean HbA1c-level increased gradually from ages 4-14 without significant difference between genders. The youngest children had the lowest HbA1c (mean 8.2%) and the lowest rate of severe hypoglycaemic events (4.6 events per 100 patient years). The subgroup of children without any hypoglycaemic events had the significantly lowest mean HbA1c-level (8.6%, P=0.028). CONCLUSIONS: The Danish Registry for Childhood Diabetes provided useful data for quality improvement, but had to be supplemented with data from questionnaires on the structure and process indicators. Outcome of paediatric diabetes management in Denmark was unsatisfactory. Centres need feedback on ways to improve care to lower the children's risk of developing severe diabetes complications.

Adolescent↗
PubMed2001

Good metabolic control is associated with better quality of life in 2,101 adolescents with type 1 diabetes.

OBJECTIVE: It is unclear whether the demands of good metabolic control or the consequences of poor control have a greater influence on quality of life (QOL) for adolescents with diabetes. This study aimed to assess these relations in a large international cohort of adolescents with diabetes and their families. RESEARCH DESIGN AND METHODS: The study involved 2,101 adolescents, aged 10-18 years, from 21 centers in 17 countries in Europe, Japan, and North America. Clinical and demographic data were collected from March through August 1998. HbA(1c) was analyzed centrally (normal range 4.4-6.3%; mean 5.4%). Adolescent QOL was assessed by a previously developed Diabetes Quality of Life (DQOL) questionnaire for adolescents, measuring the impact of diabetes, worries about diabetes, satisfaction with life, and health perception. Parents and health professionals assessed family burden using newly constructed questionnaires. RESULTS: Mean HbA(1c) was 8.7% (range 4.8-17.4). Lower HbA(1c) was associated with lower impact (P < 0.0001), fewer worries (P < 0.05), greater satisfaction (P < 0.0001), and better health perception (P < 0.0001) for adolescents. Girls showed increased worries (P < 0.01), less satisfaction, and poorer health perception (P < 0.01) earlier than boys. Parent and health professional perceptions of burden decreased with age of adolescent (P < 0.0001). Patients from ethnic minorities had poorer scores for impact (P < 0.0001), worries (P < 0.05), and health perception (P < 0.01). There was no correlation between adolescent and parent or between adolescent and professional scores. CONCLUSIONS: In a multiple regression model, lower HbA(1c) was significantly associated with better adolescent-rated QOL on all four subscales and with lower perceived family burden as assessed by parents and health professionals.

Adolescent↗
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

Rapid appearance and onset of action of insulin aspart in paediatric subjects with type 1 diabetes.

UNLABELLED: The pharmacokinetics of the novel, rapid-acting insulin aspart were compared with those of soluble human insulin following subcutaneous administration in nine children (aged 6-12 years) and nine adolescents (aged 13-17 years) with stable type 1 diabetes. The study had a randomised, double-blind, two-period crossover design. Each patient received a single subcutaneous dose of insulin aspart or human insulin (0.15 IU/kg body weight) 5 min before breakfast and the plasma insulin and glucose concentrations were measured at intervals during the following 5 h. The pharmacokinetic profile of insulin aspart differed significantly from that of human insulin with a higher mean maximum serum insulin (Cmax ins), 881 +/- 321 (SD) pmol/l versus 422 +/- 193 pmol/l for human insulin (P < 0.001); and with a shorter median serum insulin tmax ins, 40.0 min (interquartile range: 40-50 min) versus 75.0 min (interquartile range: 60-120 min) for human insulin, (P < 0.001). An age-related effect on Cmax ins and area under the curve (AUC0-5 h ins) was observed with higher values in adolescents than in children for both insulin aspart and human insulin. Postprandial glycaemic control was improved with insulin aspart; the baseline-adjusted delta Cmax glu being lower for insulin aspart compared with human insulin (increase of 7.6 +/- 5.1 versus 9.4 +/- 4.4 mmol/l respectively, P < 0.05). The incidence of adverse events was similar for the two insulin types. CONCLUSION: The more rapid onset of action of insulin aspart versus human insulin, previously observed in adults, is confirmed in a paediatric population with type 1 diabetes.

Adolescent↗
PubMed1999

Metabolic control and prevalence of microvascular complications in young Danish patients with Type 1 diabetes mellitus. Danish Study Group of Diabetes in Childhood.

AIMS: After Danish nationwide investigations (1987, 1989) demonstrated unacceptable blood glucose control in unselected young diabetic patients, we set out to estimate the present glycaemic control and the prevalence of microvascular complications in a cohort of children and adolescents participating in the two previous studies. METHODS: This follow-up represents 339 patients (47% of the inception cohort), median age 21.1 years (range 12.0-26.9), median diabetes duration 13.2 years (range 8.9-24.5). A standardized questionnaire, fundus photographs (with central reading) and a physical examination were performed. HbA1c and overnight albumin excretion rate (AER) were analysed centrally. RESULTS: Although 88% (n= 309) of the young persons were treated with three or more daily insulin injections, HbA1c (nondiabetic range 4.3-5.8, mean 5.3%) was 9.7+/-1.7% (mean+/-SD). Males had higher HbA1c values than females (P < 0.015). Mean daily insulin dose was 0.92+/-0.25 IU.kg(-1).24h(-1). Microalbuminuria (AER > 20-150 microg/min) and macroalbuminuria (AER > 150 microg/min) were found in 9.0% and 3.7% of the patients, respectively, and was associated with increased diastolic blood pressure (P<0.01) and presence of retinopathy (P<0.01). Retinopathy was present in approximately 60% of the patients and was associated with age, diabetes duration, HbA1c, diastolic blood pressure and AER (all P<0.01). Subclinical neuropathy (vibration perception threshold by biothesiometry > 6.5 V) was found in 62% and showed a significant association with age, linear height, diastolic blood pressure (all P < 0.01) and diabetic retinopathy (P = 0.01). CONCLUSIONS: In spite of the majority of the patients being on multiple insulin injections, only 11% had HbA1c values below 8% and the prevalence of diabetic microvascular complications in kidneys, eyes and nerves was unacceptable high.

Adolescent↗
PubMed1998

Insulin management and metabolic control of type 1 diabetes mellitus in childhood and adolescence in 18 countries. Hvidøre Study Group on Childhood Diabetes.

Insulin regimens and metabolic control in children and adolescents with Type 1 diabetes mellitus were evaluated in a cross-sectional, non-population-based investigation, involving 22 paediatric departments, from 18 countries in Europe, Japan, and North America. Blood samples and information were collected from 2873 children from March to August 1995. HbA1c was determined once and analysed centrally (normal range 4.4-6.3%, mean 5.4%). Year of birth, sex, duration of diabetes, height, body weight, number of daily insulin injections, types and doses of insulin were recorded. Average HbA1c in children under 11 years was 8.3 +/- 1.3% (mean +/- SD) compared with 8.9 +/- 1.8% in those aged 12-18 years. The average insulin dose per kg body weight was almost constant (0.65 U kg(-1) 24 h(-1)) in children aged 2-9 years for both sexes, but there was a sharp increase during the pubertal years, particularly in girls. The increase in BMI of children with diabetes was much faster during adolescence compared to healthy children, especially in females. Sixty per cent of the children (n = 1707) used two daily insulin injections while 37% (n = 1071) used three or more. Of those on two or three injections daily, 37% used pre-mixed insulins, either alone or in combination with short- and intermediate-acting insulin. Pre-adolescent children on pre-mixed insulin showed similar HbA1c levels to those on a combination of short- and long-acting insulins, whereas in adolescents significantly better HbA1c values were achieved with individual combinations. Very young children were treated with a higher proportion of long-acting insulin. Among adolescent boys, lower HbA1c was related to use of more short-acting insulin. This association was not found in girls. We conclude that numerous insulin injection regimens are currently used in paediatric diabetes centres around the world, with an increasing tendency towards intensive diabetes management, particularly in older adolescents. Nevertheless, the goal of near normoglycaemia is achieved in only a few.

Adolescent↗
PubMed1998

Practical aspects of managing diabetes in adolescents.

In 1988 and 1990 screening for HbA1c and albumin excretion rate in diabetic children was carried out throughout Denmark. Each study included approximately 1000 diabetic patients. Raised levels of HbA1c (9.5-10%) were found despite 60% of these young people receiving three or more insulin injections daily. The prevalence of persistent microalbuminuria was 4.3%, which was associated only with age and diastolic blood pressure. A recent international survey of HbA1c and insulin treatment involving 2873 children found an average HbA1c of 8.6%+/-1.7%, which varied significantly (p < 0. 0001) between centres. Severe hypoglycaemia was related to a young age (0-8 y) and low HbA1c. There were no significant differences in glycaemic control between adolescents treated with two, three, four or more insulin injections daily. Adolescents on four or more injections received significantly (p < 0.001) more insulin. Girls receiving four or more injections had a significantly (p < 0.01) higher body mass index than girls on twice-daily insulin. Preadolescent children on premixed insulin showed similar HbA1c levels to those on a combination of short- and long-acting insulin, whereas in adolescents, significantly better HbA1c values were achieved with individual combinations. Despite intensive diabetes management, particularly in adolescence, near normoglycaemia is achieved only in a few individuals. control, glycosylated, haemoglobin

Adolescent↗
PubMed1998

Outcome of quality management in pediatric diabetes care.

In 1988 and 1990 screening for HbAlc and albumin excretion rate (AER) in diabetic children was carried out throughout Denmark. Each study included about 1,000 diabetic patients and found HbAlc and insulin requirements increased during maturation in both sexes. No significant differences in HbAlc were seen among adolescents treated with two, three or more daily insulin injections. The prevalence of persistent microalbuminuria was 4.3% which was associated only with age and diastolic blood pressure. An international survey on HbAlc and insulin treatment, involving 2,873 children, showed HbAlc to vary significantly between centers. Severe hypoglycemia was related to younger age (0-8 years) and lower HbAlc. Of the children on twice and three times daily injections, 37% used a premixed form of insulin. Very young children were treated with a higher proportion of long-acting insulin. Among adolescent boys, lower HbAlc was related to the use of more short-acting insulin. The data confirm that current treatment of childhood diabetes is inadequate.

Albuminuria↗
PubMed1997

Comparison of metabolic control in a cross-sectional study of 2,873 children and adolescents with IDDM from 18 countries. The Hvidøre Study Group on Childhood Diabetes.

OBJECTIVE: To obtain an estimate of the current level of metabolic control in children and adolescents with IDDM, the Hvidøre Study Group on Childhood Diabetes decided to establish a formal collaboration among countries to gather and exchange data for comparative purposes. RESEARCH DESIGN AND METHODS: This cross-sectional non-population-based survey involved 22 pediatric departments from 18 countries in Europe, Japan, and North America. Blood samples and information were collected from March through August 1995 on 2,873 children who were born in 1977 or later and seen in the outpatient clinics. HbA1c levels were determined once and analyzed centrally (normal range, 4.4-6.3%; mean, 5.4%). Year of birth, sex, duration of diabetes, height, body weight, insulin regimen, and number of episodes of severe hypoglycemia during the past 3 months were recorded. RESULTS: Average HbA1c was 8.6 +/- 1.7%, but varied significantly (P < 0.0001) between centers. Hypoglycemia resulting in unconsciousness and/or seizures was related to younger age (0-8 years) and lower HbA1c level. The incidence, based on the 3-month period, was 22 per 100 patient-years. Sixty percent of the children (n = 1,707) had two injections daily, while 37% (n = 1,071) were on three or more. HbA1c increased during maturation for both sexes. No difference in glycemic control was found among adolescents treated with two, three, and four or more daily injections. Adolescents on four or more injections received significantly (P < 0.001) more insulin. Girls on four or more injections had significantly (P < 0.01) higher BMI than girls on twice-daily insulin. CONCLUSIONS: In the participating centers with a multidisciplinary team, only one third of the patients had an HbA1c level of < 8%.

Adolescent↗
PubMed1996

[Recurrent arthritis in a child. A rare manifestation of Wilson's disease].

Wilsons disease is a rare autosomal recessive disorder of copper transportation, which is fatal if not treated. The disease often starts in adolescence, and most common symptoms are due to liver-and/or brain involvement. This paper deals with an adolescent with Wilsons disease. His clinical presentation was joint complaints for almost two years. The final diagnosis was made by mutation analysis. It is stressed that the clinician should consider Wilson's disease in cases of unexplained liver- and neurological involvement as well as cases of repetitive unexplained joint symptoms in the pubertal period.

Adolescent↗