Biomedical subjects

Bendix Carstensen

Publications and source records attributed to Bendix Carstensen.

17 recordsLinked to original sources

PubMed2006

Angiographic diagnosis, prevalence and outcomes for left ventricular noncompaction in children with congenital cardiac disease.

Little is known about the implications of left ventricular noncompaction in children with additional congenital cardiac malformations. With this in mind, we conducted a retrospective review of every left ventricular angiogram performed in a single tertiary referral centre for paediatric cardiology, in Melbourne, Australia, between 1994 and 2000 in children with congenital heart disease, looking specifically for patients with angiographic evidence of noncompaction of the left ventricle. The outcome of patients identified as having noncompaction was compared with that of patients from the same population, stratified by their primary congenital cardiac malformation. Of 1515 children undergoing left ventricular angiography, 31, with 13 being male, were found to have angiographic evidence of left ventricular noncompaction, giving a prevalence of 2% (95% CI: 1.3%-2.8%). Of 69 (22%) children with a functionally single left ventricle, 15 fulfilled the criterions for noncompaction, compared to 16 of 1446 (1.1%) children with a balanced ventricular arrangement (p is less than 0.0001). The presence of noncompaction and a functionally single left ventricle were each associated with a doubling of mortality, the effect being cumulative. Of surviving patients with left ventricular noncompaction, 19% (4%-34%) have left ventricular dysfunction at their latest follow-up. We suggest that the important late sequels of noncompaction justify careful scrutiny for this entity in children with congenital cardiac disease.

Adolescent↗

PubMed2006

Predictions of type 2 diabetes and complications in Greenland in 2014.

OBJECTIVES: The objective of this study was to predict the prevalence of type 2 diabetes and the associated burden to the health care system in Greenland posed by diabetic complications by 2014. The predictions were based on changes in demographic variables and obesity. STUDY DESIGN: Projection model based on two cross-sectional population surveys from 1993 and 1999. METHODS: The development in BMI was described and projected to 2014 under two assumptions: 1) distribution of BMI is constant from 1999, and 2) the trend in BMI found in the surveys will continue until 2014. The prevalence of type 2 diabetes was predicted under these assumptions and based on the observed association between BMI and type 2 diabetes. The prevalence of complications was estimated using the 2nd assumption, as was the prevalence of hypertension, dyslipidemia, Ischemic Heart Disease (IHD) and stroke in the non-diabetic population in 2014. RESULTS: The prevalence of type 2 diabetes was not predicted to increase by 2014 under the 1st assumption. It was predicted to increase from 11% to 23% for women, but not for men under the 2nd assumption. Approximately half of the cases of cardiovascular disease and cardiovascular risk factors predicted by 2014 were attributable to diabetes. CONCLUSIONS: The prevalence of type 2 diabetes was predicted to increase in Greenland, and the number of complications was predicted to double from 1999 to 2014. Both prophylactic and treatment initiatives are needed to deal with the extra burden posed by type 2 diabetes to the Greenlandic health care system in 2014.

Adult↗

PubMed2005

Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes.

The separate and combined effects of the PPARG Pro(12)Ala polymorphism and the KCNJ11 Glu(23)Lys polymorphisms on risk of type 2 diabetes were investigated in relatively large-scale, case-control studies. Separate effects of the variants were examined among 1187/1461 type 2 diabetic patients and 4791/4986 middle-aged, glucose-tolerant subjects. The combined analysis involved 1164 type 2 diabetic patients and 4733 middle-aged, glucose-tolerant subjects. In the separate analyses, the K allele of the KCNJ11 Glu(23)Lys associated with type 2 diabetes (odds ratio, 1.19; P = 0.0002), whereas the PPARG Pro(12)Ala showed no significant association with type 2 diabetes. The combined analysis indicated that the two polymorphisms acted in an additive manner to increase the risk of type 2 diabetes, and we found no evidence for a synergistic interaction between them. Analysis of a model with equal additive effects of the two variants showed that the odds ratio for type 2 diabetes increased with 1.14/risk allele (P = 0.003). Together, the two polymorphisms conferred a population-attributable risk for type 2 diabetes of 28%. In conclusion, our results showed no evidence of a synergistic interaction between the KCNJ11 Glu(23)Lys and PPARG Pro(12)Ala polymorphisms, but indicated that they may act in an additive manner to increase the risk of type 2 diabetes.

Adult↗

PubMed2005

Early childhood risk factors associated with type 1 diabetes--is gender important?

BACKGROUND: The incidence of childhood diabetes is increasing in Denmark as in the rest of the world. The aim of this investigation was to study intrauterine and early childhood risk factors for insulin dependent diabetes mellitus, and to evaluate gender differences in the effect of these. METHODS/MATERIAL: A number of 602 diabetic cases aged 0-14 years diagnosed 1996-1999 were identified from the Danish register of childhood diabetes. A total of 1490 non-diabetic healthy children matched by gender and date of birth were randomly selected from the Danish population register. In addition a combination of national register data and questionnaire data was used. RESULTS: High parental age, neonatal infections and pre-eclampsia were associated with type 1 diabetes in boys, whereas being preterm was associated with an increased risk in girls. An increased risk was associated with a family history of diabetes and amniocentesis, while a decreased risk was associated with increasing birth order and maternal smoking. In a multiple logistic regression analysis, the following risk factors were significantly associated with case-control status: maternal smoking (OR: 0.6(0.4-0.9)), neonatal infection in boys (OR: 5.5(1.4-21.8)), neonatal infection in girls (OR: 0.6(0.1-3.0)), amniocentesis (OR: 1.6(1.0-2.6)), preschool siblings (OR: 0.8(0.6-1.0)), introduction of cow's milk after the age of 3 months (OR: 0.7(0.4-0.9)) and a 1st degree family member with diabetes (OR: 9.1(95% CI:5.2-16)). CONCLUSION: The study showed associations between several risk factors and childhood diabetes, for some risk factors the odds ratio in boys were different from the odds ratio in girls.

Adolescent↗

PubMed2005

Incidence trends of adenocarcinoma of the cervix in 13 European countries.

Rapid increases in cervical adenocarcinoma incidence have been observed in Western countries in recent decades. Postulated explanations include an increasing specificity of subtype-the capability to diagnose the disease, an inability of cytologic screening to reduce adenocarcinoma, and heterogeneity in cofactors related to persistent human papillomavirus infection. This study examines the possible contribution of these factors in relation with trends observed in Europe. Age-period-cohort models were fitted to cervical adenocarcinoma incidence trends in women ages <75 in 13 European countries. Age-adjusted adenocarcinoma incidence rates increased throughout Europe, the rate of increase ranging from around 0.5% per annum in Denmark, Sweden, and Switzerland to >/=3% in Finland, Slovakia, and Slovenia. The increases first affected generations born in the early 1930s through the mid-1940s, with risk invariably higher in women born in the mid-1960s relative to those born 20 years earlier. The magnitude of this risk ratio varied considerably from around 7 in Slovenia to almost unity in France. Declines in period-specific risk were observed in United Kingdom, Denmark, and Sweden, primarily among women ages >30. Whereas increasing specificity of subtype with time may be responsible for some of the increases in several countries, the changing distribution and prevalence of persistent infection with high-risk human papillomavirus types, alongside an inability to detect cervical adenocarcinoma within screening programs, would accord with the temporal profile observed in Europe. The homogeneity of trends in adenocarcinoma and squamous cell carcinoma in birth cohort is consistent with the notion that they share a similar etiology irrespective of the differential capability of screen detection. Screening may have had at least some impact in reducing cervical adenocarcinoma incidence in several countries during the 1990s.

Adenocarcinoma↗

PubMed2005

A prevalent amino acid polymorphism at codon 98 (Ala98Val) of the hepatocyte nuclear factor-1alpha is associated with maturity-onset diabetes of the young and younger age at onset of type 2 diabetes in Asian Indians.

OBJECTIVE: Among Europeans, mutations in the hepatocyte nuclear factor-1alpha (HNF1alpha) gene are associated with the most common form of maturity-onset diabetes of the young (MODY)3. In Asian Indians, type 2 diabetes occurs earlier and often overlaps with MODY, but the genetics of the latter are unknown. The aim of this study was to estimate the prevalence of Ala98Val polymorphism of the HNF1alpha gene in different types of diabetes in Asian Indians. RESEARCH DESIGN AND METHODS: Genotyping of Ala98Val was done by the PCR-restriction fragment-length polymorphism method in the following groups: 1) MODY, defined as non-insulin-dependent diabetes (age at onset <25 years) and vertical transmission of diabetes through at least three generations (n = 122); 2) very-early-onset type 2 diabetes (age at onset <25 years) without family history (n = 23); 3) early-onset type 2 diabetes (age at onset between 26 and 40 years, n = 171); 4) late-onset type 2 diabetes (age at onset >40 years, n = 133); 5) type 1 diabetes (n = 150); and 6) normal glucose tolerance (n = 130). The frequency of the Val genotypes was compared in the diabetic and control groups. RESULTS: The frequency of the Val allele was significantly higher in MODY patients (P = 0.0013) compared with control groups. Furthermore, in the total group of patients with type 2-like diabetes (groups 1-4), the Val allele was associated with an earlier diagnosis of diabetes (P = 0.0002). CONCLUSIONS: Among Asian Indians, the Ala98Val polymorphism of HNF1alpha gene is associated with MODY and with earlier age at onset of type 2 diabetes.

Adolescent↗

PubMed2005

Dietary glycemic index, glycemic load, fiber, simple sugars, and insulin resistance: the Inter99 study.

OBJECTIVE: To examine the relationship between daily glycemic index, daily glycemic load, simple sugars, dietary fiber, and the prevalence of a measure of insulin resistance in 30- to 60-year-old nondiabetic Danish men and women. RESEARCH DESIGN AND METHODS: The Inter99 study is a nonpharmacological intervention study. We used baseline data and examined cross-sectional associations between carbohydrate-related dietary factors and an estimate of insulin resistance in 5,675 subjects at 30-60 years. The dietary intake was estimated from a self-administered food frequency questionnaire, and insulin resistance was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). Multiple regressions were performed with HOMA-IR as the dependent variable and carbohydrate-related factors as explanatory variables. All models were adjusted for age, sex, smoking, physical activity, total energy intake, BMI, and waist circumference. RESULTS: Intake of lactose was positively associated with HOMA-IR (P < 0.0001), whereas daily glycemic load and intake of glucose, fructose, dietary fiber, total carbohydrate, fruit, and vegetables were inversely associated with HOMA-IR (P < 0.05). Intake of dietary fiber explained the associations with daily glycemic load and total carbohydrate and attenuated the association with fruit and vegetables. No significant associations were observed for daily glycemic index or sucrose. CONCLUSIONS: Habitual intake of diets with a high glycemic index and high glycemic load or diets with a high content of total carbohydrate including simple sugars was not associated with the probability of having insulin resistance. Furthermore, intake of dietary fiber was inversely associated with the probability of having insulin resistance.

Adult↗

PubMed2004

Plasma GLP-2 levels and intestinal markers in the juvenile pig during intestinal adaptation: effects of different diet regimens.

Adaptation of the residual small bowel following resection is dependent on luminal and humoral factors. We aimed to establish if circulating levels of glucagon-like peptide (GLP-2) change under different dietary regimens following resection and to determine if there is a relationship between plasma GLP-2 levels and markers of intestinal adaptation. Four-week-old piglets underwent a 75% proximal small bowel resection (n = 31) or transection (n = 14). Postoperatively they received either pig chow (n = 14), nonpolymeric (elemental) infant formula (n = 7), or polymeric infant formula alone (n = 8) or supplemented either with fiber (n = 6) or with bovine colostrum protein concentrate (CPC; n = 10) for 8 weeks until sacrifice. Plasma GLP-2 levels were measured at weeks 0, 2, 4, and 8 postoperatively. In addition, end-stage parameters were studied at week 8 including weight gain, ileal villus height, crypt depth, and disaccharidase levels. Plasma GLP-2 levels were higher in resected animals compared to transected animals fed the same diet. Plasma GLP-2 levels were significantly increased in the colostrum protein isolate-supplemented animals following resection compared to all other diet groups. The increase in plasma GLP-2 (pM) was greatest in the first 2 weeks postresection (week 0, 15.5; week 2, 30.9), followed by a plateau at weeks 2 to 4 and a decrease in GLP-2 levels from week 4 to week 8. At week 8, no relationships were found between the plasma GLP-2 levels and the measurements of weight gain, villus height, lactase, sucrase, maltase, crypt depth, or villus/crypt ratio. Plasma GLP-2 levels increase in the first weeks following massive small intestinal resection. The increase in plasma GLP-2 levels was enhanced by supplementation of the diet with CPC. The changes in GLP-2 levels observed in this study may suggest that GLP-2 plays a role in the adaptive response in the intestine following resection in this preclinical model.

Adaptation, Physiological↗

PubMed2004

Comparing and predicting between several methods of measurement.

In studies designed to compare different methods of measurement where more than two methods are compared or replicate measurements by each method are available, standard statistical approaches such as computation of limits of agreement are not directly applicable. A model is presented for comparing several methods of measurement in the situation where replicate measurements by each method are available. Measurements are viewed as classified by method, subject and replicate. Models assuming exchangeable as well as non-exchangeable replicates are considered. A fitting algorithm is presented that allows the estimation of linear relationships between methods as well as relevant variance components. The algorithm only uses methods already implemented in most statistical software.

Algorithms↗

PubMed2004

Improved survival in patients obtaining remission of nephrotic range albuminuria in diabetic nephropathy.

BACKGROUND: The level of albuminuria is related to progression of diabetic nephropathy, and patients with nephrotic range albuminuria have advanced renal structural changes and the fastest decline in glomerular filtration rate (GFR). We have previously demonstrated that the rate of decline in GFR is diminished in patients obtaining remission of nephrotic range albuminuria, but information is scarce concerning the impact of remission of nephrotic range albuminuria on the long-term prognosis. METHODS: At the Steno Diabetes Center, we performed a prospective cohort study of all type 1 diabetic patients with nephrotic range albuminuria (N= 125), who had annual measurement of GFR [(51)chromium-ethylenediaminetetraacetic acid ((51)Cr-EDTA) plasma clearance] carried out for at least 3 years. Patients were followed from onset of nephrotic range albuminuria until death or the end of year 2003. Nephrotic range albuminuria was defined as persistent albuminuria above 2.5 g/24 hours, remission of nephrotic range albuminuria was defined as sustained albuminuria <0.6 g/24 hours for at least 1 year. RESULTS: Nephrotic range albuminuria occurred in 90 men and 35 women, age [mean (SD)] 34 (8) years, duration of diabetes 22 (8) years, and follow-up time from onset of nephrotic range albuminuria [median (range)] 12.4 (3.0 to 24.9) years. Remission was induced in 32 patients (26%), 25 predominantly treated with angiotensin-converting enzyme (ACE) inhibitors, seven with non-ACE inhibitors. The remission lasted 5.5 (1.0 to 22.4) years. At the end of follow-up, 25% in the remission group and 74% in the no remission group had reached the composite end point of end-stage renal disease (ESRD) (dialysis, transplantation) or death. A Cox proportional hazard regression analysis with gender and age as fixed covariates and remission as time-dependent covariate revealed that obtaining remission was associated with a lower risk of dialysis, transplantation, or death, relative risk (95% CI) 0.28 (0.13 to 0.59), P= 0.001, whereas older age at onset of nephrotic range albuminuria (per 10-year increase) was associated with higher risk of reaching the end point, 1.42 (1.08 to 1.87), P= 0.01. CONCLUSION: Our prospective study suggests that remission of nephrotic range albuminuria in type 1 diabetic patients, induced by aggressive antihypertensive treatment with and without ACE inhibitors, is associated with a slower progression in diabetic nephropathy and a substantially improved survival.

Adult↗

PubMed2004

A Danish diabetes risk score for targeted screening: the Inter99 study.

OBJECTIVE: To develop a simple self-administered questionnaire identifying individuals with undiagnosed diabetes with a sensitivity of 75% and minimizing the high-risk group needing subsequent testing. RESEARCH DESIGN AND METHODS: A population-based sample (Inter99 study) of 6,784 individuals aged 30-60 years completed a questionnaire on diabetes-related symptoms and risk factors. The participants underwent an oral glucose tolerance test. The risk score was derived from the first half and validated on the second half of the study population. External validation was performed based on the Danish Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care (ADDITION) pilot study. The risk score was developed by stepwise backward multiple logistic regression. RESULTS: The final risk score included age, sex, BMI, known hypertension, physical activity at leisure time, and family history of diabetes, items independently and significantly (P<0.05) associated with the presence of previously undiagnosed diabetes. The area under the receiver operating curve was 0.804 (95% CI 0.765-0.838) for the first half of the Inter99 population, 0.761 (0.720-0.803) for the second half of the Inter99 population, and 0.803 (0.721-0.876) for the ADDITION pilot study. The sensitivity, specificity, and percentage that needed subsequent testing were 76, 72, and 29%, respectively. The false-negative individuals in the risk score had a lower absolute risk of ischemic heart disease compared with the true-positive individuals (11.3 vs. 20.4%; P<0.0001). CONCLUSIONS: We developed a questionnaire to be used in a stepwise screening strategy for type 2 diabetes, decreasing the numbers of subsequent tests and thereby possibly minimizing the economical and personal costs of the screening strategy.

Adult↗

PubMed2003

Genetic variation in the Renin-Angiotensin system and progression of diabetic nephropathy.

The impact of polymorphisms in the genes coding for angiotensinogen (M235T), ACE (ID), and angiotensin II type 1 receptor (A(1166)-->C) on decline in GFR and doubling of s-creatinine or development of ESRD in patients with type 1 diabetes and diabetic nephropathy (DN) was tested. From 1985, all patients (n = 169) who had established diabetic nephropathy and were treated with angiotensin-converting enzyme inhibition (ACE-I) were identified consecutively at Steno Diabetes Center. Patients were followed for a median of 6 yr (range, 3 to 15 yr), with nine (range, three to 29) measurements of GFR ((51)Cr-EDTA). In a Cox proportional hazards model corrected for other risk factors, the D allele (ACE/ID) was associated with time to doubling of s-creatinine/ESRD (rate ratio, 1.81 per allele; 95% confidence interval, 1.09 to 3.03; P = 0.02). A new interaction hypothesis was generated demonstrating that the following variables were associated with accelerated decline in GFR: albuminuria (estimate, 2.12 ml/min per yr per 10-fold increase in albuminuria; P < 0.001), mean BP (estimate, 0.88 ml/min per yr per 10 mmHg; P = 0.02), hemoglobin A(1c) (estimate, 0.54 min/min per yr per 1%; P = 0.02), and number of M (M235T)/D (ID)/A (A(1166)-->C) alleles (estimate, 0.45 ml/min per yr per allele; P = 0.049). Number of M/D/A alleles also influenced time to doubling of s-creatinine or ESRD. In this study of patients with type 1 diabetes, the D allele of the ACE/ID polymorphism in addition to nongenetic risk factors independently accelerated progression of DN during ACE-I. Interaction between polymorphisms in the renin-angiotensin system also influenced the loss of kidney function. This new genetic interaction model needs to be confirmed in future studies.

Adult↗

PubMed2003

The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes.

The E23K polymorphism of the pancreatic beta-cell ATP-sensitive K(+) (K(ATP)) channel subunit Kir6.2 (KCNJ11) is associated with type 2 diabetes in whites, and a recent in vitro study of the E23K variant suggests that the association to diabetes might be explained by a slight inhibition of serum insulin release. In a study comprising 519 unrelated glucose-tolerant subjects, we addressed the question as to whether the E23K variant was related to reduced serum insulin release during an oral glucose tolerance test (OGTT). Furthermore, the polymorphism was examined in a case-control study comprising 803 type 2 diabetic patients and 862 glucose-tolerant control subjects. The E23K variant was associated with significant reductions in the insulinogenic index (P = 0.022) and serum insulin levels under the response curve during an OGTT (0-120 min) (P = 0.014) as well as with an increase in BMI (P = 0.013). In the present study, the association of the E23K polymorphism with type 2 diabetes was not significant (P = 0.26). However, the K23K genotype significantly associated with type 2 diabetes in a meta-analysis of white case and control subjects (n = 2,824, odds ratio [OR] 1.49, P = 0.00022). In conclusion, the widespread E23K polymorphism may have a diabetogenic effect by impairing glucose-induced insulin release and increasing BMI.

Amino Acid Substitution↗

PubMed2003

Optimal dose of candesartan for renoprotection in type 2 diabetic patients with nephropathy: a double-blind randomized cross-over study.

OBJECTIVE: We evaluated the optimal dose of the angiotensin II receptor antagonist candesartan cilexetil for renoprotection as reflected by short-term changes in albuminuria in hypertensive type 2 diabetic patients with nephropathy. RESEARCH DESIGN AND METHODS: A total of 23 hypertensive patients with type 2 diabetes and nephropathy were enrolled in this double-blind randomized cross-over trial with four treatment periods, each lasting 2 months. Each patient received placebo and candesartan: 8, 16, and 32 mg daily in random order. Antihypertensive medication was discontinued before enrollment, except for long-acting furosemide, which all patients received throughout the study in median (range) doses of 40 (30-160) mg daily. End points were albuminuria (turbidimetry), 24-h blood pressure (BP) (Takeda-TM2420), and glomerular filtration rate (GFR) (51Cr-labeled EDTA plasma clearance technique). RESULTS: Values obtained during placebo treatment: albuminuria [geometric mean (95% CI)] 700 (486-1,007) mg/24-h, 24-h BP (mean +/- SE) 147 +/- 4/78 +/- 2 mmHg, and GFR 84 +/- 6 ml/min/1.73 m2. All three doses of candesartan significantly reduced albuminuria and 24-h BP compared with placebo. Mean (95% CI) reductions in albuminuria were 33% (21-43), 59% (52-65), and 52% (44-59) with increasing doses of candesartan. Albuminuria was reduced significantly more by the two highest doses than by the lowest dose (P < 0.01); 24-h systolic BP was reduced by 9 (2-16), 9 (2-16), and 13 (6-20) mmHg and 24-h diastolic BP was reduced by 5 (2-8), 4 (1-7), and 6 (3-9) mmHg with increasing doses of candesartan. There were no significant differences in the reductions in BP between the three doses. GFR was decreased by approximately 6 ml/min/1.73 m2 by all three doses of candesartan (P < 0.05 versus placebo). CONCLUSIONS: The optimal dose of candesartan is 16 mg daily for renoprotection, as reflected by short-term reduction in albuminuria, in hypertensive type 2 diabetic patients with nephropathy.

Aged↗

PubMed2002

The fasting plasma glucose cut-point predicting a diabetic 2-h OGTT glucose level depends on the phenotype.

To assess the use of fasting plasma glucose (FPG) alone for the screening of diabetes as defined by a 2-h plasma glucose (2-h PG) > or =11.1 mmol/l following a 75-g oral glucose tolerance test, we collated the results from 17512 subjects aged 30-89 years without a previous history of diabetes from 12 general population-based Asian studies. The performance of FPG corresponding to the 2-h PG > or =11.1 mmol/l was characterized. The prevalence of diabetes was 4.0% by the FPG criteria only and 6.0% by the 2-h PG criteria only. The FPG value of 7.0 mmol/l gave a sensitivity for diabetes as defined by a 2-h PG > or =11.1 mmol/l of 46% and specificity of 99%. The FPG associated with a 2-h PG > or =11.1 mmol/l with optimal sensitivity and specificity was 5.8 mmol/l (sensitivity 79%, specificity 85%). The optimal FPG cut-point was affected by gender, age, body mass index and the presence of hypertension, and the resulting sensitivity and specificity corresponding to each optimal cut-point changed. The FPG was a specific but insensitive screening test for diabetes defined by 2-h PG > or =11.1 mmol/l. There seems to be ethnic differences with respect to optimal FPG cut-point, and different screening strategies may be necessary in different parts of the world.

Adult↗

PubMed2002

Increased risk of childhood type 1 diabetes in children born after 1985.

OBJECTIVE: The incidence rate of childhood type 1 diabetes is thought to be increasing; however, Danish studies have not confirmed this. Using a national diabetes register initiated in 1996 and two previous regional incidence studies, we studied the age-specific incidence of type 1 diabetes over 30 years. Here, we describe the incidence rates of type 1 diabetes in Danish children from 1996 to 2000 and evaluate trends in age-specific incidence rates from 1970 to 2000. RESEARCH DESIGN AND METHODS: A nationwide registration of all newly diagnosed cases of type 1 diabetes among children under the age of 15 years was established in Denmark in 1996. Incidence rates of type 1 diabetes in Denmark were obtained from this register. Age-specific incidence rates were compared with data collected from 1970 to 1976 and from 1980 to 1984, both population-based studies using existing national routine registration of hospitalizations within the survey areas. Population data were obtained from Statistics Denmark. RESULTS: During the study period, 1,421 Danish children developed type 1 diabetes before the age of 15 years. The incidence rates by age-groups were: 12.7, 19.4, and 26.3 for the 0-4, 5-9, and 10-14 years age-groups, respectively, and 19.5 for the 0-14 years age-group per 100,000 in the period 1996-2000. An age-period-cohort analysis showed a modest drift effect (yearly increase) of 1.2% (0.7-1.8) from 1970 to 2000, and a significant birth cohort effect with an increased risk for children born after 1985 was observed. CONCLUSIONS: The incidence rate of type 1 diabetes is rising in children living in Denmark. The steep increase in the youngest age-group was explained by the increased risk for cohorts born at the beginning of the 1980s.

Adolescent↗

PubMed2002

IA-2 antibody-negative status predicts remission and recovery of C-peptide levels in type 1 diabetic patients treated with cyclosporin.

OBJECTIVE: The use of cyclosporin in recent-onset type 1 diabetes has demonstrated the potential for immune intervention in the treatment and prevention of the disease. However, a proportion of patients failed to respond to cyclosporin treatment. Indicators of resistance to immune intervention would be valuable for the most effective use of such therapies in disease prevention. The aim of this study was to determine whether presence of IA-2 antibodies is such a marker. RESEARCH DESIGN AND METHODS: IA-2 antibodies were determined by radioligand binding assay in sera from patients recruited into the Canadian-European cyclosporin trial. Insulin dose requirements and glucagon-stimulated C-peptide secretion were analyzed in patients grouped according to IA-2 antibody status at entry. RESULTS: Cyclosporin treatment had no significant effect on frequency of IA-2 antibodies during the 1 year of treatment. Cyclosporin caused significant reduction in insulin requirements and significant increases in C-peptide secretion mainly in patients negative for IA-2 antibodies. Analysis of GAD antibodies in combination with antibodies to IA-2 indicated that the group most resistant to cyclosporin were IA-2 antibody positive, GAD antibody negative. CONCLUSIONS: The results demonstrate that IA-2 antibody analysis is valuable in identifying individuals for whom immunosuppressive treatment would be most effective.

Adult↗