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Gisela Dahlquist

Publications and source records attributed to Gisela Dahlquist.

16 recordsLinked to original sources
PubMed2007

A functional polymorphism in the manganese superoxide dismutase gene and diabetic nephropathy.

Oxidative stress has been suggested to contribute to the development of diabetic nephropathy. Manganese superoxide dismutase (MnSOD) protects the cells from oxidative damage by scavenging free radicals. The demand for antioxidants is increased by smoking, which could disturb the balance between antioxidants and radicals. The present study aimed to determine whether a valine/alanine polymorphism in MnSOD (V16A, rs4880), alone or in combination with smoking, can contribute to development of diabetic nephropathy in 1,510 Finnish and Swedish patients with type 1 diabetes. Overt diabetic nephropathy (n = 619) was defined as having an albumin excretion rate (AER) >200 microg/min or renal replacement therapy; incipient diabetic nephropathy was defined as having an AER of 20-200 microg/min (n = 336). The control subjects had diabetes duration of >or=20 years, without albuminuria (AER <20 microg/min) and without antihypertensive treatment (n = 555). In addition to male sex and elevated A1C, smoking was significantly associated with diabetic nephropathy (overt plus incipient), odds ratio (OR) 2.00 (95% CI 1.60-2.50). When controlling for age at onset, diabetes duration, A1C, smoking, and sex, the Val/Val genotype was associated with an increase in risk of diabetic nephropathy (1.32 [1.00-1.74], P = 0.049). When evaluating the combined effect of genotype and smoking, we used logistic regression with stratification according to smoking status and genotype. The high-risk group (ever smoking plus Val/Val genotype) had 2.52 times increased risk of diabetic nephropathy (95% CI 1.73-3.69) compared with the low-risk group, but no departure from additivity was found. Our results indicate that smoking and homozygosity for the MnSOD Val allele is associated with an increased risk of diabetic nephropathy, which supports the hypothesis that oxidative stress contributes to the development of diabetic nephropathy.

Adult↗
PubMed2006

Glu298Asp and NOS4ab polymorphisms in diabetic nephropathy.

BACKGROUND AND AIMS: The risk of diabetic nephropathy (DN) increases with increase in intraglomerular pressure, which may partly be regulated by nitric oxide (NO). NO-production can be affected by polymorphisms in the endothelial NO-synthase gene (NOS3), hyperglycaemia and smoking. We therefore studied association between DN and two polymorphisms in NOS3, Glu298Asp and NOS4ab, in Caucasian type 1 diabetes (T1D) patients. PATIENTS AND METHODS: A total of 1510 Finnish and Swedish T1D patients were included in a cross-sectional case-control study. Incipient DN was defined as an albumin excretion rate (AER) of 20-200 microg/min (n = 336). Overt DN = AER>200 microg/min or renal replacement therapy (n = 619). All patients with DN were considered as cases. The controls were T1D patients with diabetes duration 20 years, AER<20 microg/min and without antihypertensive treatment (n = 555). The genetic markers studied were a 27 bp repeat (NOS4ab) and Glu298Asp (rs1799983). RESULTS: Age at onset of diabetes, male sex, duration of diabetes, HbA1c, blood pressure and smoking were assessed as possible confounders in the logistic regression analysis, which showed that homozygosity for the Glu-allele of the Glu298Asp-polymorphism was independently associated with increased risk of DN (OR = 1.46; 95% CI = 1.12-1.91). The variables smoking (OR = 2.13; 95% CI = 1.63-2.78), male sex (OR = 1.61; 95% CI = 1.23-2.10), HbA1c (OR per % increase above upper limit of the normal reference range = 1.02; 95% CI = 1.02-1.03), systolic (OR = 1.05; 95% CI = 1.04-1.06) and diastolic blood pressure (OR = 1.04; 95% CI = 1.02-1.05) also significantly and independently increased the risk of DN when taking age at diabetes onset and diabetes duration into account. The NOS4 a-allele was not associated with DN. CONCLUSIONS: The Glu/Glu-genotype of the NOS3 Glu298Asp polymorphism may increase the risk of developing DN independently of other known risk factors.

Adult↗
PubMed2006

Fetal and perinatal risk factors for inflammatory bowel disease.

AIM: To study the influence of specific factors and events during pregnancy and the perinatal period on the risk of children developing inflammatory bowel disease. METHODS: Population-based national register study. Linkage between the Swedish Medical Birth Register and the Swedish Hospital Discharge Register during the period 1987 to 2000 identified 455 singleton infants who later developed inflammatory bowel disease. Data for these children were compared with data for all children born in Sweden during the same period. RESULTS: Smoking during early pregnancy reduced the risk of inflammatory bowel disease (odds ratio (OR) 0.71, 95% CI 0.55-0.91). For ulcerative colitis the odds ratio was 0.70 (95% CI 0.56-0.86), and for Crohn's disease 0.73 (95% CI 0.58-0.94). Infections during the neonatal period seemed to increase the risk of inflammatory bowel disease (OR 17.6, 95% CI 3.6-51.6), but the number of observed events was small. The other factors examined did not influence the risk of inflammatory bowel disease. CONCLUSION: Maternal smoking during early pregnancy reduces the risk for the child to be hospitalized with a diagnosis of inflammatory bowel disease. Severe neonatal infections may increase the risk. Thus, some exposures during the fetal and neonatal period seem to affect the risk of inflammatory bowel disease later in life.

Adolescent↗
PubMed2006

Age at onset of childhood-onset type 1 diabetes and the development of end-stage renal disease: a nationwide population-based study.

OBJECTIVE: To analyze the impact of age at onset on the development of end-stage renal disease (ESRD) due to diabetic nephropathy in a nationwide population-based cohort with childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: A record linkage between two nationwide registers, the Swedish Childhood Diabetes Registry, including 12,032 cases with childhood-onset diabetes, and the Swedish Registry for Active Treatment of Uraemia was performed. Log-rank test was used to test differences between cumulative risk curves of developing ESRD due to diabetic nephropathy in three different strata of age at onset (0-4, 5-9, and 10-14 years). RESULTS: At a maximum follow-up of 27 years, 33 patients had developed ESRD due to diabetic nephropathy and all had a diabetes duration >15 years. In total, 4,414 patients had diabetes duration >15 years, and thus the risk in this cohort to develop ESRD was 33 of 4,414 (0.7%). A significant difference in risk of developing ESRD was found between the youngest (0-4 years) and the two older (5-9 and 10-14 years) age-at-onset strata (P = 0.03 and P = 0.001, respectively). A significant difference in the risk of developing ESRD was also found between children with prepubertal (0-4 and 5-9 years, n = 2,424) and pubertal (10-14 years, n = 2000) onset of diabetes (P = 0.002). No patient with onset of diabetes before 5 years of age had developed ESRD. CONCLUSIONS: With a median duration of 21 years in this population-based Swedish cohort with childhood-onset diabetes, <1% of the patients had developed ESRD due to diabetic nephropathy, and a prepubertal onset of diabetes seems to prolong the time to development of ESRD.

Adolescent↗
PubMed2005

Mortality in childhood-onset type 1 diabetes: a population-based study.

OBJECTIVE: To describe the age- and sex-specific mortality in a cohort of young type 1 diabetic patients and to analyze the causes of death with special focus on suicide, accidents, and unexplained deaths. RESEARCH DESIGN AND METHODS: A population-based incident childhood diabetes register, covering onset cases since 1 July 1977, was linked to the Swedish Cause of Death Register up to 31 December 2000. The official Swedish population register was used to calculate age- and sex-standardized mortality rates (SMRs), excluding neonatal deaths. To analyze excess risks for specific diagnoses, case subjects were compared with five nondiabetic control subjects, matched by age, sex, and year of death. Death certificates were collected for all case and control subjects. For case subjects with an unclear diagnosis, hospital records and/or forensic autopsy reports were obtained. RESULTS: Mean age- and sex-SMR was 2.15 (95% CI 1.70-2.68) and tended to be higher among females (2.65 vs. 1.93, P = 0.045). Mean age at death was 15.2 years (range 1.2-27.3) and mean duration 8.2 years (0-20.7). Twenty-three deaths were clearly related to diabetes; 20 died of diabetic ketoacidosis. Only two case subjects died with late diabetes complications (acute coronary infarction). Thirty-three case subjects died with a diagnosis not directly related to diabetes; 7 of them committed suicide, and 14 died from accidents. There was no significant difference in traffic accidents (odds ratio 1.02 [95% CI 0.40-2.37]). Obvious suicide tended to be increased but not statistically significantly so (1.55 [0.54-3.89]). Seventeen diabetic case subjects were found deceased in bed without any cause of death found at forensic autopsy. Only two of the control subjects died of similar unexplained deaths. CONCLUSIONS: In a well-developed health care system, there is still a significant excess mortality in young type 1 diabetic patients. We confirm a very large proportion of unexplained deaths in bed, which should be further studied. There is no clear excess death rate caused by suicide or traffic accidents among young diabetic subjects.

Accidents↗
PubMed2004

Diet, growth, and the risk for type 1 diabetes in childhood: a matched case-referent study.

OBJECTIVE: To study the association between type 1 diabetes risk and previous intake of energy, accounting for body size and previous intake of nutrients and foods, accounting for the energy intake. RESEARCH DESIGN AND METHODS: We conducted an incident population-based case-referent study in Stockholm, Sweden, including 99 of 100 eligible 7- to 14-year-old diabetic children and 180 of 200 age-, sex-, and area-matched referent children identified through the Swedish population register. Average daily energy and nutrient intake 1 year before diabetes diagnosis/interview was estimated using the food frequency questionnaire with assessment of consumed food amounts. Mean SD scores of growth measurements taken during the last 4 years before the diagnosis were used. Odds ratios (ORs) were calculated by conditional logistic regression. RESULTS: Average intake of energy, carbohydrate, fat, and protein was significantly higher among the case subjects as well as mean weight-for-age SD score. Higher energy intake and weight-for-age were both associated with increased diabetes risk after adjustment for each other: OR (95% CI) for medium and high levels of energy intake were 1.33 (0.52-3.42) and 5.23 (1.67-16.38), respectively, and for weight-for-age were 3.20 (1.30-7.88) and 3.09 (1.16-8.22), respectively. High intake of carbohydrates, especially disaccharides and sucrose, increased diabetes risk. CONCLUSIONS: Higher energy intake and larger body size were independently associated with increased diabetes risk. Of the different nutrients, higher intake of carbohydrates, particularly disaccharides and sucrose, increased the risk. Lifestyle habits leading to higher energy intake and more rapid growth in childhood may contribute to the increase of childhood-onset type 1 diabetes by different mechanisms.

Child↗
PubMed2004

Early glycemic control, age at onset, and development of microvascular complications in childhood-onset type 1 diabetes: a population-based study in northern Sweden.

OBJECTIVE: The aim of this work was to study the impact of glycemic control (HbA(1c)) early in disease and age at onset on the occurrence of incipient diabetic nephropathy (MA) and background retinopathy (RP) in childhood-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: All children, diagnosed at 0-14 years in a geographically defined area in northern Sweden between 1981 and 1992, were identified using the Swedish Childhood Diabetes Registry. From 1981, a nationwide childhood diabetes care program was implemented recommending intensified insulin treatment. HbA(1c) and urinary albumin excretion were analyzed, and fundus photography was performed regularly. Retrospective data on all 94 patients were retrieved from medical records and laboratory reports. RESULTS: During the follow-up period, with a mean duration of 12 +/- 4 years (range 5-19), 17 patients (18%) developed MA, 45 patients (48%) developed RP, and 52% had either or both complications. A Cox proportional hazard regression, modeling duration to occurrence of MA or RP, showed that glycemic control (reflected by mean HbA(1c)) during the follow-up was significantly associated with both MA and RP when adjusted for sex, birth weight, age at onset, and tobacco use as potential confounders. Mean HbA(1c) during the first 5 years of diabetes was a near-significant determinant for development of MA (hazard ratio 1.41, P = 0.083) and a significant determinant of RP (1.32, P = 0.036). The age at onset of diabetes significantly influenced the risk of developing RP (1.11, P = 0.021). Thus, in a Kaplan-Meier analysis, onset of diabetes before the age of 5 years, compared with the age-groups 5-11 and >11 years, showed a longer time to occurrence of RP (P = 0.015), but no clear tendency was seen for MA, perhaps due to lower statistical power. CONCLUSIONS: Despite modern insulin treatment, >50% of patients with childhood-onset type 1 diabetes developed detectable diabetes complications after approximately 12 years of diabetes. Inadequate glycemic control, also during the first 5 years of diabetes, seems to accelerate time to occurrence, whereas a young age at onset of diabetes seems to prolong the time to development of microvascular complications.

Adolescent↗
PubMed2002

[A high standard of living can contribute to the increase of childhood diabetes. Rapid growth and weight gain are risk factors].

According to records kept by The Swedish Child Diabetes Register the incidence of childhood diabetes type I before 15 years of age has increased. The increase is most noticeable in children before the age of 5. The genetic basis of this disease is complex and the different risk genes have a low penetrance, thus indicating non-genetic factors to have a great impact. One risk factor for type I diabetes is rapid growth, measured either as weight or as height gain. As a high standard of living favours rapid growth in children this may contribute to the onset of the disease.

Adolescent↗
PubMed2002

Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes.

Age-dependent associations between type 1 diabetes risk genes HLA, INS VNTR, and CTLA-4 and autoantibodies to GAD65 (GADAs), ICA512/IA-2, insulin, and islet cells were determined by logistic regression analysis in 971 incident patients with type 1 diabetes and 702 control subjects aged 0-34 years. GADAs were associated with HLA-DQ2 in young but not in older patients (P = 0.009). Autoantibodies to insulin were negatively associated with age (P < 0.0001) but positively associated with DQ8 (P = 0.03) and with INS VNTR (P = 0.04), supporting possible immune tolerance induction. ICA512/IA-2 were negatively associated with age (P < 0.0001) and with DQ2 (P < 0.0001) but positively associated with DQ8 (P = 0.04). Males were more likely than females to be negative for GADA (P < 0.0001), autoantibodies to islet cells (P = 0.04), and all four autoantibody markers (P = 0.004). The CTLA-4 3' end microsatellite marker was not associated with any of the autoantibodies. We conclude that age and genetic factors such as HLA-DQ and INS VNTR need to be combined with islet autoantibody markers when evaluating the risk for type 1 diabetes development.

Adolescent↗
PubMedDate not supplied

Genetic association analysis of the adiponectin polymorphisms in type 1 diabetes with and without diabetic nephropathy.

OBJECTIVE: Adiponectin [adipocyte C1q and collagen domain containing (ACDC)] is the most abundant adipose-specific protein. It is beneficial in that it improves insulin sensitivity and mitigates vascular damage, in addition to the possibility of it having anti-inflammatory properties. Clinical evidences demonstrate that serum adiponectin concentrations are increased in patients with type 1 diabetes (T1D) as well as in patients with microvascular complications. However, the genetic influence of the ACDC gene in T1D and diabetic microvascular complications is still unclear. The present study aims to evaluate the association of the ACDC genetic variation in T1D and diabetic nephropathy (DN). MATERIALS AND METHODS: Ten single nucleotide polymorphisms (SNPs) of the ACDC gene were genotyped in 432 T1D patients (of which, 196 had DN) and 187 nondiabetic control subjects, who were all Swedish Caucasians, by using dynamic allele specific hybridization. RESULTS: Single-marker association analysis demonstrated that SNPs +45G15G(T/G) and +276(G/T) were strongly associated with T1D [P=.002, OR=1.855 (1.266-2.717) and P=.001, OR=1.694 (1.337-2.147)]. Further analysis for haplotypes of these two SNPs indicated that one of the common haplotype (T_G) was strongly associated with T1D [P<.001, OR=1.769 (1.430-2.188)]. However, there was no significant difference in the allele frequencies of these two SNPs between the groups of T1D patients with nephropathy and the patients without nephropathy. CONCLUSIONS: The present study thus suggests that SNPs +45G15G(T/G) and +276(G/T) in the ACDC gene are associated with T1D but not with DN among Swedish Caucasians.

Adiponectin↗