C. Forsblom - Profile on Academia.edu (original) (raw)

Papers by C. Forsblom

The low-expression variant of FABP4 is associated with cardiovascular disease in type 1 diabetes

Atherosclerosis

Acta Diabetologica

Aims Not much is known about adherence to special diets in type 1 diabetes, characteristics of in... more Aims Not much is known about adherence to special diets in type 1 diabetes, characteristics of individuals with special diets, and whether such practices should raise concerns with respect to meeting the dietary recommendations. In this study, we assessed the frequencies of adherence to special diets, in a population of individuals with type 1 diabetes, and investigated the association between special diet adherence and dietary intake, measured as dietary patterns and nutrient intakes. Methods During the Finnish Diabetic Nephropathy Study visit, participants with type 1 diabetes (n = 1429) were instructed to complete a diet questionnaire inquiring about the adherence to special diets. The participants also completed a food record, from which energy and nutrient intakes were calculated. Results In all, 36.6% participants reported adhering to some special diet. Most commonly reported special diets were lactose-free (17.1%), protein restriction (10.0%), vegetarian (7.0%), and gluten-free (5.6%) diet. Special diet adherents were more frequently women, older, had longer diabetes duration, and more frequently had various diabetes complications. Mean carbohydrate intakes were close to the lower levels of the recommendation in all diet groups, which was reflected in low mean fibre intakes but high frequencies of meeting the sucrose recommendations. The recommendation for saturated fatty acid intake was frequently unmet, with the highest frequencies observed in vegetarians. Of the micronutrients, vitamin D, folate, and iron recommendations were most frequently unmet, with some differences between the diet groups. Conclusions Special diets are frequently followed by individuals with type 1 diabetes. The adherents are more frequently women, and have longer diabetes duration and more diabetes complications. Achieving the dietary recommendations differed between diets, and depended on the nutrient in question. Overall, intakes of fibre, vitamin D, folate, and iron fell short of the recommendations. Managed by Massimo Federici.

YI-821 Cardiovascular Risk Factors in Type 1 Diabetes: A Metabonomic Study by 1H NMR Spectroscopy of Serum

Atherosclerosis Supplements, 2007

Journal of Diabetes Research, 2015

Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM), leads to c... more Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM), leads to chronic kidney disease (CKD), and, ultimately, is the main cause for end-stage kidney disease (ESKD). Beyond urinary albumin, no reliable biomarkers are available for accurate early diagnostics. Urinary extracellular vesicles (UEVs) have recently emerged as an interesting source of diagnostic and prognostic disease biomarkers. Here we used a protease and respective protease inhibitor array to profile urines of type 1 diabetes patients at different stages of kidney involvement. Urine samples were divided into groups based on the level of albuminuria and UEVs isolated by hydrostatic dialysis and screened for relative changes of 34 different proteases and 32 protease inhibitors, respectively. Interestingly, myeloblastin and its natural inhibitor elafin showed an increase in the normo- and microalbuminuric groups. Similarly, a characteristic pattern was observed in the array of protease inhib...

Diabetologia, 2003

The incidence of Type 1 diabetes has increased 2.5 times during the time period from 1966 to 2000... more The incidence of Type 1 diabetes has increased 2.5 times during the time period from 1966 to 2000 in Finland-a general trend seen in almost all developed countries that can only be explained by environmental factors. The aim of this study was to test the possible effect of a changing environment on distribution of genotypes associated with disease susceptibility. HLA DRB1-DQA1-DQB1 genes and two diabetes-associated polymorphisms at IDDM2 and IDDM12 were analyzed. The frequencies of genotypes were compared between cases diagnosed with childhood-onset Type 1 diabetes during the period of 1939-1965 (n=367) and those diagnosed between 1990 and 2001 (n=736). Chi-square statistics or the Fisher's Exact test were used for the comparison of frequencies of analyzed haplotypes and genotypes in the two groups. The frequencies of (DR3) -DQA1*05-DQB1*02 and (DR4) -DQB1*0302 risk haplotypes and the high risk (DR3) -DQA1*05-DQB1*02/DRB1*0401-DQB1*0302 genotype were higher while proportion of p...

Hepatocyte nuclear factor-1 beta (MODY5) gene mutations in Scandinavian families with early-onset diabetes or kidney disease or both

Diabetologia, 2000

Journal of Breath Research, 2013

Ammonia concentrations in exhaled breath (eNH 3) and skin gas of 20 healthy subjects were measure... more Ammonia concentrations in exhaled breath (eNH 3) and skin gas of 20 healthy subjects were measured on-line with a commercial cavity ring-down spectrometer and compared to saliva pH and plasma ammonium ion (NH + 4), urea and creatinine concentrations. Special attention was given to mouth, nose and skin sampling procedures and the accurate quantification of ammonia in humid gas samples. The obtained median concentrations were 688 parts per billion by volume (ppbv) for mouth-eNH 3 , 34 ppbv for nose-eNH 3 , and 21 ppbv for both mouth-and nose-eNH 3 after an acidic mouth wash (MW). The median ammonia emission rate from the lower forearm was 0.3 ng cm −2 minute −1. Statistically significant (p<0.05) correlations between the breath, skin and plasma ammonia/ammonium concentrations were not found. However, mouth-eNH 3 strongly (p<0.001) correlated with saliva pH. This dependence was also observed in detailed measurements of the diurnal variation and the response of eNH 3 to the acidic MW. It is concluded that eNH 3 as such does not reflect plasma but saliva and airway mucus NH + 4 concentrations and is affected by saliva and airway mucus pH. After normalization with saliva pH using the Henderson-Hasselbalch equation, mouth-eNH 3 correlated with plasma NH + 4 , which points to saliva and plasma NH + 4 being linked via hydrolysis of salivary urea.

Proton NMR metabonomics of type 1 diabetes reveals multivariate biochemical characteristics of diabetic complications

Glucose-Metabolism in Identical-Twins

Kidney International, 2006

Diabetic nephropathy shows a higher incidence in male subjects, which may in part be owing to gen... more Diabetic nephropathy shows a higher incidence in male subjects, which may in part be owing to genetic factors. The angiotensin II type 2 receptor (AT2), present in the renal glomerulus, may oppose the deleterious effects of the type I receptor (AT1) through vasodilatation and growth inhibition. We determined whether the functional intronic G1675A or A1818T polymorphism of the X-chromosomal AT2 gene is associated with blood pressure levels or with kidney function. We genotyped 996 (538 female/458 male subjects) Finnish patients with type I diabetes from the FinnDiane-study in a cross-sectional study. DNA samples were amplified using standard polymerase chain reaction protocol and the genotypes were determined by the minisequencing method. Male patients with the AA haplotype had a lower glomerular filtration rate (83732 vs 94734 ml min À1 1.73 m À2 , P ¼ 0.008) and a higher pulse pressure (PP) (62718 vs 57715 mm Hg, P ¼ 0.002; Po0.05 after adjustment for age) than did those with the GT haplotype. No differences between the genotypes or haplotypes and these variables were evident in females. In males, the G1675A was also an independent variable in a linear regression analysis with PP (r 2 ¼ 0.16, coefficient ¼ 3.64, s.e.m. ¼ 1.38, Po0.01) as the dependent variable. These data suggest a gender-specific association between the AT2 gene and kidney function and premature aging of the arterial tree in patients with type I diabetes.

Triglyceride-cholesterol imbalance across lipoprotein subclasses predicts diabetic kidney disease and mortality in type 1 diabetes: the FinnDiane Study

Journal of Internal Medicine, 2013

Circulating cholesterol (C) and triglyceride (TG) levels are associated with vascular injury in t... more Circulating cholesterol (C) and triglyceride (TG) levels are associated with vascular injury in type 1 diabetes (T1DM). Lipoproteins are responsible for transporting lipids, and alterations in their subclass distributions may partly explain the increased mortality in individuals with T1DM. A cohort of 3544 individuals with T1DM was recruited by the nationwide multicentre FinnDiane Study Group. At baseline, six very low-density lipoprotein VLDL, one intermediate-density lipoprotein IDL, three low-density lipoprotein LDL and four higher high-density lipoprotein HDL subclasses were quantified by proton nuclear magnetic resonance spectroscopy. At follow-up, the baseline data were analysed for incident micro- or macroalbuminuria (117 cases in 5.3 years), progression from microalbuminuria (63 cases in 6.1 years), progression from macroalbuminuria (109 cases in 5.9 years) and mortality (385 deaths in 9.4 years). Univariate associations were tested by age-matched cases and controls and multivariate lipoprotein profiles were analysed using the self-organizing map (SOM). TG and C levels in large VLDL were associated with incident albuminuria, TG and C in medium VLDL were associated with progression from microalbuminuria, and TG and C in all VLDL subclasses were associated with mortality. Large HDL-C was inversely associated with mortality. Three extreme phenotypes emerged from SOM analysis: (i) low C (&amp;amp;amp;amp;amp;lt;3% mortality), (ii) low TG/C ratio (6% mortality), and (iii) high TG/C ratio (40% mortality) in all subclasses. TG-C imbalance is a general lipoprotein characteristic in individuals with T1DM and high vascular disease risk.

Journal of Human Hypertension, 2000

Previous studies have suggested that the Trp460 allele of the Gly460Trp polymorphism in the ␣-add... more Previous studies have suggested that the Trp460 allele of the Gly460Trp polymorphism in the ␣-adducin gene is associated with salt sensitivity and primary hypertension. The present study was undertaken to evaluate if the Trp460 allele of this polymorphism is associated with primary hypertension in Scandinavians. To address this issue, 294 patients with primary hypertension and 265 normotensive control subjects from Sweden were examined and genotyped for the Gly460Trp polymorphism using polymerase chain reaction and restriction fragment length polymorphism methods. We then used a population of 80 patients with primary hypertension and 154 normotensive control subjects from Finland to replicate the findings. The frequency of the Trp460 allele was lower in hypertensive patients than in normotensive controls in the Swedish population (17.7% vs 23.0%; P ‫؍‬ 0.03) and in the Finnish population (14.4% vs 19.5%; NS). Therefore we also performed a pooled analysis in

Journal of Clinical Investigation, 1997

Maturity-onset diabetes of the young (MODY) type 3 is a dominantly inherited form of diabetes, wh... more Maturity-onset diabetes of the young (MODY) type 3 is a dominantly inherited form of diabetes, which is often misdiagnosed as non-insulin-dependent diabetes mellitus (NIDDM) or insulin-dependent diabetes mellitus (IDDM). Phenotypic analysis of members from four large Finnish MODY3 kindreds (linked to chromosome 12q with a maximum lod score of 15) revealed a severe impairment in insulin secretion, which was present also in those normoglycemic family members who had inherited the MODY3 gene. In contrast to patients with NIDDM, MODY3 patients did not show any features of the insulin resistance syndrome. They could be discriminated from patients with IDDM by lack of glutamic acid decarboxylase antibodies (GAD-Ab). Taken together with our recent findings of linkage between this region on chromosome 12 and an insulin-deficient form of NIDDM (NIDDM2), the data suggest that mutations at the MODY3/NIDDM2 gene(s) result in a reduced insulin secretory response, that subsequently progresses to diabetes and underlines the importance of subphenotypic classification in studies of diabetes. (

Diabetologia, 2014

Aims/hypothesis An abnormal urinary albumin excretion rate (AER) is often the first clinically de... more Aims/hypothesis An abnormal urinary albumin excretion rate (AER) is often the first clinically detectable manifestation of diabetic nephropathy. Our aim was to estimate the heritability and to detect genetic variation associated with elevated AER in patients with type 1 diabetes. The discovery phase genome-wide association study (GWAS) included 1,925 patients with type 1 diabetes and with data on 24 h AER. AER was analysed as a continuous trait and the analysis was stratified by the use of antihypertensive medication. Signals with a p value <10 -4 were followed up in 3,750 additional patients with type 1 diabetes from seven studies.

Diabetologia, 2007

Aims/hypothesis The slit diaphragm is an adhesion and signalling protein complex linking the inte... more Aims/hypothesis The slit diaphragm is an adhesion and signalling protein complex linking the interdigitating podocyte foot processes in the kidney glomerulus, and mutations in slit diaphragm-associated genes result in severe proteinuria. Here we report a genetic association analysis of four slit diaphragm genes, LRRC7, KIRREL, NPHS2 and ACTN4, in a Finnish diabetic nephropathy cohort. Materials and methods A total of 40 single nucleotide polymorphisms (SNPs) were genotyped in 1103 patients with type 1 diabetes. The patients were classified according to their renal status, and the genotype data were analysed in a cross-sectional case-control setting. To confirm positive associations, four SNPs were genotyped in 1,025 additional patients with type 1 diabetes. Results No associations with diabetic nephropathy were observed for any of the analysed SNPs. The SNPs were not associated with the time from the onset of diabetes to the diagnosis of nephropathy or with glomerular filtration rate or AER as quantitative variables. In a sex-specific sub-analysis, the variants rs979972 and rs749701 in the first intron of ACTN4 were nominally associated with diabetic nephropathy in females, with odds ratios of 1.81 (95% CI 1.18-2.79, p=0.007) and 1.93 (95% CI 1.26-2.96, p=0.003) respectively. Conclusions/interpretation Our study has not found any evidence that common variants in LRRC7, KIRREL, NPHS2 and ACTN4 contribute to susceptibility to diabetic nephropathy in Finnish patients with type 1 diabetes.

Diabetologia, 2009

Aims/hypothesis SMAD proteins are involved in multiple signalling pathways and are key modulators... more Aims/hypothesis SMAD proteins are involved in multiple signalling pathways and are key modulators of gene expression. We hypothesised that genetic variation in selected SMAD genes contributes to susceptibility to diabetic nephropathy. Methods We selected 13 haplotype tag (ht) single nucleotide polymorphisms (SNPs) from 67 variants identified by resequencing the SMAD2 and SMAD3 genes. For SMAD1, SMAD4 and SMAD5 genes, genotype data were downloaded for 217 SNPs from Phase II of the International HapMap project. Of these, 85 SNPs met our inclusion criteria, resulting in the selection of 13 tag SNPs for further investigation. A case-control approach was employed, using 267 nephropathic patients and 442 controls with type 1 diabetes from Ireland. Two further populations (totalling 1,407 patients, 2,238 controls) were genotyped to validate initial findings. Genotyping was conducted using iPLEX, TaqMan and gel electrophoresis. Results The distribution of genotypes was in Hardy-Weinberg equilibrium. Analysis by the χ 2 test of genotype and allele frequencies in patients versus controls in the Irish population (n=709) revealed evidence for the association of one allele at 5% level of significance (rs10515478, p uncorrected =0.006; p corrected =0.04). This finding represents a relatively small difference in allele frequency of 6.4% in the patient group compared with 10.7% in the control group; this difference was not supported in subsequent investigations using DNA from European individuals with similar phenotypic characteristics. Conclusions/interpretation We selected an appropriate subset of variants for the investigation of common genetic risk factors and assessed SMAD1 to SMAD5 genes for association with diabetic nephropathy. We conclude that common polymorphisms in these genes do not strongly influence genetic susceptibility to diabetic nephropathy in white individuals with type 1 diabetes mellitus.

Diabetic Medicine, 2008

Aims Patients with Type 1 diabetes have an increased risk of cardiovascular mortality. Notably, a... more Aims Patients with Type 1 diabetes have an increased risk of cardiovascular mortality. Notably, a prolonged heart rate adjusted QT interval (QTc) is a predictor of sudden cardiovascular death. Therefore, the objectives of this study were to investigate whether acute hyperglycaemia affects the QTc duration and the QTc dispersion in patients with Type 1 diabetes and in healthy volunteers. Methods Acute hyperglycaemia (15 mmol/l) for 120 min was induced in 35 males (22 men with Type 1 diabetes and 13 age-matched non-diabetic volunteers). All participants were non-smokers without any diabetic complications. Electrocardiogram recordings were performed at normoglycaemia and at 0, 60 and 120 min of hyperglycaemia. Results Compared with normoglycaemia, acute hyperglycaemia increased the QTc interval in both patients with Type 1 diabetes (390 ± 6 vs. 415 ± 5 ms, P < 0.001) and in healthy volunteers (378 ± 5 vs. 412 ± 8 ms, P < 0.01). During hyperglycaemia, the QTc dispersion was prolonged in healthy volunteers (36 ± 4 ms vs. 54 ± 7 ms, P < 0.05) but not in patients with Type 1 diabetes (45 ± 3 ms at baseline vs. 48 ± 5 ms, NS). Conclusions Acute hyperglycaemia alters myocardial ventricular repolarization in patients with Type 1 diabetes and in healthy volunteers and might consequently be an additional risk factor for cardiovascular events.

Patients with Type 1 diabetes consuming alcoholic spirits have an increased risk of microvascular complications

Diabetic Medicine, 2014

Our aim was to evaluate the effect of the amount of alcohol consumption and the type of beverage ... more Our aim was to evaluate the effect of the amount of alcohol consumption and the type of beverage on the risk of diabetic nephropathy and severe diabetic retinopathy. The alcohol consumption data were available from 3608 patients with Type 1 diabetes participating in the Finnish Diabetic Nephropathy Study (FinnDiane). We assessed the cross-sectional association between alcohol consumption and diabetic nephropathy as well as retinopathy. Patients were divided into different groups according to the amount of alcohol and the type of beverage they were consuming. In the multivariate analysis, the odds ratio for nephropathy was 1.39 (95% CI 1.05-1.84) for abstainers and 2.44 (95% CI 1.49-3.99) for former users compared with light consumers. The results were similar in retinopathy, with an odds ratio of 1.42 (95% CI 1.11-1.82) for abstainers and 1.73 (95% CI 1.07-2.79) for former users. No difference between light consumers and moderate or heavy consumers was observed. Compared with wine drinkers, men consuming mostly alcoholic spirits had a higher risk of nephropathy with an odds ratio of 2.80 (95% CI 1.15-6.81). In women, there was no difference in the risk of nephropathy between the different beverage types. Alcoholic spirit consumers had a higher risk of retinopathy with an odds ratio of 2.32 (95% CI 1.35-4.00). There was no difference between wine and beer consumers. Alcoholic spirit drinkers carry a higher risk of nephropathy and severe retinopathy compared with wine drinkers. Lifelong abstainers and former users of alcohol have a higher risk of nephropathy and severe retinopathy compared with light consumers.

Diabetes Research and Clinical Practice, 2008

Aims: Evidence suggests that chronic hyperglycaemia predicts not only microvascular disease but a... more Aims: Evidence suggests that chronic hyperglycaemia predicts not only microvascular disease but also macrovascular disease, however it is not known whether it is the glucose variability per se or the total glucose exposure that confers risk. The objective of this study was to investigate whether daily glucose variability influence blood pressure and arterial stiffness, an early sign of macrovascular disease, at baseline and during a hyperglycaemic clamp in patients with type 1 diabetes. Methods: Twenty-two non-smoking male patients with type 1 diabetes without any diabetic complications, participated in the study. The patients were monitored for 72-h using a continuous glucose monitoring system. Before and during a 2-h hyperglycaemic clamp, blood pressure as well as pulse wave analysis and pulse wave velocity (PWV) were performed to assess arterial stiffness. Results: No correlation was observed between mean amplitude of glycaemic excursions (MAGE) and arterial stiffness at baseline. There was a correlation between mean daily glucose and aortic PWV even after adjusting for BMI, HbA 1c , and duration of diabetes in a multiple regression analysis (r = 0.48; P < 0.01). MAGE (r = 0.52; P < 0.01) correlated independently with the change in aortic DBP during the clamp. Conclusions: This study suggests that high mean daily blood glucose but not glucose variability per se is associated with arterial stiffness in patients with T1D. Daily glucose variability is positively associated with the change in central blood pressure during a hyperglycaemic clamp.

Diabetes Care, 2013

ON BEHALF OF THE FINNDIANE STUDY GROUP* OBJECTIVEdDiabetic nephropathy (DN) has mainly been consi... more ON BEHALF OF THE FINNDIANE STUDY GROUP* OBJECTIVEdDiabetic nephropathy (DN) has mainly been considered a glomerular disease, although tubular dysfunction may also play a role. This study assessed the predictive value for progression of a tubular marker, urinary liver-type fatty acid-binding protein (L-FABP), at all stages of DN. RESEARCH DESIGN AND METHODSdAt baseline, 1,549 patients with type 1 diabetes had an albumin excretion rate (AER) within normal reference ranges, 334 had microalbuminuria, and 363 had macroalbuminuria. Patients were monitored for a median of 5.8 years (95% CI 5.7-5.9). In addition, 208 nondiabetic subjects were studied. L-FABP was measured by ELISA and normalized with urinary creatinine. Different Cox proportional hazard models for the progression at every stage of DN were used to evaluate the predictive value of L-FABP. The potential benefit of using L-FABP alone or together with AER was assessed by receiver operating characteristic curve analyses. RESULTSdL-FABP was an independent predictor of progression at all stages of DN. As would be expected, receiver operating characteristic curves for the prediction of progression were significantly larger for AER than for L-FABP, except for patients with baseline macroalbuminuria, in whom the areas were similar. Adding L-FABP to AER in the models did not significantly improve risk prediction of progression in favor of the combination of L-FABP plus AER compared with AER alone. CONCLUSIONSdL-FABP is an independent predictor of progression of DN irrespective of disease stage. L-FABP used alone or together with AER may not improve the risk prediction of DN progression in patients with type 1 diabetes, but further studies are needed in this regard.