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

Papers by C. Forsblom

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

Research paper thumbnail of Adherence to special diets and its association with meeting the nutrient recommendations in individuals with type 1 diabetes

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

Atherosclerosis Supplements, 2007

Research paper thumbnail of Proteases and Protease Inhibitors of Urinary Extracellular Vesicles in Diabetic Nephropathy

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...

Research paper thumbnail of Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes--indication of an increased environmental pressure?

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...

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

Research paper thumbnail of Ammonia in breath and emitted from skin

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.

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

Research paper thumbnail of Glucose-Metabolism in Identical-Twins

Research paper thumbnail of The AT2 gene may have a gender-specific effect on kidney function and pulse pressure in type I diabetic patients

Kidney International, 2006

Research paper thumbnail of 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;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.

Research paper thumbnail of Role of the Gly460Trp polymorphism of the α-adducin gene in primary hypertension in Scandinavians

Journal of Human Hypertension, 2000

Research paper thumbnail of Characterization of the MODY3 phenotype. Early-onset diabetes caused by an insulin secretion defect

Journal of Clinical Investigation, 1997

Research paper thumbnail of Genome-wide association study of urinary albumin excretion rate in patients with type 1 diabetes

Research paper thumbnail of Association analysis of podocyte slit diaphragm genes as candidates for diabetic nephropathy

Research paper thumbnail of Investigation of DNA polymorphisms in SMAD genes for genetic predisposition to diabetic nephropathy in patients with type 1 diabetes mellitus

Research paper thumbnail of Acute hyperglycaemia disturbs cardiac repolarization in Type 1 diabetes

Research paper thumbnail of 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.

Research paper thumbnail of Glucose variability, blood pressure and arterial stiffness in type 1 diabetes

Diabetes Research and Clinical Practice, 2008

Research paper thumbnail of Urinary Liver-Type Fatty Acid-Binding Protein and Progression of Diabetic Nephropathy in Type 1 Diabetes

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.

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

Research paper thumbnail of Adherence to special diets and its association with meeting the nutrient recommendations in individuals with type 1 diabetes

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

Atherosclerosis Supplements, 2007

Research paper thumbnail of Proteases and Protease Inhibitors of Urinary Extracellular Vesicles in Diabetic Nephropathy

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...

Research paper thumbnail of Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes--indication of an increased environmental pressure?

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...

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

Research paper thumbnail of Ammonia in breath and emitted from skin

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.

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

Research paper thumbnail of Glucose-Metabolism in Identical-Twins

Research paper thumbnail of The AT2 gene may have a gender-specific effect on kidney function and pulse pressure in type I diabetic patients

Kidney International, 2006

Research paper thumbnail of 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;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.

Research paper thumbnail of Role of the Gly460Trp polymorphism of the α-adducin gene in primary hypertension in Scandinavians

Journal of Human Hypertension, 2000

Research paper thumbnail of Characterization of the MODY3 phenotype. Early-onset diabetes caused by an insulin secretion defect

Journal of Clinical Investigation, 1997

Research paper thumbnail of Genome-wide association study of urinary albumin excretion rate in patients with type 1 diabetes

Research paper thumbnail of Association analysis of podocyte slit diaphragm genes as candidates for diabetic nephropathy

Research paper thumbnail of Investigation of DNA polymorphisms in SMAD genes for genetic predisposition to diabetic nephropathy in patients with type 1 diabetes mellitus

Research paper thumbnail of Acute hyperglycaemia disturbs cardiac repolarization in Type 1 diabetes

Research paper thumbnail of 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.

Research paper thumbnail of Glucose variability, blood pressure and arterial stiffness in type 1 diabetes

Diabetes Research and Clinical Practice, 2008

Research paper thumbnail of Urinary Liver-Type Fatty Acid-Binding Protein and Progression of Diabetic Nephropathy in Type 1 Diabetes

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.