Carol Forsblom
University of Helsinki
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Featured researches published by Carol Forsblom.
Diabetes | 2009
Per-Henrik Groop; Merlin C. Thomas; John Moran; Johan Wadén; Lena M. Thorn; Ville Petteri Mäkinen; Milla Rosengård-Bärlund; Markku Saraheimo; Kustaa Hietala; Outi Heikkilä; Carol Forsblom
OBJECTIVES This study aimed to identify clinical features associated with premature mortality in a large contemporary cohort of adults with type 1 diabetes. RESEARCH DESIGN AND METHODS The Finnish Diabetic Nephropathy (FinnDiane) study is a national multicenter prospective follow-up study of 4,201 adults with type 1 diabetes from 21 university and central hospitals, 33 district hospitals, and 26 primary health care centers across Finland. RESULTS During a median 7 years of follow-up, there were 291 deaths (7%), 3.6-fold (95% CI 3.2–4.0) more than that observed in the age- and sex-matched general population. Excess mortality was only observed in individuals with chronic kidney disease. Individuals with normoalbuminuria showed no excess mortality beyond the general population (standardized mortality ratio [SMR] 0.8, 95% CI 0.5–1.1), independent of the duration of diabetes. The presence of microalbuminuria, macroalbuminuria, and end-stage kidney disease was associated with 2.8, 9.2, and 18.3 times higher SMR, respectively. The increase in mortality across each stage of albuminuria was equivalent to the risk conferred by preexisting macrovascular disease. In addition, the glomerular filtration rate was independently associated with mortality, such that individuals with impaired kidney function, as well as those demonstrating hyperfiltration, had an increased risk of death. CONCLUSIONS An independent graded association was observed between the presence and severity of kidney disease and mortality in a large contemporary cohort of individuals with type 1 diabetes. These findings highlight the clinical and public health importance of chronic kidney disease and its prevention in the management of type 1 diabetes.
Diabetes | 1996
Leif Groop; Carol Forsblom; Mikko Lehtovirta; Tlinamaija Tuomi; Samuel Karanko; Michael Nissén; Björn-Olof Ehrnström; Björn Forsén; Bo Isomaa; Börje Snickars; Marja-Riitta Taskinen
Although a strong genetic susceptibility has been established for NIDDM and a maternal transmission of the disease predominates in some populations, a relationship between parental diabetes status and metabolic abnormalities in nondiabetic offspring has not been shown in humans. To address this question, we studied 2,152 first-degree relatives of patients with NIDDM (FH+) and 528 age- and weight-matched spouses without a family history of NIDDM (FH−) in Western Finland (the Botnia study). A subset of the subjects underwent a euglycemic insulin clamp combined with indirect calorimetry to measure insulin sensitivity and energy expenditure. Despite similar amounts of total body fat, persons with a family history of NIDDM had a greater waist-to-hip ratio (WHR) than spouses without a family history of diabetes (P < 0.003). They also had a decreased resting metabolic rate (P = 0.005), but this difference disappeared when adjusted for the difference in WHR. Insulin-stimulated glucose metabolism (P = 0.002), particularly nonoxidative glucose metabolism (P = 0.009), was reduced in FH+ compared with FH− subjects, and this difference remained after adjustment for WHR. A parental history of NIDDM influenced the insulin response to the oral glucose load, with male offspring of diabetic mothers showing the lowest insulin values (P = 0.011). Moreover, a parental effect was also observed on HDL and HDL2 cholesterol concentrations with female offspring of diabetic mothers showing lower values than female offspring of diabetic fathers (both P < 0.002). We conclude that abdominal obesity, insulin resistance, and decreased resting metabolic rate are characteristic features of first-degree relatives of patients with NIDDM and that the decrease in resting metabolic rate is partially related to the degree of abdominal obesity. A sex-specific paternal effect was observed on insulin and HDL cholesterol concentrations. Therefore, one has to consider the possibility of unprecedented maternal or paternal inheritance of different NIDDM phenotypes.
Diabetologia | 1993
Leif Groop; Agneta Ekstrand; Carol Forsblom; Elisabeth Widen; Per-Henrik Groop; A. M. Teppo; Johan G. Eriksson
SummaryWe examined the impact of hypertension and microalbuminuria on insulin sensitivity in patients with Type 2 (non-insulin-dependent) diabetes mellitus using the euglycaemic insulin clamp technique in 52 Type 2 diabetic patients and in 19 healthy control subjects. Twenty-five diabetic patients had hypertension and 19 had microalbuminuria. Hypertension per se was associated with a 27% reduction in the rate of total glucose metabolism and a 40% reduction in the rate of non-oxidative glucose metabolism compared with normotensive Type 2 diabetic patients (both p<0.001). Glucose metabolism was also impaired in normotensive microalbuminuric patients compared with normotensive normoalbuminuric patients (29.4±2.2 vs 40.5±2.8 μmol · kg lean body mass−1 · min−1; p=0.012), primarily due to a reduction in non-oxidative glucose metabolism (12.7±2.9 vs 21.1±2.6 μmol · kg lean body mass−1 ·min−1; p=0.06). In a factorial ANOVA design, however, only hypertension (p=0.008) and the combination of hypertension and microalbuminuria (p=0.030) were significantly associated with the rate of glucose metabolism. The highest triglyceride and lowest HDL cholesterol concentrations were observed in Type 2 diabetic patients with both hypertension and microalbuminuria. Of note, glucose metabolism was indistinguishable from that in control subjects in Type 2 diabetic patients without hypertension and microalbuminuria (40.5±2.8 vs 44.4±2.8 μmol · kg lean body mass−1 · min−1). We conclude that insulin resistance in Type 2 diabetes is predominantly associated with either hypertension or microalbuminuria or with both.
Diabetologia | 2003
Robert Hermann; Mikael Knip; Riitta Veijola; Olli Simell; A.P. Laine; Hans K. Åkerblom; Per-Henrik Groop; Carol Forsblom; K. Pettersson-Fernholm; Jorma Ilonen
Aims/hypothesisThe 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.MethodsHLA 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 Fishers Exact test were used for the comparison of frequencies of analyzed haplotypes and genotypes in the two groups.ResultsThe 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 patients carrying protective haplotypes—(DR15)-DQB1*0602 and (DR1301)-DQB1*0603—or protective genotypes was lower in patients diagnosed before 1965 as compared to those who developed disease after 1990. No temporal variation was found in the frequencies of genotypes at IDDM2 and IDDM12.Conclusion/interpretationOur data suggest that the need for genetic susceptibility to develop Type 1 diabetes has decreased over time due to an increasing environmental pressure and this results in a higher disease progression rate especially in subjects with protective HLA genotypes.
Diabetes Care | 2011
Mariann I. Lassenius; Kirsi H. Pietiläinen; Kati Kaartinen; Pirkko J. Pussinen; Jaana Syrjänen; Carol Forsblom; Ilkka Pörsti; Aila Rissanen; Jaakko Kaprio; Jukka Mustonen; Per-Henrik Groop; Mika Lehto
OBJECTIVE To investigate whether bacterial lipopolysaccharide (LPS) activity in human serum is associated with the components of the metabolic syndrome (MetS) in type 1 diabetic patients with various degrees of kidney disease and patients with IgA glomerulonephritis (IgAGN). RESEARCH DESIGN AND METHODS Serum LPS activity was determined with the Limulus Amoebocyte Lysate chromogenic end point assay in type 1 diabetic patients with a normal albumin excretion rate (n = 587), microalbuminuria (n = 144), macroalbuminuria (n = 173); patients with IgAGN (n = 98); and in nondiabetic control subjects (n = 345). The relationships of the LPS/HDL ratio and MetS-associated variables were evaluated with Pearson correlation. RESULTS The MetS was more prevalent in type 1 diabetic patients (48%) than in patients with IgAGN (15%). Diabetic patients with macroalbuminuria had a significantly higher serum LPS/HDL ratio than patients with IgAGN. In the normoalbuminuric type 1 diabetic group, patients in the highest LPS/HDL quartile were diagnosed as having the MetS three times more frequently than patients in the lowest quartile (69 vs. 22%; P < 0.001). High LPS activity was associated with higher serum triglyceride concentration, earlier onset of diabetes, increased diastolic blood pressure, and elevated urinary excretion of monocyte chemoattractant protein-1. CONCLUSIONS High serum LPS activity is strongly associated with the components of the MetS. Diabetic patients with kidney disease seem to be more susceptible to metabolic endotoxemia than patients with IgAGN. Bacterial endotoxins may thus play an important role in the development of the metabolic and vascular abnormalities commonly seen in obesity and diabetes-related diseases.
Diabetes Care | 2011
Merlin C. Thomas; John Moran; Carol Forsblom; Valma Harjutsalo; Lena M. Thorn; Aila J. Ahola; Johan Wadén; Nina Tolonen; Markku Saraheimo; Daniel Gordin; Per-Henrik Groop
OBJECTIVE Many guidelines recommend reduced consumption of salt in patients with type 1 diabetes, but it is unclear whether dietary sodium intake is associated with mortality and end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS In a nationwide multicenter study (the FinnDiane Study) between 1998 and 2002, 2,807 enrolled adults with type 1 diabetes without ESRD were prospectively followed. Baseline urinary sodium excretion was estimated on a 24-h urine collection. The predictors of all-cause mortality and ESRD were determined by Cox regression and competing risk modeling, respectively. RESULTS The median follow-up for survival analyses was 10 years, during which 217 deaths were recorded (7.7%). Urinary sodium excretion was nonlinearly associated with all-cause mortality, such that individuals with the highest daily urinary sodium excretion, as well as the lowest excretion, had reduced survival. This association was independent age, sex, duration of diabetes, the presence and severity of chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] and log albumin excretion rate), the presence of established cardiovascular disease, and systolic blood pressure. During follow-up, 126 patients developed ESRD (4.5%). Urinary sodium excretion was inversely associated with the cumulative incidence of ESRD, such that individuals with the lowest sodium excretion had the highest cumulative incidence of ESRD. CONCLUSIONS In patients with type 1 diabetes, sodium was independently associated with all-cause mortality and ESRD. Although we have not demonstrated causality, these findings support the calls for caution before applying salt restriction universally. Clinical trials must be performed in diabetic patients to formally test the utility/risk of sodium restriction in this setting.
Journal of Clinical Investigation | 1997
Markku Lehto; Tiinamaija Tuomi; Melanie M. Mahtani; Elisabeth Widen; Carol Forsblom; L Sarelin; M Gullström; B Isomaa; M Lehtovirta; A Hyrkkö; Timo Kanninen; Marju Orho; S Manley; R C Turner; Thomas Brettin; Andrew Kirby; J Thomas; Geoffrey M. Duyk; Eric S. Lander; M.-R. Taskinen; Leif Groop
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.
Diabetes | 2009
Johan Wadén; Carol Forsblom; Lena M. Thorn; Daniel Gordin; Markku Saraheimo; Per-Henrik Groop
OBJECTIVE Recent data from the Diabetes Control and Complications Trial (DCCT) indicated that A1C variability is associated with the risk of diabetes microvascular complications. However, these results might have been influenced by the interventional study design. Therefore, we investigated the longitudinal associations between A1C variability and diabetes complications in patients with type 1 diabetes in the observational Finnish Diabetic Nephropathy (FinnDiane) Study. RESEARCH DESIGN AND METHODS A total of 2,107 patients in the FinnDiane Study had complete data on renal status and serial measurements of A1C from baseline to follow-up (median 5.7 years), and 1,845 patients had similar data on cardiovascular disease (CVD) events. Intrapersonal SD of serially measured A1C was considered a measure of variability. RESULTS During follow-up, 10.2% progressed to a higher albuminuria level or to end-stage renal disease, whereas 8.6% had a CVD event. The SD of serial A1C was 1.01 versus 0.75 (P < 0.001) for renal status and 0.87 versus 0.79 (P = 0.023) for CVD in progressors versus nonprogressors, respectively. In a Cox regression model, SD of serial A1C was independently associated with progression of renal disease (hazard ratio 1.92 [95% CI 1.49–2.47]) and of a CVD event (1.98 [1.39–2.82]) even when adjusting for mean A1C and traditional risk factors. Interestingly for CVD, mean serial A1C itself was not predictive even though SD of A1C was. CONCLUSIONS In patients with type 1 diabetes, A1C variability was not only predictive of incident microalbuminuria and progression of renal disease but also of incident CVD events.
Molecular Systems Biology | 2008
Ville Petteri Mäkinen; Pasi Soininen; Carol Forsblom; Maija Parkkonen; Petri Ingman; Kimmo Kaski; Per-Henrik Groop; Mika Ala-Korpela
Subtle metabolic changes precede and accompany chronic vascular complications, which are the primary causes of premature death in diabetes. To obtain a multimetabolite characterization of these high‐risk individuals, we measured proton nuclear magnetic resonance (1H NMR) data from the serum of 613 patients with type I diabetes and a diverse spread of complications. We developed a new metabonomics framework to visualize and interpret the data and to link the metabolic profiles to the underlying diagnostic and biochemical variables. Our results indicate complex interactions between diabetic kidney disease, insulin resistance and the metabolic syndrome. We illustrate how a single 1H NMR protocol is able to identify the polydiagnostic metabolite manifold of type I diabetes and how its alterations translate to clinical phenotypes, clustering of micro‐ and macrovascular complications, and mortality during several years of follow‐up. This work demonstrates the diffuse nature of complex vascular diseases and the limitations of single diagnostic biomarkers. However, it also promises cost‐effective solutions through high‐throughput analytics and advanced computational methods, as applied here in a case that is representative of the real clinical situation.
Diabetologia | 1998
B Isomaa; M. Henricsson; Markku Lehto; Carol Forsblom; S. Karanko; Leena Sarelin; M. Häggblom; Leif Groop
Summary MODY3 diabetes, which is caused by a mutation in the hepatocyte nuclear factor-1α gene (HNF-1α) on chromosome 12, represents a relatively common monogenic form of diabetes in Finland. Age at onset of the disease can vary from 10 to 60 years, but little is known about the natural course of the disease, particularly the development of diabetes-related chronic complications. The availability of genetic markers now allows description of the clinical course of the disease. In order to examine the prevalence of chronic diabetic complications in MODY3, we examined 57 carriers with HNF-1α mutations for the presence of micro- and macrovascular complications. Thirty-four percent of the MODY patients had mild and 13 % had severe non-proliferative or proliferative retinopathy; this figure did not differ from the figures in insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) patients matched for duration and glycaemic control but not for age. Neither did the prevalence of microalbuminuria differ between MODY3 and IDDM or NIDDM patients (19 vs 24 and 23 %). Neuropathy was observed with the same frequency as previously reported in IDDM. Hypertension was less frequent in MODY3 and IDDM than in NIDDM (24.5 and 19 vs 53.7 %; p < 0.001). Coronary heart disease was more common in MODY3 than in IDDM (16 vs 4.5 %; p < 0.02) but less common than in the older NIDDM patients (33.3 %; p < 0.02). In a multiple logistic regression analysis, poor glycaemic control was an independent risk factor for retinopathy (p = 0.03), microalbuminuria (p < 0.04) and neuropathy (p = 0.03). In conclusion, microangiopathic complications are observed with the same frequency in patients with MODY3 diabetes as in IDDM and NIDDM and are strongly related to poor glycaemic control. [Diabetologia (1998) 41: 467–473]