Papers by Markku Saraheimo
Microcirculation, 2020
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial ... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
Diabetes Care, Aug 1, 2005
PER-HENRIK GROOP, MD, DMSC 1,2 ON BEHALF OF THE FINNDIANE STUDY GROUP OBJECTIVE-The aim of this s... more PER-HENRIK GROOP, MD, DMSC 1,2 ON BEHALF OF THE FINNDIANE STUDY GROUP OBJECTIVE-The aim of this study was to estimate the prevalence of the metabolic syndrome in Finnish type 1 diabetic patients and to assess whether it is associated with diabetic nephropathy or poor glycemic control. RESEARCH DESIGN AND METHODS-In all, 2,415 type 1 diabetic patients (51% men, mean age 37 years, duration of diabetes 22 years) participating in the nationwide, multicenter Finnish Diabetic Nephropathy (FinnDiane) study were included. Metabolic syndrome was defined according to the National Cholesterol Education Program diagnostic criteria. Patients were classified as having normal albumin excretion rate (AER) (n ϭ 1,261), microalbuminuria (n ϭ 326), macroalbuminuria (n ϭ 383), or end-stage renal disease (ESRD) (n ϭ 164). Glycemic control was classified as good (HbA 1c Ͻ7.5%), intermediate (7.5-9.0%), or poor (Ͼ9.0%). Creatinine clearance was estimated with the Cockcroft-Gault formula. RESULTS-The overall prevalence of metabolic syndrome was 38% in men and 40% in women. The prevalence was 28% in those with normal AER, 44% in microalbuminuric patients, 62% in macroalbuminuric patients, and 68% in patients with ESRD (P Ͻ 0.001). Patients with metabolic syndrome had a 3.75-fold odds ratio for diabetic nephropathy (95% CI 2.89-4.85), and all of the separate components of the syndrome were independently associated with diabetic nephropathy. The prevalence of metabolic syndrome was 31% in patients with good glycemic control, 36% in patients with intermediate glycemic control, and 51% in patients with poor glycemic control (P Ͻ 0.001). Similarly, metabolic syndrome increased with worsening creatinine clearance. CONCLUSIONS-The metabolic syndrome is a frequent finding in type 1 diabetes and increases with advanced diabetic nephropathy and worse glycemic control.
Diabetes Care, Mar 10, 2007
Acta Diabetologica, May 22, 2019
Aims Insulin possesses both vasodilatory and sympathomimetic activities. The aim was to examine t... more Aims Insulin possesses both vasodilatory and sympathomimetic activities. The aim was to examine the relationship between changes in insulin exposure and arterial stiffness in type 2 diabetes (T2D). Methods Patients with T2D with (n = 22) or without (n = 24) albuminuria, and non-diabetic controls (n = 25) were randomized to a crossover study having a breakfast with or without pre-meal rapid-acting insulin. Pulse wave velocity (PWV) was measured at 30 min before and at 60-min intervals up to 240 min after the breakfast. Results At baseline, both postprandial aortic (p = 0.022) and brachial (p = 0.011) PWV were higher in individuals with T2D than in healthy controls irrespective of the presence of albuminuria. In patients with albuminuria, weight-adjusted insulin dose correlated inversely with the excursion of the aortic (r = − 0.412, p = 0.006) and brachial (r = − 0.372; p = 0.014) PWV. Similarly, circulating endogenous insulin concentrations correlated inversely with the aortic (r = − 0.347, p = 0.026) and brachial (r = − 0.622, p = <0.001) PWV. No correlations between insulin and PWV were observed in patients without albuminuria or in healthy controls. Conclusions The inverse correlation between insulin and PWV in T2D with albuminuria may reflect a vasorelaxing effect of insulin. Clinical trial registration number The study was registered (clinicaltrials.gov) with the identifier of NCT01159938.
Diabetic Medicine, Nov 29, 2018
What's new? Data on the association between dietary intake and glycaemia in people with Type 1 ... more What's new? Data on the association between dietary intake and glycaemia in people with Type 1 diabetes are mixed and fibre intake is not always accounted for in analyses. In this study, conducted in a large cohort of well-defined individuals with Type 1 diabetes, reported fibre intake was associated with lower mean blood glucose measurements. Reported protein intake, compared with all other macronutrients, was associated with lower glucose variability.
Diabetologia, May 24, 2018
Aims/hypothesis This study aimed to assess the use of ambulatory BP monitoring (ABPM) to identify... more Aims/hypothesis This study aimed to assess the use of ambulatory BP monitoring (ABPM) to identify the presence of masked, nocturnal and white-coat hypertension in individuals with type 1 diabetes, patterns that could not be detected by regular officebased BP monitoring alone. We also analysed associations between BP patterns and arterial stiffness in order to identify individuals at cardiovascular risk. Methods This substudy included 140 individuals with type 1 diabetes from the Helsinki metropolitan area, who attended the Finnish Diabetic Nephropathy Study (FinnDiane) Centre in Helsinki between January 2013 and August 2017. Twenty-four hour ABPM and pulse wave analysis were performed simultaneously using a validated non-invasive brachial oscillometric device (Mobil-O-Graph). Definitions of hypertension were based on the European Society of Hypertension guidelines. Masked hypertension was defined as normal office BP (BP obtained using a standardised automated BP device) but elevated 24 h ABPM, and white-coat hypertension as elevated office BP but normal 24 h ABPM. Results A total of 38% of individuals were normotensive and 33% had sustained hypertension, while 23% had masked and 6% had white-coat hypertension. About half of the cohort had increased absolute levels of night-time BP, half of whom were untreated. In the ambulatory setting, central BP and pulse wave velocity (PWV) were higher in participants with masked hypertension than in those with normotension (p ≤ 0.001). In a multivariable linear regression model adjusted for age, sex, BMI, antihypertensive treatment and eGFR, masked hypertension was independently associated with higher 24 h PWV (β 0.50 [95% CI 0.34, 0.66]), but not with PWV obtained during resting conditions (adjusted β 0.28 [95% CI −0.53, 1.10]), using normotension as the reference group. Conclusions/interpretation ABPM analysis revealed that one-quarter of the participants with type 1 diabetes had masked hypertension; these individuals would not have been detected by office BP alone. Moreover, arterial stiffness was increased in individuals with masked hypertension. These findings support the use of ABPM to identify individuals at risk of cardiovascular disease.
Journal of Clinical & Translational Endocrinology, 2016
We studied the association between fear of hypoglycaemia (FoH) and various diabetes selfmanagemen... more We studied the association between fear of hypoglycaemia (FoH) and various diabetes selfmanagement practices. Methods: Data from 798 individuals with type 1 diabetes participating in the FinnDiane Study were included. Self-reported questionnaires were used to assess FoH and self-management practices (e.g. dietary intake, insulin administration, physical activity). For glycaemic control, we used both the latest HbA1c measurements and the serial HbA1c measurements from the medical files. Factor analysis was used to reveal underlying constructs within the food frequency section of the diet questionnaire. Results: In all, 44% and 63% of men and women reported FoH, respectively. In men, FoH was associated with higher mean serial HbA1c levels, higher number of reported self-monitoring of blood glucose (SMBG), higher carbohydrate intake, and lower scores in the "high-fat" factor. In women, FoH was associated with a higher number of reported SMBGs and higher energy intake. No difference was observed in physical activity and insulin administration. Conclusions: FoH has various implications for the self-management of diabetes. More studies are however needed to assess on one hand the association between FoH and diabetes self-management, and on the other hand, FoH and its long term consequences, such as the emergence of diabetic complications and mortality.
Journal of diabetes mellitus, 2013
Aims: We estimated long-term trends in prescription medication utilization and costs in patients ... more Aims: We estimated long-term trends in prescription medication utilization and costs in patients with type 1 diabetes in two different transplant cohorts (Group 1: transplantation 1986-1999, n = 180; Group 2: transplantation 2000-2008, n = 150). Methods: Data obtained from the Finnish Diabetic Nephropathy Study were linked with the Drug Prescription Register (purchases of medications 1995-2009). Generalized linear mixed models under gamma distribution were used to evaluate the medication costs. Results: The total costs of medication decreased (Group 1 from €11,290 to €8760; Group 2 from €12,800 to €9790) during the follow-up (P < 0.0001). The same trend was observed for immunosuppressive drug costs (P < 0.0001). Although the cost profiles were similar for the groups (P = 0.9), the cost level in Group 2 was higher than in Group 1 (P < 0.0001). In Group 1 the most common immunosuppressive combination was cyclosporine, azathioprine and corticosteroid, while cyclosporine, mycophenolate mofetil (MMF) with/without corticosteroid was the most common in Group 2. The estimated average costs of cyclosporine in combination with MMF were 84% (€4130) higher than with azathioprine. Conclusions: Since diabetes or other drugs had only marginal impact on the total costs, the decreasing trend was mainly due to the costs of immunosuppressants. This finding is consistent with the recent guidelines which recommend reducing doses of immunosuppressants over time to minimize sideeffects. The cost levels differed depending on the combinations of immunosuppressive drugs in use. Those who had MMF in the regimen generated higher costs.
Diabetes Care, 2005
WSTEP . Celem badania by³o oszacowanie czesto¶ci zespo³u metabolicznego w zamieszka³ej w Finlandi... more WSTEP . Celem badania by³o oszacowanie czesto¶ci zespo³u metabolicznego w zamieszka³ej w Finlandii populacji chorych na cukrzyce typu 1 oraz ocena zwi±zku zespo³u metabolicznego z nefropati± cukrzycow± i z³± kontrol± glikemii. MATERIA£ I METODY . Do badania w³±czono ogo³em 2415 chorych na cukrzyce typu 1 (51% stanowili me¼czy¼ni, ¶r. wieku 37 lat, ¶r. czasu trwania cukrzycy 22 lata), ktorzy byli uczestnikami wieloo¶rodkowego badania Finnish Diabetic Nephropathy (FinnDiane) przeprowadzonego w ca³ej Finlandii. Zespo³ metaboliczny zdefiniowano zgodnie z kryteriami diagnostycznymi National Cholesterol Education Program (NCEP). W¶rod chorych wyro?niono grupe z prawid³owym wydalaniem albuminy (AER, albumin excretion rate ) (n = 1261), z mikroalbuminuri± (n = 326), makroalbuminuri± (n = 383) oraz ze schy³kow± niewydolno¶ci± nerek (ESRD, end-stage renal disease ) (n = 164). Kontrole glikemii okre¶lano jako dobr± (HbA1c 9,0%). Klirens kreatyniny wyliczano za pomoc± wzoru Cockrofta-Gaulta. WY...
Acta Medica Marisiensis, 2015
The aim of the present study was to investigate differences regarding 24-hour blood pressure and ... more The aim of the present study was to investigate differences regarding 24-hour blood pressure and arterial stiffness in a cohort of office normotensive obese and non-obese children and adolescents, and to evaluate correlations of these parameters with some anthropometric indices. We retrospectively evaluated ABPM records in 71 children (42 boys); 31 obese compared with 40 normal-weight children.: Mean 24-hour, day-time and night-time SBP was significantly higher in the obese group than in the control group (p <0.01 during the entire period). Significantly higher AASI values were found in obese children compared to controls (0.45 vs. 0.41, p <0.05), the difference being more obvious for day-time AASI (p <0.001).: This research confirms that SBP and AASI are increased in obese children. AASI is a useful index of arterial stiffness that can be easily measured under ambulatory circumstances in children.
Diabetes, Jul 27, 2018
Identification of sequence variants robustly associated with predisposition to diabetic kidney di... more Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined (T1D+T2D) GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 diabetic subjects (and 18,582 DKD cases).Analysis of specific DKD phenotypes identified a novel signal near (rs9942471, =4.5×10) associated with 'microalbuminuria' in European T2D cases. However, no replication of this signal was observed in Asian subjects with T2D, or in the equivalent T1D analysis. Th...
PLoS Genetics, 2012
Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and th... more Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of endstage renal disease (ESRD) that requires dialysis treatment or kidney transplantation. In addition to the decrease in the quality of life, DN accounts for a large proportion of the excess mortality associated with type 1 diabetes (T1D). Whereas the degree of glycemia plays a pivotal role in DN, a subset of individuals with poorly controlled T1D do not develop DN. Furthermore, strong familial aggregation supports genetic susceptibility to DN. However, the genes and the molecular mechanisms behind the disease remain poorly understood, and current therapeutic strategies rarely result in reversal of DN. In the GEnetics of Nephropathy: an International Effort (GENIE) consortium, we have undertaken a meta-analysis of genomewide association studies (GWAS) of T1D DN comprising ,2.4 million single nucleotide polymorphisms (SNPs) imputed in 6,691 individuals. After additional genotyping of 41 top ranked SNPs representing 24 independent signals in 5,873 individuals, combined meta-analysis revealed association of two SNPs with ESRD: rs7583877 in the AFF3 gene (P = 1.2610 28) and an intergenic SNP on chromosome 15q26 between the genes RGMA and MCTP2, rs12437854 (P = 2.0610 29). Functional data suggest that AFF3 influences renal tubule fibrosis via the transforming growth factor-beta (TGF-b1) pathway. The strongest association with DN as a primary phenotype was seen for an intronic SNP in the ERBB4 gene (rs7588550, P = 2.1610 27), a gene with type 2 diabetes DN differential expression and in the same intron as a variant with cis-eQTL expression of ERBB4. All these detected associations represent new signals in the pathogenesis of DN.
Diabetologia, 2016
Aims/hypothesis Cardiovascular disease (CVD) is the most common cause of premature death and disa... more Aims/hypothesis Cardiovascular disease (CVD) is the most common cause of premature death and disability among patients with type 1 diabetes. Diabetic nephropathy accounts for the increased cardiovascular morbidity and mortality of these patients. We recently showed that the intensity of exercise predicts the incidence and progression of diabetic nephropathy in patients with type 1 diabetes. Little is known about the relationship between physical activity and CVD. Therefore, we studied how physical activity affects the risk of CVD events in patients with type 1 diabetes. Methods A 10 year follow-up study including 2180 type 1 diabetes patients from the nationwide multicentre Finnish Diabetic Nephropathy Study (FinnDiane). Leisure time physical activity (LTPA) was assessed by a previously validated self-report questionnaire. A CVD event was defined as a verified myocardial infarction, coronary procedure or stroke. Patients were analysed separately for the risk of developing a first ever CVD event and for the risk of a recurrent CVD event following a baseline event. Results A total of 206 patients had an incident CVD event during follow-up. A higher total LTPA and higher intensity, frequency and duration of activity were associated with a lower risk of incident CVD events. The observed association between exercise frequency and incident CVD remained significant when adjusted for classic risk factors. Exercise intensity also had a borderline effect on the recurrence-free time in patients with a major CVD event at baseline. Conclusions/interpretation This study suggests that exercise, particularly high frequency and high intensity exercise, may reduce the risk of CVD events in patients with type 1 diabetes. Keywords Cardiovascular disease. Exercise. Leisure-time physical activity. Type 1 diabetes Abbreviations CVD Cardiovascular disease ESRD End-stage renal disease Electronic supplementary material The online version of this article
The Journal of Clinical Endocrinology & Metabolism, 2016
Context: Patients with type 2 diabetes (T2D) are at an increased risk of cardiovascular disease. ... more Context: Patients with type 2 diabetes (T2D) are at an increased risk of cardiovascular disease. Objective: The objective of the study was to determine whether postprandial hyperglycemia affects arterial function in T2D. Design: A single-center, open-label study of three groups of men were studied: 1) T2D patients with albuminuria (n ϭ 22), 2) T2D patients without albuminuria (n ϭ 24), and 3) nondiabetic controls (n ϭ 25). Patients were randomized to a two-period crossover study schedule, ingesting breakfast, with or without insulin lispro (to induce low or high postprandial glycemia). Main Outcome Measures: Arterial stiffness was assessed by calculating pulse wave velocity (PWV) and augmentation index using applanation tonometry, and endothelial dysfunction was assessed using peripheral arterial tonometry, 30 minutes before breakfast and up to 240 minutes after breakfast. Results: At baseline, arterial stiffness was increased in patients. When adjusted for age and body mass index, in a combined group of patients with and without albuminuria, brachial PWV was higher during low (P ϭ .032) and high (P ϭ .038) postprandial glycemia vs controls. These differences were driven by the albuminuria group vs controls during low (P ϭ .014) and high (P ϭ .018) postprandial glycemia. No differences were observed in aortic PWV, augmentation index, or peripheral arterial tonometry ratio between patients and controls. Endothelin-1 and IL-6 were higher, and superoxide dismutase was lower, during postprandial hyperglycemia in T2D patients vs controls. Conclusions: In patients with T2D and albuminuria, brachial PWV was higher under postprandial hyperglycemic conditions, relative to controls. These data suggest that hyperglycemia induces an increase in stiffness of intermediate-sized arteries. We found no changes in other parts of the arterial bed.
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Papers by Markku Saraheimo