Markku Saraheimo

• MD. DMSc
• Folkhälsan Research Center

Various initiatives within Europe are in search for the identification and scaling up of ‘good practices’ within the field of integrated care. However, the operationalisation of a ‘good practice’ and how to best learn from its impact given a certain context, seems to be oversimplified or overlooked.

Aims The aim of this study was to investigate whether leisure-time physical activity (LTPA) is associated with the development of severe diabetic retinopathy in individuals with type 1 diabetes. Methods Prospective observational analysis as part of the Finnish diabetic nephropathy (FinnDiane) Study with a mean follow-up time of 10.7 years was perf...

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...

Aims To study the association between dietary intake and glycaemia in Type 1 diabetes. Methods Data on energy and nutrient intakes, and the mean and coefficient of variation of self‐monitored blood glucose measurements were obtained from records completed by 1000 adults with Type 1 diabetes. Associations between these measures of glycaemia and die...

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 office-based BP monitoring alone. We also analysed associations between BP patterns and arterial stiffne...

Aims/hypothesis: Our aim was to assess regression of albuminuria and its clinical consequences in type 1 diabetes. Methods: The analysis included 3642 participants from the Finnish Diabetic Nephropathy (FinnDiane) Study with a 24 h urine sample and a history of albuminuria available at baseline. A total of 2729 individuals had normal AER, 438 a...

International Diabetes Federation (I.D.F.) 2017 Congress Abu Dhabi U.A.E. Session Title: Care Delivery Session Type: Poster - Education and Integrated Care

Objective: The aims of the study were to assess how baseline leisure-time physical activity (LTPA) and its exercise components intensity, duration, and frequency are associated with all-cause and cardiovascular mortality in patients with type 1 diabetes 1) overall, 2) stratified by presence or absence of chronic kidney disease (CKD), and 3) strati...

An Integrated Care Pathway (ICP) is a plan of anticipated clinical practice for a group of patients with a particular diagnosis or a set of symptoms. Modern information technologies (IT) can support ICPs by enabling patient empowerment, more ef cient management and communication, and monitoring of care by multidisciplinary teams. An analysis of bes...

Aims/hypothesis: In type 1 diabetes, cardiovascular disease (CVD) and diabetic nephropathy progress in parallel, thereby potentiating the risk of premature death during their development. Since urinary liver-type fatty acid binding protein (L-FABP) predicts the progression of diabetic nephropathy, the aim of this study was to investigate whether u...

Introduction Integrated Care Pathways (ICPs) are a method for the mutual decision-making and organization of care for a well-defined group of patients during a well-defined period. The aim of a care pathway is to enhance the quality of care by improving patient outcomes, promoting patient safety, increasing patient satisfaction, and optimizing the...

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...

Aims: Inflammation plays an important role in the pathogenesis of cardiovascular diseases. Diet, as a modifiable risk factor, may in turn impact systemic inflammation. We therefore assessed whether adherence to the dietary recommendations is associated with high-sensitivity C-reactive protein (hs-CRP) concentrations in type 1 diabetes. Methods:...

To move the integration of care processes for diabetes in Europe forward, an expert group was constituted. The goal of the group’s activities was to develop a recommendation for integrated care pathways, targeting people with diabetes and comorbidities. Integrated care is an organising principle to achieve the delivery of improved patient care thro...

The physicians and nurses at each centre participating in the collection of patients.

Context: Patients with type 2 diabetes (T2D) are at increased risk of cardiovascular disease. Objective: To determine whether postprandial hyperglycemia affects arterial function in T2D. Design: A single-center, open-label study of 3 groups of men: (1) T2D patients with albuminuria (N=22), (2) T2D patients without albuminuria (N=24), (3) non-d...

This study investigated the prevalence of nonalbuminuric chronic kidney disease in type 1 diabetes to assess whether it increases the risk of cardiovascular and renal outcomes as well as all-cause mortality. This was an observational follow-up of 3,809 patients with type 1 diabetes from the Finnish Diabetic Nephropathy Study. All patients were Cauc...

OBJECTIVE: We evaluated the predictive value and clinical benefit of urinary kidney injury molecule (KIM)-1 for progression of diabetic nephropathy (DN) in type 1 diabetes. We also investigated its causal role for the decrease of estimated glomerular filtration rate (eGFR) by a Mendelian randomization (MR) approach. RESEARCH DESIGN AND METHODS: W...

We evaluated the predictive value and clinical benefit of urinary kidney injury molecule (KIM)-1 for progression of diabetic nephropathy (DN) in type 1 diabetes. We also investigated its causal role for the decrease of estimated glomerular filtration rate (eGFR) by a Mendelian randomization (MR) approach. We followed 1,573 patients with type 1 diab...

We investigated the predictive value of urinary adiponectin (uADP) for the progression of diabetic nephropathy (DN) as well as for the principal determinants of uADP concentrations. uADP was measured in 2,090 patients with type 1 diabetes followed for a median of 5.8 (4.4-6.9) years and in 111 subjects without diabetes. Progression was defined as a...

The aim of this study was to assess how physical activity predicts the development and progression of diabetic nephropathy in patients with type 1 diabetes. This prospective study (follow-up time 6.4 ± 3.1 years) included 1,390 patients (48.5% men, mean age 37.0 ± 12.4 years, duration of diabetes 20.4 ± 12.3 years) participating in the nationwide m...

Background and purpose: Despite the fact that patients with type 1 diabetes mellitus have a markedly increased risk of experiencing a stroke, independent risk factors for stroke and its subtypes in these patients have remained unclear. Methods: A total of 4083 patients with type 1 diabetes mellitus from the Finnish Diabetic Nephropathy (FinnDian...

Objective: Recent studies have suggested that circulating levels of the tumor necrosis factor-α receptor 1 (sTNFαR1) may be a useful predictor for the risk of end-stage renal disease (ESRD) in patients with diabetes. However, its potential utility as a biomarker has not been formally quantified. Research design and methods: Circulating levels of...

AIMS/HYPOTHESIS: Diabetic nephropathy is a major diabetic complication, and diabetes is the leading cause of end-stage renal disease (ESRD). Family studies suggest a hereditary component for diabetic nephropathy. However, only a few genes have been associated with diabetic nephropathy or ESRD in diabetic patients. Our aim was to detect novel geneti...

To study how the targets of glycemic, blood pressure (BP) and lipid control based on the American Diabetes Association (ADA) guidelines have been implemented, and to assess the risk of cardiovascular events (CVD) and mortality in patients with type 1 diabetes stratified by nephropathy (DN) status. A nationally representative cohort of patients with...

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...

Kirjoittajat ovat täydentäneet Lääkärilehdessä 21/2012 julkaistua artikkelia 12.12.2013. -Lisäys koskee kokemuksia insuliinin ja -inkretiinimimeetin yhteiskäytöstä sekä uusia GLP-1-analogeja. Lisäys esitetään sivulla 29. Täydennystä ei ole vertaisarvioitu. Insuliinipumppu voi olla monipistoshoidon vaihtoehto sellaisille tyypin 1 diabetesta sairasta...

Insulin pump therapy utilizes continuous infusion for the basic supply of insulin. As compared with multiple daily injections, pump therapy enables a clearly more precise targeting of the insulin therapy with respect to both time and quantity. This is important for insulin-sensitive patients such as small children, adults susceptible to hypoglycemi...

Objective To assess blood pressure (BP) control, antihypertensive treatment, and prevalence of resistant hypertension (RH) in patients with type 1 diabetes stratified by stage of diabetic nephropathy.Research Design and Methods This cross-sectional study included a nationally representative cohort of patients with type 1 diabetes (N=3,678) from the...

OBJECTIVE Osteoprotegerin (OPG) is involved in the process of vascular calcification. We investigated whether OPG is associated with the development and progression of diabetes complications in adults with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Serum OPG was measured in 1,939 adults with T1D participating in the Finnish Diabetic Nephro...

OBJECTIVE Diabetic 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 METHODS At baseline, 1,549 patients with...

AIMS: It is recommended that individuals with diabetes restrict their dietary sodium intake. But while salt intake is correlated with blood pressure, it also partly determines the activation state of renin-angiotensin-aldosterone-system (RAAS), a key mediator of diabetes-associated atherosclerosis. METHODS: ApolipoproteinE KO mice were allocated fo...

Background: Successful management of type 1 diabetes depends on the self-care practices. Sense of coherence has been associated with various measures of lifestyle choices. We aimed to study the associations between sense of coherence and self-care practices in patients with type 1 diabetes. We hypothesized that patients with weak sense of coherenc...

Worldwide, healthcare systems are considered unsustainable due to an increase in demand for care and an associated rise in healthcare costs. Ageing of societies and the growth of populations with chronic conditions are making a paradigm shift in western healthcare systems necessary. The Chronic Care Model (CCM) provides a framework for healthcare c...

Box and whisker plots of normalized ERBB4 expression intensities in glomerulus (A,B) and tubulointerstitium (C,D) by genotype showing eQTL associations in tubulointerstitium. Both SNPs show significant eQTL associations in tubulointerstitial kidney biopsies of Pima Indians with type 2 diabetes and DN (P = 0.018 for rs1718640, P = 0.024 for rs174188...

Longitudinal analyses in FinnDiane for rs7583877 (AFF3) and rs12437854 (chromosome 15q26). Analyses assume an additive model of the SNP effects. The plotted survival curves have been truncated at the point at which fewer than five participants remained with the corresponding genotype. The genotype legend in each figure indicates the number of sampl...

Top ranked SNPs selected for DN, ESRD vs. non ESRD, and ESRD vs. normoalbuminuria phenotypes. (DOC)

Clinical characteristics and information on genotyping of the phase two cohorts. (XLS)

Gene expression in early DN versus living donor kidney biopsies. All genes within a 2 Mb window (1 Mb upstream and downstream) of the three main signals (rs7583877/AFF3, rs12437854/15q26, rs7588550/ERBB4) were studied. (DOC)

P-value for association with DN related traits for the main signals after combined meta-analysis of DN and ESRD phenotypes. A1 is associated with increasing risk of ESRD/DN. (DOC)

Manhattan and QQ-plots for DN and ESRD phenotypes. Manhattan plots (panels A and C) highlighting P values from the discovery meta-analysis where dotted horizontal lines represent the threshold for follow up, P<1×10−5, and the solid horizontal lines indicate the threshold for genome-wide significance, P<5×10−8. The nearest genes are indicated above...

Rooted Principal Component Analysis of the discovery cohorts. Two first principal components (PC1 and PC2) are shown for (A) UK-ROI, (B) FinnDiane and (C) GoKinD US. Principal Component Analysis was calculated with EIGENSTRAT software including CEU, YRI and CBT from HapMap II as reference samples. (TIF)

Gene ontology analysis of all genes within ±1 Mbp of top GWAS signals: rs7583877/AFF3; rs12437854/15q26; rs7588550/ERBB4. (DOC)

Significantly enriched pathways (Genomatix Pathway System) for the ERBB4-correlated genes in early diabetic nephropathy. (DOC)

GENIE GWAS associations for SNPs that have been previously associated with T1D or chronic kidney disease. (DOC)

Quality control and filtering for the discovery GWAS data. (DOC)

Physicians and nurses participating in the collection of the FinnDiane study subjects. (DOC)

Additional kidney phenotype analysis results for the three main loci. (DOC)

Number of patients included in the study. (DOC)

The DCCT/EDIC Study Research Group. (DOC)

Cross-sectional and longitudinal analyses in FinnDiane for rs7583877 (AFF3) and rs12437854 (chromosome 15q26). (DOC)

Gene set enrichment analysis with MAGENTA. Gene sets with nominal P-value<0.01 for the three analyzed phenotypes. (DOC)

Supplementary Methods: Detailed explanation of employed methods. (DOC)

Diabetic kidney disease, or diabetic nephropathy (DN), is a major complication of diabetes and the leading cause of end-stage 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...

We formed the GEnetics of Nephropathy-an International Effort (GENIE) consortium to examine previously reported genetic associations with diabetic nephropathy (DN) in type 1 diabetes. GENIE consists of 6,366 similarly ascertained participants of European ancestry with type 1 diabetes, with and without DN, from the All Ireland-Warren 3-Genetics of K...

Graphical interpretation of non-linear relationships of HbA1c (a) and HDL-cholesterol (b) with all cause mortality in adults with type 1 diabetes from the FinnDianecohort, as described in the multivariate model detailed in Table 3

Objective: We estimated trends in prescription medication costs in out-patients with type 1 diabetes by various stages of diabetic nephropathy (DN), before the development of end-stage renal disease, between 1995 and 2005. Methods: Patients with normo- (n = 1,334), micro- (n = 206), and macroalbuminuria (n = 365) were identified from the Finnish...

Hyperfiltration is widely regarded as a contributing factor to the development of microalbuminuria and progressive nephropathy in type 1 diabetes. However, recent studies have questioned this conclusion. To address this conflicting evidence, we examined the association between hyperfiltration and progression to microalbuminuria in 2,318 adults with...

Individuals with diabetes have increased mortality rates compared with the general population. In patients with type 2 diabetes depression further contributes to the increased mortality. Depression and mortality rates in patients with type 1 diabetes are an understudied phenomenon. We therefore studied their association in a prospective setting. We...

To estimate short-term cost-effectiveness of insulin detemir vs. NPH insulin based on the incidence of mild hypoglycaemia in subjects with Type 1 diabetes in Denmark, Sweden, Finland and the Netherlands. A model was developed to evaluate cost-effectiveness based on mild (self-treated) hypoglycaemia and pharmacy costs over 1 year. Published rates of...

Adiponectin is widely regarded as an anti-atherogenic, antioxidant and anti-inflammatory molecule. However, adiponectin concentration is paradoxically increased in individuals with type 1 diabetes, in whom it is positively associated with adverse clinical outcomes. To explore the association between serum adiponectin concentration and mortality out...

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). In a nationwide multicenter study (the FinnDiane Study) between 1998 and 2002, 2,807 enrolled adults with type 1 diabetes without ESRD were prospecti...

Pulse pressure (PP), an estimate of arterial stiffness, has been shown to be associated with incident cardiovascular disease (CVD) in patients with type 1 diabetes (T1D). However, diabetic kidney disease, a strong predictor of CVD, was not previously taken into account. Furthermore, the role of PP as a predictor of diabetic nephropathy is not known...

Patients with both type 1 diabetes and CKD have an increased risk of adverse outcomes. The competing risks of death and ESRD may confound the estimates of risk for each outcome. Here, we sought to determine the major predictors of the cumulative incidence of ESRD and pre-ESRD mortality in patients with type 1 diabetes and macroalbuminuria while inc...

Sense of coherence (SOC) has been associated with various self-care behaviours in the general population. As the management of type 1 diabetes heavily relies on self-management, the SOC concept could also prove important in this population. This paper is a report of a study conducted among patients with type 1 diabetes to assess the associations be...

Diabetes questionnaire. Questionnaire on patients' conception of their disease.

While patients with type 1 diabetes (T1D) are known to suffer from early cardiovascular disease (CVD), we examined associations between arterial stiffness and diabetic complications in a large patient group with T1D. This study included 807 subjects (622 T1D and 185 healthy volunteers (age 40.6 ± 0.7 versus 41.6 ± 1.2 years; P = NS)). Arterial stif...

Both depression and the metabolic syndrome are frequently found among patients with type 1 diabetes, but their potential association has not yet been investigated. In this paper the relationship between depression and the metabolic syndrome among patients with type 1 diabetes was evaluated. A total of 1226 patients participating in the Finnish Diab...

Many factors contribute to the need for prandial insulin in Type 1 diabetes. However, patients' success in achieving normal postprandial glucose concentration is understudied. The aim of the present study was to determine how often patients with Type 1 diabetes achieve normal postprandial glucose concentrations and to evaluate factors associated wi...

Diabetic nephropathy has been associated with low-grade inflammation and activation of the complement system in cross-sectional studies. Data from prospective studies are sparse. We investigated the associations of the complement activator mannose-binding lectin (MBL) and the inflammatory marker high-sensitivity C-reactive protein (hsCRP) with the...

The daily treatment of type 1 diabetes with frequent monitoring of blood glucose levels and nuisance caused by insulin administration may affect patients' health-related quality of life (HRQoL). Type 1 diabetes is further burdened with an increased risk of complications which may additionally reduce a patient's HRQoL. We aimed to assess HRQoL and i...

We studied the impact of baseline lipid variables on the progression of renal disease in a large nationwide prospective cohort of patients with type 1 diabetes. A total of 2,304 adult patients with type 1 diabetes and available lipid profiles participating in the Finnish Diabetic Nephropathy Study (FinnDiane) were evaluated. Data on progression of...

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 c...

Short adult stature has previously been associated with cardiovascular disease, but its relationship with the microvascular complications of diabetes is uncertain. Therefore, we evaluated the association between adult stature and prevalence and incidence of diabetic microvascular complications. This cross-sectional and longitudinal study comprises...

Mannose-binding lectin (MBL) is an essential component of the acute-phase immune response and may thus play a role in the pathogenesis of type 1 diabetes and diabetic nephropathy. The serum concentration of MBL is mainly genetically determined, and elevated concentrations have been associated with both type 1 diabetes and diabetic nephropathy. Prev...

This study aimed to identify clinical features associated with premature mortality in a large contemporary cohort of adults with type 1 diabetes. 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 hospital...

To assess the predictive value of the metabolic syndrome in patients with type 1 diabetes. Patients were from the prospective Finnish Diabetic Nephropathy (FinnDiane) Study (n = 3,783): mean age 37 +/- 12 years and diabetes duration 23 +/- 12 years. Metabolic syndrome was defined according to World Health Organization (WHO), National Cholesterol Ed...

The purpose of this study was to study the association between a parental history of type 2 diabetes and the metabolic profile as well as the presence of the metabolic syndrome and diabetes complications in patients with type 1 diabetes. This was a cross-sectional study design in 1,860 patients with type 1 diabetes from the Finnish Diabetic Nephrop...

Poor glycemic control, elevated triglycerides, and albuminuria are associated with vascular complications in diabetes. However, few studies have investigated combined associations between metabolic markers, diabetic kidney disease, retinopathy, hypertension, obesity, and mortality. Here, the goal was to reveal previously undetected association patt...

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 arte...

The purpose of this study was to elucidate whether serum adiponectin is associated with progression of diabetic nephropathy in type 1 diabetic patients. This was a prospective follow-up study as a part of the nationwide Finnish Diabetic Nephropathy Study; 1,330 type 1 diabetic patients were followed for 5.0 +/- 2.2 years. Patients were divided at b...

Diabetic nephropathy is associated with low-grade inflammation and activation of the complement system. Defensins, as part of the innate immune system, may play a regulatory role in the complement cascade and may also augment the production of proinflammatory cytokines. The aim of this study was therefore to elucidate whether alpha-defensin is asso...