ORCID Profile
0000-0002-8293-6982
Current Organisations
University of Helsinki
,
Folkhälsans forskningscentrum
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Publisher: American Diabetes Association
Date: 12-01-2022
DOI: 10.2337/DC21-0974
Abstract: In iduals with type 1 diabetes are at a high lifetime risk of coronary artery disease (CAD), calling for early interventions. This study explores the use of a genetic risk score (GRS) for CAD risk prediction, compares it to established clinical markers, and investigates its performance according to the age and pharmacological treatment. This study in 3,295 in iduals with type 1 diabetes from the Finnish Diabetic Nephropathy Study (467 incident CAD, 14.8 years follow-up) used three risk scores: a GRS, a validated clinical score, and their combined score. Hazard ratios (HR) were calculated with Cox regression, and model performances were compared with the Harrell C-index (C-index). A HR of 6.7 for CAD was observed between the highest and the lowest 5th percentile of the GRS (P = 1.8 × 10−6). The performance of GRS (C-index = 0.562) was similar to HbA1c (C-index = 0.563, P = 0.96 for difference), HDL (C-index = 0.571, P = 0.6), and total cholesterol (C-index = 0.594, P = 0.1). The GRS was not correlated with the clinical score (r = −0.013, P = 0.5). The combined score outperformed the clinical score (C-index = 0.813 vs. C-index = 0.820, P = 0.003). The GRS performed better in in iduals below the median age (38.6 years) compared with those above (C-index = 0.637 vs. C-index = 0.546). A GRS identified in iduals at high risk of CAD and worked better in younger in iduals. GRS was also an independent risk factor for CAD, with a predictive power comparable to that of HbA1c and HDL and total cholesterol, and when incorporated into a clinical model, modestly improved the predictions. The GRS promises early risk stratification in clinical practice by enhancing the prediction of CAD.
Publisher: Cold Spring Harbor Laboratory
Date: 23-12-2021
DOI: 10.1101/2021.12.21.473644
Abstract: Vascular endothelial growth factor (VEGF) plays a key role in diabetic retinopathy (DR). L-type calcium channel blockers (LTCCBs) have been widely used as antihypertensive medication (AHM), but their association with VEGF and DR is still unclear. Therefore, we explored the effect of LTCCBs compared to other AHMs on VEGF concentrations in retinal cells and human serum. Furthermore, we evaluated the association between the use of LTCCBs and the risk of severe diabetic eye disease (SDED). Müller cells (MIO-M1) were cultured as per recommended protocol and treated with LTCCBs and other AHMs. VEGF secreted from cells were collected at 24 hours intervals. In an interventional study, 39 in iduals received LTCCBs or other AHM for four weeks with a four-week wash-out placebo period between treatments. VEGF was measured during the medication and placebo periods. Finally, we evaluated the risk of SDED associated with LTCCB usage in 192 in iduals from the FinnDiane Study in an oberservational setting. In the cell cultures, medium VEGF concentration increased time-dependently after amlodipine (p .01) treatment, but not after losartan (p .01), or lisinopril (p .01). Amlodipine, but no other AHM, increased serum VEGF concentration (p .05) during the interventional clinical study. The usage of LTCCB was not associated with the risk of SDED in the observational study. LTCCB increases VEGF concentrations in retinal cells and human serum. However, the usage of LTCCBs does not appear to be associated with SDED in adults with type 1 diabetes.
Publisher: Springer Science and Business Media LLC
Date: 29-10-2020
DOI: 10.1038/S41598-020-75667-5
Abstract: Visceral fat is associated with cardiovascular and kidney disease. However, the relationship between body composition and anthropometric measures in type 1 diabetes is unknown. Using z-statistics, we ranked the ability of body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), waist-height ratio (WHtR) and a body shape index (ABSI) to capture measures of body composition from 603 Dual-energy-X-Ray-Absorptiometry scans of adults with type 1 diabetes. Albuminuria was defined as urinary albumin excretion rate of at least 30 mg/24 h. Women with albuminuria had higher visceral fat mass % (VFM%) (0.9 vs. 0.5%, p = 0.0017) and lower appendicular lean mass % (AppLM%) (25.4 vs 26.4%, p = 0.03) than those without. Men with albuminuria had higher VFM% (1.5 vs. 1.0%, p = 0.0013) and lower AppLM% (30.0 vs 32.3, p 0.0001) than those without. In men, WHtR estimated VFM% best (z-statistics = 21.1), followed by WC (z = 19.6), BMI (z = 15.1), WHR (z = 14.6) and ABSI (z = 10.1). In women, the ranking was WC (z = 28.9), WHtR (z = 27.3), BMI (z = 20.5), WHR (z = 12.7) and ABSI (z = 10.5). Overall, the ranking was independent of albuminuria. Adults with type 1 diabetes and albuminuria have greater VFM% and lower AppLM% than those without. WHtR and WC best estimate the VFM% in this population, independently of albuminuria and sex.
Publisher: Public Library of Science (PLoS)
Date: 13-04-2023
DOI: 10.1371/JOURNAL.PONE.0284364
Abstract: Vascular endothelial growth factor (VEGF) plays a key role in diabetic retinopathy (DR). Previously, we have reported an association between mutations in a gene coding for the L-type calcium channel subunit, VEGF and DR. L-type calcium channel blockers (LTCCBs) have been widely used as antihypertensive medication (AHM), but their association with VEGF and DR is still unclear. Therefore, we explored the effect of LTCCBs compared to other AHMs on VEGF concentrations in retinal cells and human serum. Furthermore, we evaluated the association between the use of LTCCBs and the risk of severe diabetic eye disease (SDED). Müller cells (MIO-M1) were cultured as per recommended protocol and treated with LTCCBs and other AHMs. VEGF secreted from cells were collected at 24 hours intervals. In an interventional study, 39 in iduals received LTCCBs or other AHM for four weeks with a four-week wash-out placebo period between treatments. VEGF was measured during the medication and placebo periods. Finally, we evaluated the risk of SDED associated with LTCCB usage in 192 in iduals from the FinnDiane Study in an observational setting. In the cell cultures, the medium VEGF concentration increased time-dependently after amlodipine (P .01) treatment, but not after losartan (P .01), or lisinopril (P .01). Amlodipine, but no other AHM, increased the serum VEGF concentration (P .05) during the interventional clinical study. The usage of LTCCB was not associated with the risk of SDED in the observational study. LTCCB increases VEGF concentrations in retinal cells and human serum. However, the usage of LTCCBs does not appear to be associated with SDED in adults with type 1 diabetes.
Publisher: Oxford University Press (OUP)
Date: 26-06-2019
DOI: 10.1093/IJE/DYY113
Abstract: Large-scale epidemiological and population data provide opportunities to identify subgroups of people who are at risk of disease or exposed to adverse environments. Clustering algorithms are popular data-driven tools to identify these subgroups however, relying exclusively on algorithms may not produce the best results if the dataset does not have a clustered structure. For this reason, we propose a framework (the R-library Numero) that combines the self-organizing map algorithm, permutation analysis for statistical evidence and a final expert-driven subgrouping step. We used Numero to define subgroups in two ex les without an obvious clustering structure: a biomedical dataset of kidney disease and another dataset of community-level socioeconomic indicators. We benchmarked the Numero subgroupings against popular clustering algorithms (principal components, K-means and hierarchical clustering). The Numero subgroupings were more intuitive and easier to interpret without losing mathematical quality. Therefore, we expect Numero to be useful for exploratory analyses of population-based epidemiological datasets.
Publisher: Cold Spring Harbor Laboratory
Date: 25-10-2020
DOI: 10.1101/2020.10.21.20215921
Abstract: This study examines associations between 51 urinary metabolites and risk of progression of diabetic nephropathy in in iduals with type 1 diabetes by employing an automated nuclear magnetic resonance (NMR) metabolomics technique suitable for large-scale urine s le collections. For 2,670 in iduals with type 1 diabetes from the FinnDiane Study, we collected 24-hour urine s les and measured metabolite concentrations by NMR. In iduals were followed for 9.0 ± 5.0 years until their first sign of progression of diabetic nephropathy, end-stage kidney disease or study end. Cox regression analyses were performed on the entire study population (overall progression), on 1,999 in iduals with normoalbuminuria and 347 in iduals with macroalbuminuria at baseline. Seven urinary metabolites were associated with overall progression after adjustment for baseline albuminuria and chronic kidney disease stage (p 8 × 10 -4 ): Leucine (hazard ratio 1.47, 95% confidence interval [1.30, 1.66] per 1-SD creatinine-scaled metabolite concentration), valine (1.38 [1.22, 1.56]), isoleucine (1.33 [1.18, 1.50]), pseudouridine (1.25 [1.11, 1.42]), threonine (1.27 [1.11, 1.46]) and citrate (0.84 [0.75, 0.93]). 2-hydroxyisobutyrate was associated with overall (1.30 [1.16, 1.45]) and also progression from normoalbuminuria (1.56 [1.25, 1.95]). Six amino acids and pyroglutamate were associated with progression from macroalbuminuria. Branched-amino acids and other urinary metabolites were associated with the progression of diabetic nephropathy on top of baseline albuminuria and chronic kidney disease. We found differences in associations for overall progression and progression from normo- and macroalbuminuria. These novel biomarker discoveries illustrate the utility of analysing urinary metabolites in entire population cohorts. In iduals with type 1 diabetes are vulnerable to diabetic nephropathy and would benefit from earlier detection of disease progression. Urinary metabolites as a direct read-out of kidney function are potential progression markers. However, analytical tools to quantify a broad panel of urinary metabolites at large scale and low cost are lacking. Recent developments in nuclear magnetic resonance address this need. This study in 2,670 in iduals with type 1 diabetes identified ten urinary metabolites associated with progression of diabetic nephropathy. Importantly, different albuminuria categories had different urinary profiles: 2-hydroxyisobutyrate was associated with progression from normoalbuminuria and branched-chain amino acids with progression from macroalbuminuria. These results provide new potential biomarkers and highlight the potential of analysing urinary metabolites on a larger scale.
Publisher: Springer Berlin Heidelberg
Date: 2009
Publisher: American Diabetes Association
Date: 22-05-2020
DOI: 10.2337/DC20-0170
Abstract: To estimate the risk of diabetic nephropathy (DN) progression, incident coronary heart disease (CHD) and stroke, and all-cause mortality associated with resistant hypertension (RH) in in iduals with type 1 diabetes stratified by stages of DN, renal function, and sex. This prospective study included a nationally representative cohort of in iduals with type 1 diabetes from the Finnish Diabetic Nephropathy Study who had purchases of antihypertensive drugs at (±6 months) baseline visit (1995–2008). In iduals (N = 1,103) were ided into three groups: 1) RH, 2) uncontrolled blood pressure (BP) but no RH, and 3) controlled BP. DN progression, cardiovascular events, and deaths were identified from the in iduals’ health care records and national registries until 31 December 2015. At baseline, 18.7% of the participants had RH, while 23.4% had controlled BP. After full adjustments for clinical confounders, RH was associated with increased risk of DN progression (hazard ratio 1.95 [95% CI 1.37, 2.79], P = 0.0002), while no differences were observed in those with no RH (1.05 [0.76, 1.44], P = 0.8) compared with those who had controlled BP. The risk of incident CHD, incident stroke, and all-cause mortality was higher in in iduals with RH compared with those who had controlled BP but not beyond albuminuria and reduced kidney function. Notably, in those with normo- and microalbuminuria, the risk of stroke remained higher in the RH compared with the controlled BP group (3.49 [81.20, 10.15], P = 0.02). Our findings highlight the importance of identifying and providing diagnostic and therapeutic counseling to these very-high-risk in iduals with RH.
Publisher: Springer Science and Business Media LLC
Date: 05-08-2019
Publisher: Springer Science and Business Media LLC
Date: 22-10-2021
DOI: 10.1007/S00125-021-05584-3
Abstract: This prospective, observational study examines associations between 51 urinary metabolites and risk of progression of diabetic nephropathy in in iduals with type 1 diabetes by employing an automated NMR metabolomics technique suitable for large-scale urine s le collections. We collected 24-h urine s les for 2670 in iduals with type 1 diabetes from the Finnish Diabetic Nephropathy study and measured metabolite concentrations by NMR. In iduals were followed up for 9.0 ± 5.0 years until their first sign of progression of diabetic nephropathy, end-stage kidney disease or study end. Cox regressions were performed on the entire study population (overall progression), on 1999 in iduals with normoalbuminuria and 347 in iduals with macroalbuminuria at baseline. Seven urinary metabolites were associated with overall progression after adjustment for baseline albuminuria and chronic kidney disease stage ( p 8 × 10 −4 ): leucine (HR 1.47 [95% CI 1.30, 1.66] per 1-SD creatinine-scaled metabolite concentration), valine (1.38 [1.22, 1.56]), isoleucine (1.33 [1.18, 1.50]), pseudouridine (1.25 [1.11, 1.42]), threonine (1.27 [1.11, 1.46]) and citrate (0.84 [0.75, 0.93]). 2-Hydroxyisobutyrate was associated with overall progression (1.30 [1.16, 1.45]) and also progression from normoalbuminuria (1.56 [1.25, 1.95]). Six amino acids and pyroglutamate were associated with progression from macroalbuminuria. Branched-chain amino acids and other urinary metabolites were associated with the progression of diabetic nephropathy on top of baseline albuminuria and chronic kidney disease. We found differences in associations for overall progression and progression from normo- and macroalbuminuria. These novel discoveries illustrate the utility of analysing urinary metabolites in entire population cohorts.
Publisher: American Diabetes Association
Date: 28-12-2021
DOI: 10.2337/DCI21-0045
Publisher: Springer Science and Business Media LLC
Date: 10-12-2020
DOI: 10.1007/S11306-019-1626-Y
Abstract: Meta-analysis is the cornerstone of robust biomedical evidence. We investigated whether statistical reporting practices facilitate metabolomics meta-analyses. A literature review of 44 studies that used a comparable platform. Non-numeric formats were used in 31 studies. In half of the studies, less than a third of all measures were reported. Unadjusted P-values were missing from 12 studies and exact P-values from 9 studies. Reporting practices can be improved. We recommend (i) publishing all results as numbers, (ii) reporting effect sizes of all measured metabolites and (iii) always reporting unadjusted exact P-values.
Publisher: Springer Berlin Heidelberg
Date: 2008
Publisher: American Diabetes Association
Date: 26-01-2023
DOI: 10.2337/DC22-1935
Publisher: Springer Science and Business Media LLC
Date: 21-08-2018
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.DIABRES.2022.110178
Abstract: The early prediction of health outcomes for people with diabetes mellitus is desirable, as are adjunct therapies to reduce the related chronic complications and risk of premature death. The length of telomeres, protective caps on chromosome ends, is influenced by genetic and acquired factors, and shorter telomeres have been associated with and predictive of adverse cardiometabolic outcomes. Many studies have shown associations between telomere length in white blood cells (WBC) and diabetes per se and its chronic complications, and some studies show that telomeres do not always progressively shorten in people with diabetes. With the pandemic of diabetes and taking into consideration the calculations of residual risk using existent risk equations, additional tests to stratify subject risk are desirable. In this evolving era of precision medicine for people with diabetes, this 'global biomarker' of WBC telomere length may be useful to help predict health outcomes, to monitor health status, and may be a therapeutic target. We comment on the field of telomere investigations in diabetes, including recommending areas for further clinical research.
Publisher: Elsevier BV
Date: 06-2016
Publisher: American Diabetes Association
Date: 24-05-2021
DOI: 10.2337/DC20-3175
Abstract: Obesity, which is associated with nonalcoholic fatty liver (NAFL), has increased among people with type 1 diabetes. Therefore, we explored the associations between body fat distribution and NAFL in this population. This study included 121 adults with type 1 diabetes from the Finnish Diabetic Nephropathy (FinnDiane) Study for whom NAFL was determined by magnetic resonance imaging. Body composition was assessed by dual-energy X-ray absorptiometry. Genetic data concerning PNPLA3 rs738409 and TM6SF2 rs58542926 were available as a directly genotyped polymorphism. Associations between body fat distribution, waist-to-height ratio (WHtR), BMI, and NAFL were explored using logistic regression. A receiver operating characteristic (ROC) curve was used to determine the WHtR and BMI thresholds with the highest sensitivity and specificity to detect NAFL. Median age was 38.5 (33–43.7) years, duration of diabetes was 21.2 (17.9–28.4) years, 52.1% were women, and the prevalence of NAFL was 11.6%. After adjusting for sex, age, duration of diabetes, and PNPLA3 rs738409, the volume (P = 0.03) and percentage (P = 0.02) of visceral adipose tissue were associated with NAFL, whereas gynoid, appendicular, and total adipose tissues were not. The area under the curve between WHtR and NAFL was larger than BMI and NAFL (P = 0.04). The WHtR cutoff of 0.5 showed the highest sensitivity (86%) and specificity (55%), whereas the BMI of 26.6 kg/m2 showed 79% sensitivity and 57% specificity. Visceral adipose tissue is associated with NAFL in adults with type 1 diabetes, and WHtR may be considered when screening for NAFL in this population.
Publisher: American Diabetes Association
Date: 06-2020
DOI: 10.2337/DB20-516-P
Abstract: People living with type 1 diabetes have increased risk to develop diabetic nephropathy. No targeted cure exists, but the progression can be slowed down if detected early. We tested whether metabolic biomarkers measured in urine could predict progression of diabetic nephropathy (DN) in the Finnish nationwide FinnDiane Study. At baseline, 18 urine metabolites were measured with nuclear magnetic resonance metabolomics and scaled relative to urine creatinine. In iduals were followed for DN status for 9.0 years (± 5.1 years) until they progressed to their most severe DN status (334 events) or the latest known DN status for non-progressors. A Bonferroni-corrected P& .003 was considered significant. Five out of 18 urine metabolites were robustly associated with risk for DN progression in Cox regression models adjusted for sex, year of diabetes diagnosis as well as baseline age, DN status, BMI and eGFR. In iduals with elevated urinary levels of alanine (Hazard Ratio (HR) = 1.49 [1.26, 1.77] per 1-SD creatinine-scaled metabolite concentration, , P=3×10-6), valine (HR = 1.34 [1.22, 1.48], P=4×10-9), 2–hydroxyisobutyrate (HR = 1.48 [1.30, 1.67], P=1×10-9), cis-Aconitate (HR = 1.17 [1.06, 1.28], P=9×10-4) and pseudouridine (HR = 1.45 [1.24, 1.69], P=4×10-6) showed higher DN progression rate. We conclude that urinary biomarkers are indicative of kidney disease progression in type 1 diabetes, independently of baseline microalbuminuria and eGFR. The urinary biomarkers span multiple metabolic pathways, including microbial metabolism, citric acid cycle, and amino acids reflecting adiposity and dietary quality. S. Mutter: None. E.A. Valo: None. V. Aittomäki: Employee Self Nightingale Health Ltd. Other Relationship Self Nightingale Health Ltd. C. Forsblom: None. P. Groop: Advisory Panel Self Boehringer Ingelheim International GmbH, Sanofi, Sanofi. Speaker’s Bureau Self Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medscape, Merck Sharp & Dohme Corp., Mundipharma International. P. Wurtz: Employee Self Nightingale Health Ltd. Stock/Shareholder Self Nightingale Health Ltd. Folkhälsan Finland Novo Nordisk Foundation Academy of Finland
Publisher: Springer Science and Business Media LLC
Date: 19-10-2023
Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.DIABRES.2022.109926
Abstract: We aimed to determine how white blood cell (WBC) telomeres and telomere length change over time are associated with health status in type 1 diabetes. Relative telomere length (rTL) was measured in WBC DNA from two time-points (median 6.8 years apart) in 618 in iduals from the Finnish Diabetic Nephropathy Study by quantitative PCR, with interassay CV ≤ 4%. Baseline rTL correlated inversely with age and was shorter in men. In iduals in the shortest vs. longest rTL tertile had adverse cardiometabolic profiles, worse renal function, and were prescribed more antihypertensive and lipid-lowering drugs. While overall rTL tended to decrease during the median 6.8-years of follow-up, telomeres shortened in 55.3% of subjects, lengthened in 40.0%, and did not change in 4.7%. Baseline rTL correlated inversely with rTL change. Telomere lengthening was associated with higher HDL-Cholesterol (HDL-C), HDL-C/ApoA1, and with antihypertensive drug and (inversely) with lipid-lowering drug commencement during follow-up. Correlates of rTL percentage change per-annum (adjusted model) were baseline BMI, eGFR, previous retinal laser treatment, HDL-C, and HDL-C/ApoA1. Telomere length measurements may facilitate the treatment and monitoring of the health status of in iduals with type 1 diabetes.
Publisher: MDPI AG
Date: 21-10-2017
DOI: 10.3390/NU9101153
Publisher: Springer Science and Business Media LLC
Date: 09-2021
Publisher: Springer Science and Business Media LLC
Date: 27-12-2019
DOI: 10.1038/S41598-019-56541-5
Abstract: We assessed meal timing, meal frequency, and breakfast consumption habits of adult in iduals with type 1 diabetes (n = 1007) taking part in the Finnish Diabetic Nephropathy Study, and studied whether they are associated with glycaemic control. Data on dietary intake and blood glucose measurements were retrieved from food records. HbA 1c was measured at the study visit. In the whole s le, four peaks of energy intake emerged. Energy intake was the greatest in the evening, followed by midday. Altogether 7% of the participants reported no energy intake between 05:00 and 09:59 (breakfast skippers). While breakfast skippers reported lower number of meals, no difference was observed in the total energy intake between those eating and omitting breakfast. In a multivariable model, skipping breakfast was associated with higher mean blood glucose concentrations and lower odds of good glycaemic control. A median of 6 daily meals was reported. Adjusted for confounders, the number of meals was negatively associated with HbA 1c , and the mean of the blood glucose measurements, but positively associated with the variability of these measurements. Our observations support the habit of a regular meal pattern, including consumption of breakfast and multiple smaller meals for good glycaemic control in adults with type 1 diabetes. However, an increase in the blood glucose variability may additionally be expected with an increase in the number of meals eaten.
Location: Australia
No related grants have been discovered for Stefan Mutter.