Browsing by Subject "Type 2 diabetes"

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  • Laine, Merja K.; Eriksson, Johan G.; Kujala, Urho M.; Wasenius, Niko S.; Kaprio, Jaakko; Backmand, Heli M.; Peltonen, Markku; Mertsalmi, Tuomas H.; Sarna, Seppo (2014)
  • Ahluwalia, Tarunveer S.; Schulz, Christina-Alexandra; Waage, Johannes; Skaaby, Tea; Sandholm, Niina; van Zuydam, Natalie; Charmet, Romain; Bork-Jensen, Jette; Almgren, Peter; Thuesen, Betina H.; Bedin, Mathilda; Brandslund, Ivan; Christensen, Cramer K.; Linneberg, Allan; Ahlqvist, Emma; Groop, Per-Henrik; Hadjadj, Samy; Tregouet, David-Alexandre; Jorgensen, Marit E.; Grarup, Niels; Pedersen, Oluf; Simons, Matias; Groop, Leif; Orho-Melander, Marju; McCarthy, Mark I.; Melander, Olle; Rossing, Peter; Kilpeläinen, Tuomas O.; Hansen, Torben (2019)
    Aims/hypothesisIdentifying rare coding variants associated with albuminuria may open new avenues for preventing chronic kidney disease and end-stage renal disease, which are highly prevalent in individuals with diabetes. Efforts to identify genetic susceptibility variants for albuminuria have so far been limited, with the majority of studies focusing on common variants.MethodsWe performed an exome-wide association study to identify coding variants in a two-stage (discovery and replication) approach. Data from 33,985 individuals of European ancestry (15,872 with and 18,113 without diabetes) and 2605 Greenlanders were included.ResultsWe identified a rare (minor allele frequency [MAF]: 0.8%) missense (A1690V) variant in CUBN (rs141640975, =0.27, p=1.3x10(-11)) associated with albuminuria as a continuous measure in the combined European meta-analysis. The presence of each rare allele of the variant was associated with a 6.4% increase in albuminuria. The rare CUBN variant had an effect that was three times stronger in individuals with type 2 diabetes compared with those without (p(interaction)=7.0x10(-4), with diabetes=0.69, without diabetes=0.20) in the discovery meta-analysis. Gene-aggregate tests based on rare and common variants identified three additional genes associated with albuminuria (HES1, CDC73 and GRM5) after multiple testing correction (p(Bonferroni)
  • Tuomisto, Jouko; Airaksinen, Riikka; Kiviranta, Hannu; Tukiainen, Erkki; Pekkanen, Juha; Tuomisto, Jouni T. (2016)
    A number of studies have found an association between the concentrations of persistent organic pollutants (POP) and type 2 diabetes. Causality has remained uncertain. This study describes the pharmacokinetic behavior of PCDD/Fs (polychlorinated dibenzo-p-dioxins and dibenzofurans) both in a theoretical model based on elimination rate constants, and in a group of 409 adult surgical patients with known PCDD/F concentrations and dietary information. A model assuming 10% annual decrease in past PCDD/F intake, predicted the measured profile of TEQ (toxic equivalents) in the patient population fairly well. The dominant determinant of PCDD/F level was age, and the level in patients was also associated with consumption of animal source products. Predicted daily intakes correlated with diet, but also with body mass index (BMI), indicating that high BMI was preceded by high consumption of foods containing PCDD/Fs. The results suggest that a third factor, e. g. high intake of animal source foods, could explain both higher levels of POPs in the body and higher incidence of type 2 diabetes, and BMI is not sufficient in describing the confounding caused by diet. Thus, to fully address the causality between POPs and type 2 diabetes, careful studies considering the pharmacokinetics of the studied compounds, and including the analysis of food consumption, are needed. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
  • Kochumon, Shihab; Arefanian, Hossein; Sindhu, Sardar; Shenouda, Steve; Thomas, Reeby; Al-Mulla, Fahd; Tuomilehto, Jaakko; Ahmad, Rasheed (2021)
    Steroid receptor RNA activator 1 (SRA1) is involved in pathophysiological responses of adipose tissue (AT) in obesity. In vitro and animal studies have elucidated its role in meta-inflammation. Since SRA1 AT expression in obesity/type 2 diabetes (T2D) and the relationship with immune-metabolic signatures remains unclear, we assessed AT SRA1 expression and its association with immune–metabolic markers in individuals with obesity/T2D. For this, 55 non-diabetic and 53 T2D individuals classified as normal weight (NW; lean), overweight, and obese were recruited and fasting blood and subcutaneous fat biopsy samples were collected. Plasma metabolic markers were assessed using commercial kits and AT expression of SRA1 and selected immune markers using RT-qPCR. SRA1 expression was significantly higher in non-diabetic obese compared with NW individuals. SRA1 expression associated with BMI, PBF, serum insulin, and HOMA-IR in the total study population and people without diabetes. SRA1 associated with waist circumference in people without diabetes and NW participants, whereas it associated inversely with HbA1c in overweight participants. In most study subgroups AT SRA1 expression associated directly with CXCL9, CXCL10, CXCL11, TNF-α, TGF-β, IL2RA, and IL18, but inversely with CCL19 and CCR2. TGF-β/IL18 independently predicted the SRA1 expression in people without diabetes and in the total study population, while TNF-α/IL-2RA predicted SRA1 only in people with diabetes. TNF-α also predicted SRA1 in both NW and obese people regardless of the diabetes status. In conclusion, AT SRA1 expression is elevated in people with obesity which associates with typical immunometabolic markers of obesity/T2D, implying that SRA1 may have potential as a biomarker of metabolic derangements.
  • Kurkela, Olli; Forma, Leena; Ilanne-Parikka, Pirjo; Nevalainen, Jaakko; Rissanen, Pekka (2021)
    Aims/hypothesis Diabetes and diabetes complications are a cause of substantial morbidity, resulting in early exits from the labour force and lost productivity. The aim of this study was to examine differences in early exits between people with type 1 and 2 diabetes and to assess the role of chronic diabetes complications on early exit. We also estimated the economic burden of lost productivity due to early exits. Methods People of working age (age 17-64) with diabetes in 1998-2011 in Finland were detected using national registers (N-type 1 = 45,756, N-type 2 = 299,931). For the open cohort, data on pensions and deaths, healthcare usage, medications and basic demographics were collected from the registers. The outcome of the study was early exit from the labour force defined as pension other than old age pension beginning before age 65, or death before age 65. We analysed the early exit outcome and its risk factors using the Kaplan-Meier method and extended Cox regression models. We fitted linear regression models to investigate the risk factors of lost working years and productivity costs among people with early exit. Results The difference in median age at early exit from the labour force between type 1 (54.0) and type 2 (58.3) diabetes groups was 4.3 years. The risk of early exit among people with type 1 diabetes increased faster after age 40 compared with people with type 2 diabetes. Each of the diabetes complications was associated with an increase in the hazard of early exit regardless of diabetes type compared with people without the complication, with eye-related complications as an exception. Diabetes complications partly but not completely explained the difference between diabetes types. The mean lost working years was 6.0 years greater in the type 1 diabetes group than in the type 2 diabetes group among people with early exit. Mean productivity costs of people with type 1 diabetes and early exit were found to be 1.4-fold greater compared with people with type 2 diabetes. The total productivity costs of incidences of early exits in the type 2 diabetes group were notably higher compared with the type 1 group during the time period (euro14,400 million, euro2800 million). Conclusions/interpretation We found a marked difference in the patterns of risk of early exit between people with type 1 and type 2 diabetes. The difference was largest close to statutory retirement age. On average, exits in the type 1 diabetes group occurred at an earlier age and resulted in higher mean lost working years and mean productivity costs. The potential of prevention, timely diagnosis and management of diabetes is substantial in terms of avoiding reductions in individual well-being and productivity.
  • CVD-REAL Investigators Study Grp; Khunti, Kamlesh; Kosiborod, Mikhail; Kim, Dae Jung; Eriksson, Johan G.; Fenici, Peter (2021)
    Background Randomized, controlled cardiovascular outcome trials may not be fully representative of the management of patients with type 2 diabetes across different geographic regions. We conducted analyses of data from the multinational CVD-REAL consortium to determine the association between initiation of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and cardiovascular outcomes, including subgroup analyses based on patient characteristics. Methods De-identified health records from 13 countries across three continents were used to identify patients newly-initiated on SGLT-2i or other glucose-lowering drugs (oGLDs). Propensity scores for SGLT-2i initiation were developed in each country, with 1:1 matching for oGLD initiation. In the matched groups hazard ratios (HRs) for hospitalization for heart failure (HHF), all-cause death (ACD), the composite of HHF or ACD, myocardial infarction (MI) and stroke were estimated by country, and pooled using a weighted meta-analysis. Multiple subgroup analyses were conducted across patient demographic and clinical characteristics to examine any heterogeneity in treatment effects. Results Following matching, 440,599 new users of SGLT-2i and oGLDs were included in each group. Mean follow-up time was 396 days for SGLT-2i initiation and 406 days for oGLDs initiation. SGLT-2i initiation was associated with a lower risk of HHF (HR: 0.66, 95%CI 0.58-0.75; p < 0.001), ACD (HR: 0.52, 95%CI 0.45-0.60; p < 0.001), the composite of HHF or ACD (HR: 0.60, 95%CI 0.53-0.68; p < 0.001), MI (HR: 0.85, 95%CI 0.78-0.92; p < 0.001), and stroke (HR: 0.78, 95%CI 0.72-0.85; p < 0.001); regardless of patient characteristics, including established cardiovascular disease, or geographic region. Conclusions This CVD-REAL study extends the findings from the SGLT-2i clinical trials to the broader setting of an ethnically and geographically diverse population, and across multiple subgroups. Trial registration NCT02993614
  • Welsh, Paul; Rankin, Naomi; Li, Qiang; Mark, Patrick B.; Würtz, Peter; Ala-Korpela, Mika; Marre, Michel; Poulter, Neil; Hamet, Pavel; Chalmers, John; Woodward, Mark; Sattar, Naveed (2018)
    Aims/hypotheses We aimed to quantify the association of individual circulating amino acids with macrovascular disease, microvascular disease and all-cause mortality in individuals with type 2 diabetes. Methods We performed a case-cohort study (N = 3587), including 655 macrovascular events, 342 microvascular events (new or worsening nephropathy or retinopathy) and 632 all-cause mortality events during follow-up, in a secondary analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) study. For this study, phenylalanine, isoleucine, glutamine, leucine, alanine, tyrosine, histidine and valine were measured in stored plasma samples by proton NMR metabolomics. Hazard ratios were modelled per SD increase in each amino acid. Results In models investigating associations and potential mechanisms, after adjusting for age, sex and randomised treatment, phenylalanine was positively, and histidine inversely, associated with macrovascular disease risk. These associations were attenuated to the null on further adjustment for extended classical risk factors (including eGFR and urinary albumin/creatinine ratio). After adjustment for extended classical risk factors, higher tyrosine and alanine levels were associated with decreased risk of microvascular disease (HR 0.78; 95% CI 0.67, 0.91 and HR 0.86; 95% CI 0.76, 0.98, respectively). Higher leucine (HR 0.79; 95% CI 0.69, 0.90), histidine (HR 0.89; 95% CI 0.81, 0.99) and valine (HR 0.79; 95% CI 0.70, 0.88) levels were associated with lower risk of mortality. Investigating the predictive ability of amino acids, addition of all amino acids to a risk score modestly improved classification of participants for macrovascular (continuous net reclassification index [NRI] +35.5%, p <0.001) and microvascular events (continuous NRI +14.4%, p = 0.012). Conclusions/interpretation We report distinct associations between circulating amino acids and risk of different major complications of diabetes. Low tyrosine appears to be a marker of microvascular risk in individuals with type 2 diabetes independently of fundamental markers of kidney function.
  • Ahola-Olli, Ari V.; Mustelin, Linda; Kalimeri, Maria; Kettunen, Johannes; Jokelainen, Jari; Auvinen, Juha; Puukka, Katri; Havulinna, Aki S.; Lehtimäki, Terho; Kähönen, Mika; Juonala, Markus; Keinänen-Kiukaanniemi, Sirkka; Salomaa, Veikko; Perola, Markus; Järvelin, Marjo-Riitta; Ala-Korpela, Mika; Raitakari, Olli; Wurtz, Peter (2019)
    Aims/hypothesis Metabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case-control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults. Methods NMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24-45 years). Associations between baseline metabolites and risk of developing diabetes during 8-15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up. Results Out of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59-1.50; p Conclusions/interpretation Metabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk.
  • Harris, Stewart B.; Parente, Erika B.; Karalliedde, Janaka (2022)
    Type 2 diabetes (T2D) is a progressive disease, with many individuals eventually requiring basal insulin therapy to maintain glycaemic control. However, there exists considerable therapeutic inertia to the prompt initiation and optimal titration of basal insulin therapy due to barriers that include fear of injections, hypoglycaemia, weight gain, and burdensome regimens. Hypoglycaemia is thought to be a major barrier to optimal glycaemic control and is associated with significant morbidity and mortality. Newer second-generation basal insulin analogues provide comparable glycaemic control with lower risk of hypoglycaemia compared with first-generation basal insulin analogues. The present review article discusses clinical evidence for one such second-generation basal insulin analogue, insulin glargine 300 U/mL (Gla-300), in the context of hypothetical case studies that are representative of individuals who may attend routine clinical practice. These case studies discuss individualised treatment needs for people with T2D who are insulin-naive or pre-treated. Clinical characteristics such as older age, frequent nocturnal hypoglycaemia, and renal impairment, which are known risk factors for hypoglycaemia, are also considered.
  • Rasouli, B.; Ahlqvist, E.; Alfredsson, L.; Andersson, T.; Carlsson, P.-O.; Groop, L.; Löfvenborg, J.E.; Martinell, M.; Rosengren, A.; Tuomi, T.; Wolk, A.; Carlsson, S. (2018)
    Aim. - Coffee consumption is inversely related to risk of type 2 diabetes (T2D). In contrast, an increased risk of latent autoimmune diabetes in adults (LADA) has been reported in heavy coffee consumers, primarily in a subgroup with stronger autoimmune characteristics. Our study aimed to investigate whether coffee consumption interacts with HLA genotypes in relation to risk of LADA. Methods. - This population-based study comprised incident cases of LADA (n = 484) and T2D (n = 1609), and also 885 healthy controls. Information on coffee consumption was collected by food frequency questionnaire. Odds ratios (ORs) with 95% CIs of diabetes were calculated and adjusted for age, gender, BMI, education level, smoking and alcohol intake. Potential interactions between coffee consumption and high-risk HLA genotypes were calculated by attributable proportion (AP) due to interaction. Results. - Coffee intake was positively associated with LADA in carriers of high-risk HLA genotypes (OR: 1.14 per cup/day, 95% CI: 1.02-1.28), whereas no association was observed in non-carriers (OR: 1.04, 95% CI: 0.93-1.17). Subjects with both heavy coffee consumption (>= 4 cups day) and high-risk HLA genotypes had an OR of 5.74 (95% Cl: 3.34-9.88) with an estimated AP of 0.36 (95% CI: 0.01-0.71; P = 0.04370). Conclusion. - Our findings suggest that coffee consumption interacts with HLA to promote LADA. (C) 2018 Elsevier Masson SAS. All rights reserved.
  • Herzog, Katharina; Ahlqvist, Emma; Alfredsson, Lars; Groop, Leif; Hjort, Rebecka; Löfvenborg, Josefin E.; Tuomi, Tiinamaija; Carlsson, Sofia (2021)
    Aims: We investigated the risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes in relation to a healthy lifestyle, the proportion of patients attributable to an unhealthy lifestyle, and the influence of family history of diabetes (FHD) and genetic susceptibility. Methods: The population-based study included incident LADA (n = 571), type 2 diabetes (n = 1962), and matched controls (n = 2217). A healthy lifestyle was defined by BMI < 25 kg/m2, moderate-to-high physical activity, a healthy diet, no smoking, and moderate alcohol consumption. We estimated odds ratios (OR) with 95% confidence intervals (CIs) adjusted for age, sex, education, and FHD. Results: Compared to a poor/moderate lifestyle, a healthy lifestyle was associated with a reduced risk of LADA (OR 0.51, CI 0.34-0.77) and type 2 diabetes (OR 0.09, CI 0.05-0.15). A healthy lifestyle conferred a reduced risk irrespective of FHD and high-risk HLA genotypes. Having a BMI < 25 kg/m2 conferred the largest risk reduction for both LADA (OR 0.54, CI 0.43-0.66) and type 2 diabetes (OR 0.12, CI 0.10-0.15) out of the individual items. Conclusion: People with a healthy lifestyle, especially a healthy body weight, have a reduced risk of LADA including those with genetic susceptibility to diabetes. (C) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
  • Matz, Karl; Tuomilehto, Jaakko; Teuschl, Yvonne; Dachenhausen, Alexandra; Brainin, Michael (BioMed Central, 2020)
    Abstract Background Diabetes is an increasingly important risk factor for ischemic stroke and worsens stroke prognosis. Yet a large proportion of stroke patients who are eventually diabetic are undiagnosed. Therefore, it is important to have sensitive assessment of unrecognized hyperglycaemia in stroke patients. Design Secondary outcome analysis of a randomized controlled trial focussing on parameters of glucose metabolism and detection of diabetes and prediabetes in patients with acute ischemic stroke (AIS). Methods A total of 130 consecutively admitted patients with AIS without previously known type 2 diabetes mellitus (T2DM) were screened for diabetes or prediabetes as part of secondary outcome analysis of a randomized controlled trial that tested lifestyle intervention to prevent post-stroke cognitive decline. Patients had the oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) measurements in the second week after stroke onset and after 1 year. The detection rates of diabetes and prediabetes based on the OGTT or HbA1c values were compared. Results By any of the applied tests at the second week after stroke onset 62 of 130 patients (48%) had prediabetes or T2DM. Seventy-five patients had results from both tests available, the OGTT and HbA1c; according to the OGTT 40 (53.3%) patients had normal glucose metabolism, 33 (44%) had prediabetes, two (2.7%) T2DM. In 50 (66.7%) patients the HbA1c results were normal, 24 (32%) in the prediabetic and one (1.3%) in the diabetic range. The detection rate for disorders of glucose metabolism was 10% higher (absolute difference; relative difference 29%) with the OGTT compared with HbA1c. After 1 year the detection rate for prediabetes or T2DM was 7% higher with the OGTT (26% relative difference). The study intervention led to a more favourable evolution of glycemic status after 1 year. Conclusion The OGTT is a more sensitive screening tool than HbA1c for the detection of previously unrecognized glycemic disorders in patients with acute stroke with an at least a 25% relative difference in detection rate. Therefore, an OGTT should be performed in all patients with stroke with no history of diabetes. Trial registration http://clinicaltrials.gov . Unique identifier: NCT01109836.
  • Matz, Karl; Tuomilehto, Jaakko; Teuschl, Yvonne; Dachenhausen, Alexandra; Brainin, Michael (2020)
    Background Diabetes is an increasingly important risk factor for ischemic stroke and worsens stroke prognosis. Yet a large proportion of stroke patients who are eventually diabetic are undiagnosed. Therefore, it is important to have sensitive assessment of unrecognized hyperglycaemia in stroke patients. Design Secondary outcome analysis of a randomized controlled trial focussing on parameters of glucose metabolism and detection of diabetes and prediabetes in patients with acute ischemic stroke (AIS). Methods A total of 130 consecutively admitted patients with AIS without previously known type 2 diabetes mellitus (T2DM) were screened for diabetes or prediabetes as part of secondary outcome analysis of a randomized controlled trial that tested lifestyle intervention to prevent post-stroke cognitive decline. Patients had the oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) measurements in the second week after stroke onset and after 1 year. The detection rates of diabetes and prediabetes based on the OGTT or HbA1c values were compared. Results By any of the applied tests at the second week after stroke onset 62 of 130 patients (48%) had prediabetes or T2DM. Seventy-five patients had results from both tests available, the OGTT and HbA1c; according to the OGTT 40 (53.3%) patients had normal glucose metabolism, 33 (44%) had prediabetes, two (2.7%) T2DM. In 50 (66.7%) patients the HbA1c results were normal, 24 (32%) in the prediabetic and one (1.3%) in the diabetic range. The detection rate for disorders of glucose metabolism was 10% higher (absolute difference; relative difference 29%) with the OGTT compared with HbA1c. After 1 year the detection rate for prediabetes or T2DM was 7% higher with the OGTT (26% relative difference). The study intervention led to a more favourable evolution of glycemic status after 1 year. Conclusion The OGTT is a more sensitive screening tool than HbA1c for the detection of previously unrecognized glycemic disorders in patients with acute stroke with an at least a 25% relative difference in detection rate. Therefore, an OGTT should be performed in all patients with stroke with no history of diabetes. Trial registration. Unique identifier: NCT01109836.
  • Hakkarainen, Heidi; Huopio, Hanna; Cederberg, Henna; Voutilainen, Raimo; Heinonen, Seppo (2018)
    Aims: Was to determine whether the birth weight of the infant predicts prediabetes (impaired fasting glucose, impaired glucose tolerance, or both) and type 2 diabetes (T2DM) during long-term follow-up of women with or without gestational diabetes mellitus (GDM). Methods: The women with or without GDM during their pregnancies in Kuopio University Hospital in 1989-2009 (n=876) were contacted and invited for an evaluation. They were stratified into two groups according to the newborn's birth weight: 10-90th percentile (appropriate-for-gestational-age; AGA) (n = 662) and >90th percentile (large-for-gestational-age; LGA) (n = 116). Glucose tolerance was investigated with an oral glucose tolerance test after a mean follow-up time of 7.3 (SD 5.1) years. Results: The incidence of T2DM was 11.8% and 0% in the women with and without GDM, respectively, after an LGA delivery. The incidence of prediabetes increased with offspring birth weight categories in the women with and without GDM: from 46.3% and 26.2% (AGA) to 52.9% and 29.2% (LGA), respectively. Conclusions: GDM women with LGA infants are at an increased risk for subsequent development of T2DM and therefore represent a target group for intervention to delay or prevent T2DM development. In contrast, an LGA delivery without GDM does not increase T2DM risk. (C) 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
  • Zhao, Yajie; Gardner, Eugene J.; Tuke, Marcus A.; Zhang, Huairen; Pietzner, Maik; Koprulu, Mine; Jia, Raina Y.; Ruth, Katherine S.; Wood, Andrew R.; Beaumont, Robin N.; Tyrrell, Jessica; Jones, Samuel E.; Allen, Hana Lango; Day, Felix R.; Langenberg, Claudia; Frayling, Timothy M.; Weedon, Michael N.; Perry, John R. B.; Ong, Ken K.; Murray, Anna (2022)
    Purpose: The study aimed to systematically ascertain male sex chromosome abnormalities, 47,XXY (Klinefelter syndrome [KS]) and 47,XYY, and characterize their risks of adverse health outcomes. Methods: We analyzed genotyping array or exome sequence data in 207,067 men of European ancestry aged 40 to 70 years from the UK Biobank and related these to extensive routine health record data. Results: Only 49 of 213 (23%) of men whom we identified with KS and only 1 of 143 (0.7%) with 47,XYY had a diagnosis of abnormal karyotype on their medical records or self-report. We observed expected associations for KS with reproductive dysfunction (late puberty: risk ratio [RR] = 2.7; childlessness: RR = 4.2; testosterone concentration: RR = -3.8 nmol/L, all P < 2 x 10(-8)), whereas XYY men appeared to have normal reproductive function. Despite this difference, we identified several higher disease risks shared across both KS and 47,XYY, including type 2 diabetes (RR = 3.0 and 2.6, respectively), venous thrombosis (RR = 6.4 and 7.4, respectively), pulmonary embolism (RR = 3.3 and 3.7, respectively), and chronic obstructive pulmonary disease (RR = 4.4 and 4.6, respectively) (all P Conclusion: KS and 47,XYY were mostly unrecognized but conferred substantially higher risks for metabolic, vascular, and respiratory diseases, which were only partially explained by higher levels of body mass index, deprivation, and smoking. (C) 2022 The Authors. Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.
  • Vornanen, Marleena; Konttinen, Hanna; Peltonen, Markku; Haukkala, Ari (2021)
    Background Perceived disease risk may reflect actual risk indicators and/or motivation to change lifestyle. Yet, few longitudinal studies have assessed how perceived risk relates to risk indicators among different disease risk groups. We examined in a 5-year follow-up, whether perceived risks of diabetes and cardiovascular disease predicted physical activity, body mass index (BMI kg/m(2)), and blood glucose level, or the reverse. We examined further whether perceived risk, self-efficacy, and outcome beliefs together predicted changes in these risk indicators. Method Participants were high diabetes risk participants (N = 432) and low/moderate-risk participants (N = 477) from the national FINRISK 2002 study who were followed up in 2007. Both study phases included questionnaires and health examinations with individual feedback letters. Data were analyzed using gender- and age-adjusted structural equation models. Results In cross-lagged autoregressive models, perceived risks were not found to predict 5-year changes in physical activity, BMI, or 2-h glucose. In contrast, higher BMI and 2-h glucose predicted 5-year increases in perceived risks (beta-values 0.07-0.15,P-values <0.001-0.138). These associations were similar among high- and low/moderate-risk samples. In further structural equation models, higher self-efficacy predicted increased physical activity among both samples (beta-values 0.10-0.16,P-values 0.005-0.034). Higher outcome beliefs predicted lower BMI among the low/moderate-risk sample (beta-values - 0.04 to - 0.05,P-values 0.008-0.011). Conclusion Perceived risk of chronic disease rather follows risk indicators than predicts long-term lifestyle changes. To promote sustained lifestyle changes, future intervention studies need to examine the best ways to combine risk feedback with efficient behavior change techniques.
  • Manca, Maria Laura; Solini, Anna; Haukka, Jani K.; Sandholm, Niina; Forsblom, Carol; Groop, Per Henrik; Ferrannini, Ele (2021)
    Background: Chronic kidney disease (CKD) shows different clinical features in Types1 (T1D) and 2 diabetes (T2D). Metabolomics have recently provided useful contribution to the identification of biomarkers of CKD progression in either form of the disease. However, no studies have so far compared plasma metabolomics between T1D and T2D in order to identify differential signatures of progression of estimated glomerular filtration rate (eGFR) decline. Methods: We used two large cohorts of T1D (from Finland) and T2D (from Italy) patients followed up to 7 and 3 years, respectively. In both groups, progression was defined as the top quartile of yearly decline in eGFR. Pooled data from the two groups were analysed by univariate and bivariate random forest (RF), and confirmed by bivariate partial least squares (PLS) analysis, the response variables being type of diabetes and eGFR progression. Results: In progressors, yearly eGFR loss was significantly larger in T2D [-5.3 (3.0), median (interquartile range)mL/min/1.73 m2/year] than T1D [-3.7 (3.1) mL/min/1.73 m2/year; P = 0.018]. Out of several hundreds, bivariate RF extracted 22 metabolites associated with diabetes type (all higher in T1D than T2D except for 5-methylthioadenosine, pyruvate and β-hydroxypyruvate) and 13 molecules associated with eGFR progression (all higher in progressors than non-progressors except for sphyngomyelin). Three of the selected metabolites (histidylphenylalanine, leucylphenylalanine, tryptophylasparagine) showed a significant interaction between disease type and progression. Only eight metabolites were common to both bivariate RF and PLS. Conclusions: Identification of metabolomic signatures of CKD progression is partially dependent on the statistical model. Dual analysis identified molecules specifically associated with progressive renal impairment in both T1D and T2D.
  • Landgraf, Wolfgang; Bigot, Gregory; Hess, Sibylle; Asplund, Olof; Groop, Leif; Ahlqvist, Emma; Käräjämäki, Annemari; Owens, David R.; Frier, Brian M.; Bolli, Geremia B. (2022)
    Aims: Newly-defined subgroups of type 2 diabetes mellitus (T2DM) have been reported from real-world cohorts but not in detail from randomised clinical trials (RCTs). Methods: T2DM participants, uncontrolled on different pre-study therapies (n = 12.738; 82 % Caucasian; 44 % with diabetes duration > 10 years) from 14 RCTs, were assigned to new subgroups according to age at onset of diabetes, HbA1c, BMI, and fasting C-peptide using the nearest centroid approach. Subgroup distribution, characteristics and influencing factors were analysed. Results: In both, pooled and single RCTs, “mild-obesity related diabetes” predominated (45 %) with mean BMI of 35 kg/m2. “Severe insulin-resistant diabetes” was found least often (4.6 %) and prevalence of “mild age-related diabetes” (23.9 %) was mainly influenced by age at onset of diabetes and age cut-offs. Subgroup characteristics were widely comparable to those from real-world cohorts, but all subgroups showed higher frequencies of diabetes-related complications which were associated with longer diabetes duration. A high proportion of “severe insulin-deficient diabetes” (25.4 %) was identified with poor pre-study glycaemic control. Conclusions: Classification of RCT participants into newly-defined diabetes subgroups revealed the existence of a heterogeneous population of T2DM. For future RCTs, subgroup-based randomisation of T2DM will better define the target population and relevance of the outcomes by avoiding clinical heterogeneity.
  • Mustonen, Erja; Hörhammer, Iiris; Patja, Kristiina; Absetz, Pilvikki; Lammintakanen, Johanna; Talja, Martti; Kuronen, Risto; Linna, Miika (2021)
    Background: Health coaching is a patient-centred approach to supporting self-management for the chronic conditions. However, long-term evidence of effectiveness of health coaching remains scarce. The object of this study was to evaluate the long-term effect of telephone health coaching (THC) on mortality and morbidity among people with type 2 diabetes (T2D), coronary artery disease (CAD) and congestive heart failure (CHF). Methods: 1535 T2D, CAD and CHF patients with unmet treatment targets were randomly allocated into an intervention group (n = 1034) and control group (n = 501). Intervention group received monthly individual strength-based, autonomy supportive THC sessions (average 30 min) for behavior change with a specially trained nurse for 12 months additional to usual health care. Control group received usual health care services. The primary outcome was a composite of death from cardiovascular causes or non-fatal stroke or non-fatal myocardial infarction (AMI) or unstable angina pectoris (UAP) during a follow-up of 8 years Three other composite endpoints with distinct combinations of fatal and non-fatal cardiovascular events and death from any cause were used as secondary outcomes. Other outcomes followed were the most relevant components of the composite endpoints. Randomized controlled trial (RCT) data was linked to Finnish national health and social care registries and electronic health records (EHR). Post-trial eight-year evaluation was conducted using intention-to-treat (ITT) and per-protocol (PP) analysis. Results: The composite primary outcome event rate per 100 person years was lower in the intervention group (3.45) than in control group (3.88) in ITT -analysis, but the difference was not statistically significant (hazard ratio in the intervention group 0.87; 95% CI, 0.71 to 1.07; P = 0.19). In the subgroup (T2D, CAD/CHF) analysis, there were no statistically significant effects. The secondary PP-analysis showed statistically significant benefits for those who participated in the study. Conclusions: No statistically significant effect of health coaching on mortality and morbidity was found in intention to treat analysis. The per protocol results suggest, however, that the intervention may be effective among patients who are willing and able to participate in health coaching. More research is needed to identify patients most likely to benefit from low-intensity health coaching. Trial registration: NCT00552903 (registration date: the 1st of November 2007, updated the 3rd of February 2009).
  • Simonsen, Nina; Koponen, Anne M; Suominen, Sakari (BioMed Central, 2021)
    Abstract Background Rising prevalence of type 2 diabetes (T2D), also among younger adults, constitutes a growing public health challenge. According to the person-centred Chronic Care Model, proactive care and self-management support in combination with community resources enhance quality of healthcare and health outcomes for patients with T2D. However, research is scarce concerning the importance of person-centred care and community resources for such outcomes as empowerment, and the relative impact of various patient support sources for empowerment is not known. Moreover, little is known about the association of age with these variables in this patient-group. This study, carried out among patients with T2D, examined in three age-groups (27–54, 55–64 and 65–75 years) whether person-centred care and diabetes-related social support, including community support and possibilities to influence community health issues, are associated with patient empowerment, when considering possible confounding factors, such as other quality of care indicators and psychosocial wellbeing. We also explored age differentials in empowerment and in the proposed correlates of empowerment. Method Individuals from a register-based sample with T2D participated in a cross-sectional survey (participation 56%, n = 2866). Data were analysed by descriptive statistics and multivariate logistic regression analyses. Results Respondents in the youngest age-group were more likely to have low empowerment scores, less continuity of care, and lower wellbeing than the other age-groups, and to perceive less social support, but a higher level of person-centred care than the oldest group. Community support, including possibilities to influence community health issues, was independently and consistently associated with high empowerment in all three age-groups, as was person-centred care in the two older age-groups. Community support was the social support variable with the strongest association with empowerment across age-groups. Moreover, vitality was positively and diabetes-related distress negatively associated with high empowerment in all age-groups, whereas continuity of care, i.e. having a family/regular nurse, was independently associated in the youngest age-group only. Conclusion Person-centred care and community support, including possibilities to influence community health issues, supports empowerment among adults with T2D. Findings suggest that age is related to most correlates of empowerment, and that younger adults with T2D have specific healthcare needs.