Browsing by Subject "MELLITUS"

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  • Finne, Patrik; Groop, Per-Henrik; Arffman, Martti; Kervinen, Marjo; Helve, Jaakko; Gronhagen-Riska, Carola; Sund, Reijo (2019)
    OBJECTIVE To estimate long-term cumulative risk of end-stage renal disease (ESRD) after diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS This nationwide population-based inception cohort study included 421,429 patients with type 2 diabetes diagnosed in 1990-2011; patients were followed until the end of 2013. Data linkage between several national health care registers in Finland, covering 100% of the population, enabled the inclusion of almost all inhabitants who started taking diabetes medication or were hospitalized for diabetes. Cumulative risk of ESRD and hazard ratios [HR] for ESRD and death were estimated according to age, sex, and time period of diabetes diagnosis. RESULTS Among 421,429 patients with type 2 diabetes, 1,516 developed ESRD and 150,524 died during 3,458,797 patient-years of follow-up. Cumulative risk of ESRD was 0.29% at 10 years and 0.74% at 20 years from diagnosis of diabetes. Risk was higher among men than among women (HR 1.93 [95% CI 1.72-2.16]), decreased with older age at diagnosis (HR 0.70 [95% CI 0.60-0.81] for age 60-69 vs. 40-49 years), and was lower for those diagnosed in 2000-2011 than in 1990-1994 (HR 0.72 [95% CI 0.63-0.81]). Patients diagnosed with diabetes in 2000-2011 had lower risk of death during follow-up than those diagnosed in 1990-1994 (HR 0.64 [95% CI 0.63-0.65]). CONCLUSIONS Cumulative risk of ESRD is minimal among patients with type 2 diabetes compared with their risk of death. Patients diagnosed with diabetes at an older age have a lower risk of ESRD due to higher competing mortality.
  • 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.
  • Bronsveld, Heleen K.; Jensen, Vibeke; Vahl, Pernille; De Bruin, Marie L.; Cornelissen, Sten; Sanders, Joyce; Auvinen, Anssi; Haukka, Jari; Andersee, Morten; Vestergaard, Peter; Schmidt, Marjanka K. (2017)
    Background Women with diabetes have a worse survival after breast cancer diagnosis compared to women without diabetes. This may be due to a different etiological profile, leading to the development of more aggressive breast cancer subtypes. Our aim was to investigate whether insulin and non-insulin treated women with diabetes develop specific clinicopathological breast cancer subtypes compared to women without diabetes. Methods and Findings This cross-sectional study included randomly selected patients with invasive breast cancer diagnosed in 2000-2010. Stratified by age at breast cancer diagnosis (50 years), women with diabetes were 2:1 frequency-matched on year of birth and age at breast cancer diagnosis (both in 10-year categories) to women without diabetes, to select similar to 300 patients with tumor tissue available. Tumor MicroArrays were stained by immunohistochemistry for estrogen and progesterone receptor (ER, PR), HER2, Ki67, CK5/6, CK14, and p63. A pathologist scored all stains and revised morphology and grade. Associations between diabetes/insulin treatment and clinicopathological subtypes were analyzed using multivariable logistic regression. Morphology and grade were not significantly different between women with diabetes (n = 211) and women without diabetes (n = 101), irrespective of menopausal status. Premenopausal women with diabetes tended to have more often PR-negative (OR = 2.44(95%C1:1.07-5.55)), HER2-negative (OR = 2.84(95%C1:1.11-7.22)), and basal-like (OR = 3.14(95%C1:1.03-9.60) tumors than the women without diabetes, with non-significantly increased frequencies of ER-negative (OR = 2.48(95`)/X1:0.95-6.45)) and triple negative (OR = 2.60(95%CI:0.88-7.67) tumors. After adjustment for age and BMI, the associations remained similar in size but less significant. We observed no evidence for associations of clinicopathological subtypes with diabetes in postmenopausal women, or with insulin treatment in general. Conclusions We found no compelling evidence that women with diabetes, treated with or without insulin, develop different breast cancer subtypes than women without diabetes. However, premenopausal women with diabetes tended to develop breast tumors that do not express hormonal receptors, which are typically associated with poor prognosis.
  • Kouvonen, A.; Kivimaki, M.; Pentti, J.; Aalto, V.; Oksanen, T.; Virtanen, M.; Vahtera, J. (2017)
    AimsTo investigate if diabetes is associated with a higher risk of occupational (workplace or commuting) injury. MethodsMedication data from the Finnish Prescription Register were used to identify diabetes cases in 2004 in a large employee cohort (the Finnish Public Sector study). These data were linked to injury records obtained from the Federation of Accident Insurance Institutions. A total of 1020 diabetes cases (median age 52 years, range 20 to 65 years; 66% women) and their 5234 age- and sex-matched controls were followed up until 2011. Sex-stratified Cox proportional hazards models, adjusting for age, occupational status, obesity and health behaviours, were applied. Because of the small number of men in the cohort, injury types and locations were only examined among women. ResultsDuring the median follow-up of 6.7 years, 25% of the participants with diabetes (n=252) and 20% of those without (n=1051) experienced an occupational injury. The association between diabetes and injury was stronger in women than men (P=0.048). Diabetes was associated with a higher risk of workplace (hazard ratio 1.37, 95% CI 1.11 to 1.69) and commuting (hazard ratio 1.36, 95% CI 1.03 to 1.79) injury in women. With regard to different injury types and locations, diabetes was associated with bone fractures, dislocations, sprains and strains, and injuries to upper and lower extremities. In men, there was an association between insulin-treated diabetes and commuting injury (hazard ratio 3.14, 95% CI 1.52 to 6.49). ConclusionsDiabetes was associated with workplace and commuting injuries in women. Men with insulin-treated diabetes had a higher risk of commuting injuries.
  • Räsänen, Joel; Huovinen, Joel; Korhonen, Ville E.; Junkkari, Antti; Kastinen, Sami; Komulainen, Simo; Oinas, Minna; Avellan, Cecilia; Frantzen, Janek; Rinne, Jaakko; Ronkainen, Antti; Kauppinen, Mikko; Lönnrot, Kimmo; Perola, Markus; Koivisto, Anne M.; Remes, Anne M.; Soininen, Hilkka; Hiltunen, Mikko; Helisalmi, Seppo; Kurki, Mitja I.; Jääskeläinen, Juha E.; Leinonen, Ville (2020)
    Background The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families. Methods Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their >= 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher's exact test (two-tailed), the Mann-Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses. Results Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1-12.9, p = 0.030). Conclusions Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.
  • Eranti, Antti; Kerola, Tuomas; Aro, Aapo L.; Tikkanen, Jani T.; Rissanen, Harri A.; Anttonen, Olli; Junttila, M. Juhani; Knekt, Paul; Huikuri, Heikki V. (2016)
    Background: Diabetes predisposes to sudden cardiac death (SCD). However, it is uncertain whether greater proportion of cardiac deaths are sudden among diabetes patients than other subjects. It is also unclear whether the risk of SCD is pronounced already early in the course of the disease. The relationship of impaired glucose tolerance (IGT) and SCD is scarcely documented. Methods: A general population cohort of 10594 middle-aged subjects (mean age 44 years, 52.6 % male, follow-up duration 35-41 years) was divided into diabetes patients (n = 82), subjects with IGT (n = 3806, plasma glucose = 9.58 mmol/l in one-hour glucose tolerance test), and controls (n = 6706). Results: Diabetes patients had an increased risk of SCD after adjustment confounders (hazard ratio 2.62, 95 % confidence interval 1.46-4.70, p = 0.001) but risk for non-sudden cardiac death was similarly increased and the proportion of SCD of cardiac deaths was not increased. The SCD risk persisted after exclusion of subjects with baseline cardiac disease or non-fatal cardiac events during the follow-up. Subjects with IGT were at increased risk for SCD (univariate hazard ratio 1.51; 95 % confidence interval 1.31-1.74; p <0.001) and also for non-sudden cardiac deaths and non-fatal cardiac events but adjustments for other risk factors attenuated these effects. Conclusions: Diabetes was associated with increased risk of SCD but also the risk of non-sudden cardiac death was similarly increased. The proportion of cardiac deaths being sudden in subjects with diabetes was not increased. The higher SCD risk in diabetes patients was independent of known cardiac disease at baseline or occurrence of nonfatal cardiac event during the follow-up.
  • Lehtisalo, Jenni; Lindstrom, Jaana; Ngandu, Tiia; Kivipelto, Miia; Ahtiluoto, Satu; Ilanne-Parikka, Pirjo; Keinanen-Kiukaanniemi, Sirkka; Eriksson, Johan G.; Uusitupa, Matti; Tuomilehto, Jaakko; Luchsinger, Jose A.; Finnish Diabet Prevention Study DP (2016)
    BackgroundType 2 diabetes is linked with cognitive dysfunction and dementia in epidemiological studies, but these observations are limited by lack of data on the exact timing of diabetes onset. We investigated diabetes, dysglycaemia, and cognition in the Finnish Diabetes Prevention Study, in which the timing and duration of diabetes are well documented. MethodsThe Finnish Diabetes Prevention Study comprised middle-aged, overweight participants with impaired glucose tolerance but no diabetes at baseline (n=522), randomized to lifestyle intervention or a control group. After an intervention period (mean duration 4years) and follow-up (additional 9years), cognitive assessment with the CERAD test battery and Trail Making Test A (TMT) was executed twice within a 2-year interval. Of the 364 (70%) participants with cognitive assessments, 171 (47%) had developed diabetes. ResultsCognitive function did not differ between those who developed diabetes and those who did not. Lower mean 2-h glucose at an oral glucose tolerance test (OGTT) and HbA(1C) during the intervention period predicted better performance in the TMT (p=0.012 and 0.024, respectively). Those without diabetes or with short duration of diabetes improved in CERAD total score between the two assessments (p=0.001) whereas those with long duration of diabetes did not (p=0.844). ConclusionsBetter glycemic control among persons with baseline impaired glucose tolerance predicted better cognitive performance 9years later in this secondary analysis of the Finnish Diabetes Prevention Study population. In addition, learning effects in cognitive testing were not evident in people with long diabetes duration. Copyright (c) 2015 John Wiley & Sons, Ltd.
  • The FinnDiane Study Group; Ahola, Aila J.; Forsblom, Carol; Harjutsalo, Valma; Groop, Per-Henrik (2019)
    Aims Low-carbohydrate diet (LCD) has gained interest among individuals with diabetes as a means to manage glycaemia. We investigated the adherence to LCD in the Finnish Diabetic Nephropathy Study and whether carbohydrate restriction is associated with cardio-metabolic risk factors. Methods Cross-sectional data were available from 902 individuals with type 1 diabetes (44% men, age 47±13 years). Dietary data were collected twice with a 3-day diet record. Mean of the measurements was used. Carbohydrate intake 253 g/day or >48 E%). In the whole population, carbohydrate-to-fat ratio was calculated and its association with health variables was investigated. Results Higher carbohydrate-to-fat ratio was associated with higher blood glucose variability, higher blood pressure, lower HDL cholesterol concentration, and in men with lower waist-to-hip ratio. LCD adherence (n=69) was associated with lower BMI (25.6 vs. 27.8 kg/m2, p=0.030), lower variability of blood glucose measurements (0.38 vs. 0.45 mmol/l, p=0.030), and lower diastolic blood pressure (74 vs. 79 mmHg, p=0.048). Men reporting LCD had higher total (5.1 vs. 4.0 mmol/l, p=0.007) and non-HDL cholesterol (3.4 vs. 2.7 mmol/l, p=0.021). Women with LCD had higher HDL-cholesterol concentration (1.9 vs. 1.5 mmol/l, p=0.014). Conclusions Reduced blood glucose variability, related to LCD, could have clinical relevance to individuals with type 1 diabetes.
  • Ahola, Aila J.; Freese, Riitta; Mäkimattila, Sari; Forsblom, Carol; Groop, Per-Henrik; FinnDiane Study Grp (2016)
    Aims: Diet plays an important role in the management of type 1 diabetes. However, the association between dietary intake and health has not been extensively studied in this population. We studied the cross-sectional association between dietary factors, and selected vascular health markers and complications in type 1 diabetes. Methods: Data from 874 individuals with type 1 diabetes participating in the FinnDiane Study were included. Dietary intake was assessed using a self-reported questionnaire and a diet score, expressing the extent to which individuals adhered to the dietary recommendations, was calculated. Diet questionnaire was also used to reveal dietary patterns using factor analysis. Results: Seven factors with high degree of inter-correlation were formed; healthy, traditional, vegetable, sweets, modern, low-fat cheese, and fish and eggs. In multivariate models, higher diet score and healthy factor score were associated with better glycaemic control. Higher diet score was associated with higher, while sweets, and fish and eggs patterns were associated with lower systolic blood pressure. Healthy, sweets, and fish and eggs factors were additionally associated with lower diastolic blood pressure. Conclusions: Closer adherence to the dietary recommendations, and a diet high in fresh vegetables, fruits and berries, cooked vegetables, fish dishes, and yoghurt may be beneficial for the glycaemic control in type 1 diabetes. Moreover, a diet pattern with fish and eggs may have beneficial effects for blood pressure. (C) 2016 Published by Elsevier Inc.
  • Porksen, Sven; Laborie, Lene Bjerke; Nielsen, Lotte; Andersen, Marie Louise Max; Sandal, Tone; de Wet, Heidi; Schwarcz, Erik; Aman, Jan; Swift, Peter; Kocova, Mirjana; Schoenle, Eugen J.; de Beaufort, Carine; Hougaard, Philip; Ashcroft, Frances; Molven, Anders; Knip, Mikael; Mortensen, Henrik B.; Hansen, Lars; Njolstad, Pal R.; Hvidore Study Grp Childhood Diabet (2010)
  • de Groot, Pieter F.; Belzer, Clara; Aydin, Omrum; Levin, Evgeni; Levels, Johannes H.; Aalvink, Steven; Boot, Fransje; Holleman, Frits; van Raalte, Daniel H.; Scheithauer, Torsten P.; Simsek, Suat; Schaap, Frank G.; Damink, Steven W. M. Olde; Roep, Bart O.; Hoekstra, Joost B.; de Vos, Willem M.; Nieuwdorp, Max (2017)
    Objective Environmental factors driving the development of type 1 diabetes (T1D) are still largely unknown. Both animal and human studies have shown an association between altered fecal microbiota composition, impaired production of short-chain fatty acids (SCFA) and T1D onset. However, observational evidence on SCFA and fecal and oral microbiota in adults with longstanding T1D vs healthy controls (HC) is lacking. Research design and methods We included 53 T1D patients without complications or medication and 50 HC matched for age, sex and BMI. Oral and fecal microbiota, fecal and plasma SCFA levels, markers of intestinal inflammation (fecal IgA and calprotectin) and markers of low-grade systemic inflammation were measured. Results Oral microbiota were markedly different in T1D (eg abundance of Streptococci) compared to HC. Fecal analysis showed decreased butyrate producing species in T1D and less butyryl-CoA transferase genes. Also, plasma levels of acetate and propionate were lower in T1D, with similar fecal SCFA. Finally, fecal strains Christensenella and Subdoligranulum correlated with glycemic control, inflammatory parameters and SCFA. Conclusions We conclude that T1D patients harbor a different amount of intestinal SCFA (butyrate) producers and different plasma acetate and propionate levels. Future research should disentangle cause and effect and whether supplementation of SCFA-producing bacteria or SCFA alone can have disease-modifying effects in T1D.
  • Wackström, Nanna; Koponen, Anne M.; Suominen, Sakari; Tarkka, Ina M.; Simonsen, Nina (2020)
    ABSTRACT Background: Physical activity (PA) is a key component in management of type 2 diabetes (T2D). Pain might be a barrier to PA especially among older adults with T2D, but surprisingly few studies have investigated the association between chronic pain and PA. Our aim was to evaluate the prevalence of chronic pain among older adults with T2D and to examine the association between chronic pain and PA while taking important life-contextual factors into account. Methods: Data of this register-based, cross-sectional study were collected in a survey among adults with T2D (n=2866). In the current study, only respondents aged 65?75 years were included (response rate 63%, n=1386). Data were analysed by means of descriptive statistics and multivariate logistic regression analysis. Results: In total, 64% reported chronic pain. In specific groups, e.g. women and those who were obese, the prevalence was even higher. Among respondents experiencing chronic pain, frequent pain among women and severe pain among both genders were independently associated with decreased likelihood of being physically active. Moreover, the likelihood of being physically active decreased with higher age and BMI, whereas it increased with higher autonomous motivation and feelings of energy. Among physically active respondents suffering from chronic pain, neither intensity nor frequency of pain explained engagement in exercise (as compared with incidental PA). Instead, men were more likely to exercise regularly as were those with good perceived health and higher autonomous motivation. Conclusions: The prevalence of chronic pain is high among older adults with T2D. This study shows that among those suffering from chronic pain, severe pain is independently and inversely associated with being physically active, as is frequent pain, but only among women. Moreover, the findings show the importance of autonomous motivation and health variables for both incidental PA and exercise among older adults with T2D experiencing chronic pain.
  • Finndiane Study Grp (2018)
    Aims/hypothesisThe aim of this study was to assess the potential dose-dependent effects of smoking on the risk of CHD, heart failure and stroke in individuals with type 1 diabetes.MethodsThe study included 4506 individuals with type 1 diabetes who were participating in the Finnish Diabetic Nephropathy (FinnDiane) study. Intensity of smoking was estimated by packs per day and cumulative smoking by pack-years. Cox regression analyses were used to estimate the risk of incident CHD, heart failure or stroke during follow-up.ResultsOne pack per day significantly increased the risk of incident CHD in current smokers compared with never smokers (HR 1.45 [95% CI 1.15, 1.84]), after adjustment for age, sex, HbA(1c), hypertension, duration of diabetes and BMI. The risk of CHD in former smokers was similar to the risk in never smokers. The risk of incident heart failure was 1.43 (95% CI 1.03, 1.97) in current smokers per one pack per day and 1.37 (95% CI 1.05, 1.77) in former smokers, while the risk of incident stroke was 1.70 (95% CI 1.26, 2.29) and 1.49 (95% CI 1.14, 1.93), respectively. After further adjustments for lipids, however, the difference in the risk of heart failure in current and former smokers was no longer significant. Cumulative smoking data were similar to smoking intensity data.Conclusions/interpretationThere is a dose-dependent association between smoking and cardiovascular disease in individuals with type 1 diabetes. In men in particular, the risk of incident stroke remains high even after smoking cessation and is increased in current and former smokers independently of other risk factors.
  • Bahijri, Suhad; Al-Raddadi, Rajaa; Ajabnoor, Ghada; Jambi, Hanan; Al Ahmadi, Jawaher; Borai, Anwar; Barengo, Noël C; Tuomilehto, Jaakko (2020)
    Abstract Aims/Introduction To develop a non-invasive risk score to identify Saudis having prediabetes or undiagnosed type 2 diabetes. Methods Adult Saudis without diabetes were recruited randomly using a stratified two-stage cluster sampling method. Demographic, dietary, lifestyle variables, personal and family medical history were collected using a questionnaire. Blood pressure and anthropometric measurements were taken. Body mass index was calculated. The 1-h oral glucose tolerance test was carried out. Glycated hemoglobin, fasting and 1-h plasma glucose were measured, and obtained values were used to define prediabetes and type 2 diabetes (dysglycemia). Logistic regression models were used for assessing the association between various factors and dysglycemia, and Hosmer?Lemeshow summary statistics were used to assess the goodness-of-fit. Results A total of 791 men and 612 women were included, of whom 69 were found to have diabetes, and 259 had prediabetes. The prevalence of dysglycemia was 23%, increasing with age, reaching 71% in adults aged ≥65 years. In univariate analysis age, body mass index, waist circumference, use of antihypertensive medication, history of hyperglycemia, low physical activity, short sleep and family history of diabetes were statistically significant. The final model for the Saudi Diabetes Risk Score constituted sex, age, waist circumference, history of hyperglycemia and family history of diabetes, with the score ranging from 0 to 15. Its fit based on assessment using the receiver operating characteristic curve was good, with an area under the curve of 0.76 (95% confidence interval 0.73?0.79). The proposed cut-point for dysglycemia is 5 or 6, with sensitivity and specificity being approximately 0.7. Conclusion The Saudi Diabetes Risk Score is a simple tool that can effectively distinguish Saudis at high risk of dysglycemia.
  • Peddinti, Gopal; Cobb, Jeff; Yengo, Loic; Froguel, Philippe; Kravic, Jasmina; Balkau, Beverley; Tuomi, Tiinamaija; Aittokallio, Tero; Groop, Leif (2017)
    Aims/hypothesis The aims of this study were to evaluate systematically the predictive power of comprehensive metabolomics profiles in predicting the future risk of type 2 diabetes, and to identify a panel of the most predictive metabolic markers. Methods We applied an unbiased systems medicine approach to mine metabolite combinations that provide added value in predicting the future incidence of type 2 diabetes beyond known risk factors. We performed mass spectrometry-based targeted, as well as global untargeted, metabolomics, measuring a total of 568 metabolites, in a Finnish cohort of 543 nondiabetic individuals from the Botnia Prospective Study, which included 146 individuals who progressed to type 2 diabetes by the end of a 10 year follow-up period. Multivariate logistic regression was used to assess statistical associations, and regularised least-squares modelling was used to perform machine learning-based risk classification and marker selection. The predictive performance of the machine learning models and marker panels was evaluated using repeated nested cross-validation, and replicated in an independent French cohort of 1044 individuals including 231 participants who progressed to type 2 diabetes during a 9 year follow-up period in the DESIR (Data from an Epidemiological Study on the Insulin Resistance Syndrome) study. Results Nine metabolites were negatively associated (potentially protective) and 25 were positively associated with progression to type 2 diabetes. Machine learning models based on the entire metabolome predicted progression to type 2 diabetes (area under the receiver operating characteristic curve, AUC = 0.77) significantly better than the reference model based on clinical risk factors alone (AUC = 0.68; DeLong's p = 0.0009). The panel of metabolic markers selected by the machine learning-based feature selection also significantly improved the predictive performance over the reference model (AUC = 0.78; p = 0.00019; integrated discrimination improvement, IDI = 66.7%). This approach identified novel predictive biomarkers, such as alpha-tocopherol, bradykinin hydroxyproline, X-12063 and X-13435, which showed added value in predicting progression to type 2 diabetes when combined with known biomarkers such as glucose, mannose and alpha-hydroxybutyrate and routinely used clinical risk factors. Conclusions/interpretation This study provides a panel of novel metabolic markers for future efforts aimed at the prevention of type 2 diabetes.
  • e-PREDICE Consortium; Gabriel, Rafael; Lindström, Jaana; Tuomilehto, Jaakko (2020)
    Objectives To assess the effects of early management of hyperglycaemia with antidiabetic drugs plus lifestyle intervention compared with lifestyle alone, on microvascular function in adults with pre-diabetes. Methods Trial design: International, multicenter, randomised, partially double-blind, placebo-controlled, clinical trial. Participants Males and females aged 45–74 years with IFG, IGT or IFG+IGT, recruited from primary care centres in Australia, Austria, Bulgaria, Greece, Kuwait, Poland, Serbia, Spain and Turkey. Intervention Participants were randomized to placebo; metformin 1.700 mg/day; linagliptin 5 mg/day or fixed-dose combination of linagliptin/metformin. All patients were enrolled in a lifestyle intervention program (diet and physical activity). Drug intervention will last 2 years. Primary Outcome: composite end-point of diabetic retinopathy estimated by the Early Treatment Diabetic Retinopathy Study Score, urinary albumin to creatinine ratio, and skin conductance in feet estimated by the sudomotor index. Secondary outcomes in a subsample include insulin sensitivity, beta-cell function, biomarkers of inflammation and fatty liver disease, quality of life, cognitive function, depressive symptoms and endothelial function. Results One thousand three hundred ninety one individuals with hyperglycaemia were assessed for eligibility, 424 excluded after screening, 967 allocated to placebo, metformin, linagliptin or to fixed-dose combination of metformin + linagliptin. A total of 809 people (91.1%) accepted and initiated the assigned treatment. Study sample after randomization was well balanced among the four groups. No statistical differences for the main risk factors analysed were observed between those accepting or rejecting treatment initiation. At baseline prevalence of diabetic retinopathy was 4.2%, severe neuropathy 5.3% and nephropathy 5.7%. Conclusions ePREDICE is the first -randomized clinical trial with the aim to assess effects of different interventions (lifestyle and pharmacological) on microvascular function in people with pre-diabetes. The trial will provide novel data on lifestyle modification combined with glucose lowering drugs for the prevention of early microvascular complications and diabetes. Registration - ClinicalTrials.Gov Identifier: NCT03222765 - EUDRACT Registry Number: 2013-000418-39
  • Hyvonen, Mervi E.; Dumont, Vincent; Tienari, Jukka; Lehtonen, Eero; Ustinov, Jarkko; Havana, Marika; Jalanko, Hannu; Otonkoski, Timo; Miettinen, Päivi J.; Lehtonen, Sanna (2015)
    The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of beta-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER) at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy.
  • Vandenheede, Hadewijch; Deboosere, Patrick; Espelt, Albert; Bopp, Matthias; Borrell, Carme; Costa, Giuseppe; Eikemo, Terje Andreas; Gnavi, Roberto; Hoffmann, Rasmus; Kulhanova, Ivana; Kulik, Margarete; Leinsalu, Mall; Martikainen, Pekka; Menvielle, Gwenn; Rodriguez-Sanz, Maica; Rychtarikova, Jitka; Mackenbach, Johan P.; EURO-GBD-SE Consortium (2015)
    To evaluate educational inequalities in diabetes mortality in Europe in the 2000s, and to assess whether these inequalities differ between genders. Data were obtained from mortality registries covering 14 European countries. To determine educational inequalities in diabetes mortality, age-standardised mortality rates, mortality rate ratios, and slope and relative indices of inequality were calculated. To assess whether the association between education and diabetes mortality differs between genders, diabetes mortality was regressed on gender, educational rank and 'gender x educational rank'. An inverse association between education and diabetes mortality exists in both genders across Europe. Absolute educational inequalities are generally larger among men than women; relative inequalities are generally more pronounced among women, the relative index of inequality being 2.8 (95 % CI 2.0-3.9) in men versus 4.8 (95 % CI 3.2-7.2) in women. Gender inequalities in diabetes mortality are more marked in the highest than the lowest educated. Education and diabetes mortality are inversely related in Europe in the 2000s. This association differs by gender, indicating the need to take the socioeconomic and gender dimension into account when developing public health policies.
  • Rönö, Kristiina; Grotenfelt, Nora Elisabeth; Klemetti, Miira Marjuska; Stach-Lempinen, Beata; Huvinen, Emilia; Meinilä, Jelena; Valkama, Anita; Tiitinen, Aila; Roine, Risto Paavo; Pöyhönen-Alho, Maritta; Andersson, Sture; Laivuori, Hannele; Kautiainen, Hannu; Eriksson, Johan Gunnar; Koivusalo, Saila Birgitta (2018)
    Objective To assess the effect of lifestyle counseling on perinatal outcomes among women at high risk for gestational diabetes. Study design A total of 492 women with obesity and/or prior gestational diabetes were allocated to intervention (four sessions of lifestyle counseling, n = 249) or usual care (n = 243) before 20 weeks' gestation. Result Lifestyle indicators, gestational weight gain, or obstetric and perinatal outcomes did not differ between the two groups. An oral glucose tolerance test in the first half of pregnancy was pathological in 37.7% (n = 87/144) of intervention and 36.5% (n = 72/197) of control group women (p = 0.81). The total incidence of gestational diabetes diagnosed in the first or second half of pregnancy was 44.8% (107/239) in the intervention and 48.1% (111/231) in the control group (p = 0.48). Conclusions The high prevalence of impaired glucose metabolism was observed already in early pregnancy, which may have contributed to the lack of effect of the intervention.
  • Sahrakorpi, Niina; Rönö, Kristiina; Koivusalo, Saila B.; Stach-Lempinen, Beata; Eriksson, Johan G.; Roine, Risto P. (2019)
    Background: The incidence of gestational diabetes (GDM) is increasing and interventions to curb the detrimental effects of GDM are needed. We have previously reported that a combined diet and physical activity intervention has the potential to reduce GDM among high-risk women. It is also important to know whether the intervention affects health-related quality of life (HRQoL). Methods: A total of 378 women at high risk for GDM were randomized into an intervention (lifestyle counselling four times during pregnancy, n=192), or a control group (n=186) before 20 gestational weeks. HRQoL was assessed with the 15D-instrument six times: once during each trimester and at six weeks, six months and 12 months postpartum. Results: In this study population, the cumulative incidence of GDM was similar in the intervention and the control group (45.7 vs. 44.5%). There was no difference between the 15D scores of the control and intervention groups at any of the time points. Conclusions: Combined diet and physical activity intervention did not provide HRQoL benefits in the study. A high prevalence of GDM in both study groups may have confounded the effect of the intervention.