Browsing by Subject "DIABETES-MELLITUS"

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  • Virtanen, Eunice; Nurmi, Tapio; Soder, Per-Osten; Airila-Mansson, Stella; Soder, Birgitta; Meurman, Jukka H. (2017)
    Background: Periodontal disease associates with systemic diseases but corresponding links regarding apical periodontitis (AP) are not so clear. Hence our aim was to study association between AP and the prevalence of systemic diseases in a study population from Sweden. Methods: The subjects were 150 patients from a randomly selected epidemiological sample of 1676 individuals. 120 accepted to participate and their basic and clinical examination data were available for these secondary analyses where dental radiographs were used to record signs for endodontic treatments and AP. Periapical Index and modified Total Dental Index scores were calculated from the x-rays to classify the severity of AP and dental infection burden, respectively. Demographic and hospital record data were collected from the Swedish National Statistics Center. T-test, chi-square and univariate analysis of covariance (ANCOVA) and regressions analyses were used for statistics. Results: Of the 120 patients 41% had AP and 61% had received endodontic treatments of which 52% were radiographically unsatisfactory. AP patients were older and half of them were smokers. AP and periodontitis often appeared in the same patient (32.5%). From all hospital diagnoses, cardiovascular diseases (CVD) were most common, showing 20.4% prevalence in AP patients. Regression analyses, controlled for age, gender, income, smoking and periodontitis, showed AP to associate with CVD with odds ratio 3.83 (95% confidence interval 1.18-12.40; p = 0.025). Conclusions: The results confirmed our hypothesis by showing that AP statistically associated with cardiovascular diseases. The finding that subjects with AP also often had periodontitis indicates an increased oral inflammatory burden.
  • Jokinen, T. S.; Tiira, K.; Metsähonkala, L.; Seppala, E. H.; Hielm-Bjorkman, A.; Lohi, H.; Laitinen-Vapaavuori, O. (2015)
    BackgroundLagotto Romagnolo (LR) dogs with benign juvenile epilepsy syndrome often experience spontaneous remission of seizures. The long-term outcome in these dogs currently is unknown. In humans, behavioral and psychiatric comorbidities have been reported in pediatric and adult-onset epilepsies. Hypothesis/ObjectivesThe objectives of this study were to investigate possible neurobehavioral comorbidities in LR with a history of benign familial juvenile epilepsy (BFJE) and to assess the occurrence of seizures after the remission of seizures in puppyhood. AnimalsA total of 25 LR with a history of BFJE and 91 control dogs of the same breed. MethodsOwners of the LR dogs in the BFJE and control groups completed an online questionnaire about each dog's activity, impulsivity, and inattention. Principal component analysis (PCA) served to extract behavioral factors from the data. We then compared the scores of these factors between the 2 groups in a retrospective case-control study. We also interviewed all dog owners in the BFJE group by telephone to inquire specifically about possible seizures or other neurological problems after remission of seizures as a puppy. ResultsLagotto Romagnolo dogs with BFJE showed significantly higher scores on the factors Inattention and Excitability/Impulsivity than did the control group (P=.003; P=.021, respectively). Only 1 of the 25 BFJE LR exhibited seizures after remission of epilepsy in puppyhood. Conclusions and Clinical ImportanceAlthough the long-term seizure outcome in BFJE LR seems to be good, the dogs exhibit behavioral abnormalities resembling attention deficit hyperactivity disorder (ADHD) in humans, thus suggesting neurobehavioral comorbidities with epilepsy.
  • Palmu, Samuel; Kuneinen, Susanna; Kautiainen, Hannu; Eriksson, Johan G.; Korhonen, Päivi E. (2021)
    Background and aims: Current guidelines on prediabetes and diabetes (T2D) recommend to regularly perform an oral glucose tolerance test (OGTT) on subjects at risk of T2D. However, it is not known why women tend to have relatively higher 2-h post-load plasma (2hPG) glucose concentrations during OGTT than men. The aim of the present study is to investigate if there are sex differences in fasting plasma glucose (FPG) and 2hPG concentrations in relation to body size in apparently healthy non-diabetic subjects with normal glucose tolerance. We hypothesized that sex differences in glucose tolerance are physiological and related to different body surface area (BSA) in men and women. Methods and results: A 2-h 75 g OGTT was performed on 2010 subjects aged 45-70 years. Their BSA was calculated using the Mosteller formula. Men and women were separately divided into five BSA levels. Within the normal 2hPG range, women had higher mean 2hPG concentrations during the OGTT than men in all BSA levels estimated by sex-standardized BSA (p for linearity < 0.001). BSA adjusted for age, waist circumference, leisure-time physical activity, and smoking, showed an inverse association with 2hPG concentration in both sexes. Mean FPG concentrations were higher in men than in women. Conclusions: Body size has a negative inverse association with 2hPG concentration in an OGTT even within a physiological plasma glucose range. This may cause underestimation of glucose disorders in individuals with larger BSA and overestimation in individuals with smaller BSA when using an OGTT. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. This is an open access article under the CC BY license (
  • But, Anna; De Bruin, Marie L.; Bazelier, Marloes T.; Hjellvik, Vidar; Andersen, Morten; Auvinen, Anssi; Starup-Linde, Jakob; Schmidt, Marjanka K.; Furu, Kari; de Vries, Frank; Karlstad, Oystein; Ekstrom, Nils; Haukka, Jari (2017)
    Aims/hypothesis The aim of this work was to investigate the relationship between use of certain insulins and risk for cancer, when addressing the limitations and biases involved in previous studies. Methods National Health Registries from Denmark (1996-2010), Finland (1996-2011), Norway (2005-2010) and Sweden (2007-2012) and the UK Clinical Practice Research Datalink database (1987-2013) were used to conduct a cohort study on new insulin users (N = 327,112). By using a common data model and semi-aggregate approach, we pooled individual-level records from five cohorts and applied Poisson regression models. For each of ten cancer sites studied, we estimated the rate ratios (RRs) by duration (6 years) of cumulative exposure to insulin glargine or insulin detemir relative to that of human insulin. Results A total of 21,390 cancer cases occurred during a mean follow-up of 4.6 years. No trend with cumulative treatment time for insulin glargine relative to human insulin was observed in risk for any of the ten studied cancer types. Of the 136 associations tested in the main analysis, only a few increased and decreased risks were found: among women, a higher risk was observed for colorectal (RR 1.54, 95% CI 1.06, 2.25) and endometrial cancer (RR 1.78, 95% CI 1.07, 2.94) for 6 years (RR 0.22, 95% CI 0.05, 0.92). Comparisons of insulin detemir with human insulin also showed no consistent differences. Conclusions/interpretation The present multi-country study found no evidence of consistent differences in risk for ten cancers for insulin glargine or insulin detemir use compared with human insulin, at follow-up exceeding 5 years.
  • Badeau, Robert M.; Honka, Miikka-Juhani; Bucci, Marco; Iozzo, Patricia; Eriksson, Johan G.; Nuutila, Pirjo (2017)
    Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. The circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: Thirty-seven elderly women were separated into elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using proton nuclear magnetic resonance (1H-NMR) and insulin-dependent tissue-specific glucose uptake in skeletal muscle was assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the docosahexaenoic acid percentage of the total long-chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (p = 0.015). DHA/FA associated significantly with skeletal muscle glucose uptake (GU) (p = 0.031) and the metabolizable glucose value derived from hyperinsulinemic-euglycemic clamp technique (M-value) in the OLM group only (p = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and this association is significantly weakened in the offspring of obese mothers.
  • Kolehmainen, Anne; Pasanen, Annukka; Tuomi, Taru; Koivisto-Korander, Riitta; Bützow, Ralf; Loukovaara, Mikko (2020)
    Background Clinical factors may influence endometrial cancer survival outcomes. We examined the prognostic significance of age, body mass index (BMI), and type 2 diabetes among molecular subgroups of endometrial cancer. Methods This was a single institution retrospective study of patients who underwent surgery for endometrial carcinoma between January 2007 and December 2012. Tumors were classified into four molecular subgroups by immunohistochemistry of mismatch repair (MMR) proteins and p53, and sequencing of polymerase-epsilon (POLE). Overall, cancer-related, and non-cancer-related mortality were estimated using univariable and multivariable survival analyses. Results Age >65 years was associated with increased mortality rates in the whole cohort (n = 515) and in the "no specific molecular profile" (NSMP) (n = 218) and MMR deficient (MMR-D) (n = 191) subgroups during a median follow-up time of 81 months (range 1-136). However, hazard ratios for cancer-related mortality were non-significant for NSMP and MMR-D. Diabetes was associated with increased overall and non-cancer-related mortality in the whole cohort and MMR-D subgroup. Overweight/obesity had no effect on outcomes in the whole cohort, but was associated with decreased overall and cancer-related mortality in the NSMP subgroup, and increased overall and non-cancer-related mortality in the MMR-D subgroup. Overweight/obesity effect on cancer-related mortality in the NSMP subgroup remained unchanged after controlling for confounders. High-risk uterine factors were more common, and estrogen and progesterone receptor expression less common in NSMP subtype cancers of normal-weight patients compared with overweight/obese patients. No clinical factors were associated with outcomes in p53 aberrant (n = 69) and POLE mutant (n = 37) subgroups. No cancer-related deaths occurred in the POLE mutant subgroup. Conclusions The prognostic effects of age, BMI, and type 2 diabetes do not appear to be uniform for the molecular subgroups of endometrial cancer. Our data support further evaluation of BMI combined with genomics-based risk-assessment.
  • Ylönen, Minna; Viljamaa, Jaakko; Isoaho, Hannu; Junttila, Kristiina; Leino-Kilpi, Helena; Suhonen, Riitta (2019)
    Background: Previous research has revealed nurses' knowledge gaps in venous leg ulcer (VLU) nursing care, and continuing education is needed. The closer nurses' perceived knowledge is to their evidence-based theoretical knowledge, the better possibilities they have to conduct evidence-based VLU nursing care. Objectives: To assess the congruence between nurses' perceived and theoretical knowledge about VLU nursing care before and after an internet-based education about VLU nursing care (eVLU). Design: Quasi-experimental study with intervention and comparison groups and pre- and post-measurements. Setting: Home health care in two Finnish municipalities. Participants: Nurses (n = 946) working in home health care were invited to participate. In the intervention group, 239 nurses and 229 nurses in the comparison group met the inclusion criteria, and they were all recruited to the study. Method: Nurses were divided into intervention and comparison groups with lottery between the municipalities. Nurses in both groups took care of patients with VLU according to their organizations' instructions. In addition to this, nurses in the intervention group received a 6-week eVLU while those in the comparison group did not. Data were collected with a questionnaire about perceived and theoretical knowledge before education, at six weeks, and at 10 weeks. The percentages of congruence were calculated at every measurement point, and the McNemar test was used to detect statistical significance of changes between measurements. Results: The increase of congruence was more often statistically significant in the intervention group than in the comparison group. Conclusion: The results support the hypothesis that the congruence between perceived and theoretical knowledge will be higher among nurses receiving eVLU. Because of the low participation and drop-outs, the results should be interpreted with caution.
  • Yki-Jarvinen, Hannele (2016)
    Non-alcoholic fatty liver disease (NAFLD) increases risk of mortality from liver and cardiovascular disease (CVD) and is the major cause of hepatocellular carcinoma (HCC), which may develop without cirrhosis. NAFLD predicts type 2 diabetes, even independently of obesity. Globally, the prevalence of NAFLD averages 25% and is as common as the metabolic syndrome. The majority of patients with type 2 diabetes have NAFLD. The challenge for the diabetologist is to identify patients at risk of advanced liver disease and HCC. At a minimum, liver function tests (LFTs), despite being neither specific nor sensitive, should be performed in all patients with the metabolic syndrome or type 2 diabetes. Increases in LFTs, for which the updated reference values are lower (serum ALT approximate to 30 U/l in men and approximate to 20 U/l in women) than those hitherto used in many laboratories, should prompt assessment of fibrosis biomarkers and referral of individuals at risk to a NAFLD/hepatology clinic. Preferably, evaluation of NAFLD should be based on measurement of steatosis biomarkers or ultrasound if easily available. A large number of individuals carry the patatin-like phospholipase domain containing 3 (PNPLA3) I148M variant (30-50%) or the transmembrane 6 superfamily member 2 (TM6SF2) E167K variant (11-15%). These variants increase the risk of advanced liver disease and HCC but not of diabetes or CVD. Genotyping of selected patients for these variants is recommended. Many patients have 'double trouble', i.e. carry both a genetic risk factor and have the metabolic syndrome. Excess use of alcohol could be a cause of 'triple trouble', but such patients would be classified as having alcoholic fatty liver disease. This review summarises a presentation given at the symposium 'The liver in focus' at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Kenneth Cusi, DOI: 10.1007/s00125-016-3952-1, and by John Jones, DOI: 10.1007/s00125-016-3940-5) and a commentary by the Session Chair, Michael Roden (DOI: 10.1007/s00125-016-3911-x).
  • Nowak, Christoph; Salihovic, Samira; Ganna, Andrea; Brandmaier, Stefan; Tukiainen, Taru; Broeckling, Corey D.; Magnusson, Patrik K.; Prenni, Jessica E.; Wang-Sattler, Rui; Peters, Annette; Strauch, Konstantin; Meitinger, Thomas; Giedraitis, Vilmantas; Arnlov, Johan; Berne, Christian; Gieger, Christian; Ripatti, Samuli; Lind, Lars; Pedersen, Nancy L.; Sundstrom, Johan; Ingelsson, Erik; Fall, Tove (2016)
    Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion. In up to 910 elderly men we found associations of 52 metabolites with hyperinsulinemic-euglycemic clamp-measured IR and/or beta-cell responsiveness (disposition index) during an oral glucose tolerance test. These implicated bile acid, glycerophospholipid and caffeine metabolism for IR and fatty acid biosynthesis for impaired insulin secretion. In MR analysis in two separate cohorts (n = 2,613) followed by replication in three independent studies profiled on different metabolomics platforms (n = 7,824 / 8,961 / 8,330), we discovered and replicated causal effects of IR on lower levels of palmitoleic acid and oleic acid. A trend for a causal effect of IR on higher levels of tyrosine reached significance only in meta-analysis. In one of the largest studies combining "gold standard" measures for insulin responsiveness with non-targeted metabolomics, we found distinct metabolic profiles related to IR or impaired insulin secretion. We speculate that the causal effects on monounsaturated fatty acid levels could explain parts of the raised cardiovascular disease risk in IR that is independent of diabetes development.
  • Smura, Teemu; Natri, Olli; Ylipaasto, Petri; Hellman, Marika; Al-Hello, Haider; Piemonti, Lorenzo; Roivainen, Merja (2015)
    Enterovirus infections have been suspected to be involved in the development of type 1 diabetes. However, the pathogenetic mechanism of enterovirus-induced type 1 diabetes is not known. Pancreatic ductal cells are closely associated with pancreatic islets. Therefore, enterovirus infections in ductal cells may also affect beta-cells and be involved in the induction of type 1 diabetes. The aim of this study was to assess the ability of different enterovirus strains to infect, replicate and produce cytopathic effect in human pancreatic ductal cells. Furthermore, the viral factors that affect these capabilities were studied. The pancreatic ductal cells were highly susceptible to enterovirus infections. Both viral growth and cytolysis were detected for several enterovirus serotypes. However, the viral growth and capability to induce cytopathic effect (cpe) did not correlate completely. Some of the virus strains replicated in ductal cells without apparent cpe. Furthermore, there were strain-specific differences in the growth kinetics and the ability to cause cpe within some serotypes. Viral adaptation experiments were carried out to study the potential genetic determinants behind these phenotypic differences. The blind-passage of non-lytic CV-B6-Schmitt strain in HPDE-cells resulted in lytic phenotype and increased progeny production. This was associated with the substitution of a single amino acid (K257E) in the virus capsid protein VP1 and the viral ability to use decay accelerating factor (DAF) as a receptor. This study demonstrates considerable plasticity in the cell tropism, receptor usage and cytolytic properties of enteroviruses and underlines the strong effect of single or few amino acid substitutions in cell tropism and lytic capabilities of a given enterovirus. Since ductal cells are anatomically close to pancreatic islets, the capability of enteroviruses to infect and destroy pancreatic ductal cells may also implicate in respect to enterovirus induced type 1 diabetes. In addition, the capability for rapid adaptation to different cell types suggests that, on occasion, enterovirus strains with different pathogenetic properties may arise from less pathogenic ancestors. (C) 2015 Elsevier B.V. All rights reserved.
  • Haverinen, Annina; Kangasniemi, Marika; Luiro, Kaisu; Piltonen, Terhi; Heikinheimo, Oskari; Tapanainen, Juha S. (2021)
    Objective: To compare the effects of two formulations of combined oral contraceptives (COCs), estradiol valerate (EV) and ethinyl estradiol (EE) combined with dienogest (DNG), and DNG-only, on glucose tolerance. Study Design: We performed a randomized, controlled 9-week clinical trial. Inclusion criteria were: age 18-35 years, regular menstrual cycle (28 +/- 7 days), no polycystic ovaries, non-smoking, no contraindications for COC use and a 2-month wash-out from hormonal contraceptive use. The women were randomized to EV + DNG (n = 20), EE + DNG (n = 20), and DNG-only (n = 19), and evaluated at baseline, at 4-5 weeks and 8-9 weeks of treatment. Study medications were used continuously for 63 days. Primary outcome measure was change in the whole-body insulin sensitivity index (Matsuda index) derived from the oral glucose tolerance test (OGTT) over the treatment period. Secondary outcome measures were area under curves (AUC) of glucose and insulin, homeostatic model assessment - insulin resistance (HOMA-IR) and Insulin Sensitivity Index (ISI). Results: Fifty-nine women enrolled, and 56 women completed the study. The Matsuda index changed from baseline as follows (mean percentage change, mean change [95%CI]): DNG-only -12%, -1.45 [95%CI -3.22-0.325] P = 0.10; EV + DNG + 2.7%, -0.10 [-1.34 to 1.14] P = 0.86; EE + DNG -5.5%, -1.02 [-2.51 to 0.46] P = 0.16, comparing the groups P = 0.27. There were no clinically significant differences in glucose tolerance between the COC groups, but the DNG-only group showed an improvement in the 2-h glucose levels (5.5 [95%CI 5.0-6.0] to 4.7 mmol/l [4.2-5.2], P = 0.001). Conclusion: We found no clinically significant differences between EV and EE combined with DNG and DNG-only on glucose tolerance in healthy, young, normal-weight women, indicating that these preparations appear close to neutral regarding glucose metabolism when used continuously for nine weeks. (C) 2020 Elsevier Inc. All rights reserved.
  • Kondrashova, Anita; Nurminen, Noora; Lehtonen, Jussi; Hyöty, Marja; Toppari, Jorma; Ilonen, Jorma; Veijola, Riitta; Knip, Mikael; Hyöty, Heikki (2018)
    Objective: The function of the exocrine pancreas is decreased in patients with type 1 diabetes but it is not known when this defect develops. The current study set out to determine whether the reduced exocrine function becomes manifest after the initiation of islet autoimmunity. Methods: The study was nested in the prospective Type 1 Diabetes Prediction and Prevention study where children with human leukocyte antigen (HLA)-conferred susceptibility are observed from birth. Elastase-1 levels were analyzed from stool samples collected at the time of seroconversion to islet autoantibody positivity and at diagnosis of type 1 diabetes, as well as from samples taken from matched control children of similar age. Results: Elastase levels were lower in case children at the time of the diagnosis of diabetes when compared to the control children. However, elastase concentrations did not differ between cases and controls at the time when autoantibodies appeared. Conclusion: The results suggest that the defect in the exocrine function develops after the appearance of islet autoantibodies. Further studies are needed to assess whether reduced elastase levels predict rapid progression of islet autoimmunity to clinical disease.
  • Arroyo-Quiroz, Carmen; o'flaherty, Martin; Guzman-Castillo, Maria; Capewell, Simon; Chuquiure-Valenzuela, Eduardo; Jerjes-Sanchez, Carlos; Barrientos-Gutierrez, Tonatiuh (2020)
    Background Mexico is still in the growing phase of the epidemic of coronary heart disease (CHD), with mortality increasing by 48% since 1980. However, no studies have analyzed the drivers of these trends. We aimed to model CHD deaths between 2000 and 2012 in Mexico and to quantify the proportion of the mortality change attributable to advances in medical treatments and to changes in population-wide cardiovascular risk factors. Methods We performed a retrospective analysis using the previously validated IMPACT model to explain observed changes in CHD mortality in Mexican adults. The model integrates nationwide data at two-time points (2000 and 2012) to quantify the effects on CHD mortality attributable to changes in risk factors and therapeutic trends. Results From 2000 to 2012, CHD mortality rates increased by 33.8% in men and by 22.8% in women. The IMPACT model explained 71% of the CHD mortality increase. Most of the mortality increases could be attributed to increases in population risk factors, such as diabetes (43%), physical inactivity (28%) and total cholesterol (24%). Improvements in medical and surgical treatments together prevented or postponed 40.3% of deaths; 10% was attributable to improvements in secondary prevention treatments following MI, while 5.3% to community heart failure treatments. Conclusions CHD mortality in Mexico is increasing due to adverse trends in major risk factors and suboptimal use of CHD treatments. Population-level interventions to reduce CHD risk factors are urgently needed, along with increased access and equitable distribution of therapies
  • Matikainen, N.; Söderlund, S.; Björnson, E.; Bogl, L. H.; Pietiläinen, K. H.; Hakkarainen, A.; Lundbom, N.; Eliasson, B.; Räsänen, Sari; Rivellese, A.; Patti, L.; Prinster, A.; Riccardi, G.; Despres, J. -P.; Almeras, N.; Holst, J. J.; Deacon, C. F.; Boren, J.; Taskinen, M. -R. (2017)
    Background and aims: Incretin hormones glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are affected early on in the pathogenesis of metabolic syndrome and type 2 diabetes. Epidemiologic studies consistently link high fructose consumption to insulin resistance but whether fructose consumption impairs the incretin response remains unknown. Methods and results: As many as 66 obese (BMI 26-40 kg/m(2)) male subjects consumed fructose-sweetened beverages containing 75 g fructose/day for 12 weeks while continuing their usual lifestyle. Glucose, insulin, GLP-1 and GIP were measured during oral glucose tolerance test (OGTT) and triglycerides (TG), GLP-1, GIP and PYY during a mixed meal test before and after fructose intervention. Fructose intervention did not worsen glucose and insulin responses during OGTT, and GLP-1 and GIP responses during OGTT and fat-rich meal were unchanged. Postprandial TG response increased significantly, p = 0.004, and we observed small but significant increases in weight and liver fat content, but not in visceral or subcutaneous fat depots. However, even the subgroups who gained weight or liver fat during fructose intervention did not worsen their glucose, insulin, GLP-1 or PYY responses. A minor increase in GIP response during OGTT occurred in subjects who gained liver fat (p = 0.049). Conclusion: In obese males with features of metabolic syndrome, 12 weeks fructose intervention 75 g/day did not change glucose, insulin, GLP-1 or GIP responses during OGTT or GLP-1, GIP or PYY responses during a mixed meal. Therefore, fructose intake, even accompanied with mild weight gain, increases in liver fat and worsening of postprandial TG profile, does not impair glucose tolerance or gut incretin response to oral glucose or mixed meal challenge. (C) 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
  • Hakkarainen, Heidi; Huopio, Hanna; Cederberg, Henna; Voutilainen, Raimo; Heinonen, Seppo (2018)
    Background: Whether the delivery of a large-for-gestational-age (LGA) infant predicts future maternal metabolic syndrome (MetS) is not known. To this aim, we investigated the incidence of MetS and its components in women with or without a history of gestational diabetes mellitus (GDM) with a view to the birth weight of the offspring. Methods: Eight hundred seventy six women treated for their pregnancies in Kuopio University Hospital in 19892009 underwent a follow-up study (mean follow-up time 7.3 (SD 5.1) years), of whom 489 women with GDM and 385 normoglycemic controls. The women 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 (LGA) (n = 116). MetS and its components were evaluated in the follow-up study according to the International Diabetes Federation criteria. Results: LGA vs. AGA delivery was associated with a higher incidence of MetS at follow-up in women with a background of GDM (54.4% vs. 43.6%), but not in women without GDM. Conclusion: An LGA delivery in women with GDM is associated with a higher risk of future MetS and this group is optimal to study preventive measures for MetS. In contrast, an LGA delivery after a normoglycemic pregnancy was not associated with an increased future maternal MetS risk.
  • Hebbar, Prashantha; Abu-Farha, Mohamed; Alkayal, Fadi; Nizam, Rasheeba; Elkum, Naser; Melhem, Motasem; John, Sumi Elsa; Channanath, Arshad; Abubaker, Jehad; Bennakhi, Abdullah; Al-Ozairi, Ebaa; Tuomilehto, Jaakko; Pitkäniemi, Janne; Alsmadi, Osama; Al-Mulla, Fahd; Thanaraj, Thangavel Alphonse (2020)
    Consanguineous populations of the Arabian Peninsula, which has seen an uncontrolled rise in type 2 diabetes incidence, are underrepresented in global studies on diabetes genetics. We performed a genome-wide association study on the quantitative trait of fasting plasma glucose (FPG) in unrelated Arab individuals from Kuwait (discovery-cohort:n = 1,353; replication-cohort:n = 1,196). Genome-wide genotyping in discovery phase was performed for 632,375 markers from Illumina HumanOmniExpress Beadchip; and top-associating markers were replicated using candidate genotyping. Genetic models based on additive and recessive transmission modes were used in statistical tests for associations in discovery phase, replication phase, and meta-analysis that combines data from both the phases. A genome-wide significant association with high FPG was found at rs1002487 (RPS6KA1) (p-discovery = 1.64E-08, p-replication = 3.71E-04, p-combined = 5.72E-11; beta-discovery = 8.315; beta-replication = 3.442; beta-combined = 6.551). Further, three suggestive associations (p-values <8.2E-06) with high FPG were observed at rs487321 (CADPS), rs707927 (VARS and 2Kb upstream of VWA7), and rs12600570 (DHX58); the first two markers reached genome-wide significance in the combined analysis (p-combined = 1.83E-12 and 3.07E-09, respectively). Significant interactions of diabetes traits (serum triglycerides, FPG, and glycated hemoglobin) with homeostatic model assessment of insulin resistance were identified for genotypes heterozygous or homozygous for the risk allele. Literature reports support the involvement of these gene loci in type 2 diabetes etiology.
  • Åström, Max J.; von Bonsdorff, Mikaela B.; Salonen, Minna K.; Kajantie, Eero; Osmond, Clive; Eriksson, Johan G. (2021)
    Aim: This study aimed to assess the association between grip strength and glucose regulation in a cross-sectional setting. Methods: Using data from the Helsinki Birth Cohort Study, 924 men and 953 women were studied at a mean age of 61.6 years. Grip strength was assessed in the dominant hand using a Newtest Grip Force dynamometer. A standard 2-h 75 g oral glucose tolerance test (OGTT) was used to define glucose regulation. The participants were classified into four groups: normoglycaemia, prediabetes (impaired fasting glucose or impaired glucose tolerance), newly diagnosed diabetes and previously known diabetes. The association between grip strength and glucose regulation was assessed using multiple linear regression models. Results: Prediabetes was diagnosed in 32.2% and diabetes in 8.4% using the OGTT. A total of 7.8% of the individuals had previously known diabetes. Compared to individuals with normoglycaemia, grip strength was lower for those with newly diagnosed diabetes (-1.8 kg, 95% CI-3.2 to-0.5) as well as those with previously known diabetes (-1.8 kg, 95% CI-3.2 to-0.4) after adjusting for covariates (age, sex, body mass index, physical activity, education and smoking). No difference in grip strength was found when comparing those with pre diabetes and normoglycaemia. Conclusion: In adults, grip strength was lower among those with known and newly diagnosed diabetes compared to those with normoglycaemia. Together with previous findings on associations between grip strength and chronic diseases, these results support the use of grip strength as an overall health marker in adults.
  • Kero, A. E.; Madanat-Harjuoja, L. M.; Jarvela, L. S.; Malila, N.; Matomaki, J.; Lahteenmaki, P. M. (2016)
    Purpose: Childhood cancer survivors are at risk for developing metabolic syndrome (MetS), which subsequently leads to cardiovascular morbidity and excess mortality. Our aim was to investigate the purchases of medications associated with MetS among 7551 early onset cancer patients compared to siblings. Methods: Our nationwide Finnish population-based registry study analyzed the drug purchase of medication among early onset cancer patients diagnosed with cancer below the age of 35 years between 1994 and 2004 compared to siblings by linkage to the drug purchase registry, allowing for a maximal follow-up of 18 years. Results: The hazard ratios (HRs) for purchasing antihypertensives and diabetes drugs were higher after both childhood (HR 4.6, 95% CI 3.1-7.0; HR 3.0, 95% 1.5-6.1) and young adulthood (YA) cancer (HR 1.5, 95% CI 1.3-1.8; HR 1.6, 95% CI 1.1-2.2) compared to siblings. The HRs for purchasing lipid-lowering drugs were elevated both after childhood (HR 4.3,95% CI 0.9-19.5) and YA cancer (HR 1.6, 95% CI 1.04-2.5), but only reached significance in YA cancer patients. Among specific cancer diagnosis groups, highest HR values for antihypertensives were found in childhood acute lymphoblastic leukemia (ALL) (HR 6.1, 95% CI 3.7-10.3) and bone tumor (HR 4.3, 95% CI 1.9-9.4), and YA ALL (HR 4.8, 95% CI 3.1-7.0) and acute myeloid leukemia (AML) (HR 3.4, 95% CI 2.5-5.1) patients. Moreover, childhood ALL (HR 6.3, 95% CI 2.7-14.8), AML (HR 7.6, 95% CI 1.9-24.5) and central nervous system (CNS)-tumor (HR 3.5, 95% CI 1.3-9.2) and YA ALL (HR 3.7, 95% CI 1.2-9.5) patients showed the strongest likelihood of purchasing diabetes drugs compared to siblings. Conclusion: The purchase of medications associated with MetS was increased after early onset cancer and highly dependent on the age at cancer diagnosis and the cancer diagnosis. Prevention strategies are imperative for reducing potentially life-threatening cardiovascular complications after early onset cancer. (C) 2016 Elsevier Ltd. All rights reserved.
  • Luukkonen, Panu K.; Zhou, You; Sädevirta, Sanja; Leivonen , Marja; Arola, Johanna; Oresic, Matej; Hyotylainen, Tuulia; Yki-Jarvinen, Hannele (2016)
    Background & Aims: Recent data in mice have identified de novo ceramide synthesis as the key mediator of hepatic insulin resistance (IR) that in humans characterizes increases in liver fat due to IR ('Metabolic NAFLD' but not that due to the I148M gene variant in PNPLA3 ('PNPLA3 NAFLD'). We determined which bioactive lipids co-segregate with IR in the human liver. Methods: Liver lipidome was profiled in liver biopsies from 125 subjects that were divided into equally sized groups based on median HOMA-IR ('High and Low HOMA-IR', n = 62 and n = 63) or PNPLA3 genotype (PNPIA3(148MM/MI), n = 61 vs. PNPLA3(148II), n = 64). The subjects were also divided into 4 groups who had either IR, the I148M gene variant, both of the risk factors or neither. Results: Steatosis and NASH prevalence were similarly increased in 'High HOMA-IR' and PNPLA3(148MM/MI) groups compared to their respective control groups. The 'High HOMA-IR' but not the PNPLA3(148MM/MI) group had features of IR. The liver in 'High HOMA-IR' vs. low HOMA-IR' was markedly enriched in saturated and monounsaturated triacylglycerols and free fatty acids, dihydroceramides (markers of de novo ceramide synthesis) and ceramides. Markers of other ceramide synthetic pathways were unchanged. In PNPLA3(148MM/MI) vs. PNPLA3(148II), the increase in liver fat was due to polyunsaturated triacylglycerols while other lipids were unchanged. Similar changes were observed when data were analyzed using the 4 subgroups. Conclusions: Similar increases in liver fat and NASH are associated with a metabolically harmful saturated, ceramide-enriched liver lipidome in 'Metabolic NAFLD' but not in 'PNPLA3 NAFLD'. This difference may explain why metabolic but not PNPLA3 NAFLD increases the risk of type 2 diabetes and cardiovascular disease. (C) 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
  • Jacobson, Sara; Dahlqvist, Per; Johansson, Mattias; Svensson, Johan; Billing, Ola; Sund, Malin; Franklin, Oskar (2021)
    Objective: To determine the risk association between fasting glucose levels and pancreatic cancer using systematically collected prediagnostic blood glucose samples. Methods: Prospective nested case-control study of participants from the Northern Sweden Health and Disease Study, including 182 cases that developed pancreatic cancer and four matched controls per case. Blood glucose levels collected up to 24 years before pancreatic cancer diagnosis were analyzed. The association between fasting glucose levels and pancreatic cancer risk was determined using unconditional and conditional logistic regression models. The association between fasting glucose and the time to pancreatic cancer diagnosis, tumor stage and survival was determined using likelihood-ratio test, t test and log rank test. Results: The unadjusted risk of developing pancreatic cancer increased with increasing fasting glucose levels (OR 1.30, 95% CI 1.05-1.60, P = .015). Impaired fasting glucose (>6.1 mmol/L) was associated with an adjusted risk of 1.77 for developing pancreatic cancer (95% CI 1.05-2.99, P = .032). In subgroup analysis, fasting glucose levels were associated with an increased risk in never-smokers (OR 4.02, 95% CI 1.26-12.77, P = .018) and non-diabetics (OR 3.08, 95% CI 1.08-8.79, P = .035) (non-significant for interaction). The ratio between fasting glucose and BMI was higher among future pancreatic cancer patients and an increased ratio was associated with elevated risk of pancreatic cancer (OR 1.66, 95% CI 1.04-2.66, P = .034). Fasting glucose levels were not associated with TNM stage at diagnosis or survival. Conclusions: High fasting glucose is associated with an increased risk of being diagnosed with pancreatic cancer. (c) 2021 The Authors. Published by Elsevier B.V. on behalf of IAP and EPC. This is an open access article under the CC BY license (