Browsing by Subject "diabetes mellitus"

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Now showing items 21-31 of 31
  • Vakeva, Liisa; Lipsanen, Tuomas; Sintonen, Harri; Ranki, Annamari (2017)
    Cutaneous T-cell lymphomas (CTCL), especially mycosis fungoides, can be considered as a state of longstanding low-grade systemic inflammation. Many studies have focused on secondary cancers with CTCL, but information about comorbidities is limited. A total of 144 patients with CTCL at Helsinki University Central Hospital during 2005 to 2015 were studied to determine associated comorbidities and causes of death in this cohort. Compared with an age-standardized control population, the prevalence of type 2 diabetes mellitus was increased among patients with CTCL with no link to obesity. Patients with CTCL had a lower prevalence of hypertension, myocardial infarction and stroke than the control group. The 3 most common causes of death were CTCL, coronary artery disease and lung cancer. The increased risk of myocardial infarction or stroke reported previously was not detected in this patient group.
  • Hanson, Linda L. Magnusson; Rod, Naja Hulvej; Vahtera, Jussi; Peristera, Paraskevi; Pentti, Jaana; Rugulies, Reiner; Madsen, Ida Elisabeth Huitfeldt; LaMontagne, Anthony D.; Milner, Allison; Lange, Theis; Suominen, Sakari; Stenholm, Sari; Xu, Tianwei; Kivimäki, Mika; Westerlund, Hugo (2019)
    Objectives Several recent large-scale studies have indicated a prospective association between job strain and coronary heart disease, stroke and diabetes. Job strain is also associated with poorer mental health, a risk factor for cardiometabolic disease. This study investigates the prospective relationships between change in job strain, poor mental health and cardiometabolic disease, and whether poor mental health is a potential mediator of the relationship between job strain and cardiometabolic disease. Methods We used data from five cohort studies from Australia, Finland, Sweden and UK, including 47 757 men and women. Data on job strain across two measurements 1-5 years apart (time 1 (T1)-time 2 (T2)) were used to define increase or decrease in job strain. Poor mental health (symptoms in the top 25% of the distribution of the scales) at T2 was considered a potential mediator in relation to incident cardiometabolic disease, including cardiovascular disease and diabetes, following T2 for a mean of 5-18 years. Results An increase in job strain was associated with poor mental health (HR 1.56, 95% CI 1.38 to 1.76), and a decrease in job strain was associated with lower risk in women (HR 0.70, 95% CI 0.60-0.84). However, no clear association was observed between poor mental health and incident cardiometabolic disease (HR 1.08, 95% CI 0.96-1.23), nor between increase (HR 1.01, 95% CI 0.90-1.14) and decrease (HR 1.08, 95% CI 0.96-1.22) in job strain and cardiometabolic disease. Conclusions The results did not support that change in job strain is a risk factor for cardiometabolic disease and yielded no support for poor mental health as a mediator.
  • Hungarian Pancreatic Study Grp; Szentesi, Andrea; Parniczky, Andrea; Vincze, Aron; Sallinen, Ville; Hegyi, Peter (2019)
    Introduction: The incidence of acute pancreatitis (AP) and the prevalence of metabolic syndrome (MetS) are growing worldwide. Several studies have confirmed that obesity (OB), hyperlipidemia (HL), or diabetes mellitus (DM) can increase severity, mortality, and complications in AP. However, there is no comprehensive information on the independent or joint effect of MetS components on the outcome of AP. Our aims were (1) to understand whether the components of MetS have an independent effect on the outcome of AP and (2) to examine the joint effect of their combinations. Methods: From 2012 to 2017, 1435 AP cases from 28 centers were included in the prospective AP Registry. Patient groups were formed retrospectively based on the presence of OB, HL, DM, and hypertension (HT). The primary endpoints were mortality, severity, complications of AP, and length of hospital stay. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated. Results: 1257 patients (55.7 +/- 17.0 years) were included in the analysis. The presence of OB was an independent predictive factor for renal failure [OR: 2.98 (CI: 1.33-6.66)] and obese patients spent a longer time in hospital compared to non-obese patients (12.1 vs. 10.4 days, p = 0.008). HT increased the risk of severe AP [OR: 3.41 (CI: 1.39-8.37)], renal failure [OR: 7.46 (CI: 1.61-34.49)], and the length of hospitalization (11.8 vs. 10.5 days, p = 0.020). HL increased the risk of local complications [OR: 1.51 (CI: 1.10-2.07)], renal failure [OR: 6.4 (CI: 1.93-21.17)], and the incidence of newly diagnosed DM [OR: 2.55 (CI: 1.26-5.19)]. No relation was found between the presence of DM and the outcome of AP. 906 cases (mean age +/- SD: 56.9 +/- 16.7 years) had data on all four components of MetS available. The presence of two, three, or four MetS factors increased the incidence of an unfavorable outcome compared to patients with no MetS factors. Conclusion: OB, HT, and HL are independent risk factors for a number of complications. HT is an independent risk factor for severity as well. Components of MetS strongly synergize each other's detrimental effect. It is important to search for and follow up on the components of MetS in AP.
  • Cani, Patrice D.; de Vos, Willem M. (2017)
    Metabolic disorders associated with obesity and cardiometabolic disorders are worldwide epidemic. Among the different environmental factors, the gut microbiota is now considered as a key player interfering with energy metabolism and host susceptibility to several non-communicable diseases. Among the next-generation beneficial microbes that have been identified, Akkermansia muciniphila is a promising candidate. Indeed, A. muciniphila is inversely associated with obesity, diabetes, cardiometabolic diseases and low-grade inflammation. Besides the numerous correlations observed, a large body of evidence has demonstrated the causal beneficial impact of this bacterium in a variety of preclinical models. Translating these exciting observations to human would be the next logic step and it now appears that several obstacles that would prevent the use of A. muciniphila administration in humans have been overcome. Moreover, several lines of evidence indicate that pasteurization of A. muciniphila not only increases its stability but more importantly increases its efficacy. This strongly positions A. muciniphila in the forefront of next-generation candidates for developing novel food or pharma supplements with beneficial effects. Finally, a specific protein present on the outer membrane of A. muciniphila, termed Amuc_1100, could be strong candidate for future drug development. In conclusion, as plants and its related knowledge, known as pharmacognosy, have been the source for designing drugs over the last century, we propose that microbes and microbiomegnosy, or knowledge of our gut microbiome, can become a novel source of future therapies.
  • Viisanen, Hanna; Nuotio, Ulpukka; Kambur, Oleg; Mahato, Arun Kumar; Jokinen, Viljami; Lilius, Tuomas; Li, Wei; Santos, Hélder A; Karelson, Mati; Rauhala, Pekka; Kalso, Eija; Sidorova, Yulia A (2020)
    The glial cell line-derived neurotrophic factor (GDNF) family ligands (GFLs) alleviate symptoms of experimental neuropathy, protect and stimulate regeneration of sensory neurons in animal models of neuropathic pain, and restore their functional activity. However, clinical development of GFL proteins is complicated by their poor pharmacokinetic properties and multiple effects mediated by several receptors. Previously, we have identified a small molecule that selectively activates the major signal transduction unit of the GFL receptor complex, receptor tyrosine kinase RET, as an alternative to GFLs, for the treatment of neuropathic pain. We then introduced a series of chemical changes to improve the biological activity of these compounds and tested an optimized compound named BT44 in a panel of biological assays. BT44 efficiently and selectively stimulated the GFL receptor RET and activated the intracellular mitogene-activated protein kinase/extracellular signal-regulated kinase pathway in immortalized cells. In cultured sensory neurons, BT44 stimulated neurite outgrowth with an efficacy comparable to that of GFLs. BT44 alleviated mechanical hypersensitivity in surgery- and diabetes-induced rat models of neuropathic pain. In addition, BT44 normalized, to a certain degree, the expression of nociception-related neuronal markers which were altered by spinal nerve ligation, the neuropathy model used in this study. Our results suggest that the GFL mimetic BT44 is a promising new lead for the development of novel disease-modifying agents for the treatment of neuropathy and neuropathic pain.
  • Liimatainen, Sanna (Helsingin yliopisto, 2020)
    Parodontiitti ja diabetes ovat kroonisia, monitekijäisiä sairauksia, joiden kaksisuuntainen yhteys on ollut runsaan tutkimuksen kohteena. Molemmat ovat yleisiä, alidiagnosoituja sairauksia Suomen väestössä. Tämän kirjallisuuskatsauksena toteutettavan tutkielman tavoitteena on tarkastella parodontiitin ja diabeteksen patofysiologisia vuorovaikutusmekanismeja ja parodontologisen hoidon merkitystä diabeteksessa sekä arvioida näiden kliinistä merkitystä diabetespotilaita hoitavan lääkärin ja hammaslääkärin työssä. Tutkielmaa varten on perehdytty aiheeseen liittyviin tutkimuksiin ja kirjallisuuteen. Tutkimusten perusteella diabetespotilaat ovat suuremmassa riskissä sairastua parodontiittiin ja kiinnityskudostuho on heillä vaikea-asteisempaa. Diabeteksesta johtuvat hyperglykemia ja lipidimetabolian muutokset kiihdyttävät tulehdusta parodontaalikudoksissa muun muassa lisäämällä paikallisia proinflammatorisia sytokiineja, reaktiivisia happijohdannaisia, AGE/RAGE interaktioita ja RANKL/osteoprotegeriinin aktivaatiota. Parodontiitin aiheuttama systeeminen tulehduskuorma voi heikentää diabetespotilaan verensokeritasapainoa ja lisätä riskiä diabetekseen liittyviin komplikaatioihin. Diabetesta sairastamattomilla parodontiitti lisää riskiä sairastua prediabetekseen ja tyypin 2 diabetekseen. Parodontologisella hoidolla saattaa olla suotuisia vaikutuksia sokerihemoglobiinin ja lipidiprofiiliin tyypin 2 diabetesta sairastavilla. Diabetespotilaan suun terveys vaatii erityishuomiota hammaslääkäreiltä ja lääkäreiltä. Diabeteksen huono hoitotasapaino korreloi merkittävästi iensairauksien ongelmiin. Hoitamaton parodontiitti puolestaan voi suurentaa veren glukoosipitoisuutta.
  • Fernandez, C.; Rysä, J.; Almgren, P.; Nilsson, J.; Engström, G.; Orho-Melander, M.; Ruskoaho, H.; Melander, O. (2018)
    Background. Diabetes mellitus is linked to premature mortality of virtually all causes. Furin is a proprotein convertase broadly involved in the maintenance of cellular homeostasis; however, little is known about its role in the development of diabetes mellitus and risk of premature mortality. Objectives. To test if fasting plasma concentration of furin is associated with the development of diabetes mellitus and mortality. Methods. Overnight fasted plasma furin levels were measured at baseline examination in 4678 individuals from the population-based prospective Malmo Diet and Cancer Study. We studied the relation of plasma furin levels with metabolic and hemodynamic traits. We used multivariable Cox proportional hazards models to investigate the association between baseline plasma furin levels and incidence of diabetes mellitus and mortality during 21.3-21.7 years follow-up. Results. An association was observed between quartiles of furin concentration at baseline and body mass index, blood pressure and plasma concentration of glucose, insulin, LDL and HDL cholesterol (vertical bar 0.11 vertical bar Conclusion. Individuals with high plasma furin concentration have a pronounced dysmetabolic phenotype and elevated risk of diabetes mellitus and premature mortality.
  • Larsson, Martin; Castren, Maaret; Lindström, Veronica; von Euler, Mia; Patrone, Cesare; Wahlgren, Nils; Nathanson, David (2019)
    Objectives Hyperglycemia is a predictor for poor stroke outcome. Hyperglycemic stroke patients treated with thrombolysis have an increased risk of intracranial hemorrhage. Insulin is the gold standard for treating hyperglycemia but comes with a risk of hypoglycemia. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are drugs used in type 2 diabetes that have a low risk of hypoglycemia and have been shown to exert neuroprotective effects. The primary objective was to determine whether prehospital administration of the GLP-1RA exenatide could lower plasma glucose in stroke patients. Secondary objective was to study tolerability and safety. Materials & Methods Randomized controlled trial comparing exenatide administrated prehospitally with a control group receiving standard care for hyperglycemia. Patients with Face Arm Speech Test >= 1 and glucose >= 8 mmol/L were randomized. Glucose was monitored for 24 hours. All adverse events were recorded. Results Nineteen patients were randomized, eight received exenatide. An interim recruitment failure analysis with subsequent changes of the protocol was made. The study was stopped prematurely due to slow inclusion. No difference was observed in the main outcome of plasma glucose at 4 hours, control vs exenatide (mean, SD); 7.0 +/- 1.9 vs 7.6 +/- 1.6; P = .56). No major adverse events were reported. Conclusions We found no evidence that prehospital exenatide had effect on hyperglycemia. However, it was given without adverse events in this study with limited sample size that was prematurely stopped due to slow inclusion.
  • Huttunen-Lenz, Maija; Hansen, Sylvia; Christensen, Pia; Larsen, Thomas Meinert; Sando-Pedersen, Finn; Drummen, Mathijs; Adam, Tanja C.; Macdonald, Ian A.; Taylor, Moira A.; Alfredo Martinez, J.; Navas-Carretero, Santiago; Handjiev, Svetoslav; Poppitt, Sally D.; Silvestre, Marta P.; Fogelholm, Mikael; Pietilainen, Kirsi H.; Brand-Miller, Jennie; Berendsen, Agnes A. M.; Raben, Anne; Schlicht, Wolfgang (2018)
    Purpose: Onset of type 2 diabetes (T2D) is often gradual and preceded by impaired glucose homeostasis. Lifestyle interventions including weight loss and physical activity may reduce the risk of developing T2D, but adherence to a lifestyle change is challenging. As part of an international T2D prevention trial (PREVIEW), a behavior change intervention supported participants in achieving a healthier diet and physically active lifestyle. Here, our aim was to explore the influence of this behavioral program (PREMIT) on social-cognitive variables during an 8-week weight loss phase. Methods: PREVIEW consisted of an initial weight loss, Phase I, followed by a weight-maintenance, Phase II, for those achieving the 8-week weight loss target of >= 8% from initial bodyweight. Overweight and obese (BMI >= 25 kg/m(2))individuals aged 25 to 70 years with confirmed pre-diabetes were enrolled. Uni- and multivariate statistical methods were deployed to explore differences in intentions, self-efficacy, and outcome expectancies between those who achieved the target weight loss ("achievers") and those who did not ("non-achievers"). Results: At the beginning of Phase I, no significant differences in intentions, self-efficacy and outcome expectancies between "achievers" (1,857) and "non-achievers" (163) were found. "Non-achievers" tended to be younger, live with child/ren, and attended the PREMIT sessions less frequently. At the end of Phase I, "achievers" reported higher intentions (healthy eating chi(2)((1))=2.57; P <0.008, exercising chi(2)((1))=0.66; P <0.008), self-efficacy (F-(2;1970)=10.27, P Conclusion: Although statistically significant, effect sizes observed between the two groups were small. Behavior change, however, is multi-determined. Over a period of time, even small differences may make a cumulative effect. Being successful in behavior change requires that the "new" behavior is implemented time after time until it becomes a habit. Therefore, having even slightly higher self-efficacy, positive outcome expectancies and intentions may over time result in considerably improved chances to achieve long-term lifestyle changes.
  • Kraus, W.E.; Yates, T.; Tuomilehto, J.; Sun, J.-L.; Thomas, L.; Mcmurray, J.J.V.; Bethel, M.A.; Holman, R.R. (2018)
    Objective: Physical activity is related to clinical outcomes, even after adjusting for body mass, but is rarely assessed in randomized clinical trials. Research design and methods: We conducted an observational analysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial, in which a total of 9306 people from 40 countries with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors were randomized to receive nateglinide or placebo, in a 2-by-2 factorial design with valsartan or placebo. All were asked to also participate in a detailed lifestyle modification programme and followed-up for a median of 6.4 years with progression to diabetes as a co-primary end point. Seven-day ambulatory activity was assessed at baseline using research-grade pedometers. We assessed whether the baseline amount of physical activity was related to subsequent development of diabetes in individuals with impaired glucose tolerance. Results: Pedometer data were obtained on 7118 participants and 35.0% developed diabetes. In an unadjusted analysis each 2000-step increment in the average number of daily steps, up to 10 000, was associated with a 5.5% lower risk of progression to diabetes (HR 0.95, 95%CI 0.92 to 0.97), with >6% relative risk reduction after adjustment. Conclusions: Physical activity should be measured objectively in pharmacologic trials as it is a significant but underappreciated contributor to diabetes outcomes. It should be a regular part of clinical practice as well. © 2018 Author(s) (or their employer(s).
  • Kinnunen, Susanna; Karhapää, Pauli; Juutilainen, Auni; Finne, Patrik; Helanterä, Ilkka (2018)
    Background and objectives Infections are the most common noncardiovascular causes of death after kidney transplantation. We analyzed the current infection-related mortality among kidney transplant recipients in a nationwide cohort in Finland. Design, setting, participants, & measurements Altogether, 3249 adult recipients of a first kidney transplant from 1990 to 2012 were included. Infectious causes of death were analyzed, and the mortality rates for infections were compared between two eras (1990-1999 and 2000-2012). Risk factors for infectious deaths were analyzed with Cox regression and competing risk analyses. Results Altogether, 953 patients (29%) died during the follow-up, with 204 infection-related deaths. Mortality rate (per 1000 patient-years) due to infections was lower in the more recent cohort (4.6; 95% confidence interval, 3.5 to 6.1) compared with the older cohort (9.1; 95% confidence interval, 7.6 to 10.7); the incidence rate ratio of infectious mortality was 0.51 (95% confidence interval, 0.30 to 0.68). The main causes of infectious deaths were common bacterial infections: septicemia in 38% and pulmonary infections in 45%. Viral and fungal infections caused only 2% and 3% of infectious deaths, respectively (such as individual patients with Cytomegalovirus pneumonia, Herpes simplex virus meningoencephalitis, Varicella zoster virus encephalitis, and Pneumocystis jirovecii infection). Similarly, opportunistic bacterial infections rarely caused death; only one deathwas caused by Listeria monocytogenes, and two were caused by Mycobacterium tuberculosis. Only 23 (11%) of infection-related deaths occurred during the first post-transplant year. Older recipient age, higher plasma creatinine concentration at the end of the first post-transplant year, diabetes as a cause of ESKD, longer pretransplant dialysis duration, acute rejection, low albumin level, and earlier era of transplantation were associated with increased risk of infectious death in multivariable analysis. Conclusions The risk of death due to infectious causes after kidney transplantation in Finland dropped by one half since the 1990s. Common bacterial infections remained the most frequent cause of infection-related mortality, whereas opportunistic viral, fungal, or unconventional bacterial infections rarely caused deaths after kidney transplantation.