Browsing by Subject "diabetes mellitus"

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  • Inkeri, Niina-Mari; Karjalainen, Merja; Haanpaa, Maija; Kautiainen, Hannu; Saltevo, Juha; Mantyselka, Pekka; Tiihonen, Miia (2019)
    What is known and objective Anticholinergic drug use has been associated with a risk of central and peripheral adverse effects. There is a lack of information on anticholinergic drug use in persons with diabetes. The aim of this study is to investigate anticholinergic drug use and the association between anticholinergic drug use and self-reported symptoms in older community-dwelling persons with and without diabetes. Methods The basic population was comprised of Finnish community-dwelling primary care patients aged 65 and older. Persons with diabetes were identified according to the ICD-10 diagnostic codes from electronic patient records. Two controls adjusted by age and gender were selected for each person with diabetes. This cross-sectional study was based on electronic primary care patient records and a structured health questionnaire. The health questionnaire was returned by 430 (81.6%) persons with diabetes and 654 (73.5%) persons without diabetes. Data on prescribed drugs were obtained from the electronic patient records. Anticholinergic drug use was measured according to the Anticholinergic Risk Scale. The presence and strength of anticholinergic symptoms were asked in the health questionnaire. Results and discussion The prevalence of anticholinergic drug use was 8.9% in the total study cohort. There were no significant differences in anticholinergic drug use between persons with and without diabetes. There was no consistent association between anticholinergic drug use and self-reported symptoms. What is new and conclusion There is no difference in anticholinergic drug use in older community-dwelling persons with and without diabetes. Anticholinergic drug use should be considered individually and monitored carefully.
  • Tynjälä, Anniina; Forsblom, Carol; Groop, Per-Henrik; Gordin, Daniel; Harjutsalo, Valma (Helsingin yliopisto, 2020)
    The fact that individuals with type 1 diabetes (T1D) are at greater risk for cardiovascular disease and premature death, can only partly be explained by traditional risk factors. Interestingly, T1D is accompanied by arterial stiffening that correlates with microvascular and macrovascular complications. The aim of this study was to find out whether arterial stiffness predicts all-cause mortality in individuals with T1D. Augmentation index (AIx), a measure of arterial pulse wave reflections, is used to estimate stiffness in the resistance arteries and can be determined non-invasively from pulse wave analysis by applanation tonometry. The data consisted of 906 individuals with T1D from the FinnDiane Study that have been examined for arterial stiffness, cardiovascular risk factors and diabetic complications at baseline between 2001 and 2015. After a median follow-up of 8.2 (5.7-9.7) years, 67 individuals had died according to mortality data from Statistics Finland. They had higher baseline AIx (28 [21-33] vs. 19 [9-27] %, P < 0.001) compared to those alive. This association was independent of related risk factors (age, sex, BMI, HbA1c, triglycerides, renal function and past cardiovascular events) in Cox regression analysis (hazard ratio 1.042 [1.007-1.078], P = 0.017). Arterial stiffness estimated by AIx independently predicted all-cause mortality in T1D. Promising pharmacological agents counteracting arterial stiffness include inhibitors of the renin-angiotensin-aldosterone system and sodium-glucose co-transporter 2, and research data on their effect in individuals with T1D is constantly growing. Our finding suggests that detecting early arterial stiffening individuals with T1D could be useful in targeting a more aggressive treatment for high-risk individuals.
  • Laine, Merja K.; Wasenius, Niko S.; Lohi, Hannes; Simonen, Mika; Tiira, Katriina; Eriksson, Johan G.; Salonen, Minna K. (2019)
    Dog ownership has been reported to have beneficial effects on physical activity and emotional well-being, both known to reduce the risk for type 2 diabetes (T2D). The aim of this study was to evaluate the association between dog ownership during the whole life course and having T2D in later life. The study subjects consisted of 731 people (307 men and 424 women) from the Helsinki Birth Cohort Study. We assessed dog ownership with questionnaires, for every decade of life as well as current dog ownership. We investigated the associations between dog ownership and T2D with generalised estimating equation models and with generalised linear models. At a mean age of 71.0 (standard deviation [SD] 2.6) years, 13% of the participants had T2D. Dog ownership prior to the clinical examination was not associated with T2D (p >= 0.51). In men, but not in women, current dog owners had greater odds of having T2D compared with the non-owners when adjusted for age when clinically examined, socio-economic status, smoking, leisure-time physical activity, chronic diseases (OR = 3.32, 95% confidence interval 1.25-8.79, p = 0.016). In the age group of people around 70 years, dog ownership is not associated with reduced odds for developing T2D.
  • FinnDiane Study Grp; Eriksson, Marika; Summanen, Paula; Gordin, Daniel; Forsblom, Carol; Shams, Sara; Liebkind, Ron; Tatlisumak, Turgut; Putaala, Jukka; Groop, Per-Henrik; Martola, Juha; Thorn, Lena M. (2021)
    Introduction Cerebral small-vessel disease is common in neurologically asymptomatic individuals with type 1 diabetes. The retinal vasculature is thought to mirror the brain's vasculature, but data on this association are limited in type 1 diabetes. Our aim was to study associations between diabetic retinopathy severity and cerebral small-vessel disease in type 1 diabetes. Research design and methods For this cross-sectional study, we enrolled 189 participants with type 1 diabetes (median age 40 (33-45) years; 53% female; diabetes duration 21.6 (18.2-30.7) years) and 29 healthy age-matched and sex-matched controls as part of the Finnish Diabetic Nephropathy Study. Participants underwent a clinical investigation, brain MRI, and fundus imaging. Signs of cerebral small-vessel disease in brain MRIs were analyzed in relation to diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study (ETDRS) score). Results In type 1 diabetes, participants with cerebral small-vessel disease had higher ETDRS scores (35 (20-61) vs 20 (20-35), p=0.022) and a higher prevalence of proliferative diabetic retinopathy than those without cerebral small-vessel disease (25% vs 9%, p=0.002). In adjusted analysis, proliferative diabetic retinopathy was associated with cerebral small-vessel disease (OR 2.57 (95% CI 1.04 to 6.35)). Median ETDRS score (35 (20-65) vs 20 (20-35), p=0.024) and proliferative diabetic retinopathy prevalence were higher (29% vs 13%, p=0.002) in participants with versus without cerebral microbleeds. ETDRS scores increased by number of cerebral microbleeds (p=0.001), both ETDRS score (OR 1.05 (95% CI 1.02 to 1.09)) and proliferative diabetic retinopathy (8.52 (95% CI 1.91 to 37.94)) were associated with >2 cerebral microbleeds in separate multivariable analysis. We observed no association with white matter hyperintensities or lacunar infarcts. Conclusions Presence of cerebral small-vessel disease on brain MRI, particularly cerebral microbleeds, is associated with the severity of diabetic retinopathy.
  • Claesson, Tor-björn; Putaala, Jukka; Shams, Sara; Salli, Eero; Gordin, Daniel; Liebkind, Ron; Forsblom, Carol; Summanen, Paula A.; Tatlisumak, Turgut; Groop, Per-Henrik; Martola, Juha; Thorn, Lena M. (2020)
    Background and purpose: Degenerative change of the corpus callosum might serve as a clinically useful surrogate marker for net pathological cerebral impact of diabetes type 1. We compared manual and automatic measurements of the corpus callosum, as well as differences in callosal cross-sectional area between subjects with type 1 diabetes and healthy controls. Materials and methods: This is a cross-sectional study on 188 neurologically asymptomatic participants with type 1 diabetes and 30 healthy age- and sex-matched control subjects, recruited as part of the Finnish Diabetic Nephropathy Study. All participants underwent clinical work-up and brain MRI. Callosal area was manually measured and callosal volume quantified with FreeSurfer. The measures were normalized using manually measured mid-sagittal intracranial area and volumetric intracranial volume, respectively. Results: Manual and automatic measurements correlated well (callosal area vs. volume: rho = 0.83, p <0.001 and mid-sagittal area vs. intracranial volume: rho = 0.82, p <0.001). We found no significant differences in the callosal measures between cases and controls. In type 1 diabetes, the lowest quartile of normalized callosal area was associated with higher insulin doses (p = 0.029) and reduced insulin sensitivity (p = 0.033). In addition, participants with more than two cerebral microbleeds had smaller callosal area (p = 0.002). Conclusion: Manually measured callosal area and automatically segmented are interchangeable. The association seen between callosal size with cerebral microbleeds and insulin resistance is indicative of small vessel disease pathology in diabetes type 1.
  • Grzybowski, Andrzej; Kanclerz, Piotr; Huerva, Valentin; Ascaso, Francisco J.; Tuuminen, Raimo (2019)
    Diabetes mellitus is one of the most prevalent chronic diseases worldwide. Diabetic patients are at risk of developing cataract and present for surgery at an earlier age than non-diabetics. The aim of this study was to review the problems associated with cataract surgery in a diabetic patient. Corneal complications in diabetic patients include delayed wound healing, risk of developing epithelial defects or recurrent erosions due to the impairment of epithelial basement membranes and epithelial-stromal interactions. Diabetic patients present lower endothelial cell density and their endothelium is more susceptible to trauma associated with cataract surgery. A small pupil is common in diabetic patients making cataract surgery technically challenging. Finally diabetic patients have an increased risk for developing postoperative pseudophakic cystoid macular edema, posterior capsule opacification or endophthalmitis. In patients with pre-proliferative or proliferative diabetic retinopathy, diabetic macular edema or iris neovascularization adjunctive therapy such as an intravitreal anti-vascular endothelial growth factor injection, can inhibit exacerbation related to cataract surgery.
  • Helanterä, Ilkka; Ibrahim, Hassan N.; Lempinen, Marko; Finne, Patrik (2020)
    Background and objectives Increased donor age is one of the most important risk factors for delayed graft function (DGF), and previous studies suggest that the harmful effect of cold ischemia time is increased in kidneys from older donors. Our aim was to study the association of increased donor age and cold ischemia time with the risk of delayed graft function in a large cohort kidney transplants from the current era. Design, setting, participants, & measurements The Scientific Registry of Transplant Recipients was used for this observational, retrospective registry analysis to identify all deceased donor kidney transplantations in the United States between 2010 and September 2018, who were on dialysis pretransplantation (n=90,810). The association of donor age and cold ischemia time with the risk of DGF was analyzed in multivariable models adjusted for recipient characteristics (age, race, sex, diabetes, calculated panel-reactive antibodies, pretransplant dialysis duration) and donor characteristics (cause of death, sex, race, body mass index, creatinine, donation after circulatory death status, history of hypertension, and HLA mismatch). Results Cold ischemia time and donor age were independently associated with the risk of DGF, but the risk of DGF was not statistically significantly lower in donor age categories between 50 and 64 years, compared with donors ?65 years. The harmful association of cold ischemia time was not higher in kidneys from older donors in any age category, not even among donation after circulatory death donors. When donor risk was assessed with kidney donor profile index, although a statistically significant interaction with cold ischemia time was found, no practically meaningful increase in cold-ischemia susceptibility of kidneys with a high kidney donor profile index was found. Conclusions We were unable to demonstrate an association between donor age and DGF. The association of longer cold ischemia time with the risk of DGF was not magnified in older or more marginal donors.
  • Koopen, Annefleur; Witjes, Julia; Wortelboer, Koen; Majait, Soumia; Prodan, Andrei; Levin, Evgeni; Herrema, Hilde; Winkelmeijer, Maaike; Aalvink, Steven; Bergman, Jacques J. G. H. M.; Havik, Stephan; Hartmann, Bolette; Levels, Han; Bergh, Per-Olof; van Son, Jamie; Balvers, Manon; Bastos, Diogo Mendes; Stroes, Erik; Groen, Albert K.; Henricsson, Marcus; Kemper, Ellis Marleen; Holst, Jens; Strauch, Christopher M.; Hazen, Stanley L.; Backhed, Fredrik; De Vos, Willem M.; Nieuwdorp, Max; Rampanelli, Elena (2022)
    Objective Although gut dysbiosis is increasingly recognised as a pathophysiological component of metabolic syndrome (MetS), the role and mode of action of specific gut microbes in metabolic health remain elusive. Previously, we identified the commensal butyrogenic Anaerobutyricum soehngenii to be associated with improved insulin sensitivity in subjects with MetS. In this proof-of-concept study, we investigated the potential therapeutic effects of A. soehngenii L2-7 on systemic metabolic responses and duodenal transcriptome profiles in individuals with MetS. Design In this randomised double-blind placebo-controlled cross-over study, 12 male subjects with MetS received duodenal infusions of A. soehngenii/ placebo and underwent duodenal biopsies, mixed meal tests (6 hours postinfusion) and 24-hour continuous glucose monitoring. Results A. soehngenii treatment provoked a markedly increased postprandial excursion of the insulinotropic hormone glucagon-like peptide 1 (GLP-1) and an elevation of plasma secondary bile acids, which were positively associated with GLP-1 levels. Moreover, A. soehngenii treatment robustly shaped the duodenal expression of 73 genes, with the highest fold induction in the expression of regenerating islet-protein 1B (REG1B)-encoding gene. Strikingly, duodenal REG1B expression positively correlated with GLP-1 levels and negatively correlated with peripheral glucose variability, which was significantly diminished in the 24 hours following A. soehngenii intake. Mechanistically, Reg1B expression is induced upon sensing butyrate or bacterial peptidoglycan. Importantly, A. soehngenii duodenal administration was safe and well tolerated. Conclusions A single dose of A. soehngenii improves peripheral glycaemic control within 24 hours; it specifically stimulates intestinal GLP-1 production and REG1B expression. Further studies are needed to delineate the specific pathways involved in REG1B induction and function in insulin sensitivity.
  • Niinikoski, Iida-Maria (Helsingin yliopisto, 2019)
    This licentiate thesis consists of a literature review and a retrospective study. Diabetes mellitus is a common endocrinopathy in cats. It mainly resembles type II diabetes mellitus of humans, where the dysfunction of pancreatic beta cells together with peripheral insulin resistance causes increased blood glucose concentrations. Along with other risk factors such as breed and neuter status, obesity is closely related to the development of feline diabetes mellitus. The aim of the retrospective study was to assess risk factors and treatment protocols of diabetes mellitus. Factors influencing treatment outcome were also investigated. The results were compared with current scientific evidence. The hypotheses were that diabetic cats with an optimal body condition score (BCS) are more likely to achieve stable disease requiring administration of exogenous insulin and are more likely to achieve remission, where administration of exogenous insulin is no longer needed. The veterinary patient database ProvetNet was used to search for cats with diabetes mellitus presented to the University of Helsinki, Small Animal Teaching Hospital and the Saari Small Animal Clinic between March 2006 and March 2016. Data such as breed, gender, BCS and concurrent diseases were recorded for 123 cats. Statistical analyses were performed using GraphPad Prism. Neutered male cats had 2.8 times the risk of developing diabetes mellitus when compared to intact cats and neutered females. Domestic shorthair cats had 1.7 times the risk of developing diabetes mellitus when compared to other breeds. Remission rates were substantially lower than what has been reported in literature. The results did not support the hypotheses. Cats with an optimal BCS were not more likely to achieve stable disease or remission. However, the small sample size should be taken into consideration when interpreting the results. Investigating the relationship between BCS and diabetes mellitus was difficult due to incomplete documentation of BCS values and limitations of the veterinary patient database. Measures should be taken to develop the database so the evaluation and recording of BCS is a convenient routine. Further research into risk factors for both diabetes mellitus and obesity as well as treatment protocols resulting in remission is needed, so evidence-based data can be used for prevention and remission of the disease.
  • SUMMIT Steering Comm; CARDIOGRAMplusC4D Steering Comm; van Zuydam, Natalie R.; Ladenvall, Claes; Vlachopoulou, Efthymia; Perola, Markus; Sinisalo, Juha; Salomaa, Veikko; Groop, Leif; Ripatti, Samuli (2020)
    BACKGROUND: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D). METHODS: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D). RESULTS: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background. CONCLUSIONS: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.
  • Kallionpää, Roope A; Peltonen, Sirkku; Leppävirta, Jussi; Pöyhönen, Minna; Auranen, Kari; Järveläinen, Hannu; Peltonen, Juha (2021)
    BACKGROUND: The hereditary predisposition to diabetes is only partially explained by genes identified so far. Neurofibromatosis type 1 (NF1) is a rare monogenic dominant syndrome caused by aberrations of the NF1 gene. Here, we used a cohort of 1410 patients with NF1 to study the association of the NF1 gene with type 1 (T1D) and type 2 diabetes (T2D). METHODS: A total of 1410 patients were confirmed to fulfil the National Institutes of Health diagnostic criteria for NF1 by individually reviewing their medical records. The patients with NF1 were compared with 14 017 controls matched for age, sex and area of residence as well as 1881 non-NF1 siblings of the patients with NF1. Register-based information on purchases of antidiabetic medication and hospital encounters related to diabetes were retrieved. The Cox proportional hazards model was used to calculate the relative risk for diabetes in NF1. RESULTS: Patients with NF1 showed a lower rate of T2D when compared with a 10-fold control cohort (HR 0.27, 95% CI 0.17 to 0.43) or with their siblings without NF1 (HR 0.28, 95% CI 0.16 to 0.47). The estimates remained practically unchanged after adjusting the analyses for history of obesity and dyslipidaemias. The rate of T1D in NF1 was decreased although statistically non-significantly (HR 0.58, 95% CI 0.27 to 1.25). CONCLUSION: Haploinsufficiency of the NF1 gene may protect against T2D and probably T1D. Since NF1 negatively regulates the Ras signalling pathway, the results suggest that the Ras pathway may be involved in the pathogenesis of diabetes.
  • PLATO Investigators; Franchi, Francesco; James, Stefan K.; Lakic, Tatevik Ghukasyan; Lassila, Riitta (2019)
    Background-There are limited data on how the combination of diabetes mellitus (DM) and chronic kidney disease (CKD) affects cardiovascular outcomes as well as response to different P2Y(12) receptor antagonists, which represented the aim of the present investigation. Methods and Results-In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM+/CKD+ (n=1058), DM+/CKD- (n=2748), DM-/CKD+ (n=2160), and DM-/CKD- (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM+/CKD+ patients had a higher incidence of the primary end point compared with DM-/CKD- patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P Conclusions-In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD, with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD.
  • Mechchate, Hamza; Es-safi, Imane; Conte, Raffaele; Hano, Christophe; Amaghnouje, Amal; Jawhari, Fatima Zahra; Radouane, Nabil; Bencheikh, Noureddine; Grafov, Andriy; Bousta, Dalila (2021)
    Flaxseed is an oilseed (45-50% oil on a dry-weight basis) crop. Its oil has demonstrated multiple health benefits and industrial applications. The goal of this research was to evaluate the antidiabetic and anti-inflammatory potential of the free polyphenol fraction of flax (Linum usitatissimum L.) seeds (PLU), based on their use in traditional medicine. Mice with alloxan-induced diabetes were used to study the antidiabetic activity of PLU in vivo, with an oral administration of 25 and 50 mg/kg over 28 days. Measurements of body weight and fasting blood glucose (FBG) were carried out weekly, and biochemical parameters were evaluated. An oral glucose tolerance test was also performed. Inhibitory activities of PLU on alpha-amylase and alpha-glucosidase activities were evaluated in vitro. The anti-inflammatory was evaluated in vivo in Wistar rats using the paw edema induction Test by carrageenan, and in vitro using the hemolysis ratio test. PLU administration to diabetic mice during the study period improved their body weight and FBG levels remarkably. In vitro inhibitory activity of digestive enzymes indicated that they may be involved in the proposed mode of action of PLU extract. Qualitative results of PLU revealed the presence of 18 polyphenols. These findings support daily consumption of flaxseed for people with diabetes, and suggest that polyphenols in flaxseed may serve as dietary supplements or novel phytomedicines to treat diabetes and its complications.
  • EuroSIDA study; Mocroft, Amanda; Lundgren, Jens D.; Rockstroh, Juergen K.; Aho, Inka; Peters, Lars (2020)
    Background. The role of hepatitis C virus (HCV) coinfection and HCV-RNA in the development of diabetes mellitus (DM) in HIV-positive persons remains unclear. Methods. Poisson regression was used to compare incidence rates of DM (blood glucose >11.1 mmol/L, HbA1C >6.5% or >48 mmol/mol, starting antidiabetic medicine or physician reported date of DM onset) between current HIV/HCV groups (antiHCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, HCV-RNA-positive after HCV treatment). Results. A total of 16 099 persons were included; at baseline 10 091 (62.7%) were HCV-Ab-negative, 722 (4.5%) were spontaneous clearers, 3614 (22.4%) were chronically infected, 912 (5.7%) had been successfully treated, and 760 (4.7%) were HCV-RNApositive after treatment. During 136 084 person-years of follow-up (PYFU; median [interquartile range], 6.9 [3.6-13.2]), 1108 (6.9%) developed DM (crude incidence rate, 8.1/1000 PYFU; 95% CI, 7.7-8.6). After adjustment, there was no difference between the 5 HCV strata in incidence of DM (global P = .33). Hypertension (22.2%; 95% CI, 17.5%-26.2%) and body mass index >25 (22.0%; 95% CI, 10.4%-29.7%) had the largest population-attributable fractions for DM. Conclusions. HCV coinfection and HCV cure were not associated with DM in this large study. The biggest modifiable risk factors were hypertension and obesity, and continued efforts to manage such comorbidities should be prioritized.
  • Sares-Jäske, Laura; Knekt, Paul; Eranti, Antti; Kaartinen, Niina E.; Heliövaara, Markku; Männistö, Satu (2020)
    Introduction Observational and intervention studies have verified that weight loss predicts a reduced type 2 diabetes (T2D) risk. At the population level, knowledge on the prediction of self-report intentional weight loss (IWL) on T2D incidence is, however, sparse. We studied the prediction of self-report IWL on T2D incidence during a 15-year follow-up in a general adult population. Research design and methods The study sample from the representative Finnish Health 2000 Survey comprised 4270 individuals, aged 30-69 years. IWL was determined with questions concerning dieting attempts and weight loss during the year prior to baseline. Incident T2D cases during a 15-year follow-up were drawn from national health registers. The strength of the association between IWL and T2D incidence was estimated with the Cox model. Results During the follow-up, 417 incident cases of T2D occurred. IWL predicted an increased risk of T2D incidence (HR 1.44; 95% CI 1.11 to 1.87, p=0.008) in a multivariable model. In interaction analyses comparing individuals with and without IWL, a suggestively elevated risk emerged in men, the younger age group, among less-educated people and in individuals with unfavorable values in several lifestyle factors. Conclusions Self-report IWL may predict an increased risk of T2D in long-term, probably due to self-implemented IWL tending to fail. The initial prevention of weight gain and support for weight maintenance after weight loss deserve greater emphasis in order to prevent T2D.
  • Kangas, Heli (Helsingfors universitet, 2017)
    Tämän kirjallisuuskatsauksen tarkoituksena on perehtyä insuliinihormonin toimintaan elimistössä ja diabetes mellituksen patologiaan. Työssä esitellään lisäksi Suomen markkinoilla olevia insuliinivalmisteita ja niiden käyttömahdollisuudet koirien diabetes mellituksen hoidossa. Diabetes mellitus on yksi yleisimmistä endokrinologisista sairauksista koirilla ja sairauden kirjo on laaja. Diagnoosivaiheessa tyypillisimmin potilaalla on taustasta riippumatta haiman β-solujen toimintakyky heikentynyt niin, että tarvitaan insuliinin korvaushoitoa. Suomessa on tällä hetkellä vain yksi koiralle rekisteröity insuliinivalmiste. Eläinlääketieteen puolella pyritään yksilölliseen hoitoon ja Suomen lääkelainsäädännön kaskadisäännösten mukaisesti voidaan eläimillä käyttää myös ihmisille rekisteröityjä valmisteita, mikäli eläimen yksilöllinen hoito sen vaatii. Muita saatavilla olevia insuliinivalmisteita ovat erilaiset pitkä-, keskipitkä- ja pikavaikutteiset ihmisille rekisteröidyt insuliinivalmisteet. Synteettisten insuliinianalogien aminohappojärjestykseen on tehty muutoksia, joiden avulla imeytymisnopeus ihonalaistilasta ja sitoutuminen veren proteiineihin vaikuttaa niiden vaikutusaikaan ja -profiiliin. Toisissa insuliinivalmisteissa apuaineet vaikuttavat vastaavilla tavoilla. Yksilöllisessä hoidossa tulee insuliinivalmiste valita potilaalle sopivaksi. Mikäli aiemmin aloitetulla valmisteella ei ole haluttua hoitovastetta, tulee harkita toista valmistetta. Tätä ennen tulee kuitenkin poissulkea mahdolliset insuliiniresistenssiä aiheuttavat tilat, infektiot, vasta-aineiden muodostus ja glukoosiaineenvaihduntaan vaikuttavat sairaudet. Diabetes mellitusta sairaustavan koirapotilaan hoidossa tulee lisäksi huomioida monia muitakin asioita kuin vain insuliinihoito. Potilaan kotihoito käsittää myös ruokinnan sovelluttamisen hoitoon. Koiran ruokavalion tulee tukea hoitoa ja se vaikuttaa suuresti myös käytettävän insuliinivalmisteen valintaan. Hyvän hoitosuhteen luominen omistajaan ja hänen koiraansa auttavat havaitsemaan muutokset hoitovasteessa nopeasti. Insuliinihoidon tavoitteena on hyvinvoiva potilas, kliinisten oireiden pitäminen hallinnassa sekä haittavaikutusten minimointi. Hyvällä hoitovasteella pyritään ennaltaehkäisemään diabeettisten liitännäissairauksien syntyä tai ainakin hidastamaan jo syntyneiden sairauksien etenemistä. Hoidon eri vaiheissa voidaan potilaan sairauden kehittymistä ja hoitovastetta seurata eri laboratoriomääritysten avulla. Insuliini- tai c-peptidimäärityksillä voidaan todentaa insuliinituotannon tila. Lisäksi c-peptidillä voidaan seurata prediabeetikon sairauden kehittymistä ja insuliinikorvaushoidon aloittamista tai lääkityksen hienosäätöä. Pidempiaikaista glukoositasapainosta antavat tietoa glykolysoituneiden proteiinien laboratoriomääritykset. Fruktosamiini ja glykolysoitunut hemoglobiini (hbA1c) auttavat kliinikkoa hoitovasteen seurannassa. Koirille tehtyjä kliinisiä tutkimuksia eri insuliinivalmisteiden vaikutuksista on varsin vähän. Lisäksi tutkimusten potilasmäärät ovat vähäisiä, vaihtelua on paljon ja kriteerit potilaiden valintaan vaihtelevat. Insuliinivalmisteiden vaikutusajasta ja huippuvaikutusajankohdista vaikuttavat monet tekijät, muun muassa endogeenisen insuliinituotannon vaikutukset glukoosikäyriin. Uusia hoitomuotoja ja -tapoja ja niiden sovelluksia tulee jatkuvasti. Humaanilääketieteen puolella on kehitteillä insuliinivalmisteita, joiden kudosspesifisyys on lähempänä fysiologisen insuliinin vaikutusta. Eläinlääketieteessä taasen ollaan pohdittu muun muassa monipistoshoidon sovelluttamista koirien diabeteksen hoitoon.
  • Kylliäinen, Annika (Helsingfors universitet, 2016)
    Tutkielma koostuu kirjallisuuskatsauksesta sekä tutkimusosasta, jonka tavoitteena oli selvittää Yliopistollisessa eläinsairaalassa vuosina 2006-2015 käyneiden koirien rodun ja ylipainon merkitystä sairastua diabetes mellitukseen. Kirjallisuuskatsauksessa selvitettiin lisäksi sairauden etiologiaa, patogeneesiä ja hoitoa. Tutkimus suoritettiin retrospektiivisenä, deskriptiivisenä kohorttitutkimuksena. Koirien diabetes mellitus on yleinen endokrinologinen sairaus. Koiran diabetes muistuttaa ihmisen tyypin 1 diabetestä. Lisäksi on havaittu insuliiniresistenssistä johtuvaa diabetestä sekä narttukoirilla jälkikiiman tai tiineyden aiheuttamaa diabetestä. Kirjallisuuskatsauksessa havaittiin rotualttiuden vaihtelevan eri maissa tehtyjen tutkimusten perusteella. Rotualttius on havaittu esimerkiksi australianterriereillä, samojedinkoirilla, cavalier kingcharlesinspanielilla, pohjoisilla pystykorvaroduilla, kuten suomenpystykorvalla ja jämtlanninpystykorvilla, sekä villakoirilla. Näiden lisäksi oli useita muita rotuja mainittu tutkimuksissa. Matalan riskin rotuja puolestaan ovat esimerkiksi saksanpaimenkoira, kultainennoutaja sekä bokseri. Lihavuuden aiheuttamaa insuliiniresistenssiä ja siitä aiheutuvaa diabetes mellitusta on todettu kissalla ja ihmisellä. Lihavuuden on todettu aiheuttavan insuliiniresistenssiä koirilla, mutta se ei kuitenkaan johda tyypin 2 diabetekseen. Tutkimusosan aineistossa sairastuneita koiria oli kaikkiaan 145 kappaletta, jotka edustivat 50 eri rotua. Rodun ja kuntoluokan ohella tutkimuksessa huomioitiin useita eri tekijöitä kuten ikä ja samanaikaiset sairaudet. Rotujen riskejä sairastua arvioitiin käyttämällä suhteellista riskiä (RR). Tutkimuksessa todettiin 7 rotua, joiden riski sairastua oli tilastollisesti merkitsevä. Nämä olivat australianterrieri, bichon frisé, suomenlapinkoira, kääpiösnautseri, valkoinen länsiylämaanterrieri, cavalier kingcharlesinspanieli sekä sekarotuiset koirat. Suurimman riskin rotu oli australianterrieri 23,6-kertaisella riskillä sairastua diabetes mellitukseen muihin rotuihin nähden. Bichon friséllä riski sairastua oli 4,7-kertainen ja suomenlapinkoiralla 3,4-kertainen muihin rotuihin nähden. Muiden tutkimuksessa huomioitujen rotujen riskit sairastua olivat 2–3-kertaiset. Kuntoluokan ja ylipainon vaikutusta diabetes mellituksen syntyyn ei voitu tarkastella puutteellisen dokumentaation sekä potilasohjelman rajallisuuden vuoksi. Yliopistollisen eläinsairaalan potilastietojen dokumentaatiota tulisi yhtenäistää ja potilasohjelmaa kehittää siten, että se palvelisi jatkossa tutkimusten suorittamista. Tulevaisuudessa ehdottaisin jatkotutkimusena australianterriereillä tehtyä prospektiivista tutkimusta, jonka hypoteesina olisi, että australianterriereillä esiintyy merkitsevästi enemmän diabetes mellitusta kuin muilla roduilla.
  • Rintamäki, Karla (Helsingin yliopisto, 2021)
    Tässä kirjallisuuskatsauksessa käsitellään koirien autoimmuuniperäisten endokrinologisten sairauksien, eli kilpirauhasen vajaatoiminnan, lisäkilpirauhasen vajaatoiminnan, diabetes mellituksen eli sokeritaudin, sekä lisämunuaiskuoren vajaatoiminnan esiintyvyyttä, etiologiaa, patofysiologiaa sekä diagnostiikkaa. Tavoitteena on koota tietoa autoimmuuneista endokrinologisista sairauksista koirilla, jotta eläinlääkärit osaisivat tunnistaa sairaudet ajoissa, sekä huomioisivat myös sairauksien mahdolliset päällekkäisyydet ja niiden vaikutukset diagnostiikkaan. Kilpirauhasen vajaatoiminnan esiintyvyys vaihtelee välillä 0.2–0.9 %. Kilpirauhasen vajaatoiminta voi olla primaarista, sekundaarista tai tertiaarista. Primaarisessa muodossa, joka on yleisin muoto koirilla, autoimmuunitulehdus tuhoaa kilpirauhaskudosta, mikä johtaa kilpirauhashormonien puutokseen ja häiriöihin aineenvaihduntaprosesseissa, muun muassa rasva-, hiilihydraatti- ja proteiiniaineenvaihdunnassa, sekä hormonien ja mineraalien tuotannossa ja sydämen toiminnassa. Kilpirauhasen vajaatoiminnan diagnoosi perustuu tyypillisiin oireisiin, matalaan vapaan tyroksiinin arvoon ja samanaikaiseen korkeaan tyreotropiiniarvoon. Diagnoosia tehdessä tulee muistaa lukuisat kilpirauhasarvoihin vaikuttavat tekijät. Lisäkilpirauhasen vajaatoiminta on hyvin harvinainen sairaus koiralla, eikä sen esiintyvyydestä ole tietoa. Lisäkilpirauhasen vajaatoiminta voi olla primaarista tai sekundaarista, ja näistä primaarinen on yleisempi. Primaarisen on ajateltu olevan autoimmuuniperäistä, mutta tästä kaivattaisiin vielä lisätutkimusta. Vajaatoiminta johtaa parathormonin puutteeseen, joka puolestaan johtaa hypokalsemiaan ja sen aiheuttamiin hermosto- ja lihasoireisiin. Lisäkilpirauhasen vajaatoiminta diagnosoidaan samanaikaisella hypokalsemialla, hyperfosfatemialla ja matalalla tai viiterajojen alatasolla olevalla parathormoniarvolla. Lisäksi voidaan ottaa koepalat lisäkilpirauhasesta. Diabetes mellitus on koirien endokrinologisista autoimmuunisairauksista yleisin, esiintyvyyden ollessa 0.32–1.33 %. Diabetes voi olla tyyppiä 1 tai 2, ja lisäksi voi olla sekundaarista diabetesta. Tyypin 1 diabetes on koirilla yleisin, ja se johtuu autoimmuunireaktion aiheuttamasta betasolutuhosta, jolloin syntyy insuliinipuutos ja veren glukoosipitoisuus nousee. Diagnoosi perustuu tyypillisiin oireisiin ja samanaikaiseen korkeaan glukoositasoon sekä glukoosin esiintymiseen virtsassa. Lisämunuaiskuoren vajaatoiminta on koirilla harvinainen, ja sen esiintyvyys vaihtelee välillä 0.06–0.28 % tutkimuksesta riippuen. Etiologia voi olla primaarista tai sekundaarista, ja näistä primaarinen on yleensä autoimmuuniperäistä, mutta tämä voi myös olla ei-autoimmuunista. Sairaudessa lisämunuaiskuori ei tuota glukokortikoideja eikä mineralokortikoideja, johtaen hyponatremiaan sekä hyperkalemiaan. Varma diagnoosi tehdään ACTH-stimulaatiotestillä. Endokrinologiset sairaudet voivat esiintyä samanaikaisina, mikä tuo haasteita diagnostiikalle. Samanaikaiset sairaudet vaikuttavat laboratorioarvoihin sekä diagnostisten testien tuloksiin. Lisäksi oirekuvissa ja poikkeavissa laboratorioarvoissa voi olla päällekkäisyyksiä. Tämän vuoksi on tärkeää, että eläinlääkärit osaavat tunnistaa sairaudet erillisinä sairauksina, mutta pitävät mielessään myös mahdolliset rinnakkaissairaudet etenkin, jos diagnostiset testit eivät ole yhdenmukaisia, oirekuva ei täysin selity diagnoosilla tai jos eläintä ei saada hoitotasapainoon.
  • Kivelä, Jemina; Meinilä, Jelena; Uusitupa, Matti; Tuomilehto, Jaakko; Lindström, Jaana (2022)
    Context Circulating branched-chain amino acids (BCAAs) are associated with the risk of type 2 diabetes (T2D). Objective We examined to what extent lifestyle intervention aiming to prevent T2D interacts with this association and how BCAA concentrations change during the intervention. Methods We computed trajectory clusters by k-means clustering of serum fasting BCAAs analyzed annually by mass spectrometry during a 4-year intervention. We investigated whether baseline BCAAs, BCAA trajectories, and BCAA change trajectories predicted T2D and whether BCAAs predicted T2D differently in the intervention (n = 198) and control group (n = 196). Results Elevated baseline BCAAs predicted the incidence of T2D in the control group (hazard ratio [HR] 1.05 per 10 mu mol/L, P = 0.01), but not in the intervention group. BCAA concentration decreased during the first year in the whole cohort (mean -14.9 mu mol/L, P < 0.001), with no significant difference between the groups. We identified 5 BCAA trajectory clusters and 5 trajectory clusters for the change in BCAAs. Trajectories with high mean BCAA levels were associated with an increased HR for T2D compared with the trajectory with low BCAA levels (trajectory with highest vs lowest BCAA, HR 4.0; P = 0.01). A trajectory with increasing BCAA levels had a higher HR for T2D compared with decreasing trajectory in the intervention group only (HR 25.4, P < 0.001). Conclusion Lifestyle intervention modified the association of the baseline BCAA concentration and BCAA trajectories with the incidence of T2D. Our study adds to the accumulating evidence on the mechanisms behind the effect of lifestyle changes on the risk of T2D.
  • Wasenius, Niko S.; Isomaa, Bo A.; Östman, Bjarne; Söderström, Johan; Forsen, Björn; Lahti, Kaj; Hakaste, Liisa; Eriksson, Johan G.; Groop, Leif; Hansson, Ola; Tuomi, Tiinamaija (2020)
    Introduction To investigate the effect of an exercise prescription and a 1-year supervised exercise intervention, and the modifying effect of the family history of type 2 diabetes (FH), on long-term cardiometabolic health. Research design and methods For this prospective randomized trial, we recruited non-diabetic participants with poor fitness (n=1072, 30-70 years). Participants were randomly assigned with stratification for FH either in the exercise prescription group (PG, n=144) or the supervised exercise group (EG, n=146) group and compared with a matched control group from the same population study (CON, n=782). The PG and EG received exercise prescriptions. In addition, the EG attended supervised exercise sessions two times a week for 60 min for 12 months. Cardiometabolic risk factors were measured at baseline, 1 year, 5 years, and 6 years. The CON group received no intervention and was measured at baseline and 6 years. Results The EG reduced their body weight, waist circumference, diastolic blood pressure, and low-density lipoprotein-cholesterol (LDL-C) but not physical fitness (p=0.074) or insulin or glucose regulation (p>0.1) compared with the PG at 1 year and 5 years (p Conclusions Low-cost physical activity programs have long-term beneficial effects on cardiometabolic health regardless of the FH of diabetes. Given the feasibility and low cost of these programs, they should be advocated to promote cardiometabolic health.