Browsing by Subject "Diabetes"

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  • Ahluwalia, Tarunveer S.; Schulz, Christina-Alexandra; Waage, Johannes; Skaaby, Tea; Sandholm, Niina; van Zuydam, Natalie; Charmet, Romain; Bork-Jensen, Jette; Almgren, Peter; Thuesen, Betina H.; Bedin, Mathilda; Brandslund, Ivan; Christensen, Cramer K.; Linneberg, Allan; Ahlqvist, Emma; Groop, Per-Henrik; Hadjadj, Samy; Tregouet, David-Alexandre; Jorgensen, Marit E.; Grarup, Niels; Pedersen, Oluf; Simons, Matias; Groop, Leif; Orho-Melander, Marju; McCarthy, Mark I.; Melander, Olle; Rossing, Peter; Kilpeläinen, Tuomas O.; Hansen, Torben (2019)
    Aims/hypothesisIdentifying rare coding variants associated with albuminuria may open new avenues for preventing chronic kidney disease and end-stage renal disease, which are highly prevalent in individuals with diabetes. Efforts to identify genetic susceptibility variants for albuminuria have so far been limited, with the majority of studies focusing on common variants.MethodsWe performed an exome-wide association study to identify coding variants in a two-stage (discovery and replication) approach. Data from 33,985 individuals of European ancestry (15,872 with and 18,113 without diabetes) and 2605 Greenlanders were included.ResultsWe identified a rare (minor allele frequency [MAF]: 0.8%) missense (A1690V) variant in CUBN (rs141640975, =0.27, p=1.3x10(-11)) associated with albuminuria as a continuous measure in the combined European meta-analysis. The presence of each rare allele of the variant was associated with a 6.4% increase in albuminuria. The rare CUBN variant had an effect that was three times stronger in individuals with type 2 diabetes compared with those without (p(interaction)=7.0x10(-4), with diabetes=0.69, without diabetes=0.20) in the discovery meta-analysis. Gene-aggregate tests based on rare and common variants identified three additional genes associated with albuminuria (HES1, CDC73 and GRM5) after multiple testing correction (p(Bonferroni)
  • Smyth, L. J; Kilner, J.; Nair, V.; Liu, H.; Brennan, E.; Kerr, K.; Sandholm, N.; Cole, J.; Dahlström, E.; Syreeni, A.; Salem, R. M; Nelson, R. G; Looker, H. C; Wooster, C.; Anderson, K.; McKay, G. J; Kee, F.; Young, I.; Andrews, D.; Forsblom, C.; Hirschhorn, J. N; Godson, C.; Groop, P. H; Maxwell, A. P; Susztak, K.; Kretzler, M.; Florez, J. C; McKnight, A. J (BioMed Central, 2021)
    Abstract Background A subset of individuals with type 1 diabetes mellitus (T1DM) are predisposed to developing diabetic kidney disease (DKD), the most common cause globally of end-stage kidney disease (ESKD). Emerging evidence suggests epigenetic changes in DNA methylation may have a causal role in both T1DM and DKD. The aim of this exploratory investigation was to assess differences in blood-derived DNA methylation patterns between individuals with T1DM-ESKD and individuals with long-duration T1DM but no evidence of kidney disease upon repeated testing to identify potential blood-based biomarkers. Blood-derived DNA from individuals (107 cases, 253 controls and 14 experimental controls) were bisulphite treated before DNA methylation patterns from both groups were generated and analysed using Illumina’s Infinium MethylationEPIC BeadChip arrays (n = 862,927 sites). Differentially methylated CpG sites (dmCpGs) were identified (false discovery rate adjusted p ≤ × 10–8 and fold change ± 2) by comparing methylation levels between ESKD cases and T1DM controls at single site resolution. Gene annotation and functionality was investigated to enrich and rank methylated regions associated with ESKD in T1DM. Results Top-ranked genes within which several dmCpGs were located and supported by functional data with methylation look-ups in other cohorts include: AFF3, ARID5B, CUX1, ELMO1, FKBP5, HDAC4, ITGAL, LY9, PIM1, RUNX3, SEPTIN9 and UPF3A. Top-ranked enrichment pathways included pathways in cancer, TGF-β signalling and Th17 cell differentiation. Conclusions Epigenetic alterations provide a dynamic link between an individual’s genetic background and their environmental exposures. This robust evaluation of DNA methylation in carefully phenotyped individuals has identified biomarkers associated with ESKD, revealing several genes and implicated key pathways associated with ESKD in individuals with T1DM.
  • Junttila, Ilkka S.; Vuorio, Alpo; Budowle, Bruce; Laukkala, Tanja; Sajantila, Antti (2018)
    Diabetes mellitus (DM) could cause pilot incapacitation and result in aviation fatalities. The mechanisms could be directly as a consequence of acute hypoglycemia/subacute diabetic ketoacidosis (DKA) or indirectly as an acute cardiovascular event by contributing to the development of atherosclerosis in coronary or carotid and cerebral arteries. In this study, DM-related fatal flight accidents in the US National Transport Bureau's database between years 2011-2016 were analyzed with special emphasis on postmortem (PM) glucose levels and correlation of toxicological reports with anamnestic information on DM. Additionally, autopsy results on coronary arteries were reviewed. In 43 out of 1491 (similar to 3%) fatal accidents pilots had DM. Postmortem glucose or glycated hemoglobin percentage (Hb1Ac) was measured in 12 of the 43 cases; while antidiabetic medication was found in 14 of the cases (only two of the cases had both glucose measurements and medication). With the increasing prevalence of DM, a possibility of pilot incapacitation due to DM or complications of DM should be actively studied, even if no anamnestic information of DM was available. While PM hypoglycemia is difficult to assess, we propose a systematic investigation based on measurement of glucose, Hb1Ac%, and ketone bodies, and documentation of atherosclerotic lesions in major arteries to identify or rule out DM as a cause of pilot incapacitation.
  • Leskinen, Tuija; Stenholm, Sari; Heinonen, Olli J.; Pulakka, Anna; Aalto, Ville; Kivimäki, Mika; Vahtera, Jussi (2018)
    This study aims to examine the association between change in physical activity over time and accumulation of cardiometabolic risk factors. Four consecutive surveys (Time 1 to 4) were conducted with 4-year intervals in 1997-2013 (the Finnish Public Sector study). Physical activity of 15,634 cardio-metabolically healthy participants (mean age 43.3 (SD 8.7) years, 85% women) was assessed using four-item survey measure and was expressed as weekly metabolic equivalent (MET) hours in Time 1, 2, and 3. At each time point, participants were categorised into low (<14 MET-h/week), moderate (>= 14 to<30 MET-h/week), or high (>= 30MET-h/week) activity level and change in physical activity levels between Time 1 and 3 (over 8 years) was determined. The outcome was the number of incident cardiometabolic risk factors (hypertension, dyslipidemia, diabetes, and obesity) at Time 4. Cumulative logistic regression was used for data analysis. Compared to maintenance of low physical activity, increase in physical activity from low baseline activity level was associated with decreased accumulation of cardiometabolic risk factors in a dose-response manner (cumulative odds ratio [cOR]= 0.73, 95% CI 0.59-0.90 for low-to-moderate and cOR= 0.67, 95% CI 0.49-0.89 for low-to-high, P for trend 0.0007). Decrease in physical activity level from high to low was associated with increased accumulation of cardiometabolic risk factors (cOR= 1.60, 95% CI 1.27-2.01) compared to those who remained at high activity level. Thus even a modest long-term increase in physical activity was associated with reduction in cardiometabolic risk whereas decrease in physical activity was related to increased risk.
  • Presseau, Justin; Mackintosh, Joan; Hawthorne, Gillian; Francis, Jill J.; Johnston, Marie; Grimshaw, Jeremy M.; Steen, Nick; Coulthard, Tom; Brown, Heather; Kaner, Eileen; Elovainio, Marko; Sniehotta, Falko F. (2018)
    Background: National diabetes audits in the UK show room for improvement in the quality of care delivered to people with type 2 diabetes in primary care. Systematic reviews of quality improvement interventions show that such approaches can be effective but there is wide variability between trials and little understanding concerning what explains this variability. A national cohort study of primary care across 99 UK practices identified modifiable predictors of healthcare professionals' prescribing, advising and foot examination. Our objective was to evaluate the effectiveness of an implementation intervention to improve six guideline-recommended health professional behaviours in managing type 2 diabetes in primary care: prescribing for blood pressure and glycaemic control, providing physical activity and nutrition advice and providing updated diabetes education and foot examination. Methods: Two-armed cluster randomised trial involving 44 general practices. Primary outcomes (at 12 months follow-up): from electronic medical records, the proportion of patients receiving additional prescriptions for blood pressure and insulin initiation for glycaemic control and having a foot examination; and from a patient survey of a random sample of 100 patients per practice, reported receipt of updated diabetes education and physical activity and nutrition advice. Results: The implementation intervention did not lead to statistically significant improvement on any of the six clinical behaviours. 1,138,105 prescriptions were assessed. Intervention (29% to 37% patients) and control arms (31% to 35%) increased insulin initiation relative to baseline but were not statistically significantly different at follow-up (IRR 1.18, 95% CI 0.95-1.48). Intervention (45% to 53%) and control practices (45% to 50%) increased blood pressure prescription from baseline to follow-up but were not statistically significantly different at follow-up (IRR 1.05, 95% CI 0.96 to 1.16). Intervention (75 to 78%) and control practices (74 to 79%) increased foot examination relative to baseline; control practices increased statistically significantly more (OR 0.84, 95% CI 0.75-0.94). Fewer patients in intervention (33%) than control practices (40%) reported receiving updated diabetes education (OR = 0.74, 95% CI 0.57-0.97). No statistically significant differences were observed in patient reports of having had a discussion about nutrition (intervention = 73%; control = 72%; OR = 0.98, 95% CI 0.59-1.64) or physical activity (intervention = 57%; control = 62%; OR = 0.79, 95% CI 0. 56-1.11). Development and delivery of the intervention cost 1191 pound per practice. Conclusions: There was no measurable benefit to practices' participation in this intervention. Despite widespread use of outreach interventions worldwide, there is a need to better understand which techniques at which intensity are optimally suited to address the multiple clinical behaviours involved in improving care for type 2 diabetes.
  • Presseau, Justin; Mackintosh, Joan; Hawthorne, Gillian; Francis, Jill J; Johnston, Marie; Grimshaw, Jeremy M; Steen, Nick; Coulthard, Tom; Brown, Heather; Kaner, Eileen; Elovainio, Marko; Sniehotta, Falko F (BioMed Central, 2018)
    Abstract Background National diabetes audits in the UK show room for improvement in the quality of care delivered to people with type 2 diabetes in primary care. Systematic reviews of quality improvement interventions show that such approaches can be effective but there is wide variability between trials and little understanding concerning what explains this variability. A national cohort study of primary care across 99 UK practices identified modifiable predictors of healthcare professionals’ prescribing, advising and foot examination. Our objective was to evaluate the effectiveness of an implementation intervention to improve six guideline-recommended health professional behaviours in managing type 2 diabetes in primary care: prescribing for blood pressure and glycaemic control, providing physical activity and nutrition advice and providing updated diabetes education and foot examination. Methods Two-armed cluster randomised trial involving 44 general practices. Primary outcomes (at 12 months follow-up): from electronic medical records, the proportion of patients receiving additional prescriptions for blood pressure and insulin initiation for glycaemic control and having a foot examination; and from a patient survey of a random sample of 100 patients per practice, reported receipt of updated diabetes education and physical activity and nutrition advice. Results The implementation intervention did not lead to statistically significant improvement on any of the six clinical behaviours. 1,138,105 prescriptions were assessed. Intervention (29% to 37% patients) and control arms (31% to 35%) increased insulin initiation relative to baseline but were not statistically significantly different at follow-up (IRR 1.18, 95%CI 0.95–1.48). Intervention (45% to 53%) and control practices (45% to 50%) increased blood pressure prescription from baseline to follow-up but were not statistically significantly different at follow-up (IRR 1.05, 95%CI 0.96 to 1.16). Intervention (75 to 78%) and control practices (74 to 79%) increased foot examination relative to baseline; control practices increased statistically significantly more (OR 0.84, 95%CI 0.75–0.94). Fewer patients in intervention (33%) than control practices (40%) reported receiving updated diabetes education (OR = 0.74, 95%CI 0.57–0.97). No statistically significant differences were observed in patient reports of having had a discussion about nutrition (intervention = 73%; control = 72%; OR = 0.98, 95%CI 0.59–1.64) or physical activity (intervention = 57%; control = 62%; OR = 0.79, 95%CI 0.56–1.11). Development and delivery of the intervention cost £1191 per practice. Conclusions There was no measurable benefit to practices’ participation in this intervention. Despite widespread use of outreach interventions worldwide, there is a need to better understand which techniques at which intensity are optimally suited to address the multiple clinical behaviours involved in improving care for type 2 diabetes. Trial registration ISRCTN, ISRCTN66498413 . Registered April 4, 2013
  • Lahti-Pulkkinen, Marius; Bhattacharya, Sohinee; Wild, Sarah H.; Lindsay, Robert S.; Räikkönen, Katri; Norman, Jane E.; Bhattacharya, Siladitya; Reynolds, Rebecca M. (2019)
    Aims/hypothesis Maternal obesity in pregnancy is associated with cardiovascular disease and mortality rate in the offspring. We aimed to determine whether maternal obesity is also associated with increased incidence of type 2 and type 1 diabetes in the offspring, independently of maternal diabetes as a candidate mechanistic pathway. Methods Birth records of 118,201 children from 1950 to 2011 in the Aberdeen Maternity and Neonatal Databank were linked to Scottish Care Information-Diabetes, the national register for diagnosed diabetes in Scotland, to identify incident and prevalent type 1 and type 2 diabetes up to 1 January 2012. Maternal BMI was calculated from height and weight measured at the first antenatal visit. The effect of maternal obesity on offspring outcomes was tested using time-to-event analysis with Cox proportional hazards regression to compare outcomes in offspring of mothers in underweight, overweight or obese categories of BMI, compared with offspring of women with normal BMI. Results Offspring of obese (BMI >= 30 kg/m(2)) and overweight (BMI 25-29.9 kg/m(2)) mothers had an increased hazard of type 2 diabetes compared with mothers with normal BMI, after adjustment for gestation when weight was measured, maternal history of diabetes before pregnancy, maternal history of hypertension, age at delivery, parity, socioeconomic status, and sex of the offspring: HR 3.48 (95% CI 2.33, 5.06) and HR 1.39 (1.06, 1.83), respectively. Conclusions/interpretation Maternal obesity is associated with increased incidence of type 2 diabetes in the offspring. Evidence-based strategies that reduce obesity among women of reproductive age and that might reduce the incidence of diabetes in their offspring are urgently required.
  • Laine, M. K.; Kujala, R.; Eriksson, J. G.; Kautiainen, H.; Sarna, S.; Kujala, U. M. (2017)
    Aims Regular physical activity plays a major role, in both prevention and treatment of type 2 diabetes. Less is known whether vigorous physical activity during young adulthood is associated with costs of diabetes medication in later life. The aim of this study is to evaluate this question. Methods The study population consisted of 1314 former elite-class athletes and 860 matched controls. The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports. Information on purchases of diabetes medication between 1995 and 2009 was obtained from the drug purchase register of the Finnish Social Insurance Institution. Results The total cost of diabetes medication per person year was significantly lower among the former endurance (mean 81 theta [95% CI 33-151 theta ]) and mixed group athletes (mean 272 theta [95% CI 181- 388 theta]) compared with the controls (mean 376 theta [95% CI 284- 485 theta]), (p <0.001 and p = 0.045, respectively). Of the former endurance athletes, 0.4% used insulin, while 5.2% of the controls used insulin (p = 0.018). Conclusions A career as former endurance, sprint, jumper or team game athlete seems to reduce the costs of diabetes medication in later life.
  • Iozzo, Patricia; Holmes, Megan; Schmidt, Mathias V.; Cirulli, Francesca; Guzzardi, Maria Angela; Berry, Alessandra; Balsevich, Georgia; Andreassi, Maria Grazia; Wesselink, Jan-Jaap; Liistro, Tiziana; Gomez-Puertas, Paulino; Eriksson, Johan G.; Seckl, Jonathan (2014)
  • Reinikainen, Sami (Helsingin yliopisto, 2019)
    Tyypin 2 diabetes on merkittävä maailmanlaajuinen terveysriski ja sen yleisyys kasvaa jatkuvaa tahtia maailmalla. Suuri osa sairastaa diabetesta tietämättään. Diabeteksen aiheuttama systeeminen tulehdustila vaikuttaa haitallisesti ympäri kehoa. Diabeteksen ja suunterveyden yhteyttä on tutkittu paljon ja diabeteksen on osoitettu lisäävän parodontiitin, karieksen ja hammaspuutosten syntyä. Vaikutusmekanismit näiden välillä ovat kuitenkin vielä epäselvät. Tutkielman tavoitteena oli vertailla diabeetikkojen suunterveyttä muihin poikkileikkausasetelmassa. Tutkimusaineistona oli Helsingin kaupungilta kerätyt yli 29-vuotiaiden potilastiedot vuosilta 2001-2003. Suunterveyttä mitattiin hampaiden lukumäärällä, DMFS-indeksillä ja parodontologisilla toimenpiteillä. Lisäksi tarkasteluun otettiin mukaan diabeetikkojen yleisterveys sekä sosioekonominen asema. Tutkielman tulokset olivat samassa linjassa aiheesta aiemmin tehtyjen tutkimusten kanssa. Diabeetikkojen suun terveys oli selvästi huonompi muihin verrattuna ja diabetesta esiintyy enemmän alhaisemmissa sosioekonomisissa luokissa. Regressioanalyysissa diabeteksen esiintyvyyden riskiin olivat yhteydessä merkittävästi ikä, miessukupuoli, parodontiitti, korkea DMF-indeksi ja puuttuvat hampaat. Tyypin 2 diabetes on paljolti huonoista elämäntavoista johtuva sairaus, jonka vuoksi tutkielman tulosten perusteella ei voida olettaa, että näiden välillä olisi syy-yhteys. Tutkielmasta puuttui tiedot potilaiden painoindeksin, tupakoinnin, liikunnan ja ruokailutottumusten suhteen. Nämä tekijät ovat kaikki suuria diabeteksen riskitekijöitä. Tutkielma osoittaa kuitenkin selkeästi diabeetikkojen suurentuneen suunterveyden hoitotarpeen. Tyypin 2 diabetes on yhdistetty huonompaan omahoitoon ja täten olisikin tärkeää ohjeistaa diabeetikkoja suunterveyden tärkeydestä.
  • Räsänen, Joel; Huovinen, Joel; Korhonen, Ville E.; Junkkari, Antti; Kastinen, Sami; Komulainen, Simo; Oinas, Minna; Avellan, Cecilia; Frantzen, Janek; Rinne, Jaakko; Ronkainen, Antti; Kauppinen, Mikko; Lönnrot, Kimmo; Perola, Markus; Koivisto, Anne M.; Remes, Anne M.; Soininen, Hilkka; Hiltunen, Mikko; Helisalmi, Seppo; Kurki, Mitja I.; Jääskeläinen, Juha E.; Leinonen, Ville (2020)
    Background The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families. Methods Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their >= 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher's exact test (two-tailed), the Mann-Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses. Results Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1-12.9, p = 0.030). Conclusions Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.
  • Räsänen, Joel; Huovinen, Joel; Korhonen, Ville E; Junkkari, Antti; Kastinen, Sami; Komulainen, Simo; Oinas, Minna; Avellan, Cecilia; Frantzen, Janek; Rinne, Jaakko; Ronkainen, Antti; Kauppinen, Mikko; Lönnrot, Kimmo; Perola, Markus; Koivisto, Anne M; Remes, Anne M; Soininen, Hilkka; Hiltunen, Mikko; Helisalmi, Seppo; Kurki, Mitja I; Jääskeläinen, Juha E; Leinonen, Ville (BioMed Central, 2020)
    Abstract Background The pathophysiological basis of idiopathic normal pressure hydrocephalus (iNPH) is still unclear. Previous studies have shown a familial aggregation and a potential heritability when it comes to iNPH. Our aim was to conduct a novel case-controlled comparison between familial iNPH (fNPH) patients and their elderly relatives, involving multiple different families. Methods Questionnaires and phone interviews were used for collecting the data and categorising the iNPH patients into the familial (fNPH) and the sporadic groups. Identical questionnaires were sent to the relatives of the potential fNPH patients. Venous blood samples were collected for genetic studies. The disease histories of the probable fNPH patients (n = 60) were compared with their ≥ 60-year-old relatives with no iNPH (n = 49). A modified Charlson Comorbidity Index (CCI) was used to measure the overall disease burden. Fisher’s exact test (two-tailed), the Mann–Whitney U test (two-tailed) and a multivariate binary logistic regression analysis were used to perform the statistical analyses. Results Diabetes (32% vs. 14%, p = 0.043), arterial hypertension (65.0% vs. 43%, p = 0.033), cardiac insufficiency (16% vs. 2%, p = 0.020) and depressive symptoms (32% vs. 8%, p = 0.004) were overrepresented among the probable fNPH patients compared to their non-iNPH relatives. In the age-adjusted multivariate logistic regression analysis, diabetes remained independently associated with fNPH (OR = 3.8, 95% CI 1.1–12.9, p = 0.030). Conclusions Diabetes is associated with fNPH and a possible risk factor for fNPH. Diabetes could contribute to the pathogenesis of iNPH/fNPH, which motivates to further prospective and gene-environmental studies to decipher the disease modelling of iNPH/fNPH.
  • 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).
  • Virtanen, Tomi; Eskelinen, Saana; Sailas, Eila; Suvisaari, Jaana (Helsingfors universitet, 2016)
    Background Constipation and dyspepsia are disturbing gastrointestinal symptoms that are often ignored in research on physical comorbidities of schizophrenia. Aims Our aim was to assess dyspepsia and constipation in a sample of outpatients with schizophrenia spectrum psychoses. Methods A general practitioner performed a thorough physical health check for 275 outpatients and diagnosed constipation and dyspepsia. We assessed the possible contribution of several sociodemographic, lifestyle, and clinical variables to constipation and dyspepsia using logistic regression analysis. We also assessed whether these symptoms were associated with abnormal laboratory findings. Results The prevalence of constipation was 31.3%, and of dyspepsia 23.6%. Paracetamol (OR=3.07, 95% CI 1.34–7.02) and clozapine use (OR=5.48, 95% CI 2.75–10.90), older age (OR=1.04, 95% CI 1.01–1.06), and living in sheltered housing (OR=2.49, 95% CI 1.16–5.33) were risk factors for constipation. For dyspepsia the risk factors were female sex (OR=2.10, 95% CI 1.15–3.83), non-steroidal anti-inflammatory drugs (OR=2.47, 95% CI 1.13–5.39), and diabetes medication (OR=2.42, 95% CI 1.12–5.25). Patients with dyspepsia had lower hemoglobin and hematocrit and higher glucose values than those without dyspepsia. Patients with constipation had lower thrombocyte values than patients without constipation. However, these findings were explained by factors predisposing to constipation and dyspepsia. Conclusions Clozapine use markedly increases the risk of constipation and may lead to life-threatening complications. In addition, analgesics and diabetes medication were related to gastrointestinal symptoms. These medications and their association to gastrointestinal symptoms should be kept in mind when treating patients with schizophrenia.
  • Veronese, N.; Sergi, G.; Stubbs, B.; Bourdel-Marchasson, I.; Tessier, D.; Sieber, C.; Strandberg, T.; Gillain, S.; Barbagallo, M.; Crepaldi, G.; Maggi, S.; Manzato, E.; EUGMS Special Interest Grp Diabet (2017)
    Background/aim: Deficiency of acetyl-L-carnitine (ALC) and L-carnitine (LC) appears to play a role in peripheral diabetic neuropathy, although the evidence in humans is still limited. We conducted a systematic review and meta-analysis investigating the effect of ALC on pain and electromyographic parameters in people with diabetic neuropathy. Methods: A literature search in major databases, without language restriction, was undertaken. Eligible studies were randomized controlled trials (RCTs) or pre-and post-test studies. The effect of ALC supplementation on pain perception and electromyographic parameters in patients with diabetic neuropathy was compared vs. a control group (RCTs). The effect of ALC/LC on electromyographic parameters were also calculated vs. baseline values. Standardized mean differences (SMD) and 95% confidence intervals (CIs) were used for summarizing outcomes. Results: Six articles, with a total of 711 diabetic participants, were included. Three RCTs (340 treated with ALC vs. 203 placebo and 115 with methylcobalamine) showed that ALC reduces pain perception (SMD = -0.45; 95% CI: -0.86 to -0.04; P = 0.03; I-2 = 85%). Compared to controls, ALC supplementation improved nerve conduction velocity and amplitude response for ulnar nerve (both sensory and motor component). Compared to baseline values, ALC/LC supplementation improved nerve conduction velocity for all the sensory and motor nerves (except ulnar and peroneal) investigated and the amplitude of all nerves. The onset of adverse events was generally limited to minor side effects. Conclusion: ALC appears to be effective in reducing pain due to diabetic neuropathy compared to active or placebo controls and improving electromyographic parameters in these patients. (C) 2017 Elsevier Masson SAS and European Union Geriatric Medicine Society. All rights reserved.
  • Karjalainen, M.; Saltevo, J.; Tiihonen, M.; Haanpää, M.; Kautiainen, H.; Mäntyselkä, P. (2018)
    Background: The association between pain and diabetes in older people has been largely unexplored. The aim of this survey was to analyze the prevalence and characteristics of pain among Finnish men and women 65 or older with and without diabetes in primary care. Methods: All home-dwelling persons 65 years or older with diabetes (N = 527) and age and gender matched controls (N = 890) were identified from electronic patient records. Frequent pain was regarded as any pain experienced more often than once a week, and it was divided into pain experienced several times a week but not daily and pain experienced daily or continuously. The Numeric Rating Scale (0-10) (NRS) was used to assess the intensity and interference of the pain. Results: The number of subjects who returned the questionnaire was 1084 (76.5%). The prevalence of frequent pain in the preceding week was 50% among women without diabetes and 63% among women with diabetes (adjusted, p = 0.22). In men, the corresponding proportions were 42% without diabetes and 47% with diabetes (adjusted, p = 0.58). In both genders, depressive symptoms and the number of comorbidities were associated with pain experienced more often than once a week and with daily pain. Diabetes was not associated with pain intensity or pain interference in either women or men. Conclusions: Pain in older adults is associated with depressive symptoms and the number of comorbidities more than with diabetes itself.
  • EUROASPIRE IV Investigator; EUROASPIRE V Investigator; Ferrannini, Giulia; De Bacquer, Dirk; Vynckier, Pieter; Tuomilehto, Jaakko; Ryden, Lars (2021)
    BackgroundGender disparities in the management of dysglycaemia, defined as either impaired glucose tolerance (IGT) or type 2 diabetes (T2DM), in coronary artery disease (CAD) patients are a medical challenge. Recent data from two nationwide cohorts of patients suggested no gender difference as regards the risk for diabetes-related CV complications but indicated the presence of a gender disparity in risk factor management. The aim of this study was to investigate gender differences in screening for dysglycaemia, cardiovascular risk factor management and prognosis in dysglycemic CAD patients.MethodsThe study population (n=16,259; 4077 women) included 7998 patients from the ESC-EORP EUROASPIRE IV (EAIV: 2012-2013, 79 centres in 24 countries) and 8261 patients from the ESC-EORP EUROASPIRE V (EAV: 2016-2017, 131 centres in 27 countries) cross-sectional surveys. In each centre, patients were investigated with standardised methods by centrally trained staff and those without known diabetes were offered an oral glucose tolerance test (OGTT). The first of CV death or hospitalisation for non-fatal myocardial infarction, stroke, heart failure or revascularization served as endpoint. Median follow-up time was 1.7 years. The association between gender and time to the occurrence of the endpoint was evaluated using Cox survival modelling, adjusting for age.ResultsKnown diabetes was more common among women (32.9%) than men (28.4%, p
  • Ferrannini, Giulia; De Bacquer, Dirk; Vynckier, Pieter; De Backer, Guy; Gyberg, Viveca; Kotseva, Kornelia; Mellbin, Linda; Norhammar, Anna; Tuomilehto, Jaakko; Wood, David; Rydén, Lars (BioMed Central, 2021)
    Abstract Background Gender disparities in the management of dysglycaemia, defined as either impaired glucose tolerance (IGT) or type 2 diabetes (T2DM), in coronary artery disease (CAD) patients are a medical challenge. Recent data from two nationwide cohorts of patients suggested no gender difference as regards the risk for diabetes-related CV complications but indicated the presence of a gender disparity in risk factor management. The aim of this study was to investigate gender differences in screening for dysglycaemia, cardiovascular risk factor management and prognosis in dysglycemic CAD patients. Methods The study population (n = 16,259; 4077 women) included 7998 patients from the ESC-EORP EUROASPIRE IV (EAIV: 2012–2013, 79 centres in 24 countries) and 8261 patients from the ESC-EORP EUROASPIRE V (EAV: 2016–2017, 131 centres in 27 countries) cross-sectional surveys. In each centre, patients were investigated with standardised methods by centrally trained staff and those without known diabetes were offered an oral glucose tolerance test (OGTT). The first of CV death or hospitalisation for non-fatal myocardial infarction, stroke, heart failure or revascularization served as endpoint. Median follow-up time was 1.7 years. The association between gender and time to the occurrence of the endpoint was evaluated using Cox survival modelling, adjusting for age. Results Known diabetes was more common among women (32.9%) than men (28.4%, p < 0.0001). OGTT (n = 8655) disclosed IGT in 17.2% of women vs. 15.1% of men (p = 0.004) and diabetes in 13.4% of women vs. 14.6% of men (p = 0.078). In both known diabetes and newly detected dysglycaemia groups, women were older, with higher proportions of hypertension, dyslipidaemia and obesity. HbA1c was higher in women with known diabetes. Recommended targets of physical activity, blood pressure and cholesterol were achieved by significantly lower proportions of women than men. Women with known diabetes had higher risk for the endpoint than men (age-adjusted HR 1.22; 95% CI 1.04–1.43). Conclusions Guideline-recommended risk factor control is poorer in dysglycemic women than men. This may contribute to the worse prognosis in CAD women with known diabetes.
  • Balboa, Diego; Prasad, Rashmi B.; Groop, Leif; Otonkoski, Timo (2019)
    Understanding the molecular mechanisms behind beta cell dysfunction is essential for the development of effective and specific approaches for diabetes care and prevention. Physiological human beta cell models are needed for this work. We review the possibilities and limitations of currently available human beta cell models and how they can be dramatically enhanced using genome-editing technologies. In addition to the gold standard, primary isolated islets, other models now include immortalised human beta cell lines and pluripotent stem cell-derived islet-like cells. The scarcity of human primary islet samples limits their use, but valuable gene expression and functional data from large collections of human islets have been made available to the scientific community. The possibilities for studying beta cell physiology using immortalised human beta cell lines and stem cell-derived islets are rapidly evolving. However, the functional immaturity of these cells is still a significant limitation. CRISPR-Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated protein 9) has enabled precise engineering of specific genetic variants, targeted transcriptional modulation and genome-wide genetic screening. These approaches can now be exploited to gain understanding of the mechanisms behind coding and non-coding diabetes-associated genetic variants, allowing more precise evaluation of their contribution to diabetes pathogenesis. Despite all the progress, genome editing in primary pancreatic islets remains difficult to achieve, an important limitation requiring further technological development.
  • Yuan, Xiaojing; Liu, Huikun; Wang, Leishen; Zhang, Shuang; Zhang, Cuiping; Leng, Junhong; Dong, Ling; Lv, Li; Lv, Fengjun; Tian, Huiguang; Qi, Lu; Tuomilehto, Jaakko; Hu, Gang (2016)
    Aims: We aimed to examine the association of gestational hypertension and chronic hypertension at the inter-conception examination with type 2 diabetes risk among women with a history of gestational diabetes. Methods: We conducted a population-based study among 1261 women who had a history of gestational diabetes at 1-5 years after delivery in Tianjin, China. Logistic regression or Cox regression was used to assess the associations of gestational hypertension and chronic hypertension at the inter-conception examination with pre-diabetes and type 2 diabetes risks. Results: Gestational diabetic women who had a history of gestational hypertension but did not use antihypertensive drugs during pregnancy had a 3.94-fold higher risk (95% CI: 1.94-8.02) of developing type 2 diabetes compared with those who were normotensive in index pregnancy. Compared with gestational diabetic women who had normal blood pressure at the inter-conception examination, hypertensive women at the inter-conception examination were 3.38 times (95% CI: 1.66-6.87) and 2.97 times (95% CI: 1.75-5.05) more likely to develop diabetes and prediabetes, respectively. The odds ratios of type 2 diabetes and prediabetes associated with each 5 mmHg increase in systolic blood pressure were 125 (95% CI: 1.03-1.51) and 120 (95% CI: 1.06-135). Each 5 mmHg increase in diastolic blood pressure contributed to a 1.49-fold higher risk (95% CI: 1.18-1.88) for type 2 diabetes and a 1.42-fold higher risk (95% CI: 1.22-1.65) for prediabetes. Conclusions: For women with prior gestational diabetes, gestational hypertension and chronic hypertension at the inter-conception examination were risk factors for type 2 diabetes. (C) 2016 Elsevier Inc. All rights reserved.