Browsing by Subject "HYPERGLYCEMIA"

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  • Deelen, Joris; Kettunen, Johannes; Fischer, Krista; van der Spek, Ashley; Trompet, Stella; Kastenmueller, Gabi; Boyd, Andy; Zierer, Jonas; van den Akker, Erik B.; Ala-Korpela, Mika; Amin, Najaf; Demirkan, Ayse; Ghanbari, Mohsen; van Heemst, Diana; Ikram, M. Arfan; van Klinken, Jan Bert; Mooijaart, Simon P.; Peters, Annette; Salomaa, Veikko; Sattar, Naveed; Spector, Tim D.; Tiemeier, Henning; Verhoeven, Aswin; Waldenberger, Melanie; Wuertz, Peter; Smith, George Davey; Metspalu, Andres; Perola, Markus; Menni, Cristina; Geleijnse, Johanna M.; Drenos, Fotios; Beekman, Marian; Jukema, J. Wouter; van Duijn, Cornelia M.; Slagboom, P. Eline (2019)
    Predicting longer-term mortality risk requires collection of clinical data, which is often cumbersome. Therefore, we use a well-standardized metabolomics platform to identify metabolic predictors of long-term mortality in the circulation of 44,168 individuals (age at baseline 18-109), of whom 5512 died during follow-up. We apply a stepwise (forward-backward) procedure based on meta-analysis results and identify 14 circulating biomarkers independently associating with all-cause mortality. Overall, these associations are similar in men and women and across different age strata. We subsequently show that the prediction accuracy of 5- and 10-year mortality based on a model containing the identified biomarkers and sex (C-statistic = 0.837 and 0.830, respectively) is better than that of a model containing conventional risk factors for mortality (C-statistic = 0.772 and 0.790, respectively). The use of the identified metabolic profile as a predictor of mortality or surrogate endpoint in clinical studies needs further investigation.
  • Keikkala, Elina; Mustaniemi, Sanna; Koivunen, Sanna; Kinnunen, Jenni; Viljakainen, Matti; Männistö, Tuija; Ijäs, Hilkka; Pouta, Anneli; Kaaja, Risto; Eriksson, Johan G.; Laivuori, Hannele; Gissler, Mika; Erkinheimo, Tiina-Liisa; Keravuo, Ritva; Huttunen, Merja; Metsälä, Jenni; Stach‑Lempinen, Beata; Klemetti, Miira M.; Tikkanen, Minna; Kajantie, Eero; Vääräsmäki, Marja (2020)
  • Eskian, Mahsa; Alavi, Abass; Khorasanizadeh, MirHojjat; Viglianti, Benjamin L.; Jacobsson, Hans; Barwick, Tara D.; Meysamie, Alipasha; Yi, Sun K.; Iwano, Shingo; Bybel, Bohdan; Caobelli, Federico; Lococo, Filippo; Gea, Joaquim; Sancho-Munoz, Antonio; Schildt, Jukka; Tatci, Ebru; Lapa, Constantin; Keramida, Georgia; Peters, Michael; Boktor, Raef R.; John, Joemon; Pitman, Alexander G.; Mazurek, Tomasz; Rezaei, Nima (2019)
    Objectives To evaluate the effect of pre-scan blood glucose levels (BGL) on standardized uptake value (SUV) in F-18-FDG-PET scan. Methods A literature review was performed in the MEDLINE, Embase, and Cochrane library databases. Multivariate regression analysis was performed on individual datum to investigate the correlation of BGL with SUVmax and SUVmean adjusting for sex, age, body mass index (BMI), diabetes mellitus diagnosis, F-18-FDG injected dose, and time interval. The ANOVA test was done to evaluate differences in SUVmax or SUVmean among five different BGL groups (200 mg/dl). Results Individual data for a total of 20,807 SUVmax and SUVmean measurements from 29 studies with 8380 patients was included in the analysis. Increased BGL is significantly correlated with decreased SUVmax and SUVmean in brain (p <0.001, p <0.001,) and muscle (p <0.001, p <0.001) and increased SUVmax and SUVmean in liver (p = 0.001, p = 0004) and blood pool (p=0.008, p200 mg/dl had significantly lower SUVmax. Conclusion If BGL is lower than 200mg/dl no interventions are needed for lowering BGL, unless the liver is the organ of interest. Future studies are needed to evaluate sensitivity and specificity of FDG-PET scan in diagnosis of malignant lesions in hyperglycemia.
  • Grotenfelt, N. E.; Wasenius, N.; Eriksson, J. G.; Huvinen, E.; Stach-Lempinen, B.; Koivusalo, S. B.; Rönö, K. (2020)
    Aim. - To assess in women at high risk of gestational diabetes mellitus (GDM) the effect of a lifestyle intervention on the metabolic health of their offspring around 5 years after delivery. Methods. - For the original Finnish gestational diabetes prevention study (RADIEL), 720 women with a prepregnancy body mass index (BMI) >= 30 kg/m(2) and/or previous GDM were enrolled before or during early pregnancy and allocated to either an interventional (n = 126) or conventional (n = 133) care group. The present 5-year follow-up substudy assessed the metabolic health outcomes of their offspring. Ageand gender-standardized residuals of metabolic health components (waist circumference, mean arterial pressure, high-density lipoprotein and triglyceride levels, and fasting insulin/glucose ratio) were also combined to determine the accumulation of metabolic effects. Body composition was assessed by electrical bioimpedance. Results. - Offspring of women in the intervention group had a less optimal metabolic profile after the 5-year follow-up compared with offspring in the usual care group (P = 0.014). This difference in metabolic health was primarily related to lipid metabolism, and was more prominent among boys (P = 0.001) than girls (P = 0.74). Neither GDM, gestational weight gain, prepregnancy BMI, offspring age nor timing of randomization (before or during pregnancy) could explain the detected difference, which was also more pronounced among the offspring of GDM pregnancies (P= 0.010). Offspring body composition was similar in both groups (P> 0.05). Conclusion. - The lifestyle intervention aimed at GDM prevention was associated with unfavourable metabolic outcomes among offspring at around 5 years of age. (C) 2019 Elsevier Masson SAS. All rights reserved.
  • Vencio, Sergio; Manosalva, Juan P.; Mathieu, Chantal; Proot, Pieter; Lozno, Hernan Yupanqui; Paldanius, Päivi M. (2021)
    Background Patients with type 2 diabetes mellitus (T2DM) from Latin American countries face challenges in access to healthcare, leading to under-diagnosis, under-achievement of glycemic target, and long-term complications. Early diagnosis and treatment initiation are of paramount importance in this population due to the high prevalence of risk factors such as obesity and metabolic syndrome. The VERIFY study in patients with newly diagnosed T2DM (across 34 countries), assessed the normoglycemic durability (5 years), with early combination (EC) therapy approach versus the traditional stepwise approach of initiating treatment with metformin monotherapy (MET). Here we present the results from the VERIFY study for participants from eight countries in Latin America. Methods Newly diagnosed adult patients with T2DM, HbA1c 6.5-7.5% and body-mass index (BMI) of 22-40 kg/m(2) were enrolled. The primary endpoint was time to initial treatment failure (TF; HbA1c >= 7.0% at two consecutive scheduled visits 13 weeks apart). Time to second TF was evaluated when patients in both groups were receiving and failing on the vildagliptin combination. Safety and tolerability were also assessed for both treatment approaches during the study. Results A total of 537 eligible patients (female, 58.8%) were randomly assigned to receive either EC (n = 266) or MET (n = 271). EC significantly reduced the relative risk of time to initial TF by 47% versus MET [HR (95% CI) 0.53 (0.4, 0.7) p < 0.0001]. Overall, 46.4% versus 66.3% of patients achieved the primary endpoint in the EC and MET groups, with a median [interquartile range (IQR)] time to TF of 59.8 (27.5, not evaluable) and 33.4 (12.2, 60.1) months, respectively. The risk for time to second TF was 31% lower with EC (p < 0.0092). A higher proportion of patients receiving EC maintained durable HbA1c < 7.0%, < 6.5%, and < 6.0%. Both treatment approaches were well tolerated, and only 3.2% of participants discontinued the study due to adverse events. All hypoglycemic events (EC: n = 7 and MET: n = 3) were single, mild episodes and did not lead to study discontinuation. Conclusion Similar to the global population, long-term clinical benefits were achieved more frequently and without tolerability issues with EC versus standard-of-care MET in this Latin American sub-population. This study is registered with, NCT01528254.
  • Cooper, Mark E.; Perkovic, Vlado; Groop, Per-Henrik; Hocher, Berthold; Hehnke, Uwe; Meinicke, Thomas; Koitka-Weber, Audrey; van der Walt, Sandra; von Eynatten, Maximilian (2019)
    Objective: Concomitant treatment with angiotensin-converting enzyme (ACE) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors is increasingly common. Pharmacological studies have suggested a potential adverse drug interaction between ACE inhibitors and DPP-4 inhibitors resulting in unfavorable hemodynamic changes; very few studies have examined such an interaction between angiotensin II receptor blockers (ARBs) and DPP-4 inhibitors. We investigated blood pressure (BP) and heart rate (HR) during treatment with the DPP-4 inhibitor linagliptin in individuals receiving either ACE inhibitors or ARBs in the MARLINA-T2D trial. Methods: In this study, 360 individuals with type 2 diabetes and albuminuria receiving unchanged doses of ACE inhibitors or ARBs were randomized to linagliptin or placebo. Twenty-four-hour ambulatory BP monitoring, an exploratory endpoint, was conducted at baseline and after 24 weeks. Results: Ambulatory BP monitoring data were available for 208 individuals (linagliptin: n = 111; placebo: n = 97). Baseline mean +/- SD 24-h SBP and DBP were 132.5 +/- 12.4 mmHg and 75.9 +/- 9.4 mmHg, respectively; mean 24-h HR was 76.3 +/- 10.1 bpm. At week 24, no overall effect of the DPP-4 inhibitor versus placebo was seen on mean 24-h SBP, DBP, or HR. Furthermore, in the subgroups receiving either an ACE inhibitor or an ARB, no effect on these hemodynamic parameters was seen as a result of concomitant DPP-4 inhibitor treatment. Conclusion: Adding linagliptin to treatment with ACE inhibitors or ARBs was not associated with any hemodynamic changes, supporting their concomitant use in individuals with type 2 diabetes and albuminuria.
  • Huvinen, Emilia; Eriksson, Johan G.; Stach-Lempinen, Beata; Tiitinen, Aila; Koivusalo, Saila B. (2018)
    AimsGestational diabetes (GDM) affects a growing number of women and identification of individuals at risk, e.g., with risk prediction models, would be important. However, the performance of GDM risk scores has not been optimal. Here, we assess the impact of GDM heterogeneity on the performance of two top-rated GDM risk scores.MethodsThis is a substudy of the RADIEL triala lifestyle intervention study including women at high GDM risk. We assessed the GDM risk score by Teede and that developed by Van Leeuwen in our high-risk cohort of 510 women. To investigate the heterogeneity of GDM, we further divided the women according to GDM history, BMI, and parity. With the goal of identifying novel predictors of GDM, we further analyzed 319 women with normal glucose tolerance in the first trimester.ResultsBoth risk scores underestimated GDM incidence in our high-risk cohort. Among women with a BMI30kg/m(2) and/or previous GDM, 49.4% developed GDM and 37.4% received the diagnosis already in the first trimester. Van Leeuwen score estimated a 19% probability of GDM and Teede succeeded in risk identification in 61%. The lowest performance of the risk scores was seen among the non-obese women. Fasting plasma glucose, HbA(1c), and family history of diabetes were predictors of GDM in the total study population. Analysis of subgroups did not provide any further information.ConclusionsOur findings suggest that the marked heterogeneity of GDM challenges the development of risk scores for detection of GDM.
  • Huvinen, Emilia; Eriksson, Johan G.; Koivusalo, Saila B.; Grotenfelt, Nora; Tiitinen, Aila; Stach-Lempinen, Beata; Rono, Kristiina (2018)
    To assess the metabolic health of obese and non-obese women at high GDM risk 5 years postpartum. This is a secondary analysis of the 5-year follow-up of the RADIEL GDM prevention study including 333 women at high GDM risk (BMI ae 30 kg/m(2) and/or previous GDM). Five years postpartum metabolic health was assessed including anthropometric measurements, oral glucose tolerance test, lipid metabolism, and body composition as well as medical history questionnaires. For the analysis, we divided the women into four groups based on parity, BMI, and previous history of GDM. Five years postpartum impaired glucose regulation (IFG, IGT, or diabetes) was diagnosed in 15% of the women; 3.6% had type 2 diabetes. The highest prevalence was observed among obese women with a history of GDM (26%), and the lowest prevalence (8%) among primiparous obese women (p = 0.021). At follow-up 25-39% of the obese women fulfilled the diagnostic criteria for the metabolic syndrome, in the non-obese group 11% (p <0.001). This was associated with body fat percentage. The non-obese group, however, faced metabolic disturbances (IFG, IGT, diabetes, or metabolic syndrome) at a significantly lower BMI (p <0.001). Among women who were non-obese before pregnancy, 5 years postpartum, the obesity prevalence based on BMI was 14% and based on body fat percentage 58%. The prevalence of impaired glucose regulation and metabolic syndrome is high 5 years postpartum among women at high risk of GDM. There are high-risk women also among the non-obese, who develop metabolic derangements already at a lower BMI.
  • Keski-Nisula, Juho; Pesonen, Eero; Olkkola, Klaus T.; Ahlroth, Terri; Puntila, Juha; Andersson, Sture; Neuvonen, Pertti J.; Suominen, Pertti K. (2016)
    Background. The optimal dose of methylprednisolone during pediatric open heart surgical procedures is unknown. This study compared the antiinflammatory and cardioprotective effects of high and lower doses of methylprednisolone in children undergoing cardiac operations. Methods. Thirty children, between 1 and 18 months old and undergoing total correction of tetralogy of Fallot, were randomized in double-blind fashion to receive either 5 or 30 mg/kg of intravenous methylprednisolone after anesthesia induction. Plasma concentrations of methylprednisolone, interleukin-6 (IL-6), IL-8, and IL-10, troponin T, and glucose were measured at anesthesia induction before administration of the study drug, at 30 minutes on cardiopulmonary bypass (CPB), just after weaning from CPB, and at 6 hours after CPB. Troponin T and blood glucose were also measured on the first postoperative morning. Results. Significantly higher methylprednisolone concentrations were measured in patients receiving 30 mg/kg of methylprednisolone at 30 minutes on CBP, after weaning from CPB and at 6 hours after CPB (p <0.001). No differences were detected in IL-6, IL-8, IL-10, or troponin concentrations at any time point. Blood glucose levels were significantly higher in patients receiving 30 mg/kg of methylprednisolone at 6 hours after CPB (p = 0.04) and on the first postoperative morning (p = 0.02). Conclusions. Based on the measured concentrations of interleukins or troponin T, a 30 mg/kg dose of methylprednisolone during pediatric open heart operations does not offer any additional antiinflammatory or cardioprotective benefit over a 5 mg/kg dose. Higher dose of methylprednisolone exposes patients more frequently to hyperglycemia. (C) 2016 by The Society of Thoracic Surgeons
  • Masalin, Senja; Laine, Merja K.; Kautiainen, Hannu; Gissler, Mika; Raina, Marko; Pennanen, Pirjo; Eriksson, Johan G. (2019)
    Aims: To evaluate the impact of gestational diabetes mellitus (GDM) and maternal height on offspring birthweight. Methods: This is an observational cohort study, encompassing 4 111 Finnish primiparous women from Vantaa city, Finland, with singleton deliveries between 2009 and 2015. Data were obtained from the Finnish Medical Birth Register. The study population was divided into five groups according to maternal height. Cut-offs for height levels were I = 173 cm. The main outcome measure was offspring birthweight, expressed as Z-scores according to sex and gestational age. Results: Independently, both maternal height and GDM increased offspring birthweight (p <0.001 for height and GDM). When studying the interaction, a significant increase in offspring birthweight was noted only in extreme height categories; group I = 173 cm (p <0.001) and the impact was similar in both sexes. Maternal height had no impact on offspring ponderal index (p = 0.20 for trend). Conclusions: In extreme height categories, short and tall primiparous women with GDM are at risk for delivering larger offspring compared to women without GDM of similar height. (C) 2019 Elsevier B.V. All rights reserved.
  • Ijas, Hilkka; Koivunen, Sanna; Raudaskoski, Tytti; Kajantie, Eero; Gissler, Mika; Vaarasmaki, Marja (2019)
    Aims Gestational diabetes (GDM) is often accompanied by maternal overweight. Our aim was to evaluate the separate and concomitant effects of GDM and maternal overweight/obesity on perinatal outcomes. Methods We used the Finnish Medical Birth Register to identify all 24,577 women with a singleton pregnancy who delivered in 2009 in Finland and underwent an oral glucose tolerance test (OGTT). Women were divided into groups according to the result of OGTT (GDM/no GDM) and pre-pregnancy body mass index (BMI): normal weight (= 30.0 kg/m(2)). Primary outcomes included macrosomia, caesarean delivery, and treatment at neonatal ward. Normal weight women without GDM constituted the reference group. Results Compared to reference group, overweight or obese women without GDM had an increased risk of macrosomia [odds ratio adjusted for age, parity, smoking and socio-economic status (aOR) 1.18 (95% CI 1.09-1.28) and 1.50 (95% CI 1.19-1.88)], and caesarean delivery [aORs 1.17 (95% CI 1.07-1.28) and 1.52 (95% CI 1.37-1.69)], respectively. In normal weight GDM women the risk of macrosomia [aOR 1.17 (95% CI 0.85-1.62)] and caesarean delivery [aOR 1.10 (95% CI 0.96-1.27)] was not significantly increased as compared to normal weight women without GDM. GDM increased the risk of treatment at neonatal ward in all BMI categories and maternal obesity without GDM was also a risk factor for treatment at neonatal ward. Interaction p values between BMI and GDM on these outcomes were Conclusions Maternal overweight and obesity without GDM increased the risk of macrosomia and caesarean delivery when compared to the reference group. These risks were amplified when overweight/obesity was accompanied by GDM. Obesity without GDM was a risk factor for treatment at neonatal ward; GDM increased this risk in all BMI categories. Our results suggest that especially maternal obesity should be considered as a risk factor for adverse pregnancy outcomes and GDM further amplifies this risk.
  • Tarvonen, Mikko; Hovi, Petteri; Sainio, Susanna; Vuorela, Piia; Andersson, Sture; Teramo, Kari (2021)
    Aims In previous reports, cardiotocographic (CTG) fetal heart rate (FHR) monitoring has shown only limited benefits in decreasing adverse perinatal outcomes in pregnancies complicated by gestational diabetes mellitus (GDM). The aim of the present study was to evaluate whether an association exists between the recently reported ZigZag pattern (FHR baseline amplitude changes of > 25 bpm with a duration of 2-30 min) and asphyxia-related neonatal outcomes in GDM pregnancies. Methods Intrapartal CTGs were recorded in a one-year cohort of 5150 singleton childbirths. The following CTG changes were evaluated: ZigZag pattern, saltatory pattern, late decelerations, episodes of tachycardia and bradycardia, reduced variability, and uterine tachysystole. The cohort was divided into three groups: women with GDM, women with normal oral glucose tolerance test (OGTT), and women with no OGTT performed. Umbilical artery (UA) blood gases, Apgar scores, neonatal respiratory distress, and neonatal encephalopathy were used as outcome variables. Results GDM was diagnosed in 624 (12.1%), OGTT was normal in 4115 (79.9%), and OGTT was not performed in 411 (8.0%) women. Hypoxia-related ZigZag patterns (OR 1.94, 95% CI 1.64-2.34) and late decelerations (OR 1.65, 95% CI 1.27-2.13) of FHR, as well as a greater risk of fetal asphyxia (UA pH < 7.10 and/or UA BE < -12.0 meq/L and/or Apgar scores < 7 at 5-min) (OR 6.64, 95% CI 1.84-12.03) were observed in those with GDM compared with those without GDM. Conclusions GDM is associated with intrapartal ZigZag pattern and late decelerations, cord blood acidemia and low 5-min Apgar scores at birth indicating increased occurrence of fetal hypoxia in GDM pregnancies.
  • Howe, Caitlin G.; Cox, Bianca; Fore, Ruby; Jungius, James; Kvist, Tuomas; Lent, Samantha; Miles, Harriet E.; Salas, Lucas A.; Rifas-Shiman, Sheryl; Starling, Anne P.; Yousefi, Paul; Ladd-Acosta, Christine; Baccarelli, Andrea; Binder, Elisabeth B.; Chatzi, Vaia Lida; Czamara, Darina; Dabelea, Dana; DeMeo, Dawn L.; Ghantous, Akram; Herceg, Zdenko; Kajantie, Eero; Lahti, Jari M. T.; Lawlor, Debbie A.; Litonjua, Augusto; Nawrot, Tim S.; Nohr, Ellen A.; Oken, Emily; Pizzi, Costanza; Plusquin, Michelle; Räikkönen, Katri; Relton, Caroline L.; Sharp, Gemma C.; Sorensen, Thorkild I. A.; Sunyer, Jordi; Vrijheid, Martine; Zhang, Weiming; Hivert, Marie-France; Breton, Carrie V. (2020)
    OBJECTIVE Maternal gestational diabetes mellitus (GDM) has been associated with adverse outcomes in the offspring. Growing evidence suggests that the epigenome may play a role, but most previous studies have been small and adjusted for few covariates. The current study meta-analyzed the association between maternal GDM and cord blood DNA methylation in the Pregnancy and Childhood Epigenetics (PACE) consortium. RESEARCH DESIGN AND METHODS Seven pregnancy cohorts (3,677 mother-newborn pairs [317 with GDM]) contributed results from epigenome-wide association studies, using DNA methylation data acquired by the Infinium HumanMethylation450 BeadChip array. Associations between GDM and DNA methylation were examined using robust linear regression, with adjustment for potential confounders. Fixed-effects meta-analyses were performed using METAL. Differentially methylated regions (DMRs) were identified by taking the intersection of results obtained using two regional approaches: comb-p and DMRcate. RESULTS Two DMRs were identified by both comb-p and DMRcate. Both regions were hypomethylated in newborns exposed to GDM in utero compared with control subjects. One DMR (chr 1: 248100345-248100614) was located in the OR2L13 promoter, and the other (chr 10: 135341870-135342620) was located in the gene body of CYP2E1. Individual CpG analyses did not reveal any differentially methylated loci based on a false discovery rate-adjusted P value threshold of 0.05. CONCLUSIONS Maternal GDM was associated with lower cord blood methylation levels within two regions, including the promoter of OR2L13, a gene associated with autism spectrum disorder, and the gene body of CYP2E1, which is upregulated in type 1 and type 2 diabetes. Future studies are needed to understand whether these associations are causal and possible health consequences.
  • Ahola, Aila J.; Mutter, Stefan; Forsblom, Carol; Harjutsalo, Valma; Groop, Per-Henrik (2019)
    We assessed meal timing, meal frequency, and breakfast consumption habits of adult individuals with type 1 diabetes (n = 1007) taking part in the Finnish Diabetic Nephropathy Study, and studied whether they are associated with glycaemic control. Data on dietary intake and blood glucose measurements were retrieved from food records. HbA(1c) was measured at the study visit. In the whole sample, four peaks of energy intake emerged. Energy intake was the greatest in the evening, followed by midday. Altogether 7% of the participants reported no energy intake between 05:00 and 09:59 (breakfast skippers). While breakfast skippers reported lower number of meals, no difference was observed in the total energy intake between those eating and omitting breakfast. In a multivariable model, skipping breakfast was associated with higher mean blood glucose concentrations and lower odds of good glycaemic control. A median of 6 daily meals was reported. Adjusted for confounders, the number of meals was negatively associated with HbA(1c), and the mean of the blood glucose measurements, but positively associated with the variability of these measurements. Our observations support the habit of a regular meal pattern, including consumption of breakfast and multiple smaller meals for good glycaemic control in adults with type 1 diabetes. However, an increase in the blood glucose variability may additionally be expected with an increase in the number of meals eaten.
  • Wurtz, Peter; Cook, Sarah; Wang, Qin; Tiainen, Mika; Tynkkynen, Tuulia; Kangas, Antti J.; Soininen, Pasi; Laitinen, Jaana; Viikari, Jorma; Kahonen, Mika; Lehtimaki, Terho; Perola, Markus; Blankenberg, Stefan; Zeller, Tanja; Mannisto, Satu; Salomaa, Veikko; Jarvelin, Marjo-Riitta; Raitakari, Olli T.; Ala-Korpela, Mika; Leon, David A. (2016)
    Background: High alcohol consumption is a major cause of morbidity, yet alcohol is associated with both favourable and adverse effects on cardiometabolic risk markers. We aimed to characterize the associations of usual alcohol consumption with a comprehensive systemic metabolite profile in young adults. Methods: Cross-sectional associations of alcohol intake with 86 metabolic measures were assessed for 9778 individuals from three population-based cohorts from Finland (age 24-45 years, 52% women). Metabolic changes associated with change in alcohol intake during 6-year follow-up were further examined for 1466 individuals. Alcohol intake was assessed by questionnaires. Circulating lipids, fatty acids and metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. Results: Increased alcohol intake was associated with cardiometabolic risk markers across multiple metabolic pathways, including higher lipid concentrations in HDL subclasses and smaller LDL particle size, increased proportions of monounsaturated fatty acids and decreased proportion of omega-6 fatty acids, lower concentrations of glutamine and citrate (P<0.001 for 56 metabolic measures). Many metabolic biomarkers displayed U-shaped associations with alcohol consumption. Results were coherent for men and women, consistent across the three cohorts and similar if adjusting for body mass index, smoking and physical activity. The metabolic changes accompanying change in alcohol intake during follow-up resembled the cross-sectional association pattern (R-2 = 0.83, slope = 0.7260.04). Conclusions: Alcohol consumption is associated with a complex metabolic signature, including aberrations in multiple biomarkers for elevated cardiometabolic risk. The metabolic signature tracks with long-term changes in alcohol consumption. These results elucidate the double-edged effects of alcohol on cardiovascular risk.
  • Huhtala, Mikael S.; Tertti, Kristiina; Juhila, Juuso; Sorsa, Timo; Rönnemaa, Tapani (2020)
    Background: Gestational diabetes mellitus (GDM) is characterized by disturbed glucose metabolism and activation of low-grade inflammation. We studied whether metformin treatment has favorable or unfavorable effects on inflammatory markers and insulin-like growth factor-binding protein 1 (IGFBP-1) in GDM patients compared with insulin, and whether these markers associate with major maternal or fetal clinical outcomes. Methods: This is a secondary analysis of a previous randomized controlled trial comparing metformin (n = 110) and insulin (n = 107) treatment of GDM. Fasting serum samples were collected at the time of diagnosis (baseline, mean 30 gestational weeks [gw]) and at 36 gw. Inflammatory markers serum high-sensitivity CRP (hsCRP), interleukin-6 (IL-6), matrix metalloproteinase-8 (MMP-8) and glycoprotein acetylation (GlycA) as well as three IGFBP-1 phosphoisoform concentrations were determined. Results: In the metformin and insulin groups combined, hsCRP decreased (p = 0.01), whereas IL-6 (p = 0.002), GlycA (p <0.0001) and all IGFBP-1 phosphoisoforms (p <0.0001) increased from baseline to 36 gw. GlycA (p = 0.02) and non-phosphorylated IGFBP-1 (p = 0.008) increased more in patients treated with metformin than those treated with insulin. Inflammatory markers did not clearly associate with pregnancy outcomes but non-phosphorylated IGFBP-1 was inversely associated with gestational weight gain. Conclusions: Metformin had beneficial effects on maternal serum IGFBP-1 concentrations compared to insulin, as increased IGFBP-1 related to lower total and late pregnancy maternal weight gain. GlycA increased more during metformin treatment compared to insulin. The significance of this observation needs to be more profoundly examined in further studies. There were no evident clinically relevant relations between inflammatory markers and pregnancy outcome measures.
  • Koivunen, Sanna; Viljakainen, Matti; Männistö, Tuija; Gissler, Mika; Pouta, Anneli; Kaaja, Risto; Eriksson, Johan; Laivuori, Hannele; Kajantie, Eero; Vääräsmäki, Marja (2020)
    Objective To assess the frequency and perinatal outcomes of gestational diabetes mellitus (GDM) defined by the criteria according to the International Association of Diabetes in Pregnancy Study Group (IADPSG) and the National Institute for Health and Care Excellence (NICE) diagnostic criteria for GDM. Design A retrospective cohort study. Setting Six secondary and tertiary delivery hospitals in Finland in 2009. Population Pregnant women (N = 4,033) and their offspring. Methods We used data on comprehensive screening of pregnant women with a 2-h 75-g oral glucose tolerance test (OGTT), performed between gestational weeks 24 and 40. OGTT glucose concentrations were used to identify women who fulfilled IADPSG and NICE criteria. While cut-offs according to Finnish national criteria partly overlapped with both criteria, a subgroup of IADPSG- or NICE-positive GDM women remained undiagnosed by Finnish criteria and hence non-treated. They were analysed as subgroups and compared to controls who were negative with all cut-offs. Main outcome measures GDM prevalence, birth weight SD score (BWSDS), large for gestational age (LGA) and caesarean section (CS) rates. Results Among the 4,033 women screened for GDM, 1,249 (31.0%) and 529 (13.1%) had GDM according to the IADPSG and NICE criteria, respectively. The LGA rate was similar in both groups. Regardless of the diagnostic criteria, women with GDM had a higher risk of induced delivery and CSs than controls. In IADPSG-positive non-treated women, offspring’s BWSDS and CS rate were higher than in controls. Conclusions GDM prevalence was 2.4-fold higher according to the IADPSG compared with the NICE criteria but the LGA rate did not differ. BWSDS and CS rate were increased already with mild untreated hyperglycaemia.
  • Prasad, Rashmi B.; Asplund, Olof; Shukla, Sharvari R.; Wagh, Rucha; Kunte, Pooja; Bhat, Dattatrey; Parekh, Malay; Shah, Meet; Phatak, Sanat; Karajamaki, Annemari; Datta, Anupam; Kakati, Sanjeeb; Tuomi, Tiinamaija; Saboo, Banshi; Ahlqvist, Emma; Groop, Leif; Yajnik, Chittaranjan S. (2022)
    Aim/hypothesis Five subgroups were described in European diabetes patients using a data driven machine learning approach on commonly measured variables. We aimed to test the applicability of this phenotyping in Indian individuals with young-onset type 2 diabetes. Methods We applied the European-derived centroids to Indian individuals with type 2 diabetes diagnosed before 45 years of age from the WellGen cohort (n = 1612). We also applied de novo k-means clustering to the WellGen cohort to validate the subgroups. We then compared clinical and metabolic-endocrine characteristics and the complication rates between the subgroups. We also compared characteristics of the WellGen subgroups with those of two young European cohorts, ANDIS (n = 962) and DIREVA (n = 420). Subgroups were also assessed in two other Indian cohorts, Ahmedabad (n = 187) and PHENOEINDY-2 (n = 205). Results Both Indian and European young-onset type 2 diabetes patients were predominantly classified into severe insulin-deficient (SIDD) and mild obesity-related (MOD) subgroups, while the severe insulin-resistant (SIRD) and mild age-related (MARD) subgroups were rare. In WellGen, SIDD (53%) was more common than MOD (38%), contrary to findings in Europeans (Swedish 26% vs 68%, Finnish 24% vs 71%, respectively). A higher proportion of SIDD compared with MOD was also seen in Ahmedabad (57% vs 33%) and in PHENOEINDY-2 (67% vs 23%). Both in Indians and Europeans, the SIDD subgroup was characterised by insulin deficiency and hyperglycaemia, MOD by obesity, SIRD by severe insulin resistance and MARD by mild metabolic-endocrine disturbances. In WellGen, nephropathy and retinopathy were more prevalent in SIDD compared with MOD while the latter had higher prevalence of neuropathy. Conclusions /interpretation Our data identified insulin deficiency as the major driver of type 2 diabetes in young Indians, unlike in young European individuals in whom obesity and insulin resistance predominate. Our results provide useful clues to pathophysiological mechanisms and susceptibility to complications in type 2 diabetes in the young Indian population and suggest a need to review management strategies.
  • Lind, Marcus; Tuomilehto, Jaakko; Uusitupa, Matti; Nerman, Olle; Eriksson, Johan; Ilanne-Parikka, Pirjo; Keinanen-Kiukaanniemi, Sirkka; Peltonen, Markku; Pivodic, Aldina; Lindstrom, Jaana (2014)
  • Tietäväinen, Johanna; Mäkelä, Satu; Huhtala, Heini; Pörsti, Ilkka H; Strandin, Tomas; Vaheri, Antti; Mustonen, Jukka (2021)
    Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome characterized by thrombocytopenia, increased capillary leakage, and acute kidney injury (AKI). As glucosuria at hospital admission predicts the severity of PUUV infection, we explored how plasma glucose concentration associates with disease severity. Plasma glucose values were measured during hospital care in 185 patients with PUUV infection. They were divided into two groups according to maximum plasma glucose concentration: P-Gluc < 7.8 mmol/L (n = 134) and P-Gluc >= 7.8 mmol/L (n = 51). The determinants of disease severity were analyzed across groups. Patients with P-Gluc >= 7.8 mmol/L had higher hematocrit (0.46 vs. 0.43; p < 0.001) and lower plasma albumin concentration (24 vs. 29 g/L; p < 0.001) than patients with P-Gluc < 7.8 mmol/L. They presented with higher prevalence of pulmonary infiltrations and pleural effusion in chest radiograph, higher prevalence of shock and greater weight change during hospitalization. Patients with P-Gluc >= 7.8 mmol/L were characterized by lower platelet count (50 vs. 66 x 10(9)/L; p = 0.001), more severe AKI (plasma creatinine 272 vs. 151 mu mol/L; p = 0.001), and longer hospital treatment (8 vs. 6 days; p < 0.001) than patients with P-Gluc < 7.8 mmol/L. Plasma glucose level is associated with the severity of capillary leakage, thrombocytopenia, inflammation, and AKI in patients with acute PUUV infection.