Browsing by Subject "GLUCOSE-TOLERANCE"

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  • Dayeh, Tasnim; Tuomi, Tiinamaija; Almgren, Peter; Perfilyev, Alexander; Jansson, Per-Anders; de Mello, Vanessa D.; Pihlajamaki, Jussi; Vaag, Allan; Groop, Leif; Nilsson, Emma; Ling, Charlotte (2016)
    Identification of subjects with a high risk of developing type 2 diabetes (T2D) is fundamental for prevention of the disease. Consequently, it is essential to search for new biomarkers that can improve the prediction of T2D. The aim of this study was to examine whether 5 DNA methylation loci in blood DNA (ABCG1, PHOSPHO1, SOCS3, SREBF1, and TXNIP), recently reported to be associated with T2D, might predict future T2D in subjects from the Botnia prospective study. We also tested if these CpG sites exhibit altered DNA methylation in human pancreatic islets, liver, adipose tissue, and skeletal muscle from diabetic vs. non-diabetic subjects. DNA methylation at the ABCG1 locus cg06500161 in blood DNA was associated with an increased risk for future T2D (OR = 1.09, 95% CI = 1.02-1.16, P-value = 0.007, Q-value = 0.018), while DNA methylation at the PHOSPHO1 locus cg02650017 in blood DNA was associated with a decreased risk for future T2D (OR = 0.85, 95% CI = 0.75-0.95, P-value = 0.006, Q-value = 0.018) after adjustment for age, gender, fasting glucose, and family relation. Furthermore, the level of DNA methylation at the ABCG1 locus cg06500161 in blood DNA correlated positively with BMI, HbA1c, fasting insulin, and triglyceride levels, and was increased in adipose tissue and blood from the diabetic twin among monozygotic twin pairs discordant for T2D. DNA methylation at the PHOSPHO1 locus cg02650017 in blood correlated positively with HDL levels, and was decreased in skeletal muscle from diabetic vs. non-diabetic monozygotic twins. DNA methylation of cg18181703 (SOCS3), cg11024682 (SREBF1), and cg19693031 (TXNIP) was not associated with future T2D risk in subjects from the Botnia prospective study.
  • Perälä, Mia-Maria; Valsta, Liisa M.; Kajantie, Eero; Leiviskä, Jaana; Eriksson, Johan G. (2011)
  • 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.
  • Masalin, Senja; Kautiainen, Hannu; Gissler, Mika; Pennanen, Pirjo; Eriksson, Johan G.; Laine, Merja K. (2020)
    Introduction Smoking has been shown to affect glucose homeostasis and increase the risk for type 2 diabetes mellitus. Further, gestational diabetes mellitus (GDM) and smoking are known to influence offspring birthweight. The effect of smoking on glucose homeostasis in pregnancy is less studied and the findings are inconsistent. The aim of this study was to evaluate the effect of smoking on risk for GDM and to evaluate the impact of smoking and GDM on offspring birthweight. Material and methods This is an observational cohort study encompassing 4111 Finnish primiparous women from the city of Vantaa, Finland, who delivered a singleton child between 2009 and 2015. Data were obtained from Finnish national registers. Study participants had complete oral glucose tolerance test results and were divided into three groups according to smoking status: non-smokers (I), smokers who quit during first trimester (II), and smokers who continued after first trimester (III). Results Prevalence of GDM was 19.8%, 24.3%, and 26.6% in non-smokers, those who quit, and those who continued after the first trimester, respectively (P = .004 for differences between groups). The odds ratio for GDM in smokers who continued after the first trimester compared with non-smokers was 1.65 (95% CI 1.09-2.57) after adjustments for age, prepregnancy body mass index, education, and cohabitation. In women without GDM, offspring birthweight was lowest in those who continued smoking after the first trimester (P = .010 for differences between groups). In women with GDM, smoking status did not influence offspring birthweight. Conclusions Smoking during pregnancy is associated with an increased risk for GDM. Offspring birthweight is lowest in women who continue smoking after the first trimester. If pregnancy is complicated by GDM, offspring birthweight is not influenced by smoking.
  • Tuomi, Tiinamaija; Nagorny, Cecilia L. F.; Singh, Pratibha; Bennet, Hedvig; Yu, Qian; Alenkvist, Ida; Isomaa, Bo; Ostman, Bjarne; Soderstrom, Johan; Pesonen, Anu-Katriina; Martikainen, Silja; Räikkönen, Katri; Forsen, Tom; Hakaste, Liisa; Almgren, Peter; Storm, Petter; Asplund, Olof; Shcherbina, Liliya; Fex, Malin; Fadista, Joao; Tengholm, Anders; Wierup, Nils; Groop, Leif; Mulder, Hindrik (2016)
    Type 2 diabetes (T2D) is a global pandemic. Genome-wide association studies (GWASs) have identified >100 genetic variants associated with the disease, including a common variant in the melatonin receptor 1 b gene (MTNR1B). Here, we demonstrate increased MTNR1B expression in human islets from risk G-allele carriers, which likely leads to a reduction in insulin release, increasing T2D risk. Accordingly, in insulin-secreting cells, melatonin reduced cAMP levels, and MTNR1B overexpression exaggerated the inhibition of insulin release exerted by melatonin. Conversely, mice with a disruption of the receptor secreted more insulin. Melatonin treatment in a human recall-by-genotype study reduced insulin secretion and raised glucose levels more extensively in risk G-allele carriers. Thus, our data support a model where enhanced melatonin signaling in islets reduces insulin secretion, leading to hyperglycemia and greater future risk of T2D. The findings also imply that melatonin physiologically serves to inhibit nocturnal insulin release.
  • Mardinoglu, Adil; Stancakova, Alena; Lotta, Luca A.; Kuusisto, Johanna; Boren, Jan; Bluher, Matthias; Wareham, Nicholas J.; Ferrannini, Ele; Groop, Per Henrik; Laakso, Markku; Langenberg, Claudia; Smith, Ulf (2017)
  • Mustaniemi, Sanna; Vääräsmäki, Marja; Eriksson, Johan G.; Gissler, Mika; Laivuori, Hannele; Ijäs, Hilkka; Bloigu, Aini; Kajantie, Eero; Morin-Papunen, Laure (2018)
    Objective: To study the roles of self-reported symptoms and/or prior diagnosis of polycystic ovary syndrome (PCOS) and other potential risk factors for gestational diabetes mellitus (GDM) and to clarify whether the screening of GDM in early pregnancy is beneficial for all women with PCOS. Design: The FinnGeDi multicentre case-control study including 1146 women with singleton pregnancies diagnosed with GDM and 1066 non-diabetic pregnant women. There were 174 women with PCOS (symptoms and/or diagnosis self-reported by a questionnaire) and 1767 women without PCOS (data missing for 271). Methods: The study population (N=1941) was divided into four subgroups: GDM+ PCOS (N= 105), GDM+ non-PCOS (N =909), non-GDM+PCOS (N=69), and controls (N=858). The participants' characteristics and their parents' medical histories were compared. Results: The prevalence of PCOS was 10.4% among GDM women and 7.4% among non-diabetics (odds ratios (OR) 1.44, 95% CI: 1.05-1.97), but PCOS was not an independent risk for GDM after adjustments for participants' age and pre-pregnancy BMI (OR 1.07, 95% CI: 0.74-1.54). In a multivariate logistic regression analysis, the most significant parameters associated with GDM were overweight, obesity, age >= 35 years, participant's mother's history of GDM, either parent's history of type 2 diabetes (T2D) and participant's own preterm birth. Conclusions: The increased risk of GDM in women with PCOS was related to obesity and increased maternal age rather than to PCOS itself, suggesting that routine early screening of GDM in PCOS women without other risk factors should be reconsidered. Instead, family history of GDM/T2D and own preterm birth were independent risk factors for GDM.
  • Rönö, Kristiina; Stach-Lempinen, Beata; Klemetti, Miira M; Kaaja, Risto; Pöyhönen-Alho, Maritta; Eriksson, Johan G.; Koivusalo, Saila B.; Andersson, Sture; Huvinen, Emilia; Radiel Grp (2014)
  • Laine, M. K.; Kautiainen, H.; Gissler, M.; Raina, M.; Aahos, I.; Jarvinen, K.; Eriksson, J. G. (2018)
    Objectives: Both short stature and adiposity are risk factors for gestational diabetes mellitus (GDM). The aim of this study was to simultaneously evaluate the importance of stature and degree of adiposity on development of GDM in primiparous women. Study design: Longitudinal cohort study. Methods: In the city of Vantaa, Finland, between 2009 and 2015, all together 7750 primiparous women without previously diagnosed diabetes mellitus gave birth. Of these, 5223 women were >= 18 years of age with information on height, weight, and complete data from a 75 g 2-h oral glucose tolerance test composing the study participants of this study. Results: A 155-cm tall woman with a body mass index (BMI) of 25.5 kg/m(2) had a similar risk for GDM as a 175-cm tall woman with a BMI of 27.1 kg/m(2). Women shorter than 159 cm had the highest prevalence of GDM, 28.7%, whereas women with height between 164 and 167 cm had the lowest prevalence of GDM, 19.9% (P <0.001). Height was inversely and significantly associated with both 1- and 2-h glucose values (both P <0.001). Conclusions: To avoid over diagnosis of GDM, an unbiased strategy is needed to determine and diagnose GDM in women with different stature and degree of adiposity. (c) 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.
  • Luotola, Kari; Piltonen, Terhi T; Puurunen, Johanna; Morin-Papunen, Laure C; Tapanainen, Juha S (2018)
    Objective: To study the associations between androgens, glucose homeostasis, inflammation and statin treatment in women with polycystic ovary syndrome (PCOS). Design and methods: Oral glucose tolerance tests, androgens, hs-CRP and interleukin-1 receptor antagonist (IL-1Ra) were analyzed at baseline and after 6months of atorvastatin (20 mg/d) or placebo treatment in 27 women with PCOS. Results: Testosterone associated with insulin resistance measured with ISIMatsuda independently of BMI, age and SHBG concentrations and the full model, including IL-1Ra, hs-CRP and HDL-C, also showed independency of BMI and waist circumference (p≤.042). Free androgen index (FAI) associated with ISIMatsuda independently of adiposity (p≤.025) but in the full model with waist circumference the association was insignificant. ISIMatsuda decreased with testosterone >1.2nmol/l compared with lower levels at baseline (p=.043) and at six months (p=.003). Accordingly, 30-minute insulin levels were increased with moderately elevated testosterone independently of adiposity (p≤.046). Increased fasting glucose and AUC insulin associated with statin treatment independently of adiposity and the associations attenuated after adjusting for testosterone.  Conclusions: Moderately elevated testosterone concentrations together with obesity-related inflammatory factors modify glucose homeostasis by increasing insulin resistance and early insulin secretion.
  • Enani, Sumia; Bahijri, Suhad; Malibary, Manal; Jambi, Hanan; Eldakhakhny, Basmah; Al-Ahmadi, Jawaher; Al Raddadi, Rajaa; Ajabnoor, Ghada; Boraie, Anwar; Tuomilehto, Jaakko (2020)
    Diet and other lifestyle habits have been reported to contribute to the development of dyslipidemia in various populations. Therefore, this study investigated the association between dyslipidemia and dietary and other lifestyle practices among Saudi adults. Data were collected from adults (>= 20 years) not previously diagnosed with diabetes in a cross-sectional design. Demographic, anthropometric, and clinical characteristics, as well as lifestyle and dietary habits were recorded using a predesigned questionnaire. Fasting blood samples were drawn to estimate the serum lipid profile. Out of 1385 people, 858 (62%) (491 men, 367 women) had dyslipidemia. After regression analysis to adjust for age, body mass index, and waist circumference, an intake of >= 5 cups/week of Turkish coffee, or carbonated drinks was associated with increased risk of dyslipidemia in men (OR (95% CI), 2.74 (1.53, 4.89)p= 0.001, and 1.53 (1.04, 2.26)p= 0.03 respectively), while the same intake of American coffee had a protective effect (0.53 (0.30, 0.92)p= 0.025). Sleep duration
  • Miao, Zong; Alvarez, Marcus; Ko, Arthur; Bhagat, Yash; Rahmani, Elior; Jew, Brandon; Heinonen, Sini; Munoz-Hernandez, Linda Liliana; Herrera-Hernandez, Miguel; Aguilar-Salinas, Carlos; Tusie-Luna, Teresa; Mohlke, Karen L.; Laakso, Markku; Pietiläinen, Kirsi H.; Halperin, Eran; Pajukanta, Päivi (2020)
    Reverse causality has made it difficult to establish the causal directions between obesity and prediabetes and obesity and insulin resistance. To disentangle whether obesity causally drives prediabetes and insulin resistance already in non-diabetic individuals, we utilized the UK Biobank and METSIM cohort to perform a Mendelian randomization (MR) analyses in the non-diabetic individuals. Our results suggest that both prediabetes and systemic insulin resistance are caused by obesity (p = 1.2x10(-3)and p = 3.1x10(-24)). As obesity reflects the amount of body fat, we next studied how adipose tissue affects insulin resistance. We performed both bulk RNA-sequencing and single nucleus RNA sequencing on frozen human subcutaneous adipose biopsies to assess adipose cell-type heterogeneity and mitochondrial (MT) gene expression in insulin resistance. We discovered that the adipose MT gene expression and body fat percent are both independently associated with insulin resistance (p Author summary Obesity is a global health epidemic predisposing to type 2 diabetes (T2D) and other cardiometabolic disorders. Previous studies have shown that obesity has a causal effect on T2D; however, it remains unknown whether obesity causes prediabetes and insulin resistance already in non-diabetic individuals. By utilizing almost half a million individuals from the UK Biobank and the Finnish METSIM cohort, we identified a significant causal effect of obesity on prediabetes and insulin resistance among the non-diabetic individuals. Next, we investigated the role of subcutaneous adipose tissue in these obesogenic effects. We discovered that the adipose mitochondrial gene expression and body fat percent are independently associated with insulin resistance after adjusting for the tissue heterogeneity. For the latter, we estimated the adipose cell type proportions by utilizing single-nucleus RNA sequencing of frozen adipose tissue biopsies. Moreover, we established a prediction model to estimate insulin resistance using body fat percent and adipose RNA-sequencing data, which enlightens the importance of adipose tissue in insulin resistance and provides a helpful tool to impute the insulin resistance for existing adipose RNA-sequencing cohorts. Overall, we discover the potential causal effect of obesity on prediabetes and insulin resistance and the key role of adipose tissue in insulin resistance.
  • Vrieze, A.; Holleman, F.; Zoetendal, E. G.; de Vos, W. M.; Hoekstra, J. B. L.; Nieuwdorp, M. (2010)
  • Paldanius, Paivi M.; Ivaska, Kaisa K.; Hovi, Petteri; Andersson, Sture; Eriksson, Johan G.; Vaananen, Kalervo; Kajantie, Eero; Mäkitie, Outi (2013)
  • Isokuortti, Elina; Zhou, You; Peltonen, Markku; Bugianesi, Elisabetta; Clement, Karine; Bonnefont-Rousselot, Dominique; Lacorte, Jean-Marc; Gastaldelli, Amalia; Schuppan, Detlef; Schattenberg, Joern M.; Hakkarainen, Antti; Lundbom, Nina; Jousilahti, Pekka; Mannisto, Satu; Keinanen-Kiukaanniemi, Sirkka; Saltevo, Juha; Anstee, Quentin M.; Yki-Jarvinen, Hannele (2017)
    Aims/hypothesis Recent European guidelines for nonalcoholic fatty liver disease (NAFLD) call for reference values for HOMA-IR. In this study, we aimed to determine: (1) the upper limit of normal HOMA-IR in two population-based cohorts; (2) the HOMA-IR corresponding to NAFLD; (3) the effect of sex and PNPLA3 genotype at rs738409 on HOMA-IR; and (4) inter-laboratory variations in HOMA-IR. Methods We identified healthy individuals in two population-based cohorts (FINRISK 2007 [n = 5024] and the Programme for Prevention of Type 2 Diabetes in Finland [FIN-D2D; n = 2849]) to define the upper 95th percentile of HOMA-IR. Non-obese individuals with normal fasting glucose levels, no excessive alcohol use, no known diseases and no use of any drugs were considered healthy. The optimal HOMA-IR cut-off for NAFLD (liver fat >= 5.56%, based on the Dallas Heart Study) was determined in 368 non-diabetic individuals (35% with NAFLD), whose liver fat was measured using proton magnetic resonance spectroscopy (1H-MRS). Samples from ten individuals were simultaneously analysed for HOMA-IR in seven European laboratories. Results The upper 95th percentiles of HOMA-IR were 1.9 and 2.0 in healthy individuals in the FINRISK (n = 1167) and FIN-D2D (n = 459) cohorts. Sex or PNPLA3 genotype did not influence these values. The optimal HOMA-IR cutoff for NAFLD was 1.9 (sensitivity 87%, specificity 79%). A HOMA-IR of 2.0 corresponded to normal liver fat ( Conclusions/interpretation The upper limit of HOMA-IR in population-based cohorts closely corresponds to that of normal liver fat. Standardisation of insulin assays would be the first step towards definition of normal values for HOMA-IR.
  • Mustonen, Laura; Aho, Tommi; Harno, Hanna; Sipilä, Reetta; Meretoja, Tuomo; Kalso, Eija (2019)
    Nerve injury during breast cancer surgery can cause neuropathic pain (NP). It is not known why some, but not all, patients develop chronic postsurgical neuropathic pain (CPSNP) after the same nerve injury. In this study, we examined 251 breast cancer survivors with surgeon-verified intercostobrachial nerve resection to identify factors that associate with CPSNP. The patients were recruited from a previous study of 1000 women treated for breast cancer in 2006 to 2010. This enabled us to analyze preoperative factors that associate with future CPSNP. The patients were re-examined in 2014 to 2016 to diagnose CPSNP using the revised NP diagnostic criteria. Preoperative assessments were pain in the area to be operated on, any chronic pain condition, depressive symptoms, anxiety, sleep, and experimental cold pain sensitivity using the cold pressor test (CPT). Follow-up assessments were CPT, psychological factors, sleep, any chronic pain, and basic laboratory tests. One hundred thirty-seven (55%) patients with intercostobrachial nerve resection fulfilled CPSNP diagnostic criteria after 4 to 9 years. Of them, 30 patients (22%) had moderate to severe pain in self-reports and 86 (63%) presented moderate to severe evoked pain at examination. Preoperative pain in the surgical area, other chronic pains, and breast-conserving surgery were associated with future CPSNP. Other chronic pains, increased psychological burden, and insomnia, both before surgery and at the follow-up, were associated with CPSNP. Preoperative CPT did not associate with future CPSNP. Patients with established CPSNP showed increased pain sensitivity in CPT and higher levels of inflammatory markers, suggesting that central sensitization and inflammation may associate with the maintenance of CPSNP.