Browsing by Subject "GLUCOSE"

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  • Prokopenko, Inga; Poon, Wenny; Maegi, Reedik; Prasad, Rashmi B.; Salehi, S. Albert; Almgren, Peter; Osmark, Peter; Bouatia-Naji, Nabila; Wierup, Nils; Fall, Tove; Stancakova, Alena; Barker, Adam; Lagou, Vasiliki; Osmond, Clive; Xie, Weijia; Lahti, Jari; Jackson, Anne U.; Cheng, Yu-Ching; Liu, Jie; O'Connell, Jeffrey R.; Blomstedt, Paul A.; Fadista, Joao; Alkayyali, Sami; Dayeh, Tasnim; Ahlqvist, Emma; Taneera, Jalal; Lecoeur, Cecile; Kumar, Ashish; Hansson, Ola; Hansson, Karin; Voight, Benjamin F.; Kang, Hyun Min; Levy-Marchal, Claire; Vatin, Vincent; Palotie, Aarno; Syvanen, Ann-Christine; Mari, Andrea; Weedon, Michael N.; Loos, Ruth J. F.; Ong, Ken K.; Nilsson, Peter; Isomaa, Bo; Tuomi, Tiinamaija; Wareham, Nicholas J.; Stumvoll, Michael; Widen, Elisabeth; Lakka, Timo A.; Langenberg, Claudia; Tonjes, Anke; Rauramaa, Rainer; Kuusisto, Johanna; Frayling, Timothy M.; Froguel, Philippe; Walker, Mark; Eriksson, Johan G.; Ling, Charlotte; Kovacs, Peter; Ingelsson, Erik; McCarthy, Mark I.; Shuldiner, Alan R.; Silver, Kristi D.; Laakso, Markku; Groop, Leif; Lyssenko, Valeriya (2014)
  • Kettunen, Jarno L. T.; Rantala, Elina; Dwivedi, Om P.; Isomaa, Bo; Sarelin, Leena; Kokko, Paula; Hakaste, Liisa; Miettinen, Päivi J.; Groop, Leif C.; Tuomi, Tiinamaija (2022)
    Aims/hypothesis Systematic studies on the phenotypic consequences of variants causal of HNF1A-MODY are rare. Our aim was to assess the phenotype of carriers of a single HNF1A variant and genetic and clinical factors affecting the clinical spectrum. Methods We conducted a family-based multigenerational study by comparing heterozygous carriers of the HNF1A p.(Gly292fs) variant with the non-carrier relatives irrespective of diabetes status. During more than two decades, 145 carriers and 131 non-carriers from 12 families participated in the study, and 208 underwent an OGTT at least once. We assessed the polygenic risk score for type 2 diabetes, age at onset of diabetes and measures of body composition, as well as plasma glucose, serum insulin, proinsulin, C-peptide, glucagon and NEFA response during the OGTT. Results Half of the carriers remained free of diabetes at 23 years, one-third at 33 years and 13% even at 50 years. The median age at diagnosis was 21 years (IQR 17-35). We could not identify clinical factors affecting the age at conversion; sex, BMI, insulin sensitivity or parental carrier status had no significant effect. However, for 1 SD unit increase of a polygenic risk score for type 2 diabetes, the predicted age at diagnosis decreased by 3.2 years. During the OGTT, the carriers had higher levels of plasma glucose and lower levels of serum insulin and C-peptide than the non-carriers. The carriers were also leaner than the non-carriers (by 5.0 kg, p=0.012, and by 2.1 kg/m(2) units of BMI, p=2.2 x 10(-4), using the first adult measurements) and, possibly as a result of insulin deficiency, demonstrated higher lipolytic activity (with medians of NEFA at fasting 621 vs 441 mu mol/l, p=0.0039; at 120 min during an OGTT 117 vs 64 mu mol/l, p=3.1 x 10(-5)). Conclusions/interpretation The most common causal variant of HNF1A-MODY, p.(Gly292fs), presents not only with hyperglycaemia and insulin deficiency, but also with increased lipolysis and markedly lower adult BMI. Serum insulin was more discriminative than C-peptide between carriers and non-carriers. A considerable proportion of carriers develop diabetes after young adulthood. Even among individuals with a monogenic form of diabetes, polygenic risk of diabetes modifies the age at onset of diabetes.
  • Matthews, David R.; Paldanius, Päivi M.; Stumvoll, Michael; Han, Jackie; Bader, Giovanni; Chiang, YannTong; Proot, Pieter; Del Prato, Stefano (2019)
    Aims To ensure the integrity of the planned analyses and maximize the clinical utility of the VERIFY study results by describing the detailed concepts behind its statistical analysis plan (SAP) before completion of data collection and study database lock. The SAP will be adhered to for the final primary data analysis of the VERIFY trial. Materials and Methods Vildagliptin efficacy in combination with metformin for early treatment of T2DM (VERIFY) is an ongoing, multicentre, randomized controlled trial aiming to demonstrate the clinical benefits of glycaemic durability and glucose control achieved with an early combination therapy in newly-diagnosed type 2 diabetes (T2DM) patients. Results The SAP was initially designed at the study protocol conception phase and later modified, as reported here, in collaboration between the steering committee members, statisticians, and the VERIFY study leadership team. All authors were blinded to treatment allocation. An independent statistician has additionally retrieved and presented unblinded data to the independent data safety monitoring committee. An overview of the trial design with a focus on describing the fine-tuning of the analysis plan for the primary efficacy endpoint, risk of initial treatment failure, and secondary, exploratory and pre-specified subgroup analyses is provided here. Conclusion According to optimal trial practice, the details of the statistical analysis and data-handling plan prior to locking the database are reported here. The SAP accords with high-quality standards of internal validity to minimize analysis bias and will enhance the utility of the reported results for improved outcomes in the management of T2DM.
  • Mysore, Raghavendra; Liebisch, Gerhard; Zhou, You; Olkkonen, Vesa M.; Haridas, P. A. Nidhina (2017)
    Angiopoietin-like 8 (Angptl8) inhibits lipolysis in the circulation together with Angplt3 and controls post-prandial fat storage in white adipose tissue (WAT). It is strongly induced by insulin in vivo in WAT and in vitro in adipocytes. In this study we addressed the function of Angptl8 in adipocytes by its stable lentivirus-mediated knock-down in 3T3-L1 cells, followed by analyses of triglyceride (TG) storage, lipid droplet (LD) morphology, the cellular lipidome, lipolysis, and gene expression. Depletion of Angptl8 did not drastically affect the adipocyte differentiation of 3T3-L1 cells but resulted in a moderate (18-19%) reduction of stored TGs. The lipidome analysis revealed a reduction of alkyl-phosphatidylcholines (PCs) and phosphatidylethanolamine (PE) plasmalogens, as well as saturated PCs and PEs. Importantly, the Angptl8 depleted cells displayed enhanced lipolysis as measured by release of non-esterified fatty acids (NEFA5). Consistently, mRNAs encoding Angptl4 and Leptin, which facilitate lipolysis, as well as Cpt1a, Cpt1b, and Pgc-1 alpha involved in FA oxidation, were elevated. The Angptl8 mRNA itself was suppressed by pharmacologic treatments inducing lipolysis: stimulation with the beta-adrenergic agonist isoproterenol or with the adenylate cyclase activator forskolin. To conclude, knock-down of Angptl8 in adipocytes suggests that the protein acts to inhibit intracellular lipolysis, analogous to its activity in the circulation. Depletion of Angptl8 results in an altered cellular phospholipid composition. The findings identify Angptl8 as a central insulin-regulated controller of adipocyte lipid metabolism. (C) 2017 Elsevier B.V. All rights reserved.
  • Helkkula, Pyry; Kiiskinen, Tuomo; Havulinna, Aki S.; Karjalainen, Juha; Koskinen, Seppo; Salomaa, Veikko; Daly, Mark; Palotie, Aarno; Surakka, Ida; Ripatti, Samuli (2021)
    Protein-truncating variants (PTVs) affecting dyslipidemia risk may point to therapeutic targets for cardiometabolic disease. Our objective was to identify PTVs that were associated with both lipid levels and the risk of coronary artery disease (CAD) or type 2 diabetes (T2D) and assess their possible associations with risks of other diseases. To achieve this aim, we leveraged the enrichment of PTVs in the Finnish population and tested the association of low-frequency PTVs in 1,209 genes with serum lipid levels in the Finrisk Study (n = 23,435). We then tested which of the lipid-associated PTVs were also associated with the risks of T2D or CAD, as well as 2,683 disease endpoints curated in the FinnGen Study (n = 218,792). Two PTVs were associated with both lipid levels and the risk of CAD or T2D: triglyceride-lowering variants in ANGPTL8 (-24.0[-30.4 to -16.9] mg/dL per rs760351239-T allele, P = 3.4 x 10(-9)) and ANGPTL4 (-14.4[-18.6 to -9.8] mg/dL per rs746226153-G allele, P = 4.3 x 10(-9)). The risk of T2D was lower in carriers of the ANGPTL4 PTV (OR = 0.70[0.60-0.81], P = 2.2 x 10(-6)) than noncarriers. The odds of CAD were 47% lower in carriers of a PTV in ANGPTL8 (OR = 0.53[0.37-0.76], P = 4.5 x 10(-4)) than noncarriers. Finally, the phenome-wide scan of the ANGPTL8 PTV showed that the ANGPTL8 PTV carriers were less likely to use statin therapy (68,782 cases, OR = 0.52[0.40-0.68], P = 1.7 x 10(-6)) compared to noncarriers. Our findings provide genetic evidence of potential long-term efficacy and safety of therapeutic targeting of dyslipidemias. Author summary Studying the health impacts of protein-truncating variants (PTVs) enables detecting the health impact of drugs that inhibit these same genes. Our study aimed to expand our knowledge of genes associated with cardiometabolic disease, along with the side effects of these genes. To detect PTVs associated with cardiometabolic disease, we first performed a genome-wide scan of PTVs associated with serum lipid levels in Finns. We found PTVs in two genes highly enriched in Finns, which were associated with both serum lipid levels and a lower risk of type 2 diabetes or coronary artery disease: ANGPTL4 and ANGPTL8. To evaluate the other health effects of these PTVs, we performed an association scan between the PTVs and 2,683 disease endpoints curated in the FinnGen Study (n = 218,792). We demonstrate that using human populations with PTV-enrichment, such as Finns, offers considerable boosts in statistical power to detect potential long-term efficacy and safety of pharmacologically targeting genes.
  • IDEFICS and I.Family consortia; Thumann, Barbara F.; Michels, Nathalie; Felső, Regina; Kaprio, Jaakko; Börnhorst, Claudia (2020)
    Background Short sleep duration has been suggested to lead to insulin resistance both directly by altering glucose metabolism and indirectly through obesity. This study aims to investigate associations between nocturnal sleep duration and insulin resistance considering abdominal obesity as a mediator. Methods We analysed data of 3 900 children aged 2–15 years participating in the second (2009/10) and third (2013/14) examination wave of the European IDEFICS/I.Family study (hereafter referred to as baseline and follow-up). Information on nocturnal sleep duration was collected by questionnaires and age-standardised (SLEEP z-score). The homeostasis model assessment (HOMA) was calculated from fasting insulin and fasting glucose obtained from blood samples; waist circumference (WAIST) was measured with an inelastic tape. HOMA and WAIST were used as indicators for insulin resistance and abdominal obesity, respectively, and transformed to age- and sex-specific z-scores. Cross-sectional and longitudinal associations between SLEEP z-score and HOMA z-score were investigated based on a path model considering WAIST z-score as a mediator adjusting for relevant confounders. Results Cross-sectionally, baseline SLEEP z-score was negatively associated with baseline WAIST z-score (unstandardised effect estimate -0.120, 95% confidence interval [-0.167; -0.073]). We observed no direct effect of baseline SLEEP z-score on baseline HOMA z-score but a negative indirect effect through baseline WAIST z-score (-0.042 [-0.058; -0.025]). Longitudinally, there was no direct effect of baseline SLEEP z-score on HOMA z-score at follow-up but a negative indirect effect through both baseline WAIST z-score and WAIST z-score at follow-up (-0.028 [-0.040; -0.016]). Conclusions Our results do not support the hypothesis of an association between short sleep duration and insulin resistance independent of abdominal obesity. However, longer sleep duration may exert short and long term beneficial effects on insulin resistance through its beneficial effects on abdominal obesity.
  • Henriksson, P; Sandborg, J; Soderstrom, E; Leppanen, MH; Snekkenes, V; Blomberg, M; Ortega, FB; Lof, M (2021)
    The aim of this study was to examine associations of body composition (fat mass index, % fat mass, fat-free mass index, body mass index) and physical fitness (cardiorespiratory fitness and handgrip strength) with gestational diabetes and cardiovascular health in early pregnancy. This cross-sectional study utilized baseline data (n = 303) collected in early pregnancy from the HealthyMoms trial. Body composition was measured using air-displacement plethysmography, cardiorespiratory fitness was assessed by means of the 6-min walk test and handgrip strength using a dynamometer. Logistic regression was used to estimate odds ratios (ORs) for gestational diabetes as well as high (defined as 1 SD above the mean) blood pressure, homeostatic model assessment for insulin resistance (HOMA-IR), and metabolic syndrome score (MetS score) per 1 SD increase in body composition and fitness variables. Fat mass index, % fat mass and body mass index were all strongly associated with gestational diabetes (ORs: 1.72-2.14, P = 0.61). In conclusion, accurately measured fat mass index or % fat mass were strongly associated with gestational diabetes risk and markers of cardiovascular health although associations were not stronger than the corresponding ones for body mass index. Fat-free mass index had only weak associations with gestational diabetes and cardiovascular health which support that the focus during clinical care would be on excess fat mass and not fat-free mass.
  • Kumar, Mukkesh; Ang, Li Ting; Png, Hang; Ng, Maisie; Tan, Karen; Loy, See Ling; Tan, Kok Hian; Chan, Jerry Kok Yen; Godfrey, Keith M.; Chan, Shiao-yng; Chong, Yap Seng; Eriksson, Johan G.; Feng, Mengling; Karnani, Neerja (2022)
    The increasing prevalence of gestational diabetes mellitus (GDM) is contributing to the rising global burden of type 2 diabetes (T2D) and intergenerational cycle of chronic metabolic disorders. Primary lifestyle interventions to manage GDM, including second trimester dietary and exercise guidance, have met with limited success due to late implementation, poor adherence and generic guidelines. In this study, we aimed to build a preconception-based GDM predictor to enable early intervention. We also assessed the associations of top predictors with GDM and adverse birth outcomes. Our evolutionary algorithm-based automated machine learning (AutoML) model was implemented with data from 222 Asian multi-ethnic women in a preconception cohort study, Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO). A stacked ensemble model with a gradient boosting classifier and linear support vector machine classifier (stochastic gradient descent training) was derived using genetic programming, achieving an excellent AUC of 0.93 based on four features (glycated hemoglobin A(1c) (HbA(1c)), mean arterial blood pressure, fasting insulin, triglycerides/HDL ratio). The results of multivariate logistic regression model showed that each 1 mmol/mol increase in preconception HbA(1c) was positively associated with increased risks of GDM (p = 0.001, odds ratio (95% CI) 1.34 (1.13-1.60)) and preterm birth (p = 0.011, odds ratio 1.63 (1.12-2.38)). Optimal control of preconception HbA(1c) may aid in preventing GDM and reducing the incidence of preterm birth. Our trained predictor has been deployed as a web application that can be easily employed in GDM intervention programs, prior to conception.
  • Fan, Yuxin; Wang, Leishen; Liu, Huikun; Zhang, Shuang; Tian, Huiguang; Shen, Yun; Tuomilehto, Jaakko; Yu, Zhijie; Yang, Xilin; Hu, Gang; Liu, Ming (2020)
    Introduction To evaluate the single association of postpartum beta-cell dysfunction and insulin resistance (IR), as well as different combinations of postpartum beta-cell dysfunction, IR, obesity, and a history of gestational diabetes mellitus (GDM) with postpartum type 2 diabetes risk. Research design and methods The study included 1263 women with prior GDM and 705 women without GDM. Homeostatic model assessment was used to estimate homeostatic model assessment of beta-cell secretory function (HOMA-%beta) and homeostatic model assessment of insulin resistance (HOMA-IR). Results Multivariable-adjusted ORs of diabetes across quartiles of HOMA-%beta and HOMA-IR were 1.00, 1.46, 2.15, and 6.25 (p(trend) Conclusions beta-cell dysfunction or IR was significantly associated with postpartum diabetes. IR and beta-cell dysfunction, together with obesity and a history of GDM, had the highest ORs of postpartum diabetes risk.
  • Zhang, Kaiyi; Tao, Cong; Xu, Jianping; Ruan, Jinxue; Xia, Jihan; Zhu, Wenjuan; Xin, Leilei; Ye, Huaqiong; Xie, Ning; Xia, Boce; Li, Chenxiao; Wu, Tianwen; Wang, Yanfang; Schroyen, Martine; Xiao, Xinhua; Fan, Jiangao; Yang, Shulin (2021)
    Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. We used CRISPR/Cas9 techniques to targeted knock-in three humanized disease risk genes, GIPR(dn) , hIAPP and PNPLA3(I148M) . Transgenic effect increased the risk of metabolic disorders. Triple-transgenic pigs with short-term diet intervention showed early symptoms of type 2 diabetes, including glucose intolerance, pancreatic lipid infiltration, islet hypertrophy, hepatic lobular inflammation and adipose tissue inflammation. Molecular pathways related to CD8(+) T cell function were significantly activated in the liver and visceral adipose samples from triple-transgenic pigs, including antigen processing and presentation, T-cell receptor signaling, co-stimulation, cytotoxicity, and cytokine and chemokine secretion. The similar pro-inflammatory signaling in liver and visceral adipose tissue indicated that there might be a potential immune crosstalk between the two tissues. Moreover, genes that functionally related to liver antioxidant activity, mitochondrial function and extracellular matrix showed distinct expression between the two groups, indicating metabolic stress in transgenic pigs' liver samples. We confirmed that triple-transgenic pigs had high coincidence with human metabolic diseases, especially in the scope of inflammatory signaling at early stage metaflammation. Taken together, this study provides a valuable large animal model for the clinical study of metaflammation and metabolic diseases.
  • 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.
  • D'Alessio, D.; Haering, H. -U.; Charbonnel, B.; de Pablos-Velasco, P.; Candelas, C.; Dain, M. -P.; Vincent, M.; Pilorget, V.; Yki-Jarvinen, H.; EAGLE Investigators (2015)
  • Ma, Hao; Zhou, Bo; Li, Yiqun; Argyropoulos, Dimitris S. (2012)
  • Hakkarainen, Heidi; Huopio, Hanna; Cederberg, Henna; Voutilainen, Raimo; Heinonen, Seppo (2018)
    Aims: Was to determine whether the birth weight of the infant predicts prediabetes (impaired fasting glucose, impaired glucose tolerance, or both) and type 2 diabetes (T2DM) during long-term follow-up of women with or without gestational diabetes mellitus (GDM). Methods: The women with or without GDM during their pregnancies in Kuopio University Hospital in 1989-2009 (n=876) were contacted and invited for an evaluation. They were stratified into two groups according to the newborn's birth weight: 10-90th percentile (appropriate-for-gestational-age; AGA) (n = 662) and >90th percentile (large-for-gestational-age; LGA) (n = 116). Glucose tolerance was investigated with an oral glucose tolerance test after a mean follow-up time of 7.3 (SD 5.1) years. Results: The incidence of T2DM was 11.8% and 0% in the women with and without GDM, respectively, after an LGA delivery. The incidence of prediabetes increased with offspring birth weight categories in the women with and without GDM: from 46.3% and 26.2% (AGA) to 52.9% and 29.2% (LGA), respectively. Conclusions: GDM women with LGA infants are at an increased risk for subsequent development of T2DM and therefore represent a target group for intervention to delay or prevent T2DM development. In contrast, an LGA delivery without GDM does not increase T2DM risk. (C) 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.
  • Dorenbos, Elke; Drummen, Mathijs; Adam, Tanja; Rijks, Jesse; Winkens, Bjorn; Alfredo Martinez, J.; Navas-Carretero, Santiago; Stratton, Gareth; Swindell, Nils; Stouthart, Pauline; Mackintosh, Kelly; Mcnarry, Melitta; Tremblay, Angelo; Fogelholm, Mikael; Raben, Anne; Westerterp-Plantenga, Margriet; Vreugdenhil, Anita (2021)
    Background Pubertal insulin resistance (IR) is associated with increased risk of type 2 diabetes mellitus development in adolescents with overweight/obesity. Objectives The PREVIEW study was a randomized parallel trial assessing the change in IR, analyzed by Homeostatic Model Assessment of IR (HOMA-IR), at 2 years after randomization to a high protein vs a moderate protein diet in adolescents with overweight/obesity. It was hypothesized that a high protein/low glycaemic index diet would be superior in reducing IR compared to a medium protein/medium GI diet, in insulin resistant adolescents with overweight or obesity. Methods Adolescents with overweight/obesity and IR from the Netherlands, United Kingdom and Spain were randomized into a moderate protein/moderate GI (15/55/30En% protein/carbohydrate/fat, GI >= 56) or high protein/low GI (25/45/30En% protein/carbohydrate/fat, GI < 50) diet. Anthropometric and cardiometabolic parameters, puberty, dietary intake and physical activity (PA) were measured and effects on HOMA-IR were analyzed. Results 126 adolescents were included in this study (13.6 +/- 2.2 years, BMI z-score 3.04 +/- 0.66, HOMA-IR 3.48 +/- 2.28, HP n = 68, MP n = 58). At 2 years, changes in protein intake were not significantly different between timepoints or intervention groups and no effects of the intervention on IR were observed. The retention rate was 39%, while no compliance to the diets was observed. Conclusions The PREVIEW study observed no effect of a high protein/low GI diet on IR in adolescents with overweight/obesity and IR because of lack of feasibility, due to insufficient retention and dietary compliance after 2 years.
  • Fan, Yuxin; Li, Weiqin; Liu, Huikun; Wang, Leishen; Zhang, Shuang; Liu, Hongyan; Leng, Junhong; Shen, Yun; Tuomilehto, Jaakko; Yu, Zhijie; Yang, Xilin; Liu, Ming; Hu, Gang (2019)
    Objective: To evaluate the independent or combined effects of gestational diabetes (GDM) and pre-pregnancy and postpartum BMI on the odds of postpartum diabetes and hyperglycemia. Methods: The study samples included 1263 women with prior GDM and 705 women without GDM. Postpartum 1-7 years diabetes was diagnosed by the standard oral glucose tolerance test. Results: The multivariable-adjusted odds ratios among women with prior GDM, compared with those without it, were 7.52 for diabetes and 2.27 for hyperglycemia. The multivariable-adjusted odds ratios at different postpartum BMI levels (= 28 kg/m(2)) were 1.00, 2.80, and 8.08 for diabetes (P-trend <0.001), and 1.00, 2.10, and 4.42 for hyperglycemia (P-trend <0.001), respectively. Women with high body fat (>= 31.9%) or abdominal obesity (>= 85 cm) had a 2.7-6.9-fold higher odds ratio for diabetes or hyperglycemia. Women with both obesity and prior GDM had the highest risk of diabetes or hyperglycemia compared with non-obese women without GDM. Non-obese women with prior GDM had the same risk of diabetes and hyperglycemia as non-GDM women with obesity. When using Cox regression models, the results were very close to those using logistic regression models. Conclusions: Maternal prior GDM and pre-pregnancy or postpartum obesity contribute equally to postpartum diabetes and hyperglycemia risk. (C) 2019 Elsevier B.V. All rights reserved.
  • Wu, Chuanyan; Borne, Yan; Gao, Rui; Rodriguez, Maykel Lopez; Roell, William C.; Wilson, Jonathan M.; Regmi, Ajit; Luan, Cheng; Aly, Dina Mansour; Peter, Andreas; Machann, Juergen; Staiger, Harald; Fritsche, Andreas; Birkenfeld, Andreas L.; Tao, Rongya; Wagner, Robert; Canouil, Mickael; Hong, Mun-Gwan; Schwenk, Jochen M.; Ahlqvist, Emma; Kaikkonen, Minna U.; Nilsson, Peter; Shore, Angela C.; Khan, Faisel; Natali, Andrea; Melander, Olle; Orho-Melander, Marju; Nilsson, Jan; Haering, Hans-Ulrich; Renstrom, Erik; Wollheim, Claes B.; Engstrom, Gunnar; Weng, Jianping; Pearson, Ewan R.; Franks, Paul W.; White, Morris F.; Duffin, Kevin L.; Vaag, Allan Arthur; Laakso, Markku; Stefan, Norbert; Groop, Leif; De Marinis, Yang (2021)
    The hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04-1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09-1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.
  • Tanner, Timo; Antikainen, Osmo; Ehlers, Henrik; Blanco, David; Yliruusi, Jouko (2018)
    The compression physics of powders must be considered when developing a suitable tablet formulation. In the present study, the gravitation-based high-velocity method was utilized to analyze mechanical properties of eight common pharmaceutical excipients: two grades of lactose, anhydrous glucose, anhydrous calcium hydrogen phosphate, three grades of microcrystalline cellulose and starch. Samples were compressed five times consecutively with varying pressure and speed so that Setup A produced higher pressure and longer contact time than Setup B. The important parameters obtained from samples were porosity profiles, compaction pressure, contact time, internal energy change and the amount of elastic recovery. All acquired data was only based on distance-time profile of the compression event. Lactose and glucose fragmented effectively while calcium hydrogen phosphate remained in rearrangement phase, due to its hardness and insufficient pressure applied. Microcrystalline cellulose samples showed plastic behaviour and starch was most elastic of all the samples. By utilizing the method, examined excipients could be categorized according to their compression behaviour in an accurate and cost-efficient manner.
  • Bian, Hua; Hakkarainen, Antti; Zhou, You; Lundbom, Nina; Yki-Järvinen, Hannele (2018)
    Aims: To examine the distribution of liver fat (LFAT) in non-diabetic subjects and test whether the fat in the right as compared to the left lobe correlates better with components of the metabolic syndrome or not. Methods: In this cross sectional study, we determined LFAT by H-1-MRS in the right lobe (LFAT%(MRS)), and by MRI (LFAT%(MRI)) in four regions of interest (ROIs 1-4, two in the right and two in the left lobe) in 97 non-diabetic subjects (age range 22-74 years, BMI 18-41 kg/m(2)) and compared the accuracy of LFAT(MRI) in the different ROIs in diagnosing non-alcoholic fatty liver disease (NAFLD) using areas under the receiver operator characteristic (AUROC) curves. Results: 38% of the subjects had NAFLD (LFAT%(MRS)). LFAT%(MRI) was significantly higher in the right (5.7 +/- 0.5%) than the left (5.1 +/- 0.4%) lobe (p <0.02). The AUROC for LFAT%(MRI) in the right lobe for diagnosing NAFLD was significantly better than that in the left lobe. The relationships between several metabolic parameters and LFAT%(MRI) in the left lobe were significantly worse than those for LFAT%(MRS) while there was no difference between LFAT%(MRS) and right lobe ROIs. Conclusions: Liver right lobe contains more fat and correlates better with components of the metabolic syndrome than the left in non-diabetic subjects. (C) 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
  • Cuthbertson, Daniel J.; Koskinen, Juha; Brown, Emily; Magnussen, Costan G.; Hutri-Kahonen, Nina; Sabin, Matthew; Tossavainen, Paivi; Jokinen, Eero; Laitinen, Tomi; Viikari, Jorma; Raitakari, Olli T.; Juonala, Markus (2021)
    Aims To investigate the association between overweight/obesity and fatty liver index (FLI) on the odds of incident prediabetes/type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) in 2020 participants after 10 years follow up. Methods At baseline (in 2001) 2020 participants, males and females, aged 24-39 years, were stratified according to body mass index (BMI), normal weight (= 25-= 30 kg/m(2)) and FLI (as high FLI >= 60 or low FLI