Browsing by Subject "TYPE-2"

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  • Awad, Susanne F.; Dargham, Soha R.; Toumi, Amine A.; Dumit, Elsy M.; El-Nahas, Katie G.; Al-Hamaq, Abdulla O.; Critchley, Julia A.; Tuomilehto, Jaakko; Al-Thani, Mohamed H. J.; Abu-Raddad, Laith J. (2021)
    We developed a diabetes risk score using a novel analytical approach and tested its diagnostic performance to detect individuals at high risk of diabetes, by applying it to the Qatari population. A representative random sample of 5,000 Qataris selected at different time points was simulated using a diabetes mathematical model. Logistic regression was used to derive the score using age, sex, obesity, smoking, and physical inactivity as predictive variables. Performance diagnostics, validity, and potential yields of a diabetes testing program were evaluated. In 2020, the area under the curve (AUC) was 0.79 and sensitivity and specificity were 79.0% and 66.8%, respectively. Positive and negative predictive values (PPV and NPV) were 36.1% and 93.0%, with 42.0% of Qataris being at high diabetes risk. In 2030, projected AUC was 0.78 and sensitivity and specificity were 77.5% and 65.8%. PPV and NPV were 36.8% and 92.0%, with 43.0% of Qataris being at high diabetes risk. In 2050, AUC was 0.76 and sensitivity and specificity were 74.4% and 64.5%. PPV and NPV were 40.4% and 88.7%, with 45.0% of Qataris being at high diabetes risk. This model-based score demonstrated comparable performance to a data-derived score. The derived self-complete risk score provides an effective tool for initial diabetes screening, and for targeted lifestyle counselling and prevention programs.
  • 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.
  • But, Anna; Wang, Haining; Mannisto, Satu; Pukkala, Eero; Haukka, Jari (2014)
  • Bacos, Karl; Gillberg, Linn; Volkov, Petr; Olsson, Anders H.; Hansen, Torben; Pedersen, Oluf; Gjesing, Anette Prior; Eiberg, Hans; Tuomi, Tiinamaija; Almgren, Peter; Groop, Leif; Eliasson, Lena; Vaag, Allan; Dayeh, Tasnim; Ling, Charlotte (2016)
    Aging associates with impaired pancreatic islet function and increased type 2 diabetes (T2D) risk. Here we examine whether age-related epigenetic changes affect human islet function and if blood-based epigenetic biomarkers reflect these changes and associate with future T2D. We analyse DNA methylation genome-wide in islets from 87 non-diabetic donors, aged 26-74 years. Aging associates with increased DNA methylation of 241 sites. These sites cover loci previously associated with T2D, for example, KLF14. Blood-based epigenetic biomarkers reflect age-related methylation changes in 83 genes identified in human islets (for example, KLF14, FHL2, ZNF518B and FAM123C) and some associate with insulin secretion and T2D. DNA methylation correlates with islet expression of multiple genes, including FHL2, ZNF518B, GNPNAT1 and HLTF. Silencing these genes in beta-cells alter insulin secretion. Together, we demonstrate that blood-based epigenetic biomarkers reflect age-related DNA methylation changes in human islets, and associate with insulin secretion in vivo and T2D.
  • Rasouli, B.; Ahlqvist, E.; Alfredsson, L.; Andersson, T.; Carlsson, P.-O.; Groop, L.; Löfvenborg, J.E.; Martinell, M.; Rosengren, A.; Tuomi, T.; Wolk, A.; Carlsson, S. (2018)
    Aim. - Coffee consumption is inversely related to risk of type 2 diabetes (T2D). In contrast, an increased risk of latent autoimmune diabetes in adults (LADA) has been reported in heavy coffee consumers, primarily in a subgroup with stronger autoimmune characteristics. Our study aimed to investigate whether coffee consumption interacts with HLA genotypes in relation to risk of LADA. Methods. - This population-based study comprised incident cases of LADA (n = 484) and T2D (n = 1609), and also 885 healthy controls. Information on coffee consumption was collected by food frequency questionnaire. Odds ratios (ORs) with 95% CIs of diabetes were calculated and adjusted for age, gender, BMI, education level, smoking and alcohol intake. Potential interactions between coffee consumption and high-risk HLA genotypes were calculated by attributable proportion (AP) due to interaction. Results. - Coffee intake was positively associated with LADA in carriers of high-risk HLA genotypes (OR: 1.14 per cup/day, 95% CI: 1.02-1.28), whereas no association was observed in non-carriers (OR: 1.04, 95% CI: 0.93-1.17). Subjects with both heavy coffee consumption (>= 4 cups day) and high-risk HLA genotypes had an OR of 5.74 (95% Cl: 3.34-9.88) with an estimated AP of 0.36 (95% CI: 0.01-0.71; P = 0.04370). Conclusion. - Our findings suggest that coffee consumption interacts with HLA to promote LADA. (C) 2018 Elsevier Masson SAS. All rights reserved.
  • Pettersson, Maria; Viljakainen, Heli; Loid, Petra; Mustila, Taina; Pekkinen, Minna; Armenio, Miriam; Andersson-Assarsson, Johanna C.; Makitie, Outi; Lindstrand, Anna (2017)
    Context: Only a few genetic causes for childhood obesity have been identified to date. Copy number variants (CNVs) are known to contribute to obesity, both syndromic (15q11.2 deletions, Prader-Willi syndrome) and nonsyndromic (16p11.2 deletions) obesity. Objective: To study the contribution of CNVs to early-onset obesity and evaluate the expression of candidate genes in subcutaneous adipose tissue. Design and Setting: A case-control study in a tertiary academic center. Participants: CNV analysis was performed on 90 subjects with early-onset obesity and 67 normalweight controls. Subcutaneous adipose tissue from body mass index-discordant siblings was used for the gene expression analyses. Main Outcome Measures: We used custom high-density array comparative genomic hybridization with exon resolution in 1989 genes, including all known obesity loci. The expression of candidate genes was assessed using microarray analysis of messenger RNA from subcutaneous adipose tissue. Results: We identified rare CNVs in 17 subjects (19%) with obesity and 2 controls (3%). In three cases (3%), the identified variant involved a known syndromic lesion (22q11.21 duplication, 1q21.1 deletion, and 16p11.2 deletion, respectively), although the others were not known. Seven CNVs in 10 families were inherited and segregated with obesity. Expression analysis of 37 candidate genes showed discordant expression for 10 genes (PCM1, EFEMP1, MAMLD1, ACP6, BAZ2B, SORBS1, KLF15, MACROD2, ATR, and MBD5). Conclusions: Rare CNVs contribute possibly pathogenic alleles to a substantial fraction of children with early-onset obesity. The involved genes might provide insights into pathogenic mechanisms and involved cellular pathways. These findings highlight the importance of CNV screening in children with early-onset obesity.
  • Barengo, Noel C.; Acosta, Tania; Arrieta, Astrid; Ricaurte, Carlos; Smits, Dins; Florez, Karen; Tuomilehto, Jaakko O. (2019)
    Background: The objective of the demonstration project for type 2 diabetes prevention in the Barranquilla and Juan Mina (DEMOJUAN) study was to investigate the extent to which it is possible to reach normal glucose metabolism with early lifestyle interventions in people at high risk of type 2 diabetes (prediabetes), compared with those who receive standard usual care. Methods: DEMOJUAN was a randomized controlled trial conducted in Juan Mina and Barranquilla, Northern Colombia. Eligible participants were randomized into one of three groups (control group, initial nutritional intervention, and initial physical activity intervention). The duration of the intervention was 24 months. The main study outcome in the present analysis was reversion to normoglycemia. Relative risks and their corresponding 95% confidence intervals were calculated for reversal to normoglycemia and T2D incidence. Results: There was no statistically significant association between the intervention groups and reversion to normoglycemia. The relative risk of reversion to normoglycemia was 0.88 (95% CI 0.70-1.12) for the initial nutritional intervention group participants and 0.95 (95% CI 0.75-1.20) for the initial physical activity intervention group participants. Conclusions: Our study did not find any statistically significant differences in reversion to normoglycemia or the development of type 2 diabetes between the intervention groups and the control group in this population.
  • Strain, William David; Paldánius, Päivi Maria (2020)
    Aim: Clinical inertia is a multifactorial phenomenon, with contributing factors from people with diabetes and their healthcare team. It is widely cited that clinical inertia is minimised by participation in clinical trials. We assessed whether trial participation per se improves metabolic parameters in people with diabetes, or a specific focus on glycaemia is required. Methods: We compared improvement in glycaemic control in a pooled set of people assigned to the "placebo" arm from 25 glycaemia-focused trials with a pooled group of people with diabetes allocated to sham or non-pharmacological intervention for the treatment of diabetic retinal disease. Mean change in HbA1c (ANCOVA) was evaluated. Results: The overall placebo effect in studies focused on glucose control (N = 3081) was comparable between strata groups with and without complications. Adjusted least square mean change in HbA1c at 24 weeks was between-0.23% (-2.50 mmol/mol) and -0.32% (-3.50 mmol/mol). In studies focused on retinal disease (N = 288), the change from baseline in HbA1c was +0.10% (1.10 mmol/mol) and fasting plasma glucose was +0.50 mmol/L showing no improvement in metabolic parameters at 12 months. Conclusions: Clinical trial participation alone does not seem to improve metabolic parameters in people living with diabetes. The benefits observed in glycaemia-focused studies were independent of age and comorbidities. (C) 2020 Elsevier B.V. All rights reserved.
  • Lofvenborg, J. E.; Andersson, T.; Carlsson, P-O; Dorkhan, M.; Groop, L.; Martinell, M.; Tuomi, T.; Wolk, A.; Carlsson, S. (2014)
  • Hebbar, Prashantha; Abu-Farha, Mohamed; Alkayal, Fadi; Nizam, Rasheeba; Elkum, Naser; Melhem, Motasem; John, Sumi Elsa; Channanath, Arshad; Abubaker, Jehad; Bennakhi, Abdullah; Al-Ozairi, Ebaa; Tuomilehto, Jaakko; Pitkäniemi, Janne; Alsmadi, Osama; Al-Mulla, Fahd; Thanaraj, Thangavel Alphonse (2020)
    Consanguineous populations of the Arabian Peninsula, which has seen an uncontrolled rise in type 2 diabetes incidence, are underrepresented in global studies on diabetes genetics. We performed a genome-wide association study on the quantitative trait of fasting plasma glucose (FPG) in unrelated Arab individuals from Kuwait (discovery-cohort:n = 1,353; replication-cohort:n = 1,196). Genome-wide genotyping in discovery phase was performed for 632,375 markers from Illumina HumanOmniExpress Beadchip; and top-associating markers were replicated using candidate genotyping. Genetic models based on additive and recessive transmission modes were used in statistical tests for associations in discovery phase, replication phase, and meta-analysis that combines data from both the phases. A genome-wide significant association with high FPG was found at rs1002487 (RPS6KA1) (p-discovery = 1.64E-08, p-replication = 3.71E-04, p-combined = 5.72E-11; beta-discovery = 8.315; beta-replication = 3.442; beta-combined = 6.551). Further, three suggestive associations (p-values <8.2E-06) with high FPG were observed at rs487321 (CADPS), rs707927 (VARS and 2Kb upstream of VWA7), and rs12600570 (DHX58); the first two markers reached genome-wide significance in the combined analysis (p-combined = 1.83E-12 and 3.07E-09, respectively). Significant interactions of diabetes traits (serum triglycerides, FPG, and glycated hemoglobin) with homeostatic model assessment of insulin resistance were identified for genotypes heterozygous or homozygous for the risk allele. Literature reports support the involvement of these gene loci in type 2 diabetes etiology.
  • Liu, Ching-Ti; Merino, Jordi; Rybin, Denis; DiCorpo, Daniel; Benke, Kelly S.; Bragg-Gresham, Jennifer L.; Canouil, Mickaël; Corre, Tanguy; Grallert, Harald; Isaacs, Aaron; Kutalik, Zoltan; Lahti, Jari; Marullo, Letizia; Marzi, Carola; Rasmussen-Torvik, Laura J.; Rocheleau, Ghislain; Rueedi, Rico; Scapoli, Chiara; Verweij, Niek; Vogelzangs, Nicole; Willems, Sara M.; Yengo, Loïc; Bakker, Stephan J. L.; Beilby, John; Hui, Jennie; Kajantie, Eero; Müller-Nurasyid, Martina; Rathmann, Wolfgang; Balkau, Beverley; Bergmann, Sven; Eriksson, Johan G.; Florez, Jose C.; Froguel, Philippe; Harris, Tamara; Hung, Joseph; James, Alan L.; Kavousi, Maryam; Miljkovic, Iva; Musk, Arthur W.; Palmer, Lyle J.; Peters, Annette; Roussel, Ronan; van der harst, Pim; van Duijn, Cornelia M.; Vollenweider, Peter; Barroso, Inês; Prokopenko, Inga; Dupuis, Josée; Meigs, James B.; Bouatia-Naji, Nabila (2019)
    Type 2 diabetes (T2D) affects the health of millions of people worldwide. The identification of genetic determinants associated with changes in glycemia over time might illuminate biological features that precede the development of T2D. Here we conducted a genome-wide association study of longitudinal fasting glucose changes in up to 13,807 non-diabetic individuals of European descent from nine cohorts. Fasting glucose change over time was defined as the slope of the line defined by multiple fasting glucose measurements obtained over up to 14 years of observation. We tested for associations of genetic variants with inverse-normal transformed fasting glucose change over time adjusting for age at baseline, sex, and principal components of genetic variation. We found no genome-wide significant association (P < 5 x 10(-8)) with fasting glucose change over time. Seven loci previously associated with T2D, fasting glucose or HbA1c were nominally (P < 0.05) associated with fasting glucose change over time. Limited power influences unambiguous interpretation, but these data suggest that genetic effects on fasting glucose change over time are likely to be small. A public version of the data provides a genomic resource to combine with future studies to evaluate shared genetic links with T2D and other metabolic risk traits.
  • Prasad, Rashmi B.; Ahlqvist, Emma; Groop, Leif (2019)
  • Zhang, Yanlei; Ning, Feng; Sun, Jianping; Pang, Zengchang; Wang, Xiaoyong; Kapur, Anil; Sintonen, Harri; Qiao, Qing (2015)
  • Liu, Huikun; Wang, Leishen; Zhang, Shuang; Leng, Junhong; Li, Nan; Li, Weiqin; Wang, Jing; Tian, Huiguang; Qi, Lu; Yang, Xilin; Yu, Zhijie; Tuomilehto, Jaakko; Hu, Gang (2018)
    Aims: To report the weight loss findings after the first year of a lifestyle intervention trial among women with gestational diabetes mellitus (GDM). Methods: A total of 1180 women with GDM were randomly assigned (1: 1) to receive a 4-year lifestyle intervention (intervention group, n = 586) or standard care (control group, n = 594) between August 2009 and July 2011. Major elements of the intervention included 6 face-to-face sessions with study dieticians and two telephone calls in the first year, and two individual sessions and two telephone calls in each subsequent year. Results: Among 79% of participants who completed the year 1 trial, mean weight loss was 0.82 kg (1.12% of initial weight) in the intervention group and 0.09 kg (0.03% of initial weight) in the control group (P=.001). In a prespecified subgroup analysis of people who completed the trial, weight loss was more pronounced in women who were overweight (body mass index = 24 kg/m(2)) at baseline: mean weight loss 2.01 kg (2.87% of initial weight) in the intervention group and 0.44 kg (0.52% of initial weight) in the control group (P Conclusion: The 1-year lifestyle intervention led to significant weight losses after delivery in women who had GDM, and the effect was more pronounced in women who were overweight at baseline.
  • Gilis-Januszewska, Aleksandra; Lindstrom, Jaana; Tuomilehto, Jaakko; Piwonska-Solska, Beata; Topor-Madry, Roman; Szybinski, Zbigniew; Peltonen, Markku; Schwarz, Peter E. H.; Windak, Adam; Hubalewska-Dydejczyk, Alicja (2017)
    Background: Real life implementation studies performed in different settings and populations proved that lifestyle interventions in prevention of type 2 diabetes can be effective. However, little is known about long term results of these translational studies. Therefore, the purpose of this study was to examine the maintenance of diabetes type 2 risk factor reduction achieved 1 year after intervention and during 3 year follow-up in primary health care setting in Poland. Methods: Study participants (n = 262), middle aged, slightly obese, with increased type 2 diabetes risk ((age 55.5 (SD = 11.3), BMI 32 (SD = 4.8), Finnish Diabetes Risk Score FINDRISC 18.4 (SD = 2.9)) but no diabetes at baseline, were invited for 1 individual and 10 group lifestyle counselling sessions as well as received 6 motivational phone calls and 2 letters followed by organized physical activity sessions combined with counselling to increase physical activity. Measurements were performed at baseline and then repeated 1 and 3 years after the initiation of the intervention. Results: One hundred five participants completed all 3 examinations (baseline age 56.6 (SD = 10.7)), BMI 31.1 (SD = 4.9)), FINDRISC 18.57 (SD = 3.09)). Males comprised 13% of the group, 10% of the patients presented impaired fasting glucose (IFG) and 14% impaired glucose tolerance (IGT). Mean weight of participants decreased by 2.27 kg (SD = 5.25) after 1 year (p = <0.001). After 3 years a weight gain by 1.13 kg (SD = 4.6) (p = 0.04) was observed. In comparison with baseline however, the mean total weight loss at the end of the study was maintained by 1.14 kg (SD = 5.8) (ns). Diabetes risk (FINDRISC) declined after one year by 2.8 (SD = 3.6) (p = 0.001) and the decrease by 2.26 (SD = 4.27) was maintained after 3 years (p = 0.001). Body mass reduction by > 5% was achieved after 1 and 3 years by 27 and 19% of the participants, respectively. Repeated measures analysis revealed significant changes observed from baseline to year 1 and year 3 in: weight (p = 0.048), BMI (p = 0.001), total cholesterol (p = 0.013), TG (p = 0.061), fasting glucose level (p = 0.037) and FINDRISC (p = 0.001) parameters. The conversion rate to diabetes was 2% after 1 year and 7% after 3 years. Conclusions: Type 2 diabetes prevention in real life primary health care setting through lifestyle intervention delivered by trained nurses leads to modest weight reduction, favorable cardiovascular risk factors changes and decrease of diabetes risk. These beneficial outcomes can be maintained at a 3-year follow-up.
  • Jambi, Hanan; Enani, Sumia; Malibary, Manal; Bahijri, Suhad; Eldakhakhny, Basmah; Al-Ahmadi, Jawaher; Al Raddadi, Rajaa; Ajabnoor, Ghada; Boraie, Anwar; Tuomilehto, Jaakko (2020)
    Objective: Study the association of dietary habits and other indicators of lifestyle with dysglycemia in Saudi adults. Methods: In a cross-sectional design, data were obtained from 1403 Saudi adults (> 20 years), not previously diagnosed with diabetes. Demographics, lifestyle variables and dietary habits were obtained using a predesigned questionnaire. Fasting plasma glucose, glycated hemoglobin and 1-hour oral glucose tolerance test were used to identify dysglycemia. Regression analysis was performed to determine the associations of dietary factors and other indicators of lifestyle with dysglycemia. Results: A total 1075 adults (596 men, and 479 women) had normoglycemia, and 328 (195 men, and 133 women) had dysglycemia. Following adjustment for age, BMI and waist circumference, in men the weekly intake of 5 portions or more of red meat and Turkish coffee were associated with decreased odds of having dysglycemia odds ratio (OR) 0.444 (95% CI: 0.223, 0.881;P = .02) and 0.387 (95% CI: 0.202, 0.74;P = .004), respectively. In women, the intake of fresh juice 1 to 4 portions per week and 5 portions or more were associated with OR 0.603 (95% CI: 0.369, 0.985;P = .043) and OR 0.511 (95% CI: 0.279, 0.935;P = .029) decreased odds of having dysglycemia, respectively compared with women who did not drink fresh juice. The intake of 5 times or more per week of hibiscus drink was associated with increased odds of having dysglycemia, OR 5.551 (95% CI: 1.576, 19.55,P = .008) compared with women not using such a drink. Other lifestyle factors were not associated with dysglycemia. Conclusion: Dietary practices by studied Saudis have some impact on risk of dysglycemia, with obvious sex differences.
  • Hiekkala, Marjo Eveliina; Vuola, Pietari; Artto, Ville; Häppölä, Paavo; Häppölä, Elisa; Vepsäläinen, Salli; Cuenca-Leon, Ester; Lal, Dennis; Gormley, Padhraig; Hämäläinen, Eija; Ilmavirta, Matti; Nissilä, Markku; Säkö, Erkki; Sumelahti, Marja-Liisa; Harno, Hanna; Havanka, Hannele; Keski-Säntti, Petra; Färkkilä, Markus; Palotie, Aarno; Wessman, Maija; Kaunisto, Mari Anneli; Kallela, Mikko (2018)
    Objective To study the position of hemiplegic migraine in the clinical spectrum of migraine with aura and to reveal the importance of CACNA1A, ATP1A2 and SCN1A in the development of hemiplegic migraine in Finnish migraine families. Methods The International Classification of Headache Disorders 3rd edition criteria were used to determine clinical characteristics and occurrence of hemiplegic migraine, based on detailed questionnaires, in a Finnish migraine family collection consisting of 9087 subjects. Involvement of CACNA1A, ATP1A2 and SCN1A was studied using whole exome sequencing data from 293 patients with hemiplegic migraine. Results Overall, hemiplegic migraine patients reported clinically more severe headache and aura episodes than non-hemiplegic migraine with aura patients. We identified two mutations, c.1816G>A (p.Ala606Thr) and c.1148G>A (p.Arg383His), in ATP1A2 and one mutation, c.1994C>T (p.Thr665Met) in CACNA1A. Conclusions The results highlight hemiplegic migraine as a clinically and genetically heterogeneous disease. Hemiplegic migraine patients do not form a clearly separate group with distinct symptoms, but rather have an extreme phenotype in the migraine with aura continuum. We have shown that mutations in CACNA1A, ATP1A2 and SCN1A are not the major cause of the disease in Finnish hemiplegic migraine patients, suggesting that there are additional genetic factors contributing to the phenotype.