Browsing by Subject "MELLITUS"

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  • Acosta, Tania; Barengo, Noel C.; Arrieta, Astrid; Ricaurte, Carlos; Tuomilehto, Jaakko O. (2018)
    Type 2 diabetes (T2D) imposes a heavy public health burden in both developed and developing countries. It is necessary to understand the effect of T2D in different settings and population groups. This report aimed to present baseline characteristics of study participants in the demonstration area for the Type 2 Diabetes Prevention in Barranquilla and Juan Mina (DEMOJUAN) project after randomization and to compare their fasting and 2-hour glucose levels according to lifestyle and T2D risk factor levels. The DEMOJUAN project is a randomized controlled field trial. Study participants were recruited from study sites using population-wide screening using the Finnish Diabetes Risk Score (FINDRISC) questionnaire. All volunteers with FINDRISC of >= 13 points were invited to undergo an oral glucose tolerance test (OGTT). Participant inclusion criteria for the upcoming field trial were either FINDRISC of >= 13 points and 2-hour post-challenge glucose level of 7.0 to 11.0mmol/L or FINDRISC of >= 13 points and fasting plasma glucose level of 6.1 to 6.9mmol/L. Lifestyle habits and risk factors for T2D were assessed by trained interviewers using a validated questionnaire. Among the 14,193 participants who completed the FINDRISC questionnaire, 35% (n=4915) had a FINDRISC score of >= 13 points and 47% (n=2306) agreed to undergo the OGTT. Approximately, 33% (n=772) of participants underwent the OGTT and met the entry criteria; these participants were randomized into 3 groups. There were no statistically significant differences found in anthropometric or lifestyle risk factors, distribution of the glucose metabolism categories, or other diabetes risk factors between the 3 groups (P>.05). Women with a past history of hyperglycaemia had significantly higher fasting glucose levels than those without previous hyperglycaemia (103 vs 99mg/dL; P Lifestyle habits and risk factors were evenly distributed among the 3 study groups. No differences were found in fasting or 2-hour glucose levels among different lifestyle or risk factor categories with the exception of body mass index, past history of hyperglycaemia, and age of 64 years in women.
  • SUMMIT Consortium (2018)
    To explore novel genetic loci for diabetic nephropathy, we performed genome-wide association studies (GWAS) for diabetic nephropathy in Japanese patients with type 2 diabetes. We analyzed the association of 5,768,242 single nucleotide polymorphisms (SNPs) in Japanese patients with type 2 diabetes, 2,380 nephropathy cases and 5,234 controls. We further performed GWAS for diabetic nephropathy using independent Japanese patients with type 2 diabetes, 429 cases and 358 controls and the results of these two GWAS were combined with an inverse variance meta-analysis (stage-1), followed by a de novo genotyping for the candidate SNP loci (p <1.0 x 10(-4)) in an independent case-control study (Stage-2; 1,213 cases and 1,298 controls). After integrating stage-1 and stage-2 data, we identified one SNP locus, significantly associated with diabetic nephropathy; rs56094641 in FTO, P = 7.74 x 10(-10). We further examined the association of rs56094641 with diabetic nephropathy in independent Japanese patients with type 2 diabetes (902 cases and 1,221 controls), and found that the association of this locus with diabetic nephropathy remained significant after integrating all association data (P = 7.62 x 10(-10)). We have identified FTO locus as a novel locus for conferring susceptibility to diabetic nephropathy in Japanese patients with type 2 diabetes.
  • Laursen, Jens Christian; Sondergaard-Heinrich, Niels; de Melo, Joana Mendes Lopes; Haddock, Bryan; Rasmussen, Ida Kirstine Bull; Safavimanesh, Farzaneh; Hansen, Christian Stevns; Storling, Joachim; Larsson, Henrik Bo Wiberg; Groop, Per-Henrik; Frimodt-Moller, Marie; Andersen, Ulrik Bjorn; Rossing, Peter (2021)
    Background: Inhibitors of the sodium-glucose cotransporter 2 (SGLT2) slow the progression of diabetic kidney disease, possibly by reducing the proximal tubule transport workload with subsequent improvement of renal oxygenation. We aimed to test this hypothesis in individuals with type 1 diabetes and albuminuria. Methods: A randomised, double-blind, placebo-controlled, crossover trial with a single 50 mg dose of the SGLT2 inhibitor dapagliflozin and placebo in random order, separated by a two-week washout period. Magnetic resonance imaging (MRI) was used to assess renal R-2* (a low value corresponds to a high tissue oxygenation), renal perfusion (arterial spin labelling) and renal artery flow (phase contrast imaging) at baseline, three- and six hours from tablet ingestion. Exploratory outcomes, including baroreflex sensitivity, peripheral blood oxygen saturation, peripheral blood mononuclear cell mitochondrial oxygen consumption rate, and biomarkers of inflammation were evaluated at baseline and 12 h from medication. The study is registered in the EU Clinical Trials Register (EudraCT 2019-004,557-92), on ClinicalTrials.gov (NCT04193566), and is completed. Findings: Between February 3, 2020 and October 23, 2020, 31 individuals were screened, and 19 eligible individuals were randomised. Three dropped out before receiving any of the interventions and one dropped out after receiving only placebo. We included 15 individuals (33% female) in the per-protocol analysis with a mean age of 58 (SD 14) years, median urinary albumin creatinine ratio of 46 [IQR 21-58] mg/g and an eGFR of 73 (32) ml/min/1.73m(2). The mean changes in renal cortical R-2* from baseline to six hours were for dapagliflozin -1.1 (SD 0.7) s(-1) and for placebo +1.3 (0.7) s(-1), resulting in a difference between interventions of -2.3 s(-1) [95% CI -4.0 to -0.6]; p = 0.012. No between-intervention differences were found in any other MRI outcomes, physiological parameters or exploratory outcomes. There were no adverse events. Interpretation: A single dose of 50 mg dapagliflozin acutely improved renal cortical R-2* without changing renal perfusion or blood flow. This suggests improved renal cortical oxygenation due to a reduced tubular transport workload in the proximal tubules. Such improved oxygenation may in part explain the long-term beneficial renal effects seen with SGLT2 inhibitors, but it remains to be determined whether the observed effects can be achieved with lower doses, with chronic treatment and if they occur in type 2 diabetes as well. (C) 2021 The Author(s). Published by Elsevier Ltd.
  • Harjutsalo, Valma; Maric-Bilkan, Christine; Forsblom, Carol; Groop, Per-Henrik; FinnDiane Study Grp (2016)
    Aims/hypothesis The aim of this study was to evaluate the relationship among age at onset of diabetes, age at onset of menarche and risk of diabetic nephropathy and laser-treated retinopathy in type 1 diabetes. Methods Data related to age at menarche were collected through questionnaires and were available for 1,304 women who participated in the Finnish Diabetic Nephropathy Study (FinnDiane). A possible association between age at menarche and diabetic nephropathy and retinopathy was investigated. Results There was an inverse relationship between the age at onset of diabetes and age at menarche: the younger the age at onset of diabetes, the higher the age at menarche (p <0.0001). A non-linear relationship between the age of menarche and risk of diabetic microvascular complications was found in patients with diabetes onset before menarche, but there was no such association in patients with diabetes onset after menarche. Women with delayed menarche (> mean age+ 2 years) had a 2.30 (95% CI 1.27, 4.17; p <0.006) times higher risk of nephropathy compared with the women who underwent menarche at the mean age +/- 2 years. Delayed menarche also increased the risk of retinopathy (OR 2.34 [95% CI 1.36, 4.01]). After excluding patients with nephropathy, the OR for retinopathy was 2.11 (95% CI 1.15, 3.90). Earlier menarche (<mean age-2 years) did not have any effect on this risk. Conclusions/interpretation Delayed menarche was associated with an increased risk of diabetic nephropathy and retinopathy, whereas early menarche was not. Delayed menarche may be used as a new tool to identify women at risk of diabetic microvascular complications.
  • Finndiane Study Grp (2018)
    Aims/hypothesis This study aimed to assess the use of ambulatory BP monitoring (ABPM) to identify the presence of masked, nocturnal and white-coat hypertension in individuals with type 1 diabetes, patterns that could not be detected by regular office-based BP monitoring alone. We also analysed associations between BP patterns and arterial stiffness in order to identify individuals at cardiovascular risk. Methods This substudy included 140 individuals with type 1 diabetes from the Helsinki metropolitan area, who attended the Finnish Diabetic Nephropathy Study (FinnDiane) Centre in Helsinki between January 2013 and August 2017. Twenty-four hour ABPM and pulse wave analysis were performed simultaneously using a validated non-invasive brachial oscillometric device (Mobil-O-Graph). Definitions of hypertension were based on the European Society of Hypertension guidelines. Masked hypertension was defined as normal office BP (BP obtained using a standardised automated BP device) but elevated 24 h ABPM, and white-coat hypertension as elevated office BP but normal 24 h ABPM. Results A total of 38% of individuals were normotensive and 33% had sustained hypertension, while 23% had masked and 6% had white-coat hypertension. About half of the cohort had increased absolute levels of night-time BP, half of whom were untreated. In the ambulatory setting, central BP and pulse wave velocity (PWV) were higher in participants with masked hypertension than in those with normotension (p <0.001). In a multivariable linear regression model adjusted for age, sex, BMI, antihypertensive treatment and eGFR, masked hypertension was independently associated with higher 24 h PWV ((3 0.50 [95% CI 0.34, 0.66]), but not with PWV obtained during resting conditions (adjusted 13 0.28 [95% CI -0.53, 1.10]), using normotension as the reference group. Conclusions/interpretation ABPM analysis revealed that one-quarter of the participants with type 1 diabetes had masked hypertension; these individuals would not have been detected by office BP alone. Moreover, arterial stiffness was increased in individuals with masked hypertension. These findings support the use of ABPM to identify individuals at risk of cardiovascular disease.
  • Nazu, Nazma Akter; Wikström, Katja; Lamidi, Marja-Leena; Lindström, Jaana; Tirkkonen, Hilkka; Rautiainen, Päivi; Laatikainen, Tiina (2020)
    Aims: To compare the quality of diabetes care among type 2 diabetes patients with and without mental disorders during six-year follow-up in North Karelia, Finland. Methods: All type 2 diabetes patients (n = 10190) were analysed using the electronic health records data from 2011-12 to 2015-16. The diabetes care was evaluated using the measurement activity and the achievement of the treatment targets for HbA1c and LDL. Results: Monitoring of HbA1c and LDL levels improved among all patient groups, except the dementia patients. The proportion of those achieving the HbA1c target declined and those achieving the LDL target improved in all patient groups. Differences in the changes of achievement of the target HbA1c level among patients with dementia and depression were observed when compared with those having only type 2 diabetes. Conclusions: This study highlights the challenge of glucose level management as the age and comorbidities of the patients related to the care and achievements of the treatment targets. Mental disorders that are likely to affect patients' adherence to medication and other treatments should be taken into account and more support for self-care should be provided to such patients. Improvement in the achievement of LDL target address the progress in the prevention of macrovascular complications. (C) 2020 The Authors. Published by Elsevier B.V.
  • Jolle, Anne; Asvold, Bjorn Olav; Holmen, Jostein; Carlsen, Sven Magnus; Tuomilehto, Jaakko; Bjorngaard, Johan Hakon; Midthjell, Kristian (2018)
    Objective Among individuals at high risk for diabetes identified through a population survey, we performed an intervention study with basic lifestyle advice aiming to prevent diabetes. Research design and methods Among 50 806 participants in the HUNT3 Survey (2006-2008), 5297 individuals with Finnish Diabetes Risc Score (FINDRISC >= 15 were invited to an oral glucose tolerance test (OGTT) and an education session with lifestyle advice, and 2634 (49.7%) attended. Among them, 2380 people without diabetes were included in the prevention study with repeated examinations and education sessions after 6, 12, and 24 months. We examined participation, diabetes incidence, glycemia, and adiposity during follow-up. Results Of 2380 participants, 1212 (50.9%) participated in >= 3 of the four examinations. Diabetes was detected in 3.5%, 3.1%, and 4.0% of individuals at the 6-month, 12-month, and 24-month examinations, respectively, indicating a 10.3% 2-year diabetes incidence. Mean (95% CI) increases from baseline to 2-year follow-up were 0.30 (0.29 to 0.32) percentage points (3.3 (3.2 to 3.5) mmol/mol) for Hemoglobin A 1c, 0.13 (0.10 to 0.16) mmol/L for fasting serum-glucose, 0.46 (0.36 to 0.56) mmol/L for 2-hour OGTT s-glucose, 0.30 (0.19 to 0.40) kg/m(2) forbody mass index (BMI) (all p<0.001) and -0.5 (-0.9 to -0.2) cm for waist circumference (p= 0.004), with broadly similar estimates by baseline age, sex, education, depressive symptoms, BMI, physical activity, and family history of diabetes. Only 206 (8.7%) participants had evidence of > 5% weight loss during follow-up; their fasting and 2-hour s-glucose did not increase, and HbA 1c increased less than in other participants. Conclusion Basic lifestyle advice given to high-risk individuals during three group sessions with 6-month intervals was not effective in reducing 2-year diabetes risk.
  • 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.
  • 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.
  • Valkama, Anita J.; Meinila, Jelena M.; Koivusalo, Saila B.; Lindstrom, Jaana; Rono, Kristiina; Tiitinen, Aila E.; Stach-Lempinen, Beata; Kautiainen, Hannu J.; Viljakainen, Heli; Andersson, Sture; Eriksson, Johan G. (2018)
    Obesity increases the risk of low 25-hydroxyvitamin D (25(OH) D) concentrations and gestational diabetes (GDM). We explored whether the association between GDM and change in 25(OH) D concentrations measured in the first (7-18 wk) and second (20-27 wk) trimesters of pregnancy is dependent on maternal BMI. The study was a prospective study of 219 women with BMI of >= 30 kg/m2, a history of GDM, or both. The participants were stratified by first-trimester BMI: BMI of = 35 kg/m(2). In the BMI group >= 35 kg/m(2), those who did not develop GDM during the follow-up showed higher increase in serum 25(OH) D concentrations compared with women who developed GDM (43.2 vs. 11.5%; P <0.001). No associations between 25(OH) D concentrations and GDM were observed in other BMI groups. These findings give an important aspect of the role of maternal body size in the association between vitamin D and GDM in high-risk women.
  • Carstensen, Bendix; Read, Stephanie H.; Friis, Soren; Sund, Reijo; Keskimaki, Ilmo; Svensson, Ann-Marie; Ljung, Rickard; Wild, Sarah H.; Kerssens, Joannes J.; Harding, Jessica L.; Magliano, Dianna J.; Gudbjornsdottir, Soffia; Diabet Canc Res Consortium (2016)
    An excess cancer incidence of 20-25% has been identified among persons with diabetes, most of whom have type 2 diabetes. We aimed to describe the association between type 1 diabetes and cancer incidence. Persons with type 1 diabetes were identified from five nationwide diabetes registers: Australia (2000-2008), Denmark (1995-2014), Finland (1972-2012), Scotland (1995-2012) and Sweden (1987-2012). Linkage to national cancer registries provided the numbers of incident cancers in people with type 1 diabetes and in the general population. We used Poisson models with adjustment for age and date of follow up to estimate hazard ratios for total and site-specific cancers. A total of 9,149 cancers occurred among persons with type 1 diabetes in 3.9 million person-years. The median age at cancer diagnosis was 51.1 years (interquartile range 43.5-59.5). The hazard ratios (HRs) (95% CIs) associated with type 1 diabetes for all cancers combined were 1.01 (0.98, 1.04) among men and 1.07 (1.04, 1.10) among women. HRs were increased for cancer of the stomach (men, HR 1.23 [1.04, 1.46]; women, HR 1.78 [1.49, 2.13]), liver (men, HR 2.00 [1.67, 2.40]; women, HR 1.55 [1.14, 2.10]), pancreas (men, HR 1.53 [1.30, 1.79]; women, HR 1.25 [1.02,1.53]), endometrium (HR 1.42 [1.27, 1.58]) and kidney (men, HR 1.30 [1.12, 1.49]; women, HR 1.47 [1.23, 1.77]). Reduced HRs were found for cancer of the prostate (HR 0.56 [0.51, 0.61]) and breast (HR 0.90 [0.85, 0.94]). HRs declined with increasing diabetes duration. Type 1 diabetes was associated with differences in the risk of several common cancers; the strength of these associations varied with the duration of diabetes.
  • Finndiane Study Grp; Eriksson, Marika; Summanen, Paula; Gordin, Daniel; Forsblom, Carol; Shams, Sara; Liebkind, Ron; Tatlisumak, Turgut; Putaala, Jukka; Groop, Per-Henrik; Martola, Juha; Thorn, Lena M. (2021)
    Introduction Cerebral small-vessel disease is common in neurologically asymptomatic individuals with type 1 diabetes. The retinal vasculature is thought to mirror the brain's vasculature, but data on this association are limited in type 1 diabetes. Our aim was to study associations between diabetic retinopathy severity and cerebral small-vessel disease in type 1 diabetes. Research design and methods For this cross-sectional study, we enrolled 189 participants with type 1 diabetes (median age 40 (33-45) years; 53% female; diabetes duration 21.6 (18.2-30.7) years) and 29 healthy age-matched and sex-matched controls as part of the Finnish Diabetic Nephropathy Study. Participants underwent a clinical investigation, brain MRI, and fundus imaging. Signs of cerebral small-vessel disease in brain MRIs were analyzed in relation to diabetic retinopathy severity (Early Treatment Diabetic Retinopathy Study (ETDRS) score). Results In type 1 diabetes, participants with cerebral small-vessel disease had higher ETDRS scores (35 (20-61) vs 20 (20-35), p=0.022) and a higher prevalence of proliferative diabetic retinopathy than those without cerebral small-vessel disease (25% vs 9%, p=0.002). In adjusted analysis, proliferative diabetic retinopathy was associated with cerebral small-vessel disease (OR 2.57 (95% CI 1.04 to 6.35)). Median ETDRS score (35 (20-65) vs 20 (20-35), p=0.024) and proliferative diabetic retinopathy prevalence were higher (29% vs 13%, p=0.002) in participants with versus without cerebral microbleeds. ETDRS scores increased by number of cerebral microbleeds (p=0.001), both ETDRS score (OR 1.05 (95% CI 1.02 to 1.09)) and proliferative diabetic retinopathy (8.52 (95% CI 1.91 to 37.94)) were associated with >2 cerebral microbleeds in separate multivariable analysis. We observed no association with white matter hyperintensities or lacunar infarcts. Conclusions Presence of cerebral small-vessel disease on brain MRI, particularly cerebral microbleeds, is associated with the severity of diabetic retinopathy.
  • 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.
  • Finnish Pediat Diabet Register; Turtinen, Maaret; Härkönen, Taina; Parkkola, Anna; Ilonen, Jorma; Knip, Mikael (2019)
    Aims/hypothesis In previous studies, the risk of developing familial type 1 diabetes has been reported to be more than two times higher in the offspring of affected fathers than in those of affected mothers. We tested the hypothesis that index children with an affected father may have a more aggressive disease process at diagnosis than those with other affected first-degree relatives. Methods A cross-sectional, observational study was performed using the Finnish Pediatric Diabetes Register. Clinical and metabolic characteristics, beta cell autoantibodies and HLA class II genetics were analysed from index children in Finland diagnosed before the age of 15 years between January 2003 and December 2016. Information on the presence of type 1 diabetes in first-degree relatives was collected at diagnosis using a structured questionnaire. Results Out of 4993 newly diagnosed index children, 519 (10.4%) had familial type 1 diabetes. More than 5% (n = 253, 5.1%) had an affected father, 2.8% (n = 141) had an affected mother, 1.9% (n = 95) had an affected sibling and 0.6% (n = 30) had two or more affected family members. All clinical and metabolic variables were markedly poorer in children with sporadic vs familial diabetes. The index children with an affected father or mother were younger than those with an affected sibling (median age 7.59 vs 6.74 vs 10.73 years, respectively; p <0.001). After age- and sex-adjusted analyses, index children with an affected father presented more often with ketoacidosis (9.7% vs 3.6%; p = 0.033) and had greater weight loss before diagnosis (3.2% vs 0%; p = 0.006) than those with an affected mother. Children with familial disease tested negative for all autoantibodies more often (3.5% vs 2.1%; p = 0.041) and had insulin autoantibodies more frequently (49.8% vs 42.2%; p = 0.004) than those with sporadic disease. Both major HLA risk haplotypes (DR3-DQ2 and DR4-DQ8) were more often lacking among children with sporadic vs familial disease (15.9% vs 11.2%; p = 0.006). The DR4-DQ8 haplotype was more frequent in the familial vs the sporadic group (75.7% vs 68.5%; p = 0.001) and especially among children with an affected father when compared with children with sporadic disease (77.5% vs 68.5%; p <0.05). When comparing index children with affected parents diagnosed before or after the birth of the index child, a clear male preponderance was seen among the affected parents diagnosed before the birth of the index child (fathers 66.2% vs mothers 33.8%; p = 0.006), whereas the proportion of fathers and mothers was similar if type 1 diabetes was diagnosed after the birth of the index child. Conclusions/interpretation The more severe metabolic derangement at diagnosis in children with sporadic type 1 diabetes compared with those with familial type 1 diabetes was confirmed. The higher frequency of diabetic ketoacidosis and increased weight loss at diagnosis in index children with an affected father compared with an affected mother support the hypothesis that paternal type 1 diabetes is associated with more severe disease in the offspring than maternal diabetes. The sex difference seen between affected parents diagnosed before and after the birth of the index child supports the hypothesis that maternal insulin treatment protects against type 1 diabetes.
  • Pöllänen, Petra M.; Lempainen, Johanna; Laine, Antti-Pekka; Toppari, Jorma; Veijola, Riitta; Ilonen, Jorma; Siljander, Heli; Knip, Mikael (2019)
    Context: Characterization of slow progression to type 1 diabetes (T1D) may reveal novel means for prevention of T1D. Slow progressors might carry natural immunomodulators that delay beta-cell destruction and mediate preservation of beta-cell function. Objective: To identify demographic, genetic, and immunological characteristics of slow progression from seroconversion to clinical T1D. Design: H LA-susceptible children (n = 7410) were observed from birth for islet cell antibody (ICA), insulin autoantibody (IAA), glutamic acid decarboxylase (GADA), and islet antigen-2 autoantibodies (IA-2A), and for clinical T1D. Disease progression that lasted >= 7.26 years (slowest) quartile from initial seroconversion to diagnosis was considered slow. Autoantibody and genetic characteristics including 45 non-HLA single nucleotide polymorphisms (SNPs) predisposing to T1D were analyzed. Results: By the end of 2015, 1528 children (21 %) had tested autoantibody positive and 247 (16%) had progressed to T1D. The median delay from seroconversion to diagnosis was 8.7 years in slow (n = 62, 25%) and 3.0 years in other progressors. Compared with other progressors, slow progressors were less often multipositive, had lower ICA and IAA titers, and lower frequency of IA-2A at seroconversion. Slow progressors were born more frequently in the fall, whereas other progressors were born more often in the spring. Compared with multipositive nonprogressors, slow progressors were younger, had higher ICA titers, and higher frequency of IAA and multiple autoantibodies at seroconversion. We found no differences in the distributions of non-HLA SNPs between progressors. Conclusions: We observed differences in autoantibody characteristics and the season of birth among progressors, but no characteristics present at seroconversion that were specifically predictive for slow progression.
  • Barrios, Clara; Zierer, Jonas; Würtz, Peter; Haller, Toomas; Metspalu, Andres; Gieger, Christian; Thorand, Barbara; Meisinger, Christa; Waldenberger, Melanie; Raitakari, Olli; Lehtimäki, Terho; Otero, Sol; Rodriguez, Eva; Pedro-Botet, Juan; Kähönen, Mika; Ala-Korpela, Mika; Kastenmüller, Gabi; Spector, Tim D.; Pascual, Julio; Menni, Cristina (2018)
    Using targeted NMR spectroscopy of 227 fasting serum metabolic traits, we searched for novel metabolic signatures of renal function in 926 type 2 diabetics (T2D) and 4838 non-diabetic individuals from four independent cohorts. We furthermore investigated longitudinal changes of metabolic measures and renal function and associations with other T2D microvascular complications. 142 traits correlated with glomerular filtration rate (eGFR) after adjusting for confounders and multiple testing: 59 in diabetics, 109 in non-diabetics with 26 overlapping. The amino acids glycine and phenylalanine and the energy metabolites citrate and glycerol were negatively associated with eGFR in all the cohorts, while alanine, valine and pyruvate depicted opposite association in diabetics (positive) and nondiabetics (negative). Moreover, in all cohorts, the triglyceride content of different lipoprotein subclasses showed a negative association with eGFR, while cholesterol, cholesterol esters (CE), and phospholipids in HDL were associated with better renal function. In contrast, phospholipids and CEs in LDL showed positive associations with eGFR only in T2D, while phospholipid content in HDL was positively associated with eGFR both cross-sectionally and longitudinally only in non-diabetics. In conclusion, we provide a wide list of kidney function-associated metabolic traits and identified novel metabolic differences between diabetic and non-diabetic kidney disease.
  • 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.
  • Loo, Evelyn Xiu Ling; Zhang, Yuqing; Yap, Qai Ven; Yu, Guoqi; Soh, Shu E.; Loy, See Ling; Lau, Hui Xing; Chan, Shiao-Yng; Shek, Lynette Pei-Chi; Luo, Zhong-Cheng; Yap, Fabian Kok Peng; Tan, Kok Hian; Chong, Yap Seng; Zhang, Jun; Eriksson, Johan Gunnar (2021)
    Background Gestational diabetes mellitus (GDM) has been associated with adverse health outcomes for mothers and offspring. Prevalence of GDM differs by country/region due to ethnicity, lifestyle and diagnostic criteria. We compared GDM rates and risk factors in two Asian cohorts using the 1999 WHO and the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Methods The Shanghai Birth Cohort (SBC) and the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort are prospective birth cohorts. Information on sociodemographic characteristics and medical history were collected from interviewer-administered questionnaires. Participants underwent a 2-h 75-g oral glucose tolerance test at 24-28 weeks gestation. Logistic regressions were performed. Results Using the 1999 WHO criteria, the prevalence of GDM was higher in GUSTO (20.8%) compared to SBC (16.6%) (p = 0.046). Family history of hypertension and alcohol consumption were associated with higher odds of GDM in SBC than in GUSTO cohort while obesity was associated with higher odds of GDM in GUSTO. Using the IADPSG criteria, the prevalence of GDM was 14.3% in SBC versus 12.0% in GUSTO. A history of GDM was associated with higher odds of GDM in GUSTO than in SBC, while being overweight, alcohol consumption and family history of diabetes were associated with higher odds of GDM in SBC. Conclusions We observed several differential risk factors of GDM among ethnic Chinese women living in Shanghai and Singapore. These findings might be due to heterogeneity of GDM reflected in diagnostic criteria as well as in unmeasured genetic, lifestyle and environmental factors.
  • Sandholm, Niina; Haukka, Jani K.; Toppila, Iiro; Valo, Erkka; Harjutsalo, Valma; Forsblom, Carol; Groop, Per-Henrik (2018)
    Urinary albumin excretion is an early sign of diabetic kidney disease, affecting every third individual with diabetes. Despite substantial estimated heritability, only variants in the GLRA3 gene have been genome-wide significantly associated (p-value <5 x 10(-8)) with diabetic albuminuria, in Finnish individuals with type 1 diabetes; However, replication attempt in non-Finnish Europeans with type 1 diabetes showed nominally significant association in the opposite direction, suggesting a population-specific effect, but simultaneously leaving the finding controversial. In this study, the association between the common rs10011025 variant in the GLRA3 locus, and albuminuria, was confirmed in 1259 independent Finnish individuals with type 1 diabetes (p = 0.0013), and meta-analysis of all Finnish individuals yielded a genome-wide significant association. The association was particularly pronounced in subjects not reaching the treatment target for blood glucose levels (HbA(1c) > 7%; N = 2560, p = 1.7 x 10(-9)). Even though further studies are needed to pinpoint the causal variants, dissecting the association at the GLRA3 locus may uncover novel molecular mechanisms for diabetic albuminuria irrespective of population background.
  • Laine, M. K.; Kujala, R.; Eriksson, J. G.; Kautiainen, H.; Sarna, S.; Kujala, U. M. (2017)
    Aims Regular physical activity plays a major role, in both prevention and treatment of type 2 diabetes. Less is known whether vigorous physical activity during young adulthood is associated with costs of diabetes medication in later life. The aim of this study is to evaluate this question. Methods The study population consisted of 1314 former elite-class athletes and 860 matched controls. The former athletes were divided into three groups based on their active career sport: endurance, mixed and power sports. Information on purchases of diabetes medication between 1995 and 2009 was obtained from the drug purchase register of the Finnish Social Insurance Institution. Results The total cost of diabetes medication per person year was significantly lower among the former endurance (mean 81 theta [95% CI 33-151 theta ]) and mixed group athletes (mean 272 theta [95% CI 181- 388 theta]) compared with the controls (mean 376 theta [95% CI 284- 485 theta]), (p <0.001 and p = 0.045, respectively). Of the former endurance athletes, 0.4% used insulin, while 5.2% of the controls used insulin (p = 0.018). Conclusions A career as former endurance, sprint, jumper or team game athlete seems to reduce the costs of diabetes medication in later life.