Publications by authors named "Johan G Eriksson"

573 Publications

Ideal Cardiovascular Health and Vascular Phenotype Associations in Mothers with Obesity and Their Six-Year-Old Children.

Diabetes Metab Syndr Obes 2021 13;14:3187-3197. Epub 2021 Jul 13.

Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Heredity and family-shared lifestyle contribute to cardiovascular risk, but the magnitude of their influence on arterial structure and function in early childhood is unknown. We aimed to assess associations between child and maternal ideal cardiovascular health, maternal subclinical atherosclerosis, and child arterial phenotype.

Methods: Cross-sectional analysis of 201 mother-child pairs originating from the Finnish Gestational Diabetes Prevention Study (RADIEL) longitudinal cohort was done at child age 6.1 ± 0.5 years with assessments of ideal cardiovascular health (BMI, blood pressure, fasting glucose, total cholesterol, diet quality, physical activity, smoking), body composition, very-high frequency ultrasound of carotid arteries (25 and 35 MHz), and pulse wave velocity.

Results: We found no association between child and maternal ideal cardiovascular health but report evidence of particular metrics correlations: total cholesterol (r=0.24, P=0.003), BMI (r=0.17, P=0.02), diastolic blood pressure (r=0.15, P=0.03), and diet quality (r=0.22, P=0.002). Child arterial phenotype was not associated with child or maternal ideal cardiovascular health. In the multivariable regression explanatory model adjusted for child sex, age, systolic blood pressure, lean body mass, and body fat percentage, child carotid intima-media thickness was independently associated only with maternal carotid intima-media thickness (0.1 mm increase [95% CI 0.05, 0.21, P=0.001] for each 1 mm increase in maternal carotid intima-media thickness). Children of mothers with subclinical atherosclerosis had decreased carotid artery distensibility (1.1 ± 0.2 vs 1.2 ± 0.2%/10 mmHg, P=0.01) and trend toward increased carotid intima-media thickness (0.37 ± 0.04 vs 0.35 ± 0.04 mm, P=0.06).

Conclusion: Ideal Cardiovascular Health metrics are heterogeneously associated in mother-child pairs in early childhood. We found no evidence of child or maternal Ideal Cardiovascular Health effect on child arterial phenotype. Maternal carotid intima-media thickness predicts child carotid intima-media thickness, but the underlying mechanisms remain unclear. Maternal subclinical atherosclerosis is associated with local carotid arterial stiffness in early childhood.
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http://dx.doi.org/10.2147/DMSO.S315402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286111PMC
July 2021

Association of increased abdominal adiposity at birth with altered ventral caudate microstructure.

Int J Obes (Lond) 2021 Jul 19. Epub 2021 Jul 19.

Singapore Institute for Clinical Sciences (SICS), A*STAR, Brenner Centre for Molecular Medicine, Singapore, Singapore.

Background: Neonatal adiposity is associated with a higher risk of obesity and cardiometabolic risk factors in later life. It is however unknown if central food intake regulating networks in the ventral striatum are altered with in-utero abdominal growth, indexed by neonatal adiposity in our current study. We aim to examine the relationship between striatal microstructure and abdominal adipose tissue compartments (AATCs) in Asian neonates from the Growing Up in Singapore Toward healthy Outcomes mother-offspring cohort.

Study Design: About 109 neonates were included in this study. Magnetic resonance imaging (MRI) was performed for the brain and abdominal regions between 5 to 17 days of life. Diffusion-weighted imaging of the brain was performed for the derivation of caudate and putamen fractional anisotropy (FA). Abdominal imaging was performed to quantify AATCs namely superficial subcutaneous adipose tissue (sSAT), deep subcutaneous adipose tissue (dSAT), and internal adipose tissue (IAT). Absolute and percentage adipose tissue of total abdominal volume (TAV) were calculated.

Results: We showed that AATCs at birth were significantly associated with increased FA in bilateral ventral caudate heads which are part of the ventral striatum (sSAT: β = 0.56, p < 0.001; β = 0.65, p < 0.001, dSAT: β = 0.43, p < 0.001; β = 0.52, p < 0.001, IAT: β = 0.30, p = 0.005; β = 0.32, p = 0.002) in neonates with low birth weights adjusted for gestational age.

Conclusions: Our study provides preliminary evidence of a potential relationship between neonatal adiposity and in-utero programming of the ventral striatum, a brain structure that governs feeding behavior.
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http://dx.doi.org/10.1038/s41366-021-00905-3DOI Listing
July 2021

Body surface area may explain sex differences in findings from the oral glucose tolerance test among subjects with normal glucose tolerance.

Nutr Metab Cardiovasc Dis 2021 May 26. Epub 2021 May 26.

Department of General Practice, Turku University and Turku University Hospital, Turku, Finland.

Background And Aims: Current guidelines on prediabetes and diabetes (T2D) recommend to regularly perform an oral glucose tolerance test (OGTT) on subjects at risk of T2D. However, it is not known why women tend to have relatively higher 2-h post-load plasma (2hPG) glucose concentrations during OGTT than men. The aim of the present study is to investigate if there are sex differences in fasting plasma glucose (FPG) and 2hPG concentrations in relation to body size in apparently healthy non-diabetic subjects with normal glucose tolerance. We hypothesized that sex differences in glucose tolerance are physiological and related to different body surface area (BSA) in men and women.

Methods And Results: A 2-h 75 g OGTT was performed on 2010 subjects aged 45-70 years. Their BSA was calculated using the Mosteller formula. Men and women were separately divided into five BSA levels. Within the normal 2hPG range, women had higher mean 2hPG concentrations during the OGTT than men in all BSA levels estimated by sex-standardized BSA (p for linearity < 0.001). BSA adjusted for age, waist circumference, leisure-time physical activity, and smoking, showed an inverse association with 2hPG concentration in both sexes. Mean FPG concentrations were higher in men than in women.

Conclusions: Body size has a negative inverse association with 2hPG concentration in an OGTT even within a physiological plasma glucose range. This may cause underestimation of glucose disorders in individuals with larger BSA and overestimation in individuals with smaller BSA when using an OGTT.
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http://dx.doi.org/10.1016/j.numecd.2021.05.018DOI Listing
May 2021

Longitudinal metabolic profiling of maternal obesity, gestational diabetes and hypertensive pregnancy disorders.

J Clin Endocrinol Metab 2021 Jun 29. Epub 2021 Jun 29.

Helsinki, Finland; Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Context: Comprehensive assessment of metabolism in maternal obesity and pregnancy disorders can provide information about the shared maternal-fetal milieu and give insight into both maternal long-term health and intergenerational transmission of disease burden.

Objective: To assess levels, profiles and change in the levels of metabolic measures during pregnancies complicated by obesity, gestational diabetes (GDM) or hypertensive disorders.

Design, Setting And Participants: A secondary analysis of two study cohorts, PREDO and RADIEL, including 741 pregnant women.

Main Outcome Measures: We assessed 225 metabolic measures by nuclear magnetic resonance in blood samples collected at median 13 (interquartile range, 12.4-13.7), 20 (19.3-23.0) and 28 (27.0-35.0) weeks of gestation.

Results: Across all three time points women with obesity (body mass index, BMI≥30kg/m 2) in comparison to normal weight (BMI 18.5-24.99 kg/m 2) had significantly higher levels of most very-low-density-lipoprotein-related measures, many fatty and most amino acids and more adverse metabolic profiles. The change in the levels of most metabolic measures during pregnancy was smaller in obese than in normal weight women. GDM, preeclampsia and chronic hypertension were associated with metabolic alterations similar to obesity. The associations of obesity held after adjustment for GDM and hypertensive disorders, but many of the associations with GDM and hypertensive disorders were rendered non-significant after adjustment for BMI and the other pregnancy disorder.

Conclusions: This study shows that the pregnancy-related metabolic change is smaller in women with obesity, who display metabolic perturbations already in early pregnancy. Metabolic alterations of obesity and pregnancy disorders resembled each other suggesting a shared metabolic origin.
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http://dx.doi.org/10.1210/clinem/dgab475DOI Listing
June 2021

Brown adipose tissue, adiposity and metabolic profile in preschool children.

J Clin Endocrinol Metab 2021 Jun 18. Epub 2021 Jun 18.

Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore.

Context: An inverse relationship between brown adipose tissue (BAT) and obesity has previously been reported in older children and adults, but unknown in young children.

Objective: We investigated the influence of BAT in thermoneutral condition on adiposity and metabolic profile in Asian preschool children.

Design, Setting And Participants: A total of 198 children aged 4.5 years from a prospective birth cohort study, Growing Up in Singapore Towards healthy Outcomes (GUSTO) were successfully studied with water-fat magnetic resonance imaging of the supraclavicular-axillary fat depot (FDSA). Regions within FDSA with fat-signal-fraction between 20% and 80% were considered BAT, and percentage BAT (%BAT), (100*BAT volume/ FDSA volume) was calculated.

Main Outcome Measures: Abdominal adipose tissue compartment volumes, ectopic fat in the soleus muscle and liver, fatty liver index, metabolic syndrome scores and markers of insulin sensitivity.

Results: A one percent unit increase in %BAT was associated with lower body mass index, difference (95%CI), -0.08 (-0.10, -0.06) kg/m 2 and smaller abdominal adipose tissue compartment volumes. Ethnicity and sex modified these associations. In addition, each unit increase in %BAT was associated with lower ectopic fat at 4.5 years in the liver, -0.008 (-0.013, -0.003) %, soleus muscle, -0.003 (-0.006, -0.001) % of water-content and lower fatty liver index at 6 years.

Conclusions: Higher %BAT is associated with a more favorable metabolic profile. BAT may thus play a role in the pathophysiology of obesity and related metabolic disorders. The observed ethnic and sex differences imply that the protective effect of BAT may vary among different groups.
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http://dx.doi.org/10.1210/clinem/dgab447DOI Listing
June 2021

Normal Gestational Weight Gain Protects From Large-for-Gestational-Age Birth Among Women With Obesity and Gestational Diabetes.

Front Public Health 2021 31;9:550860. Epub 2021 May 31.

PEDEGO Research Unit, Medical Research Center Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland.

Pre-pregnancy obesity, excess gestational weight gain (GWG), and gestational diabetes (GDM) increase fetal growth. Our aim was to assess whether normal GWG is associated with lower risk for a large-for-gestational-age (LGA; over the 90th percentile of birth weight for sex and gestational age) infant and lower birth weight standard deviation (SD) score in the presence of GDM and maternal obesity. This multicenter case-control study is part of the Finnish Gestational Diabetes (FinnGeDi) Study and includes singleton pregnancies of 1,055 women with GDM and 1,032 non-diabetic controls. Women were divided into 12 subgroups according to their GDM status, pre-pregnancy body mass index (BMI; kg/m), and GWG. Non-diabetic women with normal BMI and normal GWG (according to Institute of Medicine recommendations) served as a reference group. The prevalence of LGA birth was 12.2% among women with GDM and 6.2% among non-diabetic women ( < 0.001). Among all women, normal GWG was associated with lower odds of LGA [odds ratio (OR) 0.57, 95% CI: 0.41-0.78]. Among women with both obesity and GDM, the odds for giving birth to a LGA infant was 2.25-fold (95% CI: 1.04-4.85) among those with normal GWG and 7.63-fold (95% CI: 4.25-13.7) among those with excess GWG compared with the reference group. Compared with excess GWG, normal GWG was associated with 0.71 SD (95% CI: 0.47-0.97) lower birth weight SD score among women with GDM and obesity. Newborns of normal weight women with GDM and normal GWG had 0.28 SD (95% CI: 0.05-0.51) lower birth weight SD scores compared with their counterparts with excess GWG. In addition, in the group of normal weight non-diabetic women, normal GWG was associated with 0.46 SD (95% CI: 0.30-0.61) lower birth weight SD scores compared with excess GWG. GDM, obesity, and excess GWG are associated with higher risk for LGA infants. Interventions aiming at normal GWG have the potential to lower LGA rate and birth weight SD scores even when GDM and obesity are present.
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http://dx.doi.org/10.3389/fpubh.2021.550860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200493PMC
July 2021

The longitudinal association between early-life screen viewing and abdominal adiposity-findings from a multiethnic birth cohort study.

Int J Obes (Lond) 2021 Jun 9. Epub 2021 Jun 9.

Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore.

Importance: Screen viewing in adults has been associated with greater abdominal adiposity, with the magnitude of associations varying by sex and ethnicity, but the evidence is lacking at younger ages. We aimed to investigate sex- and ethnic-specific associations of screen-viewing time at ages 2 and 3 years with abdominal adiposity measured by magnetic resonance imaging at age 4.5 years.

Methods: The Growing Up in Singapore Towards healthy Outcomes is an ongoing prospective mother-offspring cohort study. Parents/caregivers reported the time their child spent viewing television, handheld devices, and computer screens at ages 2 and 3 years. Superficial and deep subcutaneous and visceral abdominal adipose tissue volumes were quantified from magnetic resonance images acquired at age 4.5 years. Associations between screen-viewing time and abdominal adipose tissue volumes were examined by multivariable linear regression adjusting for confounding factors.

Results: In the overall sample (n = 307), greater total screen-viewing time and handheld device times were associated with higher superficial and deep subcutaneous adipose tissue volumes, but not with visceral adipose tissue volumes. Interactions with child sex were found, with significant associations with superficial and deep subcutaneous and visceral adipose tissue volumes in boys, but not in girls. Among boys, the increases in mean (95% CI) superficial and deep subcutaneous and visceral adipose tissue volumes were 24.3 (9.9, 38.7), 17.6 (7.4, 27.8), and 7.8 (2.1, 13.6) mL per hour increase in daily total screen-viewing time, respectively. Ethnicity-specific analyses showed associations of total screen-viewing time with abdominal adiposity only in Malay children. Television viewing time was not associated with abdominal adiposity.

Conclusion: Greater total screen-viewing time (and in particular, handheld device viewing time) was associated with higher abdominal adiposity in boys and Malay children. Additional studies are necessary to confirm these associations and to examine screen-viewing interventions for preventing excessive abdominal adiposity and its adverse cardiometabolic consequences.
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http://dx.doi.org/10.1038/s41366-021-00864-9DOI Listing
June 2021

Maternal circulating SPINT1 is reduced in small-for-gestational age pregnancies at 26 weeks: Growing up in Singapore towards health outcomes (GUSTO) cohort study.

Placenta 2021 Jul 1;110:24-28. Epub 2021 Jun 1.

The Department of Obstetrics and Gynaecology, Mercy Hospital for Women, University of Melbourne, Victoria, Australia; Singapore Institute of Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore; Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Fetal growth restriction arising from placental insufficiency is a leading cause of stillbirth. We recently identified low maternal circulating SPINT1 concentrations as a novel biomarker of poor fetal growth. Here we measured SPINT1 in a prospective cohort in Singapore. Circulating SPINT1 concentrations were significantly lower among 141 pregnant women destined to deliver small-for-gestational age infants (birthweight <10th centile), compared to 772 controls (p < 0.01) at as early as 26 weeks' gestation. There were no correlations between infant body composition and circulating SPINT1 concentrations at 26 weeks. This provides validation that low maternal SPINT1 concentration is associated with poor fetal growth.
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http://dx.doi.org/10.1016/j.placenta.2021.05.007DOI Listing
July 2021

The feasibility and outcome of a community-based primary prevention program for cardiovascular disease in the 21st century.

Scand J Prim Health Care 2021 Jun 7;39(2):157-165. Epub 2021 Jun 7.

Department of General Practice, Turku University and Turku University Hospital, Turku, Finland.

Objective: There is no evidence that systematic screening and risk factor modification in an unselected, asymptomatic population will reduce cardiovascular disease (CVD) mortality. This study aimed to evaluate the effectiveness of a primary care CVD prevention program on mortality during a 13-year follow-up.

Design: A risk factor survey was sent, followed by a nurse-led lifestyle counselling to respondents with at least one CVD risk factor, and a general practitioner's (GP) appointment for high-risk persons. Screening and interventions were performed during 2005-2006.

Setting: A public health care centre in the town of Harjavalta, Finland.

Subjects: All home-dwelling 45-70-year old inhabitants without manifested CVD or diabetes.

Main Outcome Measures: All-cause and CVD mortality.

Results: Altogether 74% (2121/2856) inhabitants responded to the invitation. The intervention was received by 1465 individuals (52% of the invited population): 398 risk persons had an appointment with a nurse, followed by an appointment with a GP for 1067 high-risk persons. During the follow-up, 370 persons died. Mortality among the non-respondents was twofold compared to the participants'. In subjects who received the intervention, the age- and gender-adjusted hazard ratio for all-cause mortality was 0.44 (95% CI: 0.36 to 0.54) compared to the subjects who did not receive the intervention.

Conclusions: Reducing mortality is possible in a primary care setting by raising health awareness in the community with screening, by targeted lifestyle counselling and evidence-based preventive medication for persons at high risk for CVD. Subjects not willing to participate in health surveys have the worst prognosis.Key PointsPreviously, there is no evidence that systematic screening and risk factor modification in an unselected, asymptomatic population will reduce cardiovascular disease (CVD) mortality.With a stepwise screening program it is possible to scale the magnitude of CVD prevention in the community.Reducing mortality in a community is possible by screening, targeted lifestyle counselling, and by evidence-based preventive medication for high-risk persons.Subjects not willing to participate in health surveys have the worst prognosis.
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http://dx.doi.org/10.1080/02813432.2021.1913893DOI Listing
June 2021

Cardiovascular disease in people born to unmarried mothers in two historical periods: The Helsinki Birth Cohort Study 1934-1944.

Scand J Public Health 2021 May 31:14034948211019792. Epub 2021 May 31.

Finnish Institute for Health and Welfare, Finland.

Socio-economic conditions in early life are important contributors to cardiovascular disease - the leading cause of mortality globally - in later life. We studied coronary heart disease (CHD) and stroke in adulthood among people born out of wedlock in two historical periods: before and during World War II in Finland. We compared offspring born out of wedlock before (1934-1939) and during (1940-1944) World War II with the offspring of married mothers in the Helsinki Birth Cohort Study. The war affected the position of unmarried mothers in society. We followed the study subjects from 1971 to 2014 and identified deaths and hospital admissions from CHD and stroke. Data were analysed using a Cox regression, adjusting for other childhood and adulthood socio-economic circumstances. The rate of out-of-wedlock births was 240/4052 (5.9%) before World War II and 397/9197 (4.3%) during World War II. Among those born before World War II, out-of-wedlock birth was associated with an increased risk of stroke (hazard ratio (HR)=1.44; 95% confidence interval (CI) 1.00-2.07) and CHD (HR=1.37; 95% CI 1.02-1.86). Among those born out of wedlock during World War II, the risks of stroke (HR=0.89; 95% CI 0.58-1.36) and CHD (HR=0.70; 95% CI 0.48=1.03) were similar to those observed for the offspring of married mothers. The -values for interaction of unmarried×World War II were (=0.015) for stroke and (=0.003) for CHD.
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http://dx.doi.org/10.1177/14034948211019792DOI Listing
May 2021

Identifying nootropic drug targets via large-scale cognitive GWAS and transcriptomics.

Neuropsychopharmacology 2021 May 25. Epub 2021 May 25.

Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Broad-based cognitive deficits are an enduring and disabling symptom for many patients with severe mental illness, and these impairments are inadequately addressed by current medications. While novel drug targets for schizophrenia and depression have emerged from recent large-scale genome-wide association studies (GWAS) of these psychiatric disorders, GWAS of general cognitive ability can suggest potential targets for nootropic drug repurposing. Here, we (1) meta-analyze results from two recent cognitive GWAS to further enhance power for locus discovery; (2) employ several complementary transcriptomic methods to identify genes in these loci that are credibly associated with cognition; and (3) further annotate the resulting genes using multiple chemoinformatic databases to identify "druggable" targets. Using our meta-analytic data set (N = 373,617), we identified 241 independent cognition-associated loci (29 novel), and 76 genes were identified by 2 or more methods of gene identification. Actin and chromatin binding gene sets were identified as novel pathways that could be targeted via drug repurposing. Leveraging our transcriptomic and chemoinformatic databases, we identified 16 putative genes targeted by existing drugs potentially available for cognitive repurposing.
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http://dx.doi.org/10.1038/s41386-021-01023-4DOI Listing
May 2021

Trajectories of Systolic Blood Pressure in Children: Risk Factors and Cardiometabolic Correlates.

J Pediatr 2021 May 18. Epub 2021 May 18.

Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research (A∗STAR), Singapore, Singapore; Khoo Teck Puat-National University Children's Medical Institute, National University Hospital, National University Health System, Singapore, Singapore.

Objective: To identify systolic blood pressure (SBP) percentile trajectories in children and to describe the early-life risk factors and cardiometabolic correlates of those trajectories.

Study Design: Using age-, sex-, and height-specific SBP percentiles based on the American Academy of Pediatrics reference, we examined SBP trajectories using latent class mixed models from ages 3 to 8 years (n = 844) from the Growing Up in Singapore Towards healthy Outcomes-study, a Singaporean mother-offspring cohort study. We analyzed associations between SBP trajectories and early-life risk factors using multinomial logistic regression and differences across trajectories in cardiometabolic outcomes using multiple linear regression.

Results: Children were classified into 1 of 4 SBP percentile trajectories: "low increasing" (15%), "high stable" (47%), "high decreasing" (20%), and "low stable" (18%). Maternal hypertension during early pregnancy was a predictor of the "high stable" and "low increasing" SBP trajectories. Rapid child weight gain in the first 2 years of life was only associated with the "high stable" trajectory. Compared with children in the "low stable" trajectory, children in the "high stable" SBP trajectory had greater body mass index z scores, sum of skinfold thicknesses, waist circumference from ages 3 to 8 years, and abdominal adipose tissue (milliliters) at 4.5 years (adjusted mean difference [95% CI]: superficial and deep subcutaneous abdominal adipose tissue: 115.2 [48.1-182.3] and 85.5 [35.2-135.8]). Their fat mass (kilograms) (1.3 [0.6-2.0]), triglyceride levels (mmol/L) (0.10 [0.02-0.18]), and homeostasis model assessment of insulin resistance (0.28 [0.11 0.46]) at age 6 years were also greater but not their arterial thickness and stiffness.

Conclusions: Reducing maternal blood pressure during pregnancy and infant weight gain in the first 2 years of life might help to prevent the development of high SBP.
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http://dx.doi.org/10.1016/j.jpeds.2021.05.027DOI Listing
May 2021

Both lean and fat body mass associate with blood pressure.

Eur J Intern Med 2021 May 13. Epub 2021 May 13.

Folkhälsan Research Center, Helsinki, Finland; Department of General Practice and Primary Health Care, University of Helsinki, Helsinki, Finland; Singapore Institute for Clinical Sciences, Agency for Science, Technology, and Research, Singapore; Department of Obstetrics & Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

High body mass index (BMI) is known to be associated with elevated blood pressure (BP). The present study aims to determine the relative importance of the two components of BMI, fat mass and lean body mass index, on BP levels. We assessed body composition with bioimpedance and performed 24 hour ambulatory BP measurements in 534 individuals (mean age 61 ± 3 years) who had no cardiovascular medication. Fat mass index and lean mass index were calculated analogously to BMI as fat mass or lean body mass (kg) divided by the square of height (m). Both fat mass index and lean mass index showed a positive, small to moderate relationship with all 24 hour BP components independently of age, sex, smoking, and leisure-time physical activity. There were no interaction effects between fat mass index and lean mass index on the mean BP levels. Adult lean body mass is a significant determinant of BP levels with an equal, albeit small to moderate magnitude as fat mass. Relatively high amount of muscle mass may not be beneficial to cardiovascular health.
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http://dx.doi.org/10.1016/j.ejim.2021.04.025DOI Listing
May 2021

The association of maternal gestational hyperglycemia with breastfeeding duration and markers of milk production.

Am J Clin Nutr 2021 May 8. Epub 2021 May 8.

Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore.

Background: Previous studies focusing on the association between gestational diabetes and breastfeeding duration have been inconclusive.

Objectives: We aimed to determine whether maternal gestational hyperglycemia is associated with the duration of breastfeeding and the concentrations of markers linked to breastmilk production.

Methods: Data from the prospective, multiethnic Growing Up in Singapore Towards Healthy Outcomes study were used to assess the association of fasting plasma glucose (FPG) and 2-h postglucose challenge (2hPG) measured at 26-28 wk of gestation with duration of breastfeeding and concentrations of protein, lactose, citrate, sodium, potassium, and zinc in breastmilk 3 wk postpartum.

Results: Of the 1035 participants, 5.2% and 9.5% had elevated FPG and 2hPG, respectively, consistent with a diagnosis of gestational diabetes mellitus based on International Association of Diabetes and Pregnancy Study Groups criteria. FPG ≥5.1 mmol/L was associated with a crude reduction in median breastfeeding duration of 2.3 mo. In a model adjusted for maternal prepregnancy BMI and intention to breastfeed, FPG ≥5.1 mmol/L predicted earlier termination of any breastfeeding (adjusted HR: 1.47; 95% CI: 1.04, 2.08) but not full breastfeeding (adjusted HR: 1.08; 0.76, 1.55). 2hPG ≥8.5 mmol/L was not significantly associated with the durations of any (adjusted HR: 0.86; 95% CI: 0.62, 1.19) or full (adjusted HR: 0.85; 95% CI: 0.62, 1.18) breastfeeding. Maternal FPG was significantly and positively associated with breastmilk sodium (adjusted coefficient: 1.28; 95% CI: 1.08, 1.51) and sodium-to-potassium ratio (adjusted coefficient: 1.29; 95% CI: 1.08, 1.54) but not with other measured breastmilk components.

Conclusions: Women with FPG ≥5.1 mmol/L during pregnancy breastfeed for a shorter duration. Future work involving measurement of milk production is needed to determine whether low milk production predicts breastfeeding duration among women with elevated FPG. This trial was registered at www.clinicaltrials.gov as NCT01174875.
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http://dx.doi.org/10.1093/ajcn/nqab142DOI Listing
May 2021

Characteristics of epigenetic aging across gestational and perinatal tissues.

Clin Epigenetics 2021 Apr 29;13(1):97. Epub 2021 Apr 29.

Department of Translational Psychiatry, Max Planck Institute of Psychiatry, München, Germany.

Background: Epigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age. However, so far, only few studies have examined epigenetic aging in newborns-especially regarding different gestational or perinatal tissues. In this study, we investigated which birth- and pregnancy-related variables are most important in predicting gestational epigenetic age acceleration or deceleration (i.e., the deviation between gestational epigenetic age estimated from the DNA methylome and chronological gestational age) in chorionic villus, placenta and cord blood tissues from two independent study cohorts (ITU, n = 639 and PREDO, n = 966). We further characterized the correspondence of epigenetic age deviations between these tissues.

Results: Among the most predictive factors of epigenetic age deviations in single tissues were child sex, birth length, maternal smoking during pregnancy, maternal mental disorders until childbirth, delivery mode and parity. However, the specific factors related to epigenetic age deviation and the direction of association differed across tissues. In individuals with samples available from more than one tissue, relative epigenetic age deviations were not correlated across tissues.

Conclusion: Gestational epigenetic age acceleration or deceleration was not related to more favorable or unfavorable factors in one direction in the investigated tissues, and the relative epigenetic age differed between tissues of the same person. This indicates that epigenetic age deviations associate with distinct, tissue specific, factors during the gestational and perinatal period. Our findings suggest that the epigenetic age of the newborn should be seen as a characteristic of a specific tissue, and less as a general characteristic of the child itself.
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http://dx.doi.org/10.1186/s13148-021-01080-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082803PMC
April 2021

The EU Child Cohort Network's core data: establishing a set of findable, accessible, interoperable and re-usable (FAIR) variables.

Eur J Epidemiol 2021 May 21;36(5):565-580. Epub 2021 Apr 21.

Department of Social Medicine, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.

The Horizon2020 LifeCycle Project is a cross-cohort collaboration which brings together data from multiple birth cohorts from across Europe and Australia to facilitate studies on the influence of early-life exposures on later health outcomes. A major product of this collaboration has been the establishment of a FAIR (findable, accessible, interoperable and reusable) data resource known as the EU Child Cohort Network. Here we focus on the EU Child Cohort Network's core variables. These are a set of basic variables, derivable by the majority of participating cohorts and frequently used as covariates or exposures in lifecourse research. First, we describe the process by which the list of core variables was established. Second, we explain the protocol according to which these variables were harmonised in order to make them interoperable. Third, we describe the catalogue developed to ensure that the network's data are findable and reusable. Finally, we describe the core data, including the proportion of variables harmonised by each cohort and the number of children for whom harmonised core data are available. EU Child Cohort Network data will be analysed using a federated analysis platform, removing the need to physically transfer data and thus making the data more accessible to researchers. The network will add value to participating cohorts by increasing statistical power and exposure heterogeneity, as well as facilitating cross-cohort comparisons, cross-validation and replication. Our aim is to motivate other cohorts to join the network and encourage the use of the EU Child Cohort Network by the wider research community.
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http://dx.doi.org/10.1007/s10654-021-00733-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159791PMC
May 2021

Advanced glycation end products measured by skin autofluorescence are associated with melancholic depressive symptoms - Findings from Helsinki Birth Cohort Study.

J Psychosom Res 2021 Jun 10;145:110488. Epub 2021 Apr 10.

Folkhälsan Research Center, Helsinki, Finland; Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: Millions of people live with depression and its burden of disease. Depression has an increased comorbidity and mortality that has remained unexplained. Studies have reported connections between advanced glycation end products (AGEs) and various disease processes, including mental health. The present study evaluated associations between AGEs, depressive symptoms, and types of depressive symptoms.

Methods: From the Helsinki Birth Cohort Study, 815 participants with a mean age of 76 years were recruited for this cross-sectional study. Characteristics regarding self-reported lifestyle and medical history, as well as blood tests were obtained along with responses regarding depressive symptoms according to the Beck Depression Inventory (BDI) and Mental Health Inventory-5. Each participant had their AGE level measured non-invasively with skin autofluorescence (SAF). Statistical analyses looked at relationships between types of depressive symptoms and AGE levels by sex.

Results: Of women, 27% scored ≥10 on the BDI and 18% of men, respectively. Men had higher crude AGE levels (mean [standard deviation], arbitrary units) (2.49 [0.51]) compared to women (2.33 [0.46]) (p < 0.001). The highest crude AGE levels were found in those with melancholic depressive symptoms (2.61 [0.57]), followed by those with non-melancholic depressive symptoms (2.45 [0.45]) and those with no depressive symptoms (2.38 [0.49]) (p = 0.013). These findings remained significant in the fully adjusted model.

Conclusions: The current study shows an association between depressive symptoms and higher AGE levels. The association is likely part of a multi-factorial effect, and hence no directionality, causality, or effect can be inferred solely based on the results of this study.
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http://dx.doi.org/10.1016/j.jpsychores.2021.110488DOI Listing
June 2021

Higher carotid-radial pulse wave velocity is associated with non-melancholic depressive symptoms in men - findings from Helsinki Birth Cohort Study.

Ann Med 2021 12;53(1):531-540

Folkhälsan Research Center, Helsinki, Finland.

Background: Depression and cardiovascular disease (CVD) are major causes of global disease burden that are interrelated through mostly unknown mechanisms. We studied the relationship of melancholic and non-melancholic depressive symptoms with arterial stiffness, an important underlying mechanism of CVD.

Methods: The Helsinki Birth Cohort Study recruited 683 previously extensively phenotyped subjects for this sub-study. Cross-sectional data along with responses regarding depressive symptoms were obtained for each participant. For evaluation of depressive symptoms, the Beck Depression Inventory (BDI)and subscales were used to measure melancholic and non-melancholic depressive symptoms. Arterial stiffness was assessed as pulse wave velocity (PWV) that was measured between the carotid and radial artery, and carotid and femoral artery.

Results: Of the participants, 532 scored <10 on the BDI and were classified as not having depressive symptoms. Of the 151 participants that scored ≥10 on the BDI, 122 were classified as having non-melancholic depressive symptoms and 29 as having melancholic depressive symptoms. Men had higher carotid-radial PWV (crPWV) values than women ( < .001). A positive relationship between BDI scores and crPWV ( < .001) was found in men. We also found higher crPWV in men with non-melancholic depressive symptoms compared to all others. No such differences were found in women.

Discussion: Arterial stiffness has a relationship with depressive symptoms and subtypes of depressive symptoms, at least in men. There is a significant relationship between higher PWV and non-melancholic depressive symptoms in men. Due to the intricate nature of the disease causality or directionality is impossible to infer solely based on this study. Further studies into the subtypes of depressive symptoms may be of benefit to understanding depression.KEY MESSAGESIt is known that arterial stiffness contributes to cardiovascular disease, and is associated with depression.Higher Beck Depression Inventory scores are associated with higher carotid-radial pulse wave velocity in men.Non-melancholic depressive symptoms are associated with higher carotid-radial pulse wave velocity in men.
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http://dx.doi.org/10.1080/07853890.2021.1904277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011688PMC
December 2021

Identification and reproducibility of dietary patterns assessed with a FFQ among women planning pregnancy.

Public Health Nutr 2021 Jun 22;24(9):2437-2446. Epub 2021 Mar 22.

Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore.

Objective: To identify a posteriori dietary patterns among women planning pregnancy and assess the reproducibility of these patterns in a subsample using two dietary assessment methods.

Design: A semi-quantitative FFQ was administered to women enrolled in the Singapore PREconception Study of long-Term maternal and child Outcomes study. Dietary patterns from the FFQ were identified using exploratory factor analysis (EFA). In a subsample of women (n 289), 3-d food diaries (3DFD) were also completed and analysed. Reproducibility of the identified patterns was assessed using confirmatory factor analysis (CFA) in the subsample, and goodness of fit of the CFA models was examined using several fit indices. Subsequently, EFA was conducted in the subsample and dietary patterns of the FFQ and the 3DFD were compared.

Setting: Singapore.

Participants: 1007 women planning pregnancy (18-45 years).

Results: Three dietary patterns were identified from the FFQ: the 'Fish, Poultry/Meat and Noodles' pattern was characterised by higher intakes of fish, poultry/meat and noodles in soup; 'Fast Food and Sweetened Beverages' pattern was characterised by higher intakes of fast food, sweetened beverages and fried snacks; 'Bread, Legumes and Dairy' pattern was characterised by higher intakes of buns/ethnic breads, nuts/legumes and dairy products. The comparative fit indices from the CFA models were 0·79 and 0·34 for the FFQ and 3DFD of the subsample, respectively. In the subsample, three similar patterns were identified in the FFQ while only two for the 3DFD.

Conclusions: Dietary patterns from the FFQ are reproducible within this cohort, providing a basis for future investigations on diet and health outcomes.
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http://dx.doi.org/10.1017/S1368980021001178DOI Listing
June 2021

Combined analysis of gestational diabetes and maternal weight status from pre-pregnancy through post-delivery in future development of type 2 diabetes.

Sci Rep 2021 Mar 3;11(1):5021. Epub 2021 Mar 3.

Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, 30 Medical Drive, Singapore, 117609, Singapore.

We examined the associations of gestational diabetes mellitus (GDM) and women's weight status from pre-pregnancy through post-delivery with the risk of developing dysglycaemia [impaired fasting glucose, impaired glucose tolerance, and type 2 diabetes (T2D)] 4-6 years post-delivery. Using Poisson regression with confounder adjustments, we assessed associations of standard categorisations of prospectively ascertained pre-pregnancy overweight and obesity (OWOB), gestational weight gain (GWG) and substantial post-delivery weight retention (PDWR) with post-delivery dysglycaemia (n = 692). Women with GDM had a higher risk of later T2D [relative risk (95% CI) 12.07 (4.55, 32.02)] and dysglycaemia [3.02 (2.19, 4.16)] compared with non-GDM women. Independent of GDM, women with pre-pregnancy OWOB also had a higher risk of post-delivery dysglycaemia. Women with GDM who were OWOB pre-pregnancy and had subsequent PDWR (≥ 5 kg) had 2.38 times (1.29, 4.41) the risk of post-delivery dysglycaemia compared with pre-pregnancy lean GDM women without PDWR. No consistent associations were observed between GWG and later dysglycaemia risk. In conclusion, women with GDM have a higher risk of T2D 4-6 years after the index pregnancy. Pre-pregnancy OWOB and PDWR exacerbate the risk of post-delivery dysglycaemia. Weight management during preconception and post-delivery represent early windows of opportunity for improving long-term health, especially in those with GDM.
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http://dx.doi.org/10.1038/s41598-021-82789-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930020PMC
March 2021

Use of antidepressants among Finnish family caregivers: a nationwide register-based study.

Soc Psychiatry Psychiatr Epidemiol 2021 Mar 1. Epub 2021 Mar 1.

Folkhälsan Research Center, PO Box 211, 00251, Helsinki, Finland.

Purpose: The purpose of this study was to compare the use of antidepressants over 6 years between family caregivers providing high-intensity care and a matched control population using register-based data.

Methods: The study includes all individuals, who received family caregiver's allowance in Finland in 2012 (n = 29,846 females, mean age 66 years; n = 12,410 males, mean age 71 years) and a control population matched for age, sex, and municipality of residence (n = 59,141 females; n = 24,477 males). Information on purchases of antidepressants, including the number of defined daily doses (DDD) purchased, between 2012 and 2017 was obtained from the national drugs reimbursement register.

Results: During the follow-up, 28.5% of female caregivers and 23.5% of the female controls used antidepressants, while the numbers for males were 21.1% and 16.4%, respectively. Adjusted for socioeconomic status, female caregivers used 43.7 (95% confidence interval 42.4-45.0) and their controls used 36.2 (35.3-37.2) DDDs of antidepressants per person-year. Male caregivers used 29.6 (27.6-31.6) and their controls used 21.6 (20.2-23.0) DDDs of antidepressants per person-year. Among female caregivers, the relative risk for use of antidepressants was similar (about 1.3) from 20 to 70 years, after which the relative risk declined. In male caregivers, the relative risk was highest (about 1.4-1.5) between 45 and 65 years.

Conclusions: Family caregivers providing high-intensity care use more antidepressants and hence, are likely to have poorer mental health than the age-matched general population in virtually all age groups. However, the magnitude of the higher use varies as a function of age and gender.
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http://dx.doi.org/10.1007/s00127-021-02049-1DOI Listing
March 2021

Maternal use of sedative drugs and its effects on pregnancy outcomes: a Finnish birth cohort study.

Sci Rep 2021 Feb 24;11(1):4467. Epub 2021 Feb 24.

Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Our aim was to evaluate maternal use of sedative drugs before, during, and after pregnancy and to assess the influence of use of these drugs on pregnancy outcomes. The study cohort (N = 6231) consists of all primiparous women, who lived in the city of Vantaa, Finland, and who delivered a singleton between 2009 and 2015. Data were obtained from Finnish national health registers. Of the women, 3.2% (n = 202) purchased at least once sedative drugs within 90 days before conception, during pregnancy and/or within 90 days after delivery. Sedative drug users were older, less likely to cohabitate, more often smokers, had lower educational attainment and had more mental diseases (for all p < 0.001) compared with non-users. Sedative drug users purchased more often antidepressants and drugs for the alimentary tract, musculoskeletal and nervous system than non-users (for all p < 0.001). No adverse birth or pregnancy outcomes were found in the group using sedative drugs compared with the non-users. Studies in larger cohorts are needed to confirm our study findings.
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http://dx.doi.org/10.1038/s41598-021-84151-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904770PMC
February 2021

Children conceived by ART grow differently in early life than naturally conceived children but reach the same height and weight by age 17. Reassuring? Not so sure.

Hum Reprod 2021 03;36(4):847-849

Department of Obstetrics and Gynaecology and Human Potential Translational Research Programme, National University of Singapore, Singapore.

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http://dx.doi.org/10.1093/humrep/deab048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970726PMC
March 2021

Impact of gestational diabetes mellitus on the duration of breastfeeding in primiparous women: an observational cohort study.

Int Breastfeed J 2021 Feb 16;16(1):19. Epub 2021 Feb 16.

Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Background: The impact of gestational diabetes mellitus (GDM) on the duration of breastfeeding varies between shortening and no impact. Breastfeeding seems to reduce both maternal and offspring risk for type 2 diabetes and offspring risk for overweight or obesity later in life. The aim of our study was to evaluate in primiparous women whether GDM had an influence on the duration of breastfeeding, and further, to evaluate the factors that influenced on the duration of breastfeeding.

Methods: The study cohort (N = 1089) consisted of all primiparous women with a Finnish background excluding women with pre-existing diabetes mellitus who lived in the city of Vantaa, Finland, gave birth to a singleton living child between 2009 and 2015, and with valid data on breastfeeding available. The diagnosis of GDM was based on a standard 75 g 2-h oral glucose tolerance test. Data were obtained from Finnish national registers and from the medical records of the city of Vantaa.

Results: No differences were observed in the duration of breastfeeding between women diagnosed with GDM and without GDM, 7.5 (Standard Deviation [SD] 3.7) months versus 7.9 (SD 3.5) months (p = 0.17). Women diagnosed with GDM breastfed boys for a longer duration than girls (maternal age, pre-pregnancy body mass index, marital status, educational attainment, duration of pregnancy, and smoking habits adjusted p = 0.042). Women who breastfed < 6 months were younger, were more likely smokers, had shorter education, and higher pre-pregnancy body mass index than women who breastfed over 6 months (p <  0.001 for linearity).

Conclusions: In primiparous women GDM did not influence breastfeeding duration. The positive health effects of breastfeeding should be emphasized especially in young, overweight and less educated women in order to minimize the risk of obesity and type 2 diabetes for themselves and their offspring.
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http://dx.doi.org/10.1186/s13006-021-00369-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885226PMC
February 2021

Glucose regulation and pain in older people-The Helsinki Birth Cohort Study.

Prim Care Diabetes 2021 Jun 10;15(3):561-566. Epub 2021 Feb 10.

Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland; Department of Public Health Solutions, Public Health Promotion Unit, National Institute for Health and Welfare, Helsinki, Finland; Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore; Obstetrics & Gynecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.

Aims: To assess if individuals with diabetes or prediabetes report more pain or have increased use of pain medication compared to normoglycaemic individuals.

Methods: Using cross-sectional data, we studied 928 men and 1075 women from the Helsinki Birth Cohort Study in 2001-2004 at a mean age of 61.5 years. Glucose regulation was assessed with a 2-h 75 g oral glucose tolerance test, and applying World Health Organization criteria, participants were defined as having normoglycaemia, prediabetes (impaired fasting glucose or impaired glucose tolerance), newly diagnosed diabetes or previously diagnosed diabetes. Self-reported pain intensity and interference during the previous 4 weeks was estimated using the RAND 36-Item Health Survey 1.0. Information on use of pain medication during the past 12 months was obtained from the Social Insurance Institution of Finland.

Results: There was no difference in pain intensity or interference between glucose regulation groups for neither men nor women after adjusting for covariates (age, body mass index, education years, Beck Depression Inventory and physical activity). In addition, use of pain medication was similar between glucose regulation groups.

Conclusions: Although pain is a common symptom in the general population, impairments in glucose regulation alone does not seem to increase pain among older individuals.
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http://dx.doi.org/10.1016/j.pcd.2021.02.001DOI Listing
June 2021

Combined effects of genotype and childhood adversity shape variability of DNA methylation across age.

Transl Psychiatry 2021 02 1;11(1):88. Epub 2021 Feb 1.

Department of Translational Research in Psychiatry, Max Planck Institute of Psychiatry, Kraepelinstr. 2-10, 80804, Munich, Germany.

Lasting effects of adversity, such as exposure to childhood adversity (CA) on disease risk, may be embedded via epigenetic mechanisms but findings from human studies investigating the main effects of such exposure on epigenetic measures, including DNA methylation (DNAm), are inconsistent. Studies in perinatal tissues indicate that variability of DNAm at birth is best explained by the joint effects of genotype and prenatal environment. Here, we extend these analyses to postnatal stressors. We investigated the contribution of CA, cis genotype (G), and their additive (G + CA) and interactive (G × CA) effects to DNAm variability in blood or saliva from five independent cohorts with a total sample size of 1074 ranging in age from childhood to late adulthood. Of these, 541 were exposed to CA, which was assessed retrospectively using self-reports or verified through social services and registries. For the majority of sites (over 50%) in the adult cohorts, variability in DNAm was best explained by G + CA or G × CA but almost never by CA alone. Across ages and tissues, 1672 DNAm sites showed consistency of the best model in all five cohorts, with G × CA interactions explaining most variance. The consistent G × CA sites mapped to genes enriched in brain-specific transcripts and Gene Ontology terms related to development and synaptic function. Interaction of CA with genotypes showed the strongest contribution to DNAm variability, with stable effects across cohorts in functionally relevant genes. This underscores the importance of including genotype in studies investigating the impact of environmental factors on epigenetic marks.
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http://dx.doi.org/10.1038/s41398-020-01147-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851167PMC
February 2021

Cardiometabolic Profile of Different Body Composition Phenotypes in Children.

J Clin Endocrinol Metab 2021 Apr;106(5):e2015-e2024

Singapore Institute for Clinical Sciences, Agency for Sciences, Technology, and Research, Singapore, Singapore.

Context: Cardiometabolic profiles of different body composition phenotypes are poorly characterized in young children, where it is well established that high adiposity is unfavorable, but the role of lean mass is unclear.

Objective: We hypothesized that higher lean mass attenuates cardiometabolic risk in children with high fat mass.

Methods: In 6-year-old children (n = 377) from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) prospective birth cohort, whole-body composition was measured by quantitative magnetic resonance, a novel validated technology. Based on fat mass index (FMI) and lean mass index (LMI), 4 body composition phenotypes were derived: low FMI-low LMI (LF-LL), low FMI-high LMI (LF-HL), high FMI-low LMI (HF-LL), high FMI-high LMI (HF-HL).

Main Outcome Measures: Body mass index (BMI) z-score, fasting plasma glucose, insulin resistance, metabolic syndrome risk score, fatty liver index, and blood pressure.

Results: Compared with the LF-HL group, children in both high FMI groups had increased BMI z-score (HF-HL: 1.43 units 95% CI [1.11,1.76]; HF-LL: 0.61 units [0.25,0.96]) and metabolic syndrome risk score (HF-HL: 1.64 [0.77,2.50]; HF-LL: 1.28 [0.34,2.21]). The HF-HL group also had increased fatty liver index (1.15 [0.54,1.77]). Girls in HF-HL group had lower fasting plasma glucose (-0.29 mmol/L [-0.55,-0.04]) and diastolic blood pressure (-3.22 mmHg [-6.03,-0.41]) than girls in the HF-LL group. No similar associations were observed in boys.

Conclusion: In a multi-ethnic Asian cohort, lean mass seemed to protect against some cardiometabolic risk markers linked with adiposity, but only in girls. The FMI seemed more important than lean mass index in relation to cardiometabolic profiles of young children.
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http://dx.doi.org/10.1210/clinem/dgab003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610678PMC
April 2021

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Hum Mol Genet 2021 Apr;30(5):393-409

Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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http://dx.doi.org/10.1093/hmg/ddab023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8098112PMC
April 2021

Glucose regulation and grip strength in adults: Findings from the Helsinki Birth Cohort Study.

Arch Gerontol Geriatr 2021 May-Jun;94:104348. Epub 2021 Jan 21.

Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland; Singapore Institute for Clinical Sciences (SICS), Agency for Science, Technology and Research (A*STAR), Singapore; Obstetrics & Gynecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore.

Aim: This study aimed to assess the association between grip strength and glucose regulation in a cross-sectional setting.

Methods: Using data from the Helsinki Birth Cohort Study, 924 men and 953 women were studied at a mean age of 61.6 years. Grip strength was assessed in the dominant hand using a Newtest Grip Force dynamometer. A standard 2-h 75 g oral glucose tolerance test (OGTT) was used to define glucose regulation. The participants were classified into four groups: normoglycaemia, prediabetes (impaired fasting glucose or impaired glucose tolerance), newly diagnosed diabetes and previously known diabetes. The association between grip strength and glucose regulation was assessed using multiple linear regression models.

Results: Prediabetes was diagnosed in 32.2% and diabetes in 8.4% using the OGTT. A total of 7.8% of the individuals had previously known diabetes. Compared to individuals with normoglycaemia, grip strength was lower for those with newly diagnosed diabetes (-1.8 kg, 95% CI -3.2 to -0.5) as well as those with previously known diabetes (-1.8 kg, 95% CI -3.2 to -0.4) after adjusting for covariates (age, sex, body mass index, physical activity, education and smoking). No difference in grip strength was found when comparing those with prediabetes and normoglycaemia.

Conclusion: In adults, grip strength was lower among those with known and newly diagnosed diabetes compared to those with normoglycaemia. Together with previous findings on associations between grip strength and chronic diseases, these results support the use of grip strength as an overall health marker in adults.
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http://dx.doi.org/10.1016/j.archger.2021.104348DOI Listing
May 2021

Skin Autofluorescence in Young Adult Offspring of Women with Type 1 Diabetes: A Cross-Sectional Case-Control Study.

Diabetes Ther 2021 Mar 23;12(3):669-677. Epub 2021 Jan 23.

Department of General Practice and Primary Health Care, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

Introduction: Offspring born to women with type 1 diabetes pregnancies have an elevated risk for early-onset obesity and type 2 diabetes compared with offspring born to women without diabetes. Skin autofluorescence (SAF) is a marker of accumulated advanced glycation end products (AGEs) and it has been shown to predict type 2 diabetes, cardiovascular disease, and mortality in the general population. The aim of this study was to evaluate whether maternal type 1 diabetes influences the SAF value in young adult offspring.

Methods: This cross-sectional case-control study included 78 offspring of women with type 1 diabetes (cases) and 85 control participants (controls). All study participants, aged 18-23 years, were invited to participate in a clinical assessment including laboratory tests and questionnaires. SAF was assessed using the AGE reader from the dominant forearm of each participant.

Results: The mean SAF value did not differ between the cases (1.61 [standard deviation (SD) 0.37]) arbitrary units [AU]) and the controls (1.64 [SD 0.41] AU) (p = 0.69). After adjusting for glycated hemoglobin A, body fat percentage, smoking, and season the mean SAF value did not differ between the cases and the controls (p = 0.49) but differed between men and women (p = 0.008), without any interaction observed (p = 0.78).

Conclusion: SAF values did not differ between the young adult offspring of women with type 1 diabetes and offspring born to mothers without diabetes. Surprisingly, young adult women showed higher SAF values than men in both case and control groups.
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http://dx.doi.org/10.1007/s13300-021-01001-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947119PMC
March 2021