Plasma Acylcarnitines during Pregnancy and Neonatal Anthropometry: A Longitudinal Study in a Multiracial Cohort

As surrogate readouts reflecting mitochondrial dysfunction, elevated levels of plasma acylcarnitines have been associated with cardiometabolic disorders, such as obesity, gestational diabetes, and type 2 diabetes. This study aimed to examine prospective associations of acylcarnitine profiles across gestation with neonatal anthropometry, including birthweight, birthweight z score, body length, sum of skinfolds, and sum of body circumferences. We quantified 28 acylcarnitines using electrospray ionization tandem mass spectrometry in plasma collected at gestational weeks 10–14, 15–26, 23–31, and 33–39 among 321 pregnant women from the National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singletons. A latent-class trajectory approach was applied to identify trajectories of acylcarnitines across gestation. We examined the associations of individual acylcarnitines and distinct trajectory groups with neonatal anthropometry using weighted generalized linear models adjusting for maternal age, race/ethnicity, education, parity, gestational age at blood collection, and pre-pregnancy body mass index (BMI). We identified three distinct trajectory groups in C2, C3, and C4 and two trajectory groups in C5, C10, C5–DC, C8:1, C10:1, and C12, respectively. Women with nonlinear decreasing C12 levels across gestation (5.7%) had offspring with significantly lower birthweight (−475 g; 95% CI, −942, −6.79), birthweight z score (−0.39, −0.71, −0.06), and birth length (−1.38 cm, −2.49, −0.27) than those with persistently stable C12 levels (94.3%) (all nominal p value < 0.05). Women with consistently higher levels of C10 (6.1%) had offspring with thicker sum of skinfolds (4.91 mm, 0.85, 8.98) than did women with lower levels (93.9%) during pregnancy, whereas women with lower C10:1 levels (12.6%) had offspring with thicker sum of skinfolds (3.23 mm, 0.19, 6.27) than did women with abruptly increasing levels (87.4%) (p < 0.05). In conclusion, this study suggests that distinctive trajectories of C10, C10:1, and C12 acylcarnitine levels throughout pregnancy were significantly associated with neonatal anthropometry.

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Abstract P166: Plasma Acylcarnitines During Pregnancy And Neonatal Anthropometry: A Prospective And Longitudinal Study

Circulation ◽

10.1161/circ.143.suppl_1.p166 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Yiqing Song ◽

Chen Lyu ◽

Ming Li ◽

Mohammad Rahman ◽

Yeyi Zhu ◽

...

Keyword(s):

Generalized Linear Models ◽

Clinical Utility ◽

Latent Class ◽

Linear Models ◽

Distinct Group ◽

Blood Collection ◽

Z Score ◽

Cardiometabolic Disorders ◽

Trajectory Approach

As surrogate readouts reflecting tissue acyl-CoA pools, elevated levels of plasma acylcarnitines have been associated with cardiometabolic disorders, such as obesity, gestational diabetes, and type 2 diabetes. This study aimed to examine prospective associations of acylcarnitine profiles across gestation with neonatal anthropometry, including birthweight (BW), BW z-score, the sum of skinfolds (SS), body length, and head circumference. We quantified 28 acylcarnitines using electrospray ionization tandem mass spectrometry in plasma collected at gestational weeks 10-14, 15-26, 23-31 and 33-39 among 321 pregnant women from the NICHD Fetal Growth Studies-Singletons and performed latent-class trajectory approach to identify trajectories of acylcarnitines across gestation. We examined the associations of individual acylcarnitines and distinct trajectory groups with neonatal outcomes using weighted generalized linear models adjusting for maternal age, race, education, parity, gestational age of blood collection, and pre-pregnancy BMI. Women showed changes in plasma levels of all acylcartinines across gestation and had at least two significantly distinct group-based trajectories for 32% of acylcartinines. Longitudinally, women with increased C12 levels across gestation (5.7%) had significantly smaller BW (-475 g; 95% CI, -942, -6.79), BW z-score (-0.39, 95% CI, -0.71, -0.06), and length (-1.38, 95% CI, -2.49, -0.27) than those with persistently stable C12 levels during pregnancy (all FDR<0.05). Women with persistently higher levels of C10 (6.1%) or C10:1 (87.4%) had greater sum of skinfolds (4.91, 95%, 0.85, 8.98) than those with lower levels during pregnancy (P<0.05). In conclusion, this study identified that gestational trajectories of C10, C10:1, and C12 acylcarnitine levels were significantly associated with neonatal anthropometry. Further studies are needed to replicate and assess clinical utility of these findings.

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Plasma Acylcarnitines During Pregnancy and Neonatal Anthropometry: A Longitudinal Study in a Multiracial Cohort

Current Developments in Nutrition ◽

10.1093/cdn/nzab046_075 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 778-778

Author(s):

Chen Lyu ◽

Yiqing Song ◽

Ming Li ◽

Mohammad Rahman ◽

Yeyi Zhu ◽

...

Keyword(s):

Latent Class ◽

Linear Models ◽

Blood Collection ◽

Z Score ◽

Funding Sources ◽

Trajectory Approach ◽

Gestational Week ◽

Potential Clinical Utility ◽

Race Ethnicity ◽

Plasma Profile

Abstract Objectives Plasma profile of acylcarnitines has been suggested to associate with adverse maternal outcomes such as gestational diabetes. However, data on their associations with neonatal outcomes are sparse. Therefore, this study aimed to examine the prospective profile of acylcarnitines across gestation and its association with neonatal anthropometry, including birthweight (BW), BW z-score, the sum of skinfolds (SSF), length, and circumferences. Methods Among 321 pregnant women from the NICHD Fetal Growth Studies-Singletons cohort, we quantified 28 acylcarnitines using electrospray ionization tandem mass spectrometry in the plasma at gestational weeks 10–14, 15–26, 23–31 and 33–39, accordingly. We firstly applied a latent-class trajectory approach to identify trajectories of acylcarnitines across gestation, and secondly examined associations of individual acylcarnitine and distinct trajectory groups with neonatal anthropometry using weighted linear models with robust standard errors, adjusting for maternal age, race/ethnicity, education, parity, gestational week of blood collection, and pre-pregnancy body mass index. Results We identified three distinct trajectory groups of C2, C3 and C4, and two trajectory groups of C5, C10, C5-DC, C8:1, C10:1 and C12, respectively. Newborns of women with nonlinear decline of C12 levels across gestation (5.7%) had significantly smaller BW (−475 g; 95% CI: −942, −6.79 g), BW z-score (−0.39; −0.71, −0.06), and length (−1.38 cm; −2.49, −0.27 cm) than those with persistently stable C12 levels (94.3%). Newborns of women with consistently higher levels of C10 (6.1%) had greater sum of skinfolds (4.91 mm; 0.85, 8.98 mm) than those with lower levels (93.9%) across pregnancy, whereas newborns of women with declining C10:1 levels (12.6%) had larger sum of skinfolds (3.23 mm; 0.19, 6.27 mm) than those with abruptly increasing levels (87.4%). Conclusions In conclusion, gestational trajectories of C10, C10:1, and C12 acylcarnitine levels were significantly associated with neonatal anthropometry. Further studies are needed to verify and further explore the potential clinical utility of these findings. Funding Sources Eunice Kennedy Shriver National Institute of Child Health and Human Development intramural funding; American Recovery and Reinvestment Act funding.

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Longitudinal Maternal Vitamin D Status during Pregnancy Is Associated with Neonatal Anthropometric Measures

Nutrients ◽

10.3390/nu10111631 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1631 ◽

Cited By ~ 5

Author(s):

Ellen Francis ◽

Stefanie Hinkle ◽

Yiqing Song ◽

Shristi Rawal ◽

Sarah Donnelly ◽

...

Keyword(s):

Vitamin D ◽

Linear Models ◽

Z Score ◽

Anthropometric Measures ◽

Hydroxyvitamin D ◽

Prepregnancy Bmi ◽

Z Scores ◽

Gestational Week ◽

25 Hydroxyvitamin D ◽

Lower Birthweight

Findings on maternal 25-hydroxyvitamin D (25[OH]D) and neonatal anthropometry are inconsistent, and may at least be partly due to variations in gestational week (GW) of 25(OH)D measurement and the lack of longitudinal 25(OH)D measurements across gestation. The aim of the current study was to examine the associations of longitudinal measures of maternal 25(OH)D and neonatal anthropometry at birth. This study included 321 mother–offspring pairs enrolled in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies–Singletons. This study was a prospective cohort design without supplementation and without data on dietary supplementation. Nevertheless, measurement of plasma 25(OH)D reflects vitamin D from different sources, including supplementation. Maternal concentrations of total 25(OH)D were measured at 10–14, 15–26, 23–31, and 33–39 GW and categorized as <50 nmol/L, 50–75 nmol/L, and >75 nmol/L. Generalized linear models were used to examine associations of 25(OH)D at each time-point with neonate birthweight z-score, length, and sum of skinfolds at birth. At 10–14 GW, 16.8% and 49.2% of women had 25(OH)D <50 nmol/L and between 50–75 nmol/L, respectively. The association of maternal 25(OH)D with neonatal anthropometry differed by GW and women’s prepregnancy BMI (normal (<25.0 kg/m2), overweight/obese (25.0–44.9 kg/m2)). All analyses were stratified by prepregnancy BMI status. Among women with an overweight/obese BMI, 25(OH)D <50 nmol/L at 10–14 GW was associated with lower birthweight z-score (0.56; 95% CI: −0.99, −0.13) and length (−1.56 cm; 95% CI: −3.07, −0.06), and at 23–31 GW was associated with shorter length (−2.77 cm; 95% CI: −13.38, −4.98) and lower sum of skinfolds (−9.18 mm; 95% CI: −13.38, −4.98). Among women with a normal BMI, 25(OH)D <50 nmol/L at 10–14 GW was associated with lower sum of skinfolds (−2.64 mm; 95% CI: −5.03, −0.24), at 23–31 GW was associated with larger birthweight z-scores (0.64; 95% CI: 0.03, 1.25), and at 33-39 GW with both higher birthweight z-score (1.22; 95% CI: 0.71, 1.73) and longer length (1.94 cm; 95% CI: 0.37, 3.52). Maternal 25(OH)D status during pregnancy was associated with neonatal anthropometric measures, and the associations were specific to GW of 25(OH)D measurement and prepregnancy BMI.

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Abstract P171: A Longitudinal Study Of Maternal Thyroid Hormone Trajectories And Neonatal Anthropometric Measures

Circulation ◽

10.1161/circ.143.suppl_1.p171 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Shristi Rawal ◽

Lauren Berube ◽

Stefanie Hinkle ◽

Jing Wu ◽

Cuilin Zhang

Keyword(s):

Thyroid Hormones ◽

Fetal Growth ◽

Latent Class ◽

Blood Collection ◽

Z Score ◽

Linear Regression Models ◽

Anthropometric Measures ◽

Infant Sex ◽

Maternal Thyroid ◽

In Pregnancy

Introduction: Maternal thyroid hormones (TH) are essential for fetal growth and development. While prior studies have examined associations of TH with birthweight (BW), data on other neonatal anthropometric measures are scarce. Here we aimed to examine relations between TH and its trajectory across pregnancy with neonatal anthropometrics in a multi-racial pregnancy cohort. Hypothesis: We hypothesized that distinct TH trajectories across gestation would explain differences in neonatal anthropometrics including BW, length and sum of skinfolds (SSF). Methods: We used longitudinal data from 321 women who were included in a gestational diabetes (GDM) case-control study nested within the NICHD Fetal Growth Studies-Singletons Cohort (n=2802). Plasma free triiodothyronine (fT3), free thyroxine (fT4) and thyroid-stimulating hormone (TSH) were measured, and fT3/fT4 ratio was derived, using blood samples collected at gestational weeks (GW) 10-14, 15-26, 23-31 and 33-39. TH trajectories were identified using a latent class trajectory approach. BW was abstracted from medical records. Neonatal length and SSF were measured. To examine associations between TH levels and neonatal outcomes, we used weighted linear regression models, adjusted for maternal age, race/ethnicity, GW at blood collection, pre-pregnancy BMI, education, parity, infant sex, GDM diagnosis (33-39 GW only) and number of days post-delivery (length and SSF only). Results: Overall, neonates of women in the highest fT3 tertile at 33-39 GW had marginally higher BW (β: 205.5 g, 95% CI -23.4, 434.4) and BW z-score (β: 0.4, 95% CI 0.0, 0.8) than neonates of women in the lowest tertile. Significant interactions were observed by infant sex for associations of fT4 and BW, BW z-score and neonatal length (all p for interactions <0.05). Specifically, female neonates of women in the highest fT4 tertile had lower BW, BW z-score and length than those in the lowest tertile at 15-26 (β BW -416.3 g, 95% CI -753.7, -79.0; β BW zscore -0.5, 95% CI -0.9, -0.1; β length -1.5 cm, 95% CI -2.8, -0.1, respectively) and 23-31 GW (β BW -357.0 g, 95% CI -635.6, -78.4; β BW zscore -0.7, 95% CI -1.3, -0.1; β length -1.8 cm, 95% CI -3.3, -0.2, respectively). Across gestation, a low fT3 trajectory (class size 5.5%) was associated with lower neonatal SSF (β: -3.2 mm, 95% CI -6.0, -0.5) than an intermediate/referent trajectory (60.1%). A high fT3/fT4 ratio trajectory (16.2%) was associated with higher BW (β: 300.5 g, 95% CI 41.7, 559.4), BW z-score (β: 0.6, 95% CI 0.3, 0.8), and neonatal SSF (β: 3.3 mm, 95% CI 0.7, 5.9) than an intermediate/referent trajectory (44.3%). Conclusions: Our study suggests that both overall TH trajectory across gestation and TH levels at specific timepoints in pregnancy may be related to neonatal anthropometrics, with associations varying by infant sex. These novel data support the significance of monitoring thyroid hormones longitudinally in pregnancy.

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Cancer Signaling Transcriptome Is Upregulated in Type 2 Diabetes Mellitus

Journal of Clinical Medicine ◽

10.3390/jcm10010085 ◽

2020 ◽

Vol 10 (1) ◽

pp. 85

Author(s):

Enrique Almanza-Aguilera ◽

Álvaro Hernáez ◽

Dolores Corella ◽

Albert Sanllorente ◽

Emilio Ros ◽

...

Keyword(s):

Type 2 Diabetes ◽

Signaling Pathways ◽

Differentially Expressed Genes ◽

Differentially Expressed ◽

Log P ◽

P Value ◽

Z Score ◽

Elderly Individuals ◽

Cancer Signaling

We aimed to explore the differences in the whole transcriptome of peripheral blood mononuclear cells between elderly individuals with and without type 2 diabetes (T2D). We conducted a microarray-based transcriptome analysis of 19 individuals with T2D and 15 without. Differentially expressed genes according to linear models were submitted to the Ingenuity Pathway Analysis system to conduct a functional enrichment analysis. We established that diseases, biological functions, and canonical signaling pathways were significantly associated with T2D patients when their logarithms of Benjamini–Hochberg-adjusted p-value were >1.30 and their absolute z-scores were >2.0 (≥2.0 meant “upregulation” and ≤ −2.0 “downregulation”). Cancer signaling pathways were the most upregulated ones in T2D (z-score = 2.63, −log(p-value) = 32.3; 88.5% (n = 906) of the total differentially expressed genes located in these pathways). In particular, integrin (z-score = 2.52, −log(p-value) = 2.03) and paxillin (z-score = 2.33, −log(p-value) = 1.46) signaling pathways were predicted to be upregulated, whereas the Rho guanosine diphosphate (Rho-GDP) dissociation inhibitor signaling pathway was predicted to be downregulated in T2D individuals (z-score = −2.14, −log(p-value) = 2.41). Our results suggest that, at transcriptional expression level, elderly individuals with T2D present an increased activation of signaling pathways related to neoplastic processes, T-cell activation and migration, and inflammation.

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The Tri-ponderal Mass Index is associated with adiposity in adolescent type 2 diabetes mellitus: a cross-sectional analysis

Scientific Reports ◽

10.1038/s41598-021-88705-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Haifa Alfaraidi ◽

Brandy Wicklow ◽

Allison B. Dart ◽

Elizabeth Sellers ◽

Jonathan McGavock ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Type 2 Diabetes Mellitus ◽

Secondary Data ◽

P Value ◽

Z Score ◽

Cross Sectional ◽

The Metabolic Syndrome

AbstractPediatric type 2 diabetes mellitus (T2DM) patients are often overweight or obese, yet there are no validated clinical measures of adiposity to stratify cardiometabolic risk in this population. The tri-ponderal mass index (TMI, kg/m3) has recently been reported as a measure of adiposity in children, but there has been no validation of the association of TMI with adiposity in pediatric T2DM. We hypothesized that in children with T2DM, the TMI can serve as a more accurate measure of adiposity when compared to BMI z-score, and that it is associated with components of the metabolic syndrome. This is a cross-sectional secondary data analysis from the Improving Renal Complications in Adolescents with Type 2 Diabetes Through REsearch (iCARE) study (n = 116, age 10.20–17.90 years). Spearman’s correlations and multivariable regression were used in the analyses. When compared to DXA, TMI demonstrated significant correlation with total adiposity versus BMI z-score (TMI r = 0.74, p-value < 0.0001; BMI z-score r = − 0.08, p-value 0.403). In regression analyses, TMI was associated with WHtR (B = 35.54, 95% CI 28.81, 42.27, p-value < 0.0001), MAP dipping (B = 1.73, 95% CI 0.12, 3.33, p-value = 0.035), and HDL (B = − 5.83, 95% CI − 10.13, − 1.54, p-value = 0.008). In conclusion, TMI is associated with adiposity and components of the metabolic syndrome in pediatric T2DM patients.

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Latent Class Trajectory Analysis of Risk Factors Uncovers Progression to Type 2 Diabetes

Journal of Endocrinological Science ◽

10.29245/2767-5157/2021/1.1118 ◽

2021 ◽

Vol 3 (1) ◽

pp. 26-35

Author(s):

Qilu Yu ◽

Maurice C. Johnson ◽

Howard A. Fishbein ◽

Rebecca J. Birch ◽

Xiaoshu Zhu ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Trajectory Analysis ◽

Latent Class ◽

P Value ◽

Blood Pressures ◽

Adjusted Rate ◽

Rate Ratios ◽

Latent Class Trajectory Analysis

We identified trajectories of diabetes risk factors in the Longitudinal Epidemiologic Assessment of Diabetes Risk (LEADR) cohort analyzing 8 years of electronic health records on 1.4 million patients, and investigated associations between trajectories and progression to new onset Type 2 diabetes. Design and Methods: Analyzing LEADR data (2010-2016), we applied Latent Class Trajectory Analysis (LCTA) to classify patterns of risk factor change. There were 824,043 patients with BMIs; 955,128 patients with systolic blood pressures; 957,491 patients with diastolic blood pressures; 300,137 patients with HDLs; 267,553 patients with non-HDL cholesterols; and 297,026 patients with triglycerides. Patients had to have data for all risk factors being assessed. Association between trajectories and incidence of type 2 diabetes for 94,551 patients was assessed using negative binomial regression analysis. Results: Compared to a static BMI trajectory, those with a sustained weight increase (25%+ from starting BMI) were at higher risk of type 2 diabetes over 4.8 years of follow-up (range 2.0 to 8.0 years) (adjusted rate ratios ranged 1.53-1.62, p-value<0.05). Patients with a BMI decrease trajectory (of ~10%), were at reduced risk of diabetes (adjusted rate ratios ranged 0.54-0.74, p-value<.05). BP and lipid trajectories had significant associations with diabetes onset. Conclusions: Regardless of the starting BMI, those who increased their BMI by 25% within two years and maintained the higher weight were significantly at increased risk of type 2 diabetes. Monitoring BMI change and other known risk factor trajectories, BP and lipids, are additional tools for identifying patients at risk for type 2 diabetes.

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Association between risk of type 2 diabetes and changes in energy intake at breakfast and dinner over 14 years: a latent class trajectory analysis from the China health and nutrition Survey, 1997–2011

BMJ Open ◽

10.1136/bmjopen-2020-046183 ◽

2021 ◽

Vol 11 (7) ◽

pp. e046183

Author(s):

Xiyun Ren ◽

Jian Gao ◽

Tianshu Han ◽

Changhao Sun

Keyword(s):

Type 2 Diabetes ◽

Energy Consumption ◽

Energy Intake ◽

Latent Class ◽

Early Stage ◽

Harmful Effect ◽

Nutrition Survey ◽

Health And Nutrition ◽

Diabetes Status

ObjectiveThis study aimed to investigate the association between the trajectories of energy consumption at dinner versus breakfast and the risk of type 2 diabetes (T2D).DesignCohort study.SettingThe study was conducted in China.ParticipantsA total of 10 727 adults, including 5239 men and 5488 women, with a mean age of 42.7±11.2 years and a mean follow-up time of 9.1 years, met the study criteria and completed a questionnaire about energy intake and diabetes status from the China Health and Nutrition Survey in 1997–2011.Primary outcome measuresParticipants were divided into subgroups based on the trajectories of the ratio of energy consumption at dinner versus breakfast. Cox multivariate regression models were used to explore the associations between different trajectories and the risk of T2D after adjustment for confounders and their risk factors. Mediation analysis was performed to explore the intermediary effect of triacylglycerol (TG), total cholesterol (TC), uric acid (UA) and apolipoprotein B (ApoB) between the trajectories and the risk of T2D.ResultsFor energy consumption at dinner versus breakfast, compared with a low-stable trajectory, the adjusted HR of T2D in low-increasing from early-stage trajectory was 1.29 (95% CI 1.04 to 1.60). TG, TC, UA and ApoB were significantly higher in low-increasing from early-stage trajectory than other trajectories and play partial regulation roles between trajectories and T2D.ConclusionsThis study emphasised the harmful effect of a gradual increase in the ratio of energy consumption at dinner versus breakfast from early stage on the development of T2D and partially mediated by TG, TC, UA and ApoB, highlighting that it is necessary to intake more energy at breakfast compared with dinner to prevent T2D in adults.

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Skin autofluorescence predicts new cardiovascular disease and mortality in people with type 2 diabetes

BMC Endocrine Disorders ◽

10.1186/s12902-020-00676-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Henderikus E. Boersma ◽

Robert P. van Waateringe ◽

Melanie M. van der Klauw ◽

Reindert Graaff ◽

Andrew D. Paterson ◽

...

Keyword(s):

Blood Pressure ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Fasting Blood Glucose ◽

Multivariable Analysis ◽

Oral Glucose ◽

Skin Autofluorescence ◽

Z Score

Abstract Background Skin autofluorescence (SAF) is a non-invasive marker of tissue accumulation of advanced glycation endproducts (AGE). Recently, we demonstrated in the general population that elevated SAF levels predict the development of type 2 diabetes (T2D), cardiovascular disease (CVD) and mortality. We evaluated whether elevated SAF may predict the development of CVD and mortality in individuals with T2D. Methods We included 2349 people with T2D, available baseline SAF measurements (measured with the AGE reader) and follow-up data from the Lifelines Cohort Study. Of them, 2071 had no clinical CVD at baseline. 60% were already diagnosed with diabetes (median duration 5, IQR 2–9 years), while 40% were detected during the baseline examination by elevated fasting blood glucose ≥7.0 mmol/l) and/or HbA1c ≥6.5% (48 mmol/mol). Results Mean (±SD) age was 57 ± 12 yrs., BMI 30.2 ± 5.4 kg/m2. 11% of participants with known T2D were treated with diet, the others used oral glucose-lowering medication, with or without insulin; 6% was using insulin alone. Participants with known T2D had higher SAF than those with newly-detected T2D (SAF Z-score 0.56 ± 0.99 vs 0.34 ± 0.89 AU, p < 0.001), which reflects a longer duration of hyperglycaemia in the former group. Participants with existing CVD and T2D had the highest SAF Z-score: 0.78 ± 1.25 AU. During a median follow-up of 3.7 yrs., 195 (7.6%) developed an atherosclerotic CVD event, while 137 (5.4%) died. SAF was strongly associated with the combined outcome of a new CVD event or mortality (OR 2.59, 95% CI 2.10–3.20, p < 0.001), as well as incidence of CVD (OR 2.05, 95% CI 1.61–2.61, p < 0.001) and death (OR 2.98, 2.25–3.94, p < 0.001) as a single outcome. In multivariable analysis for the combined endpoint, SAF retained its significance when sex, systolic blood pressure, HbA1c, total cholesterol, eGFR, as well as antihypertensive and statin medication were included. In a similar multivariable model, SAF was independently associated with mortality as a single outcome, but not with incident CVD. Conclusions Measuring SAF can assist in prediction of incident cardiovascular disease and mortality in individuals with T2D. SAF showed a stronger association with future CVD events and mortality than cholesterol or blood pressure levels.

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Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001948 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001948

Author(s):

Marion Denos ◽

Xiao-Mei Mai ◽

Bjørn Olav Åsvold ◽

Elin Pettersen Sørgjerd ◽

Yue Chen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Family History ◽

Genetic Predisposition ◽

Effect Modification ◽

P Value ◽

Family History Of Diabetes ◽

Increased Risk ◽

History Of

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).ResultsOver 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).ConclusionSerum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

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