Glycemic control and neonatal outcomes in twin pregnancies with gestational diabetes mellitus.

BACKGROUND: Preliminary data suggest that strict glycemic control in twin pregnancies with gestational diabetes mellitus may not improve outcomes but might increase the risk of fetal growth restriction. OBJECTIVE: This study aimed to investigate the association of maternal glycemic control with the risk of gestational diabetes mellitus-related complications and small for gestational age in twin pregnancies complicated by gestational diabetes mellitus. STUDY DESIGN: This was a retrospective cohort study of all patients with a twin pregnancy complicated by gestational diabetes mellitus in a single tertiary center between 2011 and 2020, and a matched control group of patients with a twin pregnancy without gestational diabetes mellitus in a 1:3 ratio. The exposure was the level of glycemic control, described as the proportion of fasting, postprandial, and overall glucose values within target. Good glycemic control was defined as a proportion of values within target above the 50th percentile. The first coprimary outcome was a composite variable of neonatal morbidity, defined as at least 1 of the following: birthweight >90th centile for gestational age, hypoglycemia requiring treatment, jaundice requiring phototherapy, birth trauma, or admission to the neonatal intensive care unit at term. A second coprimary outcome was small for gestational age, defined as birthweight <10th centile or <3rd centile for gestational age. Associations between the level of glycemic control and the study outcomes were estimated using logistic regression analysis and were expressed as adjusted odds ratio with 95% confidence interval. RESULTS: A total of 105 patients with gestational diabetes mellitus in a twin pregnancy met the study criteria. The overall rate of the primary outcome was 32.4% (34/105), and the overall proportion of pregnancies with a small for gestational age newborn at birth was 43.8% (46/105). Good glycemic control was not associated with a reduction in the risk of composite neonatal morbidity when compared with suboptimal glycemic control (32.1% vs 32.7%; adjusted odds ratio, 2.06 [95% confidence interval, 0.77-5.49]). However, good glycemic control was associated with higher odds of small for gestational age compared with nongestational diabetes mellitus pregnancies, especially in the subgroup of diet-treated gestational diabetes mellitus (65.5% vs 34.0%, respectively; adjusted odds ratio, 4.17 [95% confidence interval, 1.74-10.01] for small for gestational age <10th centile; and 24.1% vs 7.0%, respectively; adjusted odds ratio, 3.97 [95% confidence interval, 1.42-11.10] for small for gestational age <3rd centile). In contrast, the rate of small for gestational age in gestational diabetes mellitus pregnancies with suboptimal control was not considerably different when compared with non-gestational diabetes mellitus pregnancies. In addition, in cases of diet-treated gestational diabetes mellitus, good glycemic control was associated with a left-shift of the distribution of birthweight centiles, whereas the distribution of birthweight centiles among gestational diabetes mellitus pregnancies with suboptimal control was similar to that of nongestational diabetes mellitus pregnancies. CONCLUSION: In patients with gestational diabetes mellitus in a twin pregnancy, good glycemic control is not associated with a reduction in the risk of gestational diabetes mellitus-related complications but may increase the risk of a small for gestational age newborn in the subgroup of patients with mild (diet-treated) gestational diabetes mellitus. These findings further question whether the gestational diabetes mellitus glycemic targets used in singleton pregnancies also apply to twin pregnancies and support the concern that applying the same diagnostic criteria and glycemic targets in twin pregnancies may result in overdiagnosis and overtreatment of gestational diabetes mellitus and potential neonatal harm.

Folic Acid Supplementation in Early Pregnancy, Homocysteine Concentration, and Risk of Gestational Diabetes Mellitus.

We used a prospective cohort of pregnant women at 12 to 20 weeks gestation between 2002 and 2008 in Ottawa and Kingston to evaluate the impact of early pregnancy folic acid supplementation on the risk of gestational diabetes mellitus. Among 7552 eligible women, 84 (1.11%) were diagnosed of gestational diabetes mellitus. Non-significant associations were observed between gestational diabetes mellitus and folate supplementation, homocysteine levels, and methylenetetrahydrofolate reductase 677 TT genotype. Although we found no significant associations between folic acid supplementation and the risk of gestational diabetes mellitus, genetic associations were not confounded by lifestyle or socioeconomic factors, which may have biased previous studies.

Serum Folate Shows an Inverse Association with Blood Pressure in a Cohort of Chinese Women of Childbearing Age: A Cross-Sectional Study.

BACKGROUND: It has been reported that higher folate intake from food and supplementation is associated with decreased blood pressure (BP). The association between serum folate concentration and BP has been examined in few studies. We aim to examine the association between serum folate and BP levels in a cohort of young Chinese women. METHODS: We used the baseline data from a pre-conception cohort of women of childbearing age in Liuyang, China, for this study. Demographic data were collected by structured interview. Serum folate concentration was measured by immunoassay, and homocysteine, blood glucose, triglyceride and total cholesterol were measured through standardized clinical procedures. Multiple linear regression and principal component regression model were applied in the analysis. RESULTS: A total of 1,532 healthy normotensive non-pregnant women were included in the final analysis. The mean concentration of serum folate was 7.5 ± 5.4 nmol/L and 55% of the women presented with folate deficiency (< 6.8 nmol/L). Multiple linear regression and principal component regression showed that serum folate levels were inversely associated with systolic and diastolic BP, after adjusting for demographic, anthropometric, and biochemical factors. CONCLUSIONS: Serum folate is inversely associated with BP in non-pregnant women of childbearing age with high prevalence of folate deficiency.

The Relationship Between Parathyroid Hormone and 25-Hydroxyvitamin D During and After Pregnancy.

CONTEXT: There is debate about whether women may need greater vitamin D supplementation when pregnant. However, it is unclear whether the 25-hydroxyvitamin D (25-OH-D) concentration required for suppression of PTH (ie, suggesting vitamin D sufficiency) differs between pregnancy and the nongravid state. OBJECTIVE: To systematically characterize the relationship between 25-OH-D and PTH during and after pregnancy. DESIGN/SETTING/PARTICIPANTS: In this study, 468 women underwent serial assessment of serum 25-OH-D and PTH in late pregnancy, at 3 months postpartum, and at 12 months postpartum. At each visit, segmented regression analysis was performed to: 1) determine the best model to fit the relationship between 25-OH-D and PTH; and 2) identify the 25-OH-D threshold above which PTH is maximally suppressed. RESULTS: Serum 25-OH-D and PTH were inversely correlated at each of the pregnancy (r = −0.33; P < .0001), 3 months postpartum (r = −0.37; P < .0001), and 12 months postpartum (r = −0.34; P < .0001) assessments. In pregnancy, PTH first rises when 25-OH-D falls below 82 nmol/L (95% confidence interval, 61­103) and follows a linear relationship with declining 25-OH-D thereafter. In contrast, at both postpartum visits, there was a curvilinear relationship between 25-OH-D and PTH below the 25-OH-D threshold at which PTH is suppressed (71 nmol/L [61­81] at 3 months and 81 nmol/L [61­100] at 12 months). The 25-OH-D thresholds for PTH suppression in pregnancy and at 3 and 12 months postpartum were not significantly different from one another (all pairwise P ≥ .26). CONCLUSION: Although the shape of the relationship between 25-OH-D and PTH differs between pregnancy and the postpartum, the 25-OH-D thresholds for PTH suppression are similar, supporting comparable targets for vitamin D supplementation.

The persistence of maternal vitamin D deficiency and insufficiency during pregnancy and lactation irrespective of season and supplementation.

BACKGROUND: Pregnancy and lactation comprise a critical window spanning all seasons during which maternal vitamin D status potentially may influence the long-term health of the newborn. Women typically receive calcium/vitamin D supplementation through antenatal vitamins, but there has been limited serial evaluation of maternal vitamin D status across this critical window. DESIGN/PATIENTS/MEASUREMENTS: In this prospective observational cohort study, 467 women in Toronto, Canada, underwent measurement of serum 25-hydroxy vitamin D (25-OH-D) at mean 29·7 ± 2·9 weeks' gestation, 3 months postpartum and 12 months postpartum, enabling serial assessment across 3 seasons. At each assessment, vitamin D status was classified as deficiency (25-OH-D<50 nmol/l), insufficiency (25-OH-D≥50 nmol/l and <75 nmol/l) or sufficiency (25-OH-D≥75 nmol/l). RESULTS: The prevalence rates of vitamin D deficiency and insufficiency were 31·5% and 35·1% in pregnancy, 33·4% and 35·3% at 3 months, and 35·6% and 33·8% at 12 months postpartum, respectively. These high rates remained stable over time (P = 0·49) despite declining usage of antenatal calcium/vitamin D supplementation from pregnancy to 3 months to 12 months postpartum (P < 0·001). Indeed, on mixed model analyses, vitamin D deficiency and insufficiency in pregnancy were independently associated with decrements in average 25-OH-D over time of 49·6 nmol/l and 26·4 nmol/l, respectively (both P < 0·001). In contrast, season of baseline assessment and use of calcium/vitamin D supplements were independently associated with changes in 25-OH-D in the range of 3-5 nmol/l (both P < 0·008). CONCLUSIONS: The persistence of vitamin D deficiency/insufficiency during pregnancy and lactation, irrespective of season and supplementation, supports the emerging concept that current vitamin D supplementation in antenatal care is likely inadequate.

Prospective association of 25(OH)D with metabolic syndrome.

CONTEXT: Vitamin D may play a role in the aetiology of the metabolic syndrome (MetS), yet the majority of previous studies have been cross-sectional, and the limited number of prospective studies has yielded inconsistent results. OBJECTIVE: To examine the prospective association of vitamin D [25-hydroxyvitamin D, 25(OH)D] with MetS in a multi-ethnic cohort of adults in Ontario, Canada. DESIGN: Nondiabetic individuals with pre-existing MetS risk factors were recruited for participation in the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study, a longitudinal study of the determinants of insulin resistance and MetS. METHODS: Of the 654 participants enrolled at baseline, 489 attended a 3-year follow-up visit. There were 301 participants eligible for the analysis of 25(OH)D with incident MetS (age 49·2 ± 9·3 years old, 75·4% female), after excluding 188 (38·5%) prevalent MetS cases at baseline. Longitudinal change in MetS components was assessed in the entire follow-up cohort. RESULTS: There were 76 (15·5%) participants who developed MetS over the 3-years of follow-up. Multivariate logistic regression analyses indicated a decreased risk of MetS at follow-up per standard deviation increase in baseline 25(OH)D after adjustment for sociodemographics, season, baseline and change in supplement use and physical activity and insulin resistance (OR = 0·63, 95% CI 0·44-0·90). Multivariate linear regression analyses revealed a significant inverse association of baseline 25(OH)D with fasting glucose at follow-up (ß = -0·0005, P = 0·025). CONCLUSIONS: There was a significant inverse association of baseline 25(OH)D with incident MetS, which may be partly driven by its association with glucose homoeostasis.

Vitamin D status and cardiometabolic assessment in infancy.

BACKGROUND: Infants are at risk of vitamin D insufficiency, owing to their limited exposure to direct sunlight and the low levels of vitamin D in breast milk. Although vitamin D insufficiency has been associated with cardiometabolic risk factors in children, these associations have not been studied in infants, despite their unique risks. Therefore, we sought to determine whether vitamin D status was associated with cardiometabolic measures in infants. METHODS: Ninety-nine full-term infants were evaluated at the age of 1 y with measurement of 25-hydroxy vitamin D (25-OH-D) and an array of traditional (fasting glucose, insulin, low-density-lipoprotein cholesterol, high-density-lipoprotein cholesterol, triglycerides) and emerging (C-reactive protein, adiponectin, leptin) cardiometabolic risk factors. On the basis of 25-OH-D levels, infants were classified as vitamin D sufficient (n = 59), vitamin D insufficient (n = 29), or vitamin D deficient (n = 11). RESULTS: Duration of exclusive breastfeeding and prevalence of nonwhite ethnicity were highest in the vitamin D-deficient group (P = 0.05 and 0.03, respectively). Current use of vitamin D supplementation was highest in the sufficient group (P = 0.02). Of note, however, there were no significant differences among the three groups in any of the cardiometabolic risk factors, on both unadjusted and covariate-adjusted analyses. CONCLUSION: Vitamin D insufficiency/deficiency is not associated with an adverse cardiometabolic risk factor profile in 1-y-old infants.

Role of vitamin D in the pathophysiology and treatment of type 2 diabetes.

The secosteroid vitamin D is best known for its role in calcium regulation and bone metabolism. Recently, however, an emerging body of evidence has suggested that vitamin D may have previously-unrecognized effects on a variety of physiologic processes, including those relating to glucose homeostasis. Indeed, vitamin D insufficiency has been linked with type 2 diabetes (T2DM). In this review, the potential association between vitamin D and T2DM will be evaluated from both a pathophysiologic and clinical perspective. We consider the biologic evidence in support of a mechanistic contribution of vitamin D insufficiency to insulin resistance and beta-cell dysfunction, the two main pathophysiologic defects underlying T2DM. We also evaluate the clinical data linking vitamin D with these metabolic defects and dysglycemia. Finally, interventional studies addressing the effect of vitamin D supplementation on glucose homeostasis are considered. At present, this evolving literature is marked by many conflicting results and methodologic limitations, such that definitive conclusion on the role of vitamin D in T2DM remains elusive. Nevertheless, in light of the widespread prevalence of both vitamin D insufficiency and T2DM, this potential relationship could hold enormous public health implications and hence demands further study to address its unresolved questions.

Prospective associations of vitamin D with ß-cell function and glycemia: the PROspective Metabolism and ISlet cell Evaluation (PROMISE) cohort study.

OBJECTIVE: To examine the prospective associations of baseline vitamin D [25-hydroxyvitamin D; 25(OH)D] with insulin resistance (IR), ß-cell function, and glucose homeostasis in subjects at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: We followed 489 subjects, aged 50 ± 10 years, for 3 years. At baseline and follow-up, 75-g oral glucose tolerance tests (OGTTs) were administered. IR was measured using the Matsuda index (IS(OGTT)) and the homeostasis model assessment of IR (HOMA-IR), ß-cell function was determined using both the insulinogenic index divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2), and glycemia was assessed using the area under the glucose curve (AUC(glucose)). Regression models were adjusted for age, sex, ethnicity, season, and baseline value of the outcome variable, as well as baseline and change in physical activity, vitamin D supplement use, and BMI. RESULTS: Multivariate linear regression analyses indicated no significant association of baseline 25(OH)D with follow-up IS(OGTT) or HOMA-IR. There were, however, significant positive associations of baseline 25(OH)D with follow-up IGI/IR (ß = 0.005, P = 0.015) and ISSI-2 (ß = 0.002, P = 0.023) and a significant inverse association of baseline 25(OH)D with follow-up AUC(glucose) (ß = -0.001, P = 0.007). Progression to dysglycemia (impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes) occurred in 116 subjects. Logistic regression analyses indicated a significant reduced risk of progression with higher baseline 25(OH)D (adjusted odds ratio 0.69 [95% CI 0.53-0.89]), but this association was not significant after additional adjustment for baseline and change in BMI (0.78 [0.59-1.02]). CONCLUSIONS: Higher baseline 25(OH)D independently predicted better ß-cell function and lower AUC(glucose) at follow-up, supporting a potential role for vitamin D in type 2 diabetes etiology.

Association of 25(OH)D and PTH with metabolic syndrome and its traditional and nontraditional components.

CONTEXT: Emerging evidence suggests that 25-hydroxy vitamin D [25(OH)D] and PTH may play a role in the etiology of the metabolic syndrome (MetS). However, evidence to date is limited and inconsistent, and few studies have examined associations with nontraditional MetS components. OBJECTIVE: The objective of the study was to examine the association of vitamin D and PTH with MetS and its traditional and nontraditional components in a large multiethnic sample. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, we examined 654 participants from London and Toronto, Ontario, Canada, aged 30 yr and older with risk factors for type 2 diabetes. MAIN OUTCOME MEASURES: Presence of MetS and its traditional and nontraditional components was measured. RESULTS: Approximately 43% of the study participants were classified as having MetS. Higher 25(OH)D was significantly associated with a reduced presence of MetS after adjustment for age, sex, season, ethnicity, supplement use, physical activity, and PTH (odds ratio 0.76, 95% confidence interval 0.62-0.93). PTH was not associated with the presence of MetS after multivariate adjustment. Multivariate linear regression analyses indicated significant adjusted inverse associations of 25(OH)D with waist circumference, triglyceride level, fasting insulin, and alanine transaminase (P < 0.041). Elevated PTH was positively associated with waist circumference and high-density lipoprotein cholesterol (P < 0.04). Other associations between PTH and MetS components were attenuated after adjustment for adiposity. CONCLUSIONS: Serum 25(OH)D, but not PTH, was significantly associated with MetS as well as a number of MetS components after multivariate adjustment. These results suggest that low 25(OH)D may play a role in the etiology of the MetS.

Association of vitamin D with insulin resistance and beta-cell dysfunction in subjects at risk for type 2 diabetes.

OBJECTIVE: To examine cross-sectional associations of serum vitamin D [25-hydroxyvitamin D, 25(OH)D] concentration with insulin resistance (IR) and beta-cell dysfunction in 712 subjects at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS: Serum 25(OH)D was determined using a chemiluminescence immunoassay. Insulin sensitivity/resistance were measured using the Matsuda insulin sensitivity index for oral glucose tolerance tests (IS(OGTT)) and homeostasis model assessment of insulin resistance HOMA-IR. beta-Cell function was determined using both the insulinogenic index (IGI) divided by HOMA-IR (IGI/IR) and the insulin secretion sensitivity index-2 (ISSI-2). RESULTS Linear regression analyses indicated independent associations of 25(OH)D with IS(OGTT) and HOMA-IR (beta = 0.004, P = 0.0003, and beta = -0.003, P = 0.0072, respectively) and with IGI/IR and ISSI-2 (beta = 0.004, P = 0.0286, and beta = 0.003, P = 0.0011, respectively) after adjusting for sociodemographics, physical activity, supplement use, parathyroid hormone, and BMI. CONCLUSIONS: Vitamin D may play a role in the pathogenesis of type 2 diabetes, as 25(OH)D concentration was independently associated with both insulin sensitivity and beta-cell function among individuals at risk of type 2 diabetes.