Long-term Cardiovascular Disease After Adverse Pregnancy Outcomes.

Cardiovascular disease (CVD) is the leading cause of death among women. Adverse pregnancy outcomes (APOs) are cardiovascular risk factors that are unique to women and include gestational diabetes (GDM) and preeclampsia. While these risk factors emerge during the reproductive years and allow for early risk reduction counseling, they are often overlooked and not elicited by providers. This mini-review focuses primarily on GDM and preeclampsia, their relationship with CVD, mechanisms by which these conditions lead to CVD, and management, pharmacological and nonpharmacological, for the clinician who is caring for a woman with a history of an APO.

Carbohydrate Intake and Oral Glucose Tolerance Test Results in the Postpartum Period.

CONTEXT: The American Diabetes Association (ADA) recommends a 3-day preparatory diet prior to a diagnostic oral glucose tolerance test (OGTT), a test often recommended in postpartum individuals with a history of gestational diabetes (GDM). OBJECTIVE: Evaluate the relationship between carbohydrate intake and OGTT glucose in 2 cohorts of postpartum individuals. METHODS: We performed analyses of postpartum individuals from 2 prospective studies with recent GDM (Balance after Baby Intervention, BABI, n = 177) or risk factors for GDM (Study of Pregnancy Regulation of INsulin and Glucose, SPRING, n = 104) .We measured carbohydrate intake using 24-hour dietary recalls (SPRING) or Food Frequency Questionnaire (BABI) and performed 2-hour 75-g OGTTs. The main outcome measure was 120-minute post-OGTT glucose. RESULTS: There was no relationship between carbohydrate intake and 120-minute post-OGTT glucose level in either study population (SPRING: ß = 0.03, [-5.5, 5.5] mg/dL, P = .99; BABI: ß = -3.1, [-9.5, 3.4] mg/dL, P = .35). Adding breastfeeding status to the model did not change results (SPRING ß = -0.14, [-5.7, 5.5] mg/dL, P = .95; BABI ß = -3.9, [-10.4, 2.7] mg/dL, P = .25). There was, however, an inverse relationship between glycemic index and 120-minute post OGTT glucose (BABI: ß = -1.1, [-2.2, -0.03] mg/dL, P = .04). CONCLUSION: Carbohydrate intake is not associated with post-OGTT glucose levels among postpartum individuals. Dietary preparation prior to the OGTT may not be necessary in this population.

Longitudinal changes in glucose during pregnancy in women with gestational diabetes risk factors.

AIMS/HYPOTHESIS: Despite recommendations to screen women with diabetes risk factors for hyperglycaemia in the first trimester, criteria for normal glucose values in early pregnancy have not been firmly established. We aimed to compare glucose levels in early pregnancy with those later in gestation and outside of pregnancy in women with diabetes risk factors. METHODS: In pregnant women (N = 123) followed longitudinally through the postpartum period, and a separate cohort of non-pregnant women (N = 65), we performed 75 g oral glucose tolerance tests. All participants had one or more risk factors for diabetes. Using linear regression, we tested for differences in glucose levels between non-pregnant and pregnant women at early (7-15 weeks) and mid-late (24-32 weeks) gestation as well as postpartum, with adjustment for maternal age, parity, marital status and BMI. In a longitudinal analysis using mixed-effects models, we tested for differences in glucose levels across early and mid-late pregnancy compared with postpartum. Differences are expressed as ß (95% CI). RESULTS: Fasting glucose was lower in pregnant compared with non-pregnant women by 0.34 (0.18, 0.51) mmol/l (p < 0.0001) in early pregnancy and by 0.45 (0.29, 0.61) mmol/l (p < 0.0001) in mid-late pregnancy. In longitudinal models, fasting glucose was lower by 0.13 (0.04, 0.21) mmol/l (p = 0.003) in early pregnancy and by 0.16 (0.08, 0.25) mmol/l (p = 0.0003) in mid-late pregnancy compared with the same women postpartum. Early pregnancy post-load glucose levels did not differ from those in non-pregnant women or the same women postpartum. In mid-late pregnancy, compared with non-pregnant women, elevations in 1 h post-load glucose level (0.60 [-0.12, 1.33] mmol/l, p = 0.10) and 2 h post-load glucose (0.49 [-0.21, 1.19] mmol/l, p = 0.17) were not statistically significant. However, in longitudinal analyses, 1 h and 2 h post-load glucose levels were higher in mid-late pregnancy (by 0.78 [0.35, 1.21] mmol/l, p = 0.0004, and 0.67 [0.30, 1.04] mmol/l, p = 0.0005, respectively) when compared with postpartum. CONCLUSIONS/INTERPRETATION: In women with diabetes risk factors, fasting glucose declines in the first trimester. Post-load glucose increases later in pregnancy. These findings may inform criteria for diagnosing hyperglycaemia early in pregnancy.

Relationship between carbohydrate intake and oral glucose tolerance test results among pregnant women.

AIMS: Evaluate the relationship between self-reported carbohydrate intake and oral glucose tolerance test (OGTT) results in pregnancy. METHODS: We measured carbohydrate intake using 24-hour dietary recall and performed a 2-hour 75-gram OGTT in 95 pregnant women with risk factors for gestational diabetes (GDM) at a median of 26 weeks' gestation. We tested for associations between carbohydrate intake in the 24 hours preceding the OGTT and 60-minute OGTT glucose, glucose at other timepoints, and glucose area under the curve (AUC) using linear regression, with adjustment for potential confounders. RESULTS: We observed an inverse linear relationship between carbohydrate intake (median 237 grams [interquartile range: 196, 303]) and 60-minute OGTT glucose. For every 50 gram reduction in carbohydrate intake, there was an 8.9 mg/dl increase in 60-minute OGTT glucose (P < 0.01) in an adjusted model. Lower carbohydrate intake was also associated with higher 30-minute (adjusted ß = -6.5 mg/dl, P < 0.01) and 120-minute OGTT glucose (adjusted ß = -8.1 mg/dl, P = 0.01) and AUC (adjusted ß = -767, P < 0.01). CONCLUSIONS: Carbohydrate intake in the day preceding an OGTT in pregnancy is associated with post-load glucose values, with lower carbohydrate intake predicting higher glucose levels and higher carbohydrate intake predicting lower glucose levels. Carbohydrate restriction or excess before an OGTT may affect GDM diagnosis.

Testosterone, dihydrotestosterone, bone density, and hip fracture risk among older men: The Cardiovascular Health Study.

BACKGROUND: Little is known about the relationships of dihydrotestosterone (DHT), a more potent androgen than testosterone (T), with bone mineral density (BMD) and fracture risk. Our objectives were to evaluate the relationships of T, DHT and sex hormone binding globulin (SHBG) with BMD, fracture risk, and lean body mass (LBM). METHODS: We evaluated 1128 older men free of cardiovascular disease in a prospective cohort study using data from the Cardiovascular Health Study. T and DHT were measured by liquid chromatography-tandem mass spectrometry and SHBG by fluoroimmunoassay. Our outcomes included incident hip fracture (n = 106) over a median of 10.2 years and BMD and LBM by dual-energy x-ray absorptiometry (n = 439). RESULTS: In Cox regression models mutually adjusted for T, SHBG, and covariates, each standard deviation increment in DHT (0.23 ng/ml) was associated with a 26% lower risk of hip fracture (adjusted hazard ratio [aHR] 0.74, 95% confidence interval (CI) 0.55-1.00, p = 0.049). Similarly, SHBG was associated with fracture in mutually adjusted models (aHR HR 1.26, 95% CI, 1.01-1.58, p = 0.045). In contrast, T (aHR, 1.16, 95% CI, 0.86-1.56, p = 0.324) was not significantly associated with fracture in mutually adjusted models. T, DHT and SHBG were not associated with BMD. T and DHT were both positively associated with LBM in individual models. CONCLUSIONS: In older men, DHT was inversely associated with hip fracture risk and SHBG was positively associated with hip fracture risk, while T was not. Future studies should elucidate the mechanisms by which DHT affects bone health.

The Use of Non-insulin Agents in Gestational Diabetes: Clinical Considerations in Tailoring Therapy.

PURPOSE OF REVIEW: To assess evidence to date for use of non-insulin agents in treatment of gestational diabetes mellitus. RECENT FINDINGS: There has been increasing interest in the use of non-insulin agents, primarily metformin and glyburide (which both cross the placenta). Metformin has been associated with less maternal weight gain; however, recent studies have shown a trend toward increased weight in offspring exposed to metformin in utero. Glyburide has been associated with increased neonatal hypoglycemia. Glycemic control during pregnancy is essential to optimize both maternal and fetal outcomes. There are a myriad of factors to consider when designing treatment programs including patient preference, phenotype, and glucose patterns. While insulin is typically recommended as first-line, some women refuse or cannot afford insulin and in those cases, non-insulin agents may be used. Further studies are needed to assess treatment in pregnancy, perinatal outcomes, and particularly long-term metabolic profiles in mothers and offspring.

Category-specific neural oscillations predict recall organization during memory search.

Retrieved-context models of human memory propose that as material is studied, retrieval cues are constructed that allow one to target particular aspects of past experience. We examined the neural predictions of these models by using electrocorticographic/depth recordings and scalp electroencephalography (EEG) to characterize category-specific oscillatory activity, while participants studied and recalled items from distinct, neurally discriminable categories. During study, these category-specific patterns predict whether a studied item will be recalled. In the scalp EEG experiment, category-specific activity during study also predicts whether a given item will be recalled adjacent to other same-category items, consistent with the proposal that a category-specific retrieval cue is used to guide memory search. Retrieved-context models suggest that integrative neural circuitry is involved in the construction and maintenance of the retrieval cue. Consistent with this hypothesis, we observe category-specific patterns that rise in strength as multiple same-category items are studied sequentially, and find that individual differences in this category-specific neural integration during study predict the degree to which a participant will use category information to organize memory search. Finally, we track the deployment of this retrieval cue during memory search: Category-specific patterns are stronger when participants organize their responses according to the category of the studied material.

Spontaneously reactivated patterns in frontal and temporal lobe predict semantic clustering during memory search.

Although it is well established that remembering an item will bring to mind memories of other semantically related items (Bousfield, 1953), the neural basis of this phenomenon is poorly understood. We studied how the similarity relations among items influence their retrieval by analyzing electrocorticographic recordings taken as 46 human neurosurgical patients studied and freely recalled lists of words. We first identified semantic components of neural activity that varied systematically with the meanings of each studied word, as defined by latent semantic analysis (Landauer and Dumais, 1997). We then examined the dynamics of these semantic components as participants attempted to recall the previously studied words. Our analyses revealed that the semantic components of neural activity were spontaneously reactivated during memory search, just before recall of the studied words. Further, the degree to which neural activity correlated with semantic similarity during recall predicted participants' tendencies to organize the sequences of their responses on the basis of semantic similarity. Thus, our work shows that differences in the neural correlates of semantic information, and how they are reactivated before recall, reveal how individuals organize and retrieve memories of words.