Rasa Kazlauskaite

Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis.

CONTEXT The diagnostic value of tests for detecting hypothalamic-pituitary adrenal insufficiency (HPAI) is controversial. OBJECTIVE Our objective was to compare standard-dose and low-dose corticotropin tests for diagnosing HPAI. DATA SOURCES We searched the PubMed database from 1966-2006 for studies reporting diagnostic value of standard-dose or low-dose corticotropin tests, with patient-level data obtained from original investigators. STUDY SELECTION Eligible studies had more than 10 patients. All subjects were evaluated because of suspicion for chronic HPAI, and patient-level data were available. We excluded studies with no accepted reference standard for HPAI (insulin hypoglycemia or metyrapone test) if test subjects were in the intensive care unit or if only normal healthy subjects were used as controls. DATA EXTRACTION We constructed receiver operator characteristic (ROC) curves using patient-level data from each study and then merged results to create summary ROC curves, adjusting for study size and cortisol assay method. Diagnostic value of tests was measured by calculating area under the ROC curve (AUC) and likelihood ratios. DATA SYNTHESIS Patient-level data from 13 of 23 studies (57%; 679 subjects) were included in the metaanalysis. The AUC were as follows: low-dose corticotropin test, 0.92 (95% confidence interval 0.89-0.94), and standard-dose corticotropin test, 0.79 (95% confidence interval 0.74-0.84). Among patients with paired data (seven studies, 254 subjects), diagnostic value of low-dose corticotropin test was superior to standard-dose test (AUC 0.94 and 0.85, respectively; P<0.001). CONCLUSIONS Low-dose corticotropin test was superior to standard-dose test for diagnosing chronic HPAI, although it has technical limitations.

Testosterone and Visceral Fat in Midlife Women: The Study of Women's Health Across the Nation (SWAN) Fat Patterning Study

Visceral fat (VF) increases with the menopause and is an independent predictor of the metabolic syndrome, diabetes, and cardiovascular disease (CVD) in women. Little is known about how hormonal changes during the menopausal transition are related to the increase in VF. We aimed to determine the relationship between bioavailable testosterone and VF in middle‐aged women at various stages of the menopausal transition and whether this relationship is independent of age and other CVD risk factors. The Study of Womens Health Across the Nation (SWAN) is a longitudinal, community‐based study. This report uses baseline data from a population‐based longitudinal ancillary study at the Chicago site to examine the cross‐sectional relationship between testosterone and computed tomography (CT)–assessed VF in women at different stages of the menopausal transition. Included are 359 women (47.2% black), aged 42–60 years, who were randomly selected from a complete community census in which a 72% participation rate was achieved. In multivariate models, bioavailable testosterone was associated with VF independent of age, race, percent total body fat, and other cardiovascular risk factors. Bioavailable testosterone was a stronger predictor than estradiol and was interchangeable in its strength of association with sex hormone–binding globulin (SHBG). As bioavailable testosterone was associated with VF even after adjusting for insulin resistance, this suggests that it plays an important role in regional fat distribution. Our findings may have direct implications in explaining the effect of menopause‐related testosterone predominance on VF accumulation and subsequent cardiovascular risk.

Variation in the Lamin A/C Gene: Associations With Metabolic Syndrome

Objective—Metabolic syndrome is associated with increased risk for cardiovascular disease and type 2 diabetes mellitus (T2DM). The lamin A/C (LMNA) gene, mutations of which cause rare syndromes of severe insulin resistance and dyslipidemia, is located on chromosome 1q21-q24, a region linked to T2DM in several genome wide scans, including in the Old Order Amish. To determine whether polymorphisms in LMNA influence susceptibility to metabolic syndrome and its constituent components. Methods and Results—We performed DNA sequence analysis of LMNA. Six single-nucleotide polymorphisms (SNPs) were identified: c.141889C>T (intron 3), c.141906G>T (intron 3), A287A (c.141253T>C; exon 5), c.140353G>A (intron 6), c.139418C>T (intron 8), and H566H (c. 138747C>T; exon 10). In 971 participants from the Amish Family Diabetes Study, the H566H polymorphism of LMNA was associated with metabolic syndrome diagnosed according to National Cholesterol Education Program ATP III criteria and also higher mean fasting triglyceride and lower mean high-density lipoprotein-cholesterol concentrations. However, no differences in allele frequencies were observed for any SNP among participants with T2DM or impaired glucose homeostasis (IGH) and normoglycemic controls. Haplotype analysis showed that >87% of individuals carried 1 of 2 common LMNA haplotypes. There were no significant differences in haplotype frequencies among subjects with metabolic syndrome T2DM, IGH, and controls. Conclusion—Sequence variation in LMNA may confer modest susceptibility for development of metabolic syndrome and dyslipidemia in the Amish.

Vitamin D is associated with atheroprotective high-density lipoprotein profile in postmenopausal women

BACKGROUND Low vitamin D has been associated with low levels of high-density lipoprotein (HDL) cholesterol, a marker of coronary risk. Whether atheroprotective HDL particle composition accounts for this association and whether fat affects this association is not known. OBJECTIVE To explore the association between HDL particle composition and 25-hydroxy vitamin D (25[OH]D) in post-menopausal women. METHODS Vitamin D levels and lipoprotein composition were assessed in fasting blood samples of apparently healthy women from a diverse Chicago community. Visceral (VAT) and subcutaneous (SAT) abdominal fat area were assessed using computed tomography. Total body fat mass was measured by dual-energy X-ray absorptiometry. RESULTS We enrolled 78 women (50% black; 50% white), age 48 to 64 years, all of whom were participants in a longitudinal study of fat patterning. They had a mean 25[OH]D of 31 ± 15 μg/L, HDL cholesterol 57±11 mg/dL, and large HDL particle subclass 8.6±3.4 μmol/L. In a multivariable-adjusted regression model, each 5 μg/L higher 25[OH]D predicted 0.57 μmol/L (95%CI 0.20-0.95) higher large HDL particles, independent of race, season, and total HDL particle concentration. This association was only partially confounded by total body fat mass (0.49, 95%CI 0.10-0.89), SAT (0.50, 95%CI 0.11-0.90), or VAT (0.37, 95%CI 0.01-0.74). Age did not significantly influence the strength of associations. CONCLUSIONS Higher 25[OH]D levels are associated with large HDL particles. This association is stronger than that of HDL cholesterol and only partially confounded by body fat. Theoretically, vitamin D may protect against cardiovascular risk by promoting formation of large HDL particles, affecting reverse cholesterol transport.

Subcutaneous adipose tissue in relation to subclinical atherosclerosis and cardiometabolic risk factors in midlife women

BACKGROUND Limited data suggest that the effects of abdominal subcutaneous adipose tissue (SAT) on cardiovascular disease risk may depend on accompanying amounts of abdominal visceral adipose tissue (VAT). OBJECTIVE The objective was to examine whether abdominal VAT area modifies the effects of abdominal SAT area on subclinical atherosclerosis and cardiometabolic risk factors in both whites and African Americans. DESIGN Computed tomographic measures of abdominal SAT and VAT were examined in relation to carotid intima-media thickness (cIMT) and cardiometabolic risk factor levels in 500 African American and white women in midlife. A VAT × SAT interaction term was evaluated. RESULTS The mean (±SD) age of the sample was 51.0 ± 2.9 y, and 37% were African American. Higher amounts of SAT and VAT were associated with higher cIMT, blood pressure, homeostasis model assessment insulin resistance index (HOMA-IR), and concentrations of glucose, triglycerides, and insulin and with lower concentrations of HDL cholesterol. However, in African Americans, but not in whites, higher amounts of VAT significantly attenuated associations between higher amounts of SAT and higher insulin concentrations (P for interaction = 0.032) and HOMA-IR (P for interaction = 0.011) and reversed associations with cIMT (P for interaction = 0.005) and glucose (P for interaction = 0.044). CONCLUSIONS These results suggest that in midlife African American but not white women, adverse associations between abdominal SAT and cardiometabolic risk factors are attenuated and, in the case of subclinical atherosclerosis, are reversed as VAT amounts increase. Given that African American women suffer disproportionately from obesity and cardiovascular disease, further research into the role of this effect modification on obesity-associated vascular disease in African American women is warranted.

B-type natriuretic peptide predicts left atrial appendage thrombus in patients with nonvalvular atrial fibrillation.

To investigate whether plasma B‐type Natriuretic peptide (BNP), a surrogate of left ventricular filling pressure (LVFP), is predictive of left atrial appendage thrombus (LAAT) in patients with nonvalvular atrial fibrillation (AF) independent of known clinical risk predictors.

Pitfalls in the Diagnosis of Central Adrenal Insufficiency in Children

The diagnosis of central adrenal insufficiency relies heavily on laboratory testing of cortisol levels in the systemic circulation. The lack of cortisol assay standardization challenges the reliability of dynamic tests of the hypothalamic-pituitary adrenal axis. Although the insulin-induced hypoglycemia or metyrapone tests remain the accepted standards for evaluating central adrenal insufficiency in children their associated risks and inconvenience make them unattractive for routine use. Corticotropin testing is an effective first step to evaluate for chronic central adrenal insufficiency for children older than 2 years who are ambulatory, have normal sleep-wake cycle and normal serum protein levels. The low-dose (1 microg) corticotropin test may be superior to standard-dose (250 mcg) for patients with suspected hypothalamic-pituitary disease.

Accuracy of self-monitored blood glucose in type 2 diabetes.

BACKGROUND The prevalence and predictors of inaccurate self-monitored blood glucose (SMBG) diaries in type 2 diabetes are not well defined. METHODS This was a cross-sectional study of adults with type 2 diabetes in a diabetes clinic at a large urban public hospital. We collected copies of SMBG diaries and downloaded data from their glucose meters if patients brought them to their clinic appointment. Trained interviewers used standard tests to assess literacy, depression, and cognitive function. The main outcome measure was accuracy of the glucose diary assessed by comparing reported values to meter memory readings and to results of hemoglobin A(1c). RESULTS Blood glucose self-monitoring was either missing or misleading for 48% (55 of 115) because (1) patients brought neither meter nor the SMBG diary (n = 26) or (2) the diary was inaccurate (n = 29). An inaccurate glucose diary (by comparison with meter readings) was predicted by normotension (odd ratio 5.6, P = 0.02) and one measure of cognitive impairment, slow Digit Symbol Coding (odds ratio 2.2, P = 0.02). A patients self-assessment of his or her diarys accuracy was unreliable (sensitivity 63%, specificity 56%). CONCLUSIONS SMBG diaries are frequently either not accurate or not brought to clinic visit. Some inaccuracy might be due to cognitive impairment. To achieve maximum benefit from glucose self-monitoring, glucose meter memory analysis is crucial before making therapy adjustments based on SMBG.

Hyperandrogenic Oligomenorrhea and Metabolic Risks Across Menopausal Transition

CONTEXT Although there is evidence of metabolic risks in young women with irregular menses and androgen excess, persistence of risks after menopause is unclear. OBJECTIVE The objective of the study was to determine the impact of menopause on the cardiometabolic profile in women with high androgens and a history of menstrual irregularity. METHODS Study of Womens Health Across the Nation is a longitudinal cohort study. Data from 1929 women without metabolic syndrome (MetS) at baseline were analyzed for incidence of MetS, self-reported stroke, and myocardial infarction. Cox hazard ratios (HRs) were estimated, adjusting for age, ethnicity, body mass, smoking, menopausal status, and study site. RESULTS Among MetS-free women at baseline, 497 new cases were identified during 20 249 woman-years of follow-up over 12 years. Women with hyperandrogenemia (HA) and oligomenorrhea (Oligo) developed incident cases of MetS at a comparable rate compared with their counterparts: eumenorrheic, normoandrogenic women [HR 1.4 (0.9-2.2)], oligomenorrheic, normoandrogenic women [HR 1.3 (0.8-2.2)], and eumenorrheic hyperandrogenic women [HR 1.2 (0.7-1.8)]. Smoking and obesity were the strongest predictors of incident MetS. There was no significant difference in incidence of self-reported stroke or MI by HA/Oligo status. CONCLUSIONS Longitudinal evidence suggests that a history of androgen excess and menstrual irregularity is not associated with worsening of metabolic health after menopause. Our findings challenge the notion that a history of concurrent HA and Oligo reflects ongoing cardiometabolic risk in postmenopausal women.

Covariation of change in bioavailable testosterone and adiposity in midlife women.

To determine whether menopause‐related changes in reproductive hormones were associated with change in adiposity and whether these relationships were independent of important covariates.