Blood pressure and mortality in patients with type 2 diabetes and a recent coronary event in the ELIXA trial.

BACKGROUND: The relationship between blood pressure and mortality in type 2 diabetes (T2DM) is controversial, with concern for increased risk associated with excessively lowered blood pressure. METHODS: We evaluated whether prior cardiovascular disease (CVD) altered the relationship between baseline blood pressure and all-cause mortality in 5852 patients with T2DM and a recent acute coronary syndrome (ACS) who participated in the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) trial. Risk of death was assessed in Cox models adjusted for age, sex, race, heart rate, BMI, smoking, diabetes duration, insulin use, HbA1c, eGFR, brain natriuretic peptide (BNP), urine albumin/creatinine ratio, treatment allocation and prior coronary revascularization. RESULTS: Although overall there was no significant association between systolic blood pressure (SBP) and mortality (hazard ratio per 10 mmHg lower SBP 1.05 (95% CI 0.99-1.12) P = 0.10), lower SBP was significantly associated with higher risk of death (hazard ratio per 10 mmHg lower SBP 1.13 (95% CI 1.04-1.22) P = 0.002) in 2325 patients with additional CVD (index ACS+ at least one of the following prior to randomization: myocardial infarction other than the index ACS, stroke or heart failure). In 3527 patients with only the index ACS no significant association was observed (hazard ratio per 10 mmHg lower SBP 0.95 (0.86-1.04) P = 0.26; P for interaction 0.005). CONCLUSIONS: The association between blood pressure and mortality was modified by additional CVD history in patients with type 2 diabetes and a recent coronary event. When blood pressures measured after an acute coronary event are used to assess the risk of death in patients with type 2 diabetes, the cardiovascular history needs to be taken into consideration. Trial registration ClinicalTrials.gov number NCT01147250, first posted June 22, 2010.

NT-proBNP by Itself Predicts Death and Cardiovascular Events in High-Risk Patients With Type 2 Diabetes Mellitus.

Background NT-proBNP (N-terminal pro-B-type natriuretic peptide) improves the discriminatory ability of risk-prediction models in type 2 diabetes mellitus (T2DM) but is not yet used in clinical practice. We assessed the discriminatory strength of NT-proBNP by itself for death and cardiovascular events in high-risk patients with T2DM. Methods and Results Cox proportional hazards were used to create a base model formed by 20 variables. The discriminatory ability of the base model was compared with that of NT-proBNP alone and with NT-proBNP added, using C-statistics. We studied 5509 patients (with complete data) of 8561 patients with T2DM and cardiovascular and/or chronic kidney disease who were enrolled in the ALTITUDE (Aliskiren in Type 2 Diabetes Using Cardiorenal Endpoints) trial. During a median 2.6-year follow-up period, 469 patients died and 768 had a cardiovascular composite outcome (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, stroke, or heart failure hospitalization). NT-proBNP alone was as discriminatory as the base model for predicting death (C-statistic, 0.745 versus 0.744, P=0.95) and the cardiovascular composite outcome (C-statistic, 0.723 versus 0.731, P=0.37). When NT-proBNP was added, it increased the predictive ability of the base model for death (C-statistic, 0.779 versus 0.744, P<0.001) and for cardiovascular composite outcome (C-statistic, 0.763 versus 0.731, P<0.001). Conclusions In high-risk patients with T2DM, NT-proBNP by itself demonstrated discriminatory ability similar to a multivariable model in predicting both death and cardiovascular events and should be considered for risk stratification. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT00549757.

Retinopathy, Neuropathy, and Subsequent Cardiovascular Events in Patients with Type 2 Diabetes and Acute Coronary Syndrome in the ELIXA: The Importance of Disease Duration.

INTRODUCTION: We investigated the association of diabetic retinopathy and neuropathy with increased risk of recurrent cardiovascular (CV) events in 6068 patients with type 2 diabetes mellitus (T2DM) and recent acute coronary syndrome (ACS) enrolled in the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA). METHODS: History of retinopathy and neuropathy as well as duration of T2DM were self-reported at screening. Proportional hazards regression models were used to assess relationships between retinopathy, neuropathy, and recurrent CV events. RESULTS: At screening, retinopathy and neuropathy were reported in 10.7% and 17.5% of patients, respectively, while 5.7% reported both. When adjusted for randomized treatment only, both retinopathy and neuropathy were associated with a primary composite outcome (CV death, nonfatal MI, stroke, or hospitalization for unstable angina) (retinopathy: HR 1.44, 95% CI 1.19-1.75; neuropathy: HR 1.33, 95% CI 1.12-1.57), CV composite (CV death, nonfatal MI, stroke, hospitalization for heart failure (HF)) (retinopathy: HR 1.57, 95% CI 1.31-1.88; neuropathy: HR 1.38, 95% CI 1.19-1.62), myocardial infarction (retinopathy: HR 1.38, 95% CI 1.08-1.76; neuropathy: HR 1.26, 95% CI 1.02-1.54), HF hospitalization (retinopathy: HR 2.03, 95% CI 1.48-2.78; neuropathy: HR 1.71, 95% CI 1.30-2.27), and all-cause mortality (retinopathy: HR 1.65, 95% CI 1.28-2.12; neuropathy: HR 1.43, 95% CI 1.14-1.78). When included in the same model, and adjusted for T2DM duration, there were no independent associations of either with CV outcomes, while T2DM duration remained strongly associated with all outcomes. Addition of demographic characteristics and CV risk factors did not further alter these relationships. CONCLUSIONS: In patients with T2DM and recent ACS, a history of retinopathy and/or neuropathy and longer T2DM duration could be considered clinical markers for high risk of recurrent CV events. This trial is registered with the ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome), ClinicalTrials.gov registration number NCT01147250.

Hypertension Risk Subsequent to Gestational Dysglycemia Is Modified by Race/Ethnicity.

Gestational diabetes mellitus is associated with an increased risk of type 2 diabetes mellitus and hypertension. Additionally, gestational dysglycemia has been associated with an increased risk of type 2 diabetes mellitus but not yet associated with hypertension subsequent to pregnancy in long-term follow-up. Therefore, we set out to examine this relationship as well as the role of race/ethnicity in modifying this relationship. We analyzed a prospective observational cohort followed between 1998 and 2007. There were 17 655 women with self-reported race/ethnicity and full-term, live births. A 1-hour 50 g oral glucose-load test and a 3-hour 100 g oral glucose-tolerance test enabled third trimester stratification of women into 1 of 4 glucose-tolerance groups: (1) normal (n=15 056); (2) abnormal glucose-load test (n=1558); (3) abnormal glucose-load and -tolerance tests (n=520); and (4) gestational diabetes mellitus (n=521). Women were then followed for a mean±standard deviation of 4.1±2.9 years after delivery for the development of hypertension. Although gestational diabetes mellitus was associated with an increased risk of hypertension after pregnancy (odds ratio [95% confidence interval]: 1.58 [1.02, 2.45]; P=0.04), dysglycemia defined by an abnormal glucose-load test predicted hypertension only among black women (4.52 [1.24, 16.52]; P=0.02). The risk of hypertension after pregnancy among dysglycemia groups not meeting criteria for gestational diabetes mellitus varied based on the race/ethnicity of the population. Further research on the implications of the intersection of race/ethnicity and gestational dysglycemia on subsequent hypertension is warranted.

Prevalence of Intervillous Thrombi Is Increased in Placentas from Pregnancies Complicated by Diabetes.

Intervillous thrombus (IVT) is a placental pathology of unclear cause. One possible cause is that IVT protects against fetomaternal transfusion due to trophoblastic disruption. A role for hyperglycemia in trophoblast apoptosis has been suggested. We sought to determine whether placentas from pregnancies complicated by diabetes had an increased incidence of IVT. Medical records of 206 patients with type 1 diabetes (n = 39), type 2 diabetes (n = 37), and gestational diabetes (GDM, n = 130) at the Massachusetts General Hospital were identified. Placental pathology reports were reviewed to determine prevalence of IVT. Gestational and maternal age-matched controls were selected from the pathology archives consisting of placentas examined only for the indication of group B streptococcus screen positivity; controls were confirmed euglycemic and reviewed for IVT. Fisher exact test was used for statistical analysis. An increased incidence of IVT was present in all diabetics (type 1, type 2, and GDM; 32 of 206; 15.5%; P = 0.04) and GDM exclusively (22 of 130; 16.9%; P = 0.03) versus controls (7 of 99; 7.1%). IVT were also increased in patients with type 1 diabetes (4 of 39; 10.3%) and type 2 diabetes (6 of 37; 16.2%) compared to controls (7 of 99; 7.1%), but the results did not attain statistical significance (P = 0.73 and 0.19, respectively). The incidence of IVT was increased in the placentas of patients with diabetes as a group (type 1, type 2, and GDM), and in patients with GDM in particular. This is the first report of an association between diabetes and an increased incidence of placental IVT.

Type 1, type 2 and gestational diabetes mellitus differentially impact placental pathologic characteristics of uteroplacental malperfusion.

INTRODUCTION: During a pregnancy complicated by diabetes, the placenta undergoes a number of functional and structural pathologic changes. However, differences across studies may reflect pathophysiologic differences of diabetes types under investigation. METHODS: We examined placental pathology from women ages 18-40 years with self-identified race/ethnicity; singleton, live births; and type 1 (T1DM; n = 36), type 2 (T2DM; n = 37), or gestational diabetes mellitus (GDM; n = 126). Clinical data were abstracted from medical records. Placental diagnoses were independently re-reviewed by a perinatal pathologist. Multivariable analyses adjusting for race, gestational weight gain, gestational age, and systolic blood pressure were conducted. RESULTS: Women with T1DM compared with either T2DM or GDM had higher gestational weight gain (mean ± SD, T1DM vs. T2DM: 28.5 ± 12.4 vs. 20.5 ± 13.4 kg, p = 0.03; or GDM: 21.3 ± 12.7 kg, p = 0.009) and insulin use (T2DM: 100.0% vs. 85.3%, p = 0.02; or GDM: 4.0%, p < 0.001). Women with T1DM compared with either T2DM or GDM also had a similarly lower prevalence of placental infarcts in univariate analyses; however, these findings did not remain significant after multivariable adjustment. Also, placentas from women with T2DM compared to GDM had higher rates of decidual vasculopathy when excluding women with preeclampsia (10.3 vs. 1.6%, p = 0.049) and diffuse chorangiosis (62.2 vs. 32.5%, p < 0.001) but a lower rate of villous immaturity (10.8 vs. 90.5%, p = 0.007) after full adjustment. DISCUSSION: Placental vasculopathic abnormalities differ by maternal diabetes type, potentially reflecting underlying pathophysiologic mechanisms. Further research on placental pathology and metabolic derangements is warranted.

MENTAL HEALTH DISORDERS SUBSEQUENT TO GESTATIONAL DIABETES MELLITUS DIFFER BY RACE/ETHNICITY.

INTRODUCTION: The relationship between gestational diabetes mellitus (GDM) and postpregnancy mental health disorders has been inconsistently reported. Additionally, race/ethnicity data are limited. We sought to elucidate the intersection of these relationships. METHODS: We analyzed 18,109 women aged 18-40 with self-reported race/ethnicity. Women with (n = 659) and without (n = 14,461) GDM were followed for a median of 4.4 (interquartile range 1.4-6.8) and 4.0 (1.5-6.4) years, respectively, for incident mental health disorders. Multivariable repeated measures analyses were conducted to examine associations between GDM and postpregnancy mental health disorders, race/ethnicity, and the interaction of these factors. RESULTS: Women with compared to women without GDM were older (mean ± standard deviation, 32 ± 5 vs. 30 ± 5 years; P < .001) and had higher body mass index (29.0 ± 7.2 vs. 25.3 ± 5.2 kg/m(2) ; P < .001). GDM was associated with increased risk for depression and anxiety after adjusting for age and pregnancy complications; however, loss of significance in the fully adjusted model for depression (odds ratio [95% CI]: 1.29 [0.98, 1.70]; P = .064) and anxiety (1.14 [0.83, 1.57], P = .421) suggested that clinical and socioeconomic factors influence this relationship. Hispanic compared to white women had a greater risk for depression (1.40 [1.15, 1.72]; P = .001), even after multivariable adjustment. The interaction between GDM and race was evident in complication-adjusted but not fully adjusted models. CONCLUSIONS: The incidence of mental health disorders subsequent to GDM was attenuated after adjustment for clinical and socioeconomic factors. Moreover, race/ethnicity influenced this relationship. Further investigation is warranted to clarify potential underlying mechanisms.

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo.

BACKGROUND: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagon-like peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. METHODS: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. RESULTS: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m(2), and duration of T2DM was 9.3 ± 8.2 years. The qualifying ACS was a myocardial infarction in 83% and unstable angina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. CONCLUSION: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk.

Metabolomic profiling in the prediction of gestational diabetes mellitus.

AIMS/HYPOTHESIS: Metabolomic profiling in populations with impaired glucose tolerance has revealed that branched chain and aromatic amino acids (BCAAs) are predictive of type 2 diabetes. Because gestational diabetes mellitus (GDM) shares pathophysiological similarities with type 2 diabetes, the metabolite profile predictive of type 2 diabetes could potentially identify women who will develop GDM. METHODS: We conducted a nested case-control study of 18- to 40-year-old women who participated in the Massachusetts General Hospital Obstetrical Maternal Study between 1998 and 2007. Participants were enrolled during their first trimester of a singleton pregnancy and fasting serum samples were collected. The women were followed throughout pregnancy and identified as having GDM or normal glucose tolerance (NGT) in the third trimester. Women with GDM (n = 96) were matched to women with NGT (n = 96) by age, BMI, gravidity and parity. Liquid chromatography-mass spectrometry was used to measure the levels of 91 metabolites. RESULTS: Data analyses revealed the following characteristics (mean ± SD): age 32.8 ± 4.4 years, BMI 28.3 ± 5.6 kg/m(2), gravidity 2 ± 1 and parity 1 ± 1. Six metabolites (anthranilic acid, alanine, glutamate, creatinine, allantoin and serine) were identified as having significantly different levels between the two groups in conditional logistic regression analyses (p < 0.05). The levels of the BCAAs did not differ significantly between GDM and NGT. CONCLUSIONS/INTERPRETATION: Metabolic markers identified as being predictive of type 2 diabetes may not have the same predictive power for GDM. However, further study in a racially/ethnically diverse population-based cohort is necessary.

A systematic review of metabolite profiling in gestational diabetes mellitus.

AIMS/HYPOTHESIS: Gestational diabetes mellitus is associated with adverse maternal and fetal outcomes during, as well as subsequent to, pregnancy, including increased risk of type 2 diabetes and cardiovascular disease. Because of the importance of early risk stratification in preventing these complications, improved first-trimester biomarker determination for diagnosing gestational diabetes would enhance our ability to optimise both maternal and fetal health. Metabolomic profiling, the systematic study of small molecule products of biochemical pathways, has shown promise in the identification of key metabolites associated with the pathogenesis of several metabolic diseases, including gestational diabetes. This article provides a systematic review of the current state of research on biomarkers and gestational diabetes and discusses the clinical relevance of metabolomics in the prediction, diagnosis and management of gestational diabetes. METHODS: We conducted a systematic search of MEDLINE (PubMed) up to the end of February 2014 using the key term combinations of 'metabolomics,' 'metabonomics,' 'nuclear magnetic spectroscopy,' 'mass spectrometry,' 'metabolic profiling' and 'amino acid profile' combined (AND) with 'gestational diabetes'. Additional articles were identified through searching the reference lists from included studies. Quality assessment of included articles was conducted through the use of QUADOMICS. RESULTS: This systematic review included 17 articles. The biomarkers most consistently associated with gestational diabetes were asymmetric dimethylarginine and NEFAs. After QUADOMICS analysis, 13 of the 17 included studies were classified as 'high quality'. CONCLUSIONS/INTERPRETATION: Existing metabolomic studies of gestational diabetes present inconsistent findings regarding metabolite profile characteristics. Further studies are needed in larger, more racially/ethnically diverse populations.

Placental histomorphometry in gestational diabetes mellitus: the relationship between subsequent type 2 diabetes mellitus and race/ethnicity.

OBJECTIVES: We examined placental histomorphometry in gestational diabetes mellitus (GDM) for factors associated with race/ethnicity and subsequent type 2 diabetes mellitus (T2DM). METHODS: We identified 124 placentas from singleton, full-term live births whose mothers had clinically defined GDM and self-reported race/ethnicity. Clinical and placental diagnoses were abstracted from medical records. RESULTS: Forty-eight white and 76 nonwhite women were followed for 4.1 years (median, range 0.0-8.9 years). White women developed less T2DM (12.5% vs 35.5%; P = .005) but had higher systolic (mean ± SD, 116 ± 13 vs 109 ± 11 mm Hg; P < .001) and diastolic (71 ± 9 vs 68 ± 7 mm Hg; P = .02) blood pressure, more smoking (35.4% vs 10.5%; P = .004), and more chorangiosis (52.1% vs 30.3%; P = .02) than nonwhite women. CONCLUSIONS: Although more nonwhite women developed T2DM, more white women had chorangiosis, possibly secondary to the higher percentage of smokers among them. Further study is necessary to elucidate the relationship among chorangiosis, subsequent maternal T2DM, and race.

Effect of race/ethnicity on hypertension risk subsequent to gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) prevalence is greater in racially/ethnically diverse groups compared with non-Hispanic white populations. Although race has been shown to modify other cardiovascular disease risk factors in postpartum women, the role of race/ethnicity on GDM and subsequent hypertension has yet to be examined. The aim of this study was to evaluate the impact of race/ethnicity in relation to GDM and subsequent hypertension in a retrospective analysis of women who delivered at Massachusetts General Hospital from 1998 to 2007. Multivariate analyses were used to determine the associations between GDM and (1) race/ethnicity, (2) hypertension, and (3) the interaction with hypertension and race/ethnicity. Women were monitored for a median of 3.8 years from the date of delivery. In our population of 4,010 women, GDM was more common in nonwhite participants (p<0.0001). GDM was also associated with hypertension subsequent to delivery after adjusting for age, race, parity, first-trimester systolic blood pressure, body mass index, maternal gestational weight gain, and preeclampsia (hazard ratio [HR] 1.75, 95% confidence interval [CI] 1.28 to 2.37, p=0.0004). Moreover, Hispanic (HR 3.25, 95% CI 1.85 to 5.72, p<0.0001) and white (HR 1.68, 95% CI 1.10 to 2.57, p=0.02) women with GDM had greater hypertension risk relative to their race/ethnicity-specific counterparts without GDM in race-stratified multivariable analyses. In conclusion, Hispanic women compared with white women have an increased risk of hypertension. Hispanic and white women with GDM are at a greater risk for hypertension compared with those without GDM. Because the present study may have had limited power to detect effects among black and Asian women with GDM, further research is warranted to elucidate the need for enhanced hypertension risk surveillance in these young women.

Reasons for discontinuation of lipid-lowering medications in patients with chronic kidney disease.

BACKGROUND/AIMS: Many patients with chronic kidney disease (CKD) do not receive lipid-lowering therapy despite their high cardiovascular risk. The reasons for this are unknown. METHODS: We have conducted a retrospective cohort study of discontinuation of lipid-lowering drugs in patients with CKD stage 3 and higher treated in practices affiliated with two academic medical centers between 2000 and 2010. Information on medication discontinuation and its reasons was obtained from electronic medical records, including natural language processing of electronic notes using previously validated software. RESULTS: Out of 14,034 patients in the study cohort, 10,072 (71.8%) stopped their lipid-lowering drugs at least once, and 2,444 (17.4%) stopped them for at least 1 month. Patients who had a comorbidity associated with higher cardiovascular risk were less likely to stop lipid-lowering drugs. Insurance request was the most common explicitly documented reason for discontinuation, and adverse reactions were the most common reason for long-term discontinuation. In a multivariable analysis, patients were more likely to stop a lipid-lowering drug because of an insurance request if they had government insurance and they were also more likely to stop a lipid-lowering drug because of adverse reactions if they had a history of multiple adverse reactions to other medications. There was no significant relationship between CKD stage and the reason for discontinuation of lipid-lowering drugs. CONCLUSIONS: Patients with CKD frequently stop lipid-lowering drugs. Insurance requests and adverse reactions are common reasons for the discontinuation. Further research is needed to ensure appropriate lipid-lowering therapy for these individuals at high cardiovascular risk.

Ovarian hypertension: polycystic ovary syndrome.

Hypertension is a significant contributor to the risk for cardiovascular disease. The increased prevalence of hypertension in women with polycystic ovary syndrome (PCOS) may contribute to the increased risk of cardiovascular disease in these women. Whether hypertension is associated with PCOS independent of obesity remains controversial. Nevertheless, detection and subsequent treatment of hypertension in this population should decrease the adverse sequelae from hypertensive cardiovascular disease. Treatment of risk factors inherent to PCOS, such as hyperandrogenism, insulin resistance, and obesity, may minimize the risk not only for the development of hypertension but also for incident cardiovascular disease independent of hypertension.

Barriers to follow-up for women with a history of gestational diabetes.

Women with gestational diabetes (GDM) are at increased risk for type 2 diabetes (T2DM), but many do not receive recommended follow-up. We sought to identify barriers to follow-up screening. We surveyed primary care providers (PCPs) and obstetric and gynecology care providers (OBCPs) in a large health system. We also assessed documentation of GDM history in the health care system's electronic medical record. Four hundred seventy-eight clinicians were surveyed, among whom 207 responded. Most participants (81.1%) gave an accurate estimate of risk of progression to T2DM. PCPs were less likely than OBCPs to ask patients about history of GDM (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.20 to 0.90), but they were far more likely to indicate that they order glucose screening for women with a known history (OR 4.31, 95% CI 2.01 to 9.26). Providers identified poor communication between OBCPs and PCPs as a major barrier to screening. Fewer than half (45.8%) of 450 women with GDM by glucose tolerance test criteria had that history documented on their electronic problem list. Clinicians are aware that women with GDM are at high risk of developing type 2 diabetes, but they do not routinely assess and screen patients, and communication between OBCPs and PCPs can be improved.

Late cardiovascular consequences of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM), defined as carbohydrate intolerance of any degree first recognized during pregnancy, complicates approximately 4% of all pregnancies in the United States. Several factors can increase one's risk of developing GDM, including obesity, family history of type 2 diabetes mellitus (T2DM), and race/ethnicity. Conversely, a history of GDM can increase the risk of developing not only T2DM but also cardiovascular disease (CVD) independent of a diagnosis of T2DM. Several investigations have explored GDM relationships with CVD risk factors, CVD surrogate markers, and clinically evident CVD. These studies have included evaluations of biochemical parameters, such as inflammatory and endothelial biomarkers; endothelial dysfunction, such as that seen in impaired brachial artery flow-mediated vasodilation; and vascular dysfunction, manifest as cardiac dysfunction or in diseases such as hypertension. This article will review these studies and examine factors considered to be responsible for promoting CVD in women with a history of GDM, such as T2DM and metabolic syndrome and its components. In addition, studies evidencing CVD in women with a history of GDM will be explored.

A comparison of prediction equations for estimating glomerular filtration rate in pregnancy.

OBJECTIVE: To compare existing glomerular filtration rate (GFR) prediction equations with the gold standard, inulin clearance, in pregnancy. METHODS: Five equations were assessed for precision, bias, and accuracy in prediction of true GFR, measured by inulin clearance in 12 healthy, pregnant women during the second (T2) and third (T3) trimesters and in postpartum (PP). RESULTS: Precision was greatest with 24-hour creatinine clearance estimation of GFR (R(2) = 13% (T2), R(2) = 26% (T3)). Other than 100/SCr, all equations underestimated true GFR. 30% accuracy was greatest in 100/SCr (83% (T2), 92% (T3)). CONCLUSIONS: Current GFR prediction formulae do not appear to be sufficient for estimating GFR in the gravid state.

Dietary sodium alters the prevalence of electrocardiogram determined left ventricular hypertrophy in hypertension.

BACKGROUND: Determination of left ventricular hypertrophy (LVH) via electrocardiogram (ECG) is a known independent risk factor for cardiovascular morbidity and mortality in hypertension (HTN). Dietary sodium and HTN are both associated with unfavorable alterations in left ventricular mass, however, to what extent their interplay affects ECG screening for LVH is unclear. METHODS: The effects of controlled dietary sodium manipulation on ECG determinants of LVH in hypertensive subjects were evaluated using well-established voltage criteria for LVH. ECGs from 80 hypertensive subjects were evaluated following random sequence assignment to 7 days of high sodium (HS) intake (200 mEq/24 h), and then 7 days of low sodium (LS) intake (10 mEq/24 h). RESULTS: Sodium restriction over 7 days resulted in significant decreases in overall, and LVH-specific, ECG voltages. Most subjects exhibited decrements in overall ECG voltage with sodium restriction (72%); however, a smaller subset displayed higher voltages when on LS intake (28%). The prevalence of ECG-determined LVH was significantly lowered with LS diet (HS diet 22/80 (28%) vs. LS diet 8/80 (10%), P < 0.05). Subjects exhibiting reversal of LVH status with sodium restriction were younger, demonstrated salt sensitivity of blood pressure, and lower LVH-specific ECG voltage. CONCLUSIONS: Short-term dietary sodium fluctuations can significantly alter overall ECG voltage and the prevalence of ECG-determined LVH in hypertensive individuals. Inclusion of dietary sodium assessment when screening hypertensive subjects for LVH by ECG may improve the consistency of cardiac risk assessment.

Gestational diabetes mellitus: postpartum opportunities for the diagnosis and prevention of type 2 diabetes mellitus.

Gestational diabetes mellitus (GDM) affects approximately 4% of all pregnant women in the US and represents 90% of all cases of diabetes mellitus diagnosed during pregnancy. In addition to the adverse pregnancy outcomes associated with this complication, a history of GDM predisposes women to the future development of type 2 diabetes mellitus (T2DM). Incidence rates of GDM are increasing in the US. As a consequence, a growing number of women are now at increased risk for T2DM. Opportunities to diagnose and prevent T2DM in women with a history of GDM include early diagnosis by postpartum screening and implementation of diabetes prevention measures. In this Review, we discuss current guidelines for postpartum screening, how they might be implemented, and who should take responsibility for screening individuals at risk of T2DM. In addition, we describe measures to prevent the onset of T2DM in women with a history of GDM, focusing on lifestyle modifications, such as diet and breast-feeding.