Higher Risk Of Cardiometabolic Diseases Research Articles

Abstract MP58: Intermuscular Fat Density: Novel Risk Factor for Cardiometabolic Risk Factors in African-Ancestry Men

Background: While overall obesity remains a major risk factor for cardiometabolic diseases, the location of stored fat is also thought to play a role. In addition to fat storage in ectopic sites, the density of fat, a marker of fat quality, is emerging as a novel risk factor for cardiometabolic diseases. Previous studies have focused primarily on visceral (VAT) and abdominal subcutaneous (SAT) adipose tissue density and in predominantly white cohorts; however, studies in populations of African ancestry who are at higher risk of cardiometabolic diseases are lacking. Additionally, information is lacking on associations of density of other relevant ectopic fat depots, such as intermuscular adipose tissue (IMAT), with cardiometabolic risk factors. Methods: We investigated whether VAT, SAT, or thigh IMAT densities were associated with cardiometabolic measures in 648 black men aged 50-91 years (mean age 63.6 years, mean BMI 27.7 kg/m 2 ). Adipose tissue volume (cm 3 ) and density (Hounsfield units, HU) was measured in the abdomen (between L4 and L5) and mid-thigh from computed tomography scans. Cardiometabolic measures, including blood pressure, fasting serum glucose and insulin homeostasis, and serum lipids (N=476), were transformed as needed and used as outcomes in multiple linear regression models adjusting for age, lifestyle factors, medication use (antihypertensive, antidiabetic, or lipid-lowering), and corresponding fat depot volume. Results: After adjustment (Table), VAT, SAT, and IMAT densities were significantly associated with fasting insulin, insulin resistance, and lipids. Results remain similar after adjustment for BMI instead of fat volume and in a sensitivity analysis excluding those taking relevant medications. Conclusion: As reported in other studies, in our study among African ancestry individuals VAT and SAT were associated with several cardio-metabolic risk factors. Importantly, our findings suggest that thigh IMAT density may be a novel predictor of cardiometabolic risk in African ancestry men.

Early Menstrual Factors Are Associated with Adulthood Cardio-Metabolic Health in a Survey of Mexican Teachers

Objectives To evaluate whether age at menarche and time to menstrual regularity were related to cardio-metabolic risk factors in Mexican women. Methods The study population comprised 54,921 women from the 2008-2010 wave of the Mexican Teacher's Cohort. A modified Poisson approach was used; exposures were age at menarche and time to menstrual regularity (< 1year vs. ≥1year), and outcomes were prevalent obesity, type 2 diabetes, high blood pressure, and high cholesterol. Results Mean (SD) age of women was 42.1 (7.6) years, and mean (SD) menarcheal age was 12.5 (1.5) years. Compared to women with menarche age 13 years, those with menarche < 9years had a 65% (95% CI 43-90%); 27% (95% CI 4-55%); and 23% (95% CI 1-49%) higher prevalence of obesity, high blood pressure, and high cholesterol, respectively. For diabetes, there was a U-shaped association; compared to menarche age 13 years, those with menarche < 9years had an 89% higher prevalence of diabetes (95% CI 39-156%), and those with menarche ≥ 17years had a 65% higher prevalence (95% CI 16-134%). Among women with regular cycles (n = 43,113), a longer time to menstrual regularity was associated with diabetes (PR = 1.11 with 95% CI 1.02-1.22), high blood pressure (PR = 1.11 with 95% CI 1.06-1.17), and high cholesterol (PR = 1.09 with 95% CI 1.04-1.14). Conclusions for practice Mexican women with earlier and later ages at menarche and/or longer time to menstrual regularity may have higher risk of cardio-metabolic disease in adulthood.

Fasting triglycerides and glucose index is more suitable for the identification of metabolically unhealthy individuals in the Chinese adult population: A nationwide study.

Aims/IntroductionMetabolic unhealth can be defined by the components of metabolic syndrome, which is closely connected to insulin resistance. We aimed to determine a simple index to identify metabolic unhealth in the Chinese adult population.Materials and MethodsA total of 30,291 individuals were screened from the China National Diabetes and Metabolic Disorders Study carried out from June 2007 to May 2008. Metabolic unhealth was defined using components of metabolic syndrome, except waist circumference. We compared the three surrogate indices of insulin resistance: the product of fasting triglycerides and glucose (TyG), triglycerides divided by high‐density lipoprotein cholesterol and the metabolic score for insulin resistance for the evaluation of metabolic status.ResultsAll indices had high sensitivity and specificity for the identification of metabolic unhealth, especially the TyG index with an area under the curve of 0.863 for men and 0.867 for women. Participants were divided into subgroups for further analysis. The TyG index also showed high diagnostic values, especially for younger individuals and men with normal waist circumference. Sex‐specific cut‐offs for three indices were also used to define metabolic unhealth. The TyG index showed the highest agreement with κ values of 0.603 and 0.605 for men and women between the components of metabolic syndrome and three indices.ConclusionsWe propose that the TyG index, just read in one blood laboratory test report, is simpler and more suitable for the identification of metabolically unhealthy individuals as well as who have high risk of cardiometabolic diseases of the Chinese adult population.

Genetic analyses in small-for-gestational-age newborns

SGA is often defined as a birth weight and/or length < −2 SDS for gestational age and gender [43]. A frequent cause of SGA is fetal growth restriction (FGR), often associated with perinatal mortality and morbidity and also implicated in a higher risk of cardio-metabolic disease in adulthood. Currently, no tools are available to predict or prevent FGR. Both genetic and environmental factors may affect fetal growth, but the underlying molecular mechanisms are still unclear. Genetic and epigenetic factors account for 30-50% of the variation in birth weight [44]. Chromosomal anomalies account for up to 19% of FGR fetuses, while the rate of submicroscopic duplications/deletions and single-gene disorders in FGR with normal karyotype is not defined [44]. A recent study showed that genomic microarray analysis (CMA) identifies sub-microscopic anomalies in 6.8% of fetuses with early growth restriction after common aneuploidies were excluded [45]. To date, the use of CMA is recommended for a fetus with one or more major malformations identified by ultrasound. Epigenetic mechanisms also explain abnormal fetal growth in conditions such as Silver-Russell and Beckwith-Wiedemann syndrome.

Midlife development of type 2 diabetes and hypertension in women by history of hypertensive disorders of pregnancy

BackgroundWomen with history of hypertensive disorders of pregnancy (HDP) are at increased risk of early onset cardiovascular disease and type 2 diabetes (T2D). We aimed to investigate the extent to which HDP is also associated with midlife development of T2D and hypertension above and beyond established risk factors.MethodsWe included parous women who attended population-based structured clinical visits at age 50 and 60 years in Sweden 1991–2013 (N = 6587). Women with prior diabetes mellitus, stroke, or ischemic heart disease at age 50 years were excluded. Data on reproductive history were collected from registries. To study the association between history of HDP and the between-visits development of T2D, hypertension, and clinical risk factors of cardiometabolic disease (body mass index (BMI), blood pressure, and total cholesterol), we utilized multivariable adjusted regression models (logistic, log binomial, and linear regression, respectively). Models included data on outcome risk factors at age 50 years, e.g. BMI, 75 g 2 h oral glucose tolerance test result, and mean arterial pressure, respectively.ResultsBetween ages 50 and 60 years, 5.8% of initially disease-free women developed T2D and 31.6% developed hypertension. History of HDP was associated with increased risk of developing T2D between age 50 and 60 years even when adjusting for risk factors, including BMI, at age 50 years (odds ratio (OR) 1.96, 95% confidence interval (CI) 1.29–2.98). By contrast, the higher risk of developing hypertension observed in women with history of HDP (relative risk (RR) 1.47, 95% CI 1.22–1.78) was attenuated when adjusted for risk factors (RR 1.09, 95% CI 0.94–1.25). Participants with a history of HDP had higher mean BMI and blood pressure at age 50 years, with levels roughly corresponding to those observed at age 60 years in unaffected women.ConclusionsWomen with history of HDP are not only at higher risk of cardiometabolic disease during their reproductive years, but HDP is also associated with midlife T2D development above and beyond established risk factors.

Comparison of ten-years risk of fatal cardiovascular events calculated by heartscore in diabetic patients with and without post-traumatic stress disorder (PTSD) comorbidity

IntroductionCardiovascular diseases (CVD) are the leading cause of death and disability-adjusted life years lost globally. Recent studies have shown that post-traumatic stress disorder (PTSD) predicts higher risk of cardiometabolic diseases, specifically cardiovascular disease and diabetes type 2.AimsTo assess cardiovascular event risk differences between diabetic patients with and without PTSD comorbidity.ObjectivesTo explore a ten-year risk of fatal CVD events in diabetic patients with and without PTSD; to gain better insight in potential different functioning patterns in these patient subgroups.MethodsWe investigated a cross-sectional sample consisting of 390 psychiatric inpatients and outpatients. Ten-years risk of fatal CVD events calculated by HeartScore, European society of cardiology. Europe high-risk version was used. The risk estimation is made based on: gender, age, smoking, systolic blood pressure and total cholesterol.ResultsBy analysis of covariance, we controlled possible confounding effects of gender, age, education, marital status, number of household members, work status, average monthly income per household member, body mass index (kg/m2), number of somatic comorbidities, number of psychiatric comorbidities, duration of PTSD, clinical global impression scale–severity of PTSD at diagnosis. After the adjustment for all these variables, interaction of PTSD and T2DM was significantly associated with CVD risk (P &lt; 0.001; Eta2 = 0.04).ConclusionA significant fatal CVD event risk differences between diabetic patients with and without PTSD comorbidity were found. Better awareness of possible underlying determinants provides better optimal individual approach planning, likewise effective prevention and control of cardiovascular diseases.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Effects of an Egg‐based, Carbohydrate‐restricted Diet on Body Composition, Fat Distribution, and Metabolic Health in Older Adults with Obesity: Preliminary results from a randomized controlled trial.

BackgroundAge‐related loss of lean mass, accumulation of visceral adipose tissue (VAT), and insulin resistance place aging adults with obesity at particularly high risk of cardio‐metabolic disease. By reducing insulin demand, carbohydrate (CHO)‐restricted diet patterns that include foods such as whole eggs may promote loss of body fat, specifically from the visceral cavity, without compromising lean mass and improve metabolic health in aging adults with obesity.ObjectiveThe objective of this study was to determine if consumption of an egg‐based lower‐CHO/high‐fat diet (EBD) vs a standard CHO‐based/low‐fat diet (STD) results in loss of total and visceral fat, preservation of lean mass, and improvements insulin resistance and the lipid profile.DesignIn a randomized clinical trial, 26 men and women age 60–75yrs. with obesity (BMI 30–40kg/m2) consumed either an EBD (&lt;25:25:&gt;50% energy from CHO:protein:fat) or STD (55:25:20) for 8 weeks. Participants were not asked to restrict total energy intake. The EBD group was provided eggs throughout the study, whereas the STD group was provided breakfast bars to consume. Body composition by DXA, resting energy expenditure (REE) by indirect calorimetry, and insulin, glucose, HOMA‐IR and lipids by fasting blood draw were assessed at baseline and after the 8‐week intervention.ResultsParticipants lost 11.0% and 2.3% total fat following the EBD and STD diet, resp. (p&lt;0.01 for difference between diets). The EBD group experienced ~3‐fold greater loss in VAT compared to the STD group (−23.3% vs −7.1%, p&lt;0.01 for difference between diets) and greater decrease in HOMA‐IR (p&lt;0.01), whereas there were no significant between‐group differences in change of total lean mass or REE. Among those in the EBD group, there was a significant decrease in triglycerides and increase in HDL.ConclusionsWhen compared to a standard high‐CHO, low fat diet, consumption of a diet lower in CHO supplemented with 3 whole eggs per day resulted in loss of fat mass, specifically from the visceral cavity while preserving lean mass and resting metabolic rate. This diet pattern also resulted in significant improvements in indices of metabolic health including insulin resistance, triglycerides and HDL cholesterol.Support or Funding InformationEgg Nutrition Center

Inhibition of 11β-hydroxysteroid dehydrogenase 2 by the fungicides itraconazole and posaconazole

Impaired 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2)-dependent cortisol inactivation can lead to electrolyte dysbalance, hypertension and cardiometabolic disease. Furthermore, placental 11β-HSD2 essentially protects the fetus from high maternal glucocorticoid levels, and its impaired function has been associated with altered fetal growth and a higher risk for cardio-metabolic diseases in later life. Despite its important role, 11β-HSD2 is not included in current off-target screening approaches. To identify potential 11β-HSD inhibitors among approved drugs, a pharmacophore model was used for virtual screening, followed by biological assessment of selected hits. This led to the identification of several azole fungicides as 11β-HSD inhibitors, showing a significant structure-activity relationship between azole scaffold size, 11β-HSD enzyme selectivity and inhibitory potency. A hydrophobic linker connecting the azole ring to the other, more polar end of the molecule was observed to be favorable for 11β-HSD2 inhibition and selectivity over 11β-HSD1. The most potent 11β-HSD2 inhibition, using cell lysates expressing recombinant human 11β-HSD2, was obtained for itraconazole (IC50 139±14nM), its active metabolite hydroxyitraconazole (IC50 223±31nM) and posaconazole (IC50 460±98nM). Interestingly, experiments with mouse and rat kidney homogenates showed considerably lower inhibitory activity of these compounds towards 11β-HSD2, indicating important species-specific differences. Thus, 11β-HSD2 inhibition by these compounds is likely to be overlooked in preclinical rodent studies. Inhibition of placental 11β-HSD2 by these compounds, in addition to the known inhibition of cytochrome P450 enzymes and P-glycoprotein efflux transport, might contribute to elevated local cortisol levels, thereby affecting fetal programming.

Physical activity as a vital sign in patients with bipolar disorder.

The most significant contributor to premature mortality in patients with bipolar disorder is preventable cardiovascular diseases. This study investigated if the Physical Activity Vital Sign (PAVS) assessment (two questions which clarify if a person meets the recommended 150min of physical activity per week) can identify patients with bipolar disorder at higher risk of cardio-metabolic abnormalities. Clinical differences between those who adhere and those who did not adhere to the physical activity guidelines were investigated using an ANCOVA controlling for age and gender. Sixty-five (29♂) in- and outpatients with bipolar disorder (age=45.1±9.8years) completed the PAVS-questions, underwent full-fasting metabolic screening, and performed a six-minute walk test (6MWT). Those patients not meeting the physical activity recommendations had a higher body mass index, performed worse on the 6MWT and were at a significantly higher risk for cardio-metabolic diseases. Relative risks ranged from 1.33 for having dyslipidemia to 5.33 for hyperglycemia. The current data offer the first evidence that the PAVS assessment might be a useful vital sign in the routine assessment of in- and outpatients with bipolar disorder.

Post-traumatic stress disorder and cardiometabolic disease: improving causal inference to inform practice.

Post-traumatic stress disorder (PTSD) has been declared 'a life sentence' based on evidence that the disorder leads to a host of physical health problems. Some of the strongest empirical research - in terms of methodology and findings - has shown that PTSD predicts higher risk of cardiometabolic diseases, specifically cardiovascular disease (CVD) and type 2 diabetes (T2D). Despite mounting evidence, PTSD is not currently acknowledged as a risk factor by cardiovascular or endocrinological medicine. This view is unlikely to change absent compelling evidence that PTSD causally contributes to cardiometabolic disease. This review suggests that with developments in methods for epidemiological research and the rapidly expanding knowledge of the behavioral and biological effects of PTSD the field is poised to provide more definitive answers to questions of causality. First, we discuss methods to improve causal inference using the observational data most often used in studies of PTSD and health, with particular reference to issues of temporality and confounding. Second, we consider recent work linking PTSD with specific behaviors and biological processes, and evaluate whether these may plausibly serve as mechanisms by which PTSD leads to cardiometabolic disease. Third, we evaluate how looking more comprehensively into the PTSD phenotype provides insight into whether specific aspects of PTSD phenomenology are particularly relevant to cardiometabolic disease. Finally, we discuss new areas of research that are feasible and could enhance understanding of the PTSD-cardiometabolic relationship, such as testing whether treatment of PTSD can halt or even reverse the cardiometabolic risk factors causally related to CVD and T2D.

Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses.

Sleep loss and insufficient sleep are risk factors for cardiometabolic diseases, but data on how insufficient sleep contributes to these diseases are scarce. These questions were addressed using two approaches: an experimental, partial sleep restriction study (14 cases and 7 control subjects) with objective verification of sleep amount, and two independent epidemiological cohorts (altogether 2739 individuals) with questions of sleep insufficiency. In both approaches, blood transcriptome and serum metabolome were analysed. Sleep loss decreased the expression of genes encoding cholesterol transporters and increased expression in pathways involved in inflammatory responses in both paradigms. Metabolomic analyses revealed lower circulating large HDL in the population cohorts among subjects reporting insufficient sleep, while circulating LDL decreased in the experimental sleep restriction study. These findings suggest that prolonged sleep deprivation modifies inflammatory and cholesterol pathways at the level of gene expression and serum lipoproteins, inducing changes toward potentially higher risk for cardiometabolic diseases.

Physical activity as a vital sign in patients with schizophrenia: Evidence and clinical recommendations

AimThis study investigated whether in patients with schizophrenia the Physical Activity Vital Sign (PAVS) assessment can identify those at higher risk of cardio-metabolic abnormalities. MethodsOne hundred patients with schizophrenia completed the PAVS-questions exploring whether they adhered to the general physical activity recommendations, underwent a full-fasting metabolic screening, and performed a six-minute walk test (6MWT). ResultsThose who do not adhere to the health recommendations according to the PAVS (n=61) were significantly older (37.1±11.3 versus 32.5±8.5years, P=0.033) and more likely to be women (30/36 versus 31/64, P<0.001). Patients who do not meet the physical activity recommendations have a higher BMI (27.0±6.4 versus 23.3±3.1, P=0.017) performed worse on the 6MWT (531.1±84.2m versus 657.0±98.2m, P<0.001) and are at a significantly higher risk for cardio-metabolic diseases. Relative risks ranged from 1.07 (0.84–1.36) for having dyslipidemia to 4.65 (1.77–12.17) for having hypertension. ConclusionsPAVS-baseline assessment should be included in the routine assessment of people with schizophrenia.

Polycystic ovary syndrome and metabolic syndrome in Indigenous Australian women.

Polycystic ovary syndrome (PCOS) affects around 15% of Indigenous women who are also a group at high risk of cardiometabolic disease. To explore the impact of PCOS on metabolic syndrome in Indigenous women. A cross-sectional reproductive health questionnaire, biochemical and anthropometric assessments, of 109 Indigenous women (35 with PCOS and 74 without PCOS) aged 15-44 years in and around Darwin between 2003 and 2005. PCOS was defined using the National Institutes of Health criteria, and metabolic syndrome (MetS) using the National Cholesterol Education Programme Adult Treatment Programme III criteria. The outcome was prevalence of MetS by PCOS status; relationship of PCOS with MetS before and after adjustment for markers of obesity and insulin resistance. Women with PCOS had a significantly higher body mass index (BMI) (P = 0.0001) and MetS was more frequent in women with PCOS (51%) than those without PCOS (23%) (P = 0.003). The most frequent components of MetS in both groups were a high density lipoprotein cholesterol ≤1.29 mmol/L (80% PCOS, 55% non-PCOS) and a waist circumference >88 cm (77% PCOS, 41% non-PCOS); these were significantly more frequent in women with PCOS (P = 0.01). In logistic regression models, PCOS was significantly associated with MetS by itself but not after adjustment for BMI or sex hormone binding globulin. While MetS was more common in Indigenous women with PCOS, PCOS was not an independent predictor of MetS. This may be because obesity and insulin resistance are integral parts of PCOS and are the mechanisms through which PCOS exerts metabolic effects.

Cardiometabolic risk factors in young adults who were born preterm.

Adults who were born preterm with a very low birth weight have higher blood pressure and impaired glucose regulation later in life compared with those born at term. We investigated cardiometabolic risk factors in young adults who were born at any degree of prematurity in the Preterm Birth and Early Life Programming of Adult Health and Disease (ESTER) Study, a population-based cohort study of individuals born in 1985–1989 in Northern Finland. In 2009–2011, 3 groups underwent clinical examination: 134 participants born at less than 34 gestational weeks (early preterm), 242 born at 34–36 weeks (late preterm), and 344 born at 37 weeks or later (controls). Compared with controls, adults who were born preterm had higher body fat percentages (after adjustment for sex, age, and cohort (1985–1986 or 1987–1989), for those born early preterm, difference = 6.2%, 95% confidence interval (CI): 0.4, 13.2; for those born late preterm, difference = 8.0%, 95% CI: 2.4, 13.8), waist circumferences, blood pressure (for those born early preterm, difference = 3.0 mm Hg, 95% CI: 0.9, 5.1; for those born late preterm, difference = 1.7, 95% CI: −0.1, 3.4), plasma uric acid levels (for those born early preterm, difference = 20.1%, 95% CI: 7.9, 32.3; for those born late preterm, difference = 20.2%, 95% CI: 10.7, 30.5), alanine aminotransferase levels, and aspartate transaminase levels. They were also more likely to have metabolic syndrome (for those born early preterm, odds ratio = 3.7, 95% CI: 1.6, 8.2; for those born late preterm, odds ratio = 2.5, 95% CI: 1.2, 5.3). Elevated levels of conventional and emerging risk factors suggest a higher risk of cardiometabolic disease later in life. These risk factors are also present in the large group of adults born late preterm.

Socioeconomic status is positively associated with measures of adiposity and insulin resistance, but inversely associated with dyslipidaemia in Colombian children

BackgroundLow socioeconomic status (SES) has been associated with higher risk of cardiometabolic diseases in developed societies, but investigation of SES and cardiometabolic risk in children in less economically developed populations...

Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change.

Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood. We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16-39 y; 51% women; mean ± standard deviation BMI 24 ± 4 kg/m(2)). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p<0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%-183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87% ± 3%; R(2)= 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p<0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic effects (correspondence 160% ± 2%; R(2) = 0.92). Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary.

Life's Simple 7 and incidence of diabetes among American Indians: the Strong Heart Family Study.

OBJECTIVEThe American Heart Association’s recommendations for optimal health, summarized in Life’s Simple 7, have been associated with reduced risk of cardiovascular disease (CVD)-related end points, but no studies have examined the association of these goals with incident type 2 diabetes, which is associated with high risk for CVD. The purpose of this analysis was to examine the associations of Life’s Simple 7 goals with incident diabetes among American Indians, a population at high risk of cardiometabolic diseases.RESEARCH DESIGN AND METHODSStrong Heart Family Study participants without diabetes (n = 1,639) at baseline and who participated in a follow-up examination were included in the analysis. Risk scores ranging from 0 to 7 were created using physical activity, diet, BMI, smoking, blood pressure, fasting glucose, and cholesterol metrics in accordance with Life’s Simple 7 goals. Diabetes was defined using 2003 American Diabetes Association criteria, including use of insulin or oral antidiabetes medication or a follow-up fasting plasma glucose level ≥126 mg/dL. Generalized estimating equations were used to examine the association of risk scores with incident diabetes.RESULTSDuring a mean 5-year follow-up (range 4–8 years), we identified 210 cases of incident type 2 diabetes. Compared with participants who achieved 0–1 goals, those who achieved 2–3 or 4+ goals had lower odds of diabetes, with odds ratios = 0.40 (95% CI 0.29–0.56) and 0.11 (95% CI 0.05–0.21), respectively.CONCLUSIONSThe adoption of as few as two or three Life’s Simple 7 goals is associated with a lower risk of diabetes.

Microsatellite polymorphism in the heme oxygenase-1 promoter is associated with nonsevere and late-onset preeclampsia.

Preeclampsia is a serious and phenotypically heterogeneous vascular pregnancy disorder. Heme oxygenase-1 (HO-1) is a stress response enzyme that may protect the maternal endothelium and facilitate adequate metabolic adaptation to pregnancy by its antioxidant and anti-inflammatory functions. HO-1 stress response is modulated by HO-1 gene (HMOX1) polymorphisms. Individuals with the long allele of a guanine-thymine (GTn) microsatellite repeat located in the promoter region of HMOX1 have a higher risk of cardiometabolic diseases compared with those with the short allele. We investigated whether the long GTn allele of HMOX1 is associated with subtypes of preeclampsia. The GTn repeat was genotyped in 759 patients and in 779 controls from the Finnish Genetics of Preeclampsia Consortium (FINNPEC) cohort using DNA fragment analysis. In subtype analyses, the long-long (LL) genotype was associated with nonsevere (additive model: odds ratio [OR], 1.94; 95% confidence interval [CI], 1.13-3.31; recessive model: OR, 1.39; 95% CI, 1.02-1.89) and late-onset (additive model: OR, 1.44; 95% CI, 1.02-2.05; recessive model: OR, 1.28; 95% CI, 1.02-1.59) preeclampsia and with preeclampsia without a small-for-gestational-age infant (recessive model: OR, 1.27; 95% CI, 1.02-1.58). The long allele was associated with nonsevere (OR, 1.35; 95% CI, 1.07-1.70) and late-onset (OR, 1.21; 95% CI, 1.03-1.42) preeclampsia and with preeclampsia without a small-for-gestational-age infant (OR, 1.19; 95% CI, 1.02-1.40). Moreover, both the LL genotype and the long allele were associated with preeclampsia in women who had smoked during pregnancy. In conclusion, the GTn long allele seems to predispose to late-onset, less severe form of preeclampsia. This finding supports the role of HO-1 in the pathogenesis of preeclampsia and suggests that the HO-1 pathway may provide a potential target for the treatment of preeclampsia.

Cluster analysis of cardiovascular and metabolic risk factors in women of reproductive age

To study the association between endocrine disturbances and metabolic complications in women seeking gynecologic care. Retrospective study, cluster analysis. Outpatient clinic, university medical center. 573 women, including 384 at low risk and 189 at high risk of cardiometabolic disease. None. Cardiovascular and metabolic parameters and clinical and biochemical characteristics. Risk factors for metabolic disease are associated with a low age of menarche, high levels of high-sensitivity C-reactive protein and liver enzymes, and low levels of sex hormone-binding globulin. Overweight/obese status, polycystic ovary syndrome, oligo/amenorrhea, and hyperandrogenism were found to increase the risk of cardiometabolic disease. However, hyperprolactinemia and premature ovarian failure were not associated with the risk of cardiometabolic disease. In terms of androgens, the serum total testosterone level and free androgen index but not androstenedione or dehydroepiandrosterone sulfate (DHEAS) were associated with cardiometabolic risk. Although polycystic ovary syndrome is associated with metabolic risk, obesity was the major determinant of cardiometabolic disturbances in reproductive-aged women. Hyperprolactinemia and premature ovarian failure were not associated with the risk of cardiovascular and metabolic diseases. NCT01826357.