Edematous severe acute malnutrition is characterized by hypomethylation of DNA.

Edematous severe acute childhood malnutrition (edematous SAM or ESAM), which includes kwashiorkor, presents with more overt multi-organ dysfunction than non-edematous SAM (NESAM). Reduced concentrations and methyl-flux of methionine in 1-carbon metabolism have been reported in acute, but not recovered, ESAM, suggesting downstream DNA methylation changes could be relevant to differences in SAM pathogenesis. Here, we assess genome-wide DNA methylation in buccal cells of 309 SAM children using the 450 K microarray. Relative to NESAM, ESAM is characterized by multiple significantly hypomethylated loci, which is not observed among SAM-recovered adults. Gene expression and methylation show both positive and negative correlation, suggesting a complex transcriptional response to SAM. Hypomethylated loci link to disorders of nutrition and metabolism, including fatty liver and diabetes, and appear to be influenced by genetic variation. Our epigenetic findings provide a potential molecular link to reported aberrant 1-carbon metabolism in ESAM and support consideration of methyl-group supplementation in ESAM.

Imaging for Predicting, Detecting, and Managing Complications After Transcatheter Aortic Valve Replacement.

The management of patients with valvular heart disease is increasingly reliant on multimodal cardiac imaging. In patients with severe aortic stenosis considered for transcatheter aortic valve replacement, careful pre-procedural planning with multimodal imaging is necessary to avoid and prevent complications during the procedure. During or immediately after the procedure, rapid echocardiographic assessment is important to assess the new valve's function and manage major complications. Echocardiography, cardiac computed tomography, and cardiac magnetic resonance imaging all share important roles in the post-procedural evaluation of abnormal transcatheter valve function. This review discusses the use of multimodal imaging for predicting, detecting, and managing complications after TAVR.

Pulmonary Venous Waveforms Predict Rehospitalization and Mortality After Percutaneous Mitral Valve Repair.

OBJECTIVES: In this study, the authors hypothesized that intraprocedural improvement of pulmonary venous (PV) waveforms are predictive of improved outcomes. In this report, they analyzed intraprocedural invasive and echocardiographic changes with respect to rehospitalization and mortality. BACKGROUND: The effects of hemodynamic changes during percutaneous mitral valve repair (PMVR) with MitraClip (Abbott Vascular, Santa Clara, California) are incompletely characterized. METHODS: The authors retrospectively reviewed records and intraprocedural transesophageal echocardiograms of 115 consecutive patients (age 76 ± 12 years) who underwent PMVR for mitral regurgitation (MR) from May 2013 to January 2017 at Emory University Hospital. They assessed intraprocedural PV waveforms for improvement in morphology, measured change in MR grade by semiquantitative methods, evaluated invasive changes in left atrial pressure (LAP) and V-wave, and compared with 30-day and 1-year rehospitalization and all-cause mortality. RESULTS: Ninety-three cases (80%) had PV waveforms before and after clip placement sufficient for analysis, of which 67 (73%) demonstrated intraprocedural improvement in PV morphology and 25 (27%) did not. At 24 months, 57 (85%) of those with PV improvement were living, compared with only 10 (40%) of those without improvement. Proportional hazards models demonstrated a significant survival advantage in those with PV improvement (hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.08 to 0.93, p = 0.038). By multivariable analysis, PV improvement predicted reduced 1-year cardiac rehospitalization (odds ratio [OR]: 0.18, p = 0.044). Intraprocedural assessment of MR grade and invasive hemodynamics did not consistently predict mortality and rehospitalization. CONCLUSIONS: PV waveforms are important markers of procedural success after PMVR. Our data show intraprocedural PV waveforms may predict rehospitalization and mortality after PMVR. A larger, multicenter cohort will be important to clarify this relationship.

Radioprotective strategies for interventional echocardiographers during structural heart interventions.

OBJECTIVE: We investigated radioprotective strategies for the interventional echocardiographer (IE) during structural heart interventions in comparison with the interventional cardiologist (IC). BACKGROUND: Structural heart interventions are expanding in complexity with increased reliance on IE. Recent reports have demonstrated concerning exposure and higher radiation to the IE. METHODS: We monitored 32 structural interventions - 19 transcatheter aortic valve replacements (TAVR), 6 transcatheter mitral valve repairs, 5 paravalvular leak closures, and 2 atrial septal defect closures. Seventeen utilized transesophageal echocardiography (TEE) while 15 used transthoracic echocardiography (TTE). Members of the IC and IE teams wore multiple dosimeters on different sites of the body to measure radiation dose to the total body, lens of the eye, and hand. During each case, IE utilized dedicated radiation shielding. RESULTS: Mean doses were higher for the primary IC than the primary IE: IC#1-99, 222, 378; IE#1-48, 52, 416 (body, lens, and hand doses in µSv). IE radioprotective strategies were able to reduce body and lens doses compared to IC during both TTE and TEE-guided procedures. Hand equivalent dose remained higher for the IE driven by exposure during TEE-guided procedures (IC#1 294 vs. IE#1 676 µSv). In a subgroup using radioprotective drapes during TTE-guided TAVR, IC dose was reduced without effect on the IE. CONCLUSIONS: Radiation exposure during structural heart interventions is concerning. With dedicated shielding, IE received lower doses to the body and lens than IC. Further optimization of structural suite design and shielding is needed.

Exploring putative genetic determinants of inter-individual phenotypic heterogeneity in sickle cell disease: A cross-sectional Jamaican cohort-based study.

Patients with sickle cell disease (SCD) display puzzling inter-individual phenotypic heterogeneity, conceivably related to inherent differences in antioxidant protection, hemoglobin binding, bilirubin catabolism and methyl group handling. Therefore, we explored putative associations between clinically important phenotypic measures and functional polymorphisms within specific candidate genes encoding glutathione S-transferase, haptoglobin, uridine 5'-diphospho-glucuronosyltransferase 1A1, methyl tetrahydrofolate reductase, 5-methyltetrahydrofolate-homocysteine methyltransferase, and cystathionine beta-synthase. Two-hundred and thirty SCD participants (mean age 25.1 ±â€¯2.8) were recruited from Jamaica's Annual Sickle Cell Unit Cohort Review - two-hundred and five had homozygous hemoglobin SS (HbSS) disease, twenty-five had hemoglobin SC (HbSC) disease. Regression analyses revealed some novel genotype-phenotype associations. HbSC participants had significantly lower mean lactate dehydrogenase (p = 0.01) and glutathione (p < 0.001) values than HbSS participants. Glutathione S-transferase P1 (GSTP1) was significantly associated with mean corpuscular hemoglobin concentration using univariate (p = 0.044) and multivariable regression (p = 0.012). 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) was significantly associated with hemoglobin F % using univariate (p = 0.010) and multivariable regression (p = 0.009). In conclusion, this exploratory cross-sectional study generated novel, useable, and informative genotype-phenotype estimates of association, but larger studies are needed to determine whether these specific variants are related to inter-individual phenotypic variability in SCD.

Mean Aortic pressure gradient and global longitudinal strain recovery after transcatheter aortic valve replacement - A retrospective analysis.

BACKGROUND: Global longitudinal strain (GLS) has incremental value in assessing left ventricular (LV) function in severe aortic stenosis and is related to clinical outcome after transcatheter aortic valve replacement (TAVR). We sought to identify relevant echocardiographic predictors of GLS improvement and myocardial function recovery after TAVR. METHODS: We analyzed baseline and 12-month follow-up echocardiograms for LV strain analysis from 123 patients who underwent at Emory University Hospital with the Edwards SAPIEN valve between 7/2007 and 7/2013. RESULTS: At baseline, 61 had reduced LV ejection fraction (LVEF) ≤50% (rEF), and 80 had preserved LVEF >50% (pEF). Higher baseline mean pressure gradient (MPG) and aortic peak velocity (AV Vmax) predicted myocardial function recovery defined as ≥20% improvement in global longitudinal strain (r = 0.29, p < .001; r = 0.26, p = .002). When analyzing subjects with discordant changes in GLS and LVEF at follow-up, subjects with improved GLS, although reduced LVEF after TAVR, experienced a greater reduction in MPG and AV Vmax (-40 vs. -30, p = 0.015; -2.3 vs. -1.9, p = .021) after the procedure. CONCLUSIONS: In high-risk patients undergoing TAVR for severe aortic stenosis, GLS is impaired and more impaired in patients with reduced EF. Higher baseline MPG predicts myocardial function recovery. GLS improvement after TAVR is related to relief of pressure overload.

A cross-sectional clinic-based study exploring whether variants within the glutathione S-transferase, haptoglobin and uridine 5'-diphospho-glucuronosyltransferase 1A1 genes are associated with interindividual phenotypic variation in sickle cell anaemia in Jamaica.

OBJECTIVES: To explore putative associations between specific variants in either the glutathione S-transferase (GST), haptoglobin (HP) or uridine 5'-diphospho-glucuronosyltransferase 1A1 (UGT1A1) genes and clinically important phenotypes in sickle cell anaemia (HbSS). METHODS: 371 HbSS participants were recruited from the Sickle Cell Clinic of the Sickle Cell Unit at the University of the West Indies, Kingston, Jamaica. Markers within four GST superfamily genes, the HP gene and the UGT1A1 gene were analysed using PCR-based assays. RESULTS: Multivariable regression revealed statistically significant associations between the GSTP1 Ile105Val heterozygote and HbA2 levels (P = .016), HbF percentage (P = .001), MCH concentration (P = .028) and reticulocyte count (P = .032), while the GSTM3 D/D homozygote was significantly associated with HbA2 levels (P = .032). The UGT1A1 (TA)6 /(TA)8 heterozygote showed statistically significant associations with HbA2 levels (P = .019), HbF percentage (P < .001), haemoglobin levels (P = .008), PCV values (P = .007) and RBC counts (P = .041). CONCLUSION: This exploratory cross-sectional study has generated novel and informative genotype-phenotype estimates of association, but larger studies are needed to determine whether these specific variants within the GST, UGT1A1 and HP genes are related to interindividual phenotypic variability in HbSS.

Paravalvular Regurgitation after Transcatheter Aortic Valve Replacement: Comparing Transthoracic versus Transesophageal Echocardiographic Guidance.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is increasingly being performed in cardiac catheterization laboratories using transthoracic echocardiography (TTE) to guide valve deployment. The risk of paravalvular regurgitation (PVR) remains a concern. METHODS: We retrospectively reviewed 454 consecutive patients (mean age, 82 ± 8; 58% male) who underwent transfemoral TAVR at Emory Healthcare from 2007 to 2014. Two hundred thirty-four patients underwent TAVR in the cardiac catheterization laboratory with TTE guidance (TTE-TAVR; mean Society of Thoracic Surgeons score, 10%), while 220 patients underwent the procedure in the hybrid operating room with transesophageal echocardiography (TEE) guidance (TEE-TAVR; mean Society of Thoracic Surgeons score, 11%). All patients received an Edwards valve (SAPIEN 55%, SAPIEN-XT 45%). Clinical and procedural characteristics, echocardiographic parameters, and incidence of PVR were compared. RESULTS: The incidence of at least mild PVR at discharge was comparable between TTE-TAVR and TEE-TAVR (33% vs 38%, respectively; P = .326) and did not differ when stratified by valve type. However, in the TTE-TAVR group, there was a higher incidence of second valve implantation (7% vs 2%; P = .026) and postdilation (38% vs 17%; P < .001) during the procedure. Although not independently associated with PVR at discharge (odds ratio = 1.12; 95% CI, 0.69-1.79), TTE-TAVR was associated with PVR-related events: the combined outcome of mild PVR at discharge, intraprocedural postdilation, and second valve insertion (odds ratio = 1.58; 95% CI, 1.01-2.46). There were no significant differences in PVR at 30 days, 6 months, and 1 year between the two groups. CONCLUSIONS: TTE-TAVR in a high-risk group of patients was associated with increased incidence of intraprocedure PVR-related events, although it was not associated with higher rates of PVR at follow-up. Multicenter randomized trials are required to confirm the cost-effectiveness and safety of TTE-TAVR.

Repair of prosthetic mitral valve paravalvular leak using an off-pump transapical approach.

Patients who present with significant paravalvular regurgitation after mitral valve replacement remain a difficult patient population and high-risk surgical candidates. We present 3 cases of transapical closure of mitral valve paravalvular leak (PVL) after mitral valve replacement using Amplatzer closure devices (AGA Medical Corp, Plymouth, MN). All 3 patients experienced decreased regurgitation at the site of the closure as well as symptomatic improvement in their heart failure.

Correlates of tricuspid regurgitation as determined by 3D echocardiography: pulmonary arterial pressure, ventricle geometry, annular dilatation, and papillary muscle displacement.

BACKGROUND: While it is understood that annular dilatation contributes to tricuspid regurgitation (TR), other factors are less clear. The geometry of the right ventricle (RV) and left ventricle (LV) may alter tricuspid annulus size and papillary muscle (PM) positions leading to TR. METHODS AND RESULTS: Three-dimensional echocardiographic images were obtained at Emory University Hospital using a GE Vivid 7 ultrasound system. End-diastolic area was used to classify ventricle geometry: control (n=21), isolated RV dilatation (n=17), isolated LV dilatation (n=13), and both RV and LV dilatation (n=13). GE EchoPAC was used to measure annulus area and position of the PM tips. Patients with RV dilatation had significant (P≤ 0.05) displacement of all PMs apically and the septal PM and posterior PM away from the center of the RV toward the LV. Patients with LV dilatation had significant (P≤0.05) apical displacement of the anterior PM. Pulmonary arterial pressure (r=0.66), annulus area (r=0.51), apical displacement of the anterior PM (r=0.26), posterior PM (r=0.49), and septal PM (r=0.40), lateral displacement of the septal PM (r=0.37) and posterior PM (r=0.40), and tenting area and height (r=0.54, 0.49), were significantly (P≤0.05) correlated to the grade of TR. Ventricle classification (r=0.46) and RV end-diastolic area (r=0.48) also were correlated with the grade of TR. A regression analysis found ventricle classification (P=0.001), pulmonary arterial pressure (P≤0.001) annulus area (P=0.027), and apical displacement of the anterior PM (P=0.061) to be associated with the grade of TR. CONCLUSIONS: Alterations in ventricular geometry can lead to TR by altering both tricuspid annulus size and PM position. Understanding these geometric interactions with the aim of correcting pathological alterations of the tricuspid valve apparatus may lead to more robust repairs.

Right ventricular function in adult patients with Eisenmenger physiology: insights from quantitative echocardiography.

BACKGROUND: The favorable outcomes of Eisenmenger syndrome (ES) relative to other forms of pulmonary arterial hypertension (PAH) have been partially attributed to a unique adaptation of the right ventricle (RV). However, conventional measures of RV function may not adequately express this adaptation. METHODS: We studied 23 patients with ES (age 43 ± 17 years, 16 women, pulmonary artery systolic pressure [PASP] 93 ± 26 mmHg), 25 patients with PAH (age 44 ± 13 years, 17 women, PASP 92 ± 19 mmHg), and 25 subjects without known structural disease (age 45 ± 16 years, 17 women). We evaluated long- and short-axis function of the RV with two-dimensional strain and anatomical M-mode echocardiography, respectively. RESULTS: Long-axis function of the RV was comparable between patients with ES and PAH although depressed relative to controls (global strain, -15.6 ± 4.7, -14.9 ± 4.3, and -22.4 ± 2.8%, respectively, P < 0.001; global RV systolic strain rate, -0.77 ± 0.26, -0.84 ± 0.24, and -1.11 ± 0.21 1/sec, respectively, P < 0.001). However, short-axis RV function was significantly better in patients with ES versus those with PAH and preserved relative to controls (RV fractional shortening by anatomical M-mode, median [interquartile range], 21%[14-33%], 14%[10-16%], and 26%[22-36%], respectively, P = 0.002 for ES vs. PAH, P = 0.09 for ES vs. controls). This differential was not reflected in conventional measures of RV function (fractional area change, 32 ± 10 vs. 29 ± 8% in ES and PAH, respectively, P = 0.26). CONCLUSION: In patients with ES, the RV is characterized by preserved short-axis function, despite a depressed long-axis function. Thus, conventional assessment of RV function might not be suitable for patients with ES.

Use of balloon aortic valvuloplasty to size the aortic annulus before implantation of a balloon-expandable transcatheter heart valve.

OBJECTIVES: Our aim was to describe the use of balloon aortic valvuloplasty (BAV) to select proper transcatheter heart valve (THV) size. BACKGROUND: Transesophageal echocardiogram (TEE) measurement alone of the aortic annulus may not be adequate to select a THV size. BAV can more accurately size the aortic annulus. We report our experience using this strategy in patients undergoing THV implantation. METHODS: Twenty-seven patients underwent sizing of the aortic annulus by BAV and TEE. We implanted the minimal THV size that was greater than the annulus measured by BAV. RESULTS: The annulus measured by TEE was 21.3 +/- 1.6 mm and by BAV was 22.6 +/- 1.8 mm (p < 0.001). The number of balloon inflations was 2.7 +/- 0.7 (range 2 to 4), and the balloon sizes used were 22.0 +/- 1.8 mm (range 20 to 25 mm). Fourteen patients (52%) required upsizing of the initial balloon suggested by TEE; rapid pacing duration was 8 +/- 1.3 s (range 6 to 11 s). No change in aortic insufficiency or hemodynamic instability occurred with BAV. Fifteen patients (56%) received a 23-mm THV; 12 patients a 26-mm THV. No coronary occlusion, annular damage, or THV embolization occurred. Paravalvular leak was grade

Evaluation of right intraventricular dyssynchrony by two-dimensional strain echocardiography in patients with pulmonary arterial hypertension.

BACKGROUND: Right ventricular (RV) function has major prognostic implications for patients with pulmonary arterial hypertension (PAH). Intraventricular dyssynchrony might play an important role in RV dysfunction in these patients. METHODS: Thirty-six patients with PAH without right bundle branch block (mean age 44 +/- 14 yr, 24 women) and 39 controls (mean age 43 +/- 18 yr, 26 women) were evaluated. Global and segmental RV longitudinal deformation parameters were recorded by 2-dimensional strain echocardiography from apical 4-chamber views using a 6-segment RV model. The standard deviation of the heart rate-corrected intervals from QRS onset to peak strain for the 6 segments (RV-SD(6)) was used to quantify right intraventricular dyssynchrony. RESULTS: RV-SD(6) was significantly higher in patients with PAH compared with controls (63 +/- 21 vs 25 +/- 15ms, P < .001). Dyssynchrony in patients with PAH was found to derive mainly from delayed contraction of the basal and mid RV free wall. In patients with PAH, RV-SD(6) was strongly correlated with RV fractional area change (beta = -.519, P = .002), RV myocardial performance index (beta = .427, P = .009), and RV global strain (beta = .512, P = .002); in models controlling for RV systolic pressure, RV size, and QRS duration, RV-SD(6) was still an independent predictor of RV fractional area change (beta = -.426, P = .005) and RV global strain (beta = .358, P = .031). RV function was significantly worse in the subgroup of patients with PAH (n = 25) with RV-SD(6) > 55 ms (the upper 95% limit in controls). CONCLUSION: Right intraventricular dyssynchrony, as quantified by 2-dimensional strain echocardiography, is prevalent in PAH and is associated with more pronounced RV dysfunction. The clinical implications of these findings remain to be determined in follow-up studies.

Glutathione S-transferase polymorphisms may be associated with risk of oedematous severe childhood malnutrition.

It has been estimated that more than 50 % of deaths before the age of 5 years have undernutrition as an underlying cause. Severe childhood malnutrition, an extreme form of undernutrition, occurs as oedematous and non-oedematous syndromes. The reasons why only some children develop oedematous severe childhood malnutrition (OSCM) have remained elusive, but the heterogeneity of clinical appearances among children from relatively homogeneous backgrounds suggests that interindividual variation in susceptibility to OSCM may exist. We investigated variants of four glutathione S-transferase (GST) genes in a retrospective study among subjects (n 136) previously admitted to the Tropical Metabolism Research Unit, Jamaica, for the treatment of either OSCM (cases) or non-oedematous severe childhood malnutrition (controls). We found that GSTP1 Val(105) homozygotes were significantly more common among the cases (odds ratio (OR) 3.5; 95 % CI 1.1, 10.8). We also found an association of borderline significance between non-deletion GSTT1 genotypes (i.e. +/+ or +/0) and OSCM (OR 2.4; 95 % CI 1.0, 5.9). There was no significant association between OSCM and any of the other GST variants. These preliminary findings suggest that genetic variation within the GST superfamily may contribute to the risk of OSCM. Additional, larger data sets and studies of variants in other candidate genes are required in order to properly assess the true contribution, if any, of genetic variation to risk of OSCM. Such studies may improve our understanding of the causes of clinical heterogeneity in malnutrition.

The use of echocardiography for the evaluation of dyssynchrony.

Tissue Doppler imaging (TDI), is a new imaging tool that allows measurement of dyssynchrony. In several small studies, TDI predicted clinical response and reverse remodeling after cardiac resynchronization therapy (CRT). Moreover, it allowed detection of mechanical dyssynchrony in heart failure patients with narrow QRS. Using TDI, the selection criteria for CRT might be changed to include heart failure patients with narrow QRS. Furthermore, it will help predict responders to this therapy, hence decreasing the percentage of nonresponders and allowing a more cost-effective use of this new technology.

Polymorphisms in genes involved in folate metabolism as risk factors for oedematous severe childhood malnutrition: a hypothesis-generating study.

BACKGROUND: Severe childhood malnutrition (SCM) occurs as both oedematous and non-oedematous syndromes. The reasons why some children develop oedematous SCM (OSCM) have remained elusive but differences in clinical presentation among malnourished children from similar backgrounds suggests that there might be inter-individual variation in susceptibility to OSCM. AIM: To estimate the strength of the association between variants of three genes involved in folate/methyl group metabolism [methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR) and cystathionine beta-synthase (CBS)] and risk of OSCM. METHODS: Patients previously admitted to the Tropical Metabolism Research Unit (TMRU) for treatment of either OSCM (cases, n = 74) or non-oedematous SCM (NOSCM, controls, n = 50) were recruited. Genotypes at four sites within the three genes (MTHFR C677T, MTHFR A1298C, MTR A2756G and CBS 844ins68) were determined using PCR-based assays. RESULTS: The MTHFR 677T [odds ratio (OR) 0.63, 95% CI 0.2-1.7] and MTR 2756G (OR 0.74, 95% CI 0.4-1.4) alleles were associated with moderate reduction in risk of OSCM whereas the CBS 844ins68 allele (OR 1.4, 0.7-2.4) was associated with an increased risk. None of these risks was significant at the 5% level. CONCLUSIONS: Genetic variation within folate/methyl group metabolic pathways might have a small but potentially important influence on risk of OSCM. Additional, larger data-sets will be required to test the specific hypotheses (about the putative effect size and direction of association) generated in this preliminary study. Such observations have the potential to improve our understanding of the pathogenesis of clinical heterogeneity in severe malnutrition.

The effect of aromatic amino acid supplementation on a1- antirypsin synthesis in oedematous malnutrition

OBJECTIVES: We have previously demonstrated that infected children with oedematous protein energy malnutrition have an impaired acute phase response to infection. We hypothesize that this impaired response is due to a relative shortage of aromatic amino acids. We therefore sought to determine whether supplementation of the diet of infected oedematous malnourished children with aromatic amino acids (70 mg/kg/d phenylalanine, 80 mg/kg/d N-acetyltyrosine, 30 mg/kg/d tryptophan) would increase the rate of synthesis of acute phase proteins compared with an isonitrogenous diet supplemented with alanine. METHODS: In oedematous malnourished children, a primed continuous infusion of 3H2-leucine was used to determine the in vivo synthesis rates of a1-antirypsin (a1-at), an acute phase protein, when they were infected (Study 1) and after clearing of infection (Study 2). RESULTS: There was effect of aromatic amino acid supplementation on the rate of synthesis or concentration of a1-at. CONCLUSION: Supplementation of the diet of oedematous malnourished children with aromatic amino acids did not enhance the immune response as determined by the in vivo synthesis of a1-at. (AU)

The Trp64 A rg mutation of the B3- Adrenergic Receptor Is associated with hyperglycemia and current body mass index in Jamaican women

The Trp64Arg mutation the the beta3-adrenergic receptor (beta3-AR) has been linked to earlier onset of non-insulin-dependent diabetes mellitus (NIDDM), insulin resistance, abdominal obesity, and an increase capacity to gain weight in some European and Japanese populations. We studied the prevalence of the mutation and its association with NIDDM and obesity in our population, in which both rates are high, especially in women. The frequency of the homozygous mutation was 1.53 percent, and of the Arg allele, 10.5 percent. Rates were similar in men and women. Significantly higher body mass index (BMI), weight, hip circumference, and fasting and postchallenge 2 hour blood glucose concentrations were associated with the presence of the Arg allele in women but not in men. The association with weight and hip measurements and with hyperglycemia was present only in women aged less than 55 years. In multivariate analysis, the mutation was associated with the BMI and sex in a model that also included age. The variation in fasting and 2 hour blood glucose levels were predicted by beta3-AR, gender, age and BMI. These results suggest that the presence of the mutation contributes to obesity and hyperglycemia in our female population.(AU)