clinical study cardiac diastolic evaluation in pregnant...

Hindawi Publishing CorporationJournal of Diabetes ResearchVolume 2013 Article ID 486593 6 pageshttpdxdoiorg1011552013486593

Clinical StudyCardiac Diastolic Evaluation in PregnantWomen with Abnormal Glucose ToleranceAn Opportunity to Detect the Early and SubclinicalAlterations and Prevent Cardiovascular Diseases

B Pintaudi1 G Di Vieste1 F Corrado2 M F Creazzo1 A Fazio1

A Valenti3 R DrsquoAnna2 and A Di Benedetto1

1 Department of Internal Medicine University of Messina Via Consolare Valeria 1 98125 Messina Italy2 Department of Obstetrics and Gynecology University of Messina Via Consolare Valeria 1 98125 Messina Italy3 Department of Pathology and Experimental Micropathology University of Messina Via Consolare Valeria 1 98125 Messina Italy

Correspondence should be addressed to B Pintaudi basiliopintayahooit

Received 2 May 2013 Revised 10 August 2013 Accepted 22 August 2013

Academic Editor Bruno Kotska Rodino Janeiro

Copyright copy 2013 B Pintaudi et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Objectives of this study were to assess diastolic function in pregnant women with abnormal glucose tolerance (AGT) comparedwith normal glucose tolerance (NGT) women and to evaluate the insulin resistance status and its association with Doppler-echocardiographic indexes Echocardiograms of 108 consecutive Caucasian women with singleton pregnancies were performedInsulin resistance status was estimated by the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitativeinsulin sensitivity check index (QUICKI) All the studied women showed normal diastolic patterns Patients with AGT (509)as compared with NGT women had higher HOMA-IR (170 plusmn 130 versus 101 plusmn 081 119875 = 0003) lower QUICKI (036 plusmn 0005versus 040 plusmn 006 119875 = 0004) higher lateral mitral annulus late diastolic velocity (136 plusmn 49 versus 119 plusmn 49 119875 = 003) andhigher A-wave velocity the wave responsible for the active atrial contraction component (752 plusmn 142 versus 677 plusmn 162 119875 = 001)At multivariate regression analysis HOMA-IR was the only parameter associated with A-wave velocity In conclusion women withAGT had an increased subclinical diastolic active participation which is associated with higher levels of insulin resistance For theincreased risk of deterioration of cardiac diastolic function earlier and more seriously than normal pregnancy AGT women mayhave a careful followup to detect the early signs of cardiac alteration and to prevent cardiovascular diseases

1 Introduction

Abnormal glucose tolerance (AGT) in pregnancy representsa condition in which an alteration of glucose metabolismin pregnancy is detectable It includes gestational diabetesmellitus (GDM) cases but also women with one abnormalvalue (OAV) at the oral glucose tolerance test (OGTT)GDM is the most frequent complication in pregnancy andrepresents an important risk factor for the onset of type2 diabetes (T2DM) [1] hypertension and cardiovasculardisease (CVD) in the following years after the pregnancy[2] Pregnant women with OAV as women with GDM areexposed to an increased risk for adverse perinatal outcomes[3 4] According to the new diagnostic criteria for GDM [5]

even the presence of one altered blood glucose value at theOGTT allows a diagnosis of GDM

Recently it has been assumed that cardiovascular impair-ment could start during pregnancy In fact frequently sev-eral markers of CVD risk such as inflammatory factorsdyslipidemia and hypertension are present from the firstmoment of pregnancy [6 7] For these reasons it is extremelyimportant to detect AGT cases in order to prevent all thecomplications related to this condition Many studies inwhich cardiac function in normal pregnancy was evaluatedhave been conducted but only few data are reported aboutcardiac function in particular diastolic function in pregnan-cies complicated by AGT More specifically left ventricular(LV) diastolic function of pregnant women was assessed by

2 Journal of Diabetes Research

measurement of transmitral inflow velocity by pulsed waveDoppler echocardiography [8ndash11] This method measuresdiastolic flow velocity as index of LV diastolic capacitybut is strongly influenced by ventricular loading conditionsFurthermore pregnancy is characterized by haemodynamicadaptations for which transmitral flow changes are not a validreflection of diastolic function [12] For this reason tissueDoppler imaging (TDI) an established preload independentechocardiographic technique is a more accurate method forthe evaluation of diastolic function during pregnancy [13]Given these premises the principal aim of this observationalstudy was to assess the diastolic function in pregnant womenwith AGT compared to a control group of pregnant womenwith normal glucose tolerance (NGT) In addition the studyaimed to evaluate the between group differences in the insulinresistance status and the association between metabolicparameters and Doppler-echocardiographic indexes

2 Materials and Methods

21 Study Population From March 2008 to January 2009data on 108 consecutive Caucasian women with singletonpregnancies at the 29 plusmn 3 week gestation with an abnormalresult on a 50 g glucose challenge screening test (GCT) wereevaluated All participants performed a 3 h 100 g diagnosticOGTT for the determination of glucose tolerance statusExclusion criteria were the following the presence of any car-diac signs or symptoms the history of cardiovascular diseasethe diagnosis of diabetes mellitus before pregnancy and anytreatment with corticosteroid agents thyroid hormones andmedications known to modify cardiac structure or functionIn particular women with previous diastolic dysfunctionand women with a previous pathological echocardiographicexamination were carefully excluded from the study Allpatients gave written informed consent to participate in thestudy

22 Baseline Evaluation and Laboratory Measurements AllOGTTs were performed in the morning after an overnightfast Glucose and insulin levels at fasting and at 60 120and 180 minutes after the glucose load were measuredGlucose tolerance during pregnancy was defined accordingto Coustan and Carpenter criteria [14] Briefly these criteriasuggested an evaluation for GDM to be performed between24 and 28 weeksrsquo gestation in those women not knownto have carbohydrate intolerance before the 24th week ofgestation This evaluation was done in a two-step procedureconsisting in a 50 g oral glucose challenge test (GCT)followed by a diagnostic 3 h 100 g OGTT if results of theGCT exceed a predetermined plasma glucose concentration(ge140mgdL one hour after ingestion of the glucose load)The cut-off glucose values for the diagnostic OGTT werefasting ge95mgdL 1 h postload ge180mgdL 2 h postloadge155mgdL and 3 h postloadge140mgdL Two ormore of thevenous plasma concentrations must be met or exceeded for apositive diagnosis Women with only one abnormal value forthe 100 g 3 h OGTT (OAV) are considered to have the samerisk as women with normal OGTT results [4]

The insulin sensitivity index homeostasis model assess-ment of insulin resistance (HOMA-IR) was calculatedaccording toMatthewsrsquo formula [15]The quantitative insulinsensitivity check index (QUICKI) was also calculated toestimate the insulin resistance [16] Furthermore clinical andobstetrical data were collected Prepregnancy BMI and BMIat first prenatal visit were calculated Blood pressure wasmeasured after a 10-minute rest All the patients were invitedto return to our department at a future day for ECG andechocardiographic examinations

23 Echocardiography Echocardiograms were recordedwith a commercially available ultrasound system (GeneralElectrics VIVID 3 PRO) equipped with a 35MHz phased-array transducer at 297 plusmn 26 week of pregnancy ingroup A and at 289 plusmn 40 week in group B Subjects wereexamined in the left lateral decubitus position using standardparasternal short-axis and apical views All recordings andmeasurements were obtained by the same operator whowas blinded to the clinical data of the pregnant women Todefine the reproducibility of echocardiography parameterswere examined offline from the digitally retrieved cycles ina random order by an independent operator Two operatorsindependently performed all measurements Exams averag-ing over three representative cardiac cycles were performedafter a 15 minute rest in the postprandial state to avoid theinfluence of circadian rhythm on LV diastolic function [17]LV ejection fraction was calculated by the Teicholz formula[18] in the absence of significant mitralic regurgitation andregional wall motion abnormalities LV diastolic functionwas evaluated through three parameters (a) by recordingtransmitralic flow in the zone of maximum mitralic flow byplacing the sample gate of pulsed doppler at the tips of themitral leaflets in their fully-open position in diastole thusrecording the wave expression of rapid LV filling (119864) andthe wave subordinate to the atrial contraction which is anexpression of late LV filling (119860) [19] (b) by analysing 119864 and119860peaks and the 119864119860 ratio (c) by evaluating early (1198641015840) and late(1198601015840) diastolic velocity waves recorded using TDI module byplacing the sample gate at the lateral part of mitral annulusas a result calculating the 11986410158401198601015840 average Finally 1198641198641015840 ratioa measure of LV end-diastolic pressure was calculatedThe following parameters were also evaluated left atriumanteroposterior diameter left atrium area interventricularthickness LV diastolic diameter LV posterior wall thicknessand pulmonary artery systolic pressure Cardiac diastolicfunction was evaluated according to the current diagnosticcriteria [20 21]

24 Statistical Analyses In descriptive analyses continuousvariables are summarized as mean and standard deviation(normal distribution) or median (nonnormal distributionand ordinal variables) Categorical variables are expressed aspercentages Differences among the groups were analyzed byanalysis of variance (ANOVA) or chi-square tests Pearsonrsquoscorrelation coefficient was employed to test correlationsbetween HOMA-IR QUICKI and significantly different car-diovascular markers Multivariate regression analyses were

Journal of Diabetes Research 3

Table 1 Clinical characteristics of pregnant women with abnormal glucose tolerance (AGT) in pregnancy and pregnant women with normalglucose tolerance (NGT)

Abnormal glucose tolerance woman Normal glucose tolerance woman 119875 value119873 () 55 (509) 53 (491) nsAge (yr) 346 plusmn 49

lowast316 plusmn 62 0006

Prepregnancy BMI (Kgm2) 247 plusmn 41 249 plusmn 59 nsBMI at the echocardiograms (Kgm2) 281 plusmn 42 271 plusmn 55 nsFamiliarity for type 2 diabetes 119899 ( ) 28 (509) 27 (491) nsPrevious pregnancies 119899 ( ) 76 (631)lowast 59 (369) 0003Smoke during pregnancy 119899 ( ) 5 (94) 5 (90) nsGestational age at echocardiograms (weeks) 297 plusmn 26 289 plusmn 40 nsHeart rate (beatsmin) 870 plusmn 109 839 plusmn 107 nsSystolic blood pressure (mmHg) 1087 plusmn 101 1053 plusmn 116 nsDiastolic blood pressure (mmHg) 689 plusmn 891


Fasting glucose (mgdL) 830 plusmn 154lowast

708 plusmn 102 002Fasting insulin (120583molL) 88 plusmn 56


HOMA-IR 170 plusmn 130lowast

101 plusmn 081 0003QUICKI 036 plusmn 0005


Women with OAV 119899 () 23 (213) 0 (0) 0001Data are expressed as means plusmn SD or percentages lowast119875 values lt 005 were considered statistically significant

Table 2 Echocardiographic M-mode and 2-dimensional mode measurements

Abnormal glucose tolerance woman Normal glucose tolerance woman 119875 value119873 () 55 (509) 53 (491) nsInterventricular septum during diastole IVSd (mm) 100 plusmn 11


Left ventricular end-diastolic diameter LVEDD (mm) 462 plusmn 34 456 plusmn 31 nsLeft ventricular posterior wall thickness LVPWd (mm) 99 plusmn 11 95 plusmn 12 nsEjection fraction EF () 676 plusmn 58 680 plusmn 49 nsLeft atrial area (cm2) 154 plusmn 18 149 plusmn 18 nsLeft atrial diameter (mm) 362 plusmn 30 358 plusmn 29 nsData are expressed as means plusmn SD or percentages lowast119875 values lt 005 were considered statistically significant

performed to analyze the effect of insulin resistance on thediastolic function indices The following baseline covariateswere tested BMI at the echocardiogram age gestational ageat echocardiograms and HOMA-IR 119875 values lt005 wereconsidered statistically significant Statistical analysis wasperformed with SPSS statistical package version 17 (SPSSChicago IL USA)

3 Results

31 Clinical Data Clinical characteristics of study partic-ipants are shown in Table 1 Pregnant women with AGTwhen compared with women with NGT were older hadhigher fasting glucose higher fasting insulin levels higherlevels of HOMA-IR lower QUICKI and higher levels ofdiastolic blood pressure and were more frequently at thefirst pregnancy There was no significant difference betweengroups in prepregnancy BMI BMI at the echocardiogramssystolic blood pressure and percentages of women withfamiliarity for T2DM

32 Echocardiographic Measurements (M-Mode and 2-Di-mensional Mode) Table 2 shows the M-mode and 2-di-mensional mode measurements for LV and atrial cavityThere were no differences between groups in LV poste-rior wall thickness LV end-diastolic diameter LV ejectionfraction and left atrial diameter and area Interventricularseptum during diastole was significantly larger in group Acompared to group B

33 Doppler and Tissue Doppler Parameters There were nostatistical significant differences between groups in rapidfilling wave (119864 wave) PAPs lateral mitral annulus earlydiastolic velocity (1198641015840) 1198641198641015840 ratio and 119864119860 ratio Lateralmitral annulus late diastolic velocity (1198601015840) was higher in group119860 and 11986410158401198601015840 ratio was lower in group B The velocity of thewave which is responsible for the active atrial contractioncomponent (119860 wave) was increased in group A as reportedin Table 3 When considering diastolic dysfunction gradedefined according 119864119860 ratio value no women showed anygrade of diastolic dysfunctionThe correlation analyses show


Table 3 Doppler and tissue Doppler parameters

Abnormal glucose tolerance woman Normal glucose tolerance woman 119875 value119873 () 55 (509) 53 (491) NsPulmonary artery pressure PAP (mmHg) 213 plusmn 63 203 plusmn 67 NsTransmitral 119864 velocity (cms) 810 plusmn 220 772 plusmn 200 NsTransmitral 119860 velocity (cms) 752 plusmn 142


119864119860 ratio 11 plusmn 03 12 plusmn 03 NsLateral 1198641015840 velocity (cms) 163 plusmn 32 173 plusmn 59 NsLateral 1198601015840 velocity (cms) 136 plusmn 49


1198641198641015840 ratio 50 plusmn 13 48 plusmn 15 Ns

11986410158401198601015840 ratio 13 plusmn 05


Data are expressed as means plusmn SD or percentages lowast119875 values lt 005 were considered statistically significant

Table 4 Correlation analyses between HOMA-IR QUICKI and significantly different cardiovascular markers

OVERALL woman AGT woman NGT woman119877 119875 119877 119875 119877 119875

HOMA-IRSystolic blood pressure 0304 0003 0325 003 0220 013Diastolic blood pressure 0439 lt00001 0445 0002 0338 002Interventricular septum during diastole 0199 005 0075 062 0214 015Transmitral 119860 velocity 0309 0002 0291 005 0128 039Lateral 1198601015840 velocity minus0022 083 minus0037 081 minus0201 01811986410158401198601015840 ratio minus0015 089 minus0011 094 0141 034

QUICKISystolic blood pressure minus0183 008 minus0218 015 minus0093 053Diastolic blood pressure minus0354 lt00001 minus0426 0003 minus0218 014Interventricular septum during diastole minus0158 013 minus0138 036 minus0052 073Transmitral 119860 velocity minus0367 lt00001 minus0348 002 minus0256 008Lateral 1198601015840 velocity minus0029 078 minus0048 075 0108 04711986410158401198601015840 ratio 0027 080 0011 095 minus0075 062

a positive correlation between both systolic and diastolicpressure transmitral 119860 velocity and HOMA-IR when con-sidering the overall sample We can see similar results whenconsidering only AGT women but not NGT women Similarcorrelations but in a negative sense are evident as attendedwith QUICKI (Table 4) Multivariate regression analysisadjusted for BMI at the echocardiogram age gestational ageat echocardiograms and HOMA-IR and where the 119860 wavewas the dependent variable showed that HOMA-IR was theonly parameter associated with 119860 wave velocity (120573 = minus0334119875 = 0039)

4 Discussion

The first result of our study was the evidence that all theexamined women had a normal pattern of diastolic functionBoth pregnant women with AGT and women with NGTshowed in fact no detectable echocardiographic parametersindicative of diastolic dysfunction The only between groupecho differences were related to 119860 and 1198601015840 velocities and11986410158401198601015840 ratio and the group of women with AGT shows higher

velocities of these waves which are involved in active atrial

contraction To our knowledge there is only one previousstudy in which diastolic function in patients with AGT wasanalyzed [22] In particular Freire and colleagues showeda different LV diastolic filling profile when examining dias-tolic function in 13 young patients with GDM recognizingsome cases of diastolic dysfunction Compared to their casestudy we analyzed a greater number of women who werefurthermore at an earlier week of gestation We did not findany case of diastolic dysfunction and this could be due tothe earlier gestational time of our examination We founddiastolic patterns in a normal range but the highlightedsubclinical differences between group could represent initialdiastolic abnormalities that are present since an early phaseof the pregnancy

We focused our study on cardiac diastolic functionbecause its alteration is the first recognizable in case ofdiabetes-linked cardiopathy The information provided byusing transmitral annular tissue doppler data is useful inthe assessment of diastolic dysfunction diagnosis Pregnancycauses physiological hemodynamic adaptations since the firsttrimester [23] because total vascular resistance decreasesblood volume overloads and heart rate and blood pressurecan be decreased All these changes contribute to influence


mitral inflow indices and other Doppler diastolic parameters[24] A better evaluation of LV diastolic function requiresdirect LV pressure and volume measurements by cardiaccatheterization [25] which is not simple and ethically correctfor clinical studies in healthy individuals Now it is possibleto evaluate diastolic function noninvasively using echocar-diography with Doppler measurements of transmitral bloodflow and more recently developed myocardial tissue dopplerimaging (TDI) measurements [26 27] TDI evaluation hasthe big advantage of being less dependent on preload It isdemonstrated that despite an apparent increase in functionin early normal pregnancy cardiac diastolic function in thebasal resting state appeared to deteriorate by term [28 29]

Many authors reported increased transmitral 119860 velocityand 119864119860 ratio during normal pregnancy [8ndash11 29 30] Wefound a further increase of the values of the same parametersin AGT women as compared with NGT women

The other aim of our study was to assess insulin resistancestatus and its link with Doppler-echocardiographic indexesWomen with AGT had higher levels of insulin resistance asmeasured byHOMA-IR and lower level of insulin sensibilityas measured by QUICKY than NGT women A strongcorrelation between insulin resistance and heart alterationshas been noted [31ndash33] More epidemiological lines evidenceof demonstrated that insulin resistance could predict the sub-sequent development of heart failure determining cardiomy-ocyte hypertrophy independent of all established risk factorsincluding diabetes mellitus itself [31] The state of insulinresistance is characterized by elevated circulating free fattyacid levels that are stored as intramyocardial triglycerides andcan negatively influence heartrsquos oxidative capacity [34] Inour study we found a significant between group differencein interventricular septum thickness during diastole Thiscould be explained because despite an increased thickness innormal pregnancy in the group of women with AGT therewas a higher insulin resistance status that have determinedcardiomyocyte hypertrophy Higher insulin resistance couldreasonably set these women at higher risk of developingcardiac disease in the future At multivariate analysis insulinresistance was the only parameter associated with A wavevelocity and this could represent the functional aspect ofan increased insulin resistant role in promoting impairedsubclinical diastolic cardiac function

5 Conclusions

We found a higher subclinical diastolic active participation inAGT women as compared with NGT womenThe significantdifferences in119860 wave1198601015840 and 11986410158401198601015840 ratio could be explainedby the potential effect of insulin resistance in deterioratingcardiac diastolic function of AGT women earlier and moreseriously than normal pregnancy For this reason and for thedemonstrated future cardiovascular risk women with GDMor OAV may have a careful followup to detect the early signof cardiac dysfunction and to prevent heart failure Limits ofour study are the relatively low number of women examinedalthough in the only existing work a smaller number ofwomen compared to our have been examined and the lack

of a cardiology followup after pregnancy can estimate thediastolic cardiac performance in these women with highercardiovascular risk

References

[1] L Bellamy J Casas A D Hingorani and D Williams ldquoType 2diabetes mellitus after gestational diabetes a systematic reviewandmeta-analysisrdquoTheLancet vol 373 no 9677 pp 1773ndash17792009

[2] M W Carpenter ldquoGestational diabetes pregnancy hyperten-sion and late vascular diseaserdquo Diabetes Care vol 30 no 2 ppS246ndashS250 2007

[3] F Corrado A D Benedetto M L Cannata et al ldquoA singleabnormal value of the glucose tolerance test is related toincreased adverse perinatal outcomerdquo Journal of Maternal-Fetaland Neonatal Medicine vol 22 no 7 pp 597ndash601 2009

[4] G Di Cianni G Seghieri C Lencioni et al ldquoNormal glucosetolerance and gestational diabetesmellitus what is in betweenrdquoDiabetes Care vol 30 no 7 pp 1783ndash1788 2007

[5] International Association of Diabetes and Pregnancy StudyGroups ldquoRecommendations on the diagnosis and classificationof hyperglycemia in pregnancyrdquoDiabetes Care vol 33 no 3 pp676ndash682 2010

[6] S M Heitritter C G Solomon G F Mitchell N Skali-Ounisand E W Seely ldquoSubclinical inflammation and vascular dys-function in women with previous gestational diabetes mellitusrdquoJournal of Clinical Endocrinology and Metabolism vol 90 no 7pp 3983ndash3988 2005

[7] A Di Benedetto G T Russo F Corrado et al ldquoInflammatorymarkers in women with a recent history of gestational diabetesmellitusrdquo Journal of Endocrinological Investigation vol 28 no 1pp 34ndash38 2005

[8] A Mesa C Jessurun A Hernandez et al ldquoLeft ventriculardiastolic function in normal human pregnancyrdquo Circulationvol 99 no 4 pp 511ndash517 1999

[9] W C Mabie T G DiSessa L G Crocker B M Sibai andK L Arheart ldquoA longitudinal study of cardiac output innormal human pregnancyrdquo American Journal of Obstetrics andGynecology vol 170 no 3 pp 849ndash856 1994

[10] N A Kametas F McAuliffe J Hancock J Chambers andK H Nicolaides ldquoMaternal left ventricular mass and diastolicfunction during pregnancyrdquoUltrasound in Obstetrics and Gyne-cology vol 18 no 5 pp 460ndash466 2001

[11] H Valensise G P Novelli B Vasapollo et al ldquoMaternal cardiacsystolic and diastolic function relationship with uteroplacentalresistances A Doppler and echocardiographic longitudinalstudyrdquo Ultrasound in Obstetrics and Gynecology vol 15 no 6pp 487ndash497 2000

[12] M F Stoddard A C Pearson M J Kern J Ratcliff D GMrosek and A J Labovitz ldquoInfluence of alteration in preloadon the pattern of left ventricular diastolic filling as assessed byDoppler echocardiography in humansrdquo Circulation vol 79 no6 pp 1226ndash1236 1989

[13] D Sohn I Chai D Lee et al ldquoAssessment of mitral annulusvelocity by Doppler tissue imaging in the evaluation of leftventricular diastolic functionrdquo Journal of the American Collegeof Cardiology vol 30 no 2 pp 474ndash480 1997

[14] D R Coustan and M W Carpenter ldquoThe diagnosis of gesta-tional diabetesrdquo Diabetes Care vol 21 no 2 pp B5ndashB8 1998


[15] D R Matthews J P Hosker and A S Rudenski ldquoHomeostasismodel assessment insulin resistance and 120573-cell function fromfasting plasma glucose and insulin concentrations in manrdquoDiabetologia vol 28 no 7 pp 412ndash419 1985

[16] A Katz S S Nambi K Mather et al ldquoQuantitative insulinsensitivity check index a simple accurate method for assessinginsulin sensitivity in humansrdquo Journal of Clinical Endocrinologyand Metabolism vol 85 no 7 pp 2402ndash2410 2000

[17] S Voutilainen M Kupari M Hippelainen K Karppinen andM Ventila ldquoCircadian variation of left ventricular diastolicfunction in healthy peoplerdquoHeart vol 75 no 1 pp 35ndash39 1996

[18] L E Teichholz T Kreulen M V Herman and R Gor-lin ldquoProblems in echocardiographic volume determinationsechocardiographic angiographic correlations in the presence orabsence of asynergyrdquoAmerican Journal of Cardiology vol 37 no1 pp 7ndash11 1976

[19] M R Zile and D L Brutsaert ldquoNew concepts in diastolic dys-function and diastolic heart failure part I diagnosis prognosisand measurements of diastolic functionrdquo Circulation vol 105no 11 pp 1387ndash1393 2002

[20] C Tschope and W J Paulus ldquoDoppler echocardiographyyields dubious estimates of left ventricular diastolic pressuresrdquoCirculation vol 120 no 9 pp 810ndash819 2009

[21] S J Khouri G T Maly D D Suh and T E Walsh ldquoA practicalapproach to the echocardiographic evaluation of diastolic func-tionrdquo Journal of the American Society of Echocardiography vol17 no 3 pp 290ndash297 2004

[22] C M V Freire M do Carmo Pereira Nunes M Melo Barbosaet al ldquoGestational diabetes a condition of early diastolicabnormalities in youngwomenrdquo Journal of the American Societyof Echocardiography vol 19 no 10 pp 1251ndash1256 2006

[23] J F Clapp III B L Seaward R H Sleamaker and J HiserldquoMaternal physiologic adaptations to early human pregnancyrdquoAmerican Journal of Obstetrics and Gynecology vol 159 no 6pp 1456ndash1460 1988

[24] G J Gilson M D Mosher and K P Conrad ldquoSystemichemodynamics and oxygen transport during pregnancy inchronically instrumented conscious ratsrdquo American Journal ofPhysiology vol 263 no 6 pp H1911ndashH1918 1992

[25] M R Zile C F Baicu and W H Gaasch ldquoDiastolic heartfailure-abnormalities in active relaxation and passive stiffnessof the left ventriclerdquo New England Journal of Medicine vol 350no 19 pp 1953ndash2018 2004

[26] S F Nagueh K J Middleton H A Kopelen W A Zoghbiand M A Quinones ldquoDoppler tissue imaging a noninvasivetechnique for evaluation of left ventricular relaxation andestimation of filling pressuresrdquo Journal of the American Collegeof Cardiology vol 30 no 6 pp 1527ndash1533 1997

[27] M J Garcia J D Thomas and A L Klein ldquoNew dopplerechocardiographic applications for the study of diastolic func-tionrdquo Journal of the American College of Cardiology vol 32 no4 pp 865ndash875 1998

[28] D Zenther M Du Plessis S Brennecke J Wong L Griggand S B Harrap ldquoDeterioration in cardiac systolic and diastolicfunction late in normal human pregnancyrdquoClinical Science vol116 no 7 pp 599ndash606 2009

[29] W Y Fok L Y Chan J T Wong C M Yu and T K LauldquoLeft ventricular diastolic function during normal pregnancyassessment by spectral tissue Doppler imagingrdquo Ultrasound inObstetrics and Gynecology vol 28 no 6 pp 789ndash793 2006

[30] J E Bamfo N A Kametas K H Nicolaides and J BChambers ldquoMaternal left ventricular diastolic and systolic long-axis function during normal pregnancyrdquo European Journal ofEchocardiography vol 8 no 5 pp 360ndash368 2007

[31] E Ingelsson J Sundstrom J Arnlov B Zethelius and L LindldquoInsulin resistance and risk of congestive heart failurerdquo Journalof the AmericanMedical Association vol 294 no 3 pp 334ndash3412005

[32] C Iribarren A J Karter A S Go et al ldquoGlycemic control andheart failure among adult patients with diabetesrdquo Circulationvol 103 no 22 pp 2668ndash2673 2001

[33] A Ilercil R B Devereux M J Roman et al ldquoAssociations ofinsulin levels with left ventricular structure and function inAmerican Indians the strong heart studyrdquo Diabetes vol 51 no5 pp 1543ndash1547 2002

[34] W C Stanley G D Lopaschuk and J G McCormack ldquoReg-ulation of energy substrate metabolism in the diabetic heartrdquoCardiovascular Research vol 34 no 1 pp 25ndash33 1997

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


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Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


measurement of transmitral inflow velocity by pulsed waveDoppler echocardiography [8ndash11] This method measuresdiastolic flow velocity as index of LV diastolic capacitybut is strongly influenced by ventricular loading conditionsFurthermore pregnancy is characterized by haemodynamicadaptations for which transmitral flow changes are not a validreflection of diastolic function [12] For this reason tissueDoppler imaging (TDI) an established preload independentechocardiographic technique is a more accurate method forthe evaluation of diastolic function during pregnancy [13]Given these premises the principal aim of this observationalstudy was to assess the diastolic function in pregnant womenwith AGT compared to a control group of pregnant womenwith normal glucose tolerance (NGT) In addition the studyaimed to evaluate the between group differences in the insulinresistance status and the association between metabolicparameters and Doppler-echocardiographic indexes

2 Materials and Methods

21 Study Population From March 2008 to January 2009data on 108 consecutive Caucasian women with singletonpregnancies at the 29 plusmn 3 week gestation with an abnormalresult on a 50 g glucose challenge screening test (GCT) wereevaluated All participants performed a 3 h 100 g diagnosticOGTT for the determination of glucose tolerance statusExclusion criteria were the following the presence of any car-diac signs or symptoms the history of cardiovascular diseasethe diagnosis of diabetes mellitus before pregnancy and anytreatment with corticosteroid agents thyroid hormones andmedications known to modify cardiac structure or functionIn particular women with previous diastolic dysfunctionand women with a previous pathological echocardiographicexamination were carefully excluded from the study Allpatients gave written informed consent to participate in thestudy

22 Baseline Evaluation and Laboratory Measurements AllOGTTs were performed in the morning after an overnightfast Glucose and insulin levels at fasting and at 60 120and 180 minutes after the glucose load were measuredGlucose tolerance during pregnancy was defined accordingto Coustan and Carpenter criteria [14] Briefly these criteriasuggested an evaluation for GDM to be performed between24 and 28 weeksrsquo gestation in those women not knownto have carbohydrate intolerance before the 24th week ofgestation This evaluation was done in a two-step procedureconsisting in a 50 g oral glucose challenge test (GCT)followed by a diagnostic 3 h 100 g OGTT if results of theGCT exceed a predetermined plasma glucose concentration(ge140mgdL one hour after ingestion of the glucose load)The cut-off glucose values for the diagnostic OGTT werefasting ge95mgdL 1 h postload ge180mgdL 2 h postloadge155mgdL and 3 h postloadge140mgdL Two ormore of thevenous plasma concentrations must be met or exceeded for apositive diagnosis Women with only one abnormal value forthe 100 g 3 h OGTT (OAV) are considered to have the samerisk as women with normal OGTT results [4]

The insulin sensitivity index homeostasis model assess-ment of insulin resistance (HOMA-IR) was calculatedaccording toMatthewsrsquo formula [15]The quantitative insulinsensitivity check index (QUICKI) was also calculated toestimate the insulin resistance [16] Furthermore clinical andobstetrical data were collected Prepregnancy BMI and BMIat first prenatal visit were calculated Blood pressure wasmeasured after a 10-minute rest All the patients were invitedto return to our department at a future day for ECG andechocardiographic examinations

23 Echocardiography Echocardiograms were recordedwith a commercially available ultrasound system (GeneralElectrics VIVID 3 PRO) equipped with a 35MHz phased-array transducer at 297 plusmn 26 week of pregnancy ingroup A and at 289 plusmn 40 week in group B Subjects wereexamined in the left lateral decubitus position using standardparasternal short-axis and apical views All recordings andmeasurements were obtained by the same operator whowas blinded to the clinical data of the pregnant women Todefine the reproducibility of echocardiography parameterswere examined offline from the digitally retrieved cycles ina random order by an independent operator Two operatorsindependently performed all measurements Exams averag-ing over three representative cardiac cycles were performedafter a 15 minute rest in the postprandial state to avoid theinfluence of circadian rhythm on LV diastolic function [17]LV ejection fraction was calculated by the Teicholz formula[18] in the absence of significant mitralic regurgitation andregional wall motion abnormalities LV diastolic functionwas evaluated through three parameters (a) by recordingtransmitralic flow in the zone of maximum mitralic flow byplacing the sample gate of pulsed doppler at the tips of themitral leaflets in their fully-open position in diastole thusrecording the wave expression of rapid LV filling (119864) andthe wave subordinate to the atrial contraction which is anexpression of late LV filling (119860) [19] (b) by analysing 119864 and119860peaks and the 119864119860 ratio (c) by evaluating early (1198641015840) and late(1198601015840) diastolic velocity waves recorded using TDI module byplacing the sample gate at the lateral part of mitral annulusas a result calculating the 11986410158401198601015840 average Finally 1198641198641015840 ratioa measure of LV end-diastolic pressure was calculatedThe following parameters were also evaluated left atriumanteroposterior diameter left atrium area interventricularthickness LV diastolic diameter LV posterior wall thicknessand pulmonary artery systolic pressure Cardiac diastolicfunction was evaluated according to the current diagnosticcriteria [20 21]

24 Statistical Analyses In descriptive analyses continuousvariables are summarized as mean and standard deviation(normal distribution) or median (nonnormal distributionand ordinal variables) Categorical variables are expressed aspercentages Differences among the groups were analyzed byanalysis of variance (ANOVA) or chi-square tests Pearsonrsquoscorrelation coefficient was employed to test correlationsbetween HOMA-IR QUICKI and significantly different car-diovascular markers Multivariate regression analyses were



















3 Results











11986410158401198601015840 ratio 13 plusmn 05








4 Discussion









5 Conclusions



References









































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


































3 Results











11986410158401198601015840 ratio 13 plusmn 05








4 Discussion









5 Conclusions



References









































of






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4 Discussion









5 Conclusions



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of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of




















5 Conclusions



References









































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of










































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















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