Surab Vadachkoria

University of Washington Seattle, Seattle, Washington, United States

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Publications (17)36.54 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Type 2 diabetes (T2D) and impaired glucose tolerance (IGT) are associated with increased cardiovascular diseases (CVD) morbidity and mortality. T2D and IGT prevalence and their relation to other risk factors were investigated among cardiac patients. Patients (n = 250) visiting a secondary prevention clinic at the Emergency Cardiology Centre in Tibilisi, Republic of Georgia were enrolled in the study. Information on medical and surgical histories, CVD risk factors and current medical condition was obtained using interviews, medical record abstraction, physical examination and laboratory studies. Fasting blood glucose and 2-hour post load glucose concentrations were determined. Overall 40.8% (46% among men and 33% among women) of participants had T2D while 13% had IGT (13.4 among men and 12.9 among women). Of the T2D cases, more than half were previously undiagnosed. IGT and T2D were highly associated with dyslipidaemic profiles and elevated inflammatory marker concentrations in this population. Undiagnosed T2D cases shared similar CVD risk factors as previously diagnosed T2D cases including dyslipidaemia, other metabolic syndrome components and inflammation. Both T2D (diagnosed and undiagnosed) and IGT are prevalent; and are associated with other important CVD risk factors among cardiac patients in the Republic of Georgia. Future studies assessing associations of T2D and IGT with CVD morbidity and mortality in this population, as well as studies that assess prevalence of T2D and IGT and their relation with CVD in the general population are needed.
    Acta cardiologica 11/2007; 62(5):439-44. · 0.61 Impact Factor
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    ABSTRACT: We examined the relationship of maternal plasma concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), a specific marker of endothelial dysfunction, and risk of preeclampsia. We also evaluated the relationship in the presence and absence of maternal hypertriglyceridemia and hyperhomocystein(e)mia. A total of 170 women with preeclampsia and 184 control subjects were included in this case-control study analysis. Maternal postdiagnosis plasma sVCAM-1 concentrations were determined using immunoassays. Total plasma homocysteine (tHcy) was measured using high-performance liquid chromatography with electrochemical detection procedures; and triglyceride concentrations were determined using standard enzymatic procedures. Logistic regression procedures were used to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounders. The relative risk of preeclampsia (as estimated by the OR) was increased 3.6-fold for women with sVCAM-1 concentrations >/=842 ng/mL compared with women who had lower concentrations (OR = 3.6; 95% CI 1.8 to 7.4). Of the three biological markers investigated, elevated sVCAM-1 concentrations was most strongly related to preeclampsia risk (OR = 4.6, 95% CI 1.6 to 13.5), followed by hyperhomocysten(e)mia (OR = 2.4, 95% CI 0.8 to 7.4) and hypertriglyceridemia (OR = 2.1, 95% CI 0.9 to 5.0). Compared with women who did not have any of the three risk factors, those with all three risk factors had an extremely high risk of preeclampsia (OR = 26.4; 95% CI 8.5 to 81.9). These findings suggest that elevated sVCAM-1 concentrations are associated with an increased risk of preeclampsia. Our findings extend the literature by documenting progressively increased risk with increasing numbers of biological markers of dyslipidemia and endothelial dysfunction.
    American Journal of Hypertension 04/2006; 19(3):235-42. · 3.67 Impact Factor
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    ABSTRACT: Leptin and adiponectin, two adipocytokines, may work together in regulating energy homeostasis and insulin action. Leptin gene expression has been investigated in term placental tissue complicated by gestational diabetes mellitus (GDM), but never in conjunction with all isoforms of the leptin receptor (LEPR A-D), or with adiponectin receptors (ADIPOR1 and 2). In this study we examined the association between changes in expression of these genes in placental tissue and GDM risk. We assessed placental gene expression of leptin, LEPR A-D and ADIPOR1 and 2 by real time PCR using mRNA from maternal and fetal biopsies. Tissues were collected from uncomplicated pregnancies (n=28) and those complicated by GDM (n=19). Gene expression was normalized to three endogenous housekeeping genes. Relative gene expression values were reported as fold change between groups. Adiponectin gene expression was out of the sensitive range of our assay. There were increases in leptin mRNA expression in GDM cases compared with controls for maternal-side (p=0.06), and fetal-side (p=0.09) placental biopsies. No significant changes were seen in GDM cases compared with controls in LEPR A-D or ADIPOR1 and 2. mRNA derived from maternal-side tissue was positively correlated with tissue from the fetal side for all genes studied (all p<0.01). Finally, we noted that absence or presence of GDM was a major factor in leptin mRNA expression after adjusting for maternal age, mode of delivery, parity and smoking status. In conclusion, increases in leptin mRNA expression in term placenta, but not that of its receptors, are associated with the diagnosis of GDM. Changes seen in the ligand, but not the receptor, of the leptin pathway in GDM-complicated pregnancies may also apply to the adiponectin pathway, as the ADIPOR1 and 2 mRNAs do not change with GDM diagnosis.
    Physiological research / Academia Scientiarum Bohemoslovaca 01/2006; 55(5):501-12. · 1.53 Impact Factor
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    ABSTRACT: Oxidative stress plays an important role in the pathophysiology of preeclampsia. In a case-control study of 99 women with preeclampsia and 99 controls, we assessed maternal plasma oxidized low-density lipoprotein (oxidized LDL) in relation to preeclampsia risk. Logistic regression procedures were used to derive odds ratios (OR) and 95 % confidence intervals (CI). Plasma oxidized LDL was determined using enzyme immunoassay. Maternal plasma oxidized LDL was significantly positively correlated with lipids in both cases and controls. After adjusting for nulliparity, pre-pregnancy body mass index, physical inactivity, family history of chronic hypertension and plasma vitamin C concentrations, women who had elevated oxidized LDL concentrations ( > or = 50 U/l) experienced a 2.9-fold increased risk of preeclampsia when compared with women having lower oxidized LDL concentrations (95 % CI 1.4-5.9). The risk of preeclampsia was markedly increased in women who had both elevated oxidized LDL and elevated triglyceride concentrations (OR=8.9, 95 % CI 3.1-26.2). Women with both elevated oxidized LDL and low vitamin C concentrations experienced a 9.8-fold increased risk of preeclampsia (95 % CI 3.0-32.2). Our results confirm the role of oxidative stress in the pathogenesis of preeclampsia. Prospective studies are needed to determine if elevated oxidized LDL concentrations can predict the occurrence of preeclampsia.
    Physiological research / Academia Scientiarum Bohemoslovaca 01/2006; 55(5):491-500. · 1.53 Impact Factor
  • Journal of Reproductive Immunology - J REPROD IMMUNOL. 01/2006; 71(2):159-159.
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    ABSTRACT: Insulin-like growth factor-1 (IGF-1) and IGF binding protein-1 (IGFBP-1) may be important determinants of glucose homeostasis. We examined the association between circulating concentrations of IGF-1, IGFBP-1 in early pregnancy and development of gestational diabetes mellitus (GDM). Maternal plasma (collected at 13 weeks) IGF-1, IGFBP-1, and C-peptide were measured using immunoassay. Relative risks (RR) and 95% CIs were calculated. The percentage of the cohort that developed GDM was 5.8% (n = 804). Free IGF-1 and IGFBP-1 were inversely associated with GDM risk, while C-peptide was positively associated with GDM risk (P for trend test < .05). Women with free IGF-1 > or = 1.08 ng/mL experienced a 69% reduced risk of GDM (CI 0.12-0.75) compared with women having concentrations < 0.80 ng/mL. There was a 57% reduced risk of GDM among women with IGFBP-1 > or = 68.64 ng/mL (RR = 0.43, CI 0.18-1.05). Women with C-peptide > or = 3.00 ng/mL experienced a 2.28-fold increased risk of GDM (CI 1.00-5.19) compared with women who had concentrations < 1.45 ng/mL. These associations may help to further elucidate the pathologic process of GDM.
    American journal of obstetrics and gynecology 11/2005; 193(5):1691-7. · 3.28 Impact Factor
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    ABSTRACT: Diffuse vascular endothelial dysfunction, secondary to oxidative stress, is an important pathological feature of preeclampsia. Oxidative conversion of low density lipoproteins (LDL) to oxidized-LDL (Ox-LDL) is considered an important step in transforming macrophages into lipid-laden foam cells destined to develop into early atherosclerotic-like lesions. In our study of 95 women with preeclampsia and 100 controls, we evaluated the association between maternal plasma Ox-LDL concentrations and preeclampsia risk. Ox-LDL concentrations were measured using a solid phase two-site enzyme immunoassay. Plasma lipids were measured using standard enzymatic procedures. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for confounders. Plasma Ox-LDL concentrations were positively correlated with cholesterol, triglyceride (TG), and LDL concentrations in cases and controls, (Spearman's r ranging from 0.39-0.48, p-values all <0.01). There was no evidence of an increased risk of preeclampsia across increasing quartiles of Ox-LDL. The ORs for successive quartiles, with the lowest as the reference group, were as follows: 1.0, 1.1, 0.6, and 1.2. Women with extremely high concentrations of Ox-LDL (> or =73 U/L, the upper decile), as compared with those with lower values (<73 U/L) had a 2.7-fold increased risk of preeclampsia (95% CI 1.0-6.8). Women with high Ox-LDL and high TG concentrations (> or =284 mg/dl), as compared with those without these two factors, had a 9.6-fold increased preeclampsia risk (95% CI 2.0-45.6). Elevated Ox-LDL, particularly in conjunction with elevated TG, appears to be a risk factor of preeclampsia.
    Gynecological Endocrinology 10/2005; 21(4):193-9. · 1.30 Impact Factor
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    M Meller, S Vadachkoria, D A Luthy, M A Williams
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    ABSTRACT: Preeclampsia and diabetes are complications of pregnancy that contribute to maternal and perinatal mortality worldwide. Results emerging from molecular studies of placentae may elucidate etiologically important genomic alterations. Appropriate application of real time reverse transcription (RT) PCR in comparative gene expression studies requires endogenous housekeeping genes to normalize between sample variations. Ideal housekeeping genes must have stable tissue expression, but few have been specifically studied in the placenta. We sought to identify candidate control genes by analyzing seven functionally distinct housekeeping genes (B2M, GAPDH, HMBS, HPRT, SDHA, TBP, YWHAZ) for their expression stability and level in the placenta. mRNA isolated from 20 placentae was analyzed for gene expression using RT-PCR. Expression stability (M) was assessed using normalization strategies previously used for other tissues. TBP and SDHA were the most stable, with an average expression stability of M = 0.43, followed by YWHAZ (M = 0.44) > HPRT (M = 0.53) > HMBS (M = 0.57) > GAPDH (M = 0.61) > B2M (M = 0.69). The genes tested ranged in abundance, with an approximately 300-fold increase from the lowest (HMBS) to the highest (B2M). By using TBP, SDHA and YWHAZ, with greater expression stability than those housekeeping genes commonly used in placenta studies, gene expression profile comparisons will have more sensitivity and specificity.
    Placenta 01/2005; 26(8-9):601-7. · 3.12 Impact Factor
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    ABSTRACT: Few investigators have simultaneously evaluated leptin, soluble leptin receptor (SLR) and leptin gene polymorphisms in preeclampsia cases and controls. We examined these three biomolecular markers in 40 preeclampsia cases and 39 controls. Plasma leptin and SLR concentrations were determined using immunoassays. Genotype for the tetranucleotide repeat (TTTC)(n), polymorphism in the 3 -flanking region of the leptin gene was determined using PCR. Alleles of the polymorphism were characterized by size distributions [short repeats (class I); and long repeats (class II)]. Logistic regression was used to calculate odds ratios (OR) and 95 % confidence intervals (CI). Leptin concentrations were higher in our cases than in the controls (53.1 4.7 vs. 17.7+/-2.4 ng/ml, p<0.05). SLR concentrations were slightly lower in our patients than in the controls (25.7+/-1.9 vs. 29.1+/-1.1 ng/ml, p>0.05). Elevated leptin (? 14.5 ng/ml) was associated with a 3.8-fold (CI 1.0-14.4) increased risk; whereas low SLR (< 28.5 ng/ml) was associated with a 6.3-fold (CI 1.7-23.2) increased risk of preeclampsia. The I/II genotype was associated with a 3.8-fold increased risk of preeclampsia (OR=3.8; 95 % CI 0.8-18.0); and the II/II genotype was not observed among our cases (0 % vs. 33 % p<0.001). Larger studies would be needed to confirm and further clarify the relations between functional variants in the leptin gene and preeclampsia risk.
    Physiological research / Academia Scientiarum Bohemoslovaca 01/2005; 54(2):167-74. · 1.53 Impact Factor
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    ABSTRACT: Vascular endothelial growth factor (VEGF), a disulphide-linked homodimeric glycoprotein that is selectively mitogenic for endothelial cells, plays an important role in vasculogenesis and angiogenesis. Preeclampsia, a relatively common complication of pregnancy that is characterized by diffuse endothelial dysfunction possibly secondary to impaired trophoblast invasion of the spiral arteries during implantation, has recently been associated with alterations in maternal serum/plasma concentrations of VEGF, and other related growth factors and their receptors. We examined the relationship of maternal plasma VEGF, sVEGF-R1 and PlGF levels to the risk of preeclampsia among women delivering at Harare Maternity Hospital, Zimbabwe. 131 pregnant women with preeclampsia and 175 controls were included in a case-control study. Maternal plasma concentrations of each biomarker were measured using enzymatic methods. We used logistic regression to calculate odds ratios (OR) and 95 % confidence intervals (CI). Preeclampsia risk was inversely related with quartiles of plasma VEGF (OR: 1.0, 1.0, 0.7, and 0.5, with the lowest quartile as reference; p for trend=0.06). We noted a strong positive association between preeclampsia risk and sVEGF-R1 concentrations (OR: 1.0, 6.5, 9.7, 31.6, with the first quartile as the referent group; p for trend<0.001). After adjusting for confounders, we noted that women with sVEGF-R1 concentrations in the highest quartile (>or=496 pg/ml), as compared with those in the lowest quartile (<62 pg/ml) had a 31.6-fold increased risk of preeclampsia (OR=31.6, 95 % CI 7.7-128.9). There was no clear evidence of a linear relation in risk of preeclampsia with PlGF concentrations. In conclusion, plasma VEGF, sVEGF-R1 and PlGF concentrations (measured at delivery) were altered among Zimbabwean women with preeclampsia as compared with normotensive women. Our results are consistent with some, though not all, previous reports. Prospective studies are needed to: 1) identify modifiable determinants of maternal plasma concentrations VEGF, sVEGF-R1, and PlGF; and 2) evaluate the temporal relationship between observed alterations of these biological markers in preeclamptic pregnancies.
    Physiological research / Academia Scientiarum Bohemoslovaca 01/2005; 54(6):611-22. · 1.53 Impact Factor
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    ABSTRACT: We investigated the relationship between maternal plasma free insulinlike growth factor-1 (IGF-1) and insulinlike growth factor-binding protein-1 (IGFBP-1) concentrations and risk of preeclampsia. Maternal blood samples were collected at 13 weeks' gestation on average. From the cohort, we selected 53 women who developed preeclampsia and 477 who remained normotensive. Free IGF-1 and IGFBP-1 concentrations were measured using immunoassays. Logistic regression procedures were used to calculate odds ratios (OR) and 95% confidence intervals (95% CI). Women who developed preeclampsia had 18% and 27% lower concentrations of free IGF-1 and IGFBP-1, respectively, than controls (P < 0.05). There was a 57% reduced risk of preeclampsia among women with free IGF-1 concentrations of >or= 0.81 ng/mL (OR = 0.43, 95% CI 0.23-0.83) and a 43% reduced risk among women with IGFBP-1 concentrations of >or= 72.36 ng/mL (OR = 0.53, 95% CI 0.23-1.21). Alterations of free IGF-1 and IGFBP-1 concentrations in maternal plasma during early pregnancy are associated with risk of preeclampsia. These associations may help to further elucidate the pathologic processes of preeclampsia.
    Clinical Biochemistry 12/2004; 37(11):968-73. · 2.45 Impact Factor
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    ABSTRACT: Low plasma adiponectin has been identified as a risk factor for type 2 diabetes. Our objective was to determine the extent to which low maternal plasma adiponectin is predictive of gestational diabetes mellitus (GDM), a condition that is biochemically and epidemiologically similar to type 2 diabetes. We used a prospective, nested case-control study design to compare maternal plasma adiponectin concentrations in 41 cases with 70 controls. Subjects were selected from a population of 968 women who provided blood samples in early pregnancy. Plasma adiponectin was determined using an ELISA. Adiponectin concentrations were statistically significantly lower in women with GDM than controls (4.4 vs. 8.1 micro g/ml, P < 0.001). Approximately 73% of women with GDM, compared with 33% of controls, had adiponectin concentrations less than 6.4 micro g/ml. After adjusting for confounding, women with adiponectin concentrations less than 6.4 micro g/ml experienced a 4.6-fold increased risk of GDM, as compared with those with higher concentrations (95% confidence interval, 1.8-11.6). Our findings are consistent with other reports suggesting an association between hypoadiponectemia and risk of type 2 diabetes. Our findings extend the literature to include GDM. Studies designed to examine the effect of dietary and pharmacological mediators of adiponectin concentrations in pregnant and nonpregnant subjects are warranted.
    Journal of Clinical Endocrinology &amp Metabolism 06/2004; 89(5):2306-11. · 6.43 Impact Factor
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    ABSTRACT: In a case-control study of 100 preeclamptics and 100 controls, we assessed plasma transforming growth factor-beta1 (TGF-beta1) concentrations in relation to preeclampsia risk among Peruvian women with and without systemic inflammation. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The OR of preeclampsia increased across quartiles of TGF-beta1 concentrations. Women with elevated TGF-beta1 and a proinflammatory profile experienced the highest risk of preeclampsia (OR = 15.4, 95% CI 4.7-50.4). Our results confirm an association between TGF-beta1 and risk of preeclampsia and extend the literature by indicating a strong association in women with systemic inflammation.
    American Journal of Hypertension 05/2004; 17(4):334-8. · 3.67 Impact Factor
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    ABSTRACT: Emerging evidence suggests that leptin, an adipocyte-derived hormone, may have independent direct effects on both insulin secretion and action, in addition to its well documented effects on appetite and energy expenditure. Some, but not all, previously published studies suggest that maternal leptin concentrations may be increased in pregnancies complicated by gestational diabetes mellitus (GDM). We examined the association between plasma leptin concentration and GDM risk. Women were recruited before 16 weeks of gestation and were followed up until delivery. Maternal plasma leptin concentrations (collected at 13 weeks of gestation) were measured by using immunoassay. We used generalized linear models to estimate relative risks and 95% confidence intervals. GDM developed in 5.7% of the cohort (47 of 823). Elevated leptin concentrations were positively associated with GDM risk (P for trend <.001). After adjusting for maternal prepregnancy adiposity and other confounders, women with leptin concentrations of 31.0 ng/mL or higher experienced a 4.7-fold increased risk of GDM (95% confidence interval 1.2, 18.0) as compared with women who had concentrations of 14.3 ng/mL or lower. We noted a strong linear component of trend in risk of GDM with increasing maternal plasma leptin concentration. Each 10-ng/mL increase in the leptin concentration was associated with a 20% increase in GDM risk (relative risk 1.2; 95% confidence interval 1.0, 1.3). Hyperleptinemia, independent of maternal adiposity, in early pregnancy appears to be predictive of an increased risk of GDM later in pregnancy. Additional larger prospective cohort studies are needed to confirm and more precisely assess the etiologic importance of hyperleptinemia in pregnancy. II-2
    Obstetrics and Gynecology 03/2004; 103(3):519-25. · 4.80 Impact Factor
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    ABSTRACT: Hyperhomocyst(e)inemia (HHcy) is a risk factor of endothelial dysfunction and preeclampsia. Soluble vascular cell adhesion molecule-1 (sVCAM-1), a specific marker of endothelial dysfunction, is elevated in preeclampsia. Few have assessed the joint contribution of these biomarkers in predicting preeclampsia. We assessed the extent to which HHcy and elevated sVCAM-1 are independently and jointly associated with preeclampsia. We conducted a case-control analysis of 100 preeclampsia cases and 100 controls to test our study hypothesis. Maternal plasma was collected before labor onset. Total plasma homocysteine (tHcy) was measured using high-performance liquid chromatography with electrochemical detection procedures. Plasma sVCAM-1 was determined using ELISA. Using the distribution of each analyte among controls, elevated tHcy was defined as plasma tHcy >6.6 micromol/l and elevated sVCAM-1 was defined as plasma concentrations >845 ng/ml (i.e., values above the median). Odds ratios (OR) and 95% confidence intervals (CIs) were calculated. Compared with women without elevated tHcy and without elevated sVCAM-1 (the referent group), those with elevated sVCAM-1 alone had a 4.1-fold increased risk of preeclampsia (95% CI 1.2-13.8). The OR for women with elevated tHcy alone was 2.2 (95% CI 0.6-7.9). The OR for women with elevated tHcy and sVCAM-1 was 13.2 (95% CI 4.1-42.2). Elevated tHcy and sVCAM-1 together were strongly associated with an increased risk of preeclampsia. Larger, prospective studies are needed to confirm these findings and to determine the extent to which elevated tHcy and sVCAM-1 together in early pregnancy are predictive of preeclampsia risk.
    Gynecologic and Obstetric Investigation 01/2004; 58(3):133-9. · 1.10 Impact Factor
  • American Journal of Obstetrics and Gynecology - AMER J OBSTET GYNECOL. 01/2003; 189(6).
  • American Journal of Obstetrics and Gynecology - AMER J OBSTET GYNECOL. 01/2003; 189(6).

Publication Stats

311 Citations
36.54 Total Impact Points

Institutions

  • 2004–2007
    • University of Washington Seattle
      • Department of Epidemiology
      Seattle, Washington, United States
  • 2004–2006
    • Swedish Medical Center Seattle
      • Center for Perinatal Studies
      Seattle, WA, United States
  • 2004–2005
    • Swedish Medical Center
      Englewood, Colorado, United States