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Circulating thrombomodulin levels and clinical correlates in pregnant diabetes
Volume 172, N u m b e r 1, Part 2 Am.l Obstet Gww(ol
253 CIRCULATING INTERLEUKIN-1 AS A CLINICAL MARKER IN PREGNANT DIABETICS. U, Ma~rintes. C.D. Hsu, J.A. Copel, N. Nicklessx, D.W. Chanx. Dept. OB/GYN, Yale Univ., New Haven, CT and Johns Hopkins Univ. School of Med., Baltimore, MD. OBJECTIVE: Advanced glycosylation end-products have been shown to induce macrophagn-secreted eytokines, including interleukin-I OLd), a possible etiology of endothelial cell injury in diabetics. We prospectively studied glycosylated hemoglobin (HbA1C) and IL-1 levels to determine whether IL-1 can serve as a clinical marker for vascular endothelial injury in pregnant diabetics. STUDY DESIGN: A prospective cohort study of thirty-eight pregnant diabetic women was conducted: 20 with insulin-dependant diabetes (group 1) and 18 with gestational diabetes (group 2). Group 2 included 11 women controlled by diet and 7 women who required insulin. Serial measurements of HbA1C and IL-1 were performed by column chromatography and enzyme-linked immunosorbent assay, respectively. Comparisons between groups were performed by ANOVA and student t-tests. RESULTS: The serum HbAIC (mean + SEM) was significantly higher in group 1 than in group 2 (8.17 + 0.32% vs. 6.8 + 0.32%, p<0.01). Among subjects in group 1, there was a significant correlation between HbAIC and IL-1 (r=0.597, p=0.005). There were no abnormal HbA1C values in group 2 and no correlation between IL-1 and HbA1C in that group (rffi -0.389, p=0.15) There were slightly higher IL-1 levels in group 1 than in group 2 which did not reach statistical significance (0.58 + 0.21 pg/ml vs. 0.16 + 0.12 pg/ml, p=0.11). IL-1 did not correlate with White Classification, serum creatinine, proteinuria or the presence of chronic hypertension. CONCLUSIONS: The significant correlation observed between IL-I and HbA1C suggests that IL-1 plays an important role in the pathogenesis of vascular endothelial injury ocurring in pregnant diabetics and may have a role as a clinical marker. Vascular injury that is mediated by IL-1 may be ameliorated by improved glucose control.
254 CIRCULATING THROMBOMODULIN LEVELS AND
CLINICAL CORRELATES IN PREGNANT DIABETICS. ~ , C.D. Hsu, D.W. Chartx, N. Nicklessx, LA. Copel. Dept. OB/GYN, Yale Univ., New Haven, CT and Johns Hopkins Univ. School of Med., Baltimore, MD. OBJECTIVE: Thrombomodulin (TM) is a marker of endothelial cell damage. Elevated glycosylated Hemoglobin (HbA1C) has been implicated as a cause of endothelial cell damage in nonpregnant diabetics. To investigate the relationship of TM and HbA1C, we performed a prospective study of pregnant diabetics. STUDY DESIGN: Prospective cohort study of seventy patients: 19 pregnant women with insulin dependent diabetes (group 1), 17 women with gestational diabetes (group 2) and 34 pregnant normal controls (group 3, TM only). Group 2 included 9 women whose glucose was diet controlled and 8 women who required insulin. Plasma TM was determined using a two-site enzyme-linked immunosorbent assay. HbA1C was measured by column chromatography. Comparisons between groups were performed by using analysis of variance and student's t-tests. RESULTS: HbAIC and TM (mean + SEM) of group 1 were 8.06 + 0.34% and 57.05 + 6.60 ng/ml, respectively. The mean HbA1C and TM of group 2 were 6.78 + 0.33% and 50.31 -t- 4.65 ng/ml, respectively. The mean TM of group 3 was 50.31 + 4.38 ng/ml. There was a significant difference in HbA1C between groups 1 and 2 (p=0.01) but there was no difference in TM. There was no correlation between TM and HbAIC. However, TM levels correlated positively with serum creatinine (r=0.74, p<.001) and proteinuria (r=0.826, p<.0001). TM was significantly higher in diabetics of advanced White Classification (p=0.03). CONCLUSIONS: TM has been shown to be elevated in nonpregnant diabetics with elevated HbAIC. With good control, TM does not appear to be elevated inpregnancy. TM may be a marker of endothelial damage that correlates more with the class of diabetes and renal disease than with HbA1C, which reflects short-term control.
SPO Abstracts 331
255 CLASS A1 GESTATIONAL DIABETES: DOES PREVENTION OF POSTPARANDIAL HYPERGLYCEMIA IMPROVE PERINATAL OUTCOME? C. A. Malor, M. de Veciana, M.A. Morgan, J.S. Tcobey. Dept. of OB/GYN, University of California, lrvine, Orange, CA OB,I-EC'TIVE: To determine whether strict dietary intervention with subsequent postprandial euglycemia improves the perinatal outcome in women diagnosed with Class A1 gastational diabetes (GDM). STUDY DESIGN: 73 patients were diagnosed, prior to 32 wks gestation, as having Class A1 GDM according to the National Diabetes Data Group criteria. All oftbe patients were followed with dally fasting and postprandial glucose monitoring. Euglycemia was defined as a FBS < 105mg/di and a 1 hr postprandial of <140mg/dl. All patients had normal FBS values. 38 of the 73 patients were managed with strict dietary intervention and demonstrated postprandial euglycemia (EUGLY Group). 35 patients lacked dietary intervention and glucose monitoring demonstrated persistant postprandial hyperglycemia(HYPERGLY Group). Charts were abstracted for maternal demographics and perinatal outcome variables which were then compared between the groups. Macrosomia was defined as a BW>4000gm and LGA was defined as a BW >90th percentile for GA. RESULTS: Maternal demographics were similar between the groups. OR (95% CI) VARIABLES EUGLY HYPERGLY *o valae
256 EVALUATION OF ROUTINE O P H T H A L M O L O G I C EXAMS IN PREGNANT DIABETIC PATIENTS. S-PuzaX, M. Malee, Dept of Ob/Gyn, Univ. of Penn, Philadelphia, PA. OBJECTIVE: This study sought to examine the utility of routine ophthalmologic (ophth) exams for retinopathy during gestation in diabetics (DM) categorized according m White's classiftvation. STUDY DESIGN: Hospital records, office, ophth charts of pregnant DM's were reviewed over the period of 1989-1994. Inclusion criteria for gestational DM (GDM) was a late second or early third trimester (tri) ophth exam. Inclusion criteria for Class B-R were a first tri and third tri or early postpartum exams. Background (beckgrd) and proliferative (prolif) retinopathy were graded as mild, moderate, or severe. Ophth findings during pregnancy were not used m change White's classification. RESULTS: Of 431 charts requested, 53% were available for review; 78 met inclnsion criteria. They constituted the study group. Of GDM's, controlled with diet only (11.5%) or requiring insulin (33.2%), none had evidence of retinopathy. Class B patients constituted 23% of the study group; 22% had retinopathy, with 12% progression in backgrd retinopathy; none developed severe backgrd or prolif disease. Class C patients represented 7.7% of total group; 50% had retinopathy, 16.7% with progression; none developed severe backgrd or prolif disease. 11.5% of all patients were Class D; 89% had backgrd retinopathy, in whom 29% showed progression, 22% with severe backgrd retinopathy; none developed prolif disease. Combined Classes F,R and RF were 12.8% of the total patients; 100% demonstrated retinopathy; 60% progressed, with 80% having prolif disease, 20% required laser treatment. C O N C L U S I O N S : The results of this study confirm the f'mdings of Horvat e t a l that routine ophth exams in GDM's have little utility. Although limited by its relatively small number and retrospective nature, results suggest that the need for subsequent ophth exam can be based upon White's classification and initial exam results. Classes B and C do not require every tri exams given an absence of progression to severe backgrd or prolif disease. However, rigorous follow-up is warranted in Classes DR given the high percentage of progression and potential need for treatment.
253 CIRCULATING INTERLEUKIN-1 AS A CLINICAL MARKER IN PREGNANT DIABETICS. U, Ma~rintes. C.D. Hsu, J.A. Copel, N. Nicklessx, D.W. Chanx. Dept. OB/GYN, Yale Univ., New Haven, CT and Johns Hopkins Univ. School of Med., Baltimore, MD. OBJECTIVE: Advanced glycosylation end-products have been shown to induce macrophagn-secreted eytokines, including interleukin-I OLd), a possible etiology of endothelial cell injury in diabetics. We prospectively studied glycosylated hemoglobin (HbA1C) and IL-1 levels to determine whether IL-1 can serve as a clinical marker for vascular endothelial injury in pregnant diabetics. STUDY DESIGN: A prospective cohort study of thirty-eight pregnant diabetic women was conducted: 20 with insulin-dependant diabetes (group 1) and 18 with gestational diabetes (group 2). Group 2 included 11 women controlled by diet and 7 women who required insulin. Serial measurements of HbA1C and IL-1 were performed by column chromatography and enzyme-linked immunosorbent assay, respectively. Comparisons between groups were performed by ANOVA and student t-tests. RESULTS: The serum HbAIC (mean + SEM) was significantly higher in group 1 than in group 2 (8.17 + 0.32% vs. 6.8 + 0.32%, p<0.01). Among subjects in group 1, there was a significant correlation between HbAIC and IL-1 (r=0.597, p=0.005). There were no abnormal HbA1C values in group 2 and no correlation between IL-1 and HbA1C in that group (rffi -0.389, p=0.15) There were slightly higher IL-1 levels in group 1 than in group 2 which did not reach statistical significance (0.58 + 0.21 pg/ml vs. 0.16 + 0.12 pg/ml, p=0.11). IL-1 did not correlate with White Classification, serum creatinine, proteinuria or the presence of chronic hypertension. CONCLUSIONS: The significant correlation observed between IL-I and HbA1C suggests that IL-1 plays an important role in the pathogenesis of vascular endothelial injury ocurring in pregnant diabetics and may have a role as a clinical marker. Vascular injury that is mediated by IL-1 may be ameliorated by improved glucose control.
254 CIRCULATING THROMBOMODULIN LEVELS AND
CLINICAL CORRELATES IN PREGNANT DIABETICS. ~ , C.D. Hsu, D.W. Chartx, N. Nicklessx, LA. Copel. Dept. OB/GYN, Yale Univ., New Haven, CT and Johns Hopkins Univ. School of Med., Baltimore, MD. OBJECTIVE: Thrombomodulin (TM) is a marker of endothelial cell damage. Elevated glycosylated Hemoglobin (HbA1C) has been implicated as a cause of endothelial cell damage in nonpregnant diabetics. To investigate the relationship of TM and HbA1C, we performed a prospective study of pregnant diabetics. STUDY DESIGN: Prospective cohort study of seventy patients: 19 pregnant women with insulin dependent diabetes (group 1), 17 women with gestational diabetes (group 2) and 34 pregnant normal controls (group 3, TM only). Group 2 included 9 women whose glucose was diet controlled and 8 women who required insulin. Plasma TM was determined using a two-site enzyme-linked immunosorbent assay. HbA1C was measured by column chromatography. Comparisons between groups were performed by using analysis of variance and student's t-tests. RESULTS: HbAIC and TM (mean + SEM) of group 1 were 8.06 + 0.34% and 57.05 + 6.60 ng/ml, respectively. The mean HbA1C and TM of group 2 were 6.78 + 0.33% and 50.31 -t- 4.65 ng/ml, respectively. The mean TM of group 3 was 50.31 + 4.38 ng/ml. There was a significant difference in HbA1C between groups 1 and 2 (p=0.01) but there was no difference in TM. There was no correlation between TM and HbAIC. However, TM levels correlated positively with serum creatinine (r=0.74, p<.001) and proteinuria (r=0.826, p<.0001). TM was significantly higher in diabetics of advanced White Classification (p=0.03). CONCLUSIONS: TM has been shown to be elevated in nonpregnant diabetics with elevated HbAIC. With good control, TM does not appear to be elevated inpregnancy. TM may be a marker of endothelial damage that correlates more with the class of diabetes and renal disease than with HbA1C, which reflects short-term control.
SPO Abstracts 331
255 CLASS A1 GESTATIONAL DIABETES: DOES PREVENTION OF POSTPARANDIAL HYPERGLYCEMIA IMPROVE PERINATAL OUTCOME? C. A. Malor, M. de Veciana, M.A. Morgan, J.S. Tcobey. Dept. of OB/GYN, University of California, lrvine, Orange, CA OB,I-EC'TIVE: To determine whether strict dietary intervention with subsequent postprandial euglycemia improves the perinatal outcome in women diagnosed with Class A1 gastational diabetes (GDM). STUDY DESIGN: 73 patients were diagnosed, prior to 32 wks gestation, as having Class A1 GDM according to the National Diabetes Data Group criteria. All oftbe patients were followed with dally fasting and postprandial glucose monitoring. Euglycemia was defined as a FBS < 105mg/di and a 1 hr postprandial of <140mg/dl. All patients had normal FBS values. 38 of the 73 patients were managed with strict dietary intervention and demonstrated postprandial euglycemia (EUGLY Group). 35 patients lacked dietary intervention and glucose monitoring demonstrated persistant postprandial hyperglycemia(HYPERGLY Group). Charts were abstracted for maternal demographics and perinatal outcome variables which were then compared between the groups. Macrosomia was defined as a BW>4000gm and LGA was defined as a BW >90th percentile for GA. RESULTS: Maternal demographics were similar between the groups. OR (95% CI) VARIABLES EUGLY HYPERGLY *o valae
256 EVALUATION OF ROUTINE O P H T H A L M O L O G I C EXAMS IN PREGNANT DIABETIC PATIENTS. S-PuzaX, M. Malee, Dept of Ob/Gyn, Univ. of Penn, Philadelphia, PA. OBJECTIVE: This study sought to examine the utility of routine ophthalmologic (ophth) exams for retinopathy during gestation in diabetics (DM) categorized according m White's classiftvation. STUDY DESIGN: Hospital records, office, ophth charts of pregnant DM's were reviewed over the period of 1989-1994. Inclusion criteria for gestational DM (GDM) was a late second or early third trimester (tri) ophth exam. Inclusion criteria for Class B-R were a first tri and third tri or early postpartum exams. Background (beckgrd) and proliferative (prolif) retinopathy were graded as mild, moderate, or severe. Ophth findings during pregnancy were not used m change White's classification. RESULTS: Of 431 charts requested, 53% were available for review; 78 met inclnsion criteria. They constituted the study group. Of GDM's, controlled with diet only (11.5%) or requiring insulin (33.2%), none had evidence of retinopathy. Class B patients constituted 23% of the study group; 22% had retinopathy, with 12% progression in backgrd retinopathy; none developed severe backgrd or prolif disease. Class C patients represented 7.7% of total group; 50% had retinopathy, 16.7% with progression; none developed severe backgrd or prolif disease. 11.5% of all patients were Class D; 89% had backgrd retinopathy, in whom 29% showed progression, 22% with severe backgrd retinopathy; none developed prolif disease. Combined Classes F,R and RF were 12.8% of the total patients; 100% demonstrated retinopathy; 60% progressed, with 80% having prolif disease, 20% required laser treatment. C O N C L U S I O N S : The results of this study confirm the f'mdings of Horvat e t a l that routine ophth exams in GDM's have little utility. Although limited by its relatively small number and retrospective nature, results suggest that the need for subsequent ophth exam can be based upon White's classification and initial exam results. Classes B and C do not require every tri exams given an absence of progression to severe backgrd or prolif disease. However, rigorous follow-up is warranted in Classes DR given the high percentage of progression and potential need for treatment.