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Estimates of insulin sensitivity using C-peptide from an oral glucose tolerance test (OGTT)
S52 SMFM Abstracts 153
EARLY PREGNANCY ADIPONECTIN CONCENTRATIONS ARE ASSOCIATED WITH GESTATIONAL DIABETES KRISTINE LAIN1, PAUL SPEER1, STACY MCGONIGAL1, JAMES ROBERTS1, 1University of Pittsburgh, Obstetrics, Gynecology, and Reproductive Sciences, Pittsburgh, Pennsylvania OBJECTIVE: Adiponectin is the most abundant adipose-specific protein and has anti-inflammatory, antiatherogenic, and insulin-sensitizing properties. Adiponectin is negatively associated with obesity and insulin resistance with plasma concentrations lower in individuals with polycystic ovarian syndrome, coronary artery disease, and type 2 diabetes. We hypothesized that adiponectin concentrations are lower in women early in pregnancy who later develop gestational diabetes (GDM). STUDY DESIGN: This nested case-control study utilized first-trimester samples from primiparous women enrolled in an ongoing longitudinal study. Adiponectin concentrations from women who developed GDM (N = 38) were compared to those of control patients who did not (N = 30). Adiponectin concentrations were determined by radioimmunoassay. Baseline demographic descriptors and obstetric outcomes were compared between the two groups by chi-square analysis and Student’s t test. Logistic regression was utilized to control for confounding. RESULTS: The groups were not different by baseline descriptors or obstetric outcomes. Mean gestational age of samples was 9.4 G 2.9 and 9.5 G 2.6 weeks for the control and GDM groups. Mean adiponectin concentrations were lower (P ! .001) in the women who developed GDM compared to women who did not (4.3 G 0.3 vs 6.7 G 0.6 mg/mL). Women with adiponectin concentrations !25th% were 11.2 times more likely to develop GDM (95%CI 2.2, 56.9) and this persisted after controlling for BMI and race (OR 8.2; 95%CI 1.6, 42.9). CONCLUSION: This data suggests alterations in adipocyte function as early as the first trimester in women who are later recognized to have GDM. The study is limited by the lack of first trimester glucose tolerance information and does not establish whether these women were different before pregnancy. However, given most women test normal this early in pregnancy, this finding suggests that women with glucose intolerance of pregnancy may have significant alterations in adipocyte homeostasis long before the diagnosis of GDM is made.
155
ANTEPARTUM HYPERGLYCEMIA FAILS TO PREDICT GDM OR MACROSOMIA JENNIFER AHN1, JUDITH HIBBARD1, MATTHEW CORCORAN2, 1University of Chicago, Obstetrics & Gynecology, Chicago, Illinois, 2University of Chicago, Medicine, Endocrinology Section, Chicago, Illinois OBJECTIVE: To show that periods of unrecognized hyperglycemia will predict patients who will develop Gestational Diabetes (GDM) in high risk patients. STUDY DESIGN: All new OB patients who presented to our high risk referral center were evaluated for risks toward developing GDM. Those patients who demonstrated one or more of the following risk factors were offered entry into the study: history of GDM, history of macrosomia, family history of diabetes, prepregnancy body mass index (BMI) >30 kg/m2, or Hispanic race. Those patients who had pregestational diabetes or who were diagnosed with diabetes by a first trimester glucose tolerance test were excluded from the study. The Medtronic Continuous Glucose Monitor (CGMS) was worn for 3-4 days prior to 18 weeks gestation. The subjects were followed for the duration of the pregnancy and evaluated for development of GDM and/or birth of a macrosomic infant. Hyperglycemia was defined as glucose >120 mg/dL. RESULTS: Twenty-three patients agreed to participate in the study: 4 patients changed their mind, 3 patients had sensor failure, and 1 patient was lost to follow-up. There were 15 patients who completed the study. Approximately 80% of patients experienced epsiodes of hyperglycemia while wearing the monitor. Four patients (27%) spent greater than 25% of the time on the monitor above the goal blood sugars, with peak blood sugars exceeding 200 mg/dL in 2 subjects. Despite these periods of unrecognized hyperglycemia, none of the patients developed GDM, nor did any deliver an infant with macrosomia (mean birth weight 3037 G 595 g). CONCLUSION: Unrecognized periods of hyperglycemia in a high risk population did not predict development of GDM. Furthermore, hyperglycemia evidenced in the early half of pregnancy did not predict development of macrosomia.
154
ESTIMATES OF INSULIN SENSITIVITY USING C-PEPTIDE FROM AN ORAL GLUCOSE TOLERANCE TEST (OGTT) TATJANA RADAELLI1, PATRICK CATALANO2, 1Case Western Reserve University at MetroHealth Medical Center, OB/GYN, Cleveland, Ohio, 2 Case Western Reserve University, Reproductive Biology, Cleveland, Ohio OBJECTIVE: To determine if C-peptide obtained as part of a 75 g OGTT can be used to evaluate insulin sensitivity during pregnancy. STUDY DESIGN: Eighty-one women enrolled in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study were recruited at 27.6 G 1.2 weeks (mean G SD) for a 75 g OGTT. Venous blood samples were drawn for C-peptide at 0 and 60 minutes after the glucose challenge, and glucose and insulin were obtained at 0, 30, 60, 90 and 120 minutes. The ISOGTT as described by Matsuda and DeFronzo was used to estimate insulin sensitivity based on glucose and insulin. The ISOGTT has the strongest correlation with insulin sensitivity measured by the euglycemic clamp in pregnancy (r = 0.86, P = .0001). Insulin sensitivity was also calculated for these subjects using the ISHOMA and ISQUCKI. These were calculated as follows: ISOGTT = 10,0000/O(FPG)*(FPI)*(G*I), where FGP and FPI are fasting plasma glucose and insulin respectively, while G and I are mean glucose and mean insulin from 30 to 120 minutes; ISHOMA = (FPG*FPI)/22.5; ISQUICKI = 1/[(FPI) + log(FPG)]. Insulin sensitivity was then calculated using glucose and C-peptide concentrations at 0 and 60 minutes. RESULTS: The correlations of the ISQUICKI and ISHOMA with ISOGTT were (r = 0.82) and (r = 0.75), respectively. Using the fasting glucose and C-peptide data, the correlation of ISQUICKI C-pep and ISHOMA C-pep with ISOGTT were (r = 0.64) and (r = 0.59), respectively. However, the best correlation with the ISOGTT was for ISOGTT c-pep (r = 0.80, P = .0001). CONCLUSION: Using ISOGTT c-pep (glucose and C-peptide at 0 and 60 min), we obtained an excellent correlation with the ISOGTT, comparable to the one obtained with euglycemic-hyperinsulinemic in pregnancy. These data suggest that ISOGTT c-pep can be used as a simple alternative to ISOGTT for assessment of insulin sensitivity with a 75 g OGTT during pregnancy.
156
RESISTIN: A HORMONE WHICH INDUCES INSULIN RESISTANCE IS INCREASED IN NORMAL PREGNANCY JYH KAE NIEN1, RICARDO GOMEZ2, JIMMY ESPINOZA1, LUIS GONCALVES3, JOON-SEOK HONG1, SAMUEL EDWIN1, SONIA HASSAN3, MOSHE MAZOR4, ROBERTO ROMERO1, 1Perinatology Research Branch, NICHD, NIH, DHHS, Bethesda, Maryland, 2CEDIP, Sotero del Rio Hospital, Puente Alto, Chile, Chile, 3Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, Michigan, 4Soroka University Medical Center, Beer Sheva, Israel, Israel OBJECTIVE: Normal pregnancy is a state of relative insulin resistance, yet the precise mechanism responsible for this important metabolic adaptation remains to be defined. Resistin, a recently discovered hormone (2001), is produced by adipose tissue and confers ‘‘resistance to insulin’’ and hence its name. The objective of this study was to determine if the plasma resistin concentration is increased during pregnancy and to generate a reference range for this hormone. STUDY DESIGN: A cross-sectional study was conducted in which resistin was assayed in 261 women with normal gestation and 40 nonpregnant women. Pregnant women were considered normal if they had a negative oral glucose tolerance test, delivered an appropriate for gestational age infant at term, and were free of obstetrical and medical complications. All women had body mass indices !25. Plasma resistin concentrations were determined using specific immunoassays (ELISA) with a sensitivity of 0.095 ng/mL. RESULTS: The median plasma concentration of resistin was significantly higher in pregnant women in the first trimester than in non-pregnant women [12.8 ng/mL (4.6-81.3) vs 10.4 ng/mL (6.5-11.75)]; P ! .05). The plasma concentration of resistin increased with gestational age (rho = 0.22; P ! .01). The Table provides the descriptive statistics of resistin in non-pregnant and normal pregnant women (ng/mL).
Non-pregnant 11-14 wk 15-18 wk 27-30 wk 37-42 wk
n
Percentile 10
Median
Percentile 90
40 63 68 65 65
6.5 7.3 9.2 8.1 10.9
10.2 12.8 14.3 12.8 15.7
16.1 25.9 24.3 30.3 28.5
CONCLUSION: Pregnancy is associated with an increase in the plasma concentration of resistin. This hormone may play a role in an important endocrine/metabolic adaptation of pregnancy: relative insulin resistance.
EARLY PREGNANCY ADIPONECTIN CONCENTRATIONS ARE ASSOCIATED WITH GESTATIONAL DIABETES KRISTINE LAIN1, PAUL SPEER1, STACY MCGONIGAL1, JAMES ROBERTS1, 1University of Pittsburgh, Obstetrics, Gynecology, and Reproductive Sciences, Pittsburgh, Pennsylvania OBJECTIVE: Adiponectin is the most abundant adipose-specific protein and has anti-inflammatory, antiatherogenic, and insulin-sensitizing properties. Adiponectin is negatively associated with obesity and insulin resistance with plasma concentrations lower in individuals with polycystic ovarian syndrome, coronary artery disease, and type 2 diabetes. We hypothesized that adiponectin concentrations are lower in women early in pregnancy who later develop gestational diabetes (GDM). STUDY DESIGN: This nested case-control study utilized first-trimester samples from primiparous women enrolled in an ongoing longitudinal study. Adiponectin concentrations from women who developed GDM (N = 38) were compared to those of control patients who did not (N = 30). Adiponectin concentrations were determined by radioimmunoassay. Baseline demographic descriptors and obstetric outcomes were compared between the two groups by chi-square analysis and Student’s t test. Logistic regression was utilized to control for confounding. RESULTS: The groups were not different by baseline descriptors or obstetric outcomes. Mean gestational age of samples was 9.4 G 2.9 and 9.5 G 2.6 weeks for the control and GDM groups. Mean adiponectin concentrations were lower (P ! .001) in the women who developed GDM compared to women who did not (4.3 G 0.3 vs 6.7 G 0.6 mg/mL). Women with adiponectin concentrations !25th% were 11.2 times more likely to develop GDM (95%CI 2.2, 56.9) and this persisted after controlling for BMI and race (OR 8.2; 95%CI 1.6, 42.9). CONCLUSION: This data suggests alterations in adipocyte function as early as the first trimester in women who are later recognized to have GDM. The study is limited by the lack of first trimester glucose tolerance information and does not establish whether these women were different before pregnancy. However, given most women test normal this early in pregnancy, this finding suggests that women with glucose intolerance of pregnancy may have significant alterations in adipocyte homeostasis long before the diagnosis of GDM is made.
155
ANTEPARTUM HYPERGLYCEMIA FAILS TO PREDICT GDM OR MACROSOMIA JENNIFER AHN1, JUDITH HIBBARD1, MATTHEW CORCORAN2, 1University of Chicago, Obstetrics & Gynecology, Chicago, Illinois, 2University of Chicago, Medicine, Endocrinology Section, Chicago, Illinois OBJECTIVE: To show that periods of unrecognized hyperglycemia will predict patients who will develop Gestational Diabetes (GDM) in high risk patients. STUDY DESIGN: All new OB patients who presented to our high risk referral center were evaluated for risks toward developing GDM. Those patients who demonstrated one or more of the following risk factors were offered entry into the study: history of GDM, history of macrosomia, family history of diabetes, prepregnancy body mass index (BMI) >30 kg/m2, or Hispanic race. Those patients who had pregestational diabetes or who were diagnosed with diabetes by a first trimester glucose tolerance test were excluded from the study. The Medtronic Continuous Glucose Monitor (CGMS) was worn for 3-4 days prior to 18 weeks gestation. The subjects were followed for the duration of the pregnancy and evaluated for development of GDM and/or birth of a macrosomic infant. Hyperglycemia was defined as glucose >120 mg/dL. RESULTS: Twenty-three patients agreed to participate in the study: 4 patients changed their mind, 3 patients had sensor failure, and 1 patient was lost to follow-up. There were 15 patients who completed the study. Approximately 80% of patients experienced epsiodes of hyperglycemia while wearing the monitor. Four patients (27%) spent greater than 25% of the time on the monitor above the goal blood sugars, with peak blood sugars exceeding 200 mg/dL in 2 subjects. Despite these periods of unrecognized hyperglycemia, none of the patients developed GDM, nor did any deliver an infant with macrosomia (mean birth weight 3037 G 595 g). CONCLUSION: Unrecognized periods of hyperglycemia in a high risk population did not predict development of GDM. Furthermore, hyperglycemia evidenced in the early half of pregnancy did not predict development of macrosomia.
154
ESTIMATES OF INSULIN SENSITIVITY USING C-PEPTIDE FROM AN ORAL GLUCOSE TOLERANCE TEST (OGTT) TATJANA RADAELLI1, PATRICK CATALANO2, 1Case Western Reserve University at MetroHealth Medical Center, OB/GYN, Cleveland, Ohio, 2 Case Western Reserve University, Reproductive Biology, Cleveland, Ohio OBJECTIVE: To determine if C-peptide obtained as part of a 75 g OGTT can be used to evaluate insulin sensitivity during pregnancy. STUDY DESIGN: Eighty-one women enrolled in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study were recruited at 27.6 G 1.2 weeks (mean G SD) for a 75 g OGTT. Venous blood samples were drawn for C-peptide at 0 and 60 minutes after the glucose challenge, and glucose and insulin were obtained at 0, 30, 60, 90 and 120 minutes. The ISOGTT as described by Matsuda and DeFronzo was used to estimate insulin sensitivity based on glucose and insulin. The ISOGTT has the strongest correlation with insulin sensitivity measured by the euglycemic clamp in pregnancy (r = 0.86, P = .0001). Insulin sensitivity was also calculated for these subjects using the ISHOMA and ISQUCKI. These were calculated as follows: ISOGTT = 10,0000/O(FPG)*(FPI)*(G*I), where FGP and FPI are fasting plasma glucose and insulin respectively, while G and I are mean glucose and mean insulin from 30 to 120 minutes; ISHOMA = (FPG*FPI)/22.5; ISQUICKI = 1/[(FPI) + log(FPG)]. Insulin sensitivity was then calculated using glucose and C-peptide concentrations at 0 and 60 minutes. RESULTS: The correlations of the ISQUICKI and ISHOMA with ISOGTT were (r = 0.82) and (r = 0.75), respectively. Using the fasting glucose and C-peptide data, the correlation of ISQUICKI C-pep and ISHOMA C-pep with ISOGTT were (r = 0.64) and (r = 0.59), respectively. However, the best correlation with the ISOGTT was for ISOGTT c-pep (r = 0.80, P = .0001). CONCLUSION: Using ISOGTT c-pep (glucose and C-peptide at 0 and 60 min), we obtained an excellent correlation with the ISOGTT, comparable to the one obtained with euglycemic-hyperinsulinemic in pregnancy. These data suggest that ISOGTT c-pep can be used as a simple alternative to ISOGTT for assessment of insulin sensitivity with a 75 g OGTT during pregnancy.
156
RESISTIN: A HORMONE WHICH INDUCES INSULIN RESISTANCE IS INCREASED IN NORMAL PREGNANCY JYH KAE NIEN1, RICARDO GOMEZ2, JIMMY ESPINOZA1, LUIS GONCALVES3, JOON-SEOK HONG1, SAMUEL EDWIN1, SONIA HASSAN3, MOSHE MAZOR4, ROBERTO ROMERO1, 1Perinatology Research Branch, NICHD, NIH, DHHS, Bethesda, Maryland, 2CEDIP, Sotero del Rio Hospital, Puente Alto, Chile, Chile, 3Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, Michigan, 4Soroka University Medical Center, Beer Sheva, Israel, Israel OBJECTIVE: Normal pregnancy is a state of relative insulin resistance, yet the precise mechanism responsible for this important metabolic adaptation remains to be defined. Resistin, a recently discovered hormone (2001), is produced by adipose tissue and confers ‘‘resistance to insulin’’ and hence its name. The objective of this study was to determine if the plasma resistin concentration is increased during pregnancy and to generate a reference range for this hormone. STUDY DESIGN: A cross-sectional study was conducted in which resistin was assayed in 261 women with normal gestation and 40 nonpregnant women. Pregnant women were considered normal if they had a negative oral glucose tolerance test, delivered an appropriate for gestational age infant at term, and were free of obstetrical and medical complications. All women had body mass indices !25. Plasma resistin concentrations were determined using specific immunoassays (ELISA) with a sensitivity of 0.095 ng/mL. RESULTS: The median plasma concentration of resistin was significantly higher in pregnant women in the first trimester than in non-pregnant women [12.8 ng/mL (4.6-81.3) vs 10.4 ng/mL (6.5-11.75)]; P ! .05). The plasma concentration of resistin increased with gestational age (rho = 0.22; P ! .01). The Table provides the descriptive statistics of resistin in non-pregnant and normal pregnant women (ng/mL).
Non-pregnant 11-14 wk 15-18 wk 27-30 wk 37-42 wk
n
Percentile 10
Median
Percentile 90
40 63 68 65 65
6.5 7.3 9.2 8.1 10.9
10.2 12.8 14.3 12.8 15.7
16.1 25.9 24.3 30.3 28.5
CONCLUSION: Pregnancy is associated with an increase in the plasma concentration of resistin. This hormone may play a role in an important endocrine/metabolic adaptation of pregnancy: relative insulin resistance.