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Diabetes & Metabolism
Vol 27, N° 6 - décembre 2001
pp. 675-680
Doi : DM-12-2001-27-6-1262-3636-101019-ART7 | |
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© Masson, Paris, 2001 Antepartum and early postpartum predictors of type 2 diabetes development in women with gestational diabetes mellitus Objectives This study aimed at identifying ante-partum and early post-partum (one year) clinical and metabolic characteristics capable of predicting the future development of type 2 diabetes in pregnant women of Mediterranea area affected by gestational diabetes mellitus (GDM). Material and methods Seventy GDM patients were evaluated: mean age during pregnancy, plasma glucose levels under OGTT (100 gr. glucose), fasting, 1-h post-prandial plasma glucose levels, HbA1c at the third trimester, gestational week of GDM diagnosis, insulin therapy, and weight gain were all taken into consideration. Some maternal risk factors such as pre-pregnancy BMI, and maternal and fetal outcome of index pregnancy were also assessed. One year after delivery in the same patients, BMI, fasting and 1-h post-prandial plasma glucose, plasma glucose and insulinemia under OGTT (75 gr. glucose) were measured. We focused our attention on women who presented type 2 diabetes 5 years after pregnancy or IGT and those who, one year after pregnancy, were normal. Results Five years after pregnancy 49 women were normal, 5 had developed type 1 diabetes and were not considered, 6 had developed IGT, and 10 type 2 diabetes. Analysis of variables during pregnancy showed that those variables predicting type 2 diabetes were pre-pregnancy BMI, gestational week of diagnosis, need for insulin therapy, obesity, and plasma glucose at 60' OGTT. Analysis of variables evaluated one year after pregnancy showed that BMI, fasting and post-prandial plasma glucose, plasma glucose at each point of the OGTT, and plasma insulin at 30' OGTT were predictive of the development of type 2 diabetes. Furthermore, age, post-partum fasting plasma glucose, and plasma glucose under OGTT post-partum were predictive of the development of IGT. Our data show for the first time that, also in a Caucasian Mediterranean population, markers of the future development of diabetes do exist, as reported in literature. They also stress the importance of correct identification of GDM patients, in order to screen those at greater risk of developing diabetes, for whom it is imperative to set up prevention programs. gestational diabetes mellitus
,
type 2 diabetes
,
follow up
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OGTT
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risk factors Facteurs prédictifs antepartum et postpartum précoces du développement d'un diabète de type 2 chez les femmes présentant un diabète gestationnel. Objectifs Cette étude avait pour but d'identifier les caractères cliniques et métaboliques de la période ante-partum et post-partum précoce (1 an) susceptibles d'aider à prédire le développement ultérieur d'un diabète de type 2 chez des femmes enceintes de la région méditerranéenne présentant un diabète gestationnel (DG). Matériel et méthodes Soixante-dix patientes avec DG ont été évaluées : âge pendant la grossesse, glycémie sour HGPO (100 gr. glucose), glycémie à jeûn et 1h post-prandiale, HbA1c au 3e trimestre, semaine gestationnelle du diagnostic de DG, traitement insulinique, et prise de poids ont été pris en considération. Certains facteurs de risque maternel comme le BMI pré-gravidique, et l'issue maternelle et foetale de la grossesse index ont été évalués. Un an après la délivrance chez ces patientes, le BMI, la glycémie à jeûn et 1h post-prandiale, la glycémie et l'insulinémie sou HGPO (75 gr. glucose) ont été mesurés. Nous nous sommes concentrés sur les femmmes présentant un diabète de type 2 5 ans après la grossesse ou une intolérance au glucose et celles qui étaient normales un an après la grossesse. Résultats Cinq ans après la grossesse, 49 femmes étaient normales, 5 avaient développé un diabète de type 1 et n'ont pas été étudiées, 6 avaient développé une intolérance au glucose, et 10 un diabète de type 2. L'analyse des variables pendant la grossesse a montré que les variables prédictives de diabète de type 2 étaient le BMI pré-gravidique, la semaine gestationnelle du diagnostic, le besoin d'insulinothérapie, l'obésité, et la glycémie à 60'sous HGPO. L'analyse des variables un an après la grossesse a montré que le BMI, la glycémie à jeûn et post-prandiale, la glycémie à chaque point de l'HGPO, et l'insulinémie à 30'étaient prédictifs du développement d'un diabète de type 2. En outre, l'âge, la glycémie à jeûn post-partum, et la glycémie sous HGPO post-partum étaient prédictifs du développement d'une intolérance au glucose. Nos données montrent pour la première fois que, également dans une population caucasienne méditerranéenne, les marqueurs du développement ultérieur d'un diabète existent, comme rapporté dans la littérature. Elles mettent l'accent sur l'importance d'identifier correctement les femmes avec diabète gestationel, afin de dépister celles à plus fort risque de développer un diabète, et nécessitant des mesures préventives. diabète gestationnel
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diabète de type 2
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suivi
,
HGPO
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facteurs de risque
Women with a history of gestational diabetes mellitus (GDM) are at increased risk of future diabetes, predominantly type 2 [1][2]. This prevalence after GDM varies from 3.4% to 65% of the patients studied [2], depending mainly on the different populations and the varying periods of follow-up used [3][4][5][6][7][8][9]. Thus, women with previous GDM constitute an ideal group for primary diabetes prevention. In this context, studies evaluating ante-partum and early post-partum predictors of development of type 2 diabetes are very important, because they represent a useful starting point for prevention programs. Several predictors of diabetes after GDM have been identified in various populations, i.e., severity of glucose intolerance during pregnancy and immediately post-partum [6][10][11], pre-pregnancy obesity [12][13], maternal age [14], recurrence of GDM, parity [4] and delivery of a macrosomic baby [15].
This study reports data regarding ante-partum and early post-partum metabolic assessment in women with GDM screened in the Padova district and representative of a non-diabetic non-hospitalised female population from a North Mediterranean area. In particular, some possibly clinical and/or metabolic potential predictors of future diabetes in 70 GDM patients followed for 5 years were retrospectively evaluated.
Subjects were selected from a group of about 650 women screened for GDM in 1990-1992 [16]. GDM was diagnosed according to Carpenter and Coustan's criteria after screening with the glucose challenge test (GCT) [17]. Screening was carried out in all patients between the 24 th and 28 th weeks of pregnancy; patients who were positive (i.e., plasma glucose 1 hour after GCT >= 140 mg/dl) were subjected to the oral glucose tolerance test (OGTT) with 100 gr. glucose.
GDM was diagnosed if any two of the following values were reached or exceeded: fasting plasma glucose >= 95 mg/dl, 1h >= 180 mg/dl, 2h >= 155 mg/dl, 3h >= 140 mg/dl. Pregnant women presenting one or more GDM risk factors were screened earlier [18]. They were put on a diet to allow a weight gain of 9-13.6 kg and checked by evaluation of fasting and post-prandial plasma glucose levels. If these levels were not maintained within an acceptable range (i.e., fasting plasma glucose < 95 mg/dl and/or 1h post-prandial plasma glucose < 130 mg/dl after 2 weeks), insulin treatment was started. Seventy GDM patients were selected for this study. Patients' age, family history of diabetes, pre-pregnancy body weight and BMI, previous GDM and obstetric outcome (parity, repeated abortion, macrosomia, stillbirths) were recorded. As regards index pregnancy, gestational age at the time of diagnosis of GDM, glucose levels of diagnostic OGTT, fasting, 1-h post-prandial plasma glucose and HbA1c at the third trimester of pregnancy, weight gain and insulin therapy were taken into consideration. As regards index pregnancy outcome, time and type of delivery (abortion, caesarean section, spontaneous labour) and fetal outcome (weight, birth trauma, stillbirths) were analysed. Macrosomia was considered as in fant weight >= 4 kg; Large for Gestational Age (LGA) as a birth weight > 90th percentile, Small for Gestational Age (SGA) a birth weight < 10th percentile; the ponderal index was calculated as birth weight (g)/length (cm)3 X 100. For follow-up evaluation, women were subjected to OGTT every year for 5 years after delivery. They were advised to contact the diabetologist if any symptoms suggestive of diabetes developed (polydipsia, polyuria, polyphagy, loss of weight). Patients who developed type 1 diabetes were excluded from this study. Diabetes during follow-up was diagnosed according to the World Health Organization criteria, using an OGTT with 75 gr. of glucose [19]. In the 70 patients selected for this study, body weight, BMI, OGTT with plasma glucose and insulin measurements (at 0, 30, 60 and 120 min), and fasting and post-prandial plasma glucose values one year after pregnancy, were all taken into consideration. All patients gave their informed consent to the study, which was conducted in accordance with the Helsinki declaration [20].
Plasma glucose levels were evaluated with a glucose-oxidase method [21]. Glycated haemoglobin (HbA 1c) was measured by HPLC [22] and insulin by a RIA method [23].
Values are expressed as means ± SD and evaluated by Student's t-test. Variance analysis, the exact Fisher test and χ2 analysis were used for categorical data. Differences were considered to be statistically significant at p < 0.05.
One year after pregnancy, 7 of the 70 GDM patients had developed impaired glucose tolerance (IGT), 3 type 1 diabetes (and excluded from the study) and 2 type 2 diabetes; 58 were normal.
Five years after pregnancy, 6 of the 70 GDM patients had developed IGT, 5 patients type 1 diabetes (and excluded from the study) and 10 type 2 diabetes; 49 were normal. We focused our attention on patients who, one year after pregnancy, showed normal glucose tolerance but developed type 2 diabetes or IGT after 5 years.
The clinical and metabolic data evaluated in our patients are shown in Table I. As regards clinical parameters considered, mean age was significantly higher in GDM women who developed IGT after 5 years. Mean pre-pregnancy body weight was significantly higher in GDM patients who developed type 2 diabetes after 5 years with respect to the other groups. Interestingly, in patients who developed type 2 diabetes, GDM was diagnosed earlier than in the other groups.
As regards maternal risk factors evaluated, only pre-pregnancy obesity was significantly higher in GDM patients who developed type 2 diabetes with respect to those who developed IGT and or remained normal (Table II). Patients who developed type 2 diabetes after pregnancy more frequently required insulin treatment to reach good glycemic control during pregnancy than those who developed IGT and or returned to normal after pregnancy. In these patients, a lower weight gain was also observed. As regards metabolic parameters evaluated, no differences in fasting and post-prandial plasma glucose and/or HbA1c values were observed during pregnancy in the three groups of patients. Passing on to plasma glucose levels under OGTT, mean 1-h plasma glucose levels were significantly higher in patients who developed type 2 diabetes after 5 years than in those who remained normal or developed IGT (Fig. 1). Considering obstetric outcome, no differences were found in the three groups of patients as regards frequency of abortion, caesarean section or spontaneous delivery. Neonatal outcome, mean weight and ponderal index, frequency of macrosomia, LGA and SGA, did not differ in the three groups. Lastly, there were no cases of birth trauma or stillbirths in any group (Table III).
One year after pregnancy, BMI was significantly higher in patients who developed type 2 diabetes after 5 years with respect to the other groups. Furthermore, mean fasting plasma glucose levels were significantly higher in patients who developed IGT and in those who developed type 2 diabetes after 5 years with respect to patients who remained normal. In patients who developed type 2 diabetes mean post-prandial plasma glucose levels were also significantly higher with respect to those in the other two groups.
As for OGTT evaluated 1 year after pregnancy, GDM patients who developed type 2 diabetes and or IGT within 5 years had significantly higher plasma glucose levels at 0', 30', 60' and 120' OGTT than those who developed IGT and or remained normal. Furthermore, plasma insulin levels in patients who developed type 2 diabetes after 5 years were significantly lower at 30' OGTT and were significantly higher in patients who developed IGT after 5 years at 30' and 60' OGTT with respect to those who remained normal (Fig. 2 and 3).
The patients with previous GDM who were subjected to follow-up evaluation after pregnancy were the first 70 patients with GDM we diagnosed with a screening program conducted in the Padova district from 1990 to 1992. In this group, the incidence of abnormal glucose tolerance, defined following WHO criteria, is 8.6% for IGT and 14.3% for type 2 diabetes after 5 years, according to the literature [2][3][4][5][6][7][8][9].
Looking at classical risk factors for GDM development, only pre-pregnancy obesity was more common in women with post-partum diabetes, in agreement with the results of other authors [12][13]. As for index pregnancy, women who developed type 2 diabetes 5 years after pregnancy were diagnosed as having GDM earlier and showed higher glucose values under OGTT evaluation [6][11][13]. It is therefore possible that some of these women, just before pregnancy, had some minimal impairment of glucose tolerance which was not diagnosed. Considering our patients' clinical features, GDM patients with post-partum diabetes were older and more obese than those who remained normal [12][13][14][24]. GDM patients who developed type 2 diabetes after 5 years were more frequently treated with insulin than patients who remained normal or developed IGT, confirming some previous reports that the need of insulin therapy is a good predictor of the future development of diabetes [4][13]. The greater need for insulin therapy in these women also probably reflects the good metabolic control attained, since fasting, post-prandial plasma glucose and HbA1c levels at the 3rd trimester of pregnancy in these women overlapped those of other GDM patients. Due to the fact that GDM patients who developed type 2 diabetes after 5 years were more obese, they were probably monitored more frequently. In fact, we found that their weight gain during pregnancy was significantly lower than in the other groups. Considering pregnancy outcome, no differences in type of delivery or maternal and fetal complications were observed in the three groups. In particular, we were not able to find higher incidences of macrosomia or LGA in GDM patients who developed type 2 diabetes with respect to the other groups; nor was the ponderal index significantly different in the three groups. Although this does not fit other findings [13][15], it may be explained by the fact that GDM patients who developed type 2 diabetes 5 years after pregnancy were diagnosed as having GDM earlier and were thus treated earlier. In addition, interestingly, they more frequently received insulin treatment in order to attain good metabolic control and a well-controlled weight gain during pregnancy, reflected in a frequency of macrosomia which was not different with respect to that of GDM patients who remained normal or developed IGT after pregnancy. Alternatively, the relatively small number of patients and consequently newborns examined may explain these results. Clinical and metabolic evaluations after pregnancy showed that, just one year after pregnancy, GDM patients who were normal on this occasion but developed type 2 diabetes 5 years after pregnancy, had significantly higher BMI and fasting and post-prandial plasma glucose values. Furthermore, also patients who developed IGT after pregnancy showed higher fasting plasma glucose. Looking at the OGTT evaluated one year after pregnancy, it is interesting to note that plasma glucose levels were significantly higher at each value of the curve, both in patients who later developed type 2 diabetes and in those who later developed IGT, with respect to women who remained normal. As for insulin levels, significantly lower levels of plasma insulin at 60' OGTT were found in women who developed diabetes 5 years after pregnancy. These data stress the fact that a poor insulin response due to ß cell dysfunction is a characteristic of GDM patients who later develop diabetes [11][25][26][27][28][29]. In a very elegant paper, Buchanan [25] showed that the best predictors of future diabetes, in a cohort of GDM Latino women, were post-challenge hyperglycemia, poor ß cell compensation for insulin resistance, and elevated basal glucose production during pregnancy. Our data, although certainly not as elegant as those of Buchanan, agree with those of the author and show, for the first time, that, also in a Caucasian Mediterranean population, high post-challenge levels of glycemia (although falling within the normal range) and low levels of insulinemia one year post-partum are good predictors of future diabetes in GDM patients. Unfortunately, we did not measure insulin levels under OGTT tested in GDM patients during pregnancy, which would have provided further support to data obtained after pregnancy. Patients who developed IGT 5 years after pregnancy had insulin levels under OGTT which were significantly higher at 30' and 60' with respect to patients who developed type 2 diabetes, and they were higher, although not significantly so, at 60' and 120' OGTT with respect to patients who remained normal. Perhaps these patients are more insulin-resistant than those of the other groups: unfortunately, the small number of patients examined did not allow definitive conclusions on this point [29][30]. In conclusion, we have identified for the first time some of the markers reported in the literature as predictors of future diabetes for in a cohort of Caucasian Mediterranean GDM women: pre-pregnancy obesity, gestational age at diagnosis of GDM, severity of GDM, and impaired ß cell function in early post-partum assessment [6]. On the basis of these results, early diagnosis of GDM, close obstetric and metabolic follow-up during pregnancy, and regular follow-up of GDM patients at greater risk of developing diabetes after pregnancy must be reinforced, if we are to prevent diabetes in these women [30].  Figure 1. OGTT during pregnancy. * p < 0.006.  Figure 2. OGTT 1 yr after pregnancy. IGT vs NGT ° p < 0.000; °° p < 0.005; °°° p < 0.02. DM2 vs NGT * p < 0.000; ** p < 0.004; *** p < 0.003; **** p < 0.026.  Figure 3. Insulin level during OGTT 1 yr after pregnancy. DM2 vs NGT * p < 0.006. DM2 vs IGT ° p < 0.000; °° p < 0.001. [1] O'Sullivan JB. Diabetes Mellitus after pregnancy. Diabetes, 1991, 131-135. [2] Damm P. Gestational diabetes mellitus and subsequent development of overt diabetes mellitus. Dan Med Bull, 1998, 495-509. [3] Persson B, Hanson V, Hartling S, Binder C. Follow up of women with previous GDM. Diabetes, 1991, 136-141. [4] Henry O, Beischer N. Long-term implication of gestational diabetes for the mother. Baillers Clin Obstet Gynecol, 1991, 461-483. [5] Alì Z, Alexis S. Occurrence of diabetes mellitus after gestational diabetes mellitus in Trinidad. Diabetes Care, 1990, 527-529. [6] Kjos S, Peters R, Xiang A, Henry O, Montoro M, Buchanan T. Predicting future diabetes in Latino women with gestational diabetes: utility of early postpartum glucose tolerance test. Diabetes, 1995, 586-591. [7] Pettitt DS, Knowler W, Baird R, Bennet P. Gestational diabetes: infant and maternal complications of pregnancy in relation to third trimester glucose tolerance in the Pima Indians. Diabetes Care, 1980, 458-464. [8] Benjamin E, Winters D, Mayfield S, Gohdes D. Diabetes in pregnancy in Zuni Indian women. Diabetes Care, 1993, 1231-1235. [9] Steinhart JR, Sugarman JR, Connell FA. Gestational diabetes is a herald of NIDDM in Navajo women. Diabetes Care, 1997, 943-947. [10] Catalano PM, Vargo KM, Bernstein IM, Amini SB. Incidence and risk factors associated with abnormal postpartum glucose tolerance in women with gestational diabetes mellitus. Am J Obstet Gynecol, 1991, 914-919. [11] Damm P, Krühl C, Bertelsem, Molsted-Pedersen L. Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus. Am J Obstet Gynecol, 1992, 607-616. [12] Coustan DR, Carpenter MW, O Sullivan PS, Carr SR. Predictors of subsequent disordered glucose metabolism. Am J Obsted Gynecol, 1993, 1139-1145. [13] Pallardo F, Herranz L, Garcia-Ingelmo T, Grande C, Martin-Vaguero P, Ianez M, Gonzales A. Early post-partum metabolic assessment in women with prior Gestational Diabetes. Diabetes Care, 1999, 1053-1058. [14] Metzger BE, Bybee DE, Freinkel N, Phelps RL, Radvany R, Vairsub N. Gestational diabetes mellitus: correlations between the phenotypic and genotypic characteristics of the mother and abnormal glucose tolerance during first year post-partum. Diabetes, 1985, 111-115. [15] Larsson G, Spjuth J, Raustam J, Vikbladh L, Saxtrup O, Astedt B. Prognostic significance of birth of large infant for subsequent development of maternal non insulin-dependent diabetes mellitus: a prospective study over 20-27 years. Diabetes Care, 1986, 359-364. [16] Lapolla A, Mazzon S, Marini S, Burattin G, Grella P, Fedele D. A screening programme for gestational diabetes in a north Mediterranean area. Diab Nutr Metab, 1995, 33-41. [17] Carpenter MW, Coustan DR. 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© 2001 Elsevier Masson SAS. Tous droits réservés.
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