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Type 2 diabetes in pregnancy: a growing concern
VIEWPOINT
Viewpoint
Type 2 diabetes in pregnancy: a growing concern
Denice S Feig, Valerie A Palda Over the past 30 years, great strides have been made in improving the outcomes of women with type 1 diabetes who become pregnant. However, during the past decade, type 2 diabetes in pregnancy has emerged, and is certain to become a prominent concern. Recent publications suggest that we are currently underestimating the true prevalence of type 2 diabetes in pregnancy, and that adverse maternal and fetal outcomes are as significant in these women as those we have seen in pregnant women with type 1 diabetes.
Increasing prevalence of type 2 diabetes in younger populations The global prevalence of type 2 diabetes is increasing. Although there are currently 110 million people with diabetes around the world, most of whom have type 2 diabetes, this number is expected to double by the year 2010. Additionally, the demographic pattern of type 2 diabetes is changing, with a shift to a younger age of onset. Over the past 10 years, more women of childbearing age, adolescents, and even children have developed type 2 diabetes,1 and a study of diabetes prevalence in the USA found that, whereas the prevalence of diabetes increased by 33% overall from 1990 to 1998, the prevalence in individuals aged 30–39 years increased by 70%.2 Populations with the highest prevalence of type 2 diabetes also have the highest rates of diabetes in young women and children: WHO data from 1992 showed the prevalence of diabetes in women of child-bearing age (20–39 years) to be highest in native Americans, Micronesians, rural Fijians, and aboriginal Australians, all of whom have very high populations rates of type 2 diabetes.3 In adolescents, type 2 diabetes has been increasingly noted in native Canadian and American populations, Mexican-Americans, African-Americans, Japanese people, and Libyan Arabs.4 This rise in the prevalence of type 2 diabetes in general, and in younger people in particular, has led to an increasing number of women with type 2 diabetes in pregnancy.
Correct identification of type 2 diabetes in pregnancy The true prevalence of type 2 diabetes in pregnancy has been very difficult to estimate for several reasons. First, the figures for “pregestational diabetes” frequently include patients with either type 1 or type 2 diabetes. Often women are assumed to have type 1 diabetes in Lancet 2002; 359: 1690–92 Division of Endocrinology and Metabolism, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada (D S Feig FRCPC); and Department of Medicine, University of Toronto, Toronto (V Palda FRCPC) Correspondence to: Dr Denice S Feig
1690
pregnancy if they are taking insulin. This assumption might be valid when referring to populations in which the relative prevalence of type 1 diabetes is high—eg, in Sweden and Finland. However, for populations in which the prevalence of type 2 diabetes is higher than that of type 1, more than half the pregnant diabetic women could in fact have type 2 diabetes. In Japan and Kuwait, about 75% of women with prepregnancy diabetes have type 2 diabetes.4 Furthermore, many patients with gestational diabetes are likely to have type 2 diabetes that has previously gone undiagnosed. Without population-wide screening programmes for type 2 diabetes, these women first come to the attention of the medical community because of screening for gestational diabetes. Often, these are the women who are diagnosed before 20 weeks’ gestation, or who have fasting hyperglycaemia. These are the women likely to display type 2 diabetes when tested post partum. In areas where efficient universal screening for gestational diabetes is not undertaken, these patients might even go undiagnosed throughout pregnancy. Because of the difficulty in estimating the true prevalence of type 2 diabetes in pregnancy, estimation of the true frequency of various maternal and fetal complications in this population, and the possible economic effect of such complications, is even more difficult.
Prevalence of type 2 diabetes in pregnancy Three studies have measured the prevalence of type 2 diabetes in pregnancy, either by testing of populations, or by survey. In a prospective study of 811 pregnancies in the Pima Indians of Arizona, 6·3% were known to have diabetes before pregnancy.5 A retrospective analysis of type 2 diabetes in pregnancy in the Ojibwa-Cree of northwestern Ontario, Canada, yielded a prevalence of 3·2%. The Canadian study probably underestimated the prevalence, since it included only women who were diagnosed before pregnancy and not women diagnosed early in pregnancy.6 A study of the Tohono O’odham tribe in southern Arizona, which also included women diagnosed with diabetes in the first 20 weeks of gestation, found a prevalence of 3·4%.7 Type 2 diabetes was diagnosed before pregnancy in only 60%. Therefore, 40% of patients had gone through the first part of pregnancy undiagnosed. The data from the above studies deal with specific populations and might not be generalisable. The only broad-based prevalence data come from a populationbased survey done in the USA in 1995, which also suggested an increasing prevalence of type 2 diabetes in pregnancy.8 The researchers estimated that 0·2–0·5% of all pregnancies were complicated by pregestational diabetes (type 1 or type 2), and that type 2 diabetes accounted for 65% in that year, compared with only 26% in 1980.
THE LANCET • Vol 359 • May 11, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
VIEWPOINT
Maternal and fetal complications of type 2 diabetes during pregnancy There is evidence that rising rates of type 2 diabetes in pregnancy could lead to increasing numbers of complications in pregnancy, for both mothers and fetuses. Type 2 diabetes is being recognised as representing at least as significant a risk to both mother and baby as does type 1 diabetes. Maternal complications The prevalence of maternal diabetes complications was studied in 207 deliveries, at a diabetes clinic in Japan between 1964 and 1991.4 Maternal diabetes complications were surprisingly frequent in women with type 2 diabetes. Non-proliferative retinopathy was seen in 28% of women, and proliferative retinopathy was found in 4·3%. None of the women with type 2 diabetes knew that they had proliferative retinopathy before pregnancy, since their eyes had not been previously tested. Overt diabetic nephropathy was also present in a small number of women (1·4%). The frequency of pre-eclampsia was quite high in both groups (26·5% in the patients with type 1 and 30·9% in women with type 2 diabetes). Therefore, just as in women with type 1 diabetes, maternal type 2 diabetes complications must be carefully assessed and followed throughout pregnancy. Although conclusions cannot be drawn reliably from only one study, the risk of diabetic complications in these women warrants careful assessment and follow-up. Fetal complications Although there are few published data available on perinatal mortality in women with type 2 diabetes, one study suggested that the rate of perinatal mortality in these women might be higher than that of women with type 1 diabetes.9 In that study, perinatal mortality was calculated over a 12-year period (1985–97) in women with type 2 diabetes attending a diabetes clinic in Auckland, New Zealand. Most of these women were native Maori or recent immigrants from Pacific Island nations, which might have an effect on generalisability. Perinatal mortality was significantly higher than in women with type 1 diabetes. Much of the increased mortality was due to a high rate of late fetal deaths (28 weeks’ gestation to term). Other maternal co-morbidities including obesity, higher maternal age, higher frequency of hypertension, and low socioeconomic class were also present in these women and probably contributed to the increased mortality rate. These women also presented later for care than did women with type 1 disease, and many were smokers. Many women with type 2 diabetes suffer from massive obesity, which has been associated with an increased risk of late fetal death, fetal macrosomia, and preterm delivery. Three other studies published to date reported perinatal mortality ranging from 4/1000 to 81/1000. Two studies showed no significant difference in perinatal mortality between patients with type 2 and type 1 diabetes,10,11 whereas one study reported four perinatal deaths in 113 patients with type 2 and none in the 46 patients with type 1 disease.12 Other neonatal outcomes were also examined in this study. There were no significant differences in the rates of macrosomia, caesarean section, shoulder dystocia, and neonatal hypoglycaemia between the mothers with type 1 and those with type 2 diabetes. If this finding is confirmed in other studies, and if in fact the outcomes of women with type 2 are similar to those of women with type 1, similar concern to that afforded women with type 1 diabetes should be shown towards women with type 2 diabetes and their infants.
THE LANCET • Vol 359 • May 11, 2002 • www.thelancet.com
Just as infants born of mothers with type 1 diabetes are at increased risk of congenital anomalies, so are infants of women with type 2 diabetes. In a prospective observational study of pregnancies complicated by type 2 diabetes in predominately Hispanic women in southern California, USA, a high rate of congenital anomalies was found in those who had not participated in a preconceptional diabetes care programme.13 Of the 332 infants, 56 (11·7%) were born with major congenital anomalies. This proportion was much higher than that seen at the same hospital in infants of non-diabetic women during the same period (rate of major malformations <2%). Such rates of major malformations are similar to those reported in studies of infants born to women with type 1 diabetes who also did not receive preconception care.13 And, like those with type 1 diabetes, poor glycaemic control was thought to have a major role in the cause of such anomalies. In the above study, maternal glycosylated haemoglobin concentrations at initial presentation for care were independently associated with the major malformations (p=0·0007). No difference in glycaemic control was noted between women taking oral hypoglycaemic agents during the first 8 weeks of gestation and those on insulin or diet, suggesting that the oral hypoglycaemic agents were not the cause of the malformations. Some studies have found that anomaly rates in women with type 2 diabetes are higher than in those with type 1 diabetes. In a Japanese study of women with pregestational diabetes in pregnancy, eight of 139 (5·8%) of infants born to women with type 2 diabetes had major congenital anomalies compared with none of the 70 infants born to women with type 1 diabetes.4 The higher rate of malformations was attributed to “neglect of diabetes care in the women with type 2 diabetes”. In another study of women in the UK, women with type 2 diabetes, most of whom were from the Indian subcontinent, also had twice the frequency of congenital malformations compared with women with type 1 diabetes (12·2% vs 6·1%). In that study, poorer attendance for prepregnancy care, later booking for antenatal care, and poorer glycaemic control during organogenesis were thought to have contributed to the higher rate of congenital malformations.14
Effectiveness of diabetes control in pregnancy The rate of congenital anomalies in patients with type 1 diabetes can be reduced to that of the general population if excellent glycaemic control is achieved at the time of conception. This control has been achieved in circumstances of tertiary care in specialised centres. However, in population studies, clinicians have not been nearly as successful in preventing congenital anomalies.15,16 In two recent population studies done in the UK, rates of congenital anomaly and perinatal mortality were significantly higher than that seen in the background populations. In a study looking at preconception education in women with type 1 diabetes, 61% presented in pregnancy with suboptimum control. In another study, investigators attempted to ascertain the reasons why women did not properly plan for pregnancy by ensuring optimum glycaemic control.17 They found that women who properly planned pregnancies were more likely to be white, married, older, educated, of higher socioeconomic status, privately insured, under the care of a diabetologist, and satisfied with their partner and health-care provider. Clinicians face even more of a challenge in women with type 2 diabetes. In the UK, USA, and Canada, young women with type 2 diabetes are more likely to be from minority groups or immigrant populations in which cultural and socioeconomic factors might prevent
1691
For personal use. Only reproduce with permission from The Lancet Publishing Group.
VIEWPOINT
optimum care. Additionally, clinicians need to be educated about the increased risk of congenital anomalies in women with type 2 diabetes. Physicians tend to be laid back about the care of these women, and are often not aware of the increased risk. This notion might result from the perception that women on diet therapy or oral hypoglycaemic agents have “mild” diabetes and are therefore at less risk. This mistake can lead to suboptimum care and follow-up, increasing the chance for poor glycaemic control at the onset of pregnancy, and a subsequent increase in congenital anomalies.
Furthermore, careful antenatal care, which would include surveillance for maternal diabetes complications, as well as careful obstetric surveillance, should improve maternal and fetal outcomes in this population. Further research is required to assess the true prevalence of type 2 diabetes in pregnancy. Screening of women in high-risk populations, either before pregnancy or early in the first trimester, would help differentiate these women from those with gestational diabetes. Prospective studies could then be done to assess more accurately maternal and fetal morbidity and mortality.
Diabetes begets diabetes
We thank Gail Johnston for excellent technical assistance.
The prevalence of type 2 diabetes in children and adolescents is increasing, especially in populations with a very high overall prevalence of the disease.1 There is some evidence that diabetes in pregnancy might have a role in this increased prevalence. In a study of type 2 diabetes among Pima Indian children, the prevalence rose significantly between 1967 and 1996.18 This increase was felt to be due to an increase in weight seen in the children, as well as an increased frequency of exposure to diabetes in utero. In-utero exposure to diabetes is thought to lead to fetal hyperinsulinaemia, which causes an increase in fetal fat cells, leading to obesity and insulin resistance in childhood. These symptoms in turn lead to impaired glucose tolerance and diabetes in adulthood. Therefore, a cycle is set in motion of in-utero exposure to diabetes, leading to childhood obesity and glucose intolerance, and subsequently to diabetes in pregnancy. This sequence of events has not only be noted in Pima Indian children, but also in a more heterogeneous population in Chicago, USA, where children of mothers with diabetes were found to be more obese and have higher rates of impaired glucose tolerance than children of non-diabetic mothers.19 Although this epidemic of diabetes in youth could be just a magnification of susceptibility genes in combination with society’s tendency to higher fat diets and lower levels of exercise, a study of sibling pairs argues for the role of the in-utero environment.20 Siblings born after the mother’s diagnosis of diabetes had a higher risk of diabetes than those born before the diagnosis. This finding contrasted with siblings born to fathers with diabetes, in whom there were no significant differences between the siblings. If type 2 diabetes in pregnancy does contribute to the increasing rate of type 2 diabetes in the population, knowledge of whether we can change or modify these rates by improved glycaemic control during pregnancy will be important. This question has yet to be answered.
Conclusions With the growing epidemic of type 2 diabetes in pregnancy, we should be concerned. The higher rates of type 2 diabetes in pregnancy bring with them higher rates of maternal and fetal morbidity, and might even contribute to the increasing incidence of type 2 diabetes in the world. Better recognition of this growing entity by family physicians and primary-care internists who see these patients before pregnancy, and a heightened awareness of the need for prepregnancy counselling about preconception glycaemic control, would lead to less morbidity and mortality from congenital anomalies.
1692
References 1 2 3
4
5
6
7
8
9 10
11 12
13
14
15
16
17 18
19
20
Rosenbloom A, Joe J, Young R, Winter W. Emerging epidemic of type 2 diabetes in youth. Diabetes Care 1999; 22: 345–54. Mokdad AH, Ford ES, Bowman BA, et al. Diabetes trends in the US: 1990–1998. Diabetes Care 2000; 23: 1278–83. WHO Ad Hoc Diabetes Reporting Group. Diabetes and impaired glucose tolerance in women aged 20–39 years. World Health Stat Q 1992; 45: 321–27. Omori Y, Minei S, Testuo T, et al. Current status of pregnancy in diabetic women: a comparison of pregnancy in IDDM and NIDDM mothers. Diabetes Res Clin Pract 1994; 24 (suppl): S273–78. Pettitt DJ, Knowler WC, Baird HR, Bennett PH. Gestational diabetes: infant and maternal complications of pregnancy in relation to thirdtrimester glucose tolerance in the Pima Indians. Diabetes Care 1980; 3: 458–64. Harris SB, Caulfield L, Sugamori ME, et al. The epidemiology of diabetes in pregnant Native Canadians. Diabetes Care 1997; 20: 1422–25. Livingston RC, Bachman-Carter K, Frank C, Mason WB. Diabetes mellitus in Tohono O’odham pregnancies. Diabetes Care 1993; 16: 318–21. Engelgau MM, Herman WH, Smith P, et al. The epidemiology of diabetes and pregnancy in the US, 1988. Diabetes Care 1995; 18: 1029–33. Cundy T, Gamble G, Townend K, et al. Perinatal mortality in type 2 diabetes mellitus. Diabet Med 2000; 17: 33–39. Zhu I, Nakabayashi M, Takeday Y. Statistical analysis of perinatal outcomes in pregnancy complicated with diabetes mellitus. J Obstet Gynecol Res 1997; 23: 555–63. Coetzee EJ, Jackson WPU. The management of non-insulin dependent diabetes during pregnancy. Diab Res Clin Pract 1985; 1: 281–87. Sacks DA, Chen W, Greenspoon JS, Wolde-Tsadik G. Should the same glucose values be targeted for type 1 as for type 2 diabetics in pregnancy? Am J Ostet Gynecol 1997; 177: 1113–19. Towner D, Kjos SL, Leung B, et al. Congenital malformations in pregnancies complicated by NIDDM. Diabetes Care 1995; 18: 1446–51. Brydon P, Smith T, Proffitt M, et al. Pregnancy outcome in women with type 2 diabetes mellitus needs to be addressed. Int J Clin Pract 2000; 54: 418–19. Casson IF, Clarke CA, Howard CV, et al. Outcomes of pregnancy in insulin dependent diabetic women: results of a five year population cohort study. BMJ 1997; 315: 275–78. Hawthorne G, Robson S, Ryall EA, et al. Prospective population based survey of outcome of pregnancy in diabetic women: results of the Northern Diabetic Pregnancy Audit, 1994. BMJ 1997; 315: 279–81. Holing EV, Shaw C, Brown Z, Connell F. Why don’t women with diabetes plan their pregnancies? Diabetes Care 1998; 21: 889–95. Dabelea D, Hanson RL, Bennett PH, et al. Increasing prevalence of type 2 diabetes in American Indian children. Diabetologia 1998; 41: 904–10. Silverman BL, Metzger BI, Cho NH, Loeb CA. Fetal hyperinsulinism and impaired glucose tolerance in adolescent offspring of diabetic mothers. Diabetes Care 1995; 18: 611–17. Dabelea D, Hanson RL, Lindsay RS, et al. Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes 2000; 49: 2208–11.
THE LANCET • Vol 359 • May 11, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
Viewpoint
Type 2 diabetes in pregnancy: a growing concern
Denice S Feig, Valerie A Palda Over the past 30 years, great strides have been made in improving the outcomes of women with type 1 diabetes who become pregnant. However, during the past decade, type 2 diabetes in pregnancy has emerged, and is certain to become a prominent concern. Recent publications suggest that we are currently underestimating the true prevalence of type 2 diabetes in pregnancy, and that adverse maternal and fetal outcomes are as significant in these women as those we have seen in pregnant women with type 1 diabetes.
Increasing prevalence of type 2 diabetes in younger populations The global prevalence of type 2 diabetes is increasing. Although there are currently 110 million people with diabetes around the world, most of whom have type 2 diabetes, this number is expected to double by the year 2010. Additionally, the demographic pattern of type 2 diabetes is changing, with a shift to a younger age of onset. Over the past 10 years, more women of childbearing age, adolescents, and even children have developed type 2 diabetes,1 and a study of diabetes prevalence in the USA found that, whereas the prevalence of diabetes increased by 33% overall from 1990 to 1998, the prevalence in individuals aged 30–39 years increased by 70%.2 Populations with the highest prevalence of type 2 diabetes also have the highest rates of diabetes in young women and children: WHO data from 1992 showed the prevalence of diabetes in women of child-bearing age (20–39 years) to be highest in native Americans, Micronesians, rural Fijians, and aboriginal Australians, all of whom have very high populations rates of type 2 diabetes.3 In adolescents, type 2 diabetes has been increasingly noted in native Canadian and American populations, Mexican-Americans, African-Americans, Japanese people, and Libyan Arabs.4 This rise in the prevalence of type 2 diabetes in general, and in younger people in particular, has led to an increasing number of women with type 2 diabetes in pregnancy.
Correct identification of type 2 diabetes in pregnancy The true prevalence of type 2 diabetes in pregnancy has been very difficult to estimate for several reasons. First, the figures for “pregestational diabetes” frequently include patients with either type 1 or type 2 diabetes. Often women are assumed to have type 1 diabetes in Lancet 2002; 359: 1690–92 Division of Endocrinology and Metabolism, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada (D S Feig FRCPC); and Department of Medicine, University of Toronto, Toronto (V Palda FRCPC) Correspondence to: Dr Denice S Feig
1690
pregnancy if they are taking insulin. This assumption might be valid when referring to populations in which the relative prevalence of type 1 diabetes is high—eg, in Sweden and Finland. However, for populations in which the prevalence of type 2 diabetes is higher than that of type 1, more than half the pregnant diabetic women could in fact have type 2 diabetes. In Japan and Kuwait, about 75% of women with prepregnancy diabetes have type 2 diabetes.4 Furthermore, many patients with gestational diabetes are likely to have type 2 diabetes that has previously gone undiagnosed. Without population-wide screening programmes for type 2 diabetes, these women first come to the attention of the medical community because of screening for gestational diabetes. Often, these are the women who are diagnosed before 20 weeks’ gestation, or who have fasting hyperglycaemia. These are the women likely to display type 2 diabetes when tested post partum. In areas where efficient universal screening for gestational diabetes is not undertaken, these patients might even go undiagnosed throughout pregnancy. Because of the difficulty in estimating the true prevalence of type 2 diabetes in pregnancy, estimation of the true frequency of various maternal and fetal complications in this population, and the possible economic effect of such complications, is even more difficult.
Prevalence of type 2 diabetes in pregnancy Three studies have measured the prevalence of type 2 diabetes in pregnancy, either by testing of populations, or by survey. In a prospective study of 811 pregnancies in the Pima Indians of Arizona, 6·3% were known to have diabetes before pregnancy.5 A retrospective analysis of type 2 diabetes in pregnancy in the Ojibwa-Cree of northwestern Ontario, Canada, yielded a prevalence of 3·2%. The Canadian study probably underestimated the prevalence, since it included only women who were diagnosed before pregnancy and not women diagnosed early in pregnancy.6 A study of the Tohono O’odham tribe in southern Arizona, which also included women diagnosed with diabetes in the first 20 weeks of gestation, found a prevalence of 3·4%.7 Type 2 diabetes was diagnosed before pregnancy in only 60%. Therefore, 40% of patients had gone through the first part of pregnancy undiagnosed. The data from the above studies deal with specific populations and might not be generalisable. The only broad-based prevalence data come from a populationbased survey done in the USA in 1995, which also suggested an increasing prevalence of type 2 diabetes in pregnancy.8 The researchers estimated that 0·2–0·5% of all pregnancies were complicated by pregestational diabetes (type 1 or type 2), and that type 2 diabetes accounted for 65% in that year, compared with only 26% in 1980.
THE LANCET • Vol 359 • May 11, 2002 • www.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
VIEWPOINT
Maternal and fetal complications of type 2 diabetes during pregnancy There is evidence that rising rates of type 2 diabetes in pregnancy could lead to increasing numbers of complications in pregnancy, for both mothers and fetuses. Type 2 diabetes is being recognised as representing at least as significant a risk to both mother and baby as does type 1 diabetes. Maternal complications The prevalence of maternal diabetes complications was studied in 207 deliveries, at a diabetes clinic in Japan between 1964 and 1991.4 Maternal diabetes complications were surprisingly frequent in women with type 2 diabetes. Non-proliferative retinopathy was seen in 28% of women, and proliferative retinopathy was found in 4·3%. None of the women with type 2 diabetes knew that they had proliferative retinopathy before pregnancy, since their eyes had not been previously tested. Overt diabetic nephropathy was also present in a small number of women (1·4%). The frequency of pre-eclampsia was quite high in both groups (26·5% in the patients with type 1 and 30·9% in women with type 2 diabetes). Therefore, just as in women with type 1 diabetes, maternal type 2 diabetes complications must be carefully assessed and followed throughout pregnancy. Although conclusions cannot be drawn reliably from only one study, the risk of diabetic complications in these women warrants careful assessment and follow-up. Fetal complications Although there are few published data available on perinatal mortality in women with type 2 diabetes, one study suggested that the rate of perinatal mortality in these women might be higher than that of women with type 1 diabetes.9 In that study, perinatal mortality was calculated over a 12-year period (1985–97) in women with type 2 diabetes attending a diabetes clinic in Auckland, New Zealand. Most of these women were native Maori or recent immigrants from Pacific Island nations, which might have an effect on generalisability. Perinatal mortality was significantly higher than in women with type 1 diabetes. Much of the increased mortality was due to a high rate of late fetal deaths (28 weeks’ gestation to term). Other maternal co-morbidities including obesity, higher maternal age, higher frequency of hypertension, and low socioeconomic class were also present in these women and probably contributed to the increased mortality rate. These women also presented later for care than did women with type 1 disease, and many were smokers. Many women with type 2 diabetes suffer from massive obesity, which has been associated with an increased risk of late fetal death, fetal macrosomia, and preterm delivery. Three other studies published to date reported perinatal mortality ranging from 4/1000 to 81/1000. Two studies showed no significant difference in perinatal mortality between patients with type 2 and type 1 diabetes,10,11 whereas one study reported four perinatal deaths in 113 patients with type 2 and none in the 46 patients with type 1 disease.12 Other neonatal outcomes were also examined in this study. There were no significant differences in the rates of macrosomia, caesarean section, shoulder dystocia, and neonatal hypoglycaemia between the mothers with type 1 and those with type 2 diabetes. If this finding is confirmed in other studies, and if in fact the outcomes of women with type 2 are similar to those of women with type 1, similar concern to that afforded women with type 1 diabetes should be shown towards women with type 2 diabetes and their infants.
THE LANCET • Vol 359 • May 11, 2002 • www.thelancet.com
Just as infants born of mothers with type 1 diabetes are at increased risk of congenital anomalies, so are infants of women with type 2 diabetes. In a prospective observational study of pregnancies complicated by type 2 diabetes in predominately Hispanic women in southern California, USA, a high rate of congenital anomalies was found in those who had not participated in a preconceptional diabetes care programme.13 Of the 332 infants, 56 (11·7%) were born with major congenital anomalies. This proportion was much higher than that seen at the same hospital in infants of non-diabetic women during the same period (rate of major malformations <2%). Such rates of major malformations are similar to those reported in studies of infants born to women with type 1 diabetes who also did not receive preconception care.13 And, like those with type 1 diabetes, poor glycaemic control was thought to have a major role in the cause of such anomalies. In the above study, maternal glycosylated haemoglobin concentrations at initial presentation for care were independently associated with the major malformations (p=0·0007). No difference in glycaemic control was noted between women taking oral hypoglycaemic agents during the first 8 weeks of gestation and those on insulin or diet, suggesting that the oral hypoglycaemic agents were not the cause of the malformations. Some studies have found that anomaly rates in women with type 2 diabetes are higher than in those with type 1 diabetes. In a Japanese study of women with pregestational diabetes in pregnancy, eight of 139 (5·8%) of infants born to women with type 2 diabetes had major congenital anomalies compared with none of the 70 infants born to women with type 1 diabetes.4 The higher rate of malformations was attributed to “neglect of diabetes care in the women with type 2 diabetes”. In another study of women in the UK, women with type 2 diabetes, most of whom were from the Indian subcontinent, also had twice the frequency of congenital malformations compared with women with type 1 diabetes (12·2% vs 6·1%). In that study, poorer attendance for prepregnancy care, later booking for antenatal care, and poorer glycaemic control during organogenesis were thought to have contributed to the higher rate of congenital malformations.14
Effectiveness of diabetes control in pregnancy The rate of congenital anomalies in patients with type 1 diabetes can be reduced to that of the general population if excellent glycaemic control is achieved at the time of conception. This control has been achieved in circumstances of tertiary care in specialised centres. However, in population studies, clinicians have not been nearly as successful in preventing congenital anomalies.15,16 In two recent population studies done in the UK, rates of congenital anomaly and perinatal mortality were significantly higher than that seen in the background populations. In a study looking at preconception education in women with type 1 diabetes, 61% presented in pregnancy with suboptimum control. In another study, investigators attempted to ascertain the reasons why women did not properly plan for pregnancy by ensuring optimum glycaemic control.17 They found that women who properly planned pregnancies were more likely to be white, married, older, educated, of higher socioeconomic status, privately insured, under the care of a diabetologist, and satisfied with their partner and health-care provider. Clinicians face even more of a challenge in women with type 2 diabetes. In the UK, USA, and Canada, young women with type 2 diabetes are more likely to be from minority groups or immigrant populations in which cultural and socioeconomic factors might prevent
1691
For personal use. Only reproduce with permission from The Lancet Publishing Group.
VIEWPOINT
optimum care. Additionally, clinicians need to be educated about the increased risk of congenital anomalies in women with type 2 diabetes. Physicians tend to be laid back about the care of these women, and are often not aware of the increased risk. This notion might result from the perception that women on diet therapy or oral hypoglycaemic agents have “mild” diabetes and are therefore at less risk. This mistake can lead to suboptimum care and follow-up, increasing the chance for poor glycaemic control at the onset of pregnancy, and a subsequent increase in congenital anomalies.
Furthermore, careful antenatal care, which would include surveillance for maternal diabetes complications, as well as careful obstetric surveillance, should improve maternal and fetal outcomes in this population. Further research is required to assess the true prevalence of type 2 diabetes in pregnancy. Screening of women in high-risk populations, either before pregnancy or early in the first trimester, would help differentiate these women from those with gestational diabetes. Prospective studies could then be done to assess more accurately maternal and fetal morbidity and mortality.
Diabetes begets diabetes
We thank Gail Johnston for excellent technical assistance.
The prevalence of type 2 diabetes in children and adolescents is increasing, especially in populations with a very high overall prevalence of the disease.1 There is some evidence that diabetes in pregnancy might have a role in this increased prevalence. In a study of type 2 diabetes among Pima Indian children, the prevalence rose significantly between 1967 and 1996.18 This increase was felt to be due to an increase in weight seen in the children, as well as an increased frequency of exposure to diabetes in utero. In-utero exposure to diabetes is thought to lead to fetal hyperinsulinaemia, which causes an increase in fetal fat cells, leading to obesity and insulin resistance in childhood. These symptoms in turn lead to impaired glucose tolerance and diabetes in adulthood. Therefore, a cycle is set in motion of in-utero exposure to diabetes, leading to childhood obesity and glucose intolerance, and subsequently to diabetes in pregnancy. This sequence of events has not only be noted in Pima Indian children, but also in a more heterogeneous population in Chicago, USA, where children of mothers with diabetes were found to be more obese and have higher rates of impaired glucose tolerance than children of non-diabetic mothers.19 Although this epidemic of diabetes in youth could be just a magnification of susceptibility genes in combination with society’s tendency to higher fat diets and lower levels of exercise, a study of sibling pairs argues for the role of the in-utero environment.20 Siblings born after the mother’s diagnosis of diabetes had a higher risk of diabetes than those born before the diagnosis. This finding contrasted with siblings born to fathers with diabetes, in whom there were no significant differences between the siblings. If type 2 diabetes in pregnancy does contribute to the increasing rate of type 2 diabetes in the population, knowledge of whether we can change or modify these rates by improved glycaemic control during pregnancy will be important. This question has yet to be answered.
Conclusions With the growing epidemic of type 2 diabetes in pregnancy, we should be concerned. The higher rates of type 2 diabetes in pregnancy bring with them higher rates of maternal and fetal morbidity, and might even contribute to the increasing incidence of type 2 diabetes in the world. Better recognition of this growing entity by family physicians and primary-care internists who see these patients before pregnancy, and a heightened awareness of the need for prepregnancy counselling about preconception glycaemic control, would lead to less morbidity and mortality from congenital anomalies.
1692
References 1 2 3
4
5
6
7
8
9 10
11 12
13
14
15
16
17 18
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