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Journal of the American College of Nutrition Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uacn20
Caloric restriction in gestational diabetes mellitus: when and how much? a
a
R L Phelps & B E Metzger a
Department of Medicine, Northwestern University Medical School, Chicago 60611. Published online: 02 Sep 2013.
To cite this article: R L Phelps & B E Metzger (1992) Caloric restriction in gestational diabetes mellitus: when and how much?, Journal of the American College of Nutrition, 11:3, 259-262, DOI: 10.1080/07315724.1992.10718225 To link to this article: http://dx.doi.org/10.1080/07315724.1992.10718225
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Calorie Restriction in Gestational Diabetes Mellitus: When and How Much? Richard L. Phelps, MD, and Boyd E. Metzger, MD Department of Medicine and Center for Endocrinology, Metabolism and Nutrition, Northwestern University Medical School, Chicago
Downloaded by [Deakin University Library] at 19:31 13 March 2015
Key words: gestational diabetes mellitus, hypocaloric diet, long-term outcome Variations in nutritional intake during pregnancy have measurable effects on the circulating levels of maternal nutrients, maternal weight gain, and birth weight of the offspring. A growing body of evidence indicates that alterations in maternal metabolism can also have long-term consequences in the offspring in relation to adult adiposity, glucose tolerance, and perhaps intellectual development. Therefore, recommendations for diet during pregnancy must be made with great care, and with as much scientific understanding as possible. Nutritional advice traditionally given to all pregnant women, including those with gestational diabetes mellitus (GDM) or noninsulin-dependent diabetes, does not allow for individual differences in caloric needs as a function of the degree of maternal obesity and thus, may encourage excessive weight gain. Evidence reviewed below suggests that adjusting caloric intake to meet new guidelines for weight gain during pregnancy may be advantageous in reducing maternal blood sugar and insulin levels, without producing abnormalities in other metabolic variables. Modest caloric reduction which limits excessive weight gain in the mother may also be associated with a small reduction of fetal weight. However, more stringent dietary manipulations in obese gravida should be discouraged as a routine measure until more knowledge is available from large-scale clinical trials about their effects on the entire panoply of maternal nutrients and their impact on the offspring.
Abbreviations: DM = diabetes mellitus, FFA = free fatty acids, GDM = gesta tional diabetes mellitus, NIDDM = noninsulin-dependent diabetes mellitus
OPTIMAL WEIGHT GAIN AND GENERAL NUTRITIONAL COUNSELING IN PREGNANCY
requirements thought necessary to effect this (an additional 200-300 calories/day above nongestational needs), diets have been devised and prescribed for all pregnant diabetic women, without consideration for diabetic class or pregestational maternal weight. Remarkable improvements in pregnancy outcome have taken place in the past 25 years while this nutritional approach has been used. Thus, although innovations such as effective fetal monitoring, neonatal intensive care, home glucose monitoring, multiple dose insulin regimens, and "tight control" of blood sugar have undoubtedly contrib uted greatly to improved outcome, the reluctance to make major changes in dietary treatment is understandable. For patients with Type I DM (the majority of whom are of normal weight), and in whom insulinopenia may be the single underlying metabolic abnormality, continued efforts at more physiologic insulin delivery may be the most fruitful avenue to pursue in attempting to further improve
Historical Perspective Although nutritional counseling has been a cornerstone of management since diabetes mellitus (DM) was first recognized, recommended diets have varied widely over the past several decades as additional therapies (insulin and oral agents), and improved understanding of the pathophysiology of DM and its long range complications have evolved. In a similar way, dietary recommendations for pregnancy complicated by DM have evolved with time [1]. In recent years nutritional recommendations for ges tational diabetes mellitus (GDM) have closely paralleled those for normal pregnancy. Based on epidemiological data indicating an apparent optimal weight gain during preg nancy of 22-30 lb [2], and calculations of the caloric
Address reprint requests to Boyd E. Metzger, MD, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611.
Journal of the American College of Nutrition, Vol. 11, No. 3, 259-262 (1992) Published by the American College of Nutrition
259
Calorie Restriction in GDM pregnancy outcome. Calorie and carbohydrate restriction has been approached with particular caution, because of the fear of promoting maternal ketonuria, which has been proposed to have deleterious consequences on neurological development of offspring [3-5].
Downloaded by [Deakin University Library] at 19:31 13 March 2015
Recent Innovations For pregnant women with Type II DM or GDM who are obese, presumed "normal diets" for pregnancy may be excessive and may unnecessarily enhance blood glucose levels. The recent report of the Institute of Medicine of the National Academy of Sciences entitled "Nutrition in Preg nancy" [6] suggests that such is the case. These new rec ommendations recognize the inverse relationship between prepregnancy weight and optimal weight gain during preg nancy. It is advised that desired weight gain (varying from 15 to 40 lb) and nutritional advice be individualized on the basis of pregestational maternal weight. This alone would suggest that dietary regimens commonly prescribed for GDM and Type II pregnant diabetics may be unphysiologic, and by promoting excessive gestational weight gain, exacerbate the diabetic state during and following pregnancy.
HYPOCALORIC DIET AS A THERAPEUTIC TOOL IN PREGNANCY Historical Perspective Since caloric restriction in obese nonpregnant subjects with noninsulin-dependent diabetes mellitus (NIDDM) can reduce insulin resistance and correct hyperglycemia, this approach, at least in theory, is an appealing alternative to the use of insulin therapy during pregnancy. Caloric restriction in obese pregnant women with or without DM is not a recent innovation. Pederson [7] and Jackson [8] advocated this therapy for obese pregnant women 40 years ago and did not observe any grossly apparent ill effects from this practice. However, these were not controlled trials in which detailed assessments of neonatal outcome were obtained. Recent studies concerning the effects of different nutritional regimens on maternal metabolic pa rameters and neonatal outcome, such as those reviewed by Hollingsworth and Ney in this issue of the Journal of the American College of Nutrition [9], are therefore of great interest. Maternal Weight It is clear that caloric restriction does restrain maternal weight gain. This was documented most clearly by Boberg et al [10] wherein obese nondiabetic women instructed in
260
1800-2000 calorie diets (with 150-180 g carbohydrate), were compared with a similar group eating to appetite. From 16 weeks to delivery the dieted group gained on average 6.2 kg, in contrast to the 13.6 kg gained in those eating ad libitum. Similar findings in women with GDM, the majority of whom were obese, have recently been reported from the same institution by Dornhorst et al [11]. The 35 GDM subjects who were prescribed diets ranging from 1200 to 1800 calories/day gained half as much weight as did a nondiabetic control group (matched for age, degree of obesity at entry, race, and parity) who were eating as dictated by appetite. Fetal Weight Effects on the fetus are less clear. Algeri et al [12] (in studies reviewed by Hollingsworth in this issue) prescribed 1700-1800 calorie diets to 22 obese women with GDM, and 2000-3000 calorie diets to 31 lean subjects with GDM. Food records were obtained in all subjects 2 days/week to document actual intake. Lean subjects with GDM appar ently consumed less than prescribed, since calculated mean caloric intake did not differ from obese GDM. However, neonatal weight was significantly greater in the obese pa tients (3922 ± 662 vs 3544 ± 598 g). Similar findings were reported in the study by Boberg [10] in nondiabetic preg nancy in which obese patients appeared to have heavier babies than did thin or normal weight gravida, yet meas urements of maternal blood sugar did not differ. Although the numbers were too few to allow meaningful compari sons, birth weights were no less in obese patients on restricted diets than in those on ad libitum diets. In contrast, Dornhorst et al [11] effected a reduction in birth weight in offspring of women with GDM on calorierestricted diets compared to outcome in closely matched gravida without GDM, or those with an abnormal screen ing test for GDM but with a normal 3-hour glucose toler ance test. This study reported no data on GDM treated with standard diets (2000-3000 calories). However, the mean difference in birth weight for GDM compared to their control group (untreated patients with positive screen ing test for GDM but not GDM) was only 163 g (a 4-5% reduction in birth weight). Nevertheless, the incidence of macrosomia (birth weight > 4000 g) was 23% in the control vs 6% in calorie-restricted GDM. Thus, birth weight dif ferences may be relatively modest. Jovanovic-Peterson and Peterson [13] make reference to 22 GDM treated with individually tailored calorie- and carbohydrate-restricted diets in which all neonates were in the 50-60th percentile for gestational age. Data regarding actual caloric intake, maternal weight gain, etc. were not provided, and a control population of GDM treated with standard diets was not available for comparison.
VOL. 11, NO. 3
Calorie Restriction in GDM
Downloaded by [Deakin University Library] at 19:31 13 March 2015
Metabolie Responses The effects of calorie-restricted diets on circulating ma ternal fuels and hormones have been studied by Knopp et al [14], who obtained 24-hour profiles in a limited number of obese GDM ingesting 2400 calories/day, 1600-1800 calories/day (33% reduction), and 1200 calories/day (50% reduction). When calories were reduced by 33%, fasting and 24-hour mean glucose, basal insulin and basal triglyc érides tended to be reduced. Unfortunately, circulating ketones were not reported in this group. However, plasma free fatty acids (FFA) were not higher and the women did not develop ketonuria. With 50% caloric reduction, fasting and 24-hour mean glucose levels declined significantly, as did fasting insulin and triglycéride. Plasma, FFA and ßhydroxybutyrate on the other hand increased, the latter by two- to threefold. Maresh et al [15] also obtained 24-hour profiles in subjects with GDM and nondiabetic controls in the third trimester, both before and 4-5 weeks after instituting treat ment in those with GDM. Treatment of GDM was allo cated to alternate regimens: dietary restriction alone, or dietary restriction plus subcutaneous insulin. Treatment by diet alone resulted in improved but not normal glucose profiles, whereas those with GDM also receiving subcuta neous insulin had glucose profiles identical to nondiabetic controls. Similarly, before treatment, plasma |8-hydroxybutyrate was significantly higher during much of the day in GDM than in controls. GDM treated with diet restric tion had /S-hydroxybutyrate levels at the upper normal range, whereas levels with insulin-treated GDM were not different from those in controls throughout most of the 24-hour period. The reduction in basal and postprandial insulin conse quent to diet restriction in obese nondiabetic pregnancies was also documented by Boberg et al [10], though without clear evidence of reductions in maternal blood glucose. Jovanovic-Peterson and Peterson [13] noted a reduction in postprandial blood glucose levels with caloric and car bohydrate restriction in GDM, which in their hands could be achieved without a concomitant development of keto nuria. In the studies noted above, ketonuria, when meas ured, did not appear to be enhanced in diet-restricted patients. In the study by Dornhorst [11], however, where diets as low as 1200 calories were used, data on ketonuria are not presented. Potential Long-Term Effects There is growing evidence that alterations in maternal metabolism may exert long-term as well as perinatal effects on the offspring. In experimental animals, the transgenerational influence of mild DM [16] or maternal hyperglycemia secondary to glucose infusion [ 17] during pregnancy on islet function during adult life or pregnancy leading to
impaired glucose tolerance is convincing. Similarly, off spring of Pima Indian women who develop GDM or are diabetic during pregnancy have more NIDDM by 20-24 years of age than do offspring whose mothers become diabetic subsequently [ 18]. In addition, obesity in offspring of Pima women who become diabetic during pregnancy [19], or offspring of women with GDM or pre-GDM at our center [20], manifest marked obesity during childhood. The propensity to obesity correlates with increased /3-cell function during intrauterine life [20]. These several reports suggest the potential value of identifying and treating all women with GDM. However, choice of treatment may also potentially influence longterm outcome. Thus, a protein-restricted diet during preg nancy and in the neonatal period may also be associated with permanent impairment of islet function [21]. Addi tionally, though average level of intelligence was normal, Rizzo et al [5] have recently observed inverse correlations between intelligence in childhood (ages 2-5) and indices of antepartum maternal fat metabolism (fasting plasma FFA and 0-hydroxybutyrate concentrations). Whether hyperketonuria associated with inadequately monitored hypocaloric diets may have adverse effects on neurobehavioral development remains to be evaluated with long-term follow-up.
CONCLUSIONS Summary Multiple nutrient fuels cross the placenta and maternal concentrations of several correlate directly with neonatal birth weight [22]. It seems clear that caloric restriction during pregnancy has easily discernible effects on circulat ing maternal concentrations of glucose, lipids (including ketones) and amino acids. However, the changes in mater nal nutrients in response to the hypocaloric diet are not necessarily symmetric. For example, hyperglycemia may lessen whereas FFA and ketones tend to increase. Dietary restriction may also reduce levels of maternal insulin, which in one study involving a relatively small number of subjects was reported to correlate with birth weight inde pendently of blood glucose [9]. As summarized above, dietary restriction clearly results in reduced maternal weight gain during gestation. Caloric restriction may also result in a reduction in birth weight of the offspring, although these effects are less dramatic. This may be due to direct effects of maternal obesity on birth weight, or to greater fetal hyperinsulinemia than expected from the degree of maternal hyperglycemia, perhaps re sulting from stimulation by other secretagogues, e.g., amino acids. Such hyperinsulinemia can promote fetal weight gain independently of sustained substrate excess [22,23].
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Calorie Restriction in GDM
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Recommendations The revised National Academy of Sciences guidelines [6] concerning optimal weight gain during gestation suggest that overfeeding is probably frequently recommended for women who are obese. At the very least, this practice should be avoided in pregnant diabetic women. The precise caloric level and carbohydrate content which should be prescribed when patients are first seen in the latter half of pregnancy should be individualized, taking into account prepregnancy weight and pregnancy weight gain which has already occurred. After institution of diet therapy, frequent measurements of urinary ketones should be made. Based on the studies of Knopp et al [14], caloric reductions of >33% from habitual levels should probably not be pre scribed, because they result in hyperketonemia. In our opinion, diets which effect less than optimal weight gain in either obese or normal weight women or represent >33% reduction should only be used in a research setting because potential long-term consequences of the attendant alterations in maternal metabolism have not been fully explored. Carefully controlled studies on this subject have been strongly recommended [24].
ACKNOWLEDGMENT We thank Teresa Harris-Burton for assistance in the preparation of this manuscript.
REFERENCES 1. Ney D, Hollingsworth DR: Nutritional management of preg nancy complicated by diabetes: historical perspective. Dia betes Care 4:647-655, 1991. 2. Committee on Dietary Allowances, Food and Nutrition Board: "Recommended Dietary Allowances," 9th ed. Wash ington, DC: National Academy of Sciences, US Government Printing Office, 1980. 3. Churchill JA, Berendes HW, Nemore J: Neuropsychological deficits in children of diabetic mothers: a report from the Collaborative Study of Cerebral Palsy. Am J Obstet Gynecol 105:257-268, 1968. 4. Stehbens JA, Baker GL, Kitchell M: Outcome at age 1, 3, and 5 years of children born to diabetic women. Am J Obstet Gynecol 127:408-413, 1977. 5. Rizzo T, Metzger BE, Burns WJ, Burns K: Correlations between antepartum maternal metabolism and intelligence of offspring. N Engl J Med 325:911-916, 1991. 6. National Academy of Sciences: "Nutrition in Pregnancy, Part I: Weight Gain." Washington, DC: National Academy Press, pp 10-13, 1990. 7. Pedersen J: Management of diabetic pregnancy and the new born infant. In "The Pregnancy Diabetic and Her Newborn." Copenhagen, Munksgaard, and Baltimore: Williams and Wilkins,pp 221-230, 1977.
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8. Coetzee E, Jackson WPU: Diabetes newly diagnosed during pregnancy. S Afr Med J 56:467-474, 1979. 9. Hollingsworth DF, Ney DM: Caloric restriction in pregnant diabetic women: a review of maternal obesity, glucose and insulin relationships as investigated at the University of Cali fornia, San Diego. J Am Coll Nutr 11:251-258, 1992. 10. Boberg C, Gillmer MDG, Brunner EJ, Gunn PJ, Oakley NW, Beard RW: Obesity in pregnancy. The effect of dietary advice. Diabetes Care 3:476-481, 1980. 11. Dornhorst A, Nichols JSD, Probst F, Paterson CM, Hollier KL, Elkeles RS, Beard RW: Caloric restriction for the treat ment of gestational diabetes. Diabetes 40(Suppl 2): 161-164, 1991. 12. Algert S, Shragg P, Hollingsworth DR: Moderate caloric restriction in obese women with gestational diabetes. Obstet Gynecol 65:487-491, 1985. 13. Jovanovic-Peterson L, Peterson CM: Dietary manipulation as a primary treatment strategy for pregnancies complicated by diabetes. J Am Coll Nutr 9:320-325, 1990. 14. Knopp RH, Mages MS, Rassys V, Benedetti T, Bonet B: Hypocaloric diets and ketogenesis in the management of obese gestational diabetic women. J Am Coll Nutr 10:649667, 1991. 15. Maresh M, Gillmer MDG, Beard RW, Alderson CS, Bloxham BA, Elkeles RS: The effect of diet and insulin on metabolic profiles of women with gestational diabetes mellitus. Diabetes 34(Suppl 2):89-93, 1985. 16. Van Assche FA, Aerts L, Holemans K: Metabolic alterations in adulthood after intrauterine development in mothers with mild diabetes. Diabetes 40(Suppl 2): 106-108, 1991. 17. Gauguier D, Bihoreau MT, Picon L, Ktorza A: Insulin secre tion in adult rats after intrauterine exposure to mild hyperglycemia during late gestation. Diabetes 40(Suppl 2): 109-114, 1991. 18. Pettit DJ, Aleck KA, Baird HR, Carraher MJ, Bennett PH, Knowler WC: Congenital susceptibility for NIDDM: role of intrauterine environment. Diabetes 37:622-628, 1988. 19. Pettit DJ, Knowler WC, Bennett PH, Aleck KA, Baird HR: Obesity in offspring of diabetic Pima Indian women despite normal birth weight. Diabetes Care 10:76-80, 1987. 20. Silverman BL, Rizzo T, Green OC, Cho NH, Winter RJ, Ogata ES, Richards GE, Metzger BE: Long-term prospective evaluation of offspring of diabetic mothers. Diabetes 40(Suppl 2):121-125, 1991. 21. Dahri S, Snoeck A, Reusens-Billen B, Remade C, Hoet JJ: Islet function in offspring of mothers on low-protein diet during gestation. Diabetes 40(Suppl 2): 115-120, 1991. 22. Metzger BE: Biphasic effects of maternal metabolism on fetal growth: the quintessential expression of "fuel mediated teratogenesis." Diabetes 40(Suppl 2):99-105, 1991. 23. Susa JB, Neave C, Sehgal P, Singer DB, Zeller WP, Schwartz R: Chronic hyperinsulinemia in the fetal rhesus monkey: effects of physiologic hyperinsulinemia on fetal growth and composition. Diabetes 33:656-660, 1984. 24. Metzger BE, Organizing Committee: Summary and recom mendations of the 3rd International Workshop Conference on Gestational Diabetes Mellitus. Diabetes 40(Suppl 2): 197201, 1991. Received January 1992; revision accepted February 1992.
VOL. 11, NO. 3
Journal of the American College of Nutrition Publication details, including instructions for authors and subscription information: http://www.tandfonline.com/loi/uacn20
Caloric restriction in gestational diabetes mellitus: when and how much? a
a
R L Phelps & B E Metzger a
Department of Medicine, Northwestern University Medical School, Chicago 60611. Published online: 02 Sep 2013.
To cite this article: R L Phelps & B E Metzger (1992) Caloric restriction in gestational diabetes mellitus: when and how much?, Journal of the American College of Nutrition, 11:3, 259-262, DOI: 10.1080/07315724.1992.10718225 To link to this article: http://dx.doi.org/10.1080/07315724.1992.10718225
PLEASE SCROLL DOWN FOR ARTICLE Taylor & Francis makes every effort to ensure the accuracy of all the information (the “Content”) contained in the publications on our platform. However, Taylor & Francis, our agents, and our licensors make no representations or warranties whatsoever as to the accuracy, completeness, or suitability for any purpose of the Content. Any opinions and views expressed in this publication are the opinions and views of the authors, and are not the views of or endorsed by Taylor & Francis. The accuracy of the Content should not be relied upon and should be independently verified with primary sources of information. Taylor and Francis shall not be liable for any losses, actions, claims, proceedings, demands, costs, expenses, damages, and other liabilities whatsoever or howsoever caused arising directly or indirectly in connection with, in relation to or arising out of the use of the Content. This article may be used for research, teaching, and private study purposes. Any substantial or systematic reproduction, redistribution, reselling, loan, sub-licensing, systematic supply, or distribution in any form to anyone is expressly forbidden. Terms & Conditions of access and use can be found at http:// www.tandfonline.com/page/terms-and-conditions
Calorie Restriction in Gestational Diabetes Mellitus: When and How Much? Richard L. Phelps, MD, and Boyd E. Metzger, MD Department of Medicine and Center for Endocrinology, Metabolism and Nutrition, Northwestern University Medical School, Chicago
Downloaded by [Deakin University Library] at 19:31 13 March 2015
Key words: gestational diabetes mellitus, hypocaloric diet, long-term outcome Variations in nutritional intake during pregnancy have measurable effects on the circulating levels of maternal nutrients, maternal weight gain, and birth weight of the offspring. A growing body of evidence indicates that alterations in maternal metabolism can also have long-term consequences in the offspring in relation to adult adiposity, glucose tolerance, and perhaps intellectual development. Therefore, recommendations for diet during pregnancy must be made with great care, and with as much scientific understanding as possible. Nutritional advice traditionally given to all pregnant women, including those with gestational diabetes mellitus (GDM) or noninsulin-dependent diabetes, does not allow for individual differences in caloric needs as a function of the degree of maternal obesity and thus, may encourage excessive weight gain. Evidence reviewed below suggests that adjusting caloric intake to meet new guidelines for weight gain during pregnancy may be advantageous in reducing maternal blood sugar and insulin levels, without producing abnormalities in other metabolic variables. Modest caloric reduction which limits excessive weight gain in the mother may also be associated with a small reduction of fetal weight. However, more stringent dietary manipulations in obese gravida should be discouraged as a routine measure until more knowledge is available from large-scale clinical trials about their effects on the entire panoply of maternal nutrients and their impact on the offspring.
Abbreviations: DM = diabetes mellitus, FFA = free fatty acids, GDM = gesta tional diabetes mellitus, NIDDM = noninsulin-dependent diabetes mellitus
OPTIMAL WEIGHT GAIN AND GENERAL NUTRITIONAL COUNSELING IN PREGNANCY
requirements thought necessary to effect this (an additional 200-300 calories/day above nongestational needs), diets have been devised and prescribed for all pregnant diabetic women, without consideration for diabetic class or pregestational maternal weight. Remarkable improvements in pregnancy outcome have taken place in the past 25 years while this nutritional approach has been used. Thus, although innovations such as effective fetal monitoring, neonatal intensive care, home glucose monitoring, multiple dose insulin regimens, and "tight control" of blood sugar have undoubtedly contrib uted greatly to improved outcome, the reluctance to make major changes in dietary treatment is understandable. For patients with Type I DM (the majority of whom are of normal weight), and in whom insulinopenia may be the single underlying metabolic abnormality, continued efforts at more physiologic insulin delivery may be the most fruitful avenue to pursue in attempting to further improve
Historical Perspective Although nutritional counseling has been a cornerstone of management since diabetes mellitus (DM) was first recognized, recommended diets have varied widely over the past several decades as additional therapies (insulin and oral agents), and improved understanding of the pathophysiology of DM and its long range complications have evolved. In a similar way, dietary recommendations for pregnancy complicated by DM have evolved with time [1]. In recent years nutritional recommendations for ges tational diabetes mellitus (GDM) have closely paralleled those for normal pregnancy. Based on epidemiological data indicating an apparent optimal weight gain during preg nancy of 22-30 lb [2], and calculations of the caloric
Address reprint requests to Boyd E. Metzger, MD, Northwestern University Medical School, 303 E. Chicago Ave., Chicago, IL 60611.
Journal of the American College of Nutrition, Vol. 11, No. 3, 259-262 (1992) Published by the American College of Nutrition
259
Calorie Restriction in GDM pregnancy outcome. Calorie and carbohydrate restriction has been approached with particular caution, because of the fear of promoting maternal ketonuria, which has been proposed to have deleterious consequences on neurological development of offspring [3-5].
Downloaded by [Deakin University Library] at 19:31 13 March 2015
Recent Innovations For pregnant women with Type II DM or GDM who are obese, presumed "normal diets" for pregnancy may be excessive and may unnecessarily enhance blood glucose levels. The recent report of the Institute of Medicine of the National Academy of Sciences entitled "Nutrition in Preg nancy" [6] suggests that such is the case. These new rec ommendations recognize the inverse relationship between prepregnancy weight and optimal weight gain during preg nancy. It is advised that desired weight gain (varying from 15 to 40 lb) and nutritional advice be individualized on the basis of pregestational maternal weight. This alone would suggest that dietary regimens commonly prescribed for GDM and Type II pregnant diabetics may be unphysiologic, and by promoting excessive gestational weight gain, exacerbate the diabetic state during and following pregnancy.
HYPOCALORIC DIET AS A THERAPEUTIC TOOL IN PREGNANCY Historical Perspective Since caloric restriction in obese nonpregnant subjects with noninsulin-dependent diabetes mellitus (NIDDM) can reduce insulin resistance and correct hyperglycemia, this approach, at least in theory, is an appealing alternative to the use of insulin therapy during pregnancy. Caloric restriction in obese pregnant women with or without DM is not a recent innovation. Pederson [7] and Jackson [8] advocated this therapy for obese pregnant women 40 years ago and did not observe any grossly apparent ill effects from this practice. However, these were not controlled trials in which detailed assessments of neonatal outcome were obtained. Recent studies concerning the effects of different nutritional regimens on maternal metabolic pa rameters and neonatal outcome, such as those reviewed by Hollingsworth and Ney in this issue of the Journal of the American College of Nutrition [9], are therefore of great interest. Maternal Weight It is clear that caloric restriction does restrain maternal weight gain. This was documented most clearly by Boberg et al [10] wherein obese nondiabetic women instructed in
260
1800-2000 calorie diets (with 150-180 g carbohydrate), were compared with a similar group eating to appetite. From 16 weeks to delivery the dieted group gained on average 6.2 kg, in contrast to the 13.6 kg gained in those eating ad libitum. Similar findings in women with GDM, the majority of whom were obese, have recently been reported from the same institution by Dornhorst et al [11]. The 35 GDM subjects who were prescribed diets ranging from 1200 to 1800 calories/day gained half as much weight as did a nondiabetic control group (matched for age, degree of obesity at entry, race, and parity) who were eating as dictated by appetite. Fetal Weight Effects on the fetus are less clear. Algeri et al [12] (in studies reviewed by Hollingsworth in this issue) prescribed 1700-1800 calorie diets to 22 obese women with GDM, and 2000-3000 calorie diets to 31 lean subjects with GDM. Food records were obtained in all subjects 2 days/week to document actual intake. Lean subjects with GDM appar ently consumed less than prescribed, since calculated mean caloric intake did not differ from obese GDM. However, neonatal weight was significantly greater in the obese pa tients (3922 ± 662 vs 3544 ± 598 g). Similar findings were reported in the study by Boberg [10] in nondiabetic preg nancy in which obese patients appeared to have heavier babies than did thin or normal weight gravida, yet meas urements of maternal blood sugar did not differ. Although the numbers were too few to allow meaningful compari sons, birth weights were no less in obese patients on restricted diets than in those on ad libitum diets. In contrast, Dornhorst et al [11] effected a reduction in birth weight in offspring of women with GDM on calorierestricted diets compared to outcome in closely matched gravida without GDM, or those with an abnormal screen ing test for GDM but with a normal 3-hour glucose toler ance test. This study reported no data on GDM treated with standard diets (2000-3000 calories). However, the mean difference in birth weight for GDM compared to their control group (untreated patients with positive screen ing test for GDM but not GDM) was only 163 g (a 4-5% reduction in birth weight). Nevertheless, the incidence of macrosomia (birth weight > 4000 g) was 23% in the control vs 6% in calorie-restricted GDM. Thus, birth weight dif ferences may be relatively modest. Jovanovic-Peterson and Peterson [13] make reference to 22 GDM treated with individually tailored calorie- and carbohydrate-restricted diets in which all neonates were in the 50-60th percentile for gestational age. Data regarding actual caloric intake, maternal weight gain, etc. were not provided, and a control population of GDM treated with standard diets was not available for comparison.
VOL. 11, NO. 3
Calorie Restriction in GDM
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Metabolie Responses The effects of calorie-restricted diets on circulating ma ternal fuels and hormones have been studied by Knopp et al [14], who obtained 24-hour profiles in a limited number of obese GDM ingesting 2400 calories/day, 1600-1800 calories/day (33% reduction), and 1200 calories/day (50% reduction). When calories were reduced by 33%, fasting and 24-hour mean glucose, basal insulin and basal triglyc érides tended to be reduced. Unfortunately, circulating ketones were not reported in this group. However, plasma free fatty acids (FFA) were not higher and the women did not develop ketonuria. With 50% caloric reduction, fasting and 24-hour mean glucose levels declined significantly, as did fasting insulin and triglycéride. Plasma, FFA and ßhydroxybutyrate on the other hand increased, the latter by two- to threefold. Maresh et al [15] also obtained 24-hour profiles in subjects with GDM and nondiabetic controls in the third trimester, both before and 4-5 weeks after instituting treat ment in those with GDM. Treatment of GDM was allo cated to alternate regimens: dietary restriction alone, or dietary restriction plus subcutaneous insulin. Treatment by diet alone resulted in improved but not normal glucose profiles, whereas those with GDM also receiving subcuta neous insulin had glucose profiles identical to nondiabetic controls. Similarly, before treatment, plasma |8-hydroxybutyrate was significantly higher during much of the day in GDM than in controls. GDM treated with diet restric tion had /S-hydroxybutyrate levels at the upper normal range, whereas levels with insulin-treated GDM were not different from those in controls throughout most of the 24-hour period. The reduction in basal and postprandial insulin conse quent to diet restriction in obese nondiabetic pregnancies was also documented by Boberg et al [10], though without clear evidence of reductions in maternal blood glucose. Jovanovic-Peterson and Peterson [13] noted a reduction in postprandial blood glucose levels with caloric and car bohydrate restriction in GDM, which in their hands could be achieved without a concomitant development of keto nuria. In the studies noted above, ketonuria, when meas ured, did not appear to be enhanced in diet-restricted patients. In the study by Dornhorst [11], however, where diets as low as 1200 calories were used, data on ketonuria are not presented. Potential Long-Term Effects There is growing evidence that alterations in maternal metabolism may exert long-term as well as perinatal effects on the offspring. In experimental animals, the transgenerational influence of mild DM [16] or maternal hyperglycemia secondary to glucose infusion [ 17] during pregnancy on islet function during adult life or pregnancy leading to
impaired glucose tolerance is convincing. Similarly, off spring of Pima Indian women who develop GDM or are diabetic during pregnancy have more NIDDM by 20-24 years of age than do offspring whose mothers become diabetic subsequently [ 18]. In addition, obesity in offspring of Pima women who become diabetic during pregnancy [19], or offspring of women with GDM or pre-GDM at our center [20], manifest marked obesity during childhood. The propensity to obesity correlates with increased /3-cell function during intrauterine life [20]. These several reports suggest the potential value of identifying and treating all women with GDM. However, choice of treatment may also potentially influence longterm outcome. Thus, a protein-restricted diet during preg nancy and in the neonatal period may also be associated with permanent impairment of islet function [21]. Addi tionally, though average level of intelligence was normal, Rizzo et al [5] have recently observed inverse correlations between intelligence in childhood (ages 2-5) and indices of antepartum maternal fat metabolism (fasting plasma FFA and 0-hydroxybutyrate concentrations). Whether hyperketonuria associated with inadequately monitored hypocaloric diets may have adverse effects on neurobehavioral development remains to be evaluated with long-term follow-up.
CONCLUSIONS Summary Multiple nutrient fuels cross the placenta and maternal concentrations of several correlate directly with neonatal birth weight [22]. It seems clear that caloric restriction during pregnancy has easily discernible effects on circulat ing maternal concentrations of glucose, lipids (including ketones) and amino acids. However, the changes in mater nal nutrients in response to the hypocaloric diet are not necessarily symmetric. For example, hyperglycemia may lessen whereas FFA and ketones tend to increase. Dietary restriction may also reduce levels of maternal insulin, which in one study involving a relatively small number of subjects was reported to correlate with birth weight inde pendently of blood glucose [9]. As summarized above, dietary restriction clearly results in reduced maternal weight gain during gestation. Caloric restriction may also result in a reduction in birth weight of the offspring, although these effects are less dramatic. This may be due to direct effects of maternal obesity on birth weight, or to greater fetal hyperinsulinemia than expected from the degree of maternal hyperglycemia, perhaps re sulting from stimulation by other secretagogues, e.g., amino acids. Such hyperinsulinemia can promote fetal weight gain independently of sustained substrate excess [22,23].
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Calorie Restriction in GDM
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Recommendations The revised National Academy of Sciences guidelines [6] concerning optimal weight gain during gestation suggest that overfeeding is probably frequently recommended for women who are obese. At the very least, this practice should be avoided in pregnant diabetic women. The precise caloric level and carbohydrate content which should be prescribed when patients are first seen in the latter half of pregnancy should be individualized, taking into account prepregnancy weight and pregnancy weight gain which has already occurred. After institution of diet therapy, frequent measurements of urinary ketones should be made. Based on the studies of Knopp et al [14], caloric reductions of >33% from habitual levels should probably not be pre scribed, because they result in hyperketonemia. In our opinion, diets which effect less than optimal weight gain in either obese or normal weight women or represent >33% reduction should only be used in a research setting because potential long-term consequences of the attendant alterations in maternal metabolism have not been fully explored. Carefully controlled studies on this subject have been strongly recommended [24].
ACKNOWLEDGMENT We thank Teresa Harris-Burton for assistance in the preparation of this manuscript.
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