Accelerated starvation in late pregnancy: A comparison between obese women with and without gestational diabetes mellitus Thomas A. Buchanan, MD,* Boyd E. Metzger, MD, and Norbert Freinkel, MDt Chicago, Illinois We compared the glucose, insulin, free fatty acid, and 3-hydroxybutyrate responses to a briefly extended overnight fast during the third trimester of pregnancy between two groups: obese women with normal glucose tolerance (n = 10) and age- and weight-matched women with gestational diabetes mellitus (n = 10). After a 12-hour overnight fast, plasma glucose (95 ± 4 vs. 78 ± 2 mg/dl; p < 0.01), insulin (32 ± 5 vs. 17 ± 2 fIoU/ml; p < 0.02), and free fatty acid (860 ± 63 vs. 639 ± 79 mmol/L; p < 0.05) levels were higher in the patients with gestational diabetes mellitus. 3-Hydroxybutyrate levels were similar in the two groups at that time (0.23 ± 0.04 vs. 0.18 ± 0.03 mmol/L; p > 0.3). When the fast was extended to 18 hours by having the patients skip breakfast, glucose levels fell more rapidly in the group with gestational diabetes mellitus but remained elevated compared with the nondiabetic women. Insulin levels declined at a similar rate in the two groups. Free fatty acid levels did not increase significantly in the group with gestational diabetes mellitus during the extended fast. In contrast, free fatty acid levels increased by 44% in the normal pregnant women, reaching the level observed in the group with gestational diabetes mellitus after 18 hours. 3-Hydroxybutyrate levels remained virtually identical in the two groups throughout the brief fast. Thus, compared with that of normal pregnant women, the response of obese women with gestational diabetes mellitus to brief caloric deprivation during late pregnancy was characterized by a greater fall in plasma glucose values without a greater propensity to ketosis. Our findings may have important implications for the dietary management of obese patients with gestational diabetes mellitus. (AM J OSSTET GVNECOL 1990;162:1015-20.)

Key words: Gestational diabetes, obesity, ketosis, fasting Gestational diabetes mellitus is currently defined as glucose intolerance with onset or first recognition during pregnancy. 1. 2 As such, the diagnosis of gestational diabetes mellitus is based on abnormal carbohydrate metabolism in the fed state. Diurnal studies reveal that women with gestational diabetes mellitus have fed-state abnormalities in circulating lipid and protein fuels as well.'-6 These fed-state abnormalities may result in part from defects in nutrient-stimulated insulin secretion that are present in many women with gestational diabetes mellitus. '-12

From the Departments of Medicine and Biochemistry and Molecular Biology, Northwestern University Medical School. Supported by Research Grants AMJ0699 and MRP-HDI1021, General Clinical Research Center Grant RR-48, and Training Grant AM07169 from the National Institutes of Health, United States Public Health Service. Received for publication June 15, 1989,. accepted December 4, 1989. Reprint requests: Thomas A. Buchanan, MD, Section of Diabetes and Clinical Nutrition, University of Southern California Medical School, OCD-252, 2025 Zonal Ave., Los Angeles, CA 90033. *Supported by a Clinical Research Fellowship from the Chicago Community Trust and an Individual National Research Service Award from the National Institutes of Health (AM-07008-02). tDeceased. 611118570

The fasted state in gestational diabetes mellitus has been less well characterized. It is clear that pregnancy per se normally is associated with a rapid adaptation to fat catabolism during fasting,13-18 a phenomenon we have termed "accelerated starvation."l3· 15. 18 We have postulated that this phenomenon occurs when circulating maternal insulin levels fall during fasting, leaving unopposed the catabolic effects of hormones such as human placental lactogen, estradiol, and progesterone. 19-21 Whether accelerated starvation occurs to a similar degree in women with gestational diabetes mellitus, or perhaps is exaggerated by their relative insulin deficiency, is unknown. Nonetheless, concern that accelerated starvation might be exaggerated in women with gestational diabetes mellitus has limited the use of caloric restriction as therapy for obese patients with that disease. 2 We conducted the present study to determine whether obese patients with gestational diabetes mellitus are truly at increased risk for accelerated starvation during late pregnancy.

Material and methods Subjects. The study population consisted of 20 overweight women (prepregnancy weight> 120% of ideal) who were tested between weeks 30 and 36 of singleton 1015

1016 Buchanan, Metzger, and Freinkel

April 1990 Am J Obstet Gynecol

Table I. Age, weight, and gestational age of obese normal pregnant women and obese women with gestational diabetes* Subject

Age (yr)

Prep regnancy weight (% ideal)

Pregnancy weight gain (kg)

Gestational age (wk)

Normal pregnant Gestational diabetic

28.2 ± 1.4 28.4 ± 1.3

143 ± 6 142 ± 6

10.7 ± 1.8 12.0 ± 1.4

32.8 ± 0.6 33.4 ± 0.6

*Pregnancy weight gain is the difference between prep regnancy weight and weight on the day of testing. Gestational age was determined by menstrual history and, where indicated, ultrasonography. None of the mean values differed between normal pregnant and gestational diabetic groups at the 0.05 level.

pregnancies. Ten of the women met National Diabetes Data Group criteria for gestational diabetes mellitus.' Fasting plasma glucose levels were

Accelerated starvation in late pregnancy: a comparison between obese women with and without gestational diabetes mellitus.

We compared the glucose, insulin, free fatty acid, and 3-hydroxybutyrate responses to a briefly extended overnight fast during the third trimester of ...
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