Declining Insulin Requirement in the Late First Trimester of Diabetic Pregnancy
- Lois Jovanovic, MD1,
- Robert H. Knopp, MD2,
- Zane Brown, MD3,
- Mary R. Conley, MA4,
- Eunsik Park, PHD, MD4,
- James L. Mills, MD4,
- Boyd E. Metzger, MD5,
- Jerome H. Aarons, MD6,
- Lewis B. Holmes, MD7,
- Joe L. Simpson, MD8 and
- and the National Institute of Child Health and Human Development Diabetes in Early Pregnancy Study Group
- 1Sansum Medical Research Institute, Santa Barbara, California
- 2Northwest Lipid Research Clinic, and the
- 3Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington
- 4Epidemiology and Biometry Branches, National Institute of Child Health and Human Development, Bethesda, Maryland
- 5Northwestern University Medical School, Chicago, Illinois
- 6Department of Medicine, Magee Women’s Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
- 7Genetics and Teratology Unit, Massachusetts General Hospital, Boston, Massachusetts
- 8Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas
Abstract
OBJECTIVE—To investigate whether pregnancies complicated by type 1 diabetes are associated with a decrease in first-trimester insulin requirement.
RESEARCH DESIGN AND METHODS—We examined the weekly insulin requirement (as units per kilogram per day) during the first trimester of pregnancy in diabetic women in the Diabetes in Early Pregnancy Study (DIEP) with accurate gestational dating, regular glucose monitoring, daily insulin-dose recording, and monthly glycohemoglobin measurements.
RESULTS—In pregnancies that resulted in live-born full-term singleton infants, a significant 18% increase in mean weekly dosage was observed between weeks 3 and 7 (P = 0.000), followed by a significant 9% decline from week 7 through week 15 (P = 0.000). Further testing localized a significant change in insulin dose in the interval beginning weeks 7–8 and ending weeks 11–12 (P = 0.014). Within this interval, the maximum decrease was between weeks 9 and 10 (mean), 10 and 11 (median), and 8 and 9 (most frequent maximal decrease). To determine whether prior poor glucose control exaggerated these trends, we categorized the women based on their glycohemoglobin values: <2 SDs above the mean of a normal population (subgroup 1), 2–4 SDs (subgroup 2), and >4 SDs (subgroup 3) at baseline. Late first-trimester declines in dosage were statistically significant in subgroup 2 (P = 0.002) and subgroups 2 and 3 together (P = 0.003). Similarly, women with BMI >27.0 had a greater initial insulin rise and then fall compared with leaner women.
CONCLUSIONS—Observations in the DIEP cohort disclose a mid–first-trimester decline in insulin requirement in type 1 diabetic pregnant women. Possible explanations include overinsulinization of previously poorly controlled diabetes, a transient decline in progesterone secretion during the late first-trimester luteo-placental shift in progesterone secretion, or other hormonal shifts. Clinicians should anticipate a clinically meaningful reduction in insulin requirement in the 5-week interval between weeks 7 and 12 of gestation.
- ASI, aggressive subcutaneous insulin
- CSII, continuous subcutaneous insulin infusion
- DIEP, Diabetes in Early Pregnancy Study
- NICHD, National Institute of Child Health and Human Development
Footnotes
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Address correspondence and reprint requests to Lois Jovanovic, MD, Sansum Medical Research Institute, 2219 Bath St., Santa Barbara, CA 93105. E-mail: ljovanovic{at}sansum.org.
Received for publication 22 September 2000 and accepted in revised form 7 March 2001.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
