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Declining Insulin Requirement in the Late First Trimester of Diabetic Pregnancy

¹ Sansum Medical Research Institute, Santa Barbara, California
² Northwest Lipid Research Clinic, and the
³ Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington
⁴ Epidemiology and Biometry Branches, National Institute of Child Health and Human Development, Bethesda, Maryland
⁵ Northwestern University Medical School, Chicago, Illinois
⁶ Department of Medicine, Magee Women’s Hospital, University of Pittsburgh, Pittsburgh, Pennsylvania
⁷ Genetics and Teratology Unit, Massachusetts General Hospital, Boston, Massachusetts
⁸ Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, Texas

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.

Abbreviations: ASI, aggressive subcutaneous insulin • CSII, continuous subcutaneous insulin infusion • DIEP, Diabetes in Early Pregnancy Study • NICHD, National Institute of Child Health and Human Development

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