During pregnancy, maternal tissues become increasingly insensitive to
insulin in order to liberate nutritional supply to the growing fetus, but occasionally
insulin resistance in pregnancy becomes severe and the treatment challenging. We report a rare and clinically difficult case of extreme
insulin resistance with daily
insulin requirements of 1420 IU/day during pregnancy in an obese 36-year-old woman with
type 2 diabetes (T2D) and
polycystic ovary syndrome (PCOS). The woman was referred to the outpatient clinic at gestational week 12 + 2 with a
hemoglobin A1c (HbA1c) at 59 mmol/mol.
Insulin treatment was initiated immediately using
Novomix 30, and the doses were progressively increased, peaking
at 1420 units/day at week 34 + 4. At week 35 + 0, there was an abrupt fall in
insulin requirements, but with no signs of
placental insufficiency. At week 36 + 1 a, healthy baby with no
hypoglycemia was delivered by
cesarean section. Blood samples were taken late in pregnancy to search for causes of extreme
insulin resistance and showed high levels of
C-peptide, proinsulin,
insulin-like growth factor (IGF-1),
mannan-binding-lectin (MBL) and
leptin. CRP was mildly elevated, but otherwise, levels of inflammatory markers were normal.
Insulin antibodies were undetectable, and no mutations in the
insulin receptor (INSR) gene were found. The explanation for the severe
insulin resistance, in this case, can be ascribed to PCOS,
obesity, profound
weight gain, hyperleptinemia and inactivity. This is the first case of extreme
insulin resistance during pregnancy, with
insulin requirements close to 1500 IU/day with a successful outcome, illustrating the importance of a close interdisciplinary collaboration between patient, obstetricians and endocrinologists.
LEARNING POINTS: This is the first case of extreme
insulin resistance during pregnancy, with
insulin requirements of up to 1420 IU/day with a successful outcome without significant
fetal macrosomia and
hypoglycemia.
Obesity, PCOS, T2D and high levels of
leptin and
IGF-1 are predictors of severe
insulin resistance in pregnancy. A close collaboration between patient, obstetricians and endocrinologists is crucial for tailoring the best possible treatment for pregnant women with diabetes, beneficial for both the mother and her child.