Dr Jinwen He1, Dr. Adam Morton1
1Mater Hospital, South Brisbane, Australia
Biography:
Jinwen is an obstetric medicine fellow at the Mater Hospital, Brisbane. She completed her MBBS at the University of Queensland, and her Masters of Medicine at the University of Sydney, as well as FRACP in endocrinology. Her interests include diabetes management, metabolic disorders and obstetric medicine.
Abstract:
A 39 year old was pregnant on a background of type 2 diabetes with HbA1c 10.9%. Diabetic complications included nephropathy (CKD stage 3a with nephrotic range proteinuria) and non-proliferative diabetic retinopathy. She also had hypertension with hypertensive retinopathy, and morbid obesity (BMI 37kg/m2).
During pregnancy, her diabetes was managed with daily Optisulin and TDS Novorapid. Her highest total daily insulin dose was 136 units at 21 weeks gestation. She subsequently experienced hypoglycaemia necessitating reduction in insulin, ceasing insulin by 24 weeks gestation. At 25 weeks gestation, insulin antibodies were >50 U/mL (normal 0-0.5U/mL), normal cortisol 451 nmol/L and low IGF1 <3.5 nmol/L (normal 7-25nmol/L).
Subsequently, her blood sugars began to rise, and insulin was recommenced at lower doses by 26 weeks gestation. Pre-delivery, her total daily insulin dose was 82 units. Repeat IGF1 was normal at 7.5nmol/L. There was a reduction in the insulin antibody titre – 35.1U/mL at K30 weeks and 22.2U/mL at 1 week postpartum.
She delivered at 33 weeks by caesarean section, due to worsening renal function, resistant hypertension, and pulmonary oedema. Insulin was ceased postpartum, with BSL remaining between 5-8mmol/L.
Insulin autoantibodies (IAA) can arise in insulin naïve patients or with exogenous insulin.(1) IAA can cause hyperinsulinaemic hypoglycaemia by sequestering insulin, followed by the sudden dissociation of insulin which causes hypoglycaemia.(1,2) IAA can theoretically can also cause hyperglycaemia by binding and inactivating insulin.(1) However, most studies have not shown a relationship between insulin dose and IAAs.(3) IAAs are common and not always pathological, with prevalence in patients with diabetes treated with insulin as high as 78%.(4)
Falling insulin requirements in pregnancy raises concern for placental insufficiency and pre-eclampsia (5), although insulin antibodies could theoretically also contribute. It is not clear whether IAAs have a direct impact on neonatal morbidity, including hypoglycaemia and respiratory distress syndrome.(3)
Keywords
insulin antibodies, hypoglycaemia
References
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2. Huynh T. Clinical and Laboratory Aspects of Insulin Autoantibody-Mediated Glycaemic Dysregulation and Hyperinsulinaemic Hypoglycaemia: Insulin Autoimmune Syndrome and Exogenous Insulin Antibody Syndrome. Clin Biochem Rev 2020; 41: 93-102. DOI: 10.33176/AACB-20-00008.
3. Fineberg SE, Kawabata TT, Finco-Kent D, et al. Immunological responses to exogenous insulin. Endocr Rev 2007; 28: 625-652. 20070904. DOI: 10.1210/er.2007-0002.
4. Wredling R, Lins PE and Adamson U. Prevalence of anti-insulin antibodies and its relation to severe hypoglycaemia in insulin-treated diabetic patients. Scand J Clin Lab Invest 1990; 50: 551-557. DOI: 10.1080/00365519009089170.
5. Padmanabhan S, Lee VW, McLean M, et al. The Association of Falling Insulin Requirements With Maternal Biomarkers and Placental Dysfunction: A Prospective Study of Women With Preexisting Diabetes in Pregnancy. Diabetes Care 2017; 40: 1323-1330. 20170810. DOI: 10.2337/dc17-0391.