Pregnancy and Challenging Transient Anti-GAD65 Positivity: A Case Report with Literature Review

Abstract Introduction During pregnancy, women may develop blood glucose abnormalities like gestational diabetes mellitus (GDM) or, rarely, type 1 diabetes (T1D), which can lead to complications. Anti-GAD65 is a key antibody used in diagnosing T1D. This study presents a rare case of T1D developing a week before birth, with transient anti-GAD65 positivity. Case presentation A 38-year-old patient who delivered a baby a week earlier and had high blood glucose was admitted to the hospital with shortness of breath, chest tightness, abdominal pain, generalized weakness, nausea, and repeated vomiting. She had elevated anti-GAD65 and was diagnosed with T1D and diabetic ketoacidosis. Insulin injection was prescribed, with lifestyle modifications, later oral hypoglycemic medications added. After a few months, both anti-IA2 and anti-GAD65 antibodies were negative. Literature review Seven cases of T1D during or after pregnancy were reviewed. Six reported BMI. The mean HbA1c was >7.63%. Mean anti-GAD65 was 190.74 U/mL, two were borderline and one negative. Six had previously diagnosed GDM. Treatments varied, including insulin and dietary management. All infants were safely delivered, one miscarried in a subsequent pregnancy. Insulin resistance increases during pregnancy due to hormonal changes, raising the risk of GDM, T1D, and type 2 diabetes. Emerging postpartum, often indicated by anti-GAD65 antibodies, though levels can fluctuate. Cases show complications like preeclampsia, DKA, and miscarriage. Early detection, strict glucose control, and monitoring antibody patterns are critical for managing risks and improving maternal and fetal outcomes. Conclusion Blood glucose should be monitored during pregnancy, and anti-GAD65 may signal T1D, requiring appropriate management. Introduction Type 1 diabetes (T1D) is a condition characterized by a lack of the hormone insulin due to an autoimmune response that destroys the pancreas's insulin-producing β cells [1]. During pregnancy, women may develop an abnormal tolerance to glucose, which is not severe enough to be classified as overt diabetes mellitus, known as gestational diabetes mellitus (GDM). This condition increases the possibility of type 2 diabetes (T2D) after birth, and the risk of T1D, especially if they have autoantibodies targeting the beta cells of the pancreas [2]. Around 2-17% of expectant mothers empierce GDM. While glucose metabolism typically returns to normal after childbirth, there is a high chance, between 34% up to half of the cases, that it will recur in future pregnancies, with around 6% developing into T1D [3]. Throughout an asymptomatic period of variable length, different autoantibodies targeting islet cell autoantigens can be identified, and these play a key role in recognizing individuals at an increased risk of developing clinical disease. Glutamic acid decarboxylase (GAD) is a key enzyme, antibodies against said enzyme or anti-GAD65 are one of the primary antibodies associated with T1D, with two isoforms having molecular weights of 65 kDa and 67 kDa. This antibody is found in most individuals with preclinical or recently diagnosed T1D. [4]. It is well established that pregnancies that involve T1D face a greater risk of complications affecting the mother, fetus, and newborn compared to those with uncomplicated pregnancies [5]. Poorly managed high blood glucose during pregnancy can result in serious complications, including stillbirth, miscarriage, congenital disabilities, and pregnancy-related conditions like hypertension or preeclampsia [1]. The aim of this study is to show a rare case of T1D developing a week before giving birth, with a transient anti-GAD65 positive test result, and a literature review. The references used in this case report have been checked for reliability and compiled with CaReL guidelines [6,7]. Case Presentation Patient information A 38-year-old female was admitted to the hospital with shortness of breath, chest tightness, abdominal pain, generalized weakness, nausea, and repeated vomiting that had persisted for two days before admission. She had been pregnant and had delivered a stillborn baby one week earlier at 39 weeks of gestation. Clinical findings On clinical examination, the patient appeared distressed and exhibited tachypnoea. Her heart rate was 110 beats per minute, respiratory rate was 32 cycles per minute, blood pressure was 110/70 mmHg, and her temperature was 38°C. Her BMI was 34 kg/m². She had no history of chronic disease. Diagnostic approach The patient was admitted to the hospital, resuscitated, and diagnosed with diabetic ketoacidosis (DKA), based on the presence of ketone bodies in the urine (3+) and acidosis confirmed by arterial blood gas analysis (pH 7.16, bicarbonate 12 mmol/L), her blood glucose was over 300 mg/dL. Anti-GAD test came back elevated at (65.1 U/mL), leading to a diagnosis of T1D. Therapeutic intervention Several days before her scheduled Cesarean section, she was admitted to the hospital due to elevated blood pressure and blood glucose levels. She was treated with insulin therapy to manage her condition. Following the surgery, the patient was evaluated by an endocrinologist for her hyperglycemic condition. Based on her medical history, the decision was made to discontinue insulin therapy and initiate lifestyle modifications along with oral hypoglycemic medications. However, two days after this change in treatment, she developed DKA. To treat her DKA, she received intravenous insulin infusion and was rehydrated with normal saline and received potassium. Follow-up A few months after starting insulin therapy, she underwent testing for T1D-related autoantibodies, which came back within normal ranges. The results were negative for both anti-IA2 and anti-GAD65 antibodies. Discussion The sensitivity to insulin declines during pregnancy, primarily due to the influence of placental hormones. Human growth hormone, along with human placental lactogen, plays a key role in regulating maternal metabolism and supporting the growth of the fetus, with levels gradually increasing throughout the first and second trimesters. Pregnancy is also associated with a reduced secretion of human growth hormone in response to low blood glucose, which further contributes to the resistance toward insulin. These effects are compounded by hormonal changes involving progesterone, prolactin, cortisol, adiponectin, and leptin [1]. Seven cases of T1D arising during or after pregnancies have been reviewed (Table 1) [2, 3, 8-10]. Six cases mentioned the patient’s body mass index, one of them mentioning the pre-pregnancy body mass index. The mean HbA1c was over 7.63, only one case didn’t mention performing a HbA1c test. The mean anti-GAD65 was 190.74 U/mL, with two cases being borderline at around 2 U/mL and one negative at 0.268 U/mL. Six cases were associated with GDM before T1D. Different treatments and therapeutics were used, including insulin therapy and dietary managements. All the infant were delivered safely, but one case had another pregnancy a few months later and the fetus miscarried. Table 1. Review of similar cases of type 1 diabetes arising during or after pregnancies in the literature. Author and year of publication Age Clinical findings Performed tests Diagnosis Treatment Outcome Abdelmasih et al. 2024 [8] 22 Not mentioned. Blood glucose (300 mg/dl), HbA1c (9.4%, prepartum 5.3%), postpartum blood glucose (300-400 mg/dl) C peptide (0.6 ng/dl), & anti-GAD65 (38.8 U/mL). GDM previously, later postpartum T1D. Insulin therapy, later stopped and continued on Metformin, Glipizide & Glargine added, later oral antidiabetics were stopped & prandial insulin started. Infant delivered with macrosomia. Fujishima et al. 2023 [3] 29 BMI (19.1 kg/m2), TSH receptor autoantibody +ve but low, diagnosed with Graves’ disease previously, diabetic retinopathy not observed. HbA1c (6.9%), anti-GAD65 (1210 U/mL), Fasting C-peptide (1.19 ng/mL), daily urinary C-peptide (120.6 μg/day), blood glucose 2 months after birth≥ 200 mg/dL. GDM, then postpartum T1D. Dietary management, insulin aspart, lispro, and detemir administered, & methimazole to control thyroid function. Infant delivered safely. Ikeoka et al. 2018 [2] 27 High postprandial blood glucose, diagnosed with GDM beforehand, BMI (16.9 kg/m2). Frequent postprandial blood glucose (140-180 mg/dL), 6 weeks postpartum 75-g OGTT at 2 h (258 mg/dL), 4 months postpartum 75-g OGTT at 2 h (453 mg/dL) and HbA1c (6.7%), glycated albumin (22.5%), 6 months postpartum anti-GAD65 (57.1 U/mL). GDM previously, later postpartum T1D. Dietary management, neutral protamine Hagedorn, and insulin aspart, pregnant again at 4 months postpartum and received intensive insulin therapy. 1st Infant delivered, 2nd fetus miscarried. Himuro et al. 2014 [9] 32 Fatigue and thirst, Kussmaul breathing with ketotic odor, pBMI (19.9 kg/m2). plasma glucose (489 mg/dl), anion gap (21.9), arterial pH (7.45), base excess (9.8 mmol/l), anti-GAD65 (25 U/mL), IA-2 (1.5 U/ml). DKA, with adult-onset T1D. treatment with saline, intensive insulin therapy, & diet therapy. Infant delivered safely. Bonsembiante et al. 2013 [10] 42 Pregnancy BMI (22.5 kg/m2). Postpartum HbA1c (9.5%), Postpartum OGTT at 2 h (>200 mg/dL), low blood insulin, C-peptide (1.1 ng/mL), anti-GAD65 (>2 U/mL). GDM & later T1D. Insulin therapy, & dietary management. Infant delivered safely. 39 Pregnancy BMI (20.4 kg/m2). Blood sugar (170 mg/dL), HbA1c (7.3%), C-peptide (1.2 ng/mL) & anti-GAD65 (2 U/mL). GDM & T1D in previous pregnancies. Insulin therapy before, dietary management only now. Infants delivered safely. 36 Pregnancy BMI (22.4kg/m2). anti-GAD65 (0.268 U/mL), fasting plasma C-peptide (1.8 ng/mL), mean HbA1c (6%). GDM & later T1D. Insulin therapy, & dietary manageme