Prolonged Honeymoon Period in a Thai Patient With Adult-Onset Type 1 Diabetes Mellitus - Metabolic Flexibility in Autoimmune Diabetes?

Abstract

Abstract Background: ‘Honeymoon’ period among people with type 1 diabetes mellitus (T1DM) refers to the period of time (mostly less than 1 year) which beta-cell is still able to produce insulin to maintain good glycemic control shortly following the development of diabetes. This phenomenon remained incompletely understood but previous studies showed that absence of diabetic ketoacidosis (DKA) at initial presentation, short duration of symptoms, older age at presentation, and strenuous exercise could be potential factors. Herein, we report a 24-year old Thai patient with T1DM who has been in sustained complete remission for more than 5 years while he is maintaining low carbohydrate intake and regular exercise. Clinical Case: A 24-year-old male presented with a 6-month history of polyuria, polydipsia and weight loss of 15 kilograms (baseline BMI at 27.8 kg/m2). His initial laboratory data showed plasma glucose 398 mg/dL and A1C 9.3%. No ketonemia was found. He was diagnosed with stage 3 of Type 1 DM based on clinical presentation and positive pancreatic auto-antibodies (anti-GAD and anti-IA2). Euthyroid Hashimoto’s thyroiditis was also diagnosed based on his enlarged thyroid gland and positive thyroid auto-antibodies. He was started on basal-bolus insulin regimen for only 2 month and then A1C reversed to 5.9% within 2 months. Insulin was gradually withdrawn and completely stopped. Mixed meal stimulation test (MMST) was firstly evaluated at the second year of his diagnosis. The result revealed stimulated C-peptide at 5.5 ng/dL. Next-generation sequencing panel for monogenic diabetes revealed negative results. The patient maintains healthy lifestyle habit with low carbohydrate intake and regular exercise 5–6 times per week. His body weight was maintained at 60–63 kilograms during the past 4 years. His A1C was maintained between 5.0 to 6.0% without any anti-diabetic medication for more than 5 years. Repeated MMST in every 6–12 months still revealed preserved beta-cell functions and normal stimulated plasma glucose. Interestingly, repeated pancreatic auto-antibodies at 3 years after diagnosis showed negative anti-GAD and anti-IA2, but positive anti-ZnT8. The patient was advised to maintain his bodyweight and healthy behavior together with closely regular OPD follow-up. Conclusion: Restored beta-cell function with completely insulin withdrawal in new-onset T1DM has been reported in very few cases which have some common factors as in our patient (low carbohydrate intake with regular exercise). Delaying autoimmune activity by reducing metabolic load in newly diagnosed T1DM might play a role in maintaining a honeymoon period and could lead to an innovative therapeutic option in new-onset T1DM.