Reduction of insulin requirement in type 1 diabetes induced by BCG vaccination: a case report

• Main Authors: Haydar Ali Tajuddin, Amalina, Siah, Guan Jin, Abdul Wahab, Norasyikin, Mustafa, Norlaila, Sukor, Norlela, Kamaruddin, Norazmi
• Format: Conference or Workshop Item
• Language: English; English
• Published: 2018
• Subjects: RC Internal medicine; RC648 Specialties of Internal Medicine-Diseases of The Endocrine Glands. Clinical Endocrinology
• Online Access: http://irep.iium.edu.my/85083/1/IDFWPR.pdf; http://irep.iium.edu.my/85083/7/IDFWPR2018.pdf; http://irep.iium.edu.my/85083/
• Institution: Universiti Islam Antarabangsa Malaysia

Introduction Bacillus Calmette-Guerin (BCG) vaccinations reverse disease by restoring insulin secretion in a rodent model of type 1 diabetes. It stimulates innate immunity by inducing the host to produce tumor necrosis factor (TNF), which, in turn, kills disease-causing autoimmune cells and restores pancreatic beta-cell function through regeneration. Case presentation This is a case of a 32-year-old lady with a history of gestational diabetes on metformin, who presented at 10 months postpartum with significant weight loss over 1 month period followed by severe diabetic ketoacidosis. Her family history was negative for diabetes and her BMI was normal (22.5 kg/m2). At diagnosis, her C-peptide was 81 pmol/L, markedly elevated anti-GAD Ab of > 2000 U/L and HbA1c of 16%. She attained partial remission after 1 month of insulin initiation. The basal boluses regime was resumed with total insulin dose of 36 to 40 units/day at 6 months following the remission period. Her continuous glucose monitoring readings however, showed episodes of mixed hypoglycemia (min 3.2 mmol/L) and hyperglycemia (max 10.6 mmol/L) while on the insulin regime. Methods and Results We administered experimental 0.1 ml intradermal injections containing BCG 3.2×106 colony-forming units/injection at 6 and 7 months after the onset of her type 1 diabetes followed by a planned yearly BCG vaccinations thereafter. We observed that her insulin requirement had slowly reduced after her third BCG vaccination. At 32 weeks post first BCG vaccination, she went through a month of Ramadan Fasting with ONLY a single prandial insulin at pre dinner (Break of Fast)(8 to16 units/day) without any episodes of ketoacidosis. Her SBGM ranged from 5-8 mmol/L with total caloric intake of 1200-1500 kcal/day throughout the fasting period. This was further supported by marked improvement of her HbA1c from 8.1% down to 6.5% and increased in C-peptide level from 81 to 112 pmol/L. Discussion This patient demonstrated significant improvement in glycemic control following BCG vaccination earlier than those reported in previous clinical trials, however, the sustainability of good glycaemic control in her is still long way from being adequately established. In a previous 8-year long randomized clinical trial of type 1 diabetic subjects receiving BCG vaccination, stable and long-term reductions in blood sugar and epigenetic changes of restored tolerance had been observed. The significant clinical effects took three years to occur and remained steady for at least five additional years without further clinical interventions.1 BCG appears to have the ability to switch the immune system of type 1 diabetes from high oxidative phosphorylation to augmented early aerobic glycolysis. This case demonstrated preliminary metabolic and clinical benefits of BCG vaccinations in type 1 diabetic patient as early as 32 weeks post vaccination. Nonetheless, further clinical trial is needed to assess its long term effects in subjects of all ages and durations of type 1 diabetes.