Medication non-adherence is common in patients with diabetes mellitus (DM). Cognitive dysfunction is one of the important causes of poor adherence. Metformin therapy has been implicated in vitamin B12 (B12) deficiency, which in turn can lead to cognitive dysfunction. We herein report a case of non-adherence to insulin therapy due to cognitive changes associated with B12 deficiency resulting in significant worsening of glycemic control.
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Results : N/A
A 58-year-old woman with an 8-year history of type 2 diabetes mellitus (T2DM) being treated with metformin 1000 mg twice a day and high dose concentrated regular insulin (RU-500; 200 units per day in two divided doses) was noted to have an HbA1c of >14%. Her other medications were aspirin, atorvastatin, furosemide, amlodipine, lisinopril and low dose prednisone. Her HbA1c consistently ranged from 9-11% in her previous office visits. Her diet, which consist of rice with fish 3 times per day, has not changed over time. Occurrence of symptomatic hypoglycemic events precluded insulin intensification. The patient could not afford newer anti-hyperglycemic agents as they were not covered by her insurance. On questioning, she reported worsening forgetfulness for the past few months, leading to frequently missed insulin doses. Her poor memory had also impaired other aspects of her day to day living. This prompted us to measure B12 level, which was 296 pg/mL. Her methylmalonyl-CoA level was 2.5 μmol/L. She was subsequently started on parenteral vitamin B12. On follow-up visit, she reported significant improvement in her memory and her medication compliance. Her HbA1c decreased to 11.3% from >14% without change in insulin dosage or diet.
Current guidelines do not recommend routine screening for vitamin B12 deficiency among patients with T2DM treated with metformin. Cognitive impairment from B12 deficiency could be a major contributing factor for medication non-compliance. Our case supports the idea of routine testing for vitamin B12 deficiency in patients with T2DM treated with metformin. Clinicians should consider testing B12 levels in T2DM patients, especially who are at high risk such as the elderly, and patients with dietary restrictions, alcohol abuse or use of concomitant medications such as PPIs. Measuring B12 levels should also be considered in patients who have poor medication adherence due to cognitive impairment.
Sandhya Maradana– Internal Medicine resident, Saint Vincent Hospital, Worcester, Massachusetts
Carolina Perez Carrion– Internal Medicine Resident, Saint Vincent Hospital, Worcester, Massachusetts
Trivedi Nitin– Division Director, Endocrinology, Saint Vincent Hospital, Shrewsbury, Massachusetts
Internal Medicine resident
Saint Vincent Hospital
I am Sandhya Maradana, one of PGY 2 resident at St Vincent Hospital in Worcester. I finished my medical school in India in 2016 and moved to the US to pursue my residency. Through the course of my intern year, I began developing interest in endocrinology seeing varied pathologies and evaluating the patients. I would like to pursue a career in endocrinology and see this as opportunity to explore diversity in endocrinology.
Internal Medicine Resident
Saint Vincent Hospital
I'm an Internal Medicine PGY-3 at St. Vincent hospital in Worcester, Massachusetts. I started my medical training in Ecuador where I finished my medical school in 2012. I then moved to the US and did research in non-invasive brain stimulation to then start residency in internal medicine. I am interested in pursuing a career in Endocrinology. Since the beginning of my intern year I have been interested in endocrine pathology, specially thyroid pathology. I became an AACE member this year and look forward to become a clinical endocrinologist and a researcher in the field.
Division Director, Endocrinology
Saint Vincent Hospital
Dr. Nitin Trivedi is an Associate Professor of Medicine at the University of Massachusetts Medical School and one of the Associate Program Directors in the Internal Medicine Residency Program at Saint Vincent Hospital in Worcester, MA. He is board certified in Internal Medicine and Endocrinology. He is a fellow of American College of Physicians and American Association of Clinical Endocrinologists. He has served as the President of the New England Chapter of American Association of Clinical Endocrinologists. He has received the Gilbert E. Levinson Award for the best resident voted by the faculty members and the John J Mckeever Medical Educator Award from the Department of Medicine at Saint Vincent Hospital. His research interests include management of diabetes in hospitalized patients and insulin pump use in type 2 diabetes.
Dr. Trivedi earned his medical degrees from MGM Medical College in Indore, India and completed his Internal Medicine Residency at Saint Vincent Hospital and Endocrinology Fellow at Brown Medical School. He has worked as a Research Fellow in the section of Islet Transplantation and Cell Biology at Joslin Diabetes Center, Harvard Medical School in Boston. He was an Assistant Professor at Brown Medical School from 2004 -2005.
He has authored several publications and abstracts.
1. Suzuki K, Bonner-Weir, Trivedi N, Yoon KH, Lock JH, Colton CK, Weir GC: Survival and function of macroencapsulated syngeneric islets transplanted into Streptozotocin diabetic mice. Transplantation 1998;66:21-28.
2. Trivedi N, Mithal A, Sharma AK, Mishra SK, Trivedi B, Daughaday WH. Nonislet tumor induced
hypoglycemia with acromegaloid facial and acral swelling. Clinical Endocrinology (Oxf.)
3. Trivedi N, Suzuki K, Bonner-Weir S, Hollister-Lock J, Weir GC: Islet number in an immunobarrier required to cure diabetes in mice. Transplantation Proceedings 1997;29-21-2143.
4. Trivedi N, Steil GM, Colton CK, Bonner Weir S, Weir GC: Improved vascularization on planar diffusion devices following continuous infusion of vascular endothelial growth factor. Cell Transplantation 1999;8:673-689.
5. Steil GM, Trivedi N, Jonas JC, Hasenkemp WM, Sharma A, Bonner Weir, Weir GC. Enhanced beta-cell function with normal islet gene expression following Adaptation of B-cell mass to substrate oversupply. Am J Physiology 2001;280:E788-E796.
6. Trivedi N, Keegan M, Steil GM, Hollister-Lock J, Hasenkemp WM, Colton CK, Bonner-Weir S, Weir GC. Islets in alginate macrobeads reverse diabetes despite minimal acute insulin secretory responses. Transplantation 2001;27:203-211.
7. Omer A, Duvivier-Kaul, Trivedi N, Wilmot K, Bonner-Weir S, Weir GC. Survival and maturation of microencapsulated porcine neonatal pancreatic cell clusters transplanted into immunocompetent diabetic mice. Diabetes 2003;52(1):69-75
8. Xu G, Kaneto H, Laybutt DR, Duvivier VF, Trivedi N, Suzuma K, Kiong GL, Weir GC, Bonner-Weir S. Downregulation of GLP-1 and GIP receptor expression by hyperglycemia: Possible contribution to impaired incretin effect in diabetes. Diabetes 2007;56(6):1551-8.
9. Vyas A, Fillipon N. Lynn, Vyas P, Vijayakrishnan R, Trivedi N. Successful treatment of thyroid storm in a patient with methimazole-induced toxicity. Endocrine Practice 2010;16673-675.
10. Chhabra L, Liti B, Kuraganti G, Kaul S, Trivedi N. Challenges in the management of Type 2 Diabetes Mellitus and Cardiovascular Risk Factors in Obese Subjects: What is the Evidence and What are the Myths? Int J Endocrinol Endocrinology 2013; Article ID 856793: 10 pages.
11. Alang N, Trivedi N. Secure email communication between patients and physicians is associated with better glycemic control. R I Med J (2013). 2014 Jan 3;97(1):15.
12. Sahni P, Trivedi A, Omer AO, Trivedi N. Adrenal incidentaloma: Are they getting work up appropriately? J Community Hospital Perspective 2016;6(5):32913. Doi:10.3402/jchimp.v6.32913.