Experts in four rare forms of diabetes discussed strategies for diagnosing and treating patients with these uncommon conditions during a symposium at the 81st Scientific Sessions.
Management of Atypical Diabetes, which took place Monday, June 28, can be viewed by registered meeting attendees at ADA2021.org through September 29, 2021. If you haven’t registered for the Virtual 81st Scientific Sessions, register today to access all of the valuable meeting content.
Janet B. McGill, MD, Professor of Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, said the pathogenesis of type 3c diabetes, or diabetes associated with pancreatic exocrine insufficiency (PEI), depends on age. For infants, it’s pancreatic agenesis, while childhood cases stem from pancreas divisum and genetic pancreatitis. Young adults often develop cystic fibrosis-related diabetes or carboxyl-ester lipase mutation. In adults, the most common cause is acute or chronic pancreatitis, followed by pancreatic surgery.
Patient assessment starts with a review of symptoms and history, then proceeds to screening for diabetes and imaging, followed by testing for PEI. Therapeutic goals are complicated by the increased risk for treatment-related hypoglycemia.
“Non-insulin treatment may work initially, but our options are quite limited,” Dr. McGill said. “Insulin dosing needs to be focused on low basal and adequate mealtime insulin. In those patients who need it, encourage the use of pancreatic enzymes at all meals and snacks if exocrine insufficiency is present.”
Marina Basina, MD, Clinical Professor, Division of Endocrinology, Stanford University School of Medicine, said post-transplantation diabetes mellitus (PTDM) occurs in 10% to 40% of solid-organ transplants within the first year. Most studies have involved renal transplants.
Pre-transplant, Dr. Basina said, providers should complete a medical, family, and glucose history; do fasting plasma glucose (FPG) and oral glucose tolerance (OGTT) tests to identify high-risk candidates and try to intervene before the transplant; and conduct counseling for weight loss, diet, and exercise. Post-transplant, providers should individualize immunosuppressive treatment based on patient risk, she added. Fasting glucose should be checked weekly for the first month post-transplant, then at three, six, and 12 months, and annually at a minimum going forward. OGTT should be considered if FPG is normal, as OGTT is the “gold standard” test, Dr. Basina said.
Insulin therapy is preferred during the first month or two post-transplant because research shows that early basal insulin therapy can decrease or delay the likelihood of new-onset diabetes after renal transplant, Dr. Basina continued. Clinicians should look to expand the role of diabetes management technology, including continuous glucose monitoring (CGM) to identify PTDM early.
Armen Yerevanian, MD, HMS Instructor of Medicine, Division of Endocrinology, Massachusetts General Hospital, discussed the evaluation and treatment of severe insulin resistance. Insulin resistance is ubiquitous in type 2 diabetes, but it’s not a clinical endpoint, he said. The key is to find ways to identify severe insulin resistance without directly measuring insulin resistance as a physiologic state.
Clinical presentations of insulin resistance include acanthosis nigricans, lipodystrophy, central obesity, hyperandrogenism, and hepatic steatosis, Dr. Yerevanian said. Biochemical presentations include hyperglycemia, hypertriglyceridemia, elevated fasting insulin, liver function abnormalities, and hyperinsulinemic-euglycemic clamp test, which is the gold standard test, but clinically impractical because of the cost and difficulty conducting the test, he added.
Severe insulin resistance management requires high doses of insulin (U-500). Lipodystrophies are a common cause of insulin resistance, Dr. Yerevanian noted, and should be considered in unexplained metabolic disease.
“This is a challenging population to manage, but with aggressive metabolic therapy, a lot of them do very well,” Dr. Yerevanian said.
Immunotherapy, especially the target molecules programmed death 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), has transformed cancer treatment, but it comes with the risk for immune-related adverse effects like autoimmune diabetes, noted Mark S. Anderson, MD, PhD, Interim Director, University of California-San Francisco Diabetes Center.
The onset of autoimmune diabetes is acute, often with diabetic ketoacidosis (DKA), Dr. Anderson explained. And there is great variability in the timing—some patients present early in treatment while others present up to two years after immunotherapy starts. Autoantibodies frequently aren’t present or cannot be detected in patients with autoimmune diabetes, unlike type 1 diabetes, where 80% to 90% will have autoantibodies.
Cancer patients who develop autoimmune diabetes typically have been treated with anti-PD-1 therapy, Dr. Anderson explained.
“There are a handful of cases where patients received anti-CTLA-4, but there’s a much stronger association with anti-PD-1,” he said. “The meaning of this is still being unraveled, but we do know that this is providing some sort of information about why this particular complication is arising.”
Clinical observations indicate that autoimmune diabetes is not clinically reversible. Treatment is similar to type 1 diabetes, Dr. Anderson said.