Research Overview

The mission of Dr. Toledo’s lab is to advance the scientific knowledge on diabetes mellitus and related disorders. The lab conducts clinical-translational studies in humans with a specific emphasis on the metabolic pathways involved in the pathogenesis of diabetes mellitus, as well as investigation of new treatments for diabetes.


Dr. Toledo’s lab is specialized in a broad range of sophisticated techniques that can measure glucose and lipid metabolism flux in vivo in humans. Examples include euglycemic clamps, stable-isotope tracer methods, frequently sampled intravenous glucose tolerance tests, and indirect calorimetry. Dr. Toledo’s laboratory performs DEXA scans for body composition assessments, treadmill exercise tests for studies of physical performance, and muscle and fat tissue biopsies for translational studies. Dr. Toledo’s research program merges elements of basic and clinical sciences to explain the pathogenesis of diabetes, obesity, and related disorders, as well as to discover the mechanisms by which diabetes medications can affect metabolism in humans.


Current Areas of Focus Include:

Pathophysiology of Insulin Resistance

Dr. Toledo has published extensively on the complex relationships between mitochondria, insulin resistance, and lipid accumulation in skeletal muscle in the context of type 2 diabetes, obesity, and aging. He pioneered clinical studies that demonstrated the impact of over-nutrition, weight loss, and exercise activity on mitochondria and fuel metabolism in diabetes and obesity. Recently, Dr. Toledo has been collaborating with the Department of Epidemiology on an NIH-sponsored multi-center study investigating how aging affects mitochondria and its relationship to muscle health in the elderly.


Pharmacological Treatments for Diabetes

Dr. Toledo’s lab employs methods to measure metabolism in vivo to understand the impact of medications on metabolism. He has pioneered a research program of investigator-initiated studies to examine the effects of hydroxychloroquine (an anti-inflammatory arthritis drug) on glucose and lipid metabolism and explore its pharmacological potential. He has led clinical trials that demonstrated the impact of hydroxychloroquine on skeletal muscle and hepatic glucose metabolism in individuals at risk for type 2 diabetes and showed that this medication can enhance insulin sensitivity and beta cell function.

Diabetes in Exocrine Pancreas Disease

Dr. Toledo co-authored the NIH-sponsored guidelines for the detection, evaluation, and treatment of diabetes in chronic pancreatitis. He is currently a Principal Investigator in the NIH-sponsored Type 1 Diabetes in Acute Pancreatitis Consortium (T1DAPC) and a Co-Investigator in the NIH-sponsored study titled Diabetes Caused by Pancreatic Cancer or Chronic Pancreatitis (DETECT study). Dr. Toledo is a PI in the multi-center study DREAM (Diabetes RElated to Acute Pancreatitis and its Mechanisms), which will define the role of various endocrine and immunological abnormalities in the pathogenesis of diabetes after pancreatitis.


Prevention of Type 1 Diabetes

Dr. Toledo is a Co-Investigator in TrialNet, a national NIH-funded consortium that conducts clinical trials to prevent, delay, and reverse type 1 diabetes. TrialNet studies are investigating whether immune-modulatory therapies can slow down the decline in beta cell function in type 1 diabetes.