Clues in Dolphins to Treat Diabetes
After finding an initial clue that tied dolphins to a diabetes-like state, the group analyzed dolphin research data archived forty years ago. These studies, along with a series of new investigations, have found that healthy dolphins appear to readily turn a diabetes-like state on and off. This mechanism appears to be driven by a very high-protein, very low-carbohydrate fish diet.
“While some people may eat a high protein diet to help control diabetes, dolphins appear to have developed a diabetes-like state to support a high protein diet,” stated Stephanie Venn-Watson, DVM, MPH, director of clinical research for the National Marine Mammal Foundation. Sam Ridgway, DVM, PhD, famed father of marine mammal medicine and author of The Dolphin Doctor, stated, “There is a critical need for the diabetes research community to help us better understand dolphin metabolism. This work will not only directly benefit dolphin health, but may provide important clues to treating diabetes in humans.”
Dr. Ridgway was one of the founders of the Navy’s marine mammal program and has recently transitioned, along with a handful of veterinarians, animal trainers, and researchers to a new non-profit charity called the National Marine Mammal Foundation (NMMF). The mission of the NMMF is to enhance the lives of marine mammals and humans through scientific exploration and human-animal collaboration and to inspire creative thinking and commitment to ocean conservation in future generations.
A Fasting Switch for Diabetes in Dolphins
“Several years ago, we found an unexpected clue that healthy dolphins have a diabetes-like metabolism,” says Venn-Watson, in describing a study that compared blood values among dolphins that fasted overnight to dolphins that were recently fed.
“Fasted dolphins had a series of changes in serum chemistries that matched those of people with diabetes. Interestingly, these same dolphins switched back to a non-diabetic profile after eating. There appears to be a switch that dolphins use to turn a diabetes-like state on and off.”
Recently, a fasting inducible switch for glucose metabolism has been reported in humans. In people with diabetes, this gene-based switch may remain on. Baylor College of Medicine has mapped the dolphin genome, and the NMMF is actively searching for research collaborators to use this map to find a similar fasting gene in dolphins.
“Gene-based dolphin research could lead to a better understanding of how a fasting switch, which may be uncontrolled in some people with diabetes, can be controlled using the dolphin model,” notes Venn-Watson. “Its potential application to treat diabetes is enticing.”
Fasted dolphins had a series of changes in serum chemistries that matched those of people with diabetes. Interestingly, these same dolphins switched back to a non-diabetic profile after eating. There appears to be a switch that dolphins use to turn a diabetes-like state on and off.
Research conducted in the 1980s demonstrated that humans and dolphins have remarkable similarities in how they rapidly transport large amounts of glucose in the blood. A separate study found similarly high brain-to-mass ratios, called encephalization quotients, between primates and cetaceans. These two findings have led researchers to believe that dolphins and humans need rapid blood sugar transporters to support large brains which have a high demand for readily available glucose. This research set the ground work to explain why dolphins and humans may share the condition of diabetes, a disease involving abnormal blood glucose metabolism.
Humans and dolphins may share similar complications of diabetes. Previous studies in humans have demonstrated that insulin resistance, a precursor to type 2 diabetes, is associated with hemochromatosis (iron overload) and urate kidney stones. "Dolphins appear to be susceptible to these same diseases,” says Eric Jensen, DVM, managing marine mammal veterinarian at the Navy. “While dolphins rarely die from kidney stones or hemochromatosis, we are very interested in better understanding how to prevent and treat them in dolphins.”
“We have preliminary evidence that dolphins with iron overload also have insulin resistance,” states Venn-Watson. “If this is confirmed, better understanding of how a diabetes-like state changes from an advantageous condition to a pathologic disease in dolphins may address long unanswered questions about the cause of diabetes in humans.”
Finding a Cure among Lost Research Data: Controlling Blood Glucose with High Protein Diets
Some people with type 2 diabetes are advised to eat high-protein, low-carbohydrate diets. This diet has been demonstrated in short-term feeding studies to improve control of blood glucose. There is concern, however, that a high protein diet will worsen kidney disease.
Research conducted at the Navy in the 1970s tracked blood and urine values in dolphins after feeding them a high sugar or high protein diet.
“After a series of studies that kept pointing to the dolphin as a valuable natural animal model for diabetes, we dug through Navy research data archives for additional clues,” Ridgway said. “We had thousands of data points written by hand that recorded feeding research conducted over forty years ago. We transferred these data into an electronic database and analyzed them.”
After analysis of the archived data, researchers at NMMF found that dolphins became hyperglycemic after ingesting sugars but maintained stable glucose metabolism after ingesting a high protein fish diet.
“Dolphins appear to have lost the ability to properly metabolize dietary sugars,” Venn-Watson says. “Instead, they have found a way to use fish-protein diets to generate and control the glucose they need. If proteins are fed at too high of a dose at one meal, however, this may push a healthy diabetes-like state into a pathological one.”
Venn-Watson says, “We have a compelling story that may lead to new ways to prevent, treat, and cure diabetes in humans. We are actively seeking collaborations with the diabetes research community to convert a compelling story into applicable medicine that benefits both dolphins and humans.”
Joanne Webster, a professor of parasitic diseases at the RVC, has been elected as a Fellow of the Royal Society (FRS).
