Big Brains and High-Protein Diets: An Evolutionary Advantage of Diabetes in Dolphins

The World Health Organization states that each year approximately 5% of all deaths globally are due to diabetes, and that, without urgent action, diabetes deaths are likely to increase by more than 50% in the next 10 years. A single, natural species has not been identified that fully complements diabetes in humans, and the discovery of a natural animal model may greatly advance the ability to prevent and treat this disease. Bottlenose dolphins have a prolonged glucose tolerance curve and fasting hyperglycemia that mimic diabetes mellitus in humans. After ingestion of glucose, dolphins demonstrate negligible insulin and glucagon response and a pronounced, sustained hyperglycemia. Following a high protein meal, dolphins demonstrate a dose-dependent increase in insulin and glucagon, and glucose metabolism is stabilized. Interestingly, there are populations of dolphins that have conditions associated with insulin-resistance in humans, namely urate nephrolithiasis and iron overload. High protein diets are recommended for people with diabetes, as short-term feeding studies have demonstrated that high-protein, low-carbohydrate diets may help stabilize glucose metabolism. Dolphins naturally ingest a high protein diet (estimated to be 73% protein, 24% fat, 3% carbohydrate). To assess the effects of dextrose and protein ingestion on dolphin blood and urine solutes, twelve 24h feeding studies were conducted with seven dolphins using tube-fed 2-3L 10% in ionosol G or 4.5-7kg Spanish mackerel. Changes in solutes were compared during 0 to 5h, greater than 5 to 10h, greater than 10 to 15h, and greater than 15h after feeding. The dextrose feeding trial evoked significant increases in urine flow rate during 0 to 5h (2.8±2.2 ml/min); decreases in plasma chloride, including a hypochloremic state, during 0-10h (109±2 mEq/L); and increases in plasma glucose, including hyperglycemia, during 0-10h (209±36 mEq/L) compared to greater than 15h after ingestion (1±0.4 ml/min, 115±2 mEq/L, 135±17 mEq/L, respectively). During 0 to 10h, the mackerel diet caused a higher urine flow rate (3.3±1.6 ml/min) and higher sodium, chloride, potassium, and urea urine concentrations (20±16, 23±19, 17±8 and 5.3±2.9 mEq/L, respectively) compared to greater than 15h (1.0±0.5 ml/min and 4.8±3.4, 9±4, 7±4, and 2.2±1.4 mEq/L, respectively). While there was a higher plasma glucose level during 0 to 5h compared to greater than 5h (160±30 vs. 125±25), mean plasma glucose levels remained below 200 mEq/L. Further, no other solute abnormalities were identified during the feeding study. Our results indicate that dolphins successfully maintain stable glucose metabolism and solute balance on a high protein diet. These series of studies indicate that the bottlenose dolphin may serve as the first natural animal model for diabetes. Proposed evolutionary reasons for similar glucose metabolism among cetaceans and primates are their similarly high brain-to-mass ratios and a subsequent high demand for readily available blood glucose.