Occasionally nature can provide secrets that give insights into the cause of disease. One such secret relates to a rare genetic condition that protects individuals from developing obesity and type 2 diabetes. The condition is known as essential fructosuria, and it is due to a mutation in the fructokinase gene. As you may recall, fructokinase is the key enzyme that metabolizes fructose, and so these individuals cannot activate the survival switch. They can still metabolize fructose using a glucose metabolizing enzyme known as hexokinase, but this does not activate the switch. In addition, some of the fructose they eat passes into the urine (approximately 10 percent).
People with essential fructosuria stay thin and do not develop type 2 diabetes. They have normal lives. They are very hard to find since they have no symptoms. They can eat all the sugar they want and never get fat, but the sugar is not that tasty to them and they tend to prefer salty foods. In the past they were identified when urine was being tested for sugar, such as in school screening tests. This is because the old way of doing this was to use a test known as the Clinitest, which measured all sugars including glucose and fructose. Today, however, we use specific tests for glucose, and so the presence of fructose in the urine is not noted even if it were present.