Lately, genes have been all the rage in medical research. Many people hope that genetic studies will unravel the secrets of many diseases that, strictly speaking, aren’t really genetic. Sometimes, people get so caught up in thinking about the genes that could be involved in a disease that they ignore the importance of diet to prevent and manage the disease. Yet even for a disease that is truly 100% genetic, dietary management can be important. The classic examples are the rare forms of diabetes mellitus that really are genetic. These forms of diabetes are called monogenic diabetes mellitus. Sometimes they’re called MODY, which stands for maturity-onset diabetes of the young. There are several different forms of MODY, each resulting from the mutation of a different gene. These disorders tend to be autosomal dominant, which means that if you inherit the gene from one of your parents, you have the disease. Clinically, cases of MODY tend to look like a hybrid between type 1 and type 2 diabetes. Together they account for somewhere between 1% and 5% of cases of diabetes mellitus.
Diabetes mellitus refers to several unrelated conditions that all result in high levels of sugar in the bloodstream. In the 1870s, French researchers noticed that there are two main types of diabetes mellitus. One is a catastrophic disease that tends to strike children and young adults. Before the discovery of insulin, these patients would rapidly lose weight, go into a coma, and die within a matter of days or weeks, regardless of treatment. The French researchers called it diabète maigre, or thin diabetes. English-speakers called it juvenile diabetes, then insulin-dependent diabetes, and now type 1 diabetes. In contrast, the most common form of diabetes is a much milder, reversible condition that occurs in middle-aged to elderly adults who are usually at least a bit overweight. The French called this condition diabète gras, or fat diabetes. English-speakers tactfully referred to this kind of diabetes as adult-onset, then non–insulin-dependent, and now type 2 diabetes.
If left untreated, all forms of diabetes mellitus result in abnormally high levels of a sugar called glucose in the bloodstream. In cases of type 1 diabetes, the high glucose levels result from the failure of the pancreas to produce the hormone insulin. Insulin is needed to open the gates that allow glucose to enter most of the body’s cells so that they can use it for fuel. Insulin also helps to prevent the liver from making additional glucose by breaking down glycogen and protein. When the body lacks insulin, the liver produces lots of extra glucose that cannot be burned for energy and builds up in the bloodstream.
Without insulin, the body’s cells are starved of glucose (their favorite fuel) even while the glucose builds up to toxic levels all around them. When the glucose builds up to a high enough level, it leaks through the kidneys into the urine, taking water and electrolytes along with it. That’s why high blood sugar causes the person to pee a lot and feel thirsty—the classic symptoms of diabetes. The word diabetes came from the Greek word for siphon. Years ago, English-speakers called diabetes “the pissing evil.”
When the cells cannot use sugar for energy, they have to use fats instead, thus producing byproducts called ketone bodies. Ketone bodies aren’t always a bad thing. Your brain can use them for energy when you are starving. Unfortunately, abnormally high levels of ketones in the blood (ketosis) can have effects that are even worse than the effects of high levels of glucose. Not only does ketosis cause additional loss of water and electrolytes through the kidneys, ketone bodies are acidic. If the ketone bodies build up to a high enough level in the bloodstream, they can overwhelm the body’s ability to maintain a normal blood pH. This problem is called diabetic ketoacidosis. It is a medical emergency and can be deadly.
Early on, doctors noticed that people with type 2 diabetes rarely get diabetic ketoacidosis. In severe cases, they might go into a coma because their blood sugar is so high that they get severely dehydrated, but they rarely get such severe ketosis that their blood pH is affected. That’s because people with type 2 diabetes are producing some insulin. In fact, they tend to have abnormally high levels of insulin in their bloodstream. The problem is that their cells have become resistant to the effects of insulin.
MODY was discovered in the 1960s, when physicians noticed that some children had persistent, symptomless high blood sugar that didn’t progress to ordinary type 1 diabetes. In other words, the condition looked like type 2 diabetes, except that it was happening in young people who weren’t overweight. The child’s pancreas was producing some insulin, just not enough to meet the body’s needs. By the 1970s, it was clear that this problem ran in families. At present, at least 10 forms of MODY have been described, each of them linked to a different gene.
The treatment for MODY depends on what type of MODY the patient has. Genetic testing is now available for MODY1, MODY2, MODY3, MODY4, and MODY5. MODY2 is a relatively mild disease that can be managed by diet and exercise. As in ordinary cases of type 2 diabetes, the goal is to avoid or reverse insulin resistance, so that the amount of insulin the pancreas produces on its own will be enough to regulate the patient’s blood sugar naturally. Maintaining insulin sensitivity through proper diet and exercise is undoubtedly also important in managing the other, more severe forms of MODY. Patients with MODY1, MODY3, or MODY4 are usually given a sulfonylurea drug that causes the pancreas to secrete extra insulin. MODY5 is a severe condition that is usually treated as if the patient has no pancreas whatsoever; the patient is given insulin injections as well as digestive enzymes that are taken by mouth.