Maturity Onset Diabetes of The Young - History of The Concept and Treatment of MODY

History of The Concept and Treatment of MODY

The term MODY dates back to 1964, when diabetes mellitus was considered to have two main forms: juvenile-onset and maturity-onset, which roughly corresponded to what we now call type 1 and type 2. MODY was originally applied to any child or young adult who had persistent, asymptomatic hyperglycemia without progression to diabetic ketosis or ketoacidosis. In retrospect we can now recognize that this category covered a heterogeneous collection of disorders which included cases of dominantly inherited diabetes (the topic of this article, still called MODY today), as well as cases of what we would now call type 2 diabetes occurring in childhood or adolescence, and a few even rarer types of hyperglycemia (e.g., mitochondrial diabetes or mutant insulin). Many of these patients were treated with sulfonylureas with varying degrees of success.

The current usage of the term MODY dates from a case report published in 1974. This milder form of diabetes had been recognised in the pre-insulin period. This was forgotten possibly because of Elliott P. Joslin's dictum that all young people with diabetes should be treated with insulin. With the introduction of sulphonylureas in the 1950s it was found that tolbutamide could improve or normalize carbohydrate tolerance in some young non-obese mildly diabetic patients. The genetic basis was overlooked because it was thought that diabetes was a homogeneous disease with young and old patients forming part of the same continuum. In 1973 Fajans had shown that the carbohydrate intolerance of 45 patients diagnosed under age 25 had not progressed after up to 16 years on sulphonylureas and that 43 out of 45 of these subjects had a first-degree relative with diabetes. In the same year Lestradet described a non-insulin-dependent form of childhood diabetes which was later established to be dominantly inherited. In 1974 Tattersall described three families in which diabetes, although diagnosed in adolescence, could be treated with sulphonylureas over 40 years later and was dominantly inherited. Also in 1974 Tattersall and Fajans coined the acronym MODY which was defined as 'fasting hyperglycaemia diagnosed under age 25 which could be treated without insulin for more than two years'.

By the 1990s, as the understanding of the pathophysiology of diabetes has improved, the concept and usage of MODY have become refined and narrower. It is now used as a synonym for dominantly inherited, monogenic defects of insulin secretion occurring at any age, and no longer includes any forms of type 2 diabetes.