Diabetes Diagnosis: MODY or not MODY?

If your patient was diagnosed with type 2 diabetes (T2DM), but doesn’t fit the usual body habitus of such an individual, what are the two potential subtypes of DM on your differential?

There are two, otherwise known as type 1.5 DM:

1. Latent autoimmune diabetes of adult (LADA)

2. Maturity-onset diabetes of the young (MODY).

I’ll discuss MODY this month, and some interesting clinical issues.

MODY is quite rare - it’s estimated to comprise ~1-2% of those with DM. Patients are often misdiagnosed with T1 or T2DM, and the diagnosis of MODY is often delayed; individuals may also be on incorrect treatment.¹

1. Diagnosing MODY can prove challenging.

The prevailing teaching was that MODY only appeared in those under 25. It turns out, we were incorrect. More than one-third of those with MODY develop full-on diabetes later in life, as late as in their 50s.

In some forms of MODY, the glucose elevations may be so slight that these patients aren’t being diagnosed. So while MODY is monogenic, not having either parent with a known diagnosis does not necessarily rule out this disease in children.

2. What are some features to look for?

Usually, patients are:

a. Normal weight

b. Not usually insulin-resistant

c. From families with a strong history of diabetes

3. The parents can potentially provide important clues.

Women are often first diagnosed with MODY during a first pregnancy. They usually will very rapidly develop gestational diabetes. If the MODY gene came from the individual’s father, diagnosis may be delayed or not uncovered at all.

4. What tests do you order?

Currently, the definitive tests are genetic tests - up to 6. The challenges are: they may be false-negative (47% of 12 MODY subjects in a study); they’re expensive; and they’re often not covered by insurance. One study noted, "We recommend that all patients diagnosed before age 30 and with presence of C-peptide at 3 years' duration [be] considered for molecular diagnostic analysis."²

5. How do you treat?

The short answer is: it depends on the type. The glucokinase version (MODY 2) does not require medication, but only control of carbohydrate intake. Many patients may only require PO medications, such as sulfonylureas. Most with MODY are very sensitive to insulin. They may only need ~10 to 20 units per day, if they need insulin at all. As basal insulin secretion is usually unaffected, a MODY patient may require much more prandial insulin.

Interestingly, there have been 6 subtypes of MODY identified, and it’s thought that 13% of MODY is not accounted for, so there are likely other genes we haven’t yet uncovered. We have much more to learn about this intriguing and challenging type of DM.

References:

1. Pihoker C, et al. Characteristics and clinical diagnosis of maturity onset diabetes of the young due to mutations in HNF1A, HNF4A, and glucokinase: results from the SEARCH for Diabetes in Youth. J Clin Endoclinol Metab. 2013;98:10:4055-4062.

2. Thanabalasingham G, et al. Systematic assessment of etiology in adults with a clinical diagnosis of young-onset type 2 diabetes is a successful strategy for identifying maturity-onset diabetes of the young. Diabetes Care. 2012;35(6):1206-1212.