The basic principles of the treatment of MODY are much easier than the diagnosis. This is because most patients are not diagnosed in the first place, either because clinicians don't know the family history or because they don't even consider MODY as a possibility.
This patient most likely has hepatic nuclear factor 1-a (HNF-1 alpha) MODY, also referred to as MODY-3. This is a transcription factor MODY, the type characterizing about 2/3 of all MODY patients and accounting for 61% of all MODYs.1 All transcription factor MODY patients involve genetic defects in insulin secretion; thus, insulin sensitizers (including metformin) are not indicated. As with type 1 diabetes, patients with MODY are classically thin and insulin sensitive already (although with the increasing epidemic of obesity we do now see overweight and obese MODY patients as well).
HNF-1-alpha MODY patients respond well and are quite sensitive to sulfonylureas. However, as with patients with type 2 patients, over time they lose their response to these agents and require insulin. Since HNF-1-alpha MODY patients are not ketosis-prone, ketoacidosis is not a concern. While we don’t have studies guiding us to which insulin regimens are most effectivem, I have found most of these patients require traditional basal-bolus insulin after failing sulfonlureas. From a theoretical perspective, it may be that basal insulin with daytime sulfonylurea may work well during the transition to more severe beta-cell deficiency.
It is now clear that patients with MODY can get the microvascular complications associated with type 2 diabetes;thus, glycemic targets should not be different. The exception to this is those patients who are diagnosed with glucokinase MODY (MODY-2). This type of MODY is the second most common, comprising 22% of all MODY patients.1 Their hyperglycemia is quite mild and in general no therapy is required (except perhaps during pregnancy). This patient’s A1C of 7.1%, however, is higher than would be expected for a glucokinase MODY patient, and, again, from what we know she sounds more likely to have MODY-3.
Of course, treatment would vary if the patient turned out to have yet another form of MODY, but this is also highly unlikely from what we have been told. While other types of MODY have been described, only HNF-4 a is seen in any significant numbers, comprising 4% of all MODY patients.1 Furthermore, as with MODY-3, this less common form of MODY is initially treated with sulfonylreas followed by insulin.
Down the line, other forms of therapy might also be considered, especially considering that the beta-cell lesion of MODY is obviously different than the lesions seen in either type 1 or type 2 diabetes. It is intriguing to consider how a GLP-1 agonist or DPP-4 inhibitor might both lower glucose and potentially spare beta-cell function over time. I am not aware of any anecdotal experiences with this approach, but perhaps some of our readers can enlighten us on this topic.
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