NDM is a monogenic form of diabetes that presents within the first six months of life. In approximately half of patients, the diabetes will be permanent, and in the remaining cases the diabetes will remit within a few weeks or months although it might relapse later in life . Approximately, two-thirds of TNDM cases are caused by abnormalities in an imprinted region on chromosome 6q24 [13, 14] with activating mutations in either of the genes encoding the two subunits of the K-ATP channel of the β-cell membrane (KCNJ11 or ABCC8) causing the majority of the remaining cases .
In contrast, the genetic abnormality responsible for up to 30% of PNDM cases remains unknown although the commonest known cause in outbred populations is mutations in the K-ATP channel or INS genes .
Heterozygous activating mutations in the KCNJ11 or ABCC8 gene, which encodes the Kir6.2 subunits and SUR1 regulatory subunits of the K-ATP channel, respectively, have been implicated and account for 30% to 58% of cases of PNDM diagnosed in patients less than 6 months of age [6, 11]. Mutations in the K-ATP channels lead to decreased sensitivity to ATP inhibition; consequently, the channels remain open in the presence of glucose, thereby reducing insulin secretion . SUs close K-ATP channels by an ATP-independent route thereby causing insulin secretion. Studies have shown that many patients with diabetes caused by KCNJ11 or ABCC8 mutations can successfully switch from treatment with insulin to oral SU therapy . The dose of SU therapy that is required to manage glycemia in patients with NDM, particularly to achieve insulin independence, is often higher than the maximum recommended dose for the treatment of type 2 diabetes mellitus , typically needing around 0.5 mg/kg/day of glibenclamide [11, 16]. In our case, glimepiride was chosen instead of glibenclamide (glyburide) because of the ever-evolving literature reporting a lower risk of hypoglycemia  and lower risk of all-cause and cardiovascular-related mortality with the other readily available SUs compared to glibenclamide [18, 19].
A report by Thurber et al.  found that, in patients with NDM, earlier age at initiation of SU treatment was associated with an improved response to SU therapy. This led the authors to appropriately hypothesize that perhaps the declining sensitivity to SU therapy observed with more advanced age may be due to the loss of β-cell mass over time in those treated with insulin therapy, thereby highlighting the importance of early recognition and initiation of SU therapy.
In our patient, we were able to demonstrate a rise in C-peptide as the SU dosage was increased. While it is certainly possible that the original C-peptide may have been undetectable because the patient did not follow directions (drink orange juice prior to laboratory assessment to ensure BG is over 200 mg/dL) the observed gradual rise in C-peptide, in the setting of hyperglycemia, as the SU dose was increased, demonstrates a slow increase in endogenous insulin secretion in response to the therapy. The patient did follow the directions to raise serum glucose >200 mg/dL at the time of subsequent C-peptide measures, as demonstrated in Table 1.
While the lack of genetic testing is a significant limitation of our report, this limitation does not take away from the main point of this report, that being the importance of performing a very thorough personal and family history in patients who present with a prior diagnosis of diabetes, particularly T1DM very early in life, as a near-miraculous transformation in management may be possible in a minority of patients, as was the case in our patient, even if genetic testing is not available/feasible. Other means to obtain genetic testing on this patient are actively being pursued. Genetic testing for some conditions is available free of charge on a research basis in certain academic institutions in patients diagnosed with diabetes before 6 months of age (e.g., [21–23]) .
To the best of our knowledge, we are the first to report the effective and safe use of SGLT2 inhibitors in a patient with NDM. While the HbA1c did not appear to improve significantly after the addition of dapagliflozin, the therapy did help to lower postprandial glycemic excursions, not adequately addressed by the SU therapy, and helped to reduce the frequency at which the patient took a correction dose of bolus insulin, or a dose of bolus insulin to assist with glycemic control when he consumed higher carbohydrate containing meals.