Onset of type 2 diabetes in a toddler ?

Objectives: To report a case of a normal weight Italian girl who
showed temporary diabetes in two occasions, neonatally and at the
age of two year, and successive later development of overt diabetes
of uncertain classification.
Case report: FP is the eldest daughter of a caucasian couple, born
at the end of normal pregnancy by natural delivery with a birth
weight adequate to gestational age. In the first week of live she
showed temporary hyperglycemia, glycosuria and ketonuria. Insulin
and C-peptide in serum resulted respectively 0.5 mcU/mL and < 0.3
mcg/ml. Blood glucose (BG) monitoring was started showing mainly
normoglycemia with occasional high-borderline BG values with
HbA1c in the normal range. KCNJ11 and MODY2 were excluded by
genetic test. At 2 years of life hyperglycemia, ketonuria and HbA1
of 6.9% were documented and insulin treatment was started, and
discontinued after two weeks, for complete spontaneous remission.
T1DM related antibodies (ICA, GADA, IAA, IA2, ZNT8) and HLA D3
and D4 antigens were all negative and an IVGTT showed a FPIR of
47 mcU/mL (1st centile). NGS identified two variant of the HNF1-α
gene: 79A > C (pIle27Leu) reported as associated with insulin resistance,
and G1720A > G (pSer574Gly) associated with increased risk
of type 2 diabetes. At the age of 8 year the girl developed over diabetes
(HbA1 of 8.4%, CGM reported a BG value (mean SD) of
152 40 mg/dl and a maximun glycemic value of 311 mg/dl). On
the basis of the genetic results we started treatment with metformin
(initial dose: 250 mg OD, final dose: 500 mg BID) with a progressive
reduction of both fasting and postprandial glycemia
(mean sd BG by CGM 125.5 32.1 mg/dl).
Conclusions: The interest of this case arises from the difficulty, even
in the presence of overt diabetes, to find a correct diagnostic and
therapeutic orientation. The good therapeutic response to metformin
and genetic mutations suggest the hypothesis of an exceptionally
early onset of type 2 diabetes.