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.