INS and hyperinsulinemic hypoglycemia, familial, 4: Insulin and IGF - 1 deficiency directly impair osteoblast function, which explains the generally reduced BMD observed in T1DM patients and underscores the importance of early (e.g., as recommended by International Society for Pediatric and Adolescent Diabetes, ISPAD in late adolescence) and regular BMD screening (following IOF guideline) in these patients.