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Background: Atypical clinical symptoms of juvenile hereditary hemochromatosis (JHH) often leads to misdiagnosis and underdiagnosis bringing ominous outcomes, even death., Methods: The whole exome was sequenced and interpreted. A literature review assisted to analyze and verify the phenotype-genotype relationships. We revealed the entire process of diagnosis, treatments, and outcome of two diabetic onset of JHH families to provide new insights for genotype-phenotype relation with novel compound heterozygous mutations in the hepcidin antimicrobial peptide (HAMP, OMIM: 606464)., Results: Two probands were diagnosed and treated as type 1 diabetes initially because of specific symptoms and positive islet autoantibodies. Poor control of hyperglycemia and progressive symptoms occurred. Sequencing informed that the compound heterozygous and homozygous mutations c.166C>G and c.223C>T in HAMP caused type 1 diabetic-onset JHH. The two patients accessed irregular phlebotomy treatments, and then, experienced poor prognosis. We summarized the process of overall clinical management of reported 26 cases comparing to our novel atypical diabetic onsets Juvenile Hereditary Hemochromatosis cases., Conclusion: It was first reported that positive pancreatic islet autoantibodies diabetes onset of JHH resulted from loss-of-function mutations of HAMP, of which the atypical JHH should be differentially diagnosed with type 1 diabetes at the onset. Early administration of phlebotomy and vital organs protection and surveillance might be important for the treatment of atypical JHH., (© 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Objective: To investigate insulin resistance in type 1 diabetes (T1DM) with euglycemic-hyperinsulinemic clamp., Methods: Eight cases of newly diagnosed T1DM and 8 cases of newly diagnosed type 2 diabetes (T2DM) were selected. Their insulin sensitivity index (ISI) was evaluated with euglycemic-hyperinsulinemic clamp after 2 week insulin intensive treatment and compared with that of 10 healthy volunteers (normal control group, NC group)., Results: Age, BMI, fasting insulin (FIns), fasting C-peptide in the T1DM group were significantly lower than those in the NC group, while waist-to-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, HDL-C were not significantly different between the T1DM and NC groups. Age, BMI, WHR, FIns, fasting C-peptide, SBP, TC, TG in the T1DM group were significantly lower than those in the T2DM group. The ISI of the NC, T1DM and T2DM groups were 12. 83 +/- 1.09, 9.95 +/-0.50, 3.80 +/- 0.20, respectively. There was significant difference among the three groups (P < 0.05)., Conclusion: The ISI in T1DM was significantly lower than that in NC group, but higher than that in T2DM.