ESPE Abstracts

Background: Recent studies in multiple models of type 1 diabetes mellitus (T1DM) have demonstrated the role of mitochondrial abnormalities in the pathogenesis of this disease and its complications. Humanin is a potent cyto-protective and ‘metaboloprotective’ molecule in vitro and in vivo, including the protection of β cells from apoptosis, improvements in insulin secretion and action, and both prevention and treatment of diabetes in the NOD mouse model, by ameliorating various aspects of the pathogenesis of the disease.

Objective and hypotheses: We hypothesized that humanin levels are decreased in patients with T1DM and may be related to duration or severity of disease and evaluated humanin levels in T1DM and matched controls as a function of HbA1c and microalbuminuria.

Method: Subjects with T1DM and age- and sex-matched controls were recruited from the diabetes clinic of the IDIMI-HCSBA, Santiago de Chile. A complete physical exam including Tanner staging exam was performed. Early morning a blood sample was obtained for determination of HbA1c and humanin levels (in house ELISA, previously published).

Results: T1DM (n=154) and controls (n=76), age 3–19 years old (T1DM mean 12.9, controls mean 10.8), males 57% in DM1 vs 47% in controls. New onset (<2 years) of diabetes in 32.4% of T1D (n=50). T1DM and controls were divided according to Tanner stages (1–5). Humanin levels are lower in T1DM compared to controls (974.6±498.3 in T1DM vs 1241.2±782.4 in controls, P=0.0019). This difference is observed only in girls (T1DM 1327.4±714.8 vs controls 1997.4±481, P<0.01). Humanin levels are lower in Tanner I and III inT1DM compared with controls (P<0.05). Humanin levels increased throughout puberty in controls children, but not in T1D adolescents. No association was observed between duration of T1D, albuminuria, or HbA1c.

Conclusion: T1DM patients exhibit lower humanin levels, an observation that is especially pronounced in females and early Tanner stages. There is no correlation between the degree of metabolic control or disease duration and humanin levels. Future studies will address the impact of humanin levels on pathophysiology and metabolic control of diabetes.