Context: Transsphenoidal surgery is considered first-line therapy for acromegaly; however, there is often a need for adjunctive therapy. Somatostatin analogs (SSA) have greatly improved the effectiveness of medical treatment, but one third of patients are resistant. Objective: The aim was to evaluate whether magnetic resonance imaging (MRI) signal could predict long-term response to SSA in patients with active acromegaly after neurosurgery. Patients and Methods: Sixty-two patients who were active acromegalic after surgery were included in this retrospective study. Remaining pituitary tumor was classified as hyper-, iso-, or hypointense by evaluating T2-weighted MRI signal. Treatment with SSA at maximal effective doses was prescribed and evaluated at 6 and 12 months by monitoring IGF-I, GH, and T2 MRI. Results: Complete response to SSA treatment (defined as normal IGF-I) at 6 months was observed in 30%, partial response (defined as IGF-I between 2 and 3 sd score) in 15%, and no response in 55% of patients. At 12 months, 28, 20, and 52% were observed, respectively. MRI signal was hypointense in 40%, hyperintense in 48%, and isointense in 12%. At 6 months, complete response to SSA was observed in 71% of cases having hypointense MRI signal and in 20% of hyperintense (P = 0.04). At 12 months, 62% of hypointense remained well controlled, whereas in the hyperintense group, good, partial, or no response results did not change from that observed at 6 months (P = 0.04). Conclusion: In active acromegalic patients after surgery, a hypointense T2-weighted MRI signal is associated with a better response to SSA treatment at 6 and 12 months.

The development of new therapies to induce self-tolerance has been an important medical health challenge in type 1 diabetes. An ideal immunotherapy should inhibit the autoimmune attack, avoid systemic side effects and allow β-cell regeneration. Based on the immunomodulatory effects of apoptosis, we hypothesized that apoptotic mimicry can help to restore tolerance lost in autoimmune diabetes. To generate a synthetic antigen-specific immunotherapy based on apoptosis features to specifically reestablish tolerance to β-cells in type 1 diabetes. A central event on the surface of apoptotic cells is the exposure of phosphatidylserine, which provides the main signal for efferocytosis. Therefore, phosphatidylserine-liposomes loaded with insulin peptides were generated to simulate apoptotic cells recognition by antigen presenting cells. The effect of antigen-specific phosphatidylserine-liposomes in the reestablishment of peripheral tolerance was assessed in NOD mice, the spontaneous model of autoimmune diabetes. MHC class II-peptide tetramers were used to analyze the T cell specific response after treatment with phosphatidylserine-liposomes loaded with peptides. We have shown that phosphatidylserine-liposomes loaded with insulin peptides induce tolerogenic dendritic cells and impair autoreactive T cell proliferation. When administered to NOD mice, liposome signal was detected in the pancreas and draining lymph nodes. This immunotherapy arrests the autoimmune aggression, reduces the severity of insulitis and prevents type 1 diabetes by apoptotic mimicry. MHC class II tetramer analysis showed that peptide-loaded phosphatidylserine-liposomes expand antigen-specific CD4⁺ T cells in vivo. The administration of phosphatidylserine-free liposomes emphasizes the importance of phosphatidylserine in the modulation of antigen-specific CD4⁺ T cell expansion. We conclude that this innovative immunotherapy based on the use of liposomes constitutes a promising strategy for autoimmune diseases.

The study of endogenous insulin secretion may provide relevant insight into the comparison of the natural history of adult onset latent autoimmune diabetes (LADA) with types 1 and 2 diabetes mellitus. The aim of this study was to compare the results of the C-peptide response to mixed-meal stimulation in LADA patients with different disease durations and subjects with type 2 and adult-onset type 1 diabetes. Stimulated C-peptide secretion was assessed using the mixed-meal tolerance test in patients with LADA (n = 32), type 1 diabetes mellitus (n = 33) and type 2 diabetes mellitus (n = 30). All patients were 30 to 70 years old at disease onset. The duration of diabetes in all groups ranged from 6 months to 10 years. The recruitment strategy was predefined to include at least 10 subjects in the following 3 disease onset categories for each group: 6 to 18 months, 19 months to 5 years and 5 to 10 years. At all time-points of the mixed-meal tolerance test, patients with LADA had a lower stimulated C-peptide response than the type 2 diabetes group and a higher response than the type 1 diabetes group. The same results were found when the peak or area under the C-peptide curve was measured. When the results were stratified by time since disease onset, a similar pattern of residual insulin secretory capacity was observed. The present study shows that the magnitude of stimulated insulin secretion in LADA is intermediate between that of type 1 and type 2 diabetes mellitus.