Search

Recent advances in pharmaceutical technology, aimed at overcoming poor drug permeation across the intestinal–epithelial membrane and the challenges posed by the acidic gastrointestinal environment, have led to the development of orally administered somatostatin receptor ligands (SRLs). This development represents a promising step forward in the management of acromegaly, offering an alternative to the limitations associated with injectable SRLs. Several key clinical findings have emerged in the past two years, notably including the results from the extension phase of the MPOWERED trial, which evaluated oral octreotide capsules (OOCs), and the placebo-controlled PATHFNDR-1 trial using paltusotine. This prompted us to conduct a systematic review of the literature focusing on the efficacy of oral SRLs in controlling acromegaly, based on biochemical response. Of the 136 reports identified through our search on Medline and ClinicalTrials.gov, twelve were included, encompassing data from five interventional trials. Both OOCs and paltusotine demonstrated the ability to maintain biochemical control in patients previously controlled with injectable SRLs. While long-term maintenance was confirmed for OOCs, no data are yet available for paltusotine. Several gaps remain, such as the need for head-to-head comparisons between OOCs and paltusotine, and clinical trials in patients who have not received prior injectable SRL treatment. [ABSTRACT FROM AUTHOR]

ApolipoproteinC1 (apoC1) is the main physiological inhibitor of the cholesterol ester transfer protein (CETP). Increased CETP activity is associated with macrovascular complications in patients with type 1 diabetes (T1D). ApoC1 has lost its ability to inhibit CETP in patients with T1D, and in vitro glycation of apoC1 increases CETP activity, suggesting that hyperglycemia could be a factor implicated in the loss of the inhibitory effect of apoC1 on CETP. Thus, we aimed to see whether improvement of glycemic control might restore apoC1 inhibitory effect on CETP. We studied 98 patients with T1D and HbA1c > 9% at baseline and 3 months after improvement of glycemic control by a medical intervention (insulin introduction or changes in multi-injection therapy or pump therapy introduction/therapeutic education for all patients). CETP activity was assessed by a radioactive method and plasma apoC1 levels were measured by ELISA. The different isoforms of apoC1 were determined by mass spectrometry. CETP activity was not significantly modified after improvement of glycemic control, despite a significant reduction in mean HbA1c (8.7 ± 1.7 vs. 10.8 ± 2, p < 0.0001). No association between plasma apoC1 and CETP activity was observed in patients with T1D at baseline, nor at 3 months, even in the subgroup of patients with optimal control (3-month HbA1c < 7%). We did not find any glycated form of apoC1 using mass spectrometry in people with T1D. Hyperglycemia in vivo does not seem to be a major factor implicated in the loss of apoC1 ability to inhibit CETP activity observed in T1D. Other factors, such as qualitative abnormalities of lipoproteins, could be involved. Our data emphasize the fact that hyperglycemia is not the only factor involved in lipid abnormalities and macrovascular complications in T1D. Clinical trial reg. no. NCT02816099 ClinicalTrials.gov. [ABSTRACT FROM AUTHOR]

(1) Background: high-density lipoproteins (HDLs) exhibit antioxidant and anti-inflammatory properties that play an important role in preventing the development of atherosclerotic lesions and possibly also diabetes. In turn, both type 1 diabetes (T1D) and type 2 diabetes (T2D) are susceptible to having deleterious effects on these HDL functions. The objectives of the present review are to expound upon the antioxidant and anti-inflammatory functions of HDLs in both diabetes in the setting of atherosclerotic cardiovascular diseases and discuss the contributions of these HDL functions to the onset of diabetes. (2) Methods: this narrative review is based on the literature available from the PubMed database. (3) Results: several antioxidant functions of HDLs, such as paraoxonase-1 activity, are compromised in T2D, thereby facilitating the pro-atherogenic effects of oxidized low-density lipoproteins. In addition, HDLs exhibit diminished ability to inhibit pro-inflammatory pathways in the vessels of individuals with T2D. Although the literature is less extensive, recent evidence suggests defective antiatherogenic properties of HDL particles in T1D. Lastly, substantial evidence indicates that HDLs play a role in the onset of diabetes by modulating glucose metabolism. (4) Conclusions and perspectives: impaired HDL antioxidant and anti-inflammatory functions present intriguing targets for mitigating cardiovascular risk in individuals with diabetes. Further investigations are needed to clarify the influence of glycaemic control and nephropathy on HDL functionality in patients with T1D. Furthermore, exploring the effects on HDL functionality of novel antidiabetic drugs used in the management of T2D may provide intriguing insights for future research. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, metabolic syndrome, and type 2 diabetes. NAFLD is also seen in patients with endocrinopathies. However, the relationship between endocrine diseases and the development of NAFLD is not well known. In this study, we set out to determine whether liver fat content (LFC) was associated with IGF1 levels in people with pituitary diseases (PD). Eightynine patients with pituitary diseases and 74 healthy controls were included in this study. LFC was measured using MRI. Hepatic steatosis was defined as LFC > 5.5 %. Patients with PD were older, and had a higher BMI than healthy controls. LFC was significantly higher in people with PD than in controls (6.5 % vs. 3.2 %; p < 0.001). LFC was negatively associated with the IGF1 level. The prevalence of steatosis was higher in PD patients than in controls (36.3 % vs. 14.8 %; p = 0.002). In multivariate analysis, which included patients and controls, the predictive variables for steatosis were age, BMI and IGF1 levels, whereas the presence of pituitary diseases and gender were not associated with steatosis. Our data showed that LFC was strongly associated with IGF1 levels. These results suggest that steatosis associated with PD is probably a consequence of a low IGF1 level in these patients. [ABSTRACT FROM AUTHOR]