Three months' administration of the fatty acid-bile acid conjugate Aramchol is safe, tolerable, and significantly reduces liver fat content in patients with NAFLD. The reduction in liver fat content occurred in a dose-dependent manner and was associated with a trend of metabolic improvements, indicating that Aramchol might be used for the treatment of fatty liver disease. ClinicalTrials.gov number: NCT01094158.

This study demonstrates that ghrelin levels respond in a different manner to glucose, lipid and protein loads, and are subject to modulation according to gender, obesity and insulin sensitivity.

OBJECTIVE To assess treatment satisfaction and the effectiveness of a flash glucose monitoring (FGM) system in patients with type 2 diabetes using insulin. RESEARCH DESIGN AND METHODS A total of 101 patients with type 2 diabetes on multiple daily insulin injections (MDI) for at least 1 year were assigned randomly to the FGM intervention (n = 53) or the standard care (control) group (n = 48) and followed for 10 weeks. Both groups were instructed to adjust their insulin doses in face-to-face and telephone visits. Satisfaction with treatment, quality of life, comfort using FGM, HbA1c, and frequency of hypoglycemic events were evaluated. RESULTS The intervention group found treatment significantly more flexible (P = 0.019) and would recommend it to their counterparts (P = 0.023). Satisfaction using the FGM system was high. The changes in HbA1c were –0.82% (9 mmol/mol) vs. –0.33% (3.6 mmol/mol) in the intervention and control group, respectively (P = 0.005); in nonprespecified post hoc analysis, 68.6% of the patients in the intervention group had their HbA1c reduced by ≥0.5% (5.5 mmol/mol) compared with 30.2% in the control group (P < 0.001), and 39.2% had their HbA1c reduced by ≥1.0% (10.9 mmol/mol) vs. 18.6% in the control group (P = 0.0023) without an increased frequency of hypoglycemia. CONCLUSIONS FGM tends to improve treatment satisfaction and may lead to amelioration of glycemic control in patients with type 2 diabetes on MDI without increasing the frequency of hypoglycemia.

Objective: It is still uncertain whether mild primary hyperparathyroidism (PHPT) carries the same risk for increased cardiovascular (CV) morbidity as the more severe symptomatic form. In recent years, the even more subtle normocalcemic (NC) variant is being increasingly recognized. We sought to compare the prevalence of CV risk factors in patients with NC-and hypercalcemic (HC)-PHPT, and to examine whether they differ on a battery of non-invasive vascular parameters. Design/subjects/methods: A retrospective study of two cohorts of patients with PHPT in a referral center: 32 subjects with NC-PHPT and 81 subjects with HC-PHPT, compared for the presence of clinical and biochemical risk factors, and CV morbidity. Non-invasive parameters of arterial stiffness (augmentation index; pulse wave velocity; and vascular compliance indices, C1 and C2) were extracted from the data of gender-and age-matched subsets of these patients, and were related to those of a group of matched control subjects. Results: Despite a similar prevalence of hypertension (w62%), hyperlipidemia (w30%), and impaired glucose metabolism in both PHPT groups, CV or cerebrovascular disease was more common in the HC-PHPT group (24.7 vs 3.1%, PZ0.007). Arterial stiffness parameters did not differ in the three groups, and were unrelated to serum calcium or parathyroid hormone concentration. Conclusions: NC-PHPT and HC-PHPT subjects exhibit similar high rates of traditional CV risk factors, and have comparable indices of arterial stiffness. The lower clinical CV morbidity observed with NC-PHPT remains unexplained, and requires confirmation. Until then, the CV risk associated with NC-PHPT should not be underestimated. 162 925-933 European Journal of Endocrinology

Objective: To assess arterial stiffness in a cohort of hypogonadal males and to investigate the effect of testosterone replacement therapy on arterial properties in this specific group. Design: Eighteen male patients with untreated acquired hypogonadism due to either adult-onset idiopathic hypogonadotropic hypogonadism (nZ9) or pituitary tumor (nZ9) and 12 age-, sex, and weight-matched eugonadal healthy controls were recruited for the study. Arterial properties, plasma glucose, lipid profile, total, and bioavailable testosterone (BT) levels were measured in fasting state. In the hypogonadal subjects, the effect of transdermal testosterone replacement therapy on arterial properties was studied by repeat noninvasive measurements at baseline, as well as 48 h and 90 days following the initiation of treatment. Methods: Arterial stiffness was evaluated using applanation tonometry and pulse wave analysis by three different standard devices that assess various measures of arterial stiffness: pulse wave velocity (PWV), augmentation index (AIx), and large/small artery compliance (C1 and C2). Results: Age-and blood pressure-adjusted PWV was significantly higher in hypogonadal men (8.90G 2.29 vs 6.78G1.16 m/s in the control group; PZ0.025). Testosterone therapy increased BT level from 2.01G1.04 to 4.68G2.43 and 7.83G6.2 nmol/l after 48 h and 3 months respectively (PZ0.001). PWV decreased from 8.9G2.29 to 8.24G1.39 and 8.25G1.82 m/s after 48 h and 3 months of treatment respectively (PZ0.03). Conclusions: Male hypogonadism is associated with increased PWV, which is rapidly but incompletely ameliorated by normalization of circulating testosterone levels.

This study was designed to improve blood glucose level predictability and future hypoglycemic and hyperglycemic event alerts through a novel patient‐specific supervised‐machine‐learning (SML) analysis of glucose level based on a continuous‐glucose‐monitoring system (CGM) that needs no human intervention, and minimises false‐positive alerts. The CGM data over 7 to 50 non‐consecutive days from 11 type‐1 diabetic patients aged 18 to 39 with a mean HbA1C of 7.5% ± 1.2% were analysed using four SML models. The algorithm was constructed to choose the best‐fit model for each patient. Several statistical parameters were calculated to aggregate the magnitudes of the prediction errors. The personalised solutions provided by the algorithm were effective in predicting glucose levels 30 minutes after the last measurement. The average root‐mean‐square‐error was 20.48 mg/dL and the average absolute‐mean‐error was 15.36 mg/dL when the best‐fit model was selected for each patient. Using the best‐fit‐model, the true‐positive‐hypoglycemia‐prediction‐rate was 64%, whereas the false‐positive‐ rate was 4.0%, and the false‐negative‐rate was 0.015%. Similar results were found even when only CGM samples below 70 were considered. The true‐positive‐hyperglycemia‐prediction‐rate was 61%. State‐of‐the‐art SML tools are effective in predicting the glucose level values of patients with type‐1diabetes and notifying these patients of future hypoglycemic and hyperglycemic events, thus improving glycemic control. The algorithm can be used to improve the calculation of the basal insulin rate and bolus insulin, and suitable for a closed loop “artificial pancreas” system. The algorithm provides a personalised medical solution that can successfully identify the best‐fit method for each patient.

Patients with acromegaly have significantly impaired endothelial function as assessed by FMD, but other tested vascular parameters were similar to a control group that was adequately matched for cardiovascular risk factors.

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