Patients with active acromegaly (ACRO) exhibit low hepatocellular lipids (HCL), despite pronounced insulin resistance (IR). This contrasts the strong association of IR with nonalcoholic fatty liver disease in the general population. Since low HCL levels in ACRO might be caused by changes in oxidative substrate metabolism, we investigated mitochondrial activity and plasma metabolomics/lipidomics in active ACRO. Fifteen subjects with ACRO and seventeen healthy controls, matched for age, BMI, sex, and body composition, underwent ³¹ P/ ¹ H-7-T MR spectroscopy of the liver and skeletal muscle as well as plasma metabolomic profiling and an oral glucose tolerance test. Subjects with ACRO showed significantly lower HCL levels, but the ATP synthesis rate was significantly increased compared with that in controls. Furthermore, a decreased ratio of unsaturated-to-saturated intrahepatocellular fatty acids was found in subjects with ACRO. Within assessed plasma lipids, lipidomics, and metabolomics, decreased carnitine species also indicated increased mitochondrial activity. We therefore concluded that excess of growth hormone (GH) in humans counteracts HCL accumulation by increased hepatic ATP synthesis. This was accompanied by a decreased ratio of unsaturated-to-saturated lipids in hepatocytes and by a metabolomic profile, reflecting the increase in mitochondrial activity. Thus, these findings help to better understanding of GH-regulated antisteatotic pathways and provide a better insight into potentially novel therapeutic targets for treating NAFLD.

Glucose management indicator (GMI) is frequently used as a substitute for HbA1c, especially when using telemedicine. Discordances between GMI and HbA1c were previously mostly reported in populations with type 1 diabetes (T1DM) using real-time CGM. Our aim was to investigate the accordance between GMI and HbA1c in patients with diabetes using intermittent scanning CGM (isCGM). In this retrospective cross-sectional study, patients with diabetes who used isCGM >70% of the time of the investigated time periods were included. GMI of four different time spans (between 14 and 30 days), covering a period of 3 months, reflected by the HbA1c, were investigated. The influence of clinical- and isCGM-derived parameters on the discordance was assessed. We included 278 patients (55% T1DM; 33% type 2 diabetes (T2DM)) with a mean HbA1c of 7.63%. The mean GMI of the four time periods was between 7.19% and 7.25%. On average, the absolute deviation between the four calculated GMIs and HbA1c ranged from 0.6% to 0.65%. The discordance was greater with increased BMI, a diagnosis of T2DM, and a greater difference between the most recent GMI and GMI assessed 8 to 10 weeks prior to HbA1c assessment. Our data shows that, especially in patients with increased BMI and T2DM, this difference is more pronounced and should therefore be considered when making therapeutic decisions.

Background Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of liver-related morbidity and mortality. While data on acromegaly, a state of chronic growth hormone (GH)/Insulin-like growth factor I(IGF-I) excess, suggest an inverse relationship with intrahepatic lipid content (IHL), less is known about the impact of the GH/IGF-I axis on IHL, lipid composition and phosphor metabolites in individuals without disorders of GH secretion. Methods We performed a cross-sectional study in 59 otherwise metabolically healthy individuals (30 females), of which 16 met the criteria of NAFLD with IHL of ≥5,6%. The GH/IGF-I axis was evaluated in fasting state and during an oral glucose tolerance test (OGTT). Insulin sensitivity was estimated by validated indices. IHL, lipid composition (unsaturation index:UI), and phosphate metabolites were analysed by using ¹H/³¹P magnetic resonance spectroscopy. Results In the overall cohort (40.6 ± 15years; BMI:24.5 ± 3 kg/m²; IGF-I-:68.0 ± 17%ULN), fasting GH (R = -0.31; p = 0.02), GH during OGTT (R = -0.51; p < 0.01) as well as IGF-I (R = -0.28; p = 0.03) inversely correlated with IHL. GH levels during OGTT were significantly lower in NAFLD compared to controls (47.7[22; 143]ng/ml/min vs.16.8[7; 32]ng/ml/min; p = 0.003). GH/IGF-I axis activity correlated with lipid composition, as well as with phosphor metabolites. In multiple regression analysis, the GH/IGF-I axis activity was a strong predictor for IHL and lipid composition independent from insulin sensitivity. Conclusion GH/IGF-I axis activity impacts hepatic lipid and phosphate metabolism in individuals without disorders in GH secretion. Lower GH-axis activity is associated with higher IHL and an unfavourable lipid composition, probably mediated by changes in hepatic energy metabolism.

Aims: Familial hypercholesterolaemia (FH) is a severely underdiagnosed, inherited disease, causing dyslipidaemia and premature atherosclerotic cardiovascular disease. In order to facilitate screening in a broad clinical spectrum, we aimed to analyse the current yield of routine genetic diagnostics for FH and to evaluate the performance of the Dutch Lipid Clinic Network Score (DLCNS) compared to a single value, the off-treatment LDL-cholesterol exceeding 190 mg/dL. Methods and results: We investigated all patients that underwent molecular genotyping routinely performed for FH over a 4-year period in two Austrian specialist lipid clinics. Variants reported in FH-causing genes including LDLR, APOB, PCSK9, LDLRAP, and APOE were collected and classified. For clinical classification, the DLCNS was calculated retrospectively and compared to the original scores documented in patient charts. Additionally, a literature review on comparisons of DLCNS to LDL-C was performed. Of 469 patients tested, 21.3% had a disease-causing variant. A median of 3 out of 8 (excluding genotyping results and LDL-C) DLCNS criteria were unavailable. DLCNS was documented in 48% of cases, with significant discrepancies compared to retrospective scoring (P < 0.001). DLCNS did not outperform off-treatment LDL-C alone (Δ = 0.006; P = 0.660), analogously to several reports identified in the literature. A single cut-off of 190 mg/dL LDL-C compared to DLCNS ≥ 6 showed excellent sensitivity (84.9% vs. 53.8%) and acceptable specificity (39.0% vs. 84.1%). Conclusion: Missing criteria and severe discrepancies observed between retrospective and on-site scoring by treating physicians were highly prevalent, confirming limited utility of DLCNS in clinical routine and warranting a single off-treatment LDL-C cut-off of 190 mg/dL for enhanced index-case identification.

Background: In severe obesity, hypogonadism in men and androgen excess in women are frequently observed. Sex hormones play an important role in body composition and glucose and lipid metabolism. However, whether pre-operative gonadal dysfunction impacts weight loss after bariatric surgery is not fully known. Methods: A total of 49 men and 104 women were included in a retrospective analysis. Anthropometric characteristics, glucose and lipid metabolism, and androgen concentrations were assessed pre-operatively and 17.9 ± 11 or 19.3 ± 12 months post-operatively in men and women. Men with (HYPO_male) and without (controls: CON_male) pre-operative hypogonadism, as well as women with (HYPER_female) and without (controls: CON_female) pre-operative hyperandrogenemia, were compared. Results: In men, pre-operative hypogonadism was present in 55% and linked to a higher body mass index (BMI): HYPO_male 50 ± 6 kg/m² vs. CON_male 44 ± 5 kg/m², p = 0.001. Bariatric surgery results in comparable changes in BMI in HYPO_male and CON_male − 16 ± 6 kg/m² vs. − 14 ± 5 kg/m², p = 0.30. Weight loss reversed hypogonadism in 93%. In women, androgen excess was present in 22%, independent of pre-operative BMI: CON_female 44 ± 7 kg/m² vs. HYPER_female 45 ± 7 kg/m², p = 0.57. Changes in BMI were comparable in HYPER_female and CON_female after bariatric surgery − 15 ± 6 kg/m² vs. − 15 ± 5 kg/m², p = 0.88. Hyperandrogenemia was reversed in 61%. Conclusions: Besides being frequently observed, hypogonadism in men and androgen excess in women have no impact on post-surgical improvements in body weight and glucose and lipid metabolism. Weight loss resulted in reversal of hypogonadism in almost all men and of hyperandrogenemia in the majority of women.

Purpose: Bariatric surgery reduces mortality in patients with severe obesity and is predominantly performed in women. Therefore, an analysis of sex-specific differences after bariatric surgery in a population-based dataset from Austria was performed. The focus was on deceased patients after bariatric surgery. Materials and Methods: The Austrian health insurance funds cover about 98% of the Austrian population. Medical health claims data of all Austrians who underwent bariatric surgery from 01/2010 to 12/2018 were analyzed. In total, 19,901 patients with 107,806 observed years postoperative were eligible for this analysis. Comorbidities based on International Classification of Diseases (ICD)-codes and drug intake documented by Anatomical Therapeutical Chemical (ATC)-codes were analyzed in patients deceased and grouped according to clinically relevant obesity-associated comorbidities: diabetes mellitus (DM), cardiovascular disease (CV), psychiatric disorder (PSY), and malignancy (M). Results: In total, 367 deaths were observed (1.8%) within the observation period from 01/2010 to 04/2020. The overall mortality rate was 0.34% per year of observation and significantly higher in men compared to women (0.64 vs. 0.24%; p < 0.001(Chi-squared)). Moreover, the 30-day mortality was 0.19% and sixfold higher in men compared to women (0.48 vs. 0.08%; p < 0.001). CV (82%) and PSY (55%) were the most common comorbidities in deceased patients with no sex-specific differences. Diabetes (38%) was more common in men (43 vs. 33%; p = 0.034), whereas malignant diseases (36%) were more frequent in women (30 vs. 41%; p = 0.025). Conclusion: After bariatric surgery, short-term mortality as well as long-term mortality was higher in men compared to women. In deceased patients, diabetes was more common in men, whereas malignant diseases were more common in women. Graphical