Glucose metabolism, gut-brain hormones, and acromegaly treatment: an explorative single centre descriptive analysis.

PURPOSE: Active acromegaly is associated with impaired glucose metabolism, which improves upon treatment. Treatment options include surgery, medical therapy with somatostatin analogues (SSA) and Pegvisomant (PEG), and irradiation. The objective of the study was to describe the differential effect of various treatment regimens on the secretion of glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) in patients with acromegaly. METHODS: 23 surgically treated, non-diabetic patients with acromegaly and 12 healthy controls underwent an oral glucose tolerance test (OGTT) and subsequently isoglycaemic intravenous glucose infusion on a separate day. Baseline hormone concentrations, time-to-peak and area under the curve (AUC) on the OGTT-day and incretin effect were compared according to treatment regimens. RESULTS: The patients treated with SSA (N = 15) had impaired GIP-response (AUC, P = 0.001), and numerical impairment of all other hormone responses (P > 0.3). Patients co-treated with PEG (SSA + PEG, N = 4) had increased secretion of insulin and glucagon compared to patients only treated with SSA (SSA ÷ PEG, N = 11) (insulinAUC mean ± SEM, SSA + PEG 49 ± 8.3 nmol/l*min vs SSA ÷ PEG 25 ± 3.4, P = 0.007; glucagonAUC, SSA + PEG 823 ± 194 pmol/l*min vs SSA ÷ PEG 332 ± 69, P = 0.009). GIP secretion remained significantly impaired, whereas GLP-1 secretion was numerically increased with PEG (SSA + PEG 3088 ± 366 pmol/l*min vs SSA ÷ PEG 2401 ± 239, P = 0.3). No difference was found in patients treated with/without radiotherapy nor substituted or not with hydrocortisone. CONCLUSION: SSA impaired the insulin, glucagon, and incretin hormone secretions. Co-treatment with PEG seemed to counteract the somatostatinergic inhibition of the glucagon and insulin response to OGTT. We speculate that PEG may exert its action through GH-receptors on pancreatic δ-cells. Clinical trial registration NCT02005978.

One-year mortality increases four-fold in frail patients undergoing cardiac surgery.

OBJECTIVES: An increased focus on biological age, 'frailty', is important in an ageing population including those undergoing cardiac surgery. None of the existing surgery risk scores European System for Cardiac Operative Risk Evaluation II or Society of Thoracic Surgeons score incorporates frailty. Therefore, there is a need for an additional risk score model including frailty and not simply the chronological age. The aim of this study was to evaluate the impact of frailty assessment on 1-year mortality and morbidity for patients undergoing cardiac surgery. METHODS: A total of 604 patients aged ≥65 years undergoing non-acute cardiac surgery were included in this single-centre prospective observational study. We compared 1-year mortality and morbidity in frail versus non-frail patients. The Comprehensive Assessment of Frailty (CAF) score was used: This is a score of 1-35 determined via minor physical tests. A CAF score ≥11 indicates frailty. RESULTS: The median age was 73 years and 79% were men. Twenty-five percent were deemed frail. Frail patients had four-fold, odds ratios 4.63, 95% confidence interval (CI) 2.21-9.69; P < 0.001 increased 1-year mortality and increased risk of postoperative complications, i.e. surgical wound infections and prolonged hospital length of stay. A univariable Cox proportional hazards regression showed that an increased CAF score was a risk factor of mortality at any time after undergoing cardiac surgery (hazards ratios 1.11, 95% CI 1.07-1.14; P < 0.001). CONCLUSIONS: CAF score identified frail patients undergoing cardiac surgery and was a good predictor of 1-year mortality. CLINICAL TRIAL REGISTRATION NUMBER: NCT02992587.

Comprehensive assessment of frailty score supplements the existing cardiac surgical risk scores.

OBJECTIVES: The commonly used cardiac surgery risk scores, European System for Cardiac Operative Risk Evaluation II and Society of Thoracic Surgeons score, are inaccurate in predicting mortality in the ageing patient population and do not include the biological age. This requests a need for a new risk score incorporating frailty. The aim of this study was to compare the prediction of mortality and the additive effect of comprehensive assessment of frailty score and the shortened version, frailty predicts death one year after elective cardiac surgery test on the existing risk scores. METHODS: Six hundred four patients undergoing cardiac surgery and aged ≥65 years were included in this prospective observational study. These frailty scores are based on minor physical tests. We compared these frailty score predictions of mortality and their added value to the existing risk scores evaluated by concordance-statistics (C-statistics), integrated discrimination improvement and net reclassification improvement. RESULTS: The median age was 73 years (21% female). C-statistics showed that comprehensive assessment of frailty score with a value of 0.69, frailty predicts death one year after elective cardiac surgery test 0.68, Society of Thoracic Surgeons score 0.70 and European System for Cardiac Operative Risk Evaluation 0.64. Frailty assessment, added to the existing risk scores, significantly improved integrated discrimination improvement up to 0.05, and net reclassification improvement up to 0.04. Frailty assessment also increased the C-statistics, but this did not reach statistical significance. CONCLUSIONS: Frailty scores are as good as the existing risk scores for the prediction of mortality in patients undergoing cardiac surgery. Added to the existing scores, frailty assessment improves the C-statistics and integrated discrimination improvement over time. CLINICAL TRIALS REGISTRATION NUMBER: NCT02992587.