Different glomerular filtration rate estimating formula for prescribing DOACs in oldest patients: appropriate dosage and bleeding risk. Post hoc analysis of a prospective cohort.

BACKGROUND: Direct oral anticoagulants (DOACs) pharmacokinetics depends on estimated glomerular filtration rate (eGFR), whose estimation is crucial for optimal risk/benefit balance. AIMS: To assess the concordance among different eGFR formulas and the potential impact on DOACs prescription appropriateness and bleeding risk in oldest hospitalized patients. METHODS: Post hoc analysis of a single-centre prospective cohort study. eGFR was calculated by creatinine-based (MDRD, CKD-EPICr, BIS1) and creatinine-cystatin-C-based (CKD-EPIComb and BIS2) formulas. Patients were stratified according to eGFR [severely depressed (SD) 15-29; moderately depressed (MD) 30-49; preserved/mildly depressed (PMD): ≥ 50 ml/min/1.73 m2]. Concordance between the different equations was assessed by Cohen's kappa coefficient. RESULTS: Among AF patients, 841 (59.2% women, mean age 85.9 ± 6.5 years) received DOACs. By CKD-EPICr equation, 135 patients were allocated in the SD, 255 in the MD and 451 in the PMD group. The concordance was excellent only between BIS 2 and CKD-EPIComb and MDRD and CKD-EPICr, while was worse (from good to poor) between the other formulas. Indeed, by adding cystatin-C almost over 1/3 of the patients were reallocated to a worse eGFR class. Bleeding prevalence increased by 2-3% in patients with discordant eGFR between formulas, reallocated to a worse chronic kidney disease (CKD) stage, although without reaching statistical significance. CKD-EPIComb resulted the best predictor of bleeding events (AUROC 0.71, p = 0.03). DISCUSSION: This study highlights the variability in CKD staging according to different eGFR formulas, potentially determining inappropriate DOACs dosing. Although the cystatin-C derived CKDEPIComb equation is the most accurate for stratifying patients, BIS1 may represent a reliable alternative.

Postprandial hypoglycaemia after Roux-en-Y gastric bypass in individuals with type 2 diabetes.

AIMS/HYPOTHESIS: Postprandial hypoglycaemia (PPHG) is a complication of Roux-en-Y gastric bypass (RYGB) surgery in normoglycaemic individuals. In type 2 diabetes, RYGB improves glucose metabolism, but whether this improvement is related to the later development of PPHG is not known. We investigated the presence and mechanisms of PPHG in individuals with type 2 diabetes undergoing RYGB. METHODS: A total of 35 obese individuals with type 2 diabetes underwent an OGTT before and 24 months after surgery. PPHG was defined as a plasma glucose level of ≤3.3 mmol/l when not taking glucose-lowering agents. Insulin sensitivity was assessed by oral glucose insulin sensitivity index and beta-cell function by mathematical modelling of the plasma glucose, insulin and C-peptide concentrations. RESULTS: After surgery, PPHG occurred in 11 of 35 individuals who underwent RYGB. Before surgery, BMI was lower, glycaemic control less good and time of glucose peak earlier in the PPHG vs No PPHG group, and the duration of diabetes was shorter with PPHG (all p ≤ 0.05). In addition, insulin sensitivity was greater in the PPHG than No PPHG group (p = 0.03). After surgery, BMI and fasting glucose and insulin levels decreased similarly in the two groups; insulin secretion during the first hour of the OGTT increased more in the PPHG than No PPHG group (p = 0.04). Beta-cell glucose sensitivity increased more in individuals with PPHG than those without (p = 0.002). Over the same time interval, the glucagon-like peptide 1 (GLP-1) response was lower in individuals with PPHG before surgery (p = 0.05), and increased more after surgery. At 2 h after glucose ingestion in the OGTT, postsurgery plasma glucagon level was significantly lower in the PPHG than No PPHG group. CONCLUSIONS/INTERPRETATION: In morbidly obese individuals with type 2 diabetes, spontaneous PPHG may occur after bariatric surgery independently of a remission of diabetes. Before surgery, individuals had a shorter duration and were more insulin sensitive. Two years after surgery, these individuals developed greater beta-cell glucose sensitivity, and showed greater insulin and GLP-1 release early in the OGTT.

γ-Glutamyltransferase Fractions in Obese Subjects with Type 2 Diabetes: Relation to Insulin Sensitivity and Effects of Bariatric Surgery.

BACKGROUND/OBJECTIVES: Gamma-glutamyltranspeptidase (GGT) levels are an independent risk marker for the development of type 2 diabetes (T2DM). We investigated the relationship between the newly identified serum GGT fractions and glucose metabolism in obese subjects before and after bariatric surgery. SUBJECTS/METHODS: Twenty-nine T2DM subjects, wait-listed for Roux-en-Y gastric bypass (RYGB; n = 21) or laparoscopic sleeve gastrectomy (LSG; n = 8), received a 5-h mixed meal test before (T0), 15 days (T15), and 1 year after surgery (T365). Insulin sensitivity was assessed by the OGIS index and ß-cell function by C-peptide analysis; fractional GGT (b-, s-, m-, and f-GGT) analysis was performed by gel-filtration chromatography. RESULTS: At T15, total GGT activity decreased by 40% after LSG (p = 0.007) but remained unchanged after RYGB. At T365, all patients showed a reduction in total GGT, in particular b-GGT (≥ 60%) and m-GGT (≥ 50%). In patients with biopsy-proven steatohepatitis (n = 10), total, b-, s-, and m-GGT fractions at T0 were significantly higher than in patients with low-grade steatosis (p = 0.016, 0.0003, and 0.005, respectively); at T365, there was a significant fall in total GGT as well as in each fraction in both groups. In a multiple regression model, b-GGT was the only fraction related to insulin sensitivity (p = 0.016; ß coeff. = - 14.0) independently of BMI, fasting glucose, and triglycerides. CONCLUSIONS: While GGT activity is generally associated with impaired glucose metabolism, fractional GGT analysis showed that the b-GGT fraction specifically and independently tracks with insulin resistance.

Sleeve Gastrectomy: Correlation of Long-Term Results with Remnant Morphology and Eating Disorders.

BACKGROUND: Remnant dimension is considered one of the crucial elements determining the success of sleeve gastrectomy (SG), and dilation of the gastric fundus is often believed to be the main cause of failure. OBJECTIVES: The main outcome of this study is to find correlations between remnant morphology in the immediate post-operative stage, its dilation in years, and the long-term results. The second purpose aims to correlate preoperative eating disorders, taste alteration, hunger perception, and early satiety with post-SG results. MATERIALS AND METHODS: Remnant morphology was evaluated, in the immediate post-operative stage and over the years (≥2 years), through X-ray of the oesophagus-stomach-duodenum calculating the surface in anteroposterior (AP) and right anterior oblique projection (RAO). Presurgery diagnosis of eating disorders and their evaluation through "Eating Disorder Inventory-3" (EDI3) during follow-up were performed. Change in taste perception, sense of appetite, and early satiety were evaluated. Patients were divided into two groups: "failed SGs (EWL<50%) and "efficient SGs" (EWL >50%). RESULTS: There were a total of 50 patients (37 F, 13 M), with mean age 52 years, preoperative weight 131 ± 21.8 kg, and BMI 47.4 ± 6.8 kg/m2. Post-operative remnant mean dimensions overlapped between the two groups. On a long-term basis, an increase of 57.2 and 48.4% was documented in the AP and RAO areas respectively. In "failed" SGs, dilation was significantly superior to "efficient" SGs (AP area 70.2 vs 46.1%; RAO area 59.3 vs 39%; body width 102% vs 41.7%). Preoperative eating disorders were more present in efficient SGs than in failed SGs with the exception of sweet eating. There were no significant changes to taste perception during follow-up. Fifty-two percent of efficient SGs vs 26% of failed SGs reported a persistent lack of sense of hunger; similarly, 92.5 vs 78% declared the persistence of a sense of early satiety. The two groups did not statistically differ as far as all the variables of the EDI3 are concerned. CONCLUSION: On a long-term basis, the remnant mean dilation is around 50% compared to the immediate post-operative stage but failed SGs showed larger remnant dilation than efficient SGs and, in percentage, the more dilated portion is the body of the stomach. As far as all the EDI3 variables obtained are concerned, the two groups did not statistically differ. Of all eating disorders, sweet eating seems to be weakly connected to SG failure.

Risk Factors for Spontaneously Self-Reported Postprandial Hypoglycemia After Bariatric Surgery.

CONTEXT: Postprandial hypoglycemia (PPHG) is a recognized complication of Roux-en-Y gastric bypass (RYGB) surgery. Data on PPHG after laparoscopic sleeve gastrectomy (LSG) are scant. OBJECTIVE: The objective of the study was to identify preoperative predictors of PPHG in subjects spontaneously self-reporting PPHG after RYGB or LSG. Patients, Setting, and Intervention: Nondiabetic patients spontaneously self-reporting symptoms/signs of PPHG (PPHG group, 21 RYGB and 11 LSG) were compared in a case-control design with subjects who never experienced spontaneous or oral glucose tolerance test (OGTT)-induced hypoglycemia over 24 months after surgery (No-PPHG group, 13 RYGB and 40 LSG). Paired pre- and postoperative 3-hour OGTTs were analyzed in all participants. MAIN OUTCOME MEASURES: Insulin sensitivity was assessed by the oral glucose insulin sensitivity index and ß-cell function by mathematical modeling of the C-peptide response to glucose. RESULTS: Before surgery, the body mass index was lower in PPHG than No-PPHG patients in the RYGB (P = .002) and trended similarly in the LSG group (P = .08). Fasting glycemia and the glucose-OGTT nadir were lower in the PPHG than the No-PPHG subjects in both surgery groups. Before surgery, insulin sensitivity was higher in PPHG than No-PPHG in the RYGB (393 ± 55 vs 325 ± 44 mL/min-1 · m-2, P = .001) and LSG groups (380 ± 48 vs 339 ± 60 mL/min-1 · m-2, P = .05) and improved to a similar extent in all groups after surgery. Before surgery, ß-cell glucose sensitivity was higher in PPHG than No-PPHG in both RYGB (118 ± 67 vs 65 ± 24 pmol/min-1 · m2 · mM-1) and LSG patients (114 ± 32 vs 86 ± 33) (both P = .02) and improved in all subjects after surgery. CONCLUSIONS: In subjects self-reporting PPHG after surgery, lower presurgery plasma glucose concentrations, higher insulin sensitivity, and better ß-cell glucose sensitivity are significant predictors of PPHG after both RYGB and LSG.

Subcutaneous adipose tissue blood flow and vasomotion in morbidly obese patients: long term effect of gastric bypass surgery.

Since recent findings suggest a relationship between reduction in adipose tissue blood flow (ATBF) and metabolic or vascular complications in obese patients (Ob-pts), increase in ATBF may be considered as a further goal in the treatment of obesity, besides fat mass reduction. Therefore, this preliminary study aimed at assess subcutaneous ATBF and vasomotion in morbidly obese patients and whether sustained weight loss induced by Roux-en-Y gastric bypass (RYGB) affects the same parameters. Using laser-Doppler flowmetry (LDF) and spectral Fourier analysis, subcutaneous ATBF was measured and subcutaneous ATBF oscillations (ATBF-O) were analyzed - within three frequency intervals related to vasomotion - in 16 Ob-pts, before and about one year after RYGB, and in 10 lean, healthy control subjects (CS). Before RYGB, Ob-Pts showed an important reduction in subcutaneous ATBF compared to CS (4.8 ± 2.7 PU vs 79.9 ± 34.5 PU, respectively; p < 0.0001), as well as higher normalized power spectral density (N-PSD) values of subcutaneous ATBF-O, - related to vasomotion. One year after RYGB, sustained weight loss in Ob-pts was associated with a slight but significant increase in subcutaneous ATBF (10.0 ± 6.6 PU, p < 0.05) and with almost complete normalization in N-PSD values of ATBF-O, related to vasomotion, compared to before RYGB. The slight subcutaneous ATBF increase, we observed in Ob-pts after sustained weight loss, moves toward a desirable goal. This finding suggests verifying whether an even more sustained weight loss in Ob-pts could determine a greater increase in subcutaneous ATBF and/or, more importantly, it could also determine a significant increase in visceral ATBF.