Impact of gut hormone FGF-19 on type-2 diabetes and mitochondrial recovery in a prospective study of obese diabetic women undergoing bariatric surgery

The ileal-derived hormone, fibroblast growth factor 19 (FGF-19), may promote weight loss and facilitate type-2 diabetes mellitus remission in bariatric surgical patients. We investigated the effect of different bariatric procedures on circulating FGF-19 levels and the resulting impact on mitochondrial health in white adipose tissue (AT).Obese and type-2 diabetic women (n = 39, BMI > 35 kg/m2) undergoing either biliopancreatic diversion (BPD), laparoscopic greater curvature plication (LGCP), or laparoscopic adjustable gastric banding (LAGB) participated in this ethics approved study. Anthropometry, biochemical, clinical data, serum, and AT biopsies were collected before and 6 months after surgery. Mitochondrial gene expression in adipose biopsies and serum FGF-19 levels were then assessed.All surgeries led to metabolic improvements with BPD producing the greatest benefits on weight loss (↓30%), HbA1c (↓28%), and cholesterol (↓25%) reduction, whilst LGCP resulted in similar HbA1c improvements (adjusted for BMI). Circulating FGF-19 increased in both BPD and LGCP (χ2(2) = 8.088; P = 0.018), whilst, in LAGB, FGF-19 serum levels decreased (P = 0.028). Interestingly, circulating FGF-19 was inversely correlated with mitochondrial number in AT across all surgeries (n = 39). In contrast to LGCP and LAGB, mitochondrial number in BPD patients corresponded directly with changes in 12 of 14 mitochondrial genes assayed (P  LGCP > LAGB), and highlighting mitochondria in AT as a potential target of FGF-19 during diabetes remission

Insulin sensitivity and secretion in obese Type 2 diabetic women after various bariatric operations

Objective: To compare the effects of biliopancreatic diversion (BPD) and laparoscopic gastric banding (LAGB) on insulin sensitivity and secretion with the effects of laparoscopic gastric plication (P). Methods: A total of 52 obese women (age 30-66 years) suffering from type 2 diabetes mellitus (T2DM) were prospectively recruited into three study groups: 16 BPD; 16 LAGB, and 20 P. Euglycemic clamps and mixed meal tolerance tests were performed before, at 1 month and at 6 months after bariatric surgery. Beta cell function derived from the meal test parameters was evaluated using mathematical modeling. Results: Glucose disposal per kilogram of fat free mass (a marker of peripheral insulin sensitivity) increased significantly in all groups, especially after 1 month. Basal insulin secretion decreased significantly after all three types of operations, with the most marked decrease after BPD compared with P and LAGB. Total insulin secretion decreased significantly only following the BPD. Beta cell glucose sensitivity did not change significantly post-surgery in any of the study groups. Conclusion: We documented similar improvement in insulin sensitivity in obese T2DM women after all three study operations during the 6-month postoperative follow-up. Notably, only BPD led to decreased demand on beta cells (decreased integrated insulin secretion), but without increasing the beta cell glucose sensitivity

Thyroid Cancer Detection in a Routine Clinical Setting: Performance of ACR TI-RADS, FNAC, and Molecular Testing in Prospective Cohort Study

The aim of our study was to address the potential for improvements in thyroid cancer detection in routine clinical settings using a clinical examination, the American College of Radiology Thyroid Imaging Reporting and Database System (ACR TI-RADS), and fine-needle aspiration cytology (FNAC) concurrently with molecular diagnostics. A prospective cohort study was performed on 178 patients. DNA from FNA samples was used for next-generation sequencing to identify mutations in the genes BRAF, HRAS, KRAS, NRAS, and TERT. RNA was used for real-time PCR to detect fusion genes. The strongest relevant positive predictors for malignancy were the presence of genetic mutations (p p p < 0.01). Overall, FNAC, ACR TI-RADS, and genetic testing reached a sensitivity of up to 96.1% and a specificity of 88.3%, with a diagnostic odds ratio (DOR) of 183.6. Sensitivity, specificity, and DOR decreased to 75.0%, 88.9%, and 24.0, respectively, for indeterminate (Bethesda III, IV) FNAC results. FNA molecular testing has substantial potential for thyroid malignancy detection and could lead to improvements in our approaches to patients. However, clinical examination, ACR TI-RADS, and FNAC remained relevant factors

Routine OGTT: A Robust Model Including Incretin Effect for Precise Identification of Insulin Sensitivity and Secretion in a Single Individual

<div><p>In order to provide a method for precise identification of insulin sensitivity from clinical Oral Glucose Tolerance Test (OGTT) observations, a relatively simple mathematical model (Simple Interdependent glucose/insulin MOdel SIMO) for the OGTT, which coherently incorporates commonly accepted physiological assumptions (incretin effect and saturating glucose-driven insulin secretion) has been developed. OGTT data from 78 patients in five different glucose tolerance groups were analyzed: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IFG+IGT, and Type 2 Diabetes Mellitus (T2DM). A comparison with the 2011 Salinari (COntinuos GI tract MOdel, COMO) and the 2002 Dalla Man (Dalla Man MOdel, DMMO) models was made with particular attention to insulin sensitivity indices IS_COMO, IS_DMMO and <i>k_xgi</i> (the insulin sensitivity index for SIMO). ANOVA on <i>k_xgi</i> values across groups resulted significant overall (P<0.001), and post-hoc comparisons highlighted the presence of three different groups: NGT (8.62×10⁻⁵±9.36×10⁻⁵ min⁻¹pM⁻¹), IFG (5.30×10⁻⁵±5.18×10⁻⁵) and combined IGT, IFG+IGT and T2DM (2.09×10⁻⁵±1.95×10⁻⁵, 2.38×10⁻⁵±2.28×10⁻⁵ and 2.38×10⁻⁵±2.09×10⁻⁵ respectively). No significance was obtained when comparing IS_COMO or IS_DMMO across groups. Moreover, <i>k_xgi</i> presented the lowest sample average coefficient of variation over the five groups (25.43%), with average CVs for IS_COMO and IS_DMMO of 70.32% and 57.75% respectively; <i>k_xgi</i> also presented the strongest correlations with all considered empirical measures of insulin sensitivity. While COMO and DMMO appear over-parameterized for fitting single-subject clinical OGTT data, SIMO provides a robust, precise, physiologically plausible estimate of insulin sensitivity, with which habitual empirical insulin sensitivity indices correlate well. The <i>k_xgi</i> index, reflecting insulin secretion dependency on glycemia, also significantly differentiates clinically diverse subject groups. The SIMO model may therefore be of value for the quantification of glucose homeostasis from clinical OGTT data.</p></div

Visual Predictive Check.

<p>Visual Predictive Check (VPC) for each of the 5 groups (panel A for NGT, IFG and IGT; panel B for IFG+IGT and T2DM). For each patient 200 simulations were performed with the model: the shaded area represents the 90% prediction interval, dashed lines represent the 25-th, 50-th and 75-th percentile. Observed data are reported as circles.</p

SIMO model parameter description.

<p>SIMO model parameter description.</p

Comparison between fitting with predicted and interpolated insulin concentrations.

<p>Observed glucose and insulin data (circles) for one NGT patient. The COMO fitted model (dotted line) is shown together with the SIMO model either when insulin is fitted (solid black line) or when insulin is interpolated (dashed line).</p

Empirical indices of glucose/insulin homeostasis by group.

<p>Empirical indices of glucose/insulin homeostasis by group.</p