Weight loss (WL) decreases regional depots of adipose tissue and improves insulin sensitivity, two parameters that correlate before WL. To examine the potential relation of WL-induced change in regional adiposity to improvement in insulin sensitivity, 32 obese sedentary women and men completed a 4-month WL program and had repeat determinations of body composition (dual-energy X-ray absorptiometry and computed tomography) and insulin sensitivity (euglycemic insulin infusion). There were 15 lean men and women who served as control subjects. VO2max was unaltered with WL (39.2 +/- 0.8 vs. 39.8 +/- 1.1 ml x fat-free mass [FFM](-1) x min(-1)). The WL intervention achieved significant decreases in weight (100.2 +/- 2.6 to 85.5 +/- 2.1 kg), BMI (34.3 +/- 0.6 to 29.3 +/- 0.6 kg/m2), total fat mass (FM) (36.9 +/- 1.5 to 26.1 +/- 1.3 kg), percent body fat (37.7 +/- 1.3 to 31.0 +/- 1.5%), and FFM (59.2 +/- 2.3 to 55.8 +/- 2.0 kg). Abdominal subcutaneous and visceral adipose tissue (SAT and VAT) were reduced (494 +/- 19 to 357 +/- 18 cm2 and 157 +/- 12 to 96 +/- 7 cm2, respectively). Cross-sectional area of low-density muscle (LDM) at the mid-thigh decreased from 67 +/- 5 to 55 +/- 4 cm2 after WL. Insulin sensitivity improved from 5.9 +/- 0.4 to 7.3 +/- 0.5 mg x FFM(-1) x min(-1) with WL. Rates of insulin-stimulated nonoxidative glucose disposal accounted for the majority of this improvement (3.00 +/- 0.3 to 4.3 +/- 0.4 mg x FFM(-1) x min(-1)). Serum leptin, triglycerides, cholesterol, and insulin all decreased after WL (P < 0.01). After WL, insulin sensitivity continued to correlate with generalized and regional adiposity but, with the exception of the percent decrease in VAT, the magnitude of improvement in insulin sensitivity was not predicted by the various changes in body composition. These interventional weight loss data underscore the potential importance of visceral adiposity in relation to insulin resistance and otherwise suggest that above a certain threshold of weight loss, improvement in insulin sensitivity does not bear a linear relationship to the magnitude of weight loss.
There are no registered veterinary drugs for treating insulin dysregulation and preventing insulin-associated laminitis in horses. Velagliflozin is a sodium-glucose co-transport 2 inhibitor that reduces renal glucose reabsorption, promotes glucosuria, and consequently, decreases blood glucose and insulin concentrations. This study aimed to determine if velagliflozin reduced hyperinsulinemia and prevented laminitis in insulin-dysregulated ponies fed a challenge diet high in non-structural carbohydrates (NSC). An oral glucose test (1 g dextrose/kg BW) was used to screen 75 ponies for insulin dysregulation, of which 49 ponies with the highest insulin concentrations were selected. These animals were assigned randomly to either a treated group (n = 12) that received velagliflozin (0.3 mg/kg BW, p.o., s.i.d.) throughout the study, or a control group (n = 37). All ponies were fed a maintenance diet of alfalfa hay for 3 weeks, before transferring to a challenge diet (12 g NSC/kg BW/d) for up to 18 d. Blood glucose and serum insulin concentrations were measured over 4 h after feeding, on d 2 of the diet. The maximum glucose concentration was 22% lower (P = 0.014) in treated animals, with a geometric mean (95% CI) of 9.4 (8.0–11.0) mM, versus 12.1 (10.7–13.7) mM in the controls. This was reflected by lower (45%) maximum insulin concentrations in the treated group (P = 0.017), of 149 (97–228) μIU/mL, versus 272 (207–356) μIU/mL for controls. The diet induced Obel grade 1 or 2 laminitis in 14 of the 37 controls (38%), whereas no velagliflozin-treated pony developed laminitis (P = 0.011). Velagliflozin was well-tolerated, with no hypoglycemia or any clinical signs of adverse effects. The main limitation of this study was the sample size. Velagliflozin shows promise as a safe and effective compound for treating insulin dysregulation and preventing laminitis by reducing the hyperinsulinemic response to dietary NSC.
This national analysis suggests that ACR are associated with improved survival for high-risk EHC patients, such as those with positive lymph nodes. Until randomized clinical trials are conducted, these may be the best available data to guide adjuvant therapy for resected EHC.
Background A previous six-week (wk) study demonstrated the potential of the sodium-glucose linked transport inhibitor velagliflozin as a novel treatment for equine insulin dysregulation. The present study examined the safety and efficacy of velagliflozin over 16 wk. of treatment, and over 4 wk. of withdrawal. Twenty-four insulin dysregulated ponies were selected, based on their hyper-responsiveness to a diet challenge meal containing 3.8 g non-structural carbohydrates (NSC)/kg bodyweight (BW). Ponies with serum insulin > 90 μIU/mL either 2 or 4 h after feeding were enrolled, and randomly allocated to receive either velagliflozin (0.3 mg/kg BW orally once daily, n = 12), or a placebo ( n = 10–12) for 16 wk. The subjects were fed 7.5 g NSC/kg BW/day to maintain a fat body condition. Safety was assessed through daily monitoring, veterinary examination, and the measurement of fasting blood glucose, biochemistry and haematology. Efficacy at reducing post-prandial hyperinsulinemia was assessed using a diet challenge every 8 wk. during treatment and 4 wk. after withdrawal. Results Velagliflozin was well accepted by all subjects and caused no adverse effects or hypoglycaemia. Post-prandial serum insulin (insulin C max ) did not change significantly in the control animals over the entire study period ( P = 0.101). In contrast, insulin C max (mean ± SE) concentrations fell over time in the velagliflozin-treated group from 205 ± 25 μIU/mL in wk. 0, to 119 ± 19 μIU/mL ( P = 0.015) and 117 ± 15 μIU/ml ( P = 0.029) after 8 and 16 wk. of treatment, respectively. Although the insulin C max in this group was not significantly lower than in controls at wk-8 ( P = 0.061), it was lower at wk-16 ( P = 0.003), and all 12 treated ponies were below the previously-determined risk threshold for laminitis at this time. After 4 wk. withdrawal, the insulin C max returned to 199 ± 36 μIU/mL in the treated group, with no rebound effect. Conclusions Velagliflozin appears to be a promising and safe treatment for equine insulin dysregulation, bringing post-prandial insulin concentrations below the laminitis risk threshold, albeit without normalising them. Electronic supplementary material The online version of this article (10.1186/s12917-019-1811-2) contains supplementary material, which is available to authorized users.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.