Dataset Information

The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies.

ABSTRACT: 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) ?IU/mL, versus 272 (207-356) ?IU/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.

SUBMITTER: Meier A

PROVIDER: S-EPMC6136744 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies.

Meier Alexandra A Reiche Dania D de Laat Melody M Pollitt Christopher C Walsh Donald D Sillence Martin M

PloS one 20180913 9

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 carbohy ...[more]

PMID: 30212530

Similar Datasets

Project description:BackgroundQuantifying risk factors for laminitis development requires improvement.ObjectivesTo identify the most useful physical examination, metabolic and management factors to predict laminitis development in client-owned, nonlaminitic ponies.Study designProspective cohort study.MethodsPhysical examination, metabolic and management data were collected from a pony cohort 6 monthly for up to 4 years. Ponies were monitored for the development of laminitis. Metabolic data included basal plasma concentrations of ACTH ([ACTH]), adiponectin ([adiponectin]), triglycerides and glucose. Serum insulin concentrations ([insulin]) were measured in the unfasted basal state ([insulin]T0) and 60 minutes ([insulin]T60) after administration of corn syrup (0.3ml/kg). Separate multivariable Cox proportional-hazards models were developed for physical, management/signalment and metabolic data and later combined into two final models. Low-, medium- and high-laminitis risk categories were defined based on basal or T60 [insulin].ResultsOverall, 374 ponies (age 5-32 years) and 891 pony-years were included in the main analysis. Laminitis incidence (95% confidence interval (CI)) was 4.8 (3.5-6.5) cases/100 pony-years. Laminitis development was associated with numerous univariable factors. Significant (P < .05) factors retained in the final multivariable models included [insulin]T0, [insulin]T60, [adiponectin] and divergent hoof growth. [ACTH] was not independently associated with laminitis. Based on [Insulin]T0, low- (<21.6 µIU/ml), medium- (21.6-45.2 µIU/ml) and high-risk (>45.2 µIU/ml) categories encompassed 70, 20 and 10% of the population and had estimated 4-year laminitis incidences (95%CI) of 6 (2-9)%, 22 (10-33)% and 69 (48-82)% respectively. Based on [Insulin]T60 the low- (<53.4 µIU/ml), medium- (53.4-153 µIU/ml) and high-risk (≥153 µIU/ml) categories comprised 60, 30 and 10% of the population and had estimated 4-year laminitis incidences (95%CI) of 3 (0-6)%, 20 (10-29)% and 73 (52-84)% respectively.Main limitationsResults may not apply to different insulin assays, geographical regions, breeds or management types.Conclusions[Insulin]T0 or [insulin]T60 best quantify the risk of future laminitis development in nonlaminitic ponies.

Dataset Information

The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies.

Publications

The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets