Dataset Information

Metabolic perturbations in Welsh Ponies with insulin dysregulation, obesity, and laminitis.

ABSTRACT:

Background

Metabolomics, the study of small-molecule metabolites, has increased understanding of human metabolic diseases, but has not been used to study equine metabolic syndrome (EMS).

Objectives

(1) To examine the serum metabolome of Welsh Ponies with and without insulin dysregulation before and during an oral sugar test (OST). (2) To identify differences in metabolites in ponies with insulin dysregulation, obesity, or history of laminitis.

Animals

Twenty Welsh Ponies (mean ± SD; 13.8 ± 9.0 years) classified as non-insulin dysregulated [CON] (n = 10, insulin < 30 mU/L) or insulin dysregulated [ID] (n = 10, insulin > 60 mU/L) at 75 minutes after administration of Karo syrup, obese (n = 6) or nonobese (n = 14), and history of laminitis (n = 9) or no history of laminitis (n = 11).

Methods

Case-control study. Metabolomic analysis was performed on serum obtained at 0 minutes (baseline) and 75 minutes during the OST. Data were analyzed with multivariable mixed linear models with significance set at P ≤ .05.

Results

Metabolomic analysis of 646 metabolites (506 known) detected significant metabolite differences. At baseline, 55 metabolites (insulin response), 91 metabolites (obesity status), and 136 metabolites (laminitis history) were different. At 75 minutes, 51 metabolites (insulin response), 102 metabolites (obesity status), and 124 metabolites (laminitis history) were different.

Conclusions and clinical importance

Use of metabolomics could have diagnostic utility for early detection of EMS and provide new knowledge regarding the pathophysiology of metabolic perturbations associated with this condition that might lead to improved clinical management.

SUBMITTER: Jacob SI

PROVIDER: S-EPMC5980341 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Publications

Metabolic perturbations in Welsh Ponies with insulin dysregulation, obesity, and laminitis.

Jacob Sarah I SI Murray Kevin J KJ Rendahl Aaron K AK Geor Raymond J RJ Schultz Nichol E NE McCue Molly E ME

Journal of veterinary internal medicine 20180323 3

<h4>Background</h4>Metabolomics, the study of small-molecule metabolites, has increased understanding of human metabolic diseases, but has not been used to study equine metabolic syndrome (EMS).<h4>Objectives</h4>(1) To examine the serum metabolome of Welsh Ponies with and without insulin dysregulation before and during an oral sugar test (OST). (2) To identify differences in metabolites in ponies with insulin dysregulation, obesity, or history of laminitis.<h4>Animals</h4>Twenty Welsh Ponies (m ...[more]

PMID: 29572947

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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.

Project description:BackgroundA 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.ResultsVelagliflozin was well accepted by all subjects and caused no adverse effects or hypoglycaemia. Post-prandial serum insulin (insulin Cmax) did not change significantly in the control animals over the entire study period (P = 0.101). In contrast, insulin Cmax (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 Cmax 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 Cmax returned to 199 ± 36 μIU/mL in the treated group, with no rebound effect.ConclusionsVelagliflozin 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.

Dataset Information

Metabolic perturbations in Welsh Ponies with insulin dysregulation, obesity, and laminitis.

Background

Objectives

Animals

Methods

Results

Conclusions and clinical importance

Publications

Metabolic perturbations in Welsh Ponies with insulin dysregulation, obesity, and laminitis.

Similar Datasets

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