Insulin sensitivity and postprandial insulin response in equines

A metabolic syndrome in equines was first proposed in 2002, describing a cluster of clinical abnormalities including obesity, insulin resistance (IR), fasting- and postprandial hyperinsulinemia and a predisposition for laminitis. It has been established that intake of grain-based diets rich in non-structural carbohydrates (NSC) contribute to development of IR and hyperinsulinemia. A causal link between hyperinsulinemia and laminitis in horses has also been proven. A correct diagnosis of IR requires the use of complex and expensive tests, which complicates clinical identification of horses at risk for laminitis. The overall aim for this thesis was to study factors that influence insulin sensitivity (IS) in horses and to study the relationship between IS and the postprandial insulin response. In addition, a simple field test for identification of horses with postprandial hyperinsulinemia was evaluated. By feeding horses increasing amounts of a forage-based diet low in NSC, a 9% increase in body weight was obtained, but there was no decrease in the horses’ IS. This indicates that the dietary content of NSC has a greater impact on alterations in IS in horses than short-term weight gain. An oral sugar test (OST) was developed and was found to be practical for diagnosis of postprandial hyperinsulinemia in horses under field settings. A hyperbolic relationship was found between OST-derived indices of β-cell response (based on postprandial insulin data) and quantitative measures of IS in horses. This implies that the β-cell response depend on the prevailing IS. Results also confirm that the OST primarily is a test that estimates the β-cell response rather than IS. The postprandial insulin response was evaluated using forage diets differing in NSC content. It was found that the postprandial insulin response depended on both the NSC content in forage and the horse’s IS, but the effect of IS was diminished when the forage NSC content was low. This indicates that horses with IR and an augmented β-cell response should be a fed forage diet with low content of NSC, in order to attenuate the postprandial insulin response and thereby decrease the risk for laminitis. This work adds to the knowledge about the pathophysiology, clinical management and recognition of horses with IR and hyperinsulinemia

Evaluation of fasting plasma insulin and proxy measurements to assess insulin sensitivity in horses

BackgroundProxies are mathematical calculations based on fasting glucose and/or insulin concentrations developed to allow prediction of insulin sensitivity (IS) and beta -cell response. These proxies have not been evaluated in horses with insulin dysregulation. The first objective of this study was to evaluate how fasting insulin (FI) and proxies for IS (1/Insulin, reciprocal of the square root of insulin (RISQI) and the quantitative insulin sensitivity check index (QUICKI)) and beta -cell response (the modified insulin-to-glucose ratio (MIRG) and the homeostatic model assessment of beta -cell function (HOMA-beta)) were correlated to measures of IS (M index) using the euglycemic hyperinsulinemic clamp (EHC) in horses with insulin resistance (IR) and normal IS. A second objective was to evaluate the repeatability of FI and proxies in horses based on sampling on consecutive days. The last objective was to investigate the most appropriate cut-off value for the proxies and FI.ResultsThirty-four horses were categorized as IR and 26 as IS based on the M index. The proxies and FI had coefficients of variation (CVs)= 0.89). All proxies and FI were good predictors of the M index (r=0.76-0.85; P9.5 mu IU/mL for FI.ConclusionsAll proxies and FI provided repeatable estimates of horses' IS. However, there is no advantage of using proxies instead of FI to estimate IR in the horse. Due to the heteroscedasticity of the data, proxies and FI in general are more suitable for epidemiological studies and larger clinical studies than as a diagnostic tool for measurement of IR in individual horses

Composition and short-term stability of gut microbiota in lean and spontaneously overweight healthy Labrador retriever dogs

Background The gut microbiota and its metabolic end-products act in close collaboration with the nutrient metabolism of the animal. A relationship between excess adiposity and alterations in gut microbiota composition has been identified in humans and rodents, but data are scarce for overweight dogs. This study compared composition and temporal variations of gut microbiota in healthy lean and spontaneously overweight dogs. The analysis was based on three individual fresh faeces samples from each dog during a 10-day period. Twenty-seven healthy and intact male Labrador retriever dogs were included, 12 of which were classified as lean (body condition score (BCS) 4-5 on a 9-point scale) and 15 as overweight (BCS 6-8). Gut microbiota was analysed by Illumina sequencing of the V3-V4 region of the 16S rRNA gene. Results Lean and overweight groups of dogs were not separated by principal coordinate analysis (PCoA), analysis of similarity (one-way ANOSIM, P = 0.99) or species indicator analysis (IndVal) using operational taxonomic units (OTU) data. Gut microbial taxa at phylum, family or genus level did not differ between lean and overweight dogs in mixed-model repeated measures analyses. Short-term stability, evaluated by similarity index, did not differ between lean and overweight dogs over the 10-day period. Pooled Firmicutes/Bacteroidetes (F/B) ratio was 3.1 +/- 3.7 in overweight dogs and 2.1 +/- 1.2 in lean dogs (P = 0.83). Individual dogs, irrespective of body condition (lean or overweight), displayed variation in mean alpha diversity (Chao-1 index range 122-245, Shannon index range 2.6-3.6) and mean similarity index (range 44-85%). Conclusions Healthy lean and spontaneously overweight Labrador retriever dogs had comparable gut microbiota composition and short-term stability over a 10-day sampling period. There were no alterations in microbial diversity or in relative abundance of specific taxa at phylum, family or genus level in overweight compared to lean dogs. Our findings suggest that there are few detectable differences in gut microbiota composition between healthy spontaneously overweight and lean dogs by the current method. Future application of metagenomic or metabolomic techniques could be used to investigate microbial genes or microbial end-products that may differ even when microbiota compositional analyses fail to detect a significant difference between lean and overweight dogs

Dog Owners' Perceptions of Canine Body Composition and Effect of Standardized Education for Dog Owners on Body Condition Assessment of Their Own Dogs

Simple Summary Overweight is a growing problem in dogs worldwide and negative health effects associated with excess body weight are common. The body condition score (BCS) scale is a time- and resource-effective method to assess if a dog is overweight, but its precision among dog owners has been found to vary. The aim of this study was to investigate dog owners' perceptions of various body compositions in dogs and evaluate if a short education on how to use the 9-point BCS scale might change these perceptions. This study included one survey and one clinical study of Swedish dog owners. In the indirect assessment based on photos, normal-weight dogs were underestimated by three-quarters of dog owners, and about half of the dog owners underestimated overweight dogs. Before receiving the standardized education, one-third of the owners underestimated the body composition of their own dogs, mainly for dogs with excess adiposity. The dog owners responded well to the practical education given and, thereafter, performed assessments comparable to veterinary health care personnel. These results indicate that perception of what an "ideal weight" dog should look like is sliding and that the ability to identify overweight dogs might be limited when owners evaluate body composition without previous education. Overweight in dogs is an increasing problem, with a prevalence of about 30% in Sweden. To prevent the negative health effects of overweight, it is important to identify and treat canine overweight. Dog owners are essential for such interventions. The aim of this study was to evaluate dog owners' perceptions of various canine body compositions via indirect assessment based on photos and direct assessment of their own dogs. A second aim was to evaluate the effect of a standardized practical education for dog owners on body condition score (BCS) assessment of their own dogs. The 9-point BCS scale was used, and two study samples were recruited: one was a survey sample where 564 dog owners assessed the BCS of dogs using photos, and one sample was a separate clinical sample where 82 dogs were assessed by their owners and by veterinary health care personnel. The initial BCS assessment by the dog owners in the clinical sample (mean & PLUSMN; SD) was significantly lower (4.6 & PLUSMN; 1.0) than the BCS assessed by the veterinary health care personnel (5.2 & PLUSMN; 1.1), but the owners improved significantly after receiving the standardized education (5.1 & PLUSMN; 1.0) (both p < 0.0001) and performed as accurately as the veterinary health care personnel (p = 0.99). The results should be verified in the broader dog owner population based on a randomized selection of participants. "Weight blindness", defined here as an underassessment of normal-weight dogs and an inability to identify overweight dogs, is likely to have a negative impact on canine overweight prevalence. Deeper knowledge about dog owners' perceptions can inform the development of new strategies to help prevent and manage canine overweight, whereof standardized practical education on BCS assessment is shown here to be one example

Short-term effects of canagliflozin on glucose and insulin responses in insulin dysregulated horses: A randomized, placebo-controlled, double-blind, study

Background Decreasing hyperinsulinemia is crucial in preventing laminitis in insulin dysregulated (ID) horses. Complementary pharmacological treatments that efficiently decrease postprandial hyperinsulinemia in ID horses are needed.Objectives Compare short-term effects of canagliflozin vs placebo on glucose and insulin responses to an oral sugar test (OST) as well as the effects on body weight and triglyceride concentrations in horses with ID.Animals Sixteen privately-owned ID horses.Methods A single-center, randomized, double-blind, placebo-controlled, parallel design study. The horses were randomized (ratio 1:1) to either once daily PO treatment with 0.6 mg/kg canagliflozin or placebo. The study consisted of an initial 3-day period for obtaining baseline data, a 3-week double-blind treatment period at home, and a 3-day follow-up period similar to the initial baseline period but with continued double-blind treatment. Horses were subjected to an 8-sample OST in the morning of the third day on both visits.Results Maximal geometric least square (LS) mean insulin concentration (95% confidence interval [CI]) during the OST decreased after 3 weeks of canagliflozin treatment compared with placebo (83.2; 55.4-125.0 vs 215.2; 143.2-323.2 mu IU/mL). The geometric LS mean insulin response (insulin AUC(0-180)) for canagliflozin-treated horses was >66% lower compared with placebo. Least square mean body weight decreased by 11.1 (4-18.1) kg and LS mean triglyceride concentrations increased by 0.99 (0.47-1.5) mmol/L with canagliflozin treatment.Conclusions and Clinical ImportanceCanagliflozin is a promising drug for treatment of ID horses that requires future studies

Overweight in Swedish show dogs-prevalence and association with performance in competition

Background The prevalence of overweight and obesity is increasing in companion dogs, but little is known of these conditions in show dogs. This study assessed body condition score (BCS) of show dogs of six selected popular breeds at a major Swedish dog show event and examined the association between BCS and performance in competition. Results At one of Sweden's largest dog shows, BCS of 120 dogs of six different breeds was assessed by trained animal healthcare personnel, using a 9-point BCS scale with conditional cut-off for overweight set to BCS >= 6. Prevalence of overweight in the cohort was 32% but all overweight dogs except one displayed only slight overweight (BCS 6) and no dog was assessed as obese (BCS 8-9). Prevalence of overweight differed significantly between breeds (P < 0.0001) with Labrador retrievers, Golden retrievers and French bulldogs showing the highest mean BCS (5.6-5.7) and highest prevalence of overweight (50-67%). Lean and overweight dogs received awards and higher show awards (certificates) to the same extent, and no significant association between slight overweight and performance in competition was found. Conclusions Prevalence of overweight in Swedish show dogs was relatively high and in the same range as in the Swedish dog population as a whole. Dog owners, breeders and judges should be made aware of canine obesity problems and trained in BCS assessment, to better prevent canine overweight and associated health risks. This is particularly important for retriever and brachycephalic breeds, which showed high prevalence of slight overweight and have breed-specific health problems exacerbated by overweight. Owners and breeders of traditionally sturdy dog breeds should be informed that overweight dogs do not outperform lean dogs in competition

Relationship Between β-cell Response and Insulin Sensitivity in Horses based on the Oral Sugar Test and the Euglycemic Hyperinsulinemic Clamp

Background: A hyperbolic relationship between beta-cell response and insulin sensitivity (IS) has been described in several species including rodents, dogs, and humans. This relationship has not been elucidated in the horse. Hypothesis/Objectives: To determine whether the hyperbolic relationship between beta-cell response and IS exists in horses by using indices of beta-cell response from the oral sugar test (OST) and IS measurements from the euglycemic hyperinsulinemic clamp (EHC). A second aim was to compare how well IS estimates from the OST and EHC correlate. Animals: Forty-nine horses with different degrees of insulin regulation (normal-to-severe insulin dysregulation). Methods: Cross-sectional study. Horses were examined with an OST and an EHC. Results: Decreased IS was associated with increased beta-cell response in the horses. Nine of 12 comparisons between indices of beta-cell response and IS measures fulfilled the criteria for a hyperbolic relationship. Indices of IS calculated from the OST correlated highly with the insulin-dependent glucose disposal rate (M) and the insulin-dependent glucose disposal rate per unit of insulin (M/I) determined from the EHC (r = 0.81-0.87). Conclusions and Clinical Importance: A hyperbolic relationship between beta-cell response and IS exists in horses, which suggest that horses with insulin dysregulation respond not only with postprandial hyperinsulinemia but are also insulin resistant. The OST is primarily a test for beta-cell response rather than a test for IS, but calculated indices of IS from the OST may be useful to estimate IS in horses, especially when the horse is insulin resistant