Bayesian evaluation of sensitivity and specificity of blood culture media and hypoglycemia in sepsis-suspected calves.

BACKGROUND: Sepsis is a life-threatening condition for which critically important antimicrobials are often indicated. The value of blood culture for sepsis is indisputable, but appropriate guidelines on sampling and interpretation are currently lacking in cattle. OBJECTIVE: Compare the diagnostic accuracy of 2 blood culture media (pediatric plus [PP] and plus aerobic [PA]) and hypoglycemia for bacteremia detection. Estimate the contamination risk of blood cultures in critically ill calves. ANIMALS: One hundred twenty-six critically ill calves, 0 to 114 days. METHODS: Retrospective cross-sectional study in which the performance of PP, PA and hypoglycemia to diagnose sepsis was assessed using a Bayesian latent class model. A Cox proportional hazards model was used to compare time to positivity (TTP). Potential contamination was descriptively analyzed. Isolates were considered relevant when they were; member of the Enterobacterales, isolated from both blood cultures vials, or well-known, significant bovine pathogens. RESULTS: The sensitivities for PP, PA, and hypoglycemia were higher when excluding assumed contaminants; 68.7% (95% credibility interval = 30.5%-93.7%), 87.5% (47.0%-99.5%), and 61.3% (49.7%-72.4%), respectively. Specificity was estimated at 95.1% (82.2%-99.7%), 94.2% (80.7%-99.7%), and 72.4% (64.6%-79.6%), respectively. Out of 121 interpretable samples, 14.9% grew a presumed contaminant in PA, PP, or both. There was no significant difference in the TTP between PA and PP. CONCLUSIONS AND CLINICAL IMPORTANCE: PA and PP appear to outperform hypoglycemia as diagnostic tests for sepsis. PA seems most sensitive, but a larger sample size is required to verify this. Accuracy increased greatly after excluding assumed contaminants. The type of culture did not influence TTP or the contamination rate.

Effect of sodium-glucose cotransporter 2 inhibitor canagliflozin on interstitial glucose concentration in insulin-treated diabetic dogs.

BACKGROUND: The utility of sodium-glucose cotransporter 2 inhibitors (SGLT2i) has not been reported in insulin-treated diabetic dogs. HYPOTHESIS: Canagliflozin, a PO-administered SGLT2i, decreases interstitial glucose concentration (IG) in insulin-treated diabetic dogs. ANIMALS: Five insulin-treated diabetic dogs. METHODS: Uncontrolled open label longitudinal study. Canagliflozin (2-4 mg/kg/day PO) was added to an unchanged insulin dose for 7 days. Fractional excretion of glucose was calculated by dividing the product of urine glucose and serum creatinine concentrations by the product of serum glucose and urine creatinine concentrations. Hypoglycemia was defined as IG <60 mg/dL. RESULTS: Median IG in 2869 measurements obtained while dogs were treated with insulin and canagliflozin was 87 mg/dL (range, 40-500 mg/dL) and was significantly lower than median IG in 1426 measurements obtained while dogs were treated with insulin alone (212 mg/dL; range, 41-500 mg/dL; P < .001). Median fractional excretion of glucose when dogs were treated with insulin and canagliflozin was 1.1% (range, 0.9%-2.0%), significantly higher than when dogs were treated with insulin alone (0.3%; range, 0.01%-1.0%; P = .04). The frequency of hypoglycemia was higher in dogs treated with insulin and canagliflozin (544 of 2869 IG measurements, 19%) compared with the frequency of hypoglycemia in dogs treated with insulin alone (52 of 1426 IG measurements, 4%; P < .001). CONCLUSIONS AND CLINICAL IMPORTANCE: Canagliflozin may have a role in improving glycemic control in insulin-treated diabetic dogs, but the dose of insulin should be decreased when adding canagliflozin to insulin treatment.

Hypothermia, anemia, hyperglycemia, and severe hypoglycemia are significant prognostic indicators of death in client-owned ferrets (Mustela putorius furo).

OBJECTIVE: To determine whether rectal temperature, Hct, or blood glucose at presentation were associated with all-cause mortality in ferrets (Mustela putorius furo). ANIMALS: 321 client-owned ferrets. METHODS: A medical record database was searched for ferrets from January 2012 through September 2022. Records from 1,189 individual examinations were evaluated. Inclusion criteria were rectal temperature, Hct, and/or blood glucose measured at presentation and data on survival status 7 days postpresentation. Data were included from 321 ferrets from 571 examinations. Rectal temperature in 244 ferrets from 346 examinations, Hct in 181 ferrets from 277 examinations, and blood glucose in 260 ferrets from 420 examinations were available. RESULTS: The odds of death for hypothermic ferrets (< 37.8 °C) were 3.72 times (OR, 3.72; 95% CI, 2.30 to 6.01) the odds of death for normothermic ferrets (37.8 to 40 °C). For every 0.56 °C below normal rectal temperature, the odds of death increased 1.49 times (OR, 1.49; 95% CI, 1.21 to 1.90). The odds of death for anemic ferrets (Hct < 33%) were 4.74 times (OR, 4.74; 95% CI, 1.70 to 13.21) the odds of death for ferrets with a normal Hct (33% to 57%). The odds of death for hyperglycemic ferrets (> 152 mg/dL) were 2.61 times (OR, 2.61; 95% CI, 1.29 to 5.30) the odds of death for normoglycemic ferrets (74 to 152 mg/dL). The odds of death for severely hypoglycemic ferrets (< 40 mg/dL) were 9.45 times (OR, 9.45; 95% CI, 3.18 to 28.12) the odds of death for normoglycemic ferrets. CLINICAL RELEVANCE: Hypothermia, anemia, hyperglycemia, and severe hypoglycemia were significant prognostic indicators of death in ferrets. Further investigation into the causes and management of these derangements is warranted.

Nesidioblastosis and Subsequent Diabetes Mellitus in a Dog with Hyperinsulinemic Hypoglycemia Treated with Partial Pancreatectomy.

A 6.5 yr old castrated male mixed-breed dog was presented for clinical signs associated with hypoglycemia. Hyperinsulinemic hypoglycemia was diagnosed as the cause of the persistent hypoglycemia. No obvious pancreatic mass was seen on abdominal computed tomography and exploratory laparotomy. A partial pancreatectomy was performed with the suspicion of an insulinoma-causing hyperinsulinemic hypoglycemia. Nesidioblastosis was diagnosed based clinical, biochemical, and histopathologic findings. There was beta cell hyperplasia and no evidence of neoplasia. The dog was euglycemic postoperatively after a partial pancreatectomy. Long-term follow-up after 2 yr revealed that the dog was diagnosed with diabetes mellitus.

Diabetes Mellitus Following Resection of a Hepatocellular Carcinoma in a Dog Presented with Hypoglycemia.

A 5 yr old male neutered Labradoodle presented for an episode of acute collapse. Point-of-care blood work showed hypoglycemia and abdominal ultrasonography revealed a liver mass arising from the caudate liver lobe. The dog underwent a partial liver lobectomy, and histopathology confirmed a fully resected hepatocellular carcinoma. Blood glucose levels normalized initially after surgery, but 1 wk later, the patient was diagnosed with diabetes mellitus based on the development of polyuria, polydipsia, hyperglycemia, and glucosuria. Appropriate treatment with insulin was initiated, and 1 yr following the diagnosis, the dog was still requiring administration of insulin twice daily. This case describes the uncommon development of diabetes mellitus in a dog following surgical resection of a hepatocellular carcinoma initially associated with hypoglycemia. Although very unusual, this should be considered as a potential complication of surgical treatment of such tumors, and affected patients may require long-term medical management.

Hepatic abscessation in dogs: A multicenter study of 56 cases (2010-2019).

OBJECTIVE: To investigate the clinical findings, treatment strategies, and outcomes in dogs with confirmed hepatic abscessation. DESIGN: Retrospective cohort study from 2010 to 2019. SETTING: Multicenter study. ANIMALS: Fifty-six client-owned dogs with hepatic abscessation confirmed by culture, cytology, or histopathology. MEASUREMENTS AND MAIN RESULTS: Dogs were presented for lethargy (39/56), hyporexia (31/56), and vomiting (26/56). Abnormal physical examination findings included increased temperature (41/56) and abdominal pain (22/54). CBCs revealed neutrophilia (31/49), toxic changes (25/49), anemia (28/49), and thrombocytopenia (23/49). Biochemical analyses revealed increased alkaline phosphatase (45/50), increased alanine aminotransferase (40/50), hypoalbuminemia (25/48), and hyperbilirubinemia (19/49). Hypoglycemia was found in 13 of 49 dogs. Hepatic abscesses ranging from 0.5 to 15 cm in diameter were identified ultrasonographically in 37 of 48 dogs; 19 of 37 had solitary abscesses, and 18 of 37 had multifocal abscessation. Escherichia coli was the most commonly cultured organism, isolated in 18 of 42 cases. Histopathology revealed underlying hepatic neoplasia in 10 of 47 dogs. Surgical management was performed in 41 of 49 dogs, and 35 of 41 survived to discharge. Medical management was performed in 8 of 49 dogs, and 5 of 8 survived to discharge. With univariate analysis, hypoglycemia and multifocal abscessation were associated with decreased odds of survival (odds ratio [OR]: 0.2, 95% confidence interval [CI]: 0.03-0.9, P = 0.04; OR: 0.07, 95% CI: 0.01-0.6, P = 0.02, respectively). With multivariate analysis, only multifocal abscessation was associated with decreased odds of survival (OR: 0.09, 95% CI: 0.01-0.87, P = 0.04). CONCLUSIONS: Hepatic abscessation, although rare, should remain a differential diagnosis for dogs presenting with nonspecific clinical signs and increase liver enzyme activities, especially with concurrent increased temperature and neutrophilia. Rate of survival to discharge for dogs in this study was consistent with previously reported survival rates, with 40 of 56 (71%) of the total population surviving to discharge. No variables assessed were able to predict survival to discharge; however, hypoglycemia and multifocal abscessation should be assessed in larger populations to determine prognostic significance.

Assessment of the FreeStyle Libre 2 interstitial glucose monitor in hypo- and euglycemic cats.

BACKGROUND: Continuous glucose monitoring systems have been validated for eu- and hyperglycemic cats. The FreeStyle Libre 2 (FSL2) is sufficiently accurate in people during hypoglycemia to guide critical treatment decisions without confirmation of blood glucose concentration (BG). OBJECTIVES: Assess FSL2 accuracy in cats with hypoglycemia. ANIMALS: Nine healthy, purpose-bred cats. METHODS: Hyperinsulinemic-hypoglycemic clamps were performed by IV infusion of regular insulin (constant rate) and glucose (variable rate). Interstitial glucose concentration (IG), measured by FSL2, was compared to BG measured by AlphaTrak2. Data were analyzed for all paired measurements (n = 364) and separately during stable BG (≤1 mg/dL/min change over 10 minutes). Pearson's r test, Bland-Altman test, and Parkes Error Grid analysis respectively were used to determine correlation, bias, and clinical accuracy (P < .05 considered significant). RESULTS: Overall, BG and IG correlated strongly (r = 0.83, P < .0001) in stable glycemia and moderately at all rates of change (r = 0.69, P < .0001). Interstitial glucose concentration underestimated BG in euglycemia, but the BG-IG difference was progressively smaller as BG decreased (12.9 ± 12.2, 8.8 ± 11.2, -3.2 ± 7.4, and -7.8 ± 5.2 mg/dL in the ranges of 80-120 [n = 64], 60-79 [n = 29], 50-59 [n = 71], and 29-49 mg/dL [n = 53], respectively). CONCLUSIONS: Although IG underestimates BG throughout most of the hypo-euglycemic range, IG generally overestimates BG in marked hypoglycemia (<60 mg/dL). It is therefore imperative to evaluate FSL2 results in this critical range with caution.

Phenibut toxicosis in a dog.

OBJECTIVE: To describe the successful treatment of severe neurological and cardiovascular abnormalities in a dog following ingestion of the neuropsychotropic drug, phenibut. CASE SUMMARY: A 2-year-old neutered male Weimaraner was found unresponsive and laterally recumbent in his urine after ingesting approximately 1600 mg/kg of phenibut. On presentation to an emergency clinic, the dog was neurologically inappropriate, tachycardic, hypertensive, and exhibiting a profoundly decreased respiratory rate. Because of progressive clinical signs, electrolyte abnormalities, increased hepatic enzyme activity and bilirubin concentrations, and the development of pigmenturia, referral to specialist care was sought. On presentation, the dog was intermittently somnolent and then maniacal. Sinus tachycardia persisted, and hyperthermia was documented. Hospitalization for supportive care was undertaken, and the dog was administered IV fluids, flumazenil, antiepileptics, and IV lipid emulsion therapy. The dog developed hypoglycemia and treated with dextrose supplementation. Progressive increases in liver enzyme activities as well as pronounced increase in creatine kinase activity, consistent with rhabdomyolysis, were noted. Over the course of 48 hours, the hypoglycemia resolved, and clinical signs significantly improved. Ultimately, the dog was discharged with improved clinical signs, with the owner reporting that 1 week after discharge, a full recovery had been made, and no residual clinical signs persisted. NEW INFORMATION PROVIDED: To the authors' knowledge, there are no previous reports of phenibut intoxication in small animals. The growing availability and use of this drug by people in the past several years highlight the need for a greater understanding of its effects in companion animals.

Ectopic insulinoma in a dog with insulin-induced hypoglycemia: a case report.

A 7-year-old spayed female Shih Tzu dog was presented for evaluation of recurrent hypoglycemia. Serum insulin levels during hypoglycemia were 35.3 µIU/mL. Ultrasonography and computed tomography showed a mesenteric nodule between the kidney and the portal vein, but no pancreatic mass was observed. During surgery, the nodule had neither anatomical adhesions nor vascular connections to the pancreas. Pancreatic inspection and palpation revealed no abnormalities. Hypoglycemia improved after resection of the nodule. Histopathological examination confirmed the nodule to be an islet cell carcinoma. Although extremely rare, ectopic insulinoma should be considered as a possible cause of insulin-induced hypoglycemia in dogs.

Hip sensor location for flash interstitial glucose monitoring system provides adequate clinical accuracy in non-diabetic hypoglycemic dogs.

OBJECTIVE: Flash glucose monitoring systems (FGMS) are frequently used for interstitial glucose monitoring in dogs with diabetes mellitus and are typically placed between the scapulae. We aimed to evaluate the variability between glucose measurements from FGMS placed in 2 locations (between the scapulae and over the hip) in non-diabetic dogs during rapidly induced hypoglycemia. ANIMALS: 24 apparently healthy colony dogs that were subjects in a teaching laboratory. PROCEDURES: Prospective interventional study. FGMS sensors (FreeStyle Libre 14-day system) were placed between the scapulae and over the hip of all dogs. Regular insulin was administered (0.3 u/kg IV) and subsequent hypoglycemia was corrected. Before insulin administration and every 10 minutes over 90 minutes, interstitial glucose was recorded from both locations, and blood glucose was measured with a point-of-care blood glucose monitor (AlphaTRAK 2). RESULTS: There was a constant bias of 5.6 mg/dL (95% limits of agreement: -26.3 to 37.5 mg/dL) between locations, but the proportional bias was not apparent. There was a correlation between FGMS locations (r = 0.731, P = < .001). Sensor site B was clinically accurate with 100% of paired samples within Parkes error grid zones A (83%) and B (17%) but did not meet the criteria for analytical accuracy. CLINICAL RELEVANCE: In this model of induced hypoglycemia in healthy dogs, variation between measurements from FGMS locations was unlikely to have affected the clinical outcome. Placement of FGMS over the hip may be an acceptable alternative to placement between the scapulae, but the utility in hyperglycemic dogs is unknown.

Glucose Counterregulation: Clinical Consequences of Impaired Sympathetic Responses in Diabetic Dogs and Cats.

Insulin induced hypoglycemia (IIH) is common in veterinary patients and limits the clinician's ability to obtain adequate glycemic control with insulin therapy. Not all diabetic dogs and cats with IIH exhibit clinical signs and hypoglycemia might be missed by routine blood glucose curve monitoring. In diabetic patients, counterregulatory responses to hypoglycemia are impaired (lack of decrease in insulin levels, lack of increase in glucagon, and attenuation of the parasympathetic and sympathoadrenal autonomic nervous systems) and have been documented in people and in dogs but not yet in cats. Antecedent hypoglycemic episodes increase the patient's risk for future severe hypoglycemia.

Insulin Therapy in Small Animals, Part 3: Dogs.

Insulin therapy should ideally mimic a basal-bolus pattern. Lente, NPH, NPH/regular mixes, PZI, glargine U100, and detemir are intermediate-acting formulations that are administered twice daily in dogs. To minimize hypoglycemia, intermediate-acting insulin protocols are usually geared towards alleviating (but not eliminating) clinical signs. Insulin glargine U300 and insulin degludec meet the criteria for an effective and safe basal insulin in dogs. In most dogs, good control of clinical signs is achieved when using a basal insulin alone. In a small minority, bolus insulin at the time of at least one meal per day may be added to optimize glycemic control.

Long-term field study of lispro and neutral protamine Hagedorn insulins treatment in dogs with diabetes mellitus.

BACKGROUND: The long-term clinical and biofhemical effects of basal-bolus insulin treatment with lispro and NPH in dogs with diabetes mellitus are undocumented. OBJECTIVES: To perform a prospective pilot field study of the long-term effects of lispro and NPH on clinical signs and serum fructosamine concentrations (SFC) in dogs with diabetes mellitus. METHODS: Twelve dogs received combined lispro and NPH insulins treatment twice a day and were examined every 2 weeks for 2 months (visits 1-4), and every 4 weeks for up to 4 additional months (visits 5-8). Clinical signs and SFC were recorded at each visit. Polyuria and polydipsia (PU/PD) were scored as absent (0) or present (1). RESULTS: Median (range) PU/PD scores of combined visits 5-8 (0, 0-1) were significantly lower than median scores of combined visits 1-4 (1, 0-1, p = 0.03) and at enrolment (1, 0-1, p = 0.045). Median (range) SFC of combined visits 5-8 (512 mmol/L, 401-974 mmol/L) was significantly lower than SFC of combined visits 1-4 (578 mmol/L, 302-996 mmol/L, p = 0.002) and at enrolment (662 mmol/L, 450-990 mmol/L, p = 0.03). Lispro insulin dose was significantly and negatively, albeit weakly, correlated with SFC concentration during visits 1 through 8 (r = -0.3, p = 0.013). Median duration of follow up was 6 months (range 0.5-6) and most dogs (8, 66.7%) were followed for 6 months. Four dogs withdrew from the study within 0.5-5 months because of documented or suspected hypoglycaemia, short NPH duration or sudden unexplained death. Hypoglycaemia was noted in 6 dogs. CONCLUSIONS: Long-term lispro and NPH combination therapy may improve clinical and biochemical control of some diabetic dogs with comorbidities. Risk of hypoglycaemia should be addressed with close monitoring.

Sepsis and survival in critically ill calves: Risk factors and antimicrobial use.

BACKGROUND: Sepsis is a life-threatening disease for which critically important antimicrobials (CIA) frequently are used. Diagnostic and therapeutic guidelines for sepsis and critically ill calves are largely lacking. OBJECTIVES: Identify factors associated with mortality in critically ill calves and describe bacteria obtained from blood cultures of critically ill calves with sepsis and their antimicrobial resistance. ANIMALS: Two-hundred thirty critically ill calves, mainly Belgian Blue beef cattle. METHODS: Retrospective cohort study. Logistic regression, survival analysis, and decision tree analysis were used to determine factors associated with mortality. RESULTS: Of the critically ill calves, 34.3% had sepsis and 61.3% died. The final survival model indicated that calves with sepsis (hazard risk [HR]: 1.6; 95% confidence interval [CI]: 1.0-2.5; P = .05), abnormal behavior (HR: 2.3; 95% CI: 1.3-4.0; P = .005), and hypothermia (HR: 0.82; 95% CI: 0.72-0.95; P = .01) had a significantly higher mortality risk. In a second survival model, hypothermia (HR: 0.87; 95% CI: 0.78-0.96; P = .004) and hypoglycemia (HR: 2.2; 95% CI: 1.5-3.3; P < .001) were risk factors for mortality. Decision tree analysis emphasized the importance of behavior, hypochloremia, hypoglycemia, hyperkalemia, and lung ultrasonography for mortality risk. Escherichia coli (30.6%) was most frequently isolated from blood cultures, of which 90.9% were multidrug resistant. Inappropriate use of antimicrobials was frequent for penicillin, amoxicillin, and sulfamethoxazole/trimethoprim, but less for CIA. CONCLUSIONS AND CLINICAL IMPORTANCE: Many critically ill calves have sepsis, which increases mortality risk. Bacteria involved are often resistant to first-intention antimicrobials but less resistant to CIA. The other identified risk factors for mortality can support therapeutic decision-making.

Clinical utility of serum fructosamine in long-term monitoring of diabetes mellitus in dogs.

BACKGROUND: Serum fructosamine (sFA) is used to assess glycaemic control in dogs with diabetes mellitus (DM). Nevertheless, its interpretation is hindered by several limitations. METHODS: This retrospective study evaluates the long-term diagnostic performance of sFA for monitoring clinical control of DM. sFA, bodyweight, appetite, presence of polyuria/polydipsia and clinical scores (CS; well-controlled DM, CS-0; uncontrolled DM, CS-1) were recorded. RESULTS: The study included 75 dogs (321 visits; median 3 visits/dog; range 1-19). Mean sFA was higher (p < 0.001) on visits with CS-1 (584 µmol/L; 95% confidence interval [95% CI] 561-608) than on visits with CS-0 (506 µmol/L; 95% CI 484-528). Increases in sFA increased   the odds ratio for CS-1 (1.37; 95% CI 1.24-1.52, p < 0.001). sFA was moderately predictive of the CS (area under receiver operating characteristic curve = 0.75; 95% CI 0.70-0.80; p < 0.0001), with a 486 µmol/L cutoff yielding 80% sensitivity and 59% specificity. Mean sFA was lower (p = 0.005) when hypoglycaemic episodes were suspected (496 µmol/L; 95% CI 450-541) than in their absence (572 µmol/L; 95% CI 548-596). sFA is moderately accurate for classifying CS in diabetic dogs. Decreasing sFA over follow-ups indicates improved CS but might suggest occurrence of hypoglycaemic episodes. LIMITATIONS: Retrospective design, variable treatments and comorbidities are limitations of this study. CONCLUSION: sFA has a moderate clinical utility in the long-term monitoring of diabetic dogs, but may serve as a first-line, accessible diagnostic tool. Discordant CS and sFA evaluation, or decreased sFA, warrants additional monitoring (i.e., continuous glucose monitoring).

Glucoregulatory factors in canine hepatocellular carcinoma and leiomyosarcoma with non-islet cell tumour hypoglycaemia.

INTRODUCTION: Hypoglycaemia caused by malignant tumours other than insulinoma is referred to as non-islet cell tumour hypoglycaemia (NICTH), which may be caused by hepatocellular carcinoma (HCC) and leiomyosarcoma (LMS) in veterinary medicine. However, the pathogenetic mechanism of NICTH remains unclear. Therefore, this study aimed to evaluate the gene-expression levels of glucoregulatory factors in canine HCC and LMS accompanied by hypoglycaemia. MATERIALS & METHODS: Four patients (three with HCC and one with LMS) exhibiting hypoglycemia were included in the hypoglycemic (H) group, whereas ten patients not exhibiting hypoglycemia were in the non-hypoglycaemia (NH) group. The preoperative and postoperative blood glucose and serum insulin-like growth factor-2 (IGF-2) levels, as well as the expression of genes involved regulating blood glucose levels were analysed. RESULTS: Compared with the NH group, the H group exhibited significantly decreased blood-glucose levels, which increased to normal values after surgery. Compared with the NH group, the H group exhibited significantly increased gene expression of insulin-like growth factor 1, IGF-2, and insulin-like growth factor binding protein 3 in the tumours. Conversely, expression of genes encoding glucoregulatory factors including insulin, gastric inhibitory polypeptide and glucagon was not observed. Serum IGF-2 levels were significantly higher in the H group compared with that in the control group (healthy dogs) and NH group. In two cases in the H group, serum IGF-2 levels decreased after tumour resection. CONCLUSION: These results suggest that NICTH development in dogs with HCC and LMS is mechanistically associated with IGF-2 overexpression and elevated serum IGF-2 levels.

Comparison of production-related responses to hyperinsulinemia and hypoglycemia induced by clamp procedures or heat stress of lactating dairy cattle.

Hyperinsulinemia concurrent with hypoglycemia is one of a myriad of physiological changes typically experienced by lactating dairy cows exposed to heat stress, the consequences of which are not yet well defined or understood. Therefore, the objective of this experiment was to separate the production-related effects of hyperinsulinemia with hypoglycemia from those of a hyperthermic environment. Multiparous lactating Holstein cows (n = 23; 58 ± 4 d in milk, 3.1 ± 0.3 lactations) were housed in temperature-controlled rooms and all were subjected to 4 experimental periods as follows: (1) thermoneutral (TN; temperature-humidity index of 65.1 ± 0.2; d 1-5), (2) TN + hyperinsulinemic-hypoglycemic clamp (HHC; insulin infused at 0.3 µg/kg of BW per h, glucose infused to maintain 90 ± 10% of baseline blood glucose for 96 h; d 6-10), (3) heat stress (HS; temperature-humidity index of 72.5 ± 0.2; d 16-20), and (4) HS + euglycemic clamp (EC; glucose infused to reach 100 ± 10% of TN baseline blood glucose for 96 h; d 21-25). Cows were fed and milked twice daily. Feed refusals were collected once daily for calculation of daily dry matter intake, and milk samples were collected at the beginning and end of each period for component analyses. Circulating insulin concentrations were measured in daily blood samples, whereas glucose concentrations were measured more frequently and variably in association with clamp procedures. Rectal temperatures and respiration rates were greater during HS than TN, as expected, and states of hyperinsulinemia and hypoglycemia were successfully induced by the HHC and high ambient temperatures (HS and EC). Feed intake differed based upon thermal environment as it was similar during TN and HHC periods, and declined for HS and EC. Milk production was not entirely reflective of feed intake as it was greatest during TN, intermediate during HHC, and lowest during HS and EC. All milk components differed with the experimental period, primarily in response to the thermal environment. Interestingly, TN baseline glucose concentrations were highly correlated with the change in glucose from TN to HS, and were related to glycemic status during HS. Furthermore, although few in number, those cows that failed to become hypoglycemic during HS tended to have a greater reduction in milk yield. The work presented here addresses a critical knowledge gap by broadening our understanding of the physiological response to heat stress and the related changes in glycemic state. This broadened understanding is fundamental for the development of novel, innovative management strategies as the dairy industry is compelled to become increasingly efficient in spite of global warming.

A randomized controlled trial examining the effects of treatment with propylene glycol and injectable cyanocobalamin on naturally occurring disease, milk production, and reproductive outcomes of dairy cows diagnosed with concurrent hyperketonemia and hypoglycemia.

The objective of this study was to assess the effects of treatment with propylene glycol (PG) and cyanocobalamin (B12) on health, milk production, and reproductive outcomes of cows diagnosed with hyperketonemia (HK), hypoglycemia (HG), or concurrent HKHG. Glucose and ß-hydroxybutyric acid (BHBA) concentrations were assessed in whole blood using a handheld device in lactating dairy cows (n = 2,418) between 3 and 9 d postpartum. Cows categorized as HK (n = 232, BHBA ≥1.2 mmol/L), HG (n = 161, glucose ≤2.2 mmol/L), and concurrent HKHG (n = 204, BHBA ≥1.2 mmol/L, and glucose ≤2.2 mmol/L) were randomized to receive treatment or to remain untreated (control). Treatment consisted of a single dose of B12 (10 mg, intramuscularly) and 300 mL of PG orally for 5 d, starting on the day of cow-side testing. Milk production, health, and reproductive outcomes were analyzed according to groups. Statistical analysis was carried out using SAS version 9.4 (SAS/STAT, SAS Institute Inc.). Treatment in HG cows decreased clinical ketosis, increased milk production in the fifth week of lactation for multiparous cows, and tended to increase 305-d mature-equivalent milk yield (305ME) for primiparous cows compared with untreated cows with the same metabolic profile. For cows with HKHG, treatment increased 305ME in multiparous cows and tended to increase 305ME in primiparous cows. No differences were found for treatment among any of the metabolic groups regarding reproductive outcomes, nor were any treatment effects found among HK cows. Glycemic status may help identify metabolically challenged early postpartum dairy cows, which may have differential response to PG and B12 treatment.

Characterization of metabolic profile, health, milk production, and reproductive outcomes of dairy cows diagnosed with concurrent hyperketonemia and hypoglycemia.

The objective of this prospective cohort study was to characterize the metabolic profile, health, milk production, and reproductive outcomes of cows diagnosed with hyperketonemia (HK; ß-hydroxybutyrate ≥1.2 mmol/L), hypoglycemia (HG; glucose ≤2.2 mmol/L), or concurrent HK and HG (HKHG). Glucose and ß-hydroxybutyrate concentrations in whole blood were assessed using a handheld device (Precision Xtra, Abbott Laboratories) in lactating dairy cows (n = 2,418) between 3 and 9 d postpartum. Cows were categorized into 4 groups: no HK or HG (healthy; Norm = 1,821), HK only (HK = 232), HG only (HG = 161), and concurrent HK and HG (HKHG = 204). Subsequent milk production, along with health and reproductive outcomes, as recorded by farm personnel, were analyzed according to metabolic category. Serum collected on the day of cow-side diagnosis of hyperketonemia and hypoglycemia was evaluated for total calcium (tCa), magnesium (Mg), nonesterified fatty acids (NEFA), triglycerides (TG), and urea using an automated chemistry analyzer (Randox Daytona; Randox Laboratories Ltd.). Statistical analysis was carried out using SAS version 9.4 (SAS Institute Inc.). Hyperketonemia in multiparous cows was associated with greater incidence of metabolic abnormalities (hypomagnesemia, hypocalcemia, and elevated NEFA and urea). Hyperketonemia in primiparous and multiparous cows led to increased adverse health events (culling rate, retained fetal membranes, puerperal metritis, clinical ketosis, left displaced abomasum) relative to Norm cows. Multiparous cows with HKHG had fewer metabolic disturbances (hypomagnesemia, hypocalcemia, elevated NEFA) than HK cows. Cows with HKHG had an increased incidence of clinical ketosis and left displaced abomasum relative to Norm cows. Cows with HG had similar metabolic profiles to Norm cows and had lower incidence of retained fetal membranes and puerperal metritis than cows with HK. Multiparous cows with HG produced more milk than Norm cows from wk 10 to 20, whereas multiparous cows with HK produced less milk than Norm cows. For primiparous cows, HK did not have a negative effect on milk production compared with Norm cows.

Metabolic profiling in periparturient dairy cows and its relation with metabolic diseases.

OBJECTIVE: Periparturient period is associated with multiple changes including serum concentration of macro minerals and drop in feed intake. Therefore, it is essential to know the actual concentrations of major macro minerals, glucose and ketone bodies in blood during the periparturient period. The objectives of the study were to study the dynamics of calcium, magnesium, phosphorus, and glucose in serum and ketone bodies in the urine of periparturient cows and to estimate the incidence of subclinical metabolic diseases. RESULTS: Results showed that all the urine samples were negative for ketone bodies. Incidence of subclinical form of hypocalcaemia, hypomagnesaemia, hypophosphatemia, and hypoglycemia in periparturient cows was 31.03%, 48.28%, 17.24% and 55.17%, respectively. Older cows with high BCS and milk yield were mostly affected with a subclinical form of hypocalcaemia and hypoglycemia. No significant differences were observed in serum level of macro minerals and glucose at different time points of periparturient period of cows fed with a balanced ration, and between two groups of cows those were given IV injection of calcium and magnesium on the day of parturition and those were not given. Age, parity, and milk yield had no significant effect on the concentration of calcium, magnesium, phosphorus, and glucose.