Revised Quantitative Insulin Sensitivity Check Index Research Articles

Influence of Heat Stress on Body Surface Temperature and Blood Metabolic, Endocrine, and Inflammatory Parameters and Their Correlation in Cows.

This study aimed to determine whether heat stress affected the values and correlations of metabolic, endocrinological, and inflammatory parameters as well as the rectal and body surface temperature of cows in the early and middle stages of lactation. This experiment was conducted in May (thermoneutral period), June (mild heat stress), and July (moderate to severe heat stress). In each period we included 15 cows in early lactation and 15 in mid-lactation. The increase in rectal and body surface temperatures (°C) in moderate to severe heat stress compared to the thermoneutral period in different regions was significant (p < 0.01) and the results are presented as mean and [95%CI]: rectal + 0.9 [0.81-1.02], eye + 6 [5.74-6.25], ear + 13 [11.9-14.0], nose + 3.5 [3.22-3.71], forehead + 6.6 [6.43-6.75], whole head + 7.5 [7.36-7.68], abdomen + 8.5 [8.25-8.77], udder + 7.5 [7.38-7.65], front limb + 6 [5.89-6.12], hind limb + 3.6 [3.46-3.72], and whole body + 9 [8.80-9.21]. During heat stress (in both mild and moderate to severe stress compared to a thermoneutral period), an increase in the values of extracellular heat shock protein 70 (eHsp70), tumor necrosis factor α (TNFα), cortisol (CORT), insulin (INS), revised quantitative insulin sensitivity check index (RQUICKI), urea, creatinine, total bilirubin, aspartate transpaminase (AST), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), and creatin kinase (CK) occurred, as well as a decrease in the values of triiodothyronine (T3), thyroxine (T4), non-esterified fatty acids (NEFA), glucose (GLU), β-Hydroxybutyrate (BHB), calcium, phosphorus, total protein (TPROT), albumin (ALB), triglycerides (TGCs), and cholesterol (CHOL). In cows in early lactation compared to cows in mid-lactation, there was a significantly larger increase (p < 0.01) in the values of eHsp70, TNFα, GLU, RQUICKI, and GGT, while the INS increase was smaller during the three experimental periods. The decrease in the values of Ca, CHOL, and TGC was more pronounced in cows in early lactation compared to cows in mid-lactation during the three experimental periods. Rectal temperature was related to eHsp70 (r = 0.38, p < 0.001) and TNFα (r = 0.36, p < 0.01) and showed non-significant poor correlations with other blood parameters. Blood parameters correlate with body surface temperature, with the following most common results: eHsp70 and TNFα showed a moderately to strongly significant positive correlation (r = 0.79-0.96, p < 0.001); CORT, INS, and Creat showed fairly to moderately significant positive correlations; T3, T4, NEFA and GLU showed fairly to moderately significant negative correlations (r = 0.3-0.79; p < 0.01); RQUICKI, urea, AST, and GGT showed fairly and significantly positive correlations; and TGC, CHOL, TPROT, and ALB showed fairly and significantly negative correlations (r = 0.3-0.59; p < 0.01). Measuring the surface temperature of the whole body or head can be a useful tool in evaluating the metabolic response of cows because it has demonstrated an association with inflammation (TNFα, eHsp70), endocrine response (CORT, T3, T4), the increased use of glucose and decreased use of lipids for energy purposes (INS, NEFA, GLU, and RQUICKI), and protein catabolism (ALB, TPROT, urea, Creat), which underlies thermolysis and thermogenesis in cows under heat stress. In future research, it is necessary to examine the causality between body surface area and metabolic parameters.

26 Effect of Steroidal Implants and Zinc Supplementation on Circulating Metabolites and Insulin Sensitivity in Feedlot Steers

Abstract Angus-cross steers (n = 144; 362 kg ± 20.4) were used to determine the interaction of Zn and steroidal implants on circulating metabolites and insulin sensitivity in feedlot steers. Steers (n = 6 steers/pen) were stratified by BW in a 3 × 2 factorial design. Dietary treatments were fed for 60 days pre-implant, during this time cattle were transitioned from a roughage-based to a high concentrate diet. Dietary treatments (8 pens per treatment; Zn as ZnSO4) included: 1) no supplemental Zn (analyzed 54 mg Zn/kg DM; Zn0); 2) 30 mg supplemental Zn/kg DM (Zn30); 3) 100 mg supplemental Zn/kg DM (Zn100). Within Zn treatment, steers received a steroidal implant treatment on d 0: 1) no implant; NO; or 2) high potency combination implant (TE-200, Elanco, Greenfield, IN; 200 mg TBA, 20 mg E2; TE200). Blood was collected from all steers on d 0, 20, 40, and 84 for analysis of serum glucose, insulin, non-esterified fatty acids (NEFA), and urea-N (SUN) in a subset of steers (n = 12 steers/treatment). Glucose, NEFA, and insulin concentrations were used to determine revised quantitative insulin sensitivity check index (RQUICKI) which was calculated as: RQUICKI = 1/[log(Glucose) + log(Insulin) + log(NEFA)]. Data were analyzed as repeated measures in Proc Mixed of SAS. A tendency for a Zn x day effect on serum insulin (Zn × day; P = 0.07) showed no difference between Zn treatments on d 0, 20, or 40 but on d 84 Zn100 was greater than Zn30 while Zn0 was intermediate. An implant × day effect (P = 0.02) for serum insulin was driven by a 45% increase from d 0 to 20 in NO while TE200 cattle did not change in that time. Serum insulin increased with days on feed (P = 0.01). Day 0 serum glucose concentration was greatest in Zn0 and Zn 100; however, on days 40 and 84, Zn100 had greater serum glucose concentration compared with Zn0 while Zn30 was intermediate (Zn × day; P = 0.07). Overall, serum glucose was unchanged over time until a decrease from day 40 to 84 (P = 0.01). A three-way interaction was noted for serum NEFA (Zn × implant × day; P = 0.04) driven by variation in serum NFEA concentration at d 0. Serum urea-N differed by day (P = 0.01) but was otherwise unaffected (P ≥ 0.16). RQUICK1 was greater for TE200 (P = 0.03) cattle on d 40 compared with NO cattle, indicating implanted cattle were more insulin sensitive. RQUICKI index value decreased with days on feed (P = 0.01) indicating lesser insulin sensitivity over time. These data indicate implants influence insulin sensitivity of late-stage finishing cattle and Zn and implants influence circulating metabolites indicative of energetic state.

Does the peroral chromium administration in young Hariana calves reduce the risk of calf diarrhea by ameliorating insulin response, lactose intolerance, antioxidant status, and immune response?

BackgroundThe reduction in insulin sensitivity during rumen development may predispose dairy calves towards lactose intolerance, which could be the reason behind neonatal calf diarrhea (NCD). Chromium (Cr) results in a range of effects when fed to ruminants, but most studies have shown improved insulin sensitivity. The aim of this study was to determine the effect of Cr supplementation on insulin sensitivity, lactose intolerance, diarrhoea and antioxidant, and immune response in young Hariana calves. MethodsA total of 20 milk-fed Hariana calves were randomly assigned to 1 of 2 treatments, each consisted of 10 calves: (1) a control group without supplemental Cr and (2) a 0.15 mg Cr as Cr-picolinate (CrPic)/kg BW0.75 supplemented group (Cr0.15). ResultsA more rapid glucose disappearance with unaltered insulin kinetics during intravenous glucose tolerance test (IVGTT) and oral lactose tolerance test (OLTT) indicates greater insulin sensitivity in Cr supplemented calves. Better insulin sensitivity in Cr supplemented calves was further confirmed by higher values of the quantitative insulin sensitivity check index (QUICKI), revised quantitative insulin sensitivity check index (RQUICKI) and insulin receptor substrate-1 (IRS-1) and lower (P < 0.05) values of homeostasis model assessment-insulin resistance (HOMA-IR) and glucose-to-insulin ratio in Cr supplemented calves during IVGTT. Cr supplementation resulted in a lower (P < 0.05) serum cortisol concentration, whereas serum non-esterified fatty acid (NEFA) concentrations during IVGTT did not differ among the groups. The rise in serum glucose concentrations within 2 h post lactose infusion during OLTT peaked at more than twice the basal glucose concentration, therefore calves were not considered as lactose intolerant. Within monthly blood samples, concentrations of serum insulin were similar among treatments, whereas the Cr supplemented group had lower (P < 0.05) serum glucose concentration and glucose-to-insulin ratio compared with the control group. No treatment differences were detected in the biomarkers of antioxidant status and immunity. Serum Cr concentrations were higher (P < 0.05) in Cr supplemented calves while concentrations of other studied minerals were remained unaltered. The incidence, duration of diarrhea, and faecal score were better (P < 0.05) in calves fed on Cr supplemented diet whereas, no treatment effect was observed on average daily gain (ADG). During the study period, no calves died, and no calves were found to have pneumonia, navel or joint disease. ConclusionFeeding a Cr-supplemented diet improved insulin sensitivity and reduced the risk of diarrhoea in milk-fed young calves, but had no or minimal effects on lactose intolerance, antioxidant status, immune response, and growth performance.

Dietary Chromium Picolinate Supplementation Improves Glucose Utilization in Transition Calf by Ameliorating Insulin Response.

The decrease in insulin sensitivity during the transition of preruminant calves into ruminant animals is the common denominator. Meanwhile, this adaptation predisposes dairy calves towards various health issues and metabolic disorders that occur in later life. Chromium (Cr) has been shown to potentiate insulin functioning and is thereby helpful in reducing the risk of these metabolic disorders. The aim of this study was to assess the effect of Cr supplementation on the insulin sensitivity and health status in Hariana calves during their transition period. A total of 24 preruminant Hariana calves were randomly allocated into four groups (6 calves per group) for a period of 90days. Calves either received a basal diet devoid of supplemental Cr (control; Cr0.0 group) or were supplemented with 0.05mg (Cr0.05 group), 0.10mg (Cr0.10 group), and 0.15mg (Cr0.15 group) of Cr per kg BW0.75 as Cr-picolinate (Cr-Pic). To determine the effect of Cr supplementation on the insulin response, glucose-insulin-non-esterified fatty acids (NEFAs) kinetics was studied during the intravenous glucose tolerance test (IVGTT) and oral glucose tolerance test (OGTT). A rapid glucose disappearance (p < 0.05) with unaltered insulin kinetics during IVGTT and OLTT indicates greater insulin sensitivity in calves supplemented with 0.10 and 0.15mg of Cr per kg BW0.75. Improved insulin sensitivity in the Cr0.10 and Cr0.15 groups was further confirmed by higher (p < 0.05) values of the insulin sensitivity check index (QUICKI), revised quantitative insulin sensitivity check index (RQUICKI), and lower (p < 0.05) values of the homeostasis model assessment-insulin resistance (HOMA-IR) during IVGTT. Mean serum non-esterified fatty acids (NEFAm), and insulin receptor substrate-1 (IRS-1) levels were the highest (p < 0.05) and cortisol concentrations were the lowest (p < 0.05) in the Cr0.15 groups. Unlike IVGTT, there was no effect of treatment, period, and treatment × period interaction on mean serum glucose and insulin levels during OGTT. However, Cr-supplemented calves had a higher (p < 0.05) glucose clearance rate (gCR). Serum IRS-1 concentrations during OGTT were also higher (p < 0.05) in the Cr0.10 and Cr0.15 groups than in the other groups. Serum Cr levels increased dose dependently and were the highest (p < 0.05) in calves fed a diet supplemented with 0.15mg Cr per kg BW0.75. There was no effect of treatment on average daily gain (ADG) and body condition score (BCS) while frequency and duration of diarrhea were lower and fecal score was better in Cr-supplemented calves. The current findings show that Cr supplementation improved glucose utilization and health status in calves during their transition period by improving insulin sensitivity.

Insulin resistance increases as days on feed advance in feedlot Bos indicus beef cattle offered a high-concentrate finishing diet.

This experiment evaluated the effects of advancing days on feed (DOF) on insulin resistance (IR) of finishing Bos indicus bulls offered a high-concentrate diet. On day 0, 100 Bos indicus Nellore bulls were housed in 12 feedlot pens (8 or 9 bulls/pen) for a 108-d feeding period, in a manner that all pens had an equivalent BW at the beginning of the finishing period. Bulls received the same diets throughout the 108-d feeding period. Diets were corn-based (38% starch) and were offered in amounts to ensure ad libitum intake. Individual shrunk BW was obtained on days 0 and 108 after 16 h of feed and water withdrawal, whereas unshrunk BW was recorded on days 19 and 60 for average daily gain (ADG) calculation. From days 0 to 108, feed intake and feed efficiency (FE) were calculated from each pen. Blood samples were collected on days 0, 60, and 108 to assess serum concentrations of haptoglobin, cortisol, glucose, and non-esterified fatty acids (NEFA), and insulin. Glucose, NEFA, and insulin concentrations were used to determine revised quantitative insulin sensitivity check index (RQUICKI), so that lower RQUICKI values indicate a greater IR of the herd. Pen was used as the experimental unit. Overall, DMI increased as DOF also increased (R2 = 0.71), being greater from days 19 to 60 and 60 to 108 vs. 0 to 19 (P < 0.0001), but did not differ between days 19 to 60 and 60 to 108 (P = 0.79). Conversely, ADG and FE linearly decreased as DOF increased from days 0 to 108 (P < 0.0001; R2 = 0.68 and 0.79, respectively). Log-transformed RQUICKI decreased as DOF increased up to 108 (P < 0.0001; r = -0.61). Similarly, serum concentrations of haptoglobin and cortisol increased as RQUICKI increased (P < 0.0001; r = 0.43 and 0.67, respectively). In summary, insulin resistance, per RQUICKI, increased and performance reduced in feedlot bulls with the advance of days on feed. Moreover, inflammatory markers were also positively associated with insulin resistance, suggesting that inflammation might be involved with the incidence of insulin resistance.

Supplementation of Rumen-Protected Glucose Increased the Risk of Disturbance of Hepatic Metabolism in Early Postpartum Holstein Cows.

The dual stress of reduced feed intake and increased milk yield in dairy cows early postpartum results in a negative energy balance. Rumen-protected glucose (RPG) has been reported to replenish energy, increase milk yield, and improve gut health. However, early postpartum cows often develop an insulin resistance, implying that RPG may not be well utilized and increased milk production may increase the liver’s fat oxidization burden. This study aimed to investigate the effects of RPG on the hepatic oxidative/antioxidative status and protein profile. Starting 7 d before expected calving, six pairs of cows were supplemented with rumen-protected glucose (RPG, n = 6) or with an equal amount of rumen-protecting coating fat (CON, n = 6). Liver samples were obtained from 10 cows 14 d after calving (d 14). Concentration of malondialdehyde and activity of glutathione peroxidase were increased and the activities of catalase and superoxide dismutase tended to increase in the livers of the RPG cows compared to the CON cows. The revised quantitative insulin sensitivity check index (RQUICKI) was decreased by RPG, but triacylglycerol concentration in liver was increased by RPG supplementation. The overall profiles of hepatic proteins were similar between CON and RPG. A partial least square regression was conducted to identify the proteins associated with liver lipidosis, oxidative stress, and antioxidative capacity. The top twenty proteins, according to their variable importance value, were selected for metabolic pathway enrichment analysis. Eighteen enriched KEGG pathways were identified, including metabolism, the citrate cycle, propanoate metabolism, the peroxisome, and type II diabetes mellitus. Our study showed that RPG supplementation reduced insulin sensitivity but increased the liver triglyceride concentration and the oxidative stress in early postpartum cows. Liver proteins related to lipidosis, oxidative stress, and antioxidative capacity, were positively associated with the glutamine metabolism, citric acid cycle, peroxisome, and type II diabetes pathways, which may indicate an increased risk of liver metabolic disorders caused by RPG supplementation in early postpartum cows.

Potential hemo-biological identification markers to the left displaced abomasum in dairy cows

BackgroundLeft displaced abomasum (LDA) occurs at high frequency in the early postpartum period and can affect production performance of dairy cows. Clinical diagnosis of LDA is usually done by abdominal auscultation and percussion. The purpose of this study was to explore the potential applicability of blood biomarkers for early warning and diagnosis of LDA in dairy cows.ResultsTwenty early postpartum healthy cows and thirty early postpartum LDA cows of similar parity were used. A receiver operating characteristic curve (ROC) method was used to analyze the sensitivity of hematological biomarkers to LDA including energy balance metabolic biomarkers, liver/kidney function biomarkers, and minerals. A cut-off point was defined for each of the selected hematological biomarkers deemed sensitive markers of LDA. Compared with healthy cows, body condition score (BCS), dry matter intake (DMI) and milk production were lower in LDA cows. Among energy metabolism markers, serum non-esterified fatty acid (NEFA), β-hydroxybutyric acid (BHBA), insulin (INS), and revised quantitative insulin sensitivity check index (RQUICKI) levels were lower while serum glucagon (GC) was greater in LDA cows. Among the liver/kidney function biomarkers, activities of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT), lactate dehydrogenase (LDH), the ratio of AST/ALT and levels of total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL), albumin (ALB), blood urea nitrogen (BUN), creatinine, and total protein (TP) were greater in LDA cows. Among minerals analyzed, serum Cl, Ca, and K were lower in LDA cows. After ROC analysis, it was determined that serum Ca, INS, RQUICKI, ALT, GGT, and creatinine are potential indicators for early warning and diagnosis of LDA for early postpartum dairy cows.ConclusionsDairy cows with LDA were under severe negative energy balance (NEB), had signs of liver damage and potentially lower insulin sensitivity. A combination of multi-hematological biomarkers including Ca, INS, RQUICKI, ALT, GGT and creatinine has the potential to help identify cows at risk of LDA in the early postpartum period.

Effects of body condition on the insulin resistance, lipid metabolism and oxidative stress of lactating dairy cows

BackgroundOverconditioned dairy cows are prone to greater insulin resistance in transition to successfully adapt to negative energy balance. The associations among body condition score (BCS), insulin resistance, lipid metabolism and oxidative stress in cows during late lactation with positive energy balance remain to be elucidated.MethodsThe objectives of this study were to investigate insulin sensitivity and oxidative status in late lactating dairy cows with different BCS but similar milk production, parity and days in milk. Forty-two multiparous Holstein cows were fed the same diet under the same management and divided into three groups based on BCS: low BCS (LBCS; BCS ≤ 2.75; n = 12), medium BCS (MBCS; 3.0 ≤ BCS ≤ 3.5; n = 15) or high BCS (HBCS; BCS ≥ 3.75; n = 15). Blood samples used for analysis of biochemical and hematological parameters were collected from the coccygeal vein at the end of experiment.ResultsThe concentrations of insulin and nonesterified fatty acid were higher and the revised quantitative insulin sensitivity check index (RQUICKI) was lower in HBCS cows than in LBCS and MBCS cows. These results suggest that insulin resistance exacerbates lipolysis in HBCS cows. Serum concentrations of very low-density lipoprotein, apolipoprotein A-I, and apolipoprotein B were lower in HBCS cows than in LBCS or MBCS cows. Although LBCS and MBCS cows had higher reactive oxygen species levels than did HBCS cows, the malondialdehyde concentration was not different among cows with different BCS. Ceruloplasmin activity was higher in MBCS and HBCS cows than in LBCS cows, but superoxide dismutase, glutathione peroxidase, and paraoxonase activities were not different among cows with different BCS. Despite the higher percentage of granulocytes in MBCS cows than in HBCS cows, no differences were found in leukocyte counts, red blood cell profiles and platelet profiles among the cows in the three groups.ConclusionsResults of this study showed that compared with MBCS and LBCS cows, HBCS cows at late lactation stage may have accumulated more hepatic triacylglycerol and lower antioxidant potential due to greater insulin resistance.

Cardiac, Energy and Hormonal Blood Markers, and Lactatemia in Cows with Displaced Abomasum

Background: Displaced abomasum (DA) is a common and economically important disorder that affects dairy cattle. Nutritional factors and adaptive responses that occur in the peripartum play a central role in the pathogenesis. The measurement of blood metabolites represents a useful tool for monitoring and prognostic determination in affected animals. Therefore, the objective was to evaluate cardiac, energy and hormonal blood markers, lactatemia, and insulin sensitivity in cows diagnosed with right displaced abomasum (RDA) and left displaced abomasum (LDA), comparing them with each other.Materials, Methods &amp; Results: Nineteen cases of abomasum displacement in cows were studied, including 9 cases of RDA and 10 cases of LDA. The diagnosis was established by means of physical examination and measurement of the concentration of chlorides in the ruminal fluid (&gt; 30mEq/L). After diagnosis, clinical-surgical therapeutic management was instituted. At the time of diagnosis (M1) and at the resolution of the case (M2), blood samples were collected to assess the variables: non-esterified fatty acids (NEFA), beta hydroxybutyrate (βHB), L-lactate, creatine kinase (CK), creatine kinase MB (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH), glucose, insulin, and cortisol. In addition, insulin sensitivity was estimated using the Revised Quantitative Insulin Sensitivity Check Index (RQUICKI) and RQUICKI-βHB. The means of the variables were compared, separating the effects of groups (RDA and LDA) and moments (M1 and M2), at the level of 5% probability. The concentrations of NEFA, CK-MB, L-lactate, glucose, insulin, and cortisol were higher at M1 and the RQUICKI and RQUICKI-βHB indices were lower at this moment. L-lactate, CK, and CK-MB were higher in the RDA group, while cTnI, βHB, and LDH did not present a group or moment effect. Cardiac markers correlated with the energy profile metabolites, L-lactate, and cortisol.Discussion: The high concentrations of NEFA at M1 reflected the condition of negative energy balance. βHB concentrations were stable, that may be related to the number of days postpartum in which the animals were diagnosed. The hyperglycemic condition and the increase in serum cortisol concentrations found at M1 can be induced by the condition of metabolic stress resulting from the disease. Hyperinsulinemia were recorded in the present study could be an important factor related to the pathogenesis of DA, since there seems to be a correlation between hyperinsulinemia and decreased abomasal emptying rate. The RQUICKI and RQUICKI-βHB indices was significantly lower at M1, which may indicate lower sensitivity of peripheral tissues to insulin at this time. Changes in serum activity of LDH and CK may result from tissue damage due to organ displacement, in addition to damage associated with surgery and the administration of injectable drugs, mainly intramuscularly. The elevation in plasma L-lactate at M1 and in the RDA group may be associated with abomasal hypoperfusion. The high positive correlations found between L-lactate and the variables glucose, insulin, and cortisol reinforcing the association between the concentration of L-lactate and the moment of greatest stress. The increase in cardiac biomarkers may be related to the occurrence of ischemia/reperfusion injury in the abomasum, which involves oxidative stress and the production of inflammatory mediators. The hyperglycemic condition and the higher concentrations of NEFA can also contribute to the occurrence of myocardial injury. The correlations found between cardiac biomarkers and plasma L-lactate, strengthen the idea that there is a relationship between L-lactate and myocardial injury. In this sense, the measurement of blood concentrations of cTnI, CK-MB, and L-lactate could contribute as severity markers and prognosis indicators in cattle with DA.

Serum adipokines play different roles in type I and II ketosis.

ObjectiveThis study was conducted to investigate the differences in several serum adipokines in perinatal dairy cows with type I and II ketosis, and the correlations between these adipokines and the two types of ketosis.MethodsSerum adiponectin (ADP), leptin (LEP), resistin, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels, and energy balance indicators related to ketosis were measured. Type I and II ketosis were distinguished by serum glucose (Glu) and Y values and the correlations between adipokines in the two types of ketosis were analyzed.Resultsβ-Hydroxybutyric acid of type I ketosis cows was significantly negatively correlated with insulin (INS) and LEP and had a significant positive correlation with serum ADP. In type II ketosis cows, ADP and LEP were significantly negatively correlated, and INS and resistin were significantly positively correlated. Revised quantitative INS sensitivity check index (RQUICKI) values had a significantly positive correlation with ADP and had a very significant and significant negative correlation with resistin, TNF-α, and IL-6. ADP was significantly negatively correlated with resistin and TNF-α, LEP had a significantly positive correlation with TNF-α, and a significantly positive correlation was shown among resistin, IL-6, and TNF-α. There was also a significant positive correlation between IL-6 and TNF-α.ConclusionINS, ADP, and LEP might exert biological influences to help the body recover from negative energy balance, whereas resistin, TNF-α, and IL-6 in type II ketosis cows exacerbated INS resistance and inhibited the production and secretion of ADP, weakened INS sensitivity, and liver protection function, and aggravated ketosis.

Intermittent energy restriction is comparable to continuous energy restriction for cardiometabolic health in adults with central obesity: A randomized controlled trial; the Met-IER study

Short bouts of severe energy restriction may have additional, beneficial cardiometabolic effects beyond that of weight loss. We aimed to assess the short-term effects of intermittent fasting on insulin sensitivity and related cardiometabolic mechanisms. This parallel arm, randomized controlled trial compared the short-term effects of intermittent and continuous energy restriction (IER and CER) diets on markers of cardiometabolic health in individuals with central obesity, aiming for equivalent weight loss on both diets. Outcomes were assessed in non-smoking men and women (35-75y), following 4-wk IER (48h 600kcal/d followed by 5-day healthy eating advice) or CER diets (-500kcal/d healthy eating advice). The primary outcome was the revised quantitative insulin sensitivity check index (R-QUICKI), an indirect estimate of insulin sensitivity. Secondary outcomes included ambulatory blood pressure (ABP), indicators of sympathetic activity (heart rate variability (HRV) and normetanephrine), and markers of glucose homeostasis/insulin resistance, adiposity, lipids and inflammation. Forty-three participants completed the study. Reductions in body weight were equivalent in both groups: mean loss (%)-2.6; 95% CI-3.3,-1.9 and-2.9;-3.6,-2.1 for CER and IER, respectively, P=0.464). R-QUICKI increased following IER and CER, with no between-diet differences (overall mean increase (%) 6.6; 3.6, 9.6). Fasting plasma glucose concentrations decreased after CER but not after IER (mean difference CER-IER - 4.8% (0.7, 8.9), P<0.05) and fasting plasma non-esterified fatty acid concentrations were lower after IER compared to CER (mean difference CER-IER 0.15mmol/L (0.06, 0.24), P<0.005). There were no differences in lipids, adipokine/inflammatory markers, ABP or HRV between diets. Short-term CER or IER diets are comparable in their effects on most markers of cardiometabolic risk, although adaptive changes in glucose and fatty acid metabolism occur. This study is registered at clinicaltrials.gov as NCT02679989.

Association Between Plasma Metabolites and Insulin Sensitivity Indexes in Fat-Tailed and Thin-Tailed Lambs During Negative and Positive Energy Balances

Background: Fatty acid mobilization and inflammatory response of adipose tissues vary in various depots, hence the response of fat-tailed and thin-tailed sheep breeds to different energy balances was hypothesized to be different due to differences in proportion and metabolism of various adipose depots in these breeds which may affect whole body insulin sensitivity. Objective: Current study aimed to evaluated the changes in plasma metabolites including non-esterified fatty acid (NEFA), glucose, insulin, triglyceride (TG) and tumor necrosis factor-alpha in response to negative and positive energy balances and their correlation with insulin sensitivity indexes in Lori-Bakhtiari fat-tailed and Lori-Bakhtiari × Romanov cross breed thin-tailed lambs. Methods: Thirty-six male lambs (18 fat-tailed and 18 thin-tailed lambs) were placed in individual pens and experienced periods of negative (21 d) and positive (21 d) energy balances. Lambs were bled weekly to measure plasma metabolites. Pearson correlation coefficients among variables were generated using Proc Corr of SAS. Results: In thin-tailed but not fat-tailed lambs, plasma NEFA showed a negative correlation with plasma glucose (R = -0.47; P < 0.0003) and insulin (R = -0.46; P < 0.0005) content. Plasma NEFA negatively correlated with revised quantitative insulin sensitivity check index (RQUICKI) and severity of the correlation was higher in fat-tailed (R = -0.58; P < 0.0001) comparing to thin-tailed (R = -0.40; P < 0.003) lambs. In fat-tailed lambs, plasma NEFA and insulin were the most influential factors on RQUICKI, whereas in thin-tailed lambs, insulin was the main factor affecting RQUICKI. Conclusion: The results of current study demonstrate that despite higher basal and negative energy balance induced plasma NEFA content in thin-tailed lambs, the contribution of plasma NEFA to insulin resistance was higher in fat-tailed lambs, whereas negative correlation between plasma NEFA and insulin content in thin-tailed lambs demonstrate higher sensitivity of insulin secretion capacity to plasma NEFA content.

Berberine Protects against NEFA-Induced Impairment of Mitochondrial Respiratory Chain Function and Insulin Signaling in Bovine Hepatocytes.

Fatty liver is a major lipid metabolic disease in perinatal dairy cows and is characterized by high blood levels of non-esterified fatty acid (NEFA) and insulin resistance. Berberine (BBR) has been reported to improve insulin sensitivity in mice with hepatic steatosis. Mitochondrial dysfunction is considered a causal factor that induces insulin resistance. This study investigates the underlying mechanism and the beneficial effects of BBR on mitochondrial and insulin signaling in bovine hepatocytes. Revised quantitative insulin sensitivity check index (RQUICKI) of cows with fatty liver was significantly lower than that of healthy cows. Importantly, the Akt and GSK3β phosphorylation levels, protein levels of PGC-1α and four of the five representative subunits of oxidative phosphorylation (OXPHOS) were significantly decreased in cows with fatty liver using Western Blot analysis. In bovine hepatocytes, 1.2 mmol/L NEFA reduced insulin signaling and mitochondrial respiratory chain function, and 10 and 20 umol/L BBR restored these changes. Furthermore, activation of PGC-1α played the same beneficial effects of BBR on hepatocytes treated with NEFA. BBR treatment improves NEFA-impaired mitochondrial respiratory chain function and insulin signaling by increasing PGC-1α expression in hepatocytes, which provides a potential new strategy for the prevention and treatment of fatty liver in dairy cows.

Effects of different dosages of propylene glycol in dry cows and cows in early lactation.

In this Research Paper we hypothesised that the temporary insulin resistance seen during the transition period in dairy cows may cause significant differences in the efficacy of PG at different sampling periods and that in some cases this effect will be dose dependent. Eighty four sampling sets were generated by studying 7 multiparous Holstein cows repeatedly at 4 sampling periods of 3 d length (dry cows: days 40, 39 and 38 antepartum; close up cows: days 10, 9 and 8 antepartum; fresh cows: days 3, 4 and 5 post-partum; lactating cows: days 38, 39 and 40 post-partum). On each of these days 3 h after morning feeding propylene glycol was drenched in different dosages of 100, 300 or 500 ml once per day (cross over study). The different doses were applied in an alternating order (Latin square). Blood samples were taken before, every 30 min up to 4 h, after 6 and 12 h after PG application. Following parameters have been measured: insulin, non-esterified fatty acids (NEFA), betahydroxybutyrate (BHB), bilirubin, cholesterol, potassium, aspartate aminotransferase (AST) and glutamate dehydrogenase (GLDH). Revised Quantitative Insulin Sensitivity Check Index (RQUICKI) was calculated. It was found that glucose, insulin, NEFA, BHB, bilirubin and potassium concentrations were influenced differently by the three defined dosages of propylene glycol at four different sampling periods. Whereas RQUICKI, cholesterol, AST and GLDH did not differ between the sampling periods and treatments. The major results of the study are that the effect of PG is dose-dependent and that the effect of PG is depending on the time of application according to calving. It can be concluded that in fresh cows higher dosages are necessary to provoke similar effects in comparison to dry, close up and lactating cows. Although the study did not compare to topdressing of PG from the results it is reasonable to believe that bolus application of a specific PG volume is necessary to provoke the effect.

Relationship between the indexes of insulin resistance and metabolic status in dairy cows during early lactation

Abstract Insulin resistance is a phenomenon which accompanies the ongoing metabolic adaptation in cows during early lactation. The aim of our study was to determine the linear correlations of HOMA (Homeostatic Model Assessment), QUICKI (Quantitative Insulin Sensitivity Check Index) and RQUICKI (Revised Quantitative Insulin Sensitivity Check Index) indexes of insulin resistance with the metabolic status of cows (concentration of hormones, metabolites and body condition score). The experiment included 40 Holstein-Frisian cows in the first week after calving. Indexes of insulin resistance valued: 18.68±5.43 (HOMA), 0.39±0.06 (QUICKI) and 0.45±0.06 (RQUICKI). Linear correlations were examined by testing the coefficient of correlation (r), determination (r2,%) and regression parameter beta (b) in linear equation. A negative correlation was found between HOMA and IGF-I (insulin growth factor I) (r=−0.51, r2=25.0, b=−1.1257, p&lt;0.01). HOMA showed a positive correlation with BHB (betahidroxybutyrate) (r=0.48, r2=23.2, b=0.0234, p&lt;0.01). A positive correlation was found between QUICKI and IGF-I (r=0.30, r2=10.0 b=46.7900, p&lt;0.05) and cholesterol (r=0.44, r2=18.3, b=1.9021, p&lt;0.01). In contrast, QUICKI and BHB (r=0.51, r2=27.1, b=−1.7241, p&lt;0.01), just like QUICKI and BCS (r=0.46, r2=20.9, b=−2.424, p&lt;0.01), showed a negative correlation. RQUICKI showed positive correlations with IGF-I (r=0.48, r2=22.8, b=28.1230, p&lt;0.01), T4 (r=0.47, r2=22.1, b=87.142, p&lt;0.01) and triglycerides (r=0.36, r2=13, b=0.0407, p&lt;0.05) but negative correlations with cortisol (r=−0.36, r2=13.0, b=−9.0332, p&lt;0.05), STH (somatotropic hormone) (r=−0.42, r2=17.3, b=−5.4976, p&lt;0.01), BHB (r=−0.62, r2=38.3, b=−1.1872, p&lt;0.01), total bilirubin (r=−0.58, r2=33.7, b=−7.131, p&lt;0.01) and BCS (body condition score) (r=−0.6, r2=36.4, b=−1.8347, p&lt;0.01). In conclusion, indexes of insulin resistance may be used to evaluate the metabolic status of cows in early lactation. RQUICKI might be the most appropriate predictor of metabolic status due to its linear relationship with most of the parameters included in homeorhetic process.

Different milk feeding intensities during the first 4 weeks of rearing dairy calves: Part 2: Effects on the metabolic and endocrine status during calfhood and around the first lactation

Feeding dairy calves at high intensity has been demonstrated to increase milk yield in later life. We investigated the effect of 3 different feeding regimens in the preweaning period on the metabolic and endocrine status during calfhood and in heifers at the onset of the first lactation. In trial 1, 57 German Holstein calves were allocated to 3 different feeding groups: milk replacer restricted to 6.78 kg/calf per day, 11.5% solids (MR-res, n = 20), milk replacer 13.8% solids, ad libitum (MR-ad lib, n = 17), and whole milk ad libitum (WM-ad lib, n = 20). All calves received ad libitum colostrum for 3 d postnatal (p.n.). From d 4 to 27, all calves were fed according to their respective feeding regimen, resulting in average intakes of 6.38, 9.25, and 9.47 kg/d in MR-res, MR-ad lib, and WM-ad lib, respectively. Thereafter, all calves were fed according to the MR-res regimen until weaning at d 55 (gradually until d 69 p.n.). Blood samples were collected on d 0 before colostrum intake and on d 1, 3, 11, 22, 34, 43, 52, 70, 90, and 108 p.n. Liver biopsies were taken on d 19 and 100, and on d 22, 52, and 108 p.n. intravenous glucose tolerance tests were performed. The male calves (n = 8 to 10 per group) underwent also an insulin tolerance test on d 24, 54, and 110 p.n. The females (n = 28) from trial 1 were further reared and bred as common practice, and were enrolled in trial 2 when beginning the last trimester of pregnancy. Blood samples were collected monthly antepartum starting 91 d before calving and weekly (0-70 d) postpartum. Trial 1 was subdivided into 4 phases (P): P0 (d 0-1), P1 (d 2-27), P2 (d 28-69), and P3 (d 70-110 p.n.). In trial 1, the leptin and adiponectin concentrations increased with colostrum intake. Differences in fatty acids, insulin, adiponectin, revised quantitative insulin sensitivity check index (RQUICKI), and variables from the glucose tolerance tests were largely limited to P1. The MR-res group had greater RQUICKI and fatty acid values, and lower insulin and, as a trend, adiponectin concentrations than in 1 or both ad lib groups. These differences were partly sustained in P2 (fatty acids, adiponectin, and RQUICKI) and in P3 (adiponectin). The hepatic mRNA abundance of the gluconeogenic enzymes phosphoenolpyruvate carboxykinase and pyruvatcarboxylase increased from d 19 to 100. None of the blood variables were different between the groups when tested in pregnancy and lactation. Our results do not support a sustained deflection of metabolic regulation by rearing at different feeding intensities; nevertheless, the differences observed during rearing might influence nutrient utilization in later life or the cellular development of organs, such as the mammary gland, and thereby affect milk yield. Further studies involving greater animal numbers and, thus, improved power will help to sort out the mechanisms of programming body function in later life via nutrition in early life.

The effect of subclinical ketosis on indices of insulin sensitivity and selected metabolic variables in transition dairy cattle

Up to now, there have been several endeavors describing the extent of insulin resistance (IR) in dairy cows with particular emphasis on transition period, but it is not fully explicit what IR plays in the etiology of subclinical ketosis (SCK) in transition cows. The present study was therefore conducted on a commercial dairy herd with a stock population of 730 Holstein-Friesian cows to evaluate the extent of IR in transition cows with SCK. Blood samples were collected initially from each of the transition cows (n = 24) to estimate serum levels of β-hydroxybutyrate (BHBA). Cows with no clinical signs but having serum BHBA >1.20 to 2.9 mmol/l were considered to have SCK (n = 20), while those having serum BHBA concentrations <1.00 mmol/l were considered as controls (n = 4). Blood samples were then used for estimating values of serum non-esterified fatty acid (NEFA), glucose, insulin, and cortisol. Different surrogate indices for insulin sensitivity were also calculated. Our findings demonstrated that values of BHBA, NEFA, and insulin were significantly higher in cows with SCK than those of controls (P < 0.05), while values of cortisol and glucose, despite being higher in diseased cows than controls, did not reach statistical significance (P = 0.605 and ​0.269). Indices of insulin sensitivity showed a significant decrease in revised quantitative insulin sensitivity check index (RQUICKI) (P = 0.047) and a significant increase in homeostasis model assessment (HOMA) in diseased cows compared with controls (P = 0.007). The elevated values of serum glucose, insulin, cortisol, NEFA, and BHBA are therefore suggestive of impaired whole-body insulin sensitivity and were consistent with decreased RQUICKI in the diseased cows. Further studies are needed to use prophylactic feed additives to enhance insulin sensitivity and to help mitigate the deleterious consequences of bovine ketosis during the transition phase.

Effects of excessive energy intake and supplementation with chromium propionate on insulin resistance parameters in nonlactating dairy cows1

The objective was to compare insulin resistance parameters in cows with adequate or excessive energy intake as well as in cows with excessive energy intake receiving Cr supplementation as chromium propionate. Thirteen multiparous, nonlactating Gir × Holstein cows were ranked by BW and BCS and assigned to 1 of 3 dietary treatments on d 0: 1) diet to meet their ME requirements without Cr supplementation (MAN; n = 4), 2) diet to exceed their ME requirements without Cr supplementation (HIGH; n = 4), and 3) HIGH with 2.5 g/d of chromium propionate (HIGHCR; n = 5, with 10 mg of Cr/cow daily). Diets were formulated to provide 100% of daily ME requirements of MAN and 177% of daily ME requirements of HIGH and HIGHCR cows and offered twice daily via individual self-locking head gates from d 0 to 88. Cow BW and BCS were recorded on d 0 and 88 of the experiment. Blood samples were collected before and 2 h after the morning feeding twice weekly. Preprandial revised quantitative insulin sensitivity check index (RQUICKI) was determined using serum glucose, insulin, and NEFA concentrations obtained before feeding. Glucose tolerance tests (GTT) were performed on d 32 and 88 by infusing cows with 0.5 g of glucose/kg of BW whereas blood samples were collected at -15, 0, 10, 20, 30, 45, 60, and 90 min relative to infusion. Change in BCS tended to be greater in HIGH and HIGHCR (P = 0.09) compared with MAN cows. Within samples collected twice weekly, serum concentrations of glucose, insulin (beginning on d 14 of the experiment), and NEFA (preprandial samples only) were greater (P ≤ 0.05) in HIGH compared with HIGHCR cows and tended to be greater in HIGH compared with MAN cows (P ≤ 0.10) but did not differ (P ≥ 0.52) between HIGHCR and MAN cows. Moreover, HIGH cows had reduced RQUICKI compared with MAN (P = 0.02) and HIGHCR cows (P = 0.05) whereas RQUICKI was similar between MAN and HIGHCR cows (P = 0.53). Within samples collected during the GTT, mean serum insulin concentrations and insulin:glucose ratio were greater (P < 0.01) in HIGH compared with HIGHCR cows, tended (P ≤ 0.09) to be greater in HIGH compared with MAN cows, and were similar (P ≥ 0.16) between HIGHCR and MAN cows. Serum glucose concentrations were greater (P < 0.01) for HIGH compared with MAN and HIGHCR cows 20 min relative to infusion. In conclusion, chromium propionate supplementation prevented the increase in insulin resistance caused by excessive energy intake in nonlactating dairy cows.

Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle

Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation.

Effects of bovine somatotropin injection on serum concentrations of progesterone in non-lactating dairy cows

The objective of this experiment was to evaluate the effects of bovine somatotropin administration on serum concentrations of glucose, insulin, NEFA, IGF-I, and progesterone (P4) in ovariectomized non-lactating dairy cows receiving exogenous P4, as a model to estimate treatment effects on hepatic P4 degradation. Ten non-lactating, non-pregnant, and ovariectomized Gir×Holstein cows were assigned to the experiment (d −14 to 27). On d 0, cows were ranked by BW and BCS, and randomly assigned to one of two treatments: (1) bovine somatotropin (BST; n=5) or (2) saline control (control; n=5). Cows assigned to the BST treatment were administered s.c. injections containing 500mg of sometribove zinc on d 0, 9, and 18 of the experiment, whereas control cows concurrently received a 10-mL s.c. injection of 0.9% saline. On d −2, cows were inserted with an intravaginal releasing device containing 1.9g of P4, which remained in the cows until the end the experiment (d 27). Cow BW and BCS were assessed on d −14, 0, and 27. Blood samples were collected daily from d 0 to d 27, at 0 (immediately before), 1, and 2h relative to concentrate feeding for determination of serum glucose, insulin, NEFA, P4, and IGF-I concentrations. Concentrations of glucose, NEFA, and insulin obtained prior to feeding (0h) were used to determine pre-prandial revised quantitative insulin sensitivity check index (RQUICKI). No treatment effects were detected for BW (P=0.72) and BCS change (P=0.79) during the experiment. Beginning on d 2 of the experiment, BST cows had greater (P≤0.01) serum IGF-I concentrations compared with control cohorts (treatment×day interaction; P<0.01). Cows receiving BST had greater (P≤0.05) insulin concentrations compared with control cohorts from d 8 to d 11, d 16 and 17, as well as from d 19 to d 21 of the experiment (treatment×day interaction; P<0.01). Cows receiving BST had greater (P≤0.01) mean glucose and NEFA concentrations, as well as reduced (P<0.01) mean RQUICKI during the experiment compared with control cohorts. No treatment effects, however, were detected (P=0.73) for serum P4 concentrations. In conclusion, results from this experiment indicate that hepatic P4 catabolism is not directly regulated by circulating IGF-I, whereas BST administration decreases insulin sensitivity in non-lactating dairy cows in adequate nutritional status.