Comparison of insulin sensitivity between healthy neonatal foals and horses using minimal model analysis

The equine neonate is considered to have impaired glucose tolerance due to delayed maturation of the pancreatic endocrine system. Few studies have investigated insulin sensitivity in newborn foals using dynamic testing methods. The objective of this study was to assess insulin sensitivity by comparing the insulin-modified frequently sampled intravenous glucose tolerance test (I-FSIGTT) between neonatal foals and adult horses. This study was performed on healthy neonatal foals (n = 12), 24 to 60 hours of age, and horses (n = 8), 3 to 14 years of age using dextrose (300 mg/kg IV) and insulin (0.02 IU/kg IV). Insulin sensitivity (SI), acute insulin response to glucose (AIRg), glucose effectiveness (Sg), and disposition index (DI) were calculated using minimal model analysis. Proxy measurements were calculated using fasting insulin and glucose concentrations. Nonparametric statistical methods were used for analysis and reported as median and interquartile range (IQR). SI was significantly higher in foals (18.3 L·min-1· μIU-1 [13.4–28.4]) compared to horses (0.9 L·min-1· μIU-1 [0.5–1.1]); (p < 0.0001). DI was higher in foals (12 × 103 [8 × 103−14 × 103]) compared to horses (4 × 102 [2 × 102−7 × 102]); (p < 0.0001). AIRg and Sg were not different between foals and horses. The modified insulin to glucose ratio (MIRG) was lower in foals (1.72 μIUinsulin2/10·L·mgglucose [1.43–2.68]) compared to horses (3.91 μIU insulin2/10·L·mgglucose [2.57–7.89]); (p = 0.009). The homeostasis model assessment of beta cell function (HOMA-BC%) was higher in horses (78.4% [43–116]) compared to foals (23.2% [17.8–42.2]); (p = 0.0096). Our results suggest that healthy neonatal foals are insulin sensitive in the first days of life, which contradicts current literature regarding the equine neonate. Newborn foals may be more insulin sensitive immediately after birth as an evolutionary adaptation to conserve energy during the transition to extrauterine life.

Goji Berry (Lycium barbarum) Supplementation during Pregnancy Influences Insulin Sensitivity in Rabbit Does but Not in Their Offspring

This study investigated the effects of Goji berry (Lycium barbarum) dietary supplementation during pregnancy on insulin sensitivity of rabbit does and their offspring. Starting from two months before the artificial insemination, 75 New Zealand White does were fed only commercial standard diet (C) or supplemented with 1% (G1) and 3% (G3) of Goji berries. Their offspring received a standard diet but kept the nomenclature of the mother’s group. Fasting and intravenous glucose tolerance test-derived indices were estimated at 21 days of pregnancy on rabbit does and at 90 days of age on the offspring. No difference was found in the fasting indices, while the diet modulated the response to glucose load of rabbit does. In particular, G3 group had the lowest glucose concentrations 5 min after the bolus administration (p < 0.05) and, as a result, differed in the parameters calculated during the elimination phase such as the elimination rate constant (Kel), the half-life of the exogenous glucose load (t1/2), and apparent volume of distribution (Vd; for all, p < 0.05). The high dose of Goji supplementation could thus enhance the first-phase glucose-induced insulin secretion. Findings on the offspring were inconsistent and therefore a long-term effect of Goji supplementation during pregnancy could not be demonstrated. Further study on the effect of Goji on the secretory pathway of insulin could clarify its hypoglycaemic action, while different protocols are needed to investigate its potential effects on foetal programming.

The Research on Perioperative Blood Glucose and Insulin Levels of Patients with Single Insulinoma

Background The blood glucose level is an important biochemical parameter for evaluating the resection effectiveness of insulinomas. However, whether other biochemical parameters have better evaluating ability remains unclear. The current study aims to compare the evaluating capability of blood glucose and insulin levels at several aspects, such as the accuracy and response time. Methods Between September 2017 and July 2018, 21 insulinoma patients with single tumor who underwent surgical resection were enrolled. Peripheral venous blood samples were assayed for blood glucose and insulin levels on the day of surgery and at 30 minutes, 60 minutes, 1 day, and 7 days after surgery. The evaluating abilities of blood glucose and insulin levels for resection effectiveness were recorded and compared. Results The evaluating performance of the insulin level was better than that of the blood glucose level (100% for 21 patients vs 82.4% for 17 patients), as well as the response time ( p<0.0001). Furthermore, the insulin level was not effected by intravenous glucose infusion compared to the blood glucose level. Conclusions Comparing with blood glucose level, insulin level is a better parameter for evaluating resection effectiveness of insulinomas with faster response and regardless of perioperative intravenous glucose infusion.

Impaired Insulin Clearance as the Initial Regulator of Obesity-Associated Hyperinsulinemia: Novel Insight Into the Underlying Mechanism Based on Serum Bile Acid Profiles

<b>OBJECTIVE</b> <div><p>To investigate the roles of insulin clearance and insulin secretion in the development of hyperinsulinemia in obese subjects and to reveal the association between insulin clearance and bile acids (BAs).</p> <p><b> </b></p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>In cohort 1, insulin secretion, sensitivity and endogenous insulin clearance were evaluated with an oral glucose tolerance test (OGTT) in 460 recruited participants. In cohort 2, 81 participants underwent an <a>intravenous glucose tolerance test</a> (IVGTT) and a hyperinsulinemic-euglycemic clamp to assess insulin secretion, endogenous and exogenous insulin clearance, and insulin sensitivity. Based on insulin resistance levels ranging from mild to severe, nondiabetic obese participants were further divided into 10 quantiles in cohort 1 and into tertiles in cohort 2. Forty serum BAs were measured in cohort 2 to examine the association between BAs and insulin clearance.</p> <p><b> </b></p> <p><b>RESULTS</b></p> <p>All obese participants had impaired insulin clearance, and it worsened with additional insulin resistance in nondiabetic obese subjects. However, insulin secretion was unchanged from quantile 1 to 3 in cohort 1, and no difference was found in cohort 2. After adjustments for all confounding factors, serum conjugated BAs, especially glycodeoxycholic acid (GDCA, β=-0.335, P=0.004) and taurodeoxycholic acid (TDCA, β=-0.333, P=0.003), were negatively correlated with insulin clearance<a>. The ratio of </a><a></a><a>unconjugated to conjugated BAs (UnconBA/ConBA</a>, β=0.335, P=0.002) was positively correlated with insulin clearance.</p> <p><b> </b></p> <p><b>CONCLUSIONS</b></p> <p>Hyperinsulinemia in obese subjects might be primarily induced by decreased insulin clearance rather than increased insulin secretion. Changes in circulating conjugated BAs, especially GDCA and TDCA, might play an important role in regulating insulin clearance.</p></div>

Impaired Insulin Clearance as the Initial Regulator of Obesity-Associated Hyperinsulinemia: Novel Insight Into the Underlying Mechanism Based on Serum Bile Acid Profiles

<b>OBJECTIVE</b> <div><p>To investigate the roles of insulin clearance and insulin secretion in the development of hyperinsulinemia in obese subjects and to reveal the association between insulin clearance and bile acids (BAs).</p> <p><b> </b></p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>In cohort 1, insulin secretion, sensitivity and endogenous insulin clearance were evaluated with an oral glucose tolerance test (OGTT) in 460 recruited participants. In cohort 2, 81 participants underwent an <a>intravenous glucose tolerance test</a> (IVGTT) and a hyperinsulinemic-euglycemic clamp to assess insulin secretion, endogenous and exogenous insulin clearance, and insulin sensitivity. Based on insulin resistance levels ranging from mild to severe, nondiabetic obese participants were further divided into 10 quantiles in cohort 1 and into tertiles in cohort 2. Forty serum BAs were measured in cohort 2 to examine the association between BAs and insulin clearance.</p> <p><b> </b></p> <p><b>RESULTS</b></p> <p>All obese participants had impaired insulin clearance, and it worsened with additional insulin resistance in nondiabetic obese subjects. However, insulin secretion was unchanged from quantile 1 to 3 in cohort 1, and no difference was found in cohort 2. After adjustments for all confounding factors, serum conjugated BAs, especially glycodeoxycholic acid (GDCA, β=-0.335, P=0.004) and taurodeoxycholic acid (TDCA, β=-0.333, P=0.003), were negatively correlated with insulin clearance<a>. The ratio of </a><a></a><a>unconjugated to conjugated BAs (UnconBA/ConBA</a>, β=0.335, P=0.002) was positively correlated with insulin clearance.</p> <p><b> </b></p> <p><b>CONCLUSIONS</b></p> <p>Hyperinsulinemia in obese subjects might be primarily induced by decreased insulin clearance rather than increased insulin secretion. Changes in circulating conjugated BAs, especially GDCA and TDCA, might play an important role in regulating insulin clearance.</p></div>

A feed-centric hypoglycaemia pathway ensures appropriate care escalation in at-risk infants

BackgroundThere is a lack of clarity of what constitutes the starting point of a clinical pathway for infants at-risk of hypoglycaemia. Glucose-centric pathways (GCP) identify low glucose in the first 2 hours of life that may not represent clinical hypoglycaemia and can lead to inappropriate glucose management with infusions and medications.ObjectiveTo study the impact of a feed-centric pathway (FCP) on the number of admissions for hypoglycaemia to level 2 special care nursery (SCN) and the need for parenteral glucose/medications, compared to GCP.MethodsThis project was conducted over 2 years, before and after switching from a GCP to FCP in our institution. FCP involves skin-to-skin care, early breast feeding, checking glucose at 2 hours and use of buccal glucose. The primary outcome was the number of SCN admissions for hypoglycaemia. Secondary outcomes include the number of infants needing intravenous glucose, medications and length of SCN stay.ResultsOf 23 786 live births, 4438 newborns were screened. We screened more infants at-risk for hypoglycaemia using the FCP (GCP:1462/11969, 12.2% vs FCP:2976/11817, 25.1%) but significantly reduced SCN admissions (GCP:246/1462, 16.8% vs FCP:102/2976, 3.4%; p<0.0001). Fewer but proportionally more FCP newborns required intravenous glucose (GCP: 136/246, 55% vs FCP: 88/102, 86%; p=0.000). Compared with GCP, FCP reduced the total duration of stay in SCN by 104 days per annum, reducing the cost of care. However, the mean length of SCN stay for FCP was higher (GCP:2.43 days vs FCP:3.49 days; p=0.001). There were no readmissions for neonatal hypoglycaemia to our institution.ConclusionThe use of FCP safely reduced SCN admissions, averted avoidable escalation of care and helped identify infants who genuinely required intravenous glucose and SCN care, allowing more efficient utilisation of healthcare resources.

Insulin resistance induced by long-term sleep deprivation in rhesus macaques can be attenuated by Bifidobacterium

Long-term sleep deprivation (SD) is a bad lifestyle habit, especially among specific occupational practitioners, characterized by circadian rhythm misalignment and abnormal sleep/wake cycles. SD is closely associated with an increased risk of metabolic disturbance, particularly obesity and insulin resistance. The incretin hormone, glucagon-like peptide-1 (GLP-1), is a critical insulin release determinant secreted by the intestinal L-cell upon food intake. Besides, the gut microbiota participates in metabolic homeostasis and regulates GLP-1 release in a circadian rhythm manner. As a commonly recognized intestinal probiotic, Bifidobacterium has various clinical indications regarding its curative effect. However, few studies have investigated the effect of Bifidobacterium supplementation on sleep disorders. In the present study, we explored the impact of long-term SD on the endocrine metabolism of rhesus monkeys and determined the effect of Bifidobacterium supplementation on the SD-induced metabolic status. Lipids concentrations, body weight, fast blood glucose, and insulin levels increased after SD. Furthermore, after two months of long-term SD, the intravenous glucose tolerance test (iVGTT) showed that the glucose metabolism was impaired and the insulin sensitivity decreased. Moreover, one month of Bifidobacterium oral administration significantly reduced blood glucose and attenuated insulin resistance in rhesus macaques. Overall, our results suggested that Bifidobacterium might be used to alleviate SD-induced aberrant glucose metabolism and improve insulin resistance. Also, it might help in better understanding the mechanisms governing the beneficial effects of Bifidobacterium.

Comparison of Various Indices in Identifying Insulin Resistance and Diabetes in Chronic Spinal Cord Injury

The purpose of this screening and diagnostic study was to examine the accord among indices of glucose metabolism, including the Homeostatic Model Assessment for Insulin Resistance (HOMA), HOMA2, Matsuda Index, Quantitative Insulin-sensitivity Check Index (QUICKI), hemoglobin A1C (HbA1C), and fasting plasma glucose (FPG) against intravenous glucose tolerance test-measured insulin sensitivity (Si) in individuals with chronic motor complete SCI. Persons with chronic (≥12-months post-injury) SCI (n = 29; 79% men; age 42.2 ± 11.4; body mass index 28.6 ± 6.4 kg/m2; C4-T10) were included. Measures were compared using adjusted R2 from linear regression models with Akaike information criterion (AIC, a measure of error). QUCKI had the greatest agreement with Si (adjusted R2 = 0.463, AIC = 91.1, p = 0.0001), followed by HOMA (adjusted R2 = 0.378, AIC = 95.4, p = 0.0008), HOMA2 (adjusted R2 = 0.256, AIC = 99.7, p = 0.0030), and the Matsuda Index (adjusted R2 = 0.356, AIC = 95.5, p = 0.0004). FPG (adjusted R2 = 0.056, AIC = 107.5, p = 0.1799) and HbA1C (adjusted R2 = 0.1, AIC = 106.1, p = 0.0975) had poor agreement with Si. While HbA1C and FPG are commonly used for evaluating disorders of glucose metabolism, QUICKI demonstrates the best accord with Si compared to the other measures.

Patterns of Insulin Secretion During First-Phase Insulin Secretion in Normal Chinese Adults

BackgroundThe increase in diabetes worldwide is alarming. Decreased acute insulin response to intravenous glucose tolerance test (IVGTT) during first-phase insulin secretion (FPIS) is a characteristic of diabetes. However, knowledge of the insulin secretion characteristics identified by different time to glucose peak in subjects with different metabolic state is sparse.AimsThis study aimed to find different patterns of FPIS in subjects with normal glucose tolerance (NGT) and analyzed the relationship between insulin secretion patterns and the risk for development of type 2 diabetes mellitus (T2DM).MethodsA total of 126 subjects were divided into three groups during a 10-min IVGTT, including NGT with time to glucose peak after 3 min (G1, n = 21), NGT with time to glucose peak at 3 min (G2, n = 95), and prediabetes or diabetes with time to glucose peak at 3 min (G3, n = 10). Glucose, insulin, and C-peptide concentrations at 0, 3, 5, 7, and 10 min during the IVGTT were tested. IVGTT-based indices were calculated to evaluate the insulin secretion and insulin sensitivity.ResultsAge, body mass index (BMI), waist-to-hip ratio, triglyceride (TG), and hemoglobin A1c (HbA1c) of subjects were gradually higher, while high-density lipoprotein cholesterol (HDL-C) was gradually lower from G1 to G3 (p for linear trend &lt;0.05), and the differences between G1 and G2 were also statistically significant (p &lt; 0.05). Glucose peak of most participants in G1 converged at 5 min, and the curves shape of insulin and C-peptide in G2 were the sharpest among three groups. There was no significant difference in all IVGTT-based indices between G1 and G2, but AUCIns, AUCIns/AUCGlu, and △Ins3/△Glu3 in G2 were the highest, and the p-value for linear trend of those indices among three groups were statistically significant (p &lt; 0.05).ConclusionsTwo patterns of FPIS were in subjects with NGT, while subjects with later time to glucose peak during FPIS might be less likely to develop T2DM in the future.

Effects of increasing calcium propionate in a finishing diet on dry matter intake and glucose metabolism in steers

The objective of this study was to determine if increasing propionate alters dry matter intake (DMI), glucose clearance rate, blood metabolites, insulin concentrations and hepatic gene expression in steers fed a finishing diet. Holstein steers (n = 15; BW = 243 ± 3.6 kg) were individually fed a finishing diet ad-libitum. Steers were allocated by body weight (BW) to receive: no Ca propionate (Control), 100 g/d Ca propionate (Low), or 300 g/d Ca propionate (High) in the diet. Orts were collected and weighed daily to determine DMI. Blood samples were collected on d 0, 7, and 21, and BW recorded on d 0, 14, and 28. An intravenous glucose tolerance test (IVGTT) was conducted on d 14 and 28 of the trial. Liver biopsies were collected on d 33 for gene expression analysis. Blood samples were analyzed for whole blood glucose and lactate, plasma non-esterified fatty acids (NEFA) and insulin concentrations. Data were analyzed using a mixed model with treatment, day and their interaction included, with day and minute as a repeated measure. The control treatment had greater (P &lt; 0.01) DMI than low and high steers. Body weight was increased in control steers on d 14 and 28 compared to the steers receiving the High treatment (P = 0.03 for the interaction). Blood glucose concentrations tended (P = 0.09) to be higher on d 21 than d 0 and 7 but was not affected by treatment (P = 0.58). Plasma NEFA concentrations were lower (P = 0.05) for control steers than other treatments, and greater (P = 0.002) on d 0 than d 7 and 21. Blood lactate concentrations were greater (P = 0.05) on d 7, than d 0 and 21, but not affected by treatment (P = 0.13). High steers had greater plasma insulin concentrations in response to the IVGTT than steers on the other treatments (P = 0.001). There was no treatment (P ≥ 0.16) or day effect (P ≥ 0.36) on glucose peak, plateau, or clearance rate. High steers had greater expression of solute carrier family 16 member 1 (SLC16A1; P = 0.05) and tended to have greater hepatic expression of solute carrier family 2 member 2 (SLC2A2; P = 0.07). These data indicate that increased propionate may decrease DMI and insulin sensitivity.