Peak Glucose Levels Research Articles

Efficacy and Safety of a Polysaccharide-Based Natural Substance Complex in the Treatment of Obesity and Other Metabolic Syndrome Components: A Systematic Review

Introduction: Metabolic syndrome (MetS) is increasingly common in adults as well as in children and adolescents. However, preventing and treating MetS is one of the most pressing challenges for public health services worldwide. At present, the only approved treatments for MetS are dietary changes and physical activity, which are associated with a high rate of non-compliance. On the contrary, no drugs are licensed to treat metabolic syndrome, although a number of drugs are used to treat individual metabolic abnormalities, which increases the risk of adverse events, particularly in children. Policaptil Gel Retard® (PGR), an oral macromolecule complex based on polysaccharides, has been demonstrated to significantly reduce body weight, peak blood glucose (BG) levels, insulin levels, and lipid levels, providing an interesting non-pharmacological therapeutic option for MetS-associated metabolic abnormalities, especially in younger patients.Aims: To review available studies on the use of PGR in children, adolescents, or adults with obesity or metabolic syndrome.Methods: A systematic search of electronic databases for PGR and MetS. A total of six studies were identified and included.Results: Across four randomized clinical studies and one retrospective clinical study including a total of 359 obese children and adolescents with or without MetS and 157 overweight/obese adults with or without MetS and/or T2DM, a single dose of PGR resulted in a reduction in appetite and postprandial triglyceride levels in younger patients and peak postprandial BG levels in adults. Decreased lipid levels were observed in adults following a normocaloric diet who received PGR for 30 days. As a long-term treatment, in combination with a low-glycemic index diet with or without metformin, PGR resulted in reduced body mass index and waist circumference, improved insulin sensitivity with reduction of glucose-metabolism abnormalities, increased insulin reserve and, finally, an improved circulating lipid profile, regardless of age. No safety issues were reported.Conclusion: Policaptil Gel Retard® is an effective and safe non-pharmacological approach to improve the treatment of MetS-associated cardiovascular risk factors in children, adolescents, and adults.

Investigating the influence of the gut microbiome on diabetic renal disease

BackgroundGut microbiota have been implicated in a large array of pathophysiological processes including obesity and diabetes. In this study, we utilized a diabetic renal disease model with or without oral antibiotic treatment to investigate how gut microbiota alter diabetic renal disease.MethodsGut microbiota biomass was depleted using a modified antibiotic treatment protocol with a mixture of 1g/L ampicillin, 1g/L neomycin, and 0.5 g/L vancomycin (modified from Rakoff‐Nahoum et al. 2004). C57BL/6J male and female mice (6‐week‐old) were randomly assigned to four different groups (n=8 per sex per group): control diet (CD), high‐fat diet (HFD), CD + antibiotics, HFD + antibiotics. The mice were treated with different diets and/or with antibiotics in drinking water for nine weeks. We measured body weight (BW), non‐fasting glucose, insulin, and glomerular filtration rate (GFR). In addition, we performed a glucose tolerance test (GTT), insulin tolerance test (ITT), and blood analysis. Finally, we did H&E staining of the kidney, and analyzed urine Na+.Results1) BW was significantly increased by HFD (vs CD) in both males and females regardless of antibiotic treatment. 2) Non‐fasting glucose showed no difference among these four groups in males and females. 3) Fasting glucose was dramatically elevated by HFD in males but not females (vs CD). For the GTT, both the peak glucose level and area under curve (AUC) were significantly increased in HFD vs CD, regardless of antibiotic treatment or sex. 4) For the ITT, HFD promoted insulin resistance as measured by changes in the AUC in both males and females. For males on a CD, antibiotics improved insulin responsiveness. 5) GFR was increased by HFD vs CD in both males and females, consistent with a HFD‐induced hyperfiltration, as we published previously with this same model (Halperin Kuhns, AJP Renal 2018). Intriguingly, GFR in females was also enhanced by antibiotic treatment on both the CD and HFD (week 9: CD, F: 182±12.7; HFD, F: 290±19.9, p<0.0001; CD + antibiotics, F: 282±12.6; HFD + antibiotics, F: 373±20.1; p=0.0005 CD vs. CD+antibiotics; p=0.01 HF vs. HF+antibiotics). Similarly, GFR in males also increased with antibiotic treatment in CD, but, not HFD (week 9: CD, M: 191±10.0; HFD, M: 385±19.3, p<0.0001; CD + antibiotics, M: 263±10.5; HFD + antibiotics, M: 390±32.7; p=0.04 CD vs. CD+antibiotics; p>0.99 HF vs. HF+antibiotics). Preliminary data using germ‐free (GF) mice, which do not have microbiota, show that GFR was also increased in GF males and females (vs. conventional mice with gut microbes).ConclusionIn this study, depletion of the gut microbiota via antibiotics increased GFR in both males and females on CD. Interestingly, on a HFD, GFR increased with antibiotics in females but not males. These data suggest that gut microbial signals may directly influence renal function; we are now working to confirm these findings and to explore the underlying mechanisms.

A Comparison of Postprandial Glucose Control in the Medtronic Advanced Hybrid Closed-Loop System Versus 670G.

Background: We recently reported that use of an "advanced" hybrid closed-loop system reduced hyperglycemia without increasing hypoglycemia compared to a first-generation system. The aim of this analysis was to evaluate whether this improved performance was specifically related to better mealtime glycemic control. Methods: We conducted a secondary analysis of postprandial glycemic control in an open-label, multinational, randomized crossover trial of 112 participants with type 1 diabetes, aged 14-29, of the Medtronic MiniMed™ 670G hybrid closed-loop system (670G) versus the Medtronic advanced hybrid closed-loop (AHCL) system, for 12 weeks each. We compared glycemic and insulin delivery metrics over a 3 h horizon across all meals to assess system performance and outcomes. Results: Overall meal size and premeal insulin on board were similar during run-in and between 670G and AHCL arms. Compared with 670G arm, premeal, peak, and mean glucose levels were numerically lower in the AHCL arm (167 ± 23, 231 ± 23, and 177 ± 20 mg/dL vs. 175 ± 23, 235 ± 23, and 180 ± 19 mg/dL, respectively), with a trend to lower hyperglycemia level 2 in AHCL arm. Adjusting for premeal glucose level, all postmeal outcomes between 670G and AHCL were statistically similar. Prandial insulin delivery also was similar in both treatment arms (21 ± 9 vs. 23 ± 10 U), with a shift in basal/bolus ratio from 28%/71% in 670G arm to 20%/80% in AHCL arm. Conclusions: Reduced hyperglycemia with AHCL compared to 670G was not related to early postprandial glycemic excursions after adjusting for premeal glucose level (<3 h after meal), but likely to later (>3 h) postprandial or overnight improvements. Further refinements to mealtime bolus algorithms and strategies may more optimally control prandial glycemic excursions.

Oral Glucose Tolerance Test in Patients with Cystic Fibrosis Compared to the Overweight and Obese: A Different Approach in Understanding the Results.

(1) Background: In cystic fibrosis (CF), the oral glucose tolerance test (OGTT) is recommended from 10 years old annually to screen and diagnose cystic fibrosis-related diabetes (CFRD). Alternative OGTT characteristics (glucose curve shape, time to glucose peak, one-hour glucose value, and three-hour glucose value with the new shape curve) were studied in other populations considered at high risk for diabetes; (2) Methods: The study analyses classical and alternative OGGT characteristics from 44 children (22 CF, 22 obese without CF), mean age: 12.9 ± 2.2 years evaluated in a single-center from Romania. (3) Results: In 59.1% of children with CF, the predominant OGTT pattern was: abnormal glucose metabolism or CFRD, with a monophasic curve shape, a late peak glucose level, and 1 h glucose ≥ 155 mg/dL, showing a very different pattern compared with sex and age-matched obese children. Statistical estimation agreement between the late glucose peak (K = 0.60; p = 0.005), the 1 h glucose ≥ 155 mg/dL during OGTT (K = 0.69, p = 0.001), and the classical method of interpretation was found. (4) Conclusions: Late peak glucose and 1 h glucose level ≥ 155 mg/dL during OGTT can be used for diagnosing the early glucose metabolism alteration in children with CF.

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West African Dwarf (WAD) goats are important source of animal protein, ubiquitous in rural Nigerian households and undergo necessary surgical procedures. Induction of general anaesthesia in goats is associated with resultant severe systemic side effects due to position-induced stress. This study investigated cardiopulmonary and stress responses of WAD goats to three sedatives in different body positioning. Six adult WAD bucks, weighing 11&plusmn;2.0 kg were randomly selected for three separate experiments using of xylazine (0.05 mg/kg), acepromazine (0.2 mg/kg) or midazolam (0.3 mg/kg) intramuscularly in five clinical trials lasting five days each. Goats were restrained in standing (control), Right Lateral (RL), Left Lateral (LL), supine and prone positions. Venous blood (5 ml) via jugular venipuncture was collected before and after each sedation to determine selected stress biomarkers [blood glucose (mg/dL), plasma cortisol (mmol/L) and lactate dehydrogenase LDH (U/L)]. Heart Rate-HR (beats/min), Respiratory Rate-RR (breaths/min), Mean Arterial Pressure-MAP (mmHg), Oxygen-haemoglobin Saturation-SpO2 (%) and Rectal Temperature -RT (&deg;C) were measured at intervals of 10 min for 1 h. Bucks were rested for 14 days in between clinical trials. Data were analysed using descriptive statistics and ANOVA at p&lt;0.05. In LL, supine and prone body positions, peak blood glucose levels and plasma cortisol, respectively were significantly increased with xylazine, acepromazine and midazolam compared to control. Plasma levels of LDH were significantly decreased compared to control for the RL, LL, supine and prone positions with xylazine and acepromazine sedation. Acepromazine and Midazolam had highest HR with supine position. Xylazine sedation resulted in severe hypotension and hyperglycaemia with LL and supine body positions whereas acepromazine and midazolam sedation resulted in mild hypotension and increased heart rate with LL and prone body positions. The LL and prone positioning should be used cautiously in caprine sedation. Acepromazine and midazolam were found to be safer alternatives to xylazine. Key words: Body positioning, cardiopulmonary stress responses, sedation, West African Dwarf goats.

Super Bolus: a remedy for a high glycemic index meal in children with type 1 diabetes on insulin pump therapy?\u2014study protocol for a randomized controlled trial

BackgroundPostprandial hyperglycemia (PPH) is a common clinical problem among patients with type 1 diabetes (T1D), which is related to high glycemic index (h-GI) meals. The main problem is linked to high, sharp glycemic spikes following hypoglycemia after h-GI meal consumption. There is a lack of effective and satisfactory solutions for insulin dose adjustment to cover an h-GI meal. The goal of this research was to determine whether a Super Bolus is an effective strategy to prevent PPH and late hypoglycemia after an h-GI meal compared to a Normal Bolus.MethodsA total of 72 children aged 10–18 years with T1D for at least 1 year and treated with continuous subcutaneous insulin infusion for more than 3 months will be enrolled in a double-blind, randomized, crossover clinical trial. The participants will eat a h-GI breakfast for the two following days and receive a prandial insulin bolus in the form of a Super Bolus 1 day and a Normal Bolus the next day. The glucose level 90 min after the administration of the prandial bolus will be the primary outcome measure. The secondary endpoints will refer to the glucose levels at 30, 60, 120, 150, and 180 min postprandially, the area under the blood glucose curve within 180 min postprandially, peak glucose level and the time to peak glucose level, glycemic rise, the mean amplitude of glycemic excursions, and the number of hypoglycemia episodes.DiscussionThere are still few known clinical studies on this type of bolus. A Super Bolus is defined as a 50% increase in prandial insulin dose compared to the dose calculated based on the individualized patient’s insulin-carbohydrate ratio and a simultaneous suspension of basal insulin for 2 h. Our patients reported the best experience with such a combination. A comprehensive and effective solution to this frequent clinical difficulty of PPH after an h-GI meal has not yet been found. The problem is known and important, and the presented solution is innovative and easy to apply in everyday life.Trial registrationClinicalTrials.gov NCT04019821

Provitamin A cassava hydrolysate with Lactobacillus rhamnosus GG regulates weight gain, lipids and postprandial glycemia in wistar rats and humans

PurposeThis study aims to evaluate the effect of probiotic provitamin A cassava hydrolysate with Lactobacillus rhamnosus GG (hLGG) on weight and lipid profile of Wistar rats and its glycemic index using Wistar rats and human subjects.Design/methodology/approachAdult male Wistar rats (n = 40, 120–150 g) were orally administered provitamin A cassava hydrolysate with 1 × 1010, 2 × 1010 and 4 × 1010 CFU/g encapsulated or CFU/mL free Lactobacillus rhamnosus GG for 30 days, during which weight and lipid profile of rats were monitored. Blood glucose levels of rats and human subjects were also measured in Oral Glucose Tolerance Test to determine the Glycemic indices of hLGG.FindingsRats administered the highest doses of free or encapsulated hLGG [(4 × 1010 CFU) (PHE4 and PHF4, respectively)] had the lowest (18.2 ± 0.7 and 8.0 ± 0.6%, respectively, p < 0.001) percentage body weight gain compared to control (40 ± 0.6%). Lowest cholesterol and triglyceride (42.4 ± 0.5 and 44.4 ± 0.7 g/dL, p < 0.001, respectively) were observed in rats administered PHE4, with the lowest plasma glucose concentrations in PHE4 and PHF4 groups (43 ± 1 and 49 ± 0.7 g/dL, p < 0.001, respectively). Oral Glucose Tolerance Test for rats and human subjects showed lower peak blood glucose levels and glycemic indices in hLGG groups compared to controls in a dose-dependent manner.Originality/valueConsumption of soft drinks, which supply non-nutritive energy, may lead to degenerative metabolic disorders such as obesity and diabetes. Beverages with probiotics such as Lactobacillus rhamnosus GG, on the other hand, offer a positive weight management approach. Development of non-dairy beverages such as provitamin A cassava hLGG is ongoing. Provitamin A cassava hLGG showed its ability to control weight gain, blood glucose levels and serum lipids. Thus, the beverage can be consumed as a healthy alternative to soft drinks and for weight management.

Brain Permeable AMP-Activated Protein Kinase Activator R481 Raises Glycaemia by Autonomic Nervous System Activation and Amplifies the Counterregulatory Response to Hypoglycaemia in Rats.

AimWe evaluated the efficacy of a novel brain permeable “metformin-like” AMP-activated protein kinase activator, R481, in regulating glucose homeostasis.Materials and MethodsWe used glucose sensing hypothalamic GT1-7 neuronal cells and pancreatic αTC1.9 α-cells to examine the effect of R481 on AMPK pathway activation and cellular metabolism. Glucose tolerance tests and hyperinsulinemic-euglycemic and hypoglycemic clamps were used in Sprague-Dawley rats to assess insulin sensitivity and hypoglycemia counterregulation, respectively.Results In vitro, we demonstrate that R481 increased AMPK phosphorylation in GT1-7 and αTC1.9 cells. In Sprague-Dawley rats, R481 increased peak glucose levels during a glucose tolerance test, without altering insulin levels or glucose clearance. The effect of R481 to raise peak glucose levels was attenuated by allosteric brain permeable AMPK inhibitor SBI-0206965. This effect was also completely abolished by blockade of the autonomic nervous system using hexamethonium. During hypoglycemic clamp studies, R481 treated animals had a significantly lower glucose infusion rate compared to vehicle treated controls. Peak plasma glucagon levels were significantly higher in R481 treated rats with no change to plasma adrenaline levels. In vitro, R481 did not alter glucagon release from αTC1.9 cells, but increased glycolysis. Non brain permeable AMPK activator R419 enhanced AMPK activity in vitro in neuronal cells but did not alter glucose excursion in vivo.ConclusionsThese data demonstrate that peripheral administration of the brain permeable “metformin-like” AMPK activator R481 increases blood glucose by activation of the autonomic nervous system and amplifies the glucagon response to hypoglycemia in rats. Taken together, our data suggest that R481 amplifies the counterregulatory response to hypoglycemia by a central rather than a direct effect on the pancreatic α-cell. These data provide proof-of-concept that central AMPK could be a target for future drug development for prevention of hypoglycemia in diabetes.

Application of Peak Glucose Range and Diabetes Status in Mortality Risk Stratification in Critically Ill Patients with Sepsis

The effects of diabetes and glucose on the outcomes of patients with sepsis are somewhat conflicting. This retrospective study enrolled 1214 consecutive patients with sepsis, including a subpopulation of 148 patients with immune profiles. The septic patients were stratified according to their Diabetes mellitus (DM) status or peak glucose level (three-group tool; P1: ≤140 mg/dL, P2: 141–220 mg/dL, P3: >220 mg/dL) on day 1. Although the DM group had a lower hazard ratio (HR) for 90-day mortality compared to non-DM patients, the adjusted HRs were insignificant. The modified sequential organ failure assessment-glucose (mSOFA-g) score can predict 90-day survival in patients with and without diabetes (β = 1.098, p < 0.001; β = 1.202, p < 0.001). The goodness of fit of the mSOFA-g score was 5% higher than the SOFA score of the subgroup without diabetes. The SOFA score and human leukocyte antigen-D-related (HLA-DR) expression were comparable between the groups. The P3 group had lower HLA-DR expression on days 1 and 3 and a higher 90-day mortality. The three-group tool was useful for predicting 90-day mortality in patients with separate Kaplan-Meier survival curves and mortality HRs in the construction and validation cohorts. The peak glucose level, instead of diabetes status, can be used as an easy adjunctive tool for mortality risk stratification in critically ill septic patients.

Neurodevelopment of preterm infants with glucose and sodium abnormalities

Blood glucose and serum sodium abnormalities in very low birth weight infants may cause increased morbidity and mortality, but data regarding the long-term outcomes are limited. This study aimed to investigate the association between the peak and nadir blood glucose and serum sodium levels and neurodevelopmental outcomes in very low birth weight infants. A single-center retrospective medical record of 284 infants with birth weight<1500g born between February 1, 2011 and January 31, 2015 was reviewed. We analyzed the correlation between peak and nadir blood glucose and serum sodium levels during hospitalization and Bayley Scales of Infant and Toddler Development, third edition at 6, 12, and 24 months of corrected age. A total of 284 very low birth weight premature infants were eligible, and 223, 208, and 188 patients were assessed at 6, 12, and 24 months of corrected age, respectively. Multiple linear regression analysis with generalized estimating equations showed that the BSID-III cognitive scores were significantly lower in the peak serum sodium group when sodium was ≧150mmol/L (95% confidence interval -11.681 to -0.822) than when sodium did not exceed 150mmol/L. A peak serum sodium of ≧150mmol/L is associated with poor cognitive outcomes in very low birth weight infants. Further studies are necessary to determine if this association is causal or an expression of disease severity.

Acute and Chronic Effects of Low-Volume High-Intensity Interval Training Compared to Moderate-Intensity Continuous Training on Glycemic Control and Body Composition in Older Women with Type 2 Diabetes

Objective: To compare the acute and chronic effects of low-volume high-intensity interval training (HIIT) to moderate-intensity continuous training (MICT) on glycemic control, body composition and continuous glucose monitoring (CGM) in older women with type 2 diabetes (T2D). Methods: Thirty older women (68 ± 5 years) with T2D were randomized in two groups—HIIT (75 min/week) or MICT (150 min/week). Glucose homeostasis (A1c, glucose, insulin, HOMA-IR2) and body composition (iDXA) were measured before and after the 12-week exercise intervention. During the first and last week of training (24-h before and 48-h after exercise), the following CGM-derived data were measured: 24-h and peak glucose levels, glucose variability and time spent in hypoglycemia as well as severe and mild hyperglycemia. Results: While lean body mass increased (p = 0.035), total and trunk fat mass decreased (p ≤ 0.007), without any difference between groups (p ≥ 0.81). Fasting glucose levels (p = 0.001) and A1c (p = 0.014) significantly improved in MICT only, with a significant difference between groups for fasting glucose (p = 0.02). Neither HIIT nor MICT impacted CGM-derived data at week 1 (p ≥ 0.25). However, 24-h and peak glucose levels, as well as time spent in mild hyperglycemia, decreased in HIIT at week 12 (p ≤ 0.03). Conclusion: These results suggest that 12 weeks of low-volume HIIT is enough to provide similar benefit to MICT for body composition and improve the acute effect of exercise when measured with CGM.

150-LB: Changes in OGTT-Derived Biomarkers following Lifestyle Intervention among High-Risk Youth

Background: Previous studies have identified biomarkers derived from glucose concentrations during a 2-h Oral Glucose Tolerance Test (OGTT) that differentiate type 2 diabetes risk phenotypes. Such markers include 1-h glucose concentrations (1hG), shape of the glucose response curve (GRC), and time to glucose peak (TGP). Lifestyle intervention is the first line approach to diabetes prevention, yet no studies have examined changes in OGTT-glucose phenotypes. Methods: Latino adolescents with obesity (n=48, age 15.4±1.0, BMI% 98.2±1.4, Girls 56.3%) completed a 12-week lifestyle intervention that included physical activity (3 d/wk) and nutrition education (1 d/wk). At baseline and 12 weeks, youth completed a 2-h OGTT with glucose concentrations assessed at 0’, 30’, 60’, 90’, and 120’ to derive the 3 biomarkers used to classify low and high risk phenotypes. For 1hG, ≥155mg/dL served as the threshold that classified 1hG&amp;lt;155mg/dL (low risk) and 1hG≥155mg/dL (high risk) phenotypes. For GRC, Biphasic (low risk) phenotypes reached peak glucose levels before dropping ≥4.5mg/dL and increasing again ≥4.5mg/dL, whereas remaining youth were Monophasic (high risk). For TGP, phenotypes were distinguished by whether glucose peaked at 30’ (Early Peak, low risk) or ≥30’ (Late Peak, high risk). Changes in OGTT-glucose phenotypes were assessed by Chi-square test. Results: At baseline, there was substantial heterogeneity in the prevalence of OGTT-glucose phenotypes with 38% 1hG≥155mg/dL, 81% Monophasic, and 58% Late Peak. In response to the intervention, the prevalence of Monophasic decreased to 14% (p=0.048), while the prevalence of 1hG≥155mg/dL decreased to 28% (p=0.054). The decrease in prevalence of Late Peak phenotypes was not significant (-29%, p=0.200). Conclusion: Lifestyle intervention may improve OGTT-glucose phenotypes among high-risk youth populations. Whether changes in OGTT-glucose phenotypes are associated with changes in type 2 diabetes risk factors has yet to be established. Disclosure A. Pena: None. J. Kim: None. J. A. Reyes: None. K. B. Vander wyst: None. M. Olson: None. S. Ayers: None. A. Williams: None. G. Q. Shaibi: None. Funding National Institutes of Health (P20MD002316U54, MD002316R01, DK107579F31, DK125037)

The Effects of 7 Days of Feeding Pulse-Based Diets on Digestibility, Glycemic Response and Taurine Levels in Domestic Dogs.

Grain-based carbohydrate sources such as rice comprise 30–50% of commercial pet foods. Some pet foods however have removed the use of grains and have instead incorporated pulses, such as peas and lentils, resulting in grain-free diets. The hypothesis was dog diets with higher levels of dietary fiber will produce a low glycemic response due to decreased rates of digestion and lowered bioavailability of all macronutrients and increased fecal bile salt excretion. This in turn was hypothesized to produce lower plasma concentrations of cysteine, methionine and taurine after 7 days of feeding each test diet in dogs. Six diets were formulated at an inclusion level of 20% available carbohydrate, using white rice flour (grain) or whole pulse flours from smooth pea, fava bean, red lentil or 2 different wrinkled pea varieties (CDC 4,140–4 or Amigold) and fed to beagles in a randomized, cross-over, blinded design. After 7 days feeding each diet, fasting blood glucose was the lowest in the lentil (3.5 ± 0.1 mmol/L) and wrinkled pea (4,140–4; 3.6 ± 0.1 mmol/L) diet periods, while peak glucose levels was lowest after feeding the lentil diet (4.4 ± 0.1 mmol/L) compared to the rice diet. Total tract apparent digestibility of all macronutrients as well as taurine differed among diets yet plasma taurine was not outside normal range. Decreased macronutrient and amino acid digestibility was associated with increasing amylose and dietary fiber content but the specific causative agent could not be determined from this study. Surprisingly, digestibility decreases were not due to increased bile salt loss in the feces since increasing dietary fiber content led to decreased fecal bile salt levels. In conclusion, although pulse-based canine diets have beneficial low glycemic properties, after only 7 days, these pulse-based diets decrease macronutrient and amino acid digestibility. This is likely related at least in part to the lower animal protein content, but on a long-term basis could put domestic dogs at risk for low taurine and dilated cardiomyopathy.

Evaluation of the effects of intraarticular glucocorticoid injections on blood glucose levels in diabetes mellitus and nondiabetes mellitus patients with adhesive capsulitis of the shoulder.

The aim of this study was to assess the effect of intraarticular glucocorticoid injections on blood glucose levels in diabetes mellitus (DM) and non-DM patients with adhesive capsulitis of the shoulder and investigate the risk factors for hyperglycemia. The study included 40 DM and 38 non-DM patients. The DM status, HbA1c levels, baseline fasting blood glucose (FBG) level, and post-injection 1-, 7-, 15-, and 21-day FBG levels were evaluated retrospectively. The FBG levels were significantly higher 1 and 7 day after the glucocorticoid injection as compared with the baseline levels (P = 0.001 and <0.001, respectively). The increase was greatest in DM patients and then returned to baseline levels 15-day post-injection. In terms of the mean difference in post-injection and baseline FBG levels, the increase on day 1 was statistically significantly greater in the DM group as compared with that in the non-DM group (P = 0.01). Linear regression model showed that only the baseline FBG level predicted the glucose level 1-day post-treatment (β = 0.839, P < 0.01). Intraarticular glucocorticoid injections can safely be administered as a treatment for adhesive capsulitis of the shoulder in patients with well-controlled DM. Baseline FBG levels may predict peak blood glucose levels in patients with well-controlled DM. We recommend that DM patients with adhesive capsulitis should undergo frequent monitoring of blood glucose in the 2 week following intraarticular glucocorticoid injection treatment.

Stress burden related to postreperfusion syndrome may aggravate hyperglycemia with insulin resistance during living donor liver transplantation: A propensity score-matching analysis.

We investigated the impact of postreperfusion syndrome (PRS) on hyperglycemia occurrence and connecting (C) peptide release, which acts as a surrogate marker for insulin resistance, during the intraoperative period after graft reperfusion in patients undergoing living donor liver transplantation (LDLT) using propensity score (PS)-matching analysis. Medical records from 324 adult patients who underwent elective LDLT were retrospectively reviewed, and their data were analyzed according to PRS occurrence (PRS vs. non-PRS groups) using the PS-matching method. Intraoperative levels of blood glucose and C-peptide were measured through the arterial or venous line at each surgical phase. Hyperglycemia was defined as a peak glucose level >200 mg/dL, and normal plasma concentrations of C-peptide in the fasting state were taken to range between 0.5 and 2.0 ng/mL. After PS matching, there were no significant differences in pre- and intra-operative recipient findings and donor-graft findings between groups. Although glucose and C-peptide levels continuously increased through the surgical phases in both groups, glucose and C-peptide levels during the neohepatic phase were significantly higher in the PRS group than in the non-PRS group, and larger changes in levels were observed between the preanhepatic and neohepatic phases. There were higher incidences of C-peptide levels >2.0 ng/mL and peak glucose levels >200 mg/dL in the neohepatic phase in patients with PRS than in those without. PRS adjusted for PS with or without exogenous insulin infusion was significantly associated with hyperglycemia occurrence during the neohepatic phase. Elucidating the association between PRS and hyperglycemia occurrence will help with establishing a standard protocol for intraoperative glycemic control in patients undergoing LDLT.

PSVI-32 The effects of varying amylose levels in different diets on digestibility and glycemic response in canines

Abstract This study was conducted to compare the digestibility of pulse-based diets to grain-based diets based on varying levels of amylose and study how changes in digestibility impacts glycemic response in dogs. To establish glycemic response, six diets were formulated at an inclusion level of 20% available starch with varying amylose content. A grain-based diet was formulated using rice, while pulse-based diets consisted of smooth pea, wrinkled pea (4140–4 and Amigold varieties), faba bean, or lentil. Beagles (n = 8, 4 females, 4 males) were fed the 6 different test diets for 7 days in a randomized, cross-over, blinded design. At the end of each feeding period, fecal samples were collected and beagles were fasted overnight and subjected to a glycemic test (1g/kg of diet or glucose fed). Data collected were statistically analyzed using SigmaPlot 12.0 and significance was declared at P ≤ 0.05. Amylose levels of diets varied from 4.64% to 14.82% on a dry basis. The rice-based diet had the lowest amylose content, while the wrinkled pea (Amigold variety) diet had the highest amylose content. Following the collection of glycemic response and fecal data, repeated-measures, 1-way ANOVA’s were conducted. There were significant differences observed between diets based on peak glucose levels (mmol/L, P = 0.01). The rice diet had the highest peak in glucose, while the lentil-based diet had the lowest glucose peak. Significant differences were also seen between diets based on their digestibility (P &amp;lt; 0.001). Rice, lentil, faba bean and smooth pea-based diets had the highest levels of digestibility, while wrinkled pea varieties had decreased digestibility. Furthermore, varying amylose found in diets can be viewed as an impacting factor on glycemic response and digestibility. Incorporating pulses with higher amounts of amylose could be utilized in dog diets to promote a low glycemic response through decreased rates of digestibility.

A Potential Role for Endogenous Glucagon in Preventing Post-Bariatric Hypoglycemia.

Obesity and obesity-related diseases are major public health concerns that have been exponentially growing in the last decades. Bariatric surgery is an effective long-term treatment to achieve weight loss and obesity comorbidity remission. Post-bariatric hypoglycemia (PBH) is a late complication of bariatric surgery most commonly reported after Roux-en-Y gastric bypass (RYGB). PBH is the end result of postprandial hyperinsulinemia but additional endocrine mechanisms involved are still under debate. Our aim was to characterize entero-pancreatic hormone dynamics associated with postprandial hypoglycemia after RYGB. Individuals previously submitted to RYGB (N=23) in a single tertiary hospital presenting PBH symptoms (Sym, n=14) and asymptomatic weight-matched controls (Asy, n=9) were enrolled. Participants underwent a mixed-meal tolerance test (MMTT) to assess glucose, total amino acids (total AA), insulin, C-peptide, glucagon, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), and neurotensin (NT). We found that hypoglycemia during the MMTT was equally frequent in Sym and Asy groups (p=1.000). Re-grouped according to glucose nadir during the MMTT (Hypo n=11 vs NoHypo n=12; nadir <3.05 mmol/l vs ≥3.05 mmol/l), subjects presented no differences in anthropometric (BMI: p=0.527) or metabolic features (HbA1c: p=0.358), yet distinct meal-elicited hormone dynamics were identified. Postprandial glucose excursion and peak glucose levels were similar (p>0.05), despite distinct late glycemic outcomes (t=60 min and t=90 min: p<0.01), with overall greater glycemic variability in Hypo group (minimum-to-maximum glucose ratio: p<0.001). Hypo group meal-triggered hormone profile was characterized by lower early glucagon (t=15 min: p<0.01) and higher insulin (t=30 min: p<0.05, t=45 min: p<0.001), C-peptide (t=30 min: p<0.01, t=45 min: p<0.001, t=60 min: p<0.05), and GLP-1 (t=45 min: p<0.05) levels. Hyperinsulinemia was an independent risk factor for hypoglycemia (p<0.05). After adjusting for hyperinsulinemia, early glucagon correlated with glycemic nadir (p<0.01), and prevented postprandial hypoglycemia (p<0.05). A higher insulin to glucagon balance in Hypo was observed (p<0.05). No differences were observed in total AA, GIP or NT excursions (p>0.05). In sum, after RYGB, postprandial hyperinsulinemia is key in triggering PBH, but a parallel and earlier rise in endogenous glucagon might sustain the inter-individual variability in glycemic outcome beyond the effect of hyperinsulinism, advocating a potential pivotal role for glucagon in preventing hyperinsulinemic hypoglycemia.

Post-load glucose subgroups and associated metabolic traits in individuals with type 2 diabetes: An IMI-DIRECT study.

AimSubclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D.MethodsThe study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders.ResultsAt baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1–3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18–1.92) for subgroup 2 and 1.88 (-0.08–3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose.ConclusionsDifferent glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk.

Canagliflozin extends life span in genetically heterogeneous male but not female mice.

Canagliflozin (Cana) is an FDA-approved diabetes drug that protects against cardiovascular and kidney diseases. It also inhibits the sodium glucose transporter 2 by blocking renal reuptake and intestinal absorption of glucose. In the context of the mouse Interventions Testing Program, genetically heterogeneous mice were given chow containing Cana at 180 ppm at 7 months of age until their death. Cana extended median survival of male mice by 14%. Cana also increased by 9% the age for 90th percentile survival, with parallel effects seen at each of 3 test sites. Neither the distribution of inferred cause of death nor incidental pathology findings at end-of-life necropsies were altered by Cana. Moreover, although no life span benefits were seen in female mice, Cana led to lower fasting glucose and improved glucose tolerance in both sexes, diminishing fat mass in females only. Therefore, the life span benefit of Cana is likely to reflect blunting of peak glucose levels, because similar longevity effects are seen in male mice given acarbose, a diabetes drug that blocks glucose surges through a distinct mechanism, i.e., slowing breakdown of carbohydrate in the intestine. Interventions that control daily peak glucose levels deserve attention as possible preventive medicines to protect from a wide range of late-life neoplastic and degenerative diseases.

Persistent Postoperative Hyperglycemia as a Risk Factor for Operative Treatment of Deep Wound Infection After Spine Surgery

Surgical site infections (SSIs) affect 1% to 9% of all spine surgeries. Though previous work has found diabetes mellitus type 2 (DM2) to increase the risk for wound infection, the influence of perioperative hyperglycemia is poorly described. To investigate perioperative hyperglycemia as an independent risk factor for surgical site infection. We retrospectively identified patients undergoing operative management of SSIs occurring after spinal surgery for degenerative pathologies. These patients were individually matched to controls based upon age, surgical invasiveness, ICD-10CM, race, and sex. Cases and controls were compared regarding medical comorbidities (including diabetes), postoperative hyperglycemia, and operative time. Patients in the infection group were found to have a higher BMI (33.7 vs 28.8), higher prevalence of DM2 (48.5% vs 14.7%), and longer inpatient stay (8.8 vs 4.3 d). They also had higher average (136.6 vs 119.6 mg/dL) and peak glucose levels (191.9 vs 153.1 mg/dL), as well as greater variability in glucose levels (92.1 vs 58.1 mg/dL). Multivariable logistic regression identified BMI (odds ratio [OR]=1.13), diabetes mellitus (OR=2.12), average glucose on the first postoperative day (OR=1.24), peak postoperative glucose (OR=1.31), and maximal daily glucose variation (OR=1.32) as being significant independent predictors of postoperative surgical site infection. Postoperative hyperglycemia and poor postoperative glucose control are independent risk factors for surgical site infection following surgery for degenerative spine disease. These data suggest that, particularly among high-risk diabetic patients, strict perioperative glucose control may decrease the risk of SSI.