Blood Glucose Area Under The Curve Research Articles

Plasma Levels of Neudesin and Glucose Metabolism in Obese and Overweight Children.

Childhood overweight and obesity are among the major health problems of modern times, especially in Western countries, due to their association with increased cardiovascular and cancer risk in adulthood. Neudesin, a recently discovered peptide secreted mainly in the brain and adipose tissue, is being investigated for its possible activity as a negative regulator of energy expenditure. We conducted a cross-sectional observational preliminary study with the aim of testing the hypothesis that plasma levels of neudesin can be modified in obese and overweight children and to evaluate any possible relationship between plasma neudesin levels and metabolic and anthropometric parameters. 34 Children (Tanner’s stage 1) were included and divided in two groups according to Cole’s criteria. Group A included obese and overweight children (23 patients, 17 females and 6 males, aged 4-10 years); Group B included healthy normal-weight children (11 subjects, 7 females and 4 males, aged 3-10 years). Metabolic (glucose and insulin, total, LDL- and HDL-cholesterol, triglycerides, uric acid) and hormonal (fT3, fT4, TSH, IGF-1, leptin) parameters were evaluated. HOMA-IR and QUICKI index and the area under the curve (AUC) of glucose and insulin after oral glucose load were calculated in obese and overweight children. Neudesin was measured by ELISA. Neudesin levels were significantly higher in obese/overweight children than in controls. In obese and overweight children, plasma neudesin levels were significantly directly correlated with blood glucose and glucose AUC. Taken together, these results, although preliminary, may suggest a possible age-related role of neudesin in glucose homeostasis in obese/overweight children.

Sleep Quality is an Independent Predictor of Blood Glucose and Gestational Diabetes Mellitus: A Longitudinal Study of 4550 Chinese Women.

PurposeTo investigate whether pregnant women’s subjective sleep quality during the first trimester independently predicted blood glucose and gestational diabetes mellitus (GDM).MethodsA total of 4550 pregnant women in the first trimester were enrolled in Chongqing Health Center for Women and Children, China, from January to October 2020.The Pittsburgh Sleep Quality Index (PSQI) was used to measure subjective sleep quality. Depression symptoms and anxiety were measured with the Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7). Oral glucose tolerance tests (OGTT) and blood glucose area under the curve (AUC) were used for estimation of blood glucose and diagnosis of GDM during the second trimester. Linear, mixed model, and logistic regression were used to analyze the association between PSQI and blood glucose as well as GDM.Results946/4550 were diagnosed with GDM (20.8%). In the mixed model analysis, the blood glucose level of the highest-scoring group (PSQI score = 18) was 1.94 (95% CI: 0.45~3.43, P = 0.011) mmol/L higher than that of the lowest-scoring group (PSQI score = 0). After adjusting for potential confounders, a one-point PSQI score increase was associated with a 0.014 (95% CI: 0.001~0.027, P = 0.039) mmol/L increase in blood glucose level. Blood glucose AUC was also positively associated with PSQI scores (β = 0.034, 95% CI: 0.003~0.064, P = 0.030). The results for the logistic regression model showed that PSQI was marginal positively correlated with GDM (OR = 1.146, 95% CI: 0.995~1.321, P = 0.059) when age and BMI were not controlled for. When investigating the association between PSQI and the GDM-diagnosed time window, the 1-h diagnosed GDM had a borderline positive correlation with PSQI (OR = 1.182, 95% CI: 0.993~1.405, P = 0.060).ConclusionSleep quality during the first trimester may be a risk factor for elevated blood glucose and GDM later in gestation.

Influence of type of starch and feeding management on glycaemic control in diabetic dogs.

The present study evaluated the effects of two diets with different starch sources and two feeding methods on the glycaemic control in dogs with diabetes mellitus. The diets had similar nutrient contents (40% starch and 16% dietary fibre), one formulated with 46% of broken rice and the other with 42% sorghum and 10% lentils (as-fed). Ten client-owned diabetic dogs were fed with each diet for 2months, in a crossover design. Five dogs received NPH human insulin and food every 12h (feeding method 1), and the other five received insulin every 12h but were fed three times a day (feeding method 2). In feeding method 2, morning insulin was higher than the evening dose and dogs received the second meal after 4 to 5h of the morning insulin and meal. Parameters evaluated included insulin dosage, 12- and 8-h glycaemic curves, complete blood count, biochemical profile and urinalysis. Glycaemic curves were analysed by ANOVA with repeated measures. Glycaemic control parameters (fasting, mean, minimum and maximum glycaemia and serum fructosamine) and glucose area under the curve (AUC) were calculated and analysed by paired t test (p<0.05). In feeding method 1, dogs fed the sorghum-based diet presented lower mean (p=0.04) and minimum blood glucose concentrations (p=0.03), and a tendency to lower maximum blood glucose (p=0.06) and glucose AUC (p=0.08) than when fed the rice-based diet. When food was provided twice a day, the ingestion of the rice-based diet resulted in higher post-prandial glucose response than the diet with sorghum and lentil. In feeding method 2, there was no effect of diet on the assessed parameters (p>0.05). No differences in insulin dosage were observed between groups or feeding methods (p>0.05). Providing two meals a day followed by insulin administration associated with the sorghum- and lentil-based diet improved glycaemic control in diabetic dogs.

The effect of supplementation of Isomaltooligosaccharide and emulsified medium-chain triglycerides on blood glucose, β-hydroxybutyrate and calorie intake in male Wistar rats

<h2>Summary</h2><h3>Background</h3> A high concentration of energy substrate in circulation will suppress appetite and subsequent food intake. Medium-chain triglycerides (MCT) is a natural exogenous ketone source that can act as an energy substrate, increase blood ketone and suppress appetite. MCT emulsification increases its ketogenic properties. Interestingly, Isomaltooligosaccharide (IMO), a form of dietary fiber, can absorb and retain water, induce the stomach wall distention, and therefore could induce the afferent signal that causes appetite suppression. Despite those facts, there are no data available on whether a food supplement contains a combination of IMO and emulsified MCT (FC-MCT) could induce more appetite suppression. <h3>Objectives</h3> This research investigated the effect of FC-MCT on blood glucose, β-hydroxybutyrate (βHB), and calorie intake in male Wistar rats. <h3>Methods</h3> A total of 31 male Wistar rats were divided into four groups. 1) The MC group (n = 8) - MCT 10 ml/kg of body weight; 2) the FC group (n = 8) - combination of IMO and emulsified coconut oil or FC-CO 100% (w/v) 15 ml/kg of body weight; 3) the FM group (n = 7) - FC-MCT 100% (w/v) 15 ml/kg of body weight; and 4) the SU group (n = 8) - sucrose solution 20% (w/v) 15 ml/kg of body weight. Emulsified coconut oil acted as an isocaloric adjustor for IMO to balance MCT. Blood glucose and βHB were observed for 4 h, with 1 (one) hour measurement interval, presented as the area under the curve (AUC). The food intake was measured 4 h post supplementation. <h3>Results</h3> Compared with other groups, we observed low Blood glucose AUC (p = 0.000), total calorie (p = 0.000) and food intake (p = 0.000) and high βHB AUC (p = 0.000) in the FM groups. <h3>Conclusion</h3> We could successfully demonstrate that FC-MCT supplementation before a meal could suppress appetite and calorie intake. The caloric suppression seems to be mediated through the increased blood βHB concentration.

Pharmacological inhibition of dynamin-related protein 1 attenuates skeletal muscle insulin resistance in obesity.

Dynamin‐related protein‐1 (Drp1) is a key regulator in mitochondrial fission. Excessive Drp1‐mediated mitochondrial fission in skeletal muscle under the obese condition is associated with impaired insulin action. However, it remains unknown whether pharmacological inhibition of Drp1, using the Drp1‐specific inhibitor Mitochondrial Division Inhibitor 1 (Mdivi‐1), is effective in alleviating skeletal muscle insulin resistance and improving whole‐body metabolic health under the obese and insulin‐resistant condition. We subjected C57BL/6J mice to a high‐fat diet (HFD) or low‐fat diet (LFD) for 5‐weeks. HFD‐fed mice received Mdivi‐1 or saline injections for the last week of the diet intervention. Additionally, myotubes derived from obese insulin‐resistant humans were treated with Mdivi‐1 or saline for 12 h. We measured glucose area under the curve (AUC) from a glucose tolerance test (GTT), skeletal muscle insulin action, mitochondrial dynamics, respiration, and H2O2 content. We found that Mdivi‐1 attenuated impairments in skeletal muscle insulin signaling and blood glucose AUC from a GTT induced by HFD feeding (p < 0.05). H2O2 content was elevated in skeletal muscle from the HFD group (vs. LFD, p < 0.05), but was reduced with Mdivi‐1 treatment, which may partially explain the improvement in skeletal muscle insulin action. Similarly, Mdivi‐1 enhanced the mitochondrial network structure, reduced reactive oxygen species, and improved insulin action in myotubes from obese humans (vs. saline, p < 0.05). In conclusion, inhibiting Drp1 with short‐term Mdivi‐1 administration attenuates the impairment in skeletal muscle insulin signaling and improves whole‐body glucose tolerance in the setting of obesity‐induced insulin resistance. Targeting Drp1 may be a viable approach to treat obesity‐induced insulin resistance.

13C/12C breath test ratio after the ingestion of a meal naturally enriched with (13C)carbohydrates is a surrogate marker of insulin resistance and insulin sensitivity in children and adolescents with Type 1 Diabetes

AimsTo test the hypotheses that exogenous carbohydrate oxidation affects postprandial glycaemic profiles and 13C/12C breath test could be used for estimating insulin resistance (IR) and insulin sensitivity (IS) in youths with Type 1 Diabetes (T1D). MethodsNon-randomized, cross-sectional study for repeated measures; fifteen youths (11–15 years) with T1D were enrolled. Respiratory exchanges were measured by indirect calorimetry after the ingestion of a mixed meal [13% protein, 29% fat, 58% carbohydrate (CHO; naturally enriched with [13C]carbohydrates)]. Total and exogenous CHOs oxidation was calculated by indirect calorimetry and 13C/12C breath test. IR and IS were calculated using estimated Glucose Disposal Rate (eGDR) and Insulin Sensitivity Score (ISS). ResultsThe blood glucose Area Under the Curve (BG-AUC) was significantly associated with the amount of exogenous CHOs oxidized (r = −0.67, p < 0.02) when adjusting for CHOs intake and %fat mass. A direct correlation between eGDR and ISS with exogenous CHOs oxidized (r = 0.70, p < 0.02; r = 0.61, p < 0.05 respectively) and with the differential of 13C/12C enrichment in the expired at breath test (r = 0.59, p < 0.05; r = 0.62, p < 0.05), was found. ConclusionsAssessing the capacity to oxidize exogenous CHOs (estimated by the differential of 13C/12C enrichment in the expired air at the breath test) could be used as a non-invasive surrogate marker of IR and IS in youths with T1D.

Prior ingestion of a ketone monoester supplement reduces postprandial glycemic responses in young healthy-weight individuals.

The main objective of this study was to determine whether acute ingestion of a ketone monoester (KME) supplement impacted mixed-meal tolerance test (MMTT) glucose area under the curve (AUC). Nineteen healthy young volunteers (10 males/9 females; age, 24.7 ± 4.9 years; body mass index, 22.7 ± 2.4 kg/m2) participated in a double-blind, placebo-controlled crossover study. Following overnight fasting (≥10 h), participants consumed 0.45 mL/kg of a KME supplement or taste-matched placebo followed by an MMTT 15 min later. Blood samples were collected every 15-30 min over 2.5 h. KME supplementation acutely raised β-hydroxybutyrate AUC (590%, P < 0.0001, d = 2.4) and resulted in decreases in blood glucose AUC (-9.4%, P = 0.03, d = 0.56) and nonesterified fatty acid (NEFA) AUC (-27.3%, P = 0.023, d = 0.68) compared with placebo. No differences were found for plasma insulin AUC (P = 0.70) or gastric emptying estimated by co-ingested acetaminophen AUC (P = 0.96) between ketone and placebo. Overall, results indicate that KME supplementation attenuates postprandial glycemic and NEFA responses when taken 15 min prior to a mixed meal in young healthy individuals. Future studies are warranted to investigate whether KME supplementation may benefit individuals with impaired glycemic control. Novelty: Acute ketone monoester supplementation 15 min prior to a mixed meal decreased postprandial glucose and NEFA levels without significantly impacting postprandial insulin or estimates of gastric emptying. Glucose- and NEFA-lowering effects of ketone monoester supplementation are apparently not mediated by changes in insulin release or gastric emptying.

The Acute Effect of Bovine Whey Protein Fractions on Blood Glucose and Insulin in Rats

The ingestion of whey protein (WP) leads to the reduction of postprandial blood glucose (BG) response paralleled with an increased level of insulin. However, the role of individual WP fractions: glycomacropeptide (GMP), β‐Lactoglobulin (β‐LG), and α‐Lactalbumin (α‐LA) remain unclear.The objective of this study was to investigate the effect of WP, GMP, β‐LG, and α‐LA on BG and insulin response in rats.We hypothesized that due to the difference in their amino acid profile the effect of WP fractions on short‐term BG control may differ.MethodsA randomized repeated measures study was conducted in rats fitted with jugular vein catheters and vascular access buttons (VAB). Nine male 10‐week‐old 275–300g Wistar Han rats were gavaged 350mg (allometricaly scaled from a human dosage of 10g) of either intact WP, GMP, β‐LG, α‐LA, or a glucose control dissolved in 3ml of water after being fasted for 6h during daylight. The use of a VAB allowed for the same rat to receive all five treatments in a random order, with a 48h washout period between treatments. Blood was collected at 0, 15, and 30 min for insulin, and at 0, 15, 30, 60, 90, and 120 min for glucose. Whole blood was analyzed for glucose using a HemoCue 201 Glucose Analyzer, and plasma was analyzed for insulin using a wide range ELISA. The data were tested for normality and analyzed using Two‐Way Repeated Measures ANOVA for the effect of time, treatment and a treatment by time interaction. The data for the area under the curve (AUC) for 2h BG and 30 min insulin were analyzed with One‐Way Repeated Measures ANOVA. The differences between the treatments were assessed with Tukey‐Kramer post hoc test.ResultsThere was an effect of treatment (P&lt;0.0001), time (P&lt;0.0001) and a treatment by time interaction (P&lt;0.0001) over 120 min on BG response. Whey protein, GMP, β‐LG, and α‐LA resulted in significantly lower BG compared to glucose treatment at 15 and 30 min (P&lt;0.05). Blood glucose AUC over 120 min was lower for WP, GMP, and α‐LA compared to glucose treatment (P&lt;0.05). There was an effect of treatment (P=0.02), time (P&lt;0.0001) and a treatment by time interaction (P=0.0002) on insulin response over 30 min. Glycomacropeptide had a lower insulin response at 15 min compared to glucose and β‐LG (P&lt;0.05). Insulin AUC over 30 min was lower for GMP compared to the glucose treatment (P=0.003).ConclusionAt the dose of 350mg WP, GMP, β‐LG, and α‐LA attenuated BG response at 15 and 30 min, while only WP, GMP, and α‐LA attenuated AUC over 120 min compared to the glucose control. GMP attenuated insulin response at 15 min compared to β‐LG and the glucose control, and attenuated AUC over 30 min compared to the glucose control. These data suggest that WP fractions possess unique properties not observed in WP.Support or Funding InformationSupported by the Natural Sciences and Engineering Research Council of Canada (NSERC). Erik Vandenboer has received support from NSERC and Nova Scotia Health Research Foundation.

Associations Among Indices of Insulin Resistance and Vascular Reactivity in Older, Obese Adults

Insulin resistance (IR), estimated by calculating the homeostasis model assessment of IR (HOMA-IR), independently predicts incident cardiovascular disease (CVD) events. Further, HOMA-IR is inversely associated with brachial artery flow-mediated dilation (FMD) in non-diabetics, suggesting that IR may contribute to vascular dysfunction that increases CVD risk. PURPOSE: We sought to determine associations among indices of IR/glucose control and vascular reactivity in older, obese adults. We hypothesized that brachial artery FMD and hyperemic shear rate area under the curve (AUC) would be inversely associated with indices of IR/glucose control. METHODS: Preliminary data are from older, obese adults [n = 20 (16 women); age = 64.2 ± 4.8 y; BMI = 35.3 ± 5.3 kg/m2] participating in an ongoing clinical study. Brachial artery FMD and hyperemic shear rate AUC were assessed by a trained technician using high-resolution ultrasonography following an overnight fast. Additionally, fasting blood glucose (FBG) and serum insulin concentrations, HOMA-IR, hemoglobin (Hb)A1c, and postprandial blood glucose responses (i.e., 2 h AUC) to mixed meal ingestion (0.3 g protein/kg lean body mass + 0.5 g glucose/kg lean body mass) were measured to assess IR/glucose control. Partial correlations (controlling for age and sex) were used to examine associations among these variables. RESULTS: Participants were insulin resistant (HOMA-IR = 3.7 ± 2.2) but not diabetic (FBG = 99.5 ± 9.5 mg/dL, HbA1c = 5.5 ± 0.2%). Fasting brachial artery FMD (3.4 ± 1.6%) was not correlated (all P≥0.44) with FBG (r = -0.18) or serum insulin (14.2 ± 7.5 μIU/ml; r = -0.07), HOMA-IR (r = -0.13), HbA1c (r = -0.19), or 2 h blood glucose AUC (13,430 ± 2,298 mg/min/dL; r = -0.23). Hyperemic shear rate AUC was not correlated with indices of IR/glucose control (all P≥0.11). CONCLUSIONS: Preliminary data from our ongoing clinical study show that indices of IR/glucose control are not associated with vascular reactivity in older, obese adults. Continued recruitment of participants will more definitely determine the potential contribution of IR to vascular dysfunction and CVD risk. Supported by National Institute on Aging (1R15AG055923-01).

PO-146 Effects of aerobic exercise training on GTT and ITT in apelin Knockout mice

Objective Aerobic exercise training is important to prevent and cure chronic diseases such as diabetes, cardiovascular diseases and so on. Apelin has been identified as a novel myokine in recent years, and the exogenous supplementation of apelin can promote the glucose absorption, the biosynthesis of mitochondria and the oxidation of fatty acids in skeletal muscle. Intraperitoneal glucose (GTT) and insulin tolerance tests (ITT) are useful in vivo assays that provide approximations of glucose metabolism and homeostasis. The bigger area under the curve (AUC) confirmed the decreased glucose clearance, which is evaluated by GTT. However, the mechanism of apelin mediating glucose metabolism during aerobic exercise training is not clear. Our study was to investigate the differences of GTT and ITT after four weeks training between wild-type (WT) mice (C57BL/6J) and apelin Knockout (KO) mice.&#x0D; Methods Two-month-old WT and KO were divided into trained and control groups (n=8-10/group) respectively. There are four groups: WT control (WC), apelin KO control (KC), WT trained (WT), and apelin KO trained (KT). The trained groups were trained on treadmills for four weeks (six days per week and one hour per day). In order to maintain the exercise intensity, the speed is at 70%-75% VO2max with an incline of 5 degrees. The control groups were kept at a sedentary condition. after four weeks of interventions, glucose was measured at 0, 15, 30, 45, 60, 90, 120min following GTT. Glucose was also measured at 0, 30, 60, 90, 120min following ITT.&#x0D; Results (1) blood glucose levels and AUC of the KC were significantly bigger than those of WC. ITT showed that KC also had slower insulin-stimulated glucose clearance compared with the WC. (2) Following 4-week training, KT had lower blood glucose levels and AUC of the KT was significantly smaller than those of KC. KT had faster insulin-stimulated glucose clearance compared with KC.&#x0D; Conclusions Without apelin, glucose tolerance and insulin tolerance in mice will decrease. And aerobic exercise training improves them in apelin deficiency mice.

The effects of whole-grain compared with refined wheat, rice, and rye on the postprandial blood glucose response: a systematic review and meta-analysis of randomized controlled trials

Whole grains are often referred to collectively, despite differences in their composition, physical structure, processing, and potential health benefits. The aim of this study was to compare the postprandial blood glucose response of whole-grain with refined wheat, rice, or rye, while controlling for the food delivery matrix and the processing of the grain (e.g., grinding, germination). Eleven electronic databases were systematically searched to identify studies published up to and including November 2017. Randomized controlled trials comparing the effects of whole-grain wheat, rice, or rye with those of each grain's refined counterpart on postprandial blood glucose area under the curve (AUC) were included. Pooled effect sizes were computed by using the difference in the blood glucose AUC after the consumption of the whole compared with the refined grain. Twenty publications were included, with 10, 14, and 5 strata (or active-control comparisons) on whole-grain wheat, rice, and rye, respectively. The consumption of ground (wholemeal) wheat, compared with white wheat, was not associated with a significant reduction in blood glucose AUC (-6.7 mmol/L ⋅ min; 95% CI: -25.1, 11.7 mmol/L ⋅ min; P=0.477). The consumption of wholemeal rye, compared with endosperm rye, was not associated with a significant reduction in blood glucose AUC (-5.5 mmol/L ⋅ min; 95% CI: -24.8, 13.8 mmol/L ⋅ min; P=0.576). The consumption of intact (whole-grain) rice, compared with white rice, was associated with a significant reduction in blood glucose AUC (-40.5 mmol/L ⋅ min; 95% CI: -59.6, -21.3 mmol/L ⋅ min; P<0.001). Compared with white rice, whole-grain rice significantly attenuates the postprandial blood glucose response. In most of the studies on wheat and rye, the postprandial blood glucose responses to foods formulated with wholemeal compared with refined flours were compared. Whether reductions in the blood glucose AUC can be achieved with whole-grain (as opposed to wholemeal) wheat and rye requires further investigation.

Comparison between pre-exercise casein peptide and intact casein supplementation on glucose tolerance in mice fed a high-fat diet

We hypothesized that along with exercise, casein peptide supplementation would have a higher impact on improving glucose tolerance than intact casein. Male 6-week-old ICR mice were provided a high-fat diet to induce obesity and glucose intolerance. The mice were randomly divided into 4 treatment groups: control (Con), endurance training (Tr), endurance training with intact casein supplementation (Cas+Tr), and endurance training with casein peptide supplementation (CP+Tr). The mice in each group were orally administrated water, intact casein, or casein peptide (1.0 mg/g body weight, every day), and then subjected to endurance training (15-25 m/min, 60 min, 5 times/week for 4 weeks) on a motor-driven treadmill 30 min after ingestion. Our results revealed that total intra-abdominal fat was significantly lower in CP+Tr than in Con (p < 0.05). Following an oral glucose tolerance test, the blood glucose area under the curve (AUC) was found to be significantly smaller for CP+Tr than for Con (p < 0.05). Moreover, in the soleus muscle, glucose transporter 4 (GLUT4) protein levels were significantly higher in CP+Tr than in Con (p < 0.01). However, intra-abdominal fat, blood glucose AUC, and GLUT4 protein content in the soleus muscle did not alter in Tr and Cas+Tr when compared with Con. These observations suggest that pre-exercise casein peptide supplementation has a higher effect on improving glucose tolerance than intact casein does in mice fed a high-fat diet.

Isoproterenol exacerbates hyperglycemia and modulates chromium distribution in mice fed with a high fat diet

Background and purposeIsoproterenol (ISO), a nonselective β-adrenoceptor agonist for treating bradycardia and asthma, has been proposed to raise blood glucose level. Little is known regarding the relationship between ISO treatment, the induced chromium (Cr) redistribution, and changes in glucose metabolism. We aimed to characterize the effects of a single dose of ISO on glucose homeostasis and Cr level changes in an obesity mouse model. MethodsMice (C57BL6/j strain) were first fed for a continuous period of 12 weeks with either a high fat diet (HFD), to develop an obesity animal model, or a standard diet (SD), to develop a lean animal model as controls. These groups were each separated into two subgroups to receive either a single dose of ISO or saline (control). We measured in vivo their metabolic parameters, fasting glucose level, area under the curve (AUC) for glucose level time profile, insulin level time profile, insulin sensitivity index, and chromium distribution. ResultsAfter a single dose of ISO, the SD-fed mice had slightly higher blood glucose levels compared with the SD controls, when the level was measured 30 and 60min after injection. By contrast, the ISO-treated HFD-fed mice had significantly higher blood glucose levels and AUC during the entire 120min following one administration compared with the HFD control group. Additionally, they had a substantially lower HOMA-IR index, whereas insulin levels remained unchanged. The Cr level in their bones and liver was decreased, and loss of Cr through urinary excretion was elevated. ConclusionThe results demonstrated that ISO exacerbated hyperglycemic syndrome in the obesity animal model. ISO induced a net negative Cr balance as a result of increased urinary excretion, leading to Cr mobilization that was not desirable to overcome the hyperglycemia.

The Effects of Low‐Intensity Exercise during Bed Rest in Healthy Older Adults

Aging results in the involuntary loss of muscle mass and strength. These rates of decline are exacerbated with hospitalization, illness, and injury (i.e., catabolic stressors). Acutely ill, hospitalized adults have significantly reduced daily activity (~740 steps/day) compared to their healthy counterparts (~6250 steps/day). While intense exercise is clearly not practical for older, hospitalized individuals, low‐intensity exercise may be a more practical alternative. 60 minutes of daily longitudinal loading (1G artificial gravity/centrifugation) has been shown to maintain muscle protein synthesis during bed rest in a young adult population. Thus, we hypothesized that low‐intensity exercise (2,000 steps/day) would mitigate the loss of muscle mass and function during 7‐days of bed rest in healthy older adults.We employed a 7‐day bed rest protocol as a model of the physical inactivity associated with hospitalization. Dietary intake and daily steps were strictly controlled. Volunteers were randomized into two experimental groups: bed rest alone (CON: N=10, 68±5 y) or bed rest + 2,000 daily steps (STEP: N=7, 68±6 y). Isometric strength, leg lean mass (LLM) and blood glucose area under the curve (AUC) were assessed at baseline and after 7‐days of bed rest. Changes in isokinetic extension (60°/s) (CON: −13.3±3.3 N·m vs STEP: −14.4±3.8 N·m), LLM (CON: −932.3±181.8 g vs STEP: −700.4±149.2 g), and blood glucose AUC (CON: 456.4±1016.5 mg/dl/120 min vs STEP: −901.4±986.4 mg/dl/120 min) were similar between groups.Data from this ongoing clinical trial suggests that a single bout of 2,000 steps/day is not sufficient to counter the catabolic effects of 7‐days bed rest in healthy older adults. Future exploration of the effects of a greater number of steps/day, the combined effects of nutritional support plus exercise or distributing activity across the day may be needed to have clinically translatable benefits.Support or Funding InformationSupported by RO1 NR012973, P30 AG024832.

Rosa Mosqueta Oil Prevents Oxidative Stress and Inflammation through the Upregulation of PPAR-α and NRF2 in C57BL/6J Mice Fed a High-Fat Diet

BackgroundRosa mosqueta (RM) oil is characterized by high concentrations of antioxidants and α-linolenic acid (ALA; 18:3n–3). We have previously demonstrated in male C57BL/6J mice that RM decreases hepatic steatosis, a condition strongly associated with oxidative stress and inflammation. ObjectiveWe studied the molecular mechanisms that underlie the role of RM in preventing high-fat diet (HFD)–induced oxidative stress and inflammation. MethodsMale C57BL/6J mice aged 28 d and weighing 12–14 g were divided into the following groups and fed for 12 wk: control diet (CD; 10% fat, 20% protein, and 70% carbohydrates); CD + RM (1.94 mg ALA ⋅ g body weight–1 ⋅ d–1 administered by oral gavage); HFD (60% fat, 20% protein, and 20% carbohydrates); and HFD + RM. General parameters (body weight, visceral fat, and histology); glucose metabolism [homeostasis model assessment and blood glucose area under the curve (AUC)]; oxidative stress [hepatic nuclear factor (erythroid-derived 2)-like-2 (NRF2) and heme oxygenase 1 (HO-1) concentrations]; and inflammation [hepatic peroxisome proliferator-activated receptor α (PPAR-α) and acyl-coenzyme A oxidase 1 (ACOX1) concentrations, blood tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) concentrations, and Tnfa and Il1b mRNA expression in liver and visceral adipose tissue] were evaluated. ResultsIn the HFD + RM mice, the final body weight (24.8 ± 1.1 g) was 19% lower than in the HFD mice (30.6 ± 2.8 g) (P < 0.05). Visceral fat was 34% lower in the HFD + RM mice than in the HFD mice (P < 0.05). The blood glucose AUC was 29% lower and Tnfa and Il1b expression levels were 47% and 59% lower, respectively, in the HFD + RM mice than in the HFD mice (P < 0.05). HFD + RM mice had 40% less hepatic steatosis (P < 0.05) and lower upregulation of PPAR-α (33%), ACOX1 (50%), NRF2 (39%), and HO-1 (68%) protein concentrations than did the HFD mice (P < 0.05). ConclusionsOur findings suggest that RM supplementation prevents the obese phenotype observed in HFD-fed mice by downregulating inflammatory cytokine expression and secretion and stimulating hepatic antioxidant and fatty acid oxidation markers.

Comparison of Glucose Area Under the Curve Measured Using Minimally Invasive Interstitial Fluid Extraction Technology with Continuous Glucose Monitoring System in Diabetic Patients.

BackgroundContinuous glucose monitoring (CGM) is reported to be a useful technique, but difficult or inconvenient for some patients and institutions. We are developing a glucose area under the curve (AUC) monitoring system without blood sampling using a minimally invasive interstitial fluid extraction technology (MIET). Here we evaluated the accuracy of interstitial fluid glucose (IG) AUC measured by MIET in patients with diabetes for an extended time interval and the potency of detecting hyperglycemia using CGM data as a reference.MethodsThirty-eight inpatients with diabetes undergoing CGM were enrolled. MIET comprised a pretreatment step using a plastic microneedle array and glucose accumulation step with a hydrogel patch, which was placed on two sites from 9:00 AM to 5:00 PM or from 10:00 PM to 6:00 AM. IG AUC was calculated by accumulated glucose extracted by hydrogel patches using sodium ion as standard. ResultsA significant correlation was observed between the predicted AUC by MIET and CGM in daytime (r=0.76) and nighttime (r=0.82). The optimal cutoff for the IG AUC value of MIET to predict hyperglycemia over 200 mg/dL measured by CGM for 8 hours was 1,067.3 mg·hr/dL with 88.2% sensitivity and 81.5% specificity.ConclusionWe showed that 8-hour IG AUC levels using MIET were valuable in estimating the blood glucose AUC without blood sampling. The results also supported the concept of using this technique for evaluating glucose excursion and for screening hyperglycemia during 8 hours in patients with diabetes at any time of day.

Intragastric administration of leucine or isoleucine lowers the blood glucose response to a mixed-nutrient drink by different mechanisms in healthy, lean volunteers

The branched-chain amino acids leucine and isoleucine lower blood glucose after oral glucose ingestion, and the intraduodenal infusion of leucine decreases energy intake in healthy, lean men. We investigated the effects of the intragastric administration of leucine and isoleucine on the gastric emptying of, and blood glucose responses to, a physiologic mixed-macronutrient drink and subsequent energy intake. In 2 separate studies, 12 healthy, lean subjects received on 3 separate occasions an intragastric infusion of 5 g leucine (leucine-5g) or an intragastric infusion of 10 g leucine (leucine-10g), an intragastric infusion of 5 g isoleucine (isoleucine-5g) or an intragastric infusion of 10 g isoleucine (isoleucine-10g), or a control. Fifteen minutes later, subjects consumed a mixed-nutrient drink (400 kcal, 56 g carbohydrates, 15 g protein, and 12 g fat), and gastric emptying (13C-acetate breath test) and blood glucose, plasma insulin, C-peptide, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and cholecystokinin (leucine study only) were measured for 60 min. Immediately afterward, energy intake from a cold, buffet-style meal was assessed. Compared with the control, leucine-10g decreased the blood glucose area under the curve (AUC) (P < 0.05) and tended to reduce peak blood glucose (P = 0.07), whereas effects of leucine-5g were NS. Leucine-10g, but not leucine-5g, increased plasma insulin and C-peptide AUCs (P < 0.01 for both), but neither dose affected glucagon, GLP-1, GIP, cholecystokinin, gastric emptying, or energy intake. Compared with the control, isoleucine-10g reduced the blood glucose AUC and peak blood glucose (P < 0.01), whereas effects of isoleucine-5g were NS. Neither load affected insulin, C-peptide, glucagon, GLP-1, or GIP. Isoleucine-10g, but not isoleucine-5g, slowed gastric emptying (P < 0.05), but gastric emptying was not correlated with the blood glucose AUC. Isoleucine did not affect energy intake. In healthy subjects, both leucine and isoleucine reduced blood glucose in response to a mixed-nutrient drink but did not affect subsequent energy intake. The mechanisms underlying glucose lowering appear to differ; leucine stimulated insulin, whereas isoleucine acted insulin independently. These trials were registered at www.anzctr.org.au as 12613000899741 and 12614000837628.

Improved glycemic control with teneligliptin in patients with type 2 diabetes mellitus on hemodialysis: Evaluation by continuous glucose monitoring

AimsRecent reports suggest that appropriate glycemic control without hypoglycemia could decrease mortality in patients with diabetes mellitus (DM) and end-stage renal disease (ESRD). However, an indication of oral anti-diabetic drugs is limited in this population. The aim of this study was to evaluate efficacy of teneligliptin, a novel DPP-4 inhibitor, by continuous glucose monitoring (CGM) in patients with type 2 DM (T2DM) on hemodialysis (HD). MethodsThis 4-week, open label, single arm, intervention trial included 10 diabetic patients undergoing HD and with glycated albumin (GA) level of ≥18.3%. Teneligliptin treatment was administered on days with HD sessions (HD day) and on days without HD sessions (NHD day); blood glucose values were measured by CGM. The primary endpoint was improvement of glycemic control evaluated by area under the curve (AUC). As secondary endpoints, changes in GA, HbA1c and fasting plasma glucose (FPG) were evaluated. ResultsTeneligliptin improved blood glucose AUC on both HD days (p=0.004), and NHD days (p=0.004). This was accompanied by a significant reduction in GA, HbA1c, and FPG, without severe hypoglycemia. ConclusionsTeneligliptin is one of the useful options for glycemic control in T2DM patients undergoing HD.

Clinical Biopotency of Insulin Analogues: Comparative Assessment in Different Species

ObjectiveThe clinical potency of human insulin has classically been evaluated following the U.S. Pharmacopeia (USP) guideline for comparison to an international standard (IS) of activity (IU). However, since insulin analogues cannot be standardized against IS, there is a need for a bioassay to assess clinical specific activity (U). To this extent, we compared the biopotency (U) of different insulin products in different species and used human (recombinant) and pork (natural) insulin as reference standards.Methods: New Zealand White rabbits were fasted and injected subcutaneously (s.c.) at a dose level of 0.5 U/kg. Diabetic Yucatan miniature swine (Sus scrofa) were injected s.c. at dose level of 0.1 U/kg. Normal insulin suppression tests (nIST) were conducted in primates (Macaca fascicularis) receiving a bolus intravenous (i.v.) infusion of glucose. Insulin products were given at dose level of 0.05 U/kg. Glucose levels were recorded using handheld glucometer devices. The blood glucose kinetic (BGPK), the blood glucose area under the curve (BGAUC) and the slope of the blood glucose clearance rate (kG) were used to assess clinical biopotency.Results: The BGPK for short‐acting human and pork insulin were similar in the rabbit assay but their respective BGAUCs were different (ratio of 1.2). Accordingly pork insulin was more potent during nIST in the non‐human primate (slope of ‐0.012 vs. ‐0.010; pork and human, respectively).ConclusionOur data indicate that the clinical biopotency of insulin products can be assessed using BGAUC and kG, but that only the type 1 diabetic miniature swine can discriminate between differences in clinical biopotency for all aspects of BGPK.

Organoleptic and glycemic properties of chickpea-wheat composite breads

Prevalence of obesity and type-2-diabetes requires dietary manipulation. It was hypothesized that wheat-legume-composite breads will reduce the spike of blood glucose and increase satiety. Four pan bread samples were prepared: White bread (WB) as standard, Whole-wheat bread (WWB), WWB supplemented with chickpea flour at 25% (25%ChB) and 35% (35%ChB) levels. These breads were tested in healthy female subjects for acceptability and for effect on appetite, blood glucose, and physical discomfort in digestion. The breads were rated >5.6 on a 9-point hedonic scale with WB significantly higher than all other breads. No difference in area under the curve (AUC) for appetite was found, but blood glucose AUC was reduced as follows: 35%ChB < WB and WWB, WB >25%ChB = WWB or 35%ChB. We conclude that addition of chickpea flour at 35% to whole wheat produces a bread that is acceptable to eat, causing no physical discomfort and lowers the glycemic response.