Insulin Area Under The Curve Research Articles

Pregnancy Is Enough to Provoke Deleterious Effects in Descendants of Fructose-Fed Mothers and Their Fetuses.

The role of fructose in the global obesity and metabolic syndrome epidemic is widely recognized. However, its consumption is allowed during pregnancy. We have previously demonstrated that maternal fructose intake in rats induces detrimental effects in fetuses. However, these effects only appeared in adult descendants after a re-exposure to fructose. Pregnancy is a physiological state that leads to profound changes in metabolism and hormone response. Therefore, we wanted to establish if pregnancy in the progeny of fructose-fed mothers was also able to provoke an unhealthy situation. Pregnant rats from fructose-fed mothers (10% w/v) subjected (FF) or not (FC) to a fructose supplementation were studied and compared to pregnant control rats (CC). An OGTT was performed on the 20th day of gestation, and they were sacrificed on the 21st day. Plasma and tissues from mothers and fetuses were analyzed. Although FF mothers showed higher AUC insulin values after OGTT in comparison to FC and CC rats, ISI was lower and leptinemia was higher in FC and FF rats than in the CC group. Accordingly, lipid accretion was observed both in liver and placenta in the FC and FF groups. Interestingly, fetuses from FC and FF mothers also showed the same profile observed in their mothers on lipid accumulation, leptinemia, and ISI. Moreover, hepatic lipid peroxidation was even more augmented in fetuses from FC dams than those of FF mothers. Maternal fructose intake produces in female progeny changes that alter their own pregnancy, leading to deleterious effects in their fetuses.

PSII-19 The Effects of Maternal Programming on Dairy Bull Calf Response to an Intravenous Glucose Tolerance Test

Abstract Calves are prone to health issues with high mortality observed during the first 3 weeks of life. We hypothesized that dam milk production levels and/or mastitis infection during gestation will lead to reduced insulin production and increased circulating glucose concentration in response to an Intravenous Glucose Tolerance Test (IVGTT) in young dairy bull calves. Calves (n = 45) were selected from dams classified has high producers (HI; Top 25% for herd M305; n = 7), high producers with high somatic cell count (SCC; HIMAST; SCC test during gestation over 200,000 cells/mL; n = 15), moderate producers (MOD; lower 60% for herd M305; n =17) or moderate producers with high SCC (MODMAST; n = 6). IVGTT were performed on the calves at 7 weeks of age. Blood samples were collected prior to (-30, -15 and 0 min) infusion of glucose. After glucose (0.15 grams /kg bw) administration, samples were collected at 2, 5, 10, 15, 30, 60, and 120-minutes post infusion. Serum insulin and glucose concentrations were determined at Cornell Veterinary Medical Diagnostic Laboratory (Ithica, NY). Data were analysed in SAS using Proc Mixed. Insulin:glucose ratio was analysed using Proc Mixed with repeated measures for treatment x time. No effect of maternal milk production and/or mastitis infection during gestation was observed on calf baseline insulin, insulin AUC, baseline glucose or glucose AUC (P ≥ 0.12). Similarly, no difference in Insulin:Glucose ratio was observed in these calves (P = 0.66). In conclusion, high maternal milk production and/or mastitis infection may not have an effect on circulating insulin production in calves in response to an IVGTT. Correlation analyses will be performed on these data, as well as additional analyses, to determine if insulin sensitivity or response (ie: phase 1 response) was altered further.

P007 Eating in alignment with the circadian clock: A strategy to reduce the metabolic impact of nightwork

Abstract Nightwork disrupts circadian rhythms and impairs glucose metabolism, increasing the risk for type 2 diabetes. We investigated eliminating or reducing the amount of food consumed during simulated nightwork as a countermeasure to reduce the impact of circadian disruption on glucose metabolism. N=52 healthy, non-shiftworking participants (24.4±4.9 years; 26 Females; BMI 23.8±2.5kg/m2) underwent a 7-day laboratory protocol with an 8h TIB baseline sleep, followed by 4 simulated nightshifts with 7h TIB daytime sleep and an 8h TIB recovery sleep in groups of 4 participants. Each group was randomly assigned to a meal-at-midnight (n=17, 30% energy requirements), snack-at-midnight (n=16, 10% energy requirements) or no-eating-at-midnight (n=19) condition. Total 24h energy and macronutrient intake were constant across conditions. Standard oral glucose tolerance tests (OGTT) were conducted on day2 (baseline), and day7 (recovery). Plasma was sampled at -15, 0, 15, 30, 60, 90, 120, 150 mins, assayed for glucose and insulin. Area under the curve (AUC) was the calculated. Mixed model analyses of glucose AUC found a condition-by-day interaction (p<0.001). Glucose responses to OGTT did not change with nightwork in the no-eating-at-midnight condition (p=0.219) but worsened in the meal-at-midnight (p<0.001) and snack-at-midnight (p=0.022) conditions. Insulin AUC was different by condition (p=0.047). Insulin was highest after nightwork in the no-eating-at-midnight compared to meal-at-midnight (p=0.014) but not snack-at-midnight (p=0.345). Glucose tolerance was impaired by eating-at-midnight, associated with a lower than expected insulin response. Further work is required to determine the effect of meal or snack composition as a strategy to mitigate adverse metabolic effects of nightwork.

The stimulatory effects of glucagon on cortisol and GH secretion occur independently from FGF-21.

Glucagon stimulation test (GST) is used to assess the hypothalamo-pituitary-adrenal (HPA) and growth hormone (GH) axes with an incompletely defined mechanism. We aimed to assess if glucagon acted through fibroblast growth factor-21 (FGF-21) to stimulate cortisol and GH secretion. The secondary outcome was to determine the relationship of FGF-21 with variable GH responses to GST in obesity. A total of 26 healthy participants; 11 obese (body mass index (BMI) > 30 kg/m2) and 15 leans (BMI < 25 kg/m2) were included. Basal pituitary and target hormone levels were measured and GST was performed. During GST, glucose, insulin, cortisol, GH, and FGF-21 responses were measured. The mean age of the participants was 26.3±3.6 years. Glucagon resulted in significant increases in FGF-21, glucose, insulin, cortisol, and GH levels. The levels of basal cortisol, GH, FGF-21, and IGF-1 were similar in the two groups. The peak GH and area under the curve (AUC)(GH) responses to GST in the obese group were lower than those of the normal-weight group with a different pattern of response. There were no differences between the groups in terms of peak cortisol, AUC(cortisol), peak insulin, AUC(insulin), peak FGF-21, and AUC(FGF21). Obesity was associated with significantly increased glucose and insulin responses and slightly decreased FGF-21 response to glucagon. Obesity was associated with blunted and delayed GH, but preserved cortisol responses to GST. This is the first study showing that glucagon stimulates the HPA and GH axis independently from FGF-21. The delayed GH response to GST in obesity does not seem to be related to FGF-21.

Effects of consumption of coconut oil or coconut on glycemic control and insulin sensitivity: A systematic review and meta-analysis of interventional trials

Background and aimsThe often purported claim that coconut fat is beneficial for cardiovascular health and was disputed in several recent meta-analyses. However, the evidence on the effects of coconut fat intake on glycemic control remains equivocal. We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines to determine the effects of dietary coconut fats on markers of acute and long-term glycemic control. Methods and resultsPubMed, Scopus, ProQuest, and Web-of-Science databases were searched and the records were screened by three independent reviewers to identify interventional studies examining acute and long-term (i.e., >10 days) effects of coconut fat on glycemic control. DerSimonian–Laird random-effects meta-analyses were performed using the meta-package in R (4.0.2). Seven interventional studies on acute effects and 11 interventional studies on long-term effects of coconut fat were included. Meals with coconut fat acutely increased the incremental area under the curve (AUC) of glucose (p = 0.046) and decreased the incremental AUC of insulin (p = 0.037) vs. control meals. Long-term coconut fat intake increased HOMA-IR (p = 0.049), but did not significantly affect fasting glucose, insulin, or HOMA-β vs. control meals. ConclusionsCoconut fat in meals seems to be associated with a diminished postprandial insulin response, resulting in a subtle increase in the postprandial glycemic response. Long-term intake of coconut fat seems to increase insulin resistance, yet does not seem to be beneficial for long-term glycemic control. Thus, our results disprove the popular claim that coconut fat improves glycemic control. RegistrationPROSPERO registry (CRD42020183450).

Rate of Gestational Weight Gain and Glucose-Insulin Metabolism Among Hispanic Pregnant Women With Overweight and Obesity.

Hispanic women are at elevated risk of gestational glucose intolerance and postpartum type 2 diabetes compared with non-Hispanic White women. Identification of potentially modifiable factors contributing to this trajectory of beta-cell dysfunction is warranted. We aimed to determine the association between rate of gestational weight gain (rGWG) and glucose-insulin metabolism in Hispanic pregnant women with overweight and obesity. This cross-sectional, observational study, conducted from 2018-2020 at the clinical research center at University of California, Irvine, included 33 nondiabetic Hispanic pregnant women at 28 to 30 weeks' gestation with pre-pregnancy body mass index (BMI) 25.0 to 34.9 kg/m2. Participants consumed a standardized liquid mixed meal after an overnight fast. Serial blood samples were collected at fasting and up to 2 hours postprandial. The glucose and insulin area under the curve (AUC), insulin sensitivity index (ISI) and insulin secretion sensitivity index (ISSI)-2 were computed. Average rGWG (0.36 ± 0.22 kg/week) was classified as excessive in 60% of women. While rGWG was not associated with the glucose or insulin AUC or ISI, it accounted for 13.4% of the variance in ISSI-2 after controlling for covariates (maternal age, parity, and pre-pregnancy BMI); for each 1 unit increase in rGWG, ISSI-2 decreased 2.1 units (P = 0.015). Even in the absence of gestational diabetes, rGWG was inversely associated with beta-cell function in a high-risk population of Hispanic pregnant women with overweight and obesity. Beta-cell decline is an established risk factor for transition to type 2 diabetes, and these cross-sectional findings highlight rGWG as a potentially modifiable contributor to this process.

Insulin Sensitivity After Living Donor Nephrectomy

The kidney is essential for glucose and insulin metabolism. Living kidney donors (LKDs) experience a reduction in glomerular filtration rate of 25 to 30 mL/min after donor nephrectomy. Little is known about the effect of glomerular filtration rate decline on insulin sensitivity in LKDs. We conducted a prospective pilot study on 9 LKDs (N=9) who underwent dynamic metabolic testing (mixed meal tolerance test) to measure proxies of insulin sensitivity (homeostatic model assessment of insulin resistance, the area under curve [AUC] for insulin/glucose ratio, and Matsuda insulin sensitivity index) before and 3 months after donor nephrectomy. The primary outcome was the change in insulin sensitivity indices (delta [post-nephrectomy - pre-nephrectomy]). Four of the donors had a body mass index (BMI) between 32.0 and 36.7 predonation. Post-donor nephrectomy, compared with prenephrectomy values, median insulin AUC increased from 60.7 to 101.7 hr*mU/mL (delta median 33.3, P=.04) without significant change in median glucose AUC levels from 228.9 to 209.3 hr*mg/dL (delta median 3.2, P=.77). There was an increase in the median homeostatic model assessment of insulin resistance from 2 to 2.9 (delta median 0.8, P=.03) and the AUC insulin/glucose ratio from 30.9 to 62.1 pmol/mmol (delta median 17.5, P=.001), whereas the median Matsuda insulin sensitivity index decreased from 5.9 to 2.9 (delta median -2, P=.05). The changes were more pronounced in obese (BMI >32) donors. LKDs appear to have a trend toward a decline in insulin sensitivity post-donor nephrectomy in the short term, especially in obese donors (BMI >32). Further investigation with a larger sample size and longer follow-up is needed.

The incessant increase curve during oral glucose tolerance tests in Chinese adults with type 2 diabetes and its association with gut hormone levels

Glucose curve shapes during oral glucose tolerance tests (OGTTs) are mainly classified as incessant increase, monophasic and biphasic. Youth with an incessant increase curve have worse β-cell function. The aim of this paper was to investigate the incessant increase curve in Chinese adults with type 2 diabetes (T2DM), and its association with β-cell function and gut hormone levels. Eighty-nine Chinese patients (59 males and 30 females) were included in this study with a mean age of 50.56 ± 16.00 years. They were all recently diagnosed with T2DM and underwent 180-min OGTTs. Data on demographics, β-cell function, and insulin sensitivity were also collected. Gut hormones, including glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and ghrelin, were also detected during the OGTT. A total of 39.3 % of subjects had an incessant increase in the glucose response curve, while 59.6 % had a monophasic curve. Because only one curve was classified as biphasic, patients with a biphasic curve were omitted from further research. Lower plasma C-peptide, HOMA2-β, area under the curve (AUC) of C-peptide, and ratio of AUC of insulin to AUC of glucose were found in patients with incessant increase curves compared to those with monophasic curves (P < 0.05). Higher glycated hemoglobin (HbA1c) was found in subjects with an incessant increase curve (P < 0.05). Importantly, fasting plasma ghrelin was lower and incremental ghrelin at 120 min was higher in the incessant increase group (P < 0.05), irrespective of age, sex, body mass index (BMI), fasting glucose, and fasting insulin. Time to peak is also a parameter of the OGTT curve shape. In the late-peak group, GLP-1 at 120 min and the AUC of GLP-1 were elevated compared with those in the early-peak group (P < 0.05). In Chinese adults with T2DM, the incessant increase in OGTT shape indicated impaired insulin secretion. Lower fasting ghrelin and absence of ghrelin drops after glucose load may be associated with the incessant increase OGTT shape. In addition, compensatory elevated GLP-1 dose not prevent peak delay in the OGTT curve. Gut hormones may have an effect on OGTT shapes in T2DM adults.

769-P: Effect on Insulin Secretion Six Months after the Use of CFTR Modulators in Cystic Fibrosis Patients with or without Glucose Metabolism Abnormalities

Objective: To investigate the effect of 6m CFTR modulators treatment on insulin secretion in CF patients.Methods: 21 CF patients (17 Phe.508del hom) were included in a prospective, observational study. After 6m of lumacaftor/tezacaftor+ivacaftor, AUC of glucose, insulin and C peptide were evaluated by using 5-point OGTT. GLM repeated measures test performed.Results: 21 patients initially participated, 3 were excluded: 1 had no basal OTTG, and 2 had drug intolerance. Median age 14,7yr (ICR 8,5-26,0); 57% ≥13 yr and 57% male. Initially: 8 had normal glucose metabolism (N), 1 indeterminate (IND), 2 abnormal glucose tolerance (AGT), 2 IND+AGT, and 5 CFRD. After 6m: in the N group: 5 (62,5%; 100% <18yr) worsened their glucose tolerance status and 3 (37,5%) had no group change; in the abnormal glucose group: 2 (20%) worsened their glucose tolerance status (100% <18 yr), 3 (30%) improved (66,6% adults) and 5 (50%) remained similar (60% adults). Significant increase in AUC of glucose, insulin and C-peptide were observed after 6m in the whole group, without differences after adjustment for glucose tolerance status subgroup in AUC of insulin and C-peptide (Table 1).Conclusion: Increase in AUC of insulin and C-peptide were observed after 6m with CFTR modulators, suggesting a potential role in improving insulin secretion. AUC of glucose should be analyzed prospectively.View largeDownload slideView largeDownload slide DisclosureE. Lecumberri: None. R. Y. Yelmo: None. M. Garriga: None. A. F. Lamas: None. S. Vicente: Consultant; Self; Abbott, Fresenius Medical Care, Mead Johnson Nutrition. M. Martin-frias: None. L. Nattero-chávez: None. V. Martínez-vaello: None. L. Maiz: None. C. Sánchez rodríguez: None. M. Lorenzo: None. B. Dorado avendaño: None.

A Moderate Serving of a Lower-Quality, Incomplete Protein Does Not Stimulate Skeletal Muscle Protein Synthesis

Abstract Objectives Dietary proteins can be broadly characterized by their origin (animal-or plant-based) and amino acid composition (complete vs. incomplete). Meals containing &amp;gt; 20 g of high-quality, complete protein have repeatedly been shown to robustly stimulate skeletal muscle protein synthesis. However, breakfast in many Western countries is dominated by wheat-based products. Wheat and bread are considered a “lower-quality” incomplete source of protein, containing relatively low amounts of lysine and threonine. We hypothesized that a meal containing &amp;gt; 20 g of wheat-based protein would offer no anabolic advantage over a control meal containing only 5 g of plant-based protein. Methods In a subset of healthy, middle-aged women from our recently completed trial (n = 6/17, 53 ± 7 y, 27 ± 2 kg/m2), we measured post-prandial skeletal muscle protein synthesis, blood glucose, insulin and appetite for 3 h following the ingestion of: i) a wheat-based protein meal (INCOMPLETE: 717 kcal, 23 g protein, 120 g carbohydrate, 16 g fat) or ii) a low protein, plant-based, control meal (CONTROL: 542 kcal, 5 g protein, 86 g carbohydrate and 23 g fat). Venous blood samples and vastus lateralis muscle biopsy samples were obtained during a primed (2.0 mmol/kg) constant infusion (0.08 mmol/(kg/min)) of L-[ring-13C6]phenylalanine. All analyses were performed using established, standard techniques. Results Preliminary results indicate post-prandial skeletal muscle protein synthesis was similar in both cohorts (INCOMPLETE: 0.050 ± 0.012%/h vs. CONTROL: 0.054 ± 0.025%/h; p = 0.83) and consistent with fasting values historically measured by our lab. Blood glucose area under the curve (AUC; p = 0.82), insulin AUC (p = 0.85) and hunger AUC were similar in both cohorts. Conclusions A moderate serving of incomplete protein failed to robustly stimulate skeletal muscle protein synthesis. Consumption of a higher-quality, completeprotein meal is likely required to acutely increase muscle protein anabolism. Funding Sources National Cattlemen's Beef Association

251-OR: Impact of Vegetarian and the Nordic Diet on Glucose Metabolism: A Human Intervention Study

Background: Recent epidemiological studies indicate that the so-called ‘Nordic’ diet (rich in berries, fish and nuts) as well as a vegetarian diet improve serum glucose kinetics and, thus, reduce the risk of diabetes development compared to the ‘Western’ diet. Evidence for these effects from controlled human intervention studies is limited. Methods: One hundred and twenty overweight adults with at least 1 metabolic syndrome trait (60±7 y, BMI 31.1±3.5 kg/m2, WC men 109±9 cm, women 104±9 cm) were randomized into 3 groups, adhering to Nordic diet [ND], lacto-ovo vegetarian diet [VD], or habitual control diet [HD] for 6 weeks, based on a recipe list, which was adapted to individual energy expenditure (RMR measured by QuarkRMR device, multiplied by a factor of 1.5 for physical activity). At baseline and after 6 weeks, OGTT and mixed meal tolerance test [MMTT] (180 min; postprandial measurements at 7 time points [tp]) were performed. Statistical data analysis was conducted using linear mixed-effect models (group-specific comparison: visit*diet*tp interaction). Results: As expected no changes in body weight (p=0.083) and body composition (p=0.354) were detected. Within groups, fasting glucose (p=0.760) and insulin levels (p=0.066), HbA1c (p=0.979) and HOMA index (p=0.150) did not change after 6 weeks compared to baseline. Insulin sensitivity (Matsuda index p=0.498, OGIS p=0.478, insulinogenic index p=0.203) and ß-cell function (disposition index p=0.997) showed no intergroup variations. In the group comparison, no effect was found after OGTT and MMTT on AUC of glucose (p=0.869/p=0.824) and insulin (p=0.850/p=0.999). However, compared to controls, VD improved kidney values and ND improved blood lipids, liver and kidney values. Conclusion: Our medium-term isoenergetic intervention study did not confirm earlier results. Improvements in glucose kinetics as observed in epidemiologic studies are possibly due to a loss of body weight (hypoenergetic nutrition) independent of diet composition. Disclosure H. Huber: None. B. Stoffel-wagner: None. M. Coenen: None. L. Weinhold: None. M. Schmid: None. P. Stehle: None. M. Simon: None. Funding German Federal Ministry of Education and Research (01EA1809A)

Association Between Maternal Mood State and Glycemic Response to a Mixed-Meal Among Latina Pregnant Women With Overweight and Obesity

ObjectivesTo investigate if maternal positive and negative affect state is associated with the glucose and insulin response to a standardized breakfast shake among Latina pregnant women with overweight and obesity. MethodsN = 31 non-diabetic Latina pregnant women, at gestational age 28–30 weeks, with a pre-pregnancy BMI 25–35 Kg/m2 consumed a standardized breakfast shake in the morning after an overnight fast of at least 10 hours. The Positive and Negative Affect Scale was completed while consuming the drink. Blood samples collected at fasting and 6 postprandial time points (15, 30, 45, 60, 90,120 mins) were assayed for glucose and insulin and values were log-transformed for normality. The area-under-the-curve (AUC) for glucose, insulin, glucose: insulin ratio were computed as well as the Matsuda index of insulin sensitivity (SI). ResultsThe median (IQR) values for positive and negative affect scores were 33 (27–40) and 11 (10–14) respectively. Categorizing the affect scores as high or low based on the median value, the mean AUC for glucose, insulin, and SI did not differ according to affect state (p > 0.05). However, women with a lower positive affect score had lower insulin AUC (F-1.2, p = 0.063), and consequently, a greater AUCglucose: insulin (F = 3.9, p = 0.007), which persisted after adjustment for maternal age, gestational age and BMI. A post-hoc analysis revealed significantly higher glucose: insulin ratio values at fasting (F = 0.58, p = 0.013) and 15min (F = 10.37, p = 0/008) and 60min (F = 2.65, p = 0.021) postprandial timepoints in those with low vs high positive affect. No differences in the glucose/insulin ratio were detected across levels of negative affect. ConclusionsContrary to expectations, higher positive affect in late pregnancy (i.e., more positive mood state) was associated with a less favorable postprandial insulin response in this cohort, contributing to a higher ratio of glucose: insulin, which is a sensitive predictor of insulin resistance. There is potential for unmeasured confounding which may have contributed to this unexpected direction of association between maternal affect state and insulin response in pregnant Latina women, which deserves further attention in future research. Funding SourcesNational Institute of Child Health and Human Development.

Prior undernutrition and insulin production several years later in Tanzanian adults

ABSTRACTBackgroundThe prevalence, pathology, and existence of malnutrition-associated diabetes remain uncertain, especially with respect to adult-acquired undernutrition.ObjectiveThe aim was to investigate the association of prior undernutrition (low BMI, in kg/m2), acquired in adulthood and insulin during an oral glucose tolerance test (OGTT).MethodsWe followed up 630 adults recruited 7–14 y previously for other studies. Plasma insulin was measured fasting and at 30 and 120 min during an OGTT. The main exposure was BMI measured 7–14 y prior. The main outcome of interest was plasma insulin, controlling for time during the OGTT using generalized estimating equations, and exploratory outcomes were early insulin response (relative change in insulin and glucose from 0–30 min) and relative insulin and glucose AUCs from 0 to 120 min. Current confounding factors were age, sex, BMI, HIV, socioeconomic status, and physical activity.ResultsIn unadjusted analyses, increasing severity of prior malnutrition was associated with lower insulin concentration. In multivariate adjusted analyses, only current BMI was a strong predictor of overall insulin concentration. Associations with prior BMI of insulin responses accounting for glucose were also seen in unadjusted but not adjusted analyses. For insulin concentration but not the outcomes accounting for glucose, there was a sex interaction with prior BMI such that only men had lower insulin if previously malnourished: insulin (pmol/L) at 120 min was 311 (95% CI: 272, 351) for prior BMI ≥18.5, 271 (95% CI: 221, 321) for prior BMI 17.0–18.5, and 237 (95% CI: 194, 297) for prior BMI <17.0; P = 0.03. HIV status showed limited and variable associations with insulin.ConclusionsInsulin concentration, fasting and during an OGTT, was normalized in women more than in men several years after adult malnutrition. Chronic malnutrition, as indicated by low prior and current BMI, may contribute to diabetes through low insulin secretion.

167-OR: Long-Term Follow-up after Total Pancreatectomy and Islet Cell Autotransplantation in Patients with Chronic Pancreatitis Utilizing Off-Site Islet Isolation

Context: Total pancreatectomy (TP) with islet-cell auto transplantation (IAT) is an option for pain management for patients with chronic pancreatitis (CP). IAT allows the preservation of beta cell function to reduce or prevent long-term diabetes. Objective: We performed a follow-up study up to 12 years after TPIAT surgery with an off-site isolation laboratory, to determine the efficacy and durability of the procedure. Methods: Data (August 2008 to August 2020) were obtained from a TPIAT database which included information from medical records, clinic visits, questionnaires, and follow-up telephone calls. Patient demographics were collected. Additionally, each patient was assessed with a 4-hour mixed meal tolerance test for metabolic measurements, serial glycosylated hemoglobin (HbA1c), and insulin requirements prior to surgery and during their most recent follow-up appointment. Results: Seventy-seven patients with a median age of 45.0 years underwent TP-IAT for CP due to different etiologies. At a median follow-up time of 422.5 days 12 patients were insulin independent and 65 patients were on at least one insulin injection a day. Post-operative C-peptide area under the curve (AUC) measurements (P=0.008) were a better indicator of procedure success compared to the number of islet cells transplanted (P=0.225). Patients who were insulin-dependent post-surgery demonstrated increased insulin resistance prior to surgery, by their median pre-surgery insulin AUC; insulin-independent, 626 (241, 3803); insulin-dependent, 1591 (325, 4803), HOMA-IR values 9.02. Conclusions: TPIAT improves intractable pain for patients with CP. IAT decrease insulin requirement and improve blood glucose control after TP. Insulin resistance prior to surgery may be a predictor for insulin-dependence. Intervention studies using insulin sensitizer prior surgery may be considered in evaluating long-term outcomes for these patients. Disclosure S. U. Lad: None. K. F. Ali: None. P. C. Johnston: None. V. San martin: None. Y. Lin: None. R. Bottino: None. M. Walsh: None. T. Stevens: Speaker’s Bureau; Self; AbbVie Inc. B. Hatipoglu: None.

Postprandial Glycemic, Insulinemic, and Short-Chain Fatty Acids Responses Following the Consumption of Okara and Biovalorized Okara Incorporated Biscuits

Abstract Objectives Okara is a fiber-rich food processing by-product. However, it is underutilized as food due to its rapid putrefaction and poor sensorial properties. Valorization via fermentation (biovalorization) can alleviate its undesirable qualities while augmenting its soluble fiber content. The increase in soluble fiber may improve postprandial glycemic and insulinemic responses, potentially via generation of short-chain fatty acids (SCFAs) from colonic bacteria fermentation. This study aimed to assess the effect of consuming okara and biovalorized okara-containing biscuits on postprandial glucose, insulin and SCFAs responses in older Singaporeans. Methods Fifteen healthy middle-aged and older Singaporeans participated in a randomized controlled crossover trial. Subjects underwent a 4-hour mixed meal tolerance test with 100 g ingestion of 3 types of biscuits – control (C, no okara), biovalorised okara (RO) and autoclaved okara (AOK). RO and AOK biscuits were produced by 20% substitution of wheat flour with okara powder that was fermented with Rhizopus oligosporus (7% w/w) or autoclaved. The 4-hour incremental area under the curve (iAUC) of glucose, insulin and SCFAs (acetate, propionate and butyrate) were assessed. β-cell function was evaluated based on glucose stimulated insulin secretion, using a ratio of 4-hour AUC of insulin to glucose. Estimated insulin sensitivity (ISI) and metabolic clearance rate (MCR) were assessed with Stumvoll Index. Results Although no difference in glucose response was noted, RO showed significantly lower insulin iAUC (RO: 8931 ± 1058 mU/L × min, mean ± SE; C: 10271 ± 866 mU/L × min, p = 0.021) and improved β-cell function (p = 0.028) compared to C. AOK yielded significantly greater ISI and MCR compared to C (pISI = 0.016, pMCR = 0.009) while RO showed no difference against AOK or C. Significantly higher acetate and total SCFAs iAUC were evident for both RO and AOK relative to C (C vs RO: pacetate = 0.012, ptotal SCFA = 0.001; C vs AOK: pacetate = 0.015, ptotal SCFA = 0.001). AOK also had significantly greater propionate and butyrate iAUC compared to C (C vs AOK: pacetate = 0.002, pbutyrate = 0.001). Conclusions Consumption of okara and biovalorized okara-containing biscuits offers the benefit of attenuating postprandial insulinemic response possibly via SCFAs modulation. Funding Sources Singapore Ministry of Education

Utilizing a Low-Carbohydrate/High-Protein Diet to Improve Metabolic Health in Individuals With Spinal Cord Injury

Abstract Objectives The purpose of this study is to determine if an 8-week low-carbohydrate/high-protein (LC/HP) dietary intervention will show improvements in clinically important metrics of metabolic function and body composition in individuals with spinal cord injury (SCI). Methods Twenty-one participants with long-standing SCI (≥3 years post-injury) (age: 45 ± 13 years) were randomly assigned to an 8-week iso-caloric high-protein/low-carbohydrate (HPLC) diet or their habitual control diets. Injury levels ranged between cervical vertebrate 4 to lumbar vertebrate 3. The HPLC diet included ∼30% total energy as protein (40% energy from carbohydrate) and participants were provided with all study meals if they were assigned to the HPLC group. Each participant underwent an oral glucose tolerance test (OGTT) and DXA scanning before and after the intervention after an overnight fast. Blood glucose and insulin during the OGTT were assessed, and their respective incremental areas under the curve were calculated, as well as Matsuda index, an indicator of insulin sensitivity. The blood lipid panel was analyzed using the fasting samples. A two-way repeated-measures ANOVA model was used to evaluate the main effect of diet, time, and their interaction. Results We observed no main effect of time, diet, and their interaction on the fasting concentrations of glucose, insulin, their respective concentrations at 120-minute during the OGTT, and areas under the curve, but a trend for decreased insulin AUC among participants in the HPLC group (P = 0.07). There is a trend for the diet by time interaction effect for the Matsuda index (P = 0.11). The Matsuda index quantitatively increased in the HPLC group while remained in the control group. In contrast, an interaction effect was observed for several outcomes. These outcomes were decreased in the HPLC group, and include total Cholesterol (−23.9mg/dL), LDL (−15.8 mg/dL), total body fat mass (−5%), and visceral fat mass (−11%) (P &amp;lt; 0.05 for all). Fat-free mass did not change over time. Conclusions Our results support that our HPLC diet can be safely adopted by individuals with SCI to achieve improvements in glucose metabolism and lipid profile and body composition. Funding Sources The study was funded by the National Institute on Disability, Independent Living, and Rehabilitation Research (#90SI5019).

Pancreatic hormones response-generated machine learning model to help distinguish sporadic pancreatic cancer from new-onset diabetes cohort.

e16235 Background: Diabetes mellitus (DM), a paraneoplastic phenomenon, can develop earlier than other symptoms in pancreatic cancer (PaC) patients. Enhanced surveillance is encouraged on all elderly patients with new-onset DM. However, it is a challenge to differentiate newly developed PaCDM from type 2 DM (T2DM). Thus, we investigated the differences of pancreatic hormones responses and functions between PaCDM and T2DM patients, and developed discriminative model by machine learning algorithms. Methods: PaC patients with normal blood glucose (PaCNG) or with new-onset DM (PaCDM) were recruited. For each case, age and gender matched newly developed T2DM patients and healthy volunteers were selected as controls. After ≥10 hours fasting, all participants underwent a mixed meal stimulation test (MMTT). Blood samples were collected at 0, 15, 30, 60 and 120 min to measure insulin, C-peptide, glucagon, and pancreatic polypeptide (PP). Indices of insulin sensitivity (HOMA-IS, HOMA-IR) and insulin secretion (HOMA-β, insulinogenic index 30’ and 120’) were calculated. Increases in hormone levels were compared among groups with repeated measure analysis. Four machine learning algorithms (Random Forest, Logistic Regression, Support Vector Machines, Naïve bayes) were used to develop quadri-separated discriminative models of PaCDM based on baseline characteristics, pancreatic hormones and insulin indices listed above. Results: Insulin and C-peptide responses to MMTT were blunted in PaCDM patients compared to T2DM. The AUC of insulin were comparatively lower in PaCDM; between-group differences were observed at the fasting (197.15 ± 16.59 pg/mL to 537.96 ± 118.69 pg/mL; P = 0.040) and 15 min (523.94 ± 81.15 pg/mL to 1182.51 ± 219.35 pg/mL; P = 0.036) time-points. No statistical differences among groups were found for glucagon. The mean peak PP concentration after MMTT in PaCDM group (466.67 ± 79.05 pg/mL) was higher than control group (258.54 ± 31.36 pg/mL, P = 0.034), but not statistically different to T2DM patients (452.34 ± 62.96 pg/mL, P = 0.892). PaCDM patients had lower insulin secretion capacity but better insulin sensitivity compared to T2DM patients. Eight indices (age, HbA1c, CA19-9, peak concentration of glucose, area above basal of PP, HOMA-IR, HOMA-IS, HOMA-β) were recruited for model development. And the discriminative model generated by random forest algorithm obtained best performance (AUC = 1.000, CA = 0.963, F-1 = 0.941, Precision = 0.889, Recall = 1.000, Specificity = 0.947; model verified). Conclusions: PaCDM patients tend to present with lower β-cell function and better insulin resistance compared to T2DM patients. As our model based on machine learning algorithm generates a good result for discrimination, the above findings may help with early screening for sporadic PaC in new-onset DM. Clinical trial information: ChiCTR1800018247.

Early Impairment of Insulin Sensitivity, β-Cell Responsiveness, and Insulin Clearance in Youth with Stage 1 Type 1 Diabetes.

Clinical onset of type 1 diabetes (Stage 3 T1D) is preceded by a presymptomatic phase characterized by multiple islet autoantibodies with normal glucose tolerance (Stage 1 T1D). The aim was to explore the metabolic phenotypes of β-cell function and insulin sensitivity and clearance in normoglycemic youth with Stage 1 T1D and compare them with healthy nonrelated peers during a 3-hour oral glucose tolerance test (OGTT). Twenty-eight lean youth, 14 with ≥2 islet autoantibodies (cases) and 14 healthy controls underwent a 3-hour 9-point OGTT with measurement of glucose, C-peptide, and insulin. The oral minimal model was used to quantitate β-cell responsiveness (φtotal) and insulin sensitivity (SI), allowing assessment of β-cell function by the disposition index (DI=φtotal×SI). Fasting insulin clearance (CL0) was calculated as the ratio between the fasting insulin secretion rate (ISR) and plasma insulin levels (ISR0/I0), while postload clearance (CL180) was estimated by the ratio of AUC of ISR over the plasma insulin AUC for the 3-hour OGTT (ISRAUC/IAUC). Participants with impaired fasting glucose, impaired glucose tolerance, or any OGTT glucose concentration ≥200 mg/dL were excluded. Cases (10.5 years [8, 15]) exhibited reduced DI (P < .001) due to a simultaneous reduction in both φtotal (P < 0.001) and SI (P = .008) compared with controls (11.5 years [10.4, 14.9]). CL0 and CL180 were lower in cases than in controls (P = .005 and P = .019). Presymptomatic Stage 1 T1D in youth is associated with reduced insulin sensitivity and lower β-cell responsiveness, and the presence of blunted insulin clearance.

The stimulatory effects of glucagon on cortisol and GH secretion occur independently from FGF-21

Glucagon stimulation test (GST) is used to assess the hypothalamo-pituitary-adrenal (HPA) and growth hormone (GH) axes with an incompletely defined mechanism. We aimed to assess if glucagon acted through fibroblast growth factor-21 (FGF-21) to stimulate cortisol and GH secretion. The secondary outcome was to determine the relationship of FGF-21 with variable GH responses to GST in obesity. A total of 26 healthy participants; 11 obese (body mass index (BMI) > 30 kg/m2) and 15 leans (BMI < 25 kg/m2) were included. Basal pituitary and target hormone levels were measured and GST was performed. During GST, glucose, insulin, cortisol, GH, and FGF-21 responses were measured. The mean age of the participants was 26.3±3.6 years. Glucagon resulted in significant increases in FGF-21, glucose, insulin, cortisol, and GH levels. The levels of basal cortisol, GH, FGF-21, and IGF-1 were similar in the two groups. The peak GH and area under the curve (AUC)(GH) responses to GST in the obese group were lower than those of the normal-weight group with a different pattern of response. There were no differences between the groups in terms of peak cortisol, AUC(cortisol), peak insulin, AUC(insulin), peak FGF-21, and AUC(FGF21). Obesity was associated with significantly increased glucose and insulin responses and slightly decreased FGF-21 response to glucagon. Obesity was associated with blunted and delayed GH, but preserved cortisol responses to GST. This is the first study showing that glucagon stimulates the HPA and GH axis independently from FGF-21. The delayed GH response to GST in obesity does not seem to be related to FGF-21.

012 Overnight light exposure acutely increases heart rate during sleep and decreases insulin sensitivity the following day

Abstract Introduction Prior reports indicate that exposure to light at night negatively impacts sleep quality, autonomic and metabolic function, but the interaction between these physiologically interconnected systems is not fully elucidated. We examined the acute effects of nighttime light exposure on sleep macro and microarchitecture, heart rate (HR) and response to oral glucose tolerance test (OGTT), and the relationship between these measures. Methods Twenty healthy adults (18 - 40 years) were randomized into Light or Dark groups and run in parallel for a three-day and two-night laboratory stay. The Light group (n=10) slept in the dark (&amp;lt; 3 lux) on Night 1 and slept with overhead room lights on (100 lux) on Night 2, while the Dark group (n=10) slept in the dark (&amp;lt; 3 lux) on both Nights 1 and 2. Overnight polysomnography (PSG) was used to assess sleep macro and microstructure (slow wave activity: SWA: 0.5–4 Hz, and slow oscillatory (SO) activity: 0.5–1 Hz), and beat-to-beat measurement of HR. A two-hour OGTT was completed each morning. The between groups change in PSG-derived measures and metabolic parameters from Night/Day 2 to Night/Day 1, was calculated. Results While a greater percentage of time was spent in stage 2 (p= 0.003) and a smaller percentage of time was spent in stage 3 (p= 0.04), there were no between group differences in SWA and SO activity. Time series analysis of HR changes across the night from Night 1 to Night 2 showed higher HR in the Light vs the Dark group (p&amp;lt; 0.001). The change from Day 1 to Day 2 of the initial insulin response (60-min. area under the curve, AUC) showed a higher insulin response in the Light vs the Dark group (p= 0.029). The change in HR was positively correlated with the change in the 60-min. AUC of insulin (R= 0.46, p= 0.049). Conclusion A single overnight light exposure acutely increases heart rate during sleep and decreases insulin sensitivity the following day and these responses appear to be associated, suggesting that elevated autonomic activity in response to light at night impacts next day metabolic responses. Support (if any) Center for Circadian and Sleep Medicine, UL1TR001422