Glucose Response Curve Research Articles

Postprandial Blood Glucose and Insulin Response in Healthy Adults When Lentils Replace High-Glycemic Index Food Ingredients in Muffins, Chilies and Soups.

This study aimed to assess postprandial blood glucose response (PBGR), relative glycemic response (RGR) and insulin response when 25 g available carbohydrates (AC) is replaced with cooked lentils in the formulation of muffins, chilies and soups. In randomized, crossover studies, healthy adults consumed foods containing 25 g AC from green lentils, red lentils or a control (wheat muffin, n = 24; rice chili, n = 24; potato soup, n = 20). Blood collected at fasting and at 15, 30, 45, 60, 90 and 120 min was analyzed to derive the incremental area under the response curve (iAUC) for glucose, insulin, RGR and maximum concentration (CMAX). Treatment effects were assessed with repeated measures ANOVA. A replacement of 25 g AC with green lentils significantly decreased glucose iAUC compared to chili and soup (p < 0.0001), but not muffin (p = 0.07) controls, while also eliciting a significantly lower insulin iAUC for all three foods (muffin p = 0.03; chili p = 0.0002; soup p < 0.0001). Red lentil foods significantly decreased glucose iAUC (muffin p = 0.02; chili p < 0.0001; soup p < 0.0001) compared to controls, with a significantly lower insulin iAUC for chili and soup (p < 0.0001) but not muffins (p = 0.09). The RGR for muffins, chilies and soups was 88, 58 and 61%, respectively, for green lentils, and 84, 48 and 49%, respectively, for red lentils. PBGR, insulin and RGR are decreased when lentils are incorporated into food products, providing credible evidence to promote carbohydrate replacement with lentil-based foods.

Associations of adipose insulin resistance index with pancreatic β cell function (inverse) and glucose excursion (positive) in young Japanese women

The relationship of adipose tissue insulin resistance (AT-IR, a product of fasting insulin and free fatty acids) and homeostasis-model assessment-insulin resistance (HOMA-IR) to β-cell function was studied cross-sectionally in the setting of subtle glucose dysregulation. Associations of AT-IR and HOMA-IR with fasting and post-glucose glycemia and β-cell function inferred from serum insulin kinetics during a 75 g oral glucose tolerance test were studied in 168 young female Japanese students. β-cell function was evaluated by disposition index calculated as a product of the insulinogenic index (IGI) and Matsuda index. AT-IR, not HOMA-IR, showed positive associations with post-glucose glycemia and area under the glucose response curve although both indices were associated with fasting glycemia. HOMA-IR, not AT-IR, was associated positively with log IGI whereas both indices were inversely associated with Matsuda index. AT-IR, not HOMA-IR, showed inverse associations with log disposition index. Associations of adipose tissue insulin resistance with β-cell function (inverse) and glucose excursion in young Japanese women may suggest that lipotoxicity to pancreatic β-cells for decades may be associated with β cell dysfunction found in Japanese patients with type 2 diabetes. Positive association of HOMA-IR with insulinogenic index may be associated with compensatory increased insulin secretion.

STUDY OF GLYCEMIC INDEX OF DIABETES-SPECIFIC MODIFIED FORMULA AMONG HEALTHY ADULTS

Background: People with type 2 diabetes incorporate diabetes-specific nutritional formulas (DSNFs) in their nutrition therapy to enhance glycemic control and manage body weight. Among these formulas, the GEN-DM modified formula (GEN-DM MF) has been widely used for several years. However, the glycemic index (GI) of GEN-DM MF has not yet been determined. Objective: This study aimed to assess the GI of GEN-DM MF. Methods: Ten healthy adults with normal oral glucose tolerance were included. The plasma glucose was measured at 0 (baseline), 30, 60, 90 and 120 minutes after consuming 50 grams of glucose solution. On the subsequent two days, plasma glucose measurement was repeated using 84.46 g of GEN-DM MF containing 50 g of carbohydrates. The GI was calculated by dividing the incremental area under the glucose response curve (iAUC) of GEN-DM MF by the area under the glucose response curve of the glucose solution, then multiplying the result by 100. The glycemic load (GL) was calculated by multiplying the GI by the carbohydrate amount in one serving of GEN-DM MF (40 g) /100. Results: Six healthy men and four women with an average age of 35.80 ± 6.89 years, ranging from 28 to 44, were included in the study. The plasma glucose levels at 30 and 60 minutes following the GEN-DM MF were significantly lower than the corresponding glucose levels with p= 0.002 and 0.013, respectively. The GI and GL of GEN-DM MF were 37.75 and 9, respectively, which was classified as low GI and low GL. Conclusion: GEN-DM MF is classified as a low GI and low GL food, which could significantly lower plasma glucose levels among healthy individuals.

Characteristics and Risk of Diabetes in People With Rare Glucose Response Curve During an Oral Glucose Tolerance Test.

Existing differences in persons with lower 30- or 60-minute plasma glucose (PG) levels during 75-g oral glucose tolerance test (OGTT) than fasting PG remain unclear. To clarify the characteristics of persons whose PG levels decrease after glucose administration during OGTT and their risk of incidence of diabetes in a Japanese general population. In this cohort study, a total of 3995 men and 3500 women (mean age 56.7 years) without diabetes were classified into 3 groups: (1) PG at both 30 and 60 minutes ≥ fasting PG; (2) PG at 30 minutes ≥ fasting PG and PG at 60 minutes < fasting PG; (3) PG at 30 minutes < fasting PG. The characteristics and the risk of diabetes onset were analyzed using ordered logistic regression and Cox proportional hazard regression, respectively. Among 7495 participants, the numbers of individuals in the group 1, 2, and 3 were 6552, 769, and 174, respectively. The glucose response curve of the group 3 was boat shaped. Group 3 had the youngest age, lowest percentage of men, and best health condition, followed by groups 2 and 1. Among 3897 participants analyzed prospectively, 434 developed diabetes during the mean follow-up period of 5.8 years. The hazard ratio for diabetes onset in the group 2 was 0.30 with reference to the group 1. No-one in group 3 developed diabetes. People with lower 30-minute PG than fasting PG tended to be women, young, healthy, and at low risk of diabetes onset.

Dose-Dependency of the Glycemic Response to Polyphenol-Rich Sugarcane Extract (PRSE)

Foods high in available carbohydrates, such as plain white sugar or sucrose, increase the postprandial blood glucose levels that may aggravate the risk of developing Type 2 Diabetes. One class of compounds that is gaining popularity due to its potential application in reducing the release of sugars for absorption into the body is polyphenols. The study aimed to investigate the effect of adding different doses of polyphenol-rich sugarcane extract (PRSE) to sucrose to lower the postprandial glycemia of the participants in a non-randomized study. The four test samples’ Glycemic Index (GI) values were calculated based on the standardized recommended methodology by comparing the area under the curve (AUC) of the test samples against the glucose standard. The glucose concentration curves were similar for the four test foods. The glucose response curves, and GI values were decreased in a dose-dependent manner. The results of this study indicate that PRSE-coated sugar can lower postprandial glycemia in normal individuals. Additionally, decreasing GI values with an increasing concentration of polyphenols suggests a dose-dependent effect between polyphenol levels and GI.

THU291 Successful Reversal Of Glucose Toxicity After DKA Precipitated By SGLT2 Inhibitor

Abstract Disclosure: H. Abdelrahman: None. B. DeMoranville: None. Case: A 40 year old man with history of NAFLD and type 2 diabetes mellitus with HbA1c 12.2% on metformin 750 mg daily, presented with diabetic ketoacidosis (DKA) with blood glucose 275 mg/dL and anion gap 24 (AG 10-12). He had been started on empagliflozin 25 mg daily four days prior as outpatient. He was treated with IV insulin and hydration per DKA protocol. Labs showed C-peptide 3.0 ng/mL (1.1-4.4 ng/mL), Anti-GAD Ab 0.01 nmol/L (&amp;lt;0.02 mol/L), negative anti-insulin cell Ab. He was discharged on glargine 10u qHS, lispro 2u AC plus corrective scale, and metformin 750 mg BID. On outpatient follow-up, pre-meal glucose remained under 130 mg/dL, not requiring corrective insulin. He was started on semaglutide 0.5mg weekly and insulin was discontinued. At 3 months, his HbA1c improved to 5.8%. Self-monitoring glucose levels were at goal. Discussion: This case illustrates glucotoxicity due to significant hyperglycemia causing beta-cell apoptosis and resulting in insulin deficiency. The initiation of SGLT2 inhibitors (SGLT2i) when insulin deficiency and peripheral resistance are at their peak increases risk of DKA. This patient with type 2 diabetes presented with blood glucose 275 mg/dL in DKA four days after starting empagliflozin, a SGLT2i. SGLT2i increase risk of DKA due to dehydration from glucosuria, inhibiting ketone body excretion by the kidneys, causing a state of carbohydrate deficit and hypovolemia that promotes glucagon release from alpha-cells, an increased glucagon-to-insulin ratio, and thus triggers ketogenesis.1 In glucose toxicity, intra-cellular hyperglycemia-induced molecular dysfunction results in beta-cell apoptosis. Islet cells cultured in a glucotoxic environment (20 mmol/l) had suppressed insulin content, but fully reversed the intra-cellular calcium response after one week of culturing in a euglycemic environment, demonstrating recovery of the molecular steps promoting insulin release. 2 Treatment with insulin close to euglycemic goals promotes the reversal of glucose toxicity. Our patient recovered beta-cell function several weeks after the glucotoxic episode and was able to discontinue insulin therapy. With the addition of semaglutide, a GLP-1 receptor agonist, which potentiates glucose-dependent insulin release to control post-prandial hyperglycemia, he was able to maintain euglycemia and an HbA1c 5.8%. Conclusion Patients with type 2 diabetes mellitus may present in diabetic ketoacidosis due to glucose toxicity which can be reversed with short-term insulin therapy. References 1) Nasa P, et al. Euglycemic diabetic ketoacidosis: A missed diagnosis. World J Diabetes. 2021 May 15;12(5):514-523. 2) Tariq M, et al. Prolonged culture of human pancreatic islets under glucotoxic conditions changes their acute beta cell calcium and insulin secretion glucose response curves from sigmoid to bell-shaped. Diabetologia. 2022 Dec 2. Epub ahead of print. PMID: 36459178. Presentation: Thursday, June 15, 2023

A Biphasic Glucose Response during an Oral Glucose Tolerance Test Is Associated with Greater Plasma Insulin and GLP-1 Responses and a Reduction in 1-Hour Glucose but Does Not Relate to the Rate of Gastric Emptying in Healthy, Older Adults.

The pattern of the plasma glucose response curve during an oral glucose tolerance test (OGTT) is of prognostic significance with "biphasic" when compared with "monophasic" patterns being associated with greater insulin sensitivity/secretion and a reduced risk of progression to diabetes. The relationships of the glucose response curves with gastric emptying and incretin hormone secretion are not known. Thirty-six adults (age > 65 years) without known diabetes consumed a 300 mL drink containing 75 g glucose and 150 mg C13-acetate at baseline and follow-up after 5.8 ± 0.1 years. Plasma glucose, glucagon-like peptide-1 (GLP-1), glucose independent insulinotropic polypeptide (GIP) and insulin were measured, and participants classified according to the pattern of their glucose response. Gastric emptying was measured on breath samples (stable isotope breath test). At baseline, 22 participants had a "monophasic" and 14 a "biphasic" glucose response. The 1 h plasma glucose response curve was greater and the GLP-1 AUC0-120 min and insulin secretion lower in the monophasic group. There were no differences in gastric emptying, GIP or insulin sensitivity. At the follow-up, the 1 h glucose response curve was greater again, while GLP-1 AUC0-120 min was lower in the monophasic group. A biphasic curve is associated with a higher 60 min glucose response curve and increases in GLP-1, but no difference in either GIP or gastric emptying.

Flat maternal glucose response curve and adverse pregnancy outcome.

The significance of a flat oral glucose tolerance test (OGTT) response curve in pregnancy remains unclear. We investigated the association of a flat curve with pregnancy outcomes. Retrospective cohort study. Flat OGTT curve was defined by an area under the curve below the 10th percentile. Pregnancy outcomes were compared between flat and normal curve. Of the 2673 eligible women, 269 had a flat response curve. Compared with the normal-response group, the flat-curve group had a lower mean birthweight (3363 ± 547 g vs. 3459 ± 519 g, p < 0.005), higher probability of small for gestational age (SGA) (19% vs. 12%, p < 0.005, aOR = 1.75, 95% CI 1.24-2.47), and 5-min Apgar score < 7 (1.12% vs. 0.29%, p < 0.05, aOR = 3.95, 95% CI 1.01-15.5). There were no differences in obstetric or maternal outcomes. Flat OGTT is associated with lower birthweight, higher rates of SGA, and low Apgar scores. Detecting this previously unrecognized risk group, could potentially reduce these complications.

Phenotypes Associated With Zones Defined by Area Under the Curve Glucose and C-peptide in a Population With Islet Autoantibodies.

Metabolic zones were developed to characterize heterogeneity of individuals with islet autoantibodies. Baseline 2-h oral glucose tolerance test data from 6,620 TrialNet Pathway to Prevention Study (TNPTP) autoantibody-positive participants (relatives of individuals with type 1 diabetes) were used to form 25 zones from five area under the curve glucose (AUCGLU) rows and five area under the curve C-peptide (AUCPEP) columns. Zone phenotypes were developed from demographic, metabolic, autoantibody, HLA, and risk data. As AUCGLU increased, changes of glucose and C-peptide response curves (from mean glucose and mean C-peptide values at 30, 60, 90, and 120 min) were similar within the five AUCPEP columns. Among the zones, 5-year risk for type 1 diabetes was highly correlated with islet antigen 2 antibody prevalence (r = 0.96, P < 0.001). Disease risk decreased markedly in the highest AUCGLU row as AUCPEP increased (0.88-0.41; P < 0.001 from lowest AUCPEP column to highest AUCPEP column). AUCGLU correlated appreciably less with Index60 (an indicator of insulin secretion) in the highest AUCPEP column (r = 0.33) than in other columns (r ≥ 0.78). AUCGLU was positively related to "fasting glucose × fasting insulin" and to "fasting glucose × fasting C-peptide" (indicators of insulin resistance) before and after adjustments for Index60 (P < 0.001). Phenotypes of 25 zones formed from AUCGLU and AUCPEP were used to gain insights into type 1 diabetes heterogeneity. Zones were used to examine GCRC changes with increasing AUCGLU, associations between risk and autoantibody prevalence, the dependence of glucose as a predictor of risk according to C-peptide, and glucose heterogeneity from contributions of insulin secretion and insulin resistance.

Arepas Made from High Amylose Corn Flour Produce Favorably Low Glucose and Insulin Responses in Healthy Humans

The importance of the amylose: amylopectin ratio in the postprandial glycemic and insulinemic responses to corn was studied in food products that might realistically be consumed. Healthy subjects were given test meals in the form of arepas made from ordinary (25% amylose) or high amylose (70% amylose) corn flour. The ordinary corn meal contained 45 g of potentially available starch. To exclude the possible influence of a lowered content of potentially available starch due to formation of resistant starch in the high amylose product, this product was evaluated at two levels and included either on the basis of potentially available starch (45 g) or total starch (including resistant starch) (45 g, i.e., 29 g potentially available starch), respectively. The rate of starch hydrolysis, measured in vitro employing a method based on chewing, was studied. In addition, the content of in vitro resistant starch was analyzed in all products. The meals containing high amylose corn flour produced lower areas under the glucose and insulin response curves (57 and 42% lower, respectively) than did the meals containing ordinary cornmeal. This could not be explained by a lower amount of potentially available starch. No differences were noted when subjects consumed the two high amylose meals of arepas, despite 36% lower potentially available starch in one of the meals. The rate of starch hydrolysis measured in vitro was slower in the high amylose corn products than in the ordinary corn product. Resistant starch in the ordinary product was 3 g/100 g dry matter, vs. -20 g/100 g dry matter in the high amylose products. We concluded that high amylose corn products have a potential to promote favorably low metabolic responses and high resistant starch contents.

Prolonged culture of human pancreatic islets under glucotoxic conditions changes their acute beta cell calcium and insulin secretion glucose response curves from sigmoid to bell-shaped.

The rapid remission of type 2 diabetes by a diet very low in energy correlates with a marked improvement in glucose-stimulated insulin secretion (GSIS), emphasising the role of beta cell dysfunction in the early stages of the disease. In search of novel mechanisms of beta cell dysfunction after long-term exposure to mild to severe glucotoxic conditions, we extensively characterised the alterations in insulin secretion and upstream coupling events in human islets cultured for 1-3 weeks at ~5, 8, 10 or 20 mmol/l glucose and subsequently stimulated by an acute stepwise increase in glucose concentration. Human islets from 49 non-diabetic donors (ND-islets) and six type 2 diabetic donors (T2D-islets) were obtained from five isolation centres. After shipment, the islets were precultured for 3-7 days in RPMI medium containing ~5 mmol/l glucose and 10% (vol/vol) heat-inactivated FBS with selective islet picking at each medium renewal. Islets were then cultured for 1-3 weeks in RPMI containing ~5, 8, 10 or 20 mmol/l glucose before measurement of insulin secretion during culture, islet insulin and DNA content, beta cell apoptosis and cytosolic and mitochondrial glutathione redox state, and assessment of dynamic insulin secretion and upstream coupling events during acute stepwise stimulation with glucose [NAD(P)H autofluorescence, ATP/(ATP+ADP) ratio, electrical activity, cytosolic Ca2+ concentration ([Ca2+]c)]. Culture of ND-islets for 1-3 weeks at 8, 10 or 20 vs 5 mmol/l glucose did not significantly increase beta cell apoptosis or oxidative stress but decreased insulin content in a concentration-dependent manner and increased beta cell sensitivity to subsequent acute stimulation with glucose. Islet glucose responsiveness was higher after culture at 8 or 10 vs 5 mmol/l glucose and markedly reduced after culture at 20 vs 5 mmol/l glucose. In addition, the [Ca2+]c and insulin secretion responses to acute stepwise stimulation with glucose were no longer sigmoid but bell-shaped, with maximal stimulation at 5 or 10 mmol/l glucose and rapid sustained inhibition above that concentration. Such paradoxical inhibition was, however, no longer observed when islets were acutely depolarised by 30 mmol/l extracellular K+. The glucotoxic alterations of beta cell function were fully reversible after culture at 5 mmol/l glucose and were mimicked by pharmacological activation of glucokinase during culture at 5 mmol/l glucose. Similar results to those seen in ND-islets were obtained in T2D-islets, except that their rate of insulin secretion during culture at 8 and 20 mmol/l glucose was lower, their cytosolic glutathione oxidation increased after culture at 8 and 20 mmol/l glucose, and the alterations in GSIS and upstream coupling events were greater after culture at 8 mmol/l glucose. Prolonged culture of human islets under moderate to severe glucotoxic conditions markedly increased their glucose sensitivity and revealed a bell-shaped acute glucose response curve for changes in [Ca2+]c and insulin secretion, with maximal stimulation at 5 or 10 mmol/l glucose and rapid inhibition above that concentration. This novel glucotoxic alteration may contribute to beta cell dysfunction in type 2 diabetes independently from a detectable increase in beta cell apoptosis.

Comparing the Rise in Glucose Concentration in Blood, Aqueous and Interstitial Fluid During a Glucose Tolerance Test.

The purpose of the study was to determine if aqueous glucose levels rise in a comparable time frame to interstitial fluid and could therefore be suitable for a continuous glucose monitoring (CGM) site. An intravenous glucose tolerance test was performed on five New Zealand white rabbits. Aqueous humor from the posterior and anterior chamber of the eye and venous blood were sampled for glucose concentration measurement. Glucose concentrations in the interstitial fluids were monitored using a CGM system. A compartment model was created to map the glucose response curves in each compartment. The delay in rising glucose concentrations between blood and interstitial fluid and aqueous humor in the posterior chamber and anterior chamber of the eye were analyzed. The results showed a statistically similar time lag and rate of change in glucose concentrations between blood and interstitial fluids or aqueous humor in either the posterior or anterior chamber. The results of this study add further support to the aqueous humor being used as an alternative CGM site. The study provides the basis for developing an intraocular continuous glucose sensor that can overcome limitations of current CGM systems.

LBSUN161 Relationship Of Shape Of Glucose OGTT Curves With Measures Of Cardiometabolic Health In African American Adolescents

Abstract Background and Aims Studies in youth and adults have shown that the shape of oral glucose tolerance test (OGTT) response curve may be a biomarker for insulin secretion and insulin sensitivity (IS). Individuals with monophasic (MPh) glucose response curve have lower IS and decreased beta-cell function compared to those with biphasic (BPh) pattern. The aim of this study was to assess if the shape of the glucose response curve of OGTT is associated with 2-D ECHO based indices of heart structure and function. Methods In a cross-sectional study, African American (AA) adolescents with and without obesity between the ages of 13-18 years were recruited to assess the relationship of blood pressure, obesity, and measures of cardiac health. Metabolic and inflammatory markers, 2-D ECHO and OGTT data were collected. The shape of the OGTT glucose response was classified based on a change from nadir to glucose-120 min of ≥ 4.5 mg/dL, and its association with cardiac health indices was calculated. R v.4.1.2 was used for analysis. Results Of the 276 individuals with available OGTT data (mean age 16.18 ± 1.70 years, 47.5% females), 39 (14.1%) had BPh curve. The individuals with BPh were lower in age (15.61 ± 1.68 vs 16.28 ± 1.68, p=0. 02), but similar in sex, BMI, BMIz and metabolic parameters. There was no difference in impaired glucose tolerance (27% [BPh] vs 15% [MPh], p=. 08). At 120 min, glucose (6.96 ± 0. 07 vs 6.31 ± 0. 07 mmol/L, p=. 05), and insulin (362.86 ± 13.69 vs 276.48 ± 13.61 uIU/mL, p=. 04) levels were higher in BPh. The glucose area under the curve (AUC) was lower in individuals with BPh (13.2 ± 1.23 vs 14.7 ± 1.16 mmol/L/hr, p &amp;lt;. 001) while the insulinogenic index (1.5 ± 3.79 vs 1.17 ± 2.74, p =. 03) and oral glucose disposition index were higher in both univariate analyses and after adjusting for age, sex and BMIz. The aortic root size was associated with the shape of the curve adjusting for age, sex and BMIz (p=. 03), but not ventricular or atrial mass, systolic or diastolic function. Conclusions There was lower proportion of individuals with BPh in this cohort of AA adolescents compared to published studies. Individuals with BPh had healthier beta-cell function indices. No significant relationship of the shape of the OGTT curve was seen with the metrics of heart structure or function at this age. Replication of results in adult cohort(s) is ongoing. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

The Transition From a Compensatory Increase to a Decrease in C-peptide During the Progression to Type 1 Diabetes and Its Relation to Risk.

To define the relationship between glucose and C-peptide during the progression to type 1 diabetes (T1D). We longitudinally studied glucose and C-peptide response curves (GCRCs), area under curve (AUC) for glucose, and AUC C-peptide from oral glucose tolerance tests (OGTTs), and Index60 (which integrates OGTT glucose and C-peptide values) in Diabetes Prevention Trial-Type 1 (DPT-1) (n = 72) and TrialNet Pathway to Prevention Study (TNPTP) (n = 82) participants who had OGTTs at baseline and follow-up time points before diagnosis. Similar evolutions of GCRC configurations were evident between DPT-1 and TNPTP from baseline to 0.5 years prediagnosis. Whereas AUC glucose increased throughout from baseline to 0.5 years prediagnosis, AUC C-peptide increased from baseline until 1.5 years prediagnosis (DPT-1, P = 0.004; TNPTP, P = 0.012) and then decreased from 1.5 to 0.5 years prediagnosis (DPT-1, P = 0.017; TNPTP, P = 0.093). This change was mostly attributable to change in the late AUC C-peptide response (i.e., 60- to 120-min AUC C-peptide). Median Index60 values of DPT-1 (1.44) and TNPTP (1.05) progressors to T1D 1.5 years prediagnosis (time of transition from increasing to decreasing AUC C-peptide) were used as thresholds to identify individuals at high risk for T1D in the full cohort at baseline (5-year risk of 0.75-0.88 for those above thresholds). A transition from an increase to a decrease in AUC C-peptide ∼1.5 years prediagnosis was validated in two independent cohorts. The median Index60 value at that time point can be used as a pathophysiologic-based threshold for identifying individuals at high risk for T1D.

Dietary Fibre and Organic Acids in Kiwifruit Suppress Glycaemic Response Equally by Delaying Absorption-A Randomised Crossover Human Trial with Parallel Analysis of 13C-Acetate Uptake.

Non-sugar components of kiwifruit reduce the amplitude of the glycaemic response to co-consumed cereal starch. We determined the relative contribution of different non-sugar kiwifruit components to this anti-glycaemic effect. Healthy participants (n = 9) ingested equal carbohydrate meals containing 20 g starch as wheat biscuit (WB, 30 g), and the sugar equivalent of two kiwifruit (KFsug, 20.4 g), either intrinsic or added as glucose, fructose and sucrose (2:2:1). The meals were WB+KFsug (control, no non-sugar kiwifruit components), WB + whole kiwifruit pulp (WB+KF), WB + neutralised kiwifruit pulp (WB+KFneut), WB + low-fibre kiwifruit juice (WB+KFjuice) and WB+KFsug + kiwifruit organic acids (WB+KFsug+OA). All meals were spiked with 100 mg sodium [1-13C] acetate to measure intestinal absorption. Each participant ingested all meals in random order. Blood glucose and breath 13CO2 were measured at ingestion and at 15 min intervals up to 180 min. Compared with WB+KFsug, whole kiwifruit pulp (WB+KF) almost halved glycaemic response amplitude (p < 0.001), reduced incremental area under the blood glucose response curve (iAUC) at 30 min (peak) by 50% (p < 0.001), and averted late postprandial hypoglycaemia. All other treatments suppressed response amplitude half as much as whole kiwifruit and averted acute hypoglycaemia, with little effect on iAUC. Effects on 13CO2 exhalation paralleled effects on blood glucose (R2 = 0.97). Dietary fibre and organic acids contributed equally to the anti-glycaemic effect of kiwifruit by reducing intestinal absorption rate. Kiwifruit flesh effectively attenuates glycaemic response in carbohydrate exchange, as it contains fructose, dietary fibre and organic acids.

Impact of High Protein and Low Carbohydrate Smoothie Drinks Versus a Diabetes-Specific Nutritional Formula on Postprandial Glucose Homeostasis in Type-2 Diabetes Mellitus

Abstract Objectives We aimed to determine the effect of high protein and low carbohydrate smoothie drinks on glucose homeostasis, insulin and lipid metabolism in obese type 2 diabetic individuals as compared with a diabetes-specific nutritional formula. Methods We compared between a regular high protein smoothie drink (SM) containing 39% carbohydrate, 24% protein and 37% fat or a high protein and low sugar smoothie drink (LS) containing 28% carbohydrate, 28% protein and 44% fat with a conventional diabetic enteral drink (Glucerna) containing 38% carbohydrate, 18% protein and 33% fat. A crossover design study was performed in 41 diabetic participants. Participants consumed 300 kilocalories of each drink at a time with one-week wash out period between drinks and glucose response curves at baseline, 30, 60, 90, 120, 180 and 240 minutes were monitored and compared. Results In all three diets blood glucose levels gradually decreased postprandially. Average postprandial plasma glucose levels and the area under the curve (AUC) were higher after Glucerna and SM intake as compared with LS (p-value &amp;lt; 0.05) which demonstrated that LS be the better insulin sensitive formula among of the three formulas. The peak blood glucose level was highest at 60 minutes after Glucerna intake when compared with SM and LS, respectively (p-value &amp;lt; 0.0001). Conclusions These results suggested the potential of smoothie formulas containing high protein and low carbohydrate for the nutritional support of type 2 diabetes mellitus and its related improved glycemic control. These smoothies may be a good candidate as promising functional foods for the management and supplementation for diabetes and obese people in the future. Funding Sources National Research Council of Thailand (NRCT).

61-OR: Machine Learning Framework Predicts Metabolic Subphenotypes Using Glucose Dynamics during Oral Glucose Tolerance Test

Type 2 diabetes (T2D) is classically defined by measures of glycemia which do not take into account its physiologic basis, which differs between individuals. Defining the relative contribution of fundamental physiologic processes to glucose dysregulation would facilitate targeted treatment approaches for diabetes prevention and treatment. We propose that muscle insulin resistance, beta cell dysfunction, incretin defect, and hepatic insulin resistance are present to varying degrees in individuals predisposed to T2D, who can be thus classified according to their metabolic subphenotype. While this transformative approach to T2D is appealing, traditional metabolic tests are invasive and unavailable outside research units. We tested the ability of the shape of the glucose response curve during an oral glucose tolerance test (OGTT) to identify metabolic subphenotypes. 32 participants underwent gold-standard metabolic tests including frequently-sampled 3-hour OGTT, isoglycemic intravenous glucose infusion for quantification of incretin effect, steady-state plasma glucose measurement of insulin resistance, and calculated hepatic insulin resistance. We developed a machine learning framework to predict metabolic subphenotypes of an individual using dynamic features of the glucose time series during the OGTT. Metabolic testing revealed extensive inter-individual heterogeneity and the existence of four major metabolic subphenotypes. The features of the glucose time series identified insulin resistance, beta cell deficiency, and incretin deficiency with auROCs of 94%, 76%, and 75%, respectively. These were superior to standard clinical and laboratory measures of metabolic phenotypes. We suggest that identification of distinct metabolic subphenotypes using features of the glucose time series during OGTT may both enhance early identification of at-risk individuals as well as inform targeted therapeutic approaches to prevent and treat T2D. Disclosure A.A.Metwally: None. D.Perelman: None. H.Park: None. A.L.Gloyn: Other Relationship; Genentech, Inc., Roche Pharmaceuticals. T.Mclaughlin: Board Member; January, Inc., Research Support; Merck &amp; Co., Inc., Novo Nordisk, Stock/Shareholder; Eiger BioPharmaceuticals. M.Snyder: Stock/Shareholder; January, Inc. Funding National Institutes of Health (R01DK110186-01) National Institute of Diabetes and Digestive and Kidney Diseases (U01-DK105535; U01-DK085545, UM1DK126185)

Estrogen Receptor‐a in the Subfornical Organ Controls Glucose Homeostasis During Obesity in Males

Metabolic syndrome encompasses a spectrum of conditions that increases the risk for adverse cardiovascular and metabolic diseases, including hyperglycemia associated with type II diabetes. While the etiology of type II diabetes is multifactorial, sexual dimorphism is clearly established. Specifically, the sex hormone estrogen plays a metabolic protective role in premenopausal women. However, a growing body of literature also supports a critical role for estrogen in metabolic regulation in men. Notably, male mice with a global genetic deletion of estrogen‐receptor‐a (ERa) exhibit a pronounced dysregulation of glucose homeostasis. Importantly, estrogens have tissue specific physiological effects, both positive and negative. Thus, identification of specific sites of estrogen action is imperative to develop selective estrogen therapies that can ameliorate metabolic‐syndrome related hyperglycemia. Recently, the subfornical organ (SFO), a forebrain circumventricular region lacking a blood brain barrier, has been implicated in the regulation of energy balance. Moreover, dense ERa expression is present in the SFO of males. Taken together, we hypothesized that deletion of ERa in the SFO would impair glucose control in obese male mice. To investigate this, six‐week‐old male ERfl/fl mice underwent SFO targeted delivery of an adeno‐associated vector encoding Cre‐recombinase (AAV‐Cre‐eGFP) to selectively remove SFO ERa. AAV‐eGFP served as a control (n=3/group). Following recovery, mice were fed a high fat diet (HFD; 60% fat) during which glucose tolerance testing (2g/kg body weight, i.p.) was performed at 0, 2, 5 and 10 weeks, and the area under the glucose response curve (AUC) was calculated. As expected, glucose tolerance at baseline (week 0) was not different between groups. However, removal of SFO ERa significantly reduced glucose tolerance (AUC: 46,442 ± 5648 vs. 58,175 ± 2862, AAV‐eGFP vs. AAV‐Cre‐eGFP, p&lt;0.05) within 2 weeks of HFD feeding. This reduction in glucose tolerance persisted at week 5 (AUC: 52,360 ± 4,807 vs 65,460 ± 4749, AAV‐eGFP vs. AAV‐Cre‐eGFP, p&lt;0.05), and tended to be different between groups at week 10 (AUC: 61,370 ± 2736 vs 68,077 ± 2988, AAV‐eGFP vs. AAV‐Cre‐eGFP, p=0.1). In addition, removal of SFO ERa elevated fasting blood glucose at weeks 5 (165 ± 10 vs. 205 ± 8 mg/dL, AAV‐eGFP vs. AAV‐Cre‐eGFP, p&lt;0.05) and 10 (184 ± 14 vs. 247 ± 16 mg/dL, AAV‐eGFP vs. AAV‐Cre‐eGFP, p&lt;0.05) suggesting a role for SFO ERa in homeostatic control of fasting blood glucose in males. Importantly, the alterations in glucose regulation occurred independent of body weight (10 weeks: 44.6 ± 1.3 vs. 42 ± 1.8 g, AAV‐eGFP vs. AAV‐Cre‐eGFP, p&gt;0.05), food intake, energy expenditure, and ambulatory activity, as evaluated by indirect calorimetry recordings. Collectively, these findings indicate that removal of SFO ERa reduces glucose tolerance in obese male mice, indicating that the protective role of central estrogen signaling in glucose homeostasis is not limited to females. Furthermore, these findings suggest that manipulating estrogen signaling in the SFO, in the context of obesity, may be a novel approach to target type II diabetes.

Acute effect of flaxseed-enriched snack bars on glycemic responses and satiety in healthy individuals.

The dietary glycemic index (GI) and glycemic load (GL) have garnered scholarly attention for their roles in weight management and glycemic control. Flaxseed is a good source of fiber, lignans, and omega-3 fatty acids. This study evaluated healthy individuals' acute glycemic response and satiety following the consumption of flaxseed-enriched snack bars. Nineteen healthy men and women consumed flaxseed bars or a glucose solution containing 50 g of available carbohydrates. Capillary blood glucose concentrations were obtained through the finger-prick test. The GI and GL values of the flaxseed bars were calculated using incremental area under the glucose response curve. Over 2 h, subjective satiety was examined at 0 (fasting), 15, 30, 45, 60, 90 and 120min following the consumption of flaxseed bars or saltine crackers containing 300 kcal by using a visual analogue scale (VAS). Compared with that of the glucose solution, the glucose concentrations of the flaxseed bars (15-90 min) were significantly lower (p<0.001). The GI and GL values of the flaxseed bars were 30.0±23.0 and 2.3±0.2, respectively. Compared with saltine cracker consumption, flaxseed bars consumption resulted in lower hunger and higher satiety. The satiety index score of the flaxseed bars was 1.6 times higher than that of the saltine crackers. Although further studies are warranted to evaluate the long-term effects of flaxseed-enriched snacks on glycemia and energy balance, our findings suggest that the incorporation of flaxseed into snack bars is a viable strategy for the management of obesity and diabetes.

Glycemic Responses by Coconut (Cocos nucifera) Jaggery and Cane Sugar (Saccharum officinarum): A Comparative Study

Aim: Cane sugar (Saccharum officinarum) and (Cocos nucifera) jaggery are prominent sweeteners. The aim of the this study is to evaluate Glycemic Indices (GI) of cane sugar and coconut jaggery using healthy human subjects.&#x0D; Place and Duration of Study: The research was conducted as a collaborative project with Coconut Research Institute Sri Lanka and National Hospital Colombo Sri Lanka, between 2019 to 2020.&#x0D; Methodology: Starch fractions (Total starch - TS, Resistant starch – RS and Digestible starch – DS) and sugar profile of two test foods were analyzed. Thirty six (n=36) healthy volunteers were recruited and were subjected to health screening. Fifty grams of digestible carbohydrate containing test food portions were given for each subject who had been fasting for 8 - 12 hours. Intravenous blood samples were collected to analyze blood glucose concentration and GI of food.&#x0D; Results: Cane sugar contained high percentages of TS (95.86 ± 1.58%), DS (95.73 ± 1.59%) and RS was just 0.13± 0.02%. Coconut jaggery contained a lower percentage of sucrose (76.12±1.62%) and glucose (5.22±0.11%). Healthy volunteers (25.95±3.62 years) whom were having healthy fasting blood glucose concentrations (73.54±8.89 mg/dl) and HbA1c (5.05±0.35 %) were tested with glucose, and the two test foods.&#x0D; Conclusions: There was no significant difference (P&gt;0.05) between blood glucose response curves and GI of coconut jaggery (65.19±36.53) and cane sugar (60.76±35.80), where both can be considered as moderate GI sweeteners.