Glucose Response Curve Research Articles

The Pathological Evolution of Glucose Response Curves During the Progression to Type 1 Diabetes in the TrialNet Pathway to Prevention Study.

Glucose response curves (GRCs) during oral glucose tolerance tests (OGTTs) are predictive of type 1 diabetes. We performed a longitudinal analysis in pancreatic autoantibody-positive individuals to assess 1) characteristic GRC changes during progression to type 1 diabetes and 2) GRC changes in relation to β-cell function changes and to combined glucose and C-peptide response curve (GCRC) changes. Among antibody-positive individuals with serial OGTTs in the TrialNet Pathway to Prevention study, GRC changes from first to last OGTTs were compared between progressors (n = 298) to type 1 diabetes and nonprogressors (n = 2,216). GRC changes from last OGTT before diagnosis to diagnostic OGTTs were studied in progressors. GRCs changed more frequently from biphasic (two peaks) to monophasic (one peak) GRCs between first and last OGTTs in progressors than in nonprogressors (75.4% vs. 51.0%, respectively; P < 0.001). In contrast, GRCs of progressors changed less frequently from monophasic to biphasic than those of nonprogressors (12.6% vs. 30.6%; P < 0.001). Monotonic (continuous increase) GRCs were present in 47.7% of progressors at diagnosis. The early (30-0 min) C-peptide response decreased in progressors with GRCs changing from biphasic to monophasic between first and last OGTTs (P < 0.001) and from monophasic to monotonic between last and diagnostic OGTTs (P < 0.001). Conversely, the early C-peptide response increased among nonprogressors with GRCs changing from monophasic to biphasic (P < 0.001). Changes in GRCs were related to changes in GCRCs. Characteristic GRC changes, biphasic to monophasic to monotonic, occur during the progression to type 1 diabetes. These GRC changes correspond to decreasing β-cell function.

Potential Ameliorative Effects of Chromium Supplementation on Glucose Metabolism, Obesity, and Genomic Stability in Prediabetic Rat Model.

Chromium (III) (Cr(III)) effect on improving glucose, body mass loss, and genomic stability has been extensively studied in models of type 2 diabetes. However, there is a lack of studies evaluating its effect on prediabetes. Thus, this study evaluates the effects of Cr(III) as dietetic supplementation on glucose metabolism, obesity, and genomic stability on prediabetic rat model using high-invert sugar. Male Wistar rats were divided randomly into four treatment groups: (1) control, receiving standard diet (control); (2) prediabetic (PD), receiving a 32% of invert sugar; (3) Cr(III), receiving chromium (III) chloride (CrCl3•6H2O) (58.4mg/L); and (4) Cr(III) + PD, receiving CrCl3•6H2O in combination with high-invert sugar. Cr(III) supplementation significantly reduced blood glucose (123.00 ± 8.29mg/dL vs. 115.30 ± 9.31mg/dL, p = 0.015) and partially reduced area under the 120-min blood glucose response curve (AUC) in PD rats (p = 0.227). Moreover, Cr(III) attenuated weight gain (187.29 ± 38.56g vs. 167.22 ± 29.30g, p = 0.004), significantly reducing body mass index (0.68 ± 0.04g/cm2 vs. 0.63 ± 0.04g/cm2, p < 0.001), Lee index (0.30 ± 0.01 vs. 0.28 ± 0.01, p < 0.001), and peritoneal fat (p < 0.001). Regarding genomic stability, high-invert sugar, Cr(III), or the combination of both did not produce changes in oxidative stress, DNA damage in pancreas, or cytotoxicity markers. These data suggest that Cr(III) supplementation improved partially glucose metabolism and reduced obesity in rat model PD due to high-invert sugar without influence in genomic stability.

60-OR: OGTT Glucose Response Curves (GRC), Insulin Sensitivity (IS), and ß-Cell Function (ßCF) in RISE: Youth–Adult Contrast at Randomization and in Response to Interventions to Preserve ßCF

In adults and youth without diabetes, the shape of the OGTT-GRC [Biphasic (BPh), Monophasic (MPh), Incessant Increase (IIn)], identifies individuals with impairment in IS and βCF, worst in IIn, and least in BPh. Youth in the TODAY Study with IIn OGTT-GRC had higher glycemic failure rates and accelerated decline in βCF. In RISE we examined: 1) the shape of the OGTT-GRC in youth (n=85) vs. adults (n=353) at randomization; 2) the association between OGTT-GRCs and hyperglycemic clamp-measured IS and C-peptide-derived βCF; and 3) the change in OGTT-GRC [improvement: change from IIn to MPh or BPh, or MPh to BPh; deterioration: the opposite; and no change] at month 12 (M12) in each intervention arm [Metformin (M), and Glargine followed by M (G-M)]. At randomization, more youth had a BPh curve than adults (18.8% vs. 8.2%, p=0.022), with no difference in prevalence of MPh (70.6% vs. 77.3%) or IIn (10.6% vs. 14.5%) curves. IS did not differ across OGTT-GRCs in youth or adults. However, irrespective of curve type, youth had lower IS than adults (p&amp;lt;0.05). Across OGTT-GRCs, βCF was lowest in IIn vs. MPh and BPh in youth and adults (p &amp;lt;0.05 for each). However, youth compared with adults had higher βCF in BPh and MPh curves (p&amp;lt;0.005), but not IIn. Following intervention, the change in OGTT-GRC did not differ significantly between youth and adults (improvement: 14.5% vs. 18.0%, worsening 21.0% vs. 17.3%, no change 64.5% vs. 64.6% respectively). Moreover, there was no impact of M or G-M treatment on the change in OGTT-GRC from randomization to M12 in youth and adults. In summary, despite a 2-fold higher prevalence of the most favorable BPh OGTT-GRC in youth at randomization, it did not translate to better response to interventions in youth. Moreover, OGTT-GRCs reveal that the typical β-cell hypersecretion in youth is not present with the IIn GRC, emphasizing the severity of β-cell dysfunction in youth with this least favorable OGTT curve shape. Disclosure S.A. Arslanian: Research Support; Self; National Institutes of Health. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc. L. El Ghormli: None. J. Kim: None. T.S. Hannon: None. K.J. Mather: Research Support; Self; Abbott, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. S. Caprio: None. E. Barengolts: None. K.J. Nadeau: None. K. Utzschneider: Other Relationship; Self; Medtronic. S.E. Kahn: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Janssen Scientific Affairs, LLC., Merck &amp; Co., Inc., Novo Nordisk A/S, Pfizer Inc. T. Consortium: None. Funding American Diabetes Association (1-14-RISE-01 to S.E.K.); National Institute of Diabetes and Digestive and Kidney Diseases

2297-PUB: The Shape of Glucose Response Curve during Oral Glucose Tolerance Tests (OGTT) and Long-Term Near-Normoglycemia Remission in African Americans Presenting with Hyperglycemic Crises

Approximately 70% of obese African American (AA) patients with new-onset diabetic ketoacidosis (DKA) and severe hyperglycemia (SH) achieve near-normoglycemia remission (defined as HbA1c &amp;lt;7%, fasting blood glucose [BG]&amp;lt; 130 mg/dl, and off insulin for 1 month) with intensive insulin treatment. The shape of glucose response curve during OGTT has been shown predictive of future glycemic failure and beta(β)-cell function in adolescents with diabetes and adults. Biphasic (Bφ) curves showing better glycemic control and β-cell function compared to monophasic (Mφ) or incessant rise (IR) curves. We hypothesize that in AA patients with new-onset DKA and SH, Bφ shape at remission is associated with lower hyperglycemia relapse compared to Mφ or IR curves. Seventy AA patients underwent a 75g two-hour OGTT after near-normoglycemia remission and at end of study (median follow-up, 392 days). Insulin sensitivity (Si, oral minimal model) and β-cell function (AUCi: incremental area under the curve of insulin), and disposition index (Di= Si x AUCi) were compared among the different OGTT response curves. Hyperglycemia relapse-free survival (fasting BG &amp;gt; 130 mg/dl, 2 random BG &amp;gt; 180 mg/dl or HbA1c &amp;gt; 7%) was calculated with Kaplan-Meier curve. At remission, initial OGTT showed 56% of patients with Mφ, 16% with Bφ, and 29% with IR curve shape. Baseline characteristics did not differ. Even though, more patients in the Bφ group (88%) sustained remission than the Mφ (57%) and IR (53%), hyperglycemia relapse-free survival did not differ by curve shape (log rank, p=0.26). On initial OGTT, Si (p=0.09), AUCi (p=0.12) and Di (p=0.06) did not differ between curve shapes. At last OGTT, Si (p=0.43), AUCi (0.47) and Di (p=0.22) did not differ. In obese AA patients with new-onset DKA and SH, the shape of the glucose response curve during OGTT does not predict long-term glycemic control or β-cell function. Disclosure L. Cotten: None. D. Stefanovski: None. O. Oladejo: None. G.E. Umpierrez: None. P. Vellanki: Consultant; Self; Boehringer Ingelheim Pharmaceuticals, Inc. Funding National Institutes of Health (K08DK0830361, K23DK113241-01A1, UL1TR002378, 1P30DK111024-01)

Glucose lowering and pancreato-protective effects of Abrus Precatorius (L.) leaf extract in normoglycemic and STZ/Nicotinamide – Induced diabetic rats

Ethnopharmacological relevanceAbrus precatorius (L.) leaves are used as folk medicine by the local communities in the western region of Ghana to treat diabetes mellitus; however, this health claim remains unverified scientifically. ObjectiveThe study investigated glucose lowering and pancreato-protective effects of Abrus precatorius leaf extract (APLE) in normoglycemic and STZ/nicotinamide (NIC)-induced diabetic rats.Method: after preparation of APLE, it was subjected to phytochemical screening, proximate composition and elemental assessments by using standard methods. Oral glucose tolerance test (OGTT) and maltose, lactose and sucrose oral challenge were assessed in normoglycemic rats post-APLE. Morphological characteristics of glucose response curve (time of glucose peak and shape of glucose response curve) were determined. Subsequently, diabetes mellitus was experimentally established in normoglycaemic adult Sprague-Dawley rats (weighing 150–250 g) of both sexes by sequential injection of Streptozotocin (STZ, 60 mg/kg ip)-reconstituted in sodium citrate buffer and NIC (110 mg/kg ip)-reconstituted in normal saline (1:1 v/v) for 16 weeks. Except control rats (normal saline 5 ml/kg ip; baseline fasting blood glucose [FBG] of 6.48 mmol/L), rats having FBG (stable at 11.1 mmol/L or ≥ 250 mg/dL) 3 days post-STZ/NIC injection were randomly re-assigned to one of the following groups: model (STZ/NIC-induced diabetic rats), APLE (100, 200 and 400 mg/kg respectively po) and metformin (300 mg/kg po) and treated daily for 28 days. Bodyweight and FBG were measured on weekly basis. FBG was measured by using standard glucometers. On day 28, rats were sacrificed under chloroform anesthesia, blood collected via cardiac puncture; kidney, liver and pancreas surgically harvested. While the pancreas was processed, sectioned and H&E-stained for histological examination, fresh kidney and liver were homogenized for assessment of total anti-oxidant capacity. Median cross-sectional area of pancreatic islets of Langerhans was determined for each group by using Amscope. ResultsCumulatively, APLE (100, 200 and 400 mg/kg respectively) dose-dependently decreased the initial FBG by 55.22, 76.15 and 77.77% respectively compared to model (−1.04%) and metformin (72.29%) groups. APLE treatment recovered damaged pancreatic β-cells and also increased median cross-sectional area (x106 μm2) of pancreatic islets compared to that of model group. APLE significantly (P < 0.05) increased total anti-oxidant capacity (5.21 ± 0.02 AscAE μg/mL) of plasma, kidney and liver compared to model (4.06 ± 0.04 AscAE μg/mL) and metformin (4.87 ± 0.03 AscAE μg/mL) groups. ConclusionAPLE has demonstrated glucose lowering and pancreato-protective effects in rats and arrested the characteristic loss in bodyweight associated with diabetes mellitus. This finding preliminarily confirms folk use of APLE as an anti-diabetic herbal medicine, whiles providing a rationale for further translational studies on APLE.

The Effect of Prior Gestational Diabetes on the Shape of the Glucose Response Curve during an Oral Glucose Tolerance Test 3 Years after Delivery.

Objective Monophasic glucose response (MGR) during an oral glucose tolerance test (OGTT) and gestational diabetes mellitus (GDM) are predictors of type 2 diabetes mellitus (T2DM). We investigated the association between current MGR and (1) glucose tolerance during a pregnancy 3 years before and (2) current glucose tolerance status. We also sought (3) other determinants of MGR. Research Design and Methods. We conducted a nested case-control study of GDM (n = 47 early GDM, diagnosed between 16 and 20 weeks of gestation; n = 40 late GDM, diagnosed between 24 and 28 weeks of gestation) and matched healthy controls (n = 37, normal glucose tolerance during pregnancy) all free from diabetes at follow-up 3.4 ± 0.6 years after delivery. Glucose tolerance was determined by 2-hour 75 g OGTT. Monophasic and biphasic groups were defined based on serum glucose measurements during OGTT. Results The biphasic group was younger, had lower triglyceride levels and area under the OGTT glucose curve, and was less frequently diagnosed with early GDM (25 vs. 45%, all p < 0.05). Women with a biphasic response also tended to have lower systolic blood pressure (p < 0.1). No differences were found in fasting and 2-hour glucose and insulin levels, or BMI. According to multiple logistic regression, MGR was associated with prior early GDM (OR 2.14, 95% CI 0.92-4.99) and elevated triglyceride levels (OR 2.28, 95% CI 1.03-5.03/log (mmol/l)). Conclusions We found that more severe, early-onset GDM was an independent predictor of monophasic glucose response suggesting that monophasic response may represent an intermediate state between GDM and manifest type 2 diabetes.

Shape of the glucose response curve during an oral glucose tolerance test is associated with insulin clearance and muscle insulin sensitivity in healthy non-obese men.

Individuals with a monophasic glucose response curve (GRC) during a 75‐g oral glucose tolerance test have a higher risk for type 2 diabetes than those with a biphasic GRC. However, no studies have addressed the association between GRC type and insulin clearance. Thus, we studied 49 healthy non‐obese Japanese men. We divided study participants into the monophasic or biphasic group based on the shape of their GRC. We evaluated tissue‐specific insulin sensitivity and insulin clearance using a two‐step hyperinsulinemic‐euglycemic clamp. The monophasic group had more visceral fat, lower insulin clearance and lower muscle insulin sensitivity than the biphasic group, whereas liver and adipose tissue insulin sensitivity, and insulin secretion were comparable. In conclusion, healthy non‐obese men with a monophasic GRC have lower insulin clearance and muscle insulin sensitivity.

Heritability of Curve Patterns in Oral Glucose Tolerance Test.

Type 2 diabetes, which is caused by both genetic and environmental factors, may be diagnosed using the oral glucose tolerance test (OGTT). Recent studies demonstrated specific patterns in glucose curves during OGTT associated with cardiometabolic risk profiles. As the relative contribution of genetic and environmental influences on glucose curve patterns is unknown, we aimed to investigate the heritability of these patterns. We studied twins from the Danish GEMINAKAR cohort aged 18-67 years and free from diabetes at baseline during 1997-2000; glucose concentrations were measured three times during a 2-h OGTT. Heterogeneity of the glucose response during OGTT was examined with latent class mixed-effects models, evaluating goodness of fit by Bayes information criterion. The genetic influence on curve patterns was estimated using quantitative genetic modeling based on linear structural equations. Overall, 1455 twins (41% monozygotic) had valid glucose concentrations measured from the OGTT, and four latent classes with different glucose response patterns were identified. Statistical modeling demonstrated genetic influence for belonging to a specific class or not, with heritability estimated to be between 45% and 67%. During ∼12 years of follow-up, the four classes were each associated with different incidence of type 2 diabetes. Hence, glucose response curve patterns associated with type 2 diabetes risk appear to be moderately to highly heritable.

Glycemic Index, Starch, and Protein Digestibility in Tempeh Gembus Cookies

Diabetes mellitus is directly related to diet and lifestyle. Control of blood glucose levels is needed to reduce the risk of complications, and one way is to choose foods with a low glycemic index. Cookies made from tempeh gembus/tempeh gembus flour are expected to be eaten as a snack and are safe for people with diabetes. The aim of this research was to analyze glycemic index (GI), glycemic load (GL), dietary fiber, in vitro starch, and protein digestibility of cookies with tempeh gembus flour substitution. Completely randomized design research with one primary factor used cookies with variations of 0%, 25%, and 50% tempeh gembus flour substitution. GI was calculated using the Incremental Area Under the Blood Glucose Response Curve (IAUC) method. Dietary fiber concentration analysis was done by enzymatic methods. The starch and protein digestion rates were calculated using the in vitro method. GI, GL, dietary fiber, starch digestion rate, and protein digestion rate data were analyzed with descriptive methods. Cookies with lowest GI (47.01 ± 11.08%) and GL (6.90 ± 1.63) were found in cookies with 50% tempeh gembus flour substitution. The highest dietary fiber content (24.61 ± 0.41%), digestibility of starch (48.07 ± 0.01%), and protein (20.27 ± 0.43%) cookies were found in cookies with 50% tempeh gembus flour substitution. The higher tempeh gembus flour substitution produced low GI and GL while its dietary fiber, in vitro starch, and protein digestibility were highest.

Assessment of the glycemic index of groats available on the Polish food market

Glycemic index (GI) and glycemic load (GL) are often used to assess diet quality in relation to the risk of diabetes, cardiovascular diseases and cancer development. Taking into account differences in nutritional value of food products in different countries it is often suggested to used national databases to assess dietary intake in different populations. To assess the glycemic index and glycemic load of the selected groats available on the Polish food market. GI of the following groats available on the Polish food market was assessed: couscous, buckwheat (roasted) groats, millet groats, spelt groats, barley (hulled) groats and bulgur groats. The GI was assessed as the incremental area under the blood glucose response curve of a 50g carbohydrate portion of a test food expressed as a percent of the response to the same amount of carbohydrate from a standard food taken by the same subject. GL was calculated for the 100 g of the cooked product. The lowest GI was found for buckwheat (34.7±8.2%) and barley (31.3±13.4%) groats. The GL for these groats was 8.1±1.9 and 8.0±3.4, respectively. The GI for millet, spelt and bulgur groats amounted to 56.2±20.6%, 69.8±35.0%, 64.5±36.8%, respectively, while for couscous amounted to 99.0± 36.0%. The highest GL was observed for couscous (24.7±9.0). The groats tested in this study can be classified as follows: barley and buckwheat as a low GI food, millet and bulgur as a medium GI food, spelt and couscous as a high GI food. Buckwheat and barley groats should be chosen the most often among these products, while the intake of couscous should be limited especially by people with diabetes.

The Impact of Glucose on Corticospinal and Intracortical Excitability.

Neurotransmission is highly dependent on the availability of glucose-derived energy, although it is unclear how glucose availability modulates corticospinal and intracortical excitability as assessed via transcranial magnetic stimulation (TMS). In this double-blinded placebo-controlled study, we tested the effect of acute glucose intake on motor-evoked potential (MEP) recruitment curves, short-interval intracortical inhibition (SICI), short-latency afferent inhibition (SAI) and long-latency afferent inhibition (LAI). Eighteen healthy males participated in four sessions. Session 1 involved acquisition of an individualized blood glucose response curve. This allowed measurements to be time-locked to an individualized glucose peak after consuming one of three drinks during the subsequent three sessions. Participants were administered a 300 mL concealed solution containing 75 g of glucose, sucralose, or water in separate sessions. Dependent measures were assessed at baseline and twice after drinking the solution. Secondary measures included blood glucose and mean arterial pressure. Corticospinal excitability and blood pressure increased following the drink across all treatments. No changes were observed in SICI, SAI or LAI. There was no rise in corticospinal excitability that was specific to the glucose drink, suggesting that acute changes in glucose levels do not necessarily alter TMS measures of corticospinal or intracortical excitability.

The shape of the glucose response curve during an oral glucose tolerance test heralds \u03b2\u2013cell function in a large Chinese population

BackgroundThe shape of the glucose response curve during an oral glucose tolerance test (OGTT) can predict β-cell function and insulin resistance. However, there have been few studies conducted on Chinese people. Thus, we aimed to verify the usefulness of the glucose response curve in a large Chinese population.MethodsA total of 9059 OGTT (3-h tests) were categorized into either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, the Matsuda Index, the insulinogenic index, and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT.ResultsThe shape of the OGTT glucose response curve was monophasic in 87.3% and multiphasic in 12.7% of participants. Individuals in the multiphasic group were younger compared to those in the monophasic group (38.6 ± 13.6 vs. 35.4 ± 13.5, P < 0.001). Individuals in the monophasic group had significantly higher fasting plasma glucose (FPG 5.6 ± 13.5 vs. 5.2 ± 0.6, P < 0.001), fasting insulin (FINS 14.8 ± 8.7 vs. 13.5 ± 7.9, P < 0.01), and homeostasis model assessment of insulin resistance (HOMA-IR 3.8 ± 2.6 vs. 3.1 ± 2.0, P < 0.001) and impaired β-cell function (disposition index 12.7 ± 14.1 vs. 16.6 ± 17.8, P < 0.001) compared to those in the multiphasic group.ConclusionThe monophasic OGTT glucose response curve could reflect impaired β-cell function in a large Chinese population.

187-LB: Glucose Response Curve (GRC) Shapes in Mixed Meal Tolerance Tests (MMTTs) and Prediction of Response to Intervention in the TrialNet New-Onset Clinical Trials

It is known that individuals with a biphasic (BiP; two peaks) GRC during 2-hr oral glucose tolerance tests are at lower type 1 diabetes (T1D) risk than those with monophasic (MoP; one peak) and monotonic (MoT; continuous rise) GRCs. We hypothesized that GRC shapes during MMTTs in persons with newly-diagnosed T1D can predict response to intervention and that the shape may change in response to therapy. We performed an analysis to 1) Determine if the baseline GRC shape can predict response to intervention, and 2) Evaluate GRC changes in responders (R) vs. non-responders (NR) to interventions; response=AUC C-peptide (C-P) at 12 months not &amp;lt;5% of AUC C-P at baseline. Those with complete MMTT data at baseline (within 3 months of diagnosis) and at 12 months from all TrialNet intervention trials were included in the analyses (n=389, median (IQR) age 14.6 (8.1) years, BMI-z 0.6 (1.4), 56% male). At baseline, R had higher BiP GRCs [NR: 9.4% (25/227) vs. R: 20.6% (13/63); adjusted OR 2.92 (1.36-6.27); p=0.006)]. The overall shape distribution was significantly different between R and NR at 12 months (p=0.036) with a notable higher frequency of MoT GRCs in NR [NR: 30.1% (68/226) vs. R: 15.5% (9/58), p=0.031]. There were no differences between R and NR in the odds of changing from one GRC to another (p&amp;gt;0.05 for all). In conclusion, the finding that a BiP GRC at baseline was more common in R than NR suggests that MMTT GRCs can be used to predict responses to interventions in those newly diagnosed with T1D. Further, the higher proportion of MoT GRCs in NR at 12 months suggests that MMTTs with MoT GRCs are indicative of metabolic decline. Disclosure N.N. Almutlaq: None. M.A. Cleves: None. S.E. Gitelman: Advisory Panel; Self; Avortes, Intermountain Therapeutics, Lilly Diabetes, Tolerion, Inc. Research Support; Self; Caladrius Biosciences, Inc., Janssen Research &amp; Development. Other Relationship; Self; Novo Nordisk Inc. L. DiMeglio: Research Support; Self; Amgen Inc., Caladrius Biosciences, Inc., Janssen Research &amp; Development, Medtronic, Sanofi. Other Relationship; Self; Dexcom, Inc. J.M. Sosenko: None. H.M. Ismail: None. Funding National Institutes of Health

1331-P: OGTT Glucose-Response-Curve (GRC) in Islet Cell Antibody-Positive (Ab+) vs. -Negative (Ab-) Obese Youth Clinically Diagnosed with Type 2 Diabetes (CDX-T2D)

The OGTT-GRCs [Incessant Increase (IIn), Monophasic (Mph), and Biphasic (Bph)] reflect insulin sensitivity (IS) and β-cell function (BCF), being worse in the former and best in the latter. Accordingly, the prevalence of these GRCs differ in diabetic and nondiabetic individuals (Table). While islet cell Ab- obese youth CDX-T2D have worse IS, Ab+ youth have severe impairment in BCF [Diabetes 58: 2009]. Here, we examined the prevalence of OGTT-GRC patterns, clamp-measured IS, and BCF in obese Ab+ (GAD65 and IA2) vs. Ab- youth CDX-T2D. The dominant GRC was IIn in Ab+ and Mph in Ab- youth while Bph was scarce in both (Table). In Ab+ youth, 1st- (32.5 ± 5.6 vs. 40.2 ± 8.0 µU/mL, p=0.13) and 2nd-phase insulin (39.6 ± 8.6 vs. 62.8 ± 12.2 µU/mL, p=0.04), were 20% and 40% lower in IIn vs. the other two combined. In Ab-, while 1st- (67.3 ± 19.1 vs. 122.4 ± 28.3 µU/mL, p=0.049) and 2nd-phase insulin (110.3 ± 31.4 vs. 171.6 ± 28.6 µU/mL, p=0.054) were lower in IIn vs. Mph, overall BCF was less impaired than in Ab+ youth. IS did not differ by GRC type in either group but was lower in Ab- vs. Ab+ irrespective of GRC type. The prevalence of IIn-GRC is 3-fold higher in Ab+ vs. Ab- obese youth CDX-T2D, and the prevalence in Ab- youth is similar to that in the TODAY study (Table). The higher prevalence of IIn-GRC in Ab+ obese youth signifies the severe insulin deficiency characteristic of type 1 diabetes. Disclosure J. Kim: None. N. Gebara: None. H. Tfayli: Other Relationship; Self; Sanofi. F. Bacha: Research Support; Self; National Institute of Diabetes and Digestive and Kidney Diseases, Pediatric Diabetes Consortium. Other Relationship; Self; AstraZeneca, Jaeb Center for Health Research. S.A. Arslanian: None. Funding Eunice Kennedy Shriver National Institute of Child Health and Human Development (K24-HD01357, R01HD27503 to S.A.A.); National Center for Advancing Translational Sciences (UL1TR000005); National Center for Research Resources (UL1RR024153)

1663-P: Monophasic Glucose Response Curve Reflective of Glucose Intolerance in Young Mexican Americans

The glucose response curve of an oral glucose tolerance test (OGTT) has been associated with insulin sensitivity. A monophasic curve has been shown to be more prevalent in hyperglycemic and T2D population. However, it is unknown whether shape of curve in a healthy normoglycemic population can be indicative of risk for developing T2D. Purpose: We aimed to determine if glucose response morphology, monophasic (M) versus biphasic (B), may be indicative of glucose tolerance and a family history of T2D (FH). Methods: Normoglycemic Mexican American Males (mean ± SEM; age 23.26 ± 0.66 years, BMI 25.69 ± 0.97 kg/m2) with (n=7) or without (n=7) a FH participated in this study. Body composition was measured by DXA, substrate utilization was measured by indirect calorimetry, maximal aerobic capacity (VO2max) was measured by a standardized graded exercise test. Participants consumed 75 g of glucose while fasting and blood glucose were assessed at 0, 30, 60, 90, and 120 min. Based on Tschritter et al. (2003) classification, glucose response curves were separated into M (n=10) and B (n=4) groups. Results: There were no significant differences in body weight, BMI, fat mass, fat free mass, resting substrate utilization, VO2max and fasting blood glucose (BG) between groups (all P &amp;gt; 0.05). However, M were significantly glucose intolerant compared to B evident by a greater glucose area under the curve (M: 263.63 ± 11.34 AU; B: 209.20 ± 4.46 AU; p=0.01) and a significantly greater BG levels during OGTT at minute 30 (149.97 ± 8.53 vs. 110.53 ± 12.60 mg/dl; p=0.02), 60 (149.80 ± 9.33 vs. 104.99 ± 17.21 mg/dl; p=0.03) and 90 (116.48 ± 6.62 vs. 71.71 ± 10.11 mg/dl; p&amp;lt; 0.01) compared to B. All individuals with a monophasic OGTT response had a FH whereas most individuals with biphasic OGTT response (7/10) did not. Conclusion: Although having similar fasting BG, body composition, substrate utilization, and aerobic fitness, a monophasic compared to biphasic, OGTT reflects glucose intolerance and risk for developing T2D. Disclosure J. Jenkins: None. C. Meza: None. M. Amador: None. A.J. McAinch: None. S. Bajpeyi: None.

Does type of bread ingested for breakfast contribute to lowering of glycaemic index?

Recent interest has focused on the use of high-fibre foods as potential ingredients for lowering the glycaemic index of most carbohydrate-based meals. The objective of this study was to examine glycaemic responses to two defined breakfasts. The reference breakfast and the test breakfast differed only in the type of bread (white vs. wholemeal), and were administered three times to volunteers (2 men, 8 women). Capillary blood glucose was monitored in the fasting state 15, 30, 45, 60, 75, 90, 105 and 120 min after breakfast consumption. The incremental areas under the glucose response curves were calculated for each type of breakfast and compared with those of glucose to determine the glycaemic indices. The glycaemic index of the reference breakfast was 26.6 (±6.2), with that of the test breakfast significantly lower at 18.1 (±6.0). The mixed-food test breakfast with wholemeal bread was rich in soluble fibre (β-glucans) for a lower glycaemic load than the white bread, and provided a lower glycaemic response in the volunteers. The inter-volunteer variability in glycaemic index was large, with some showing lower responses to the test breakfast (glycaemic index, 12.4–21.1) and some showing high responses to the test breakfast (glycaemic index, 25.9–27.4).

Integrative Pathophysiology of a Novel Rodent Model of Postmenopausal Heart Failure with Preserved Ejection Fraction

PurposeApproximately 50% of heart failure patients have heart failure with preserved ejection fraction (HFpEF), and currently there are no proven therapies for this population. There is an urgent need to develop animal models of HFpEF to understand the mechanisms of this disease and discover treatments. Notably, 70–85% of HFpEF patients are postmenopausal women. We hypothesized that a novel animal model that recapitulated classical risk factors for HFpEF (i.e., female sex, aging/menopause, hypertension, obesity/high fat, high sugar diet) would display cardiac abnormalities, skeletal muscle dysfunction, and exercise intolerance consistent with disease features seen in humans.MethodsFemale, ovariectomized, spontaneously hypertensive rats (SHR) were fed a Western diet (high saturated fat, high sugar) for ~16 weeks to model HFpEF pathophysiology. Female, sham surgery, lean diet, Wistar‐Kyoto rats were used as controls. We evaluated glucose tolerance, tail‐cuff blood pressure, running time to exhaustion, echocardiography, in vitro skeletal muscle force, intact mitochondrial respiration and reactive oxygen species emission, and cardiac and skeletal muscle histology. All researchers were blinded to group assignment during terminal experiments and statistical analyses. Data were compared using Student's t‐tests and are shown as mean ± SD from n = 4–8 rats per group.ResultsHFpEF rats displayed a 20±6% increase in body weight, 20±22% greater area under the glucose response curve, 36±14% higher mean arterial pressure, 70±47% elevation in liver enzymes, and 42±12% decrease in high‐intensity running endurance (p&lt;0.05). Left ventricle (LV) of HFpEF rats exhibited hypertrophy (in mg/mm: Control 17±0.5, HFpEF 21±0.7, p&lt;0.05), fibrosis (in %: Control 2±1.0, HFpEF 4±1.9, p=0.10) and elevated E wave deceleration rate indicative of restrictive LV filling (in m/s2: Control 21±5, HFpEF 35±4, p&lt;0.05). LV fractional shortening, a marker of systolic function, was preserved (in %: Control 47±7, HFpEF 44±7, p&gt;0.05). In limb skeletal muscle, HFpEF caused weakness (force in N/g: Control 17±3, HFpEF 14±1, p&lt;0.05), impaired maximal mitochondrial respiration (in pmol O2/s/mg: Control 71±27, HFpEF 39±11, p&lt;0.05), and a trend toward elevated mitochondrial H2O2 emission (in pmol/min/mg: Control 0.8±0.4, HFpEF 1.7±0.9, p=0.10). In this early stage of HFpEF, there was no limb muscle atrophy in type I (in μm2: Control 1986±526, HFpEF 1752±364), type IIa (in μm2: Control 1595±339, HFpEF 2022±663), or type IIb/x (in μm2: Control 3605±536, HFpEF 4111±653) tibalis anterior fibers (p&gt;0.05), but there was an increase in fibrosis (in %: Control 0.7±0.3, HFpEF 1.5±1, p&lt;0.05).ConclusionOur preclinical model recapitulates key cardiovascular, metabolic, and skeletal muscle features of the disease with a pronounced decrease in high intensity running endurance. The model is clinically relevant for post‐menopausal women with HFpEF ‐ the patient group that represents the majority of the HFpEF population. This model will be valuable for future studies aiming to elucidate mechanisms of disease development and novel treatments.Support or Funding InformationBREATHE T32 HL134621This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Glycemic Index (GI) and Glycemic Load (GL) Values for Dried Bisr and Tamr Dates

Date fruits can be consumed at different stages of maturity and thus might vary in glycemic response. Therefore, this study aims to evaluate the nutritional composition, glycemic index (GI) and glycemic load (GL) values of dried Bisr (mature unripe) and Tamr (mature ripe) dates. Fifteen healthy female participants (18 and 25 years), were recruited to assess the GI and GL values of dried Bisr and dried Tamr dates. Each participant was tested in three different times. Trials were separated by 1 week and proceeded in a randomized counterbalanced manner. Anthropometrics and food records were obtained for all participants. Proximate analysis revealed significant differences between Bisr and Tamr dates in moisture, ash, fat, protein, and fiber content (P&lt;0.05), whereas, carbohydrate and energy contents were comparable (P&gt;0.05). The incremental area under the blood glucose response curve was higher (164.5 ± 47.8) for the standard food in comparison with dried Bisr (88.5 ± 24.1, P &lt; 0.0001) or dried Tamr dates (88.2 ± 27.9, P&lt;0.0001), whereas, no significant differences were detected between the test foods (P&gt;0.05). Both GI (Bisr: 54.6 ± 15.2 vs. Tamr: 54.3 ± 14.3) and GL (Bisr: 13.65 vs. Tamr: 13.58) were not significantly different between the test food items (P&gt;0.05). Dried date fruits induce similar glycemic responses regardless of their maturity stage.

Glycemic index of ten commercially Indonesian rice cultivars

Ten Indonesian rice cultivars (Inpari 32, Sintanur, Inpago Unsoed 1, Sulutan Unsrat 2, Memberamo, Way Apo Buru, Bestari, Pepe, Situ Bagendit, and Logawa) were analysed for glycaemic index (GI). Wistar rats were randomly selected and after overnight fast were given a portion containing 0.44 g available carbohydrate of different cultivars cooked rice (test foods) or glucose (reference food) on separate occasions. Blood glucose responses were determined at fasting and during the postprandial periods over the next 2 h and we calculated the incremental area under the blood glucose response curve (IAUC). GI value was determined by dividing IAUC for test foods by IAUC for reference food and multiplying by 100. There were significant differences (p < 0.001) between GI values for Inpari 32 (74.54 ± 4.68), Sintanur (91.36 ± 1.28), Inpago Unsoed 1 (94.11 ± 5.93), Sulutan Unsrat 2 (83.56 ± 5.87), Memberamo (92.78 ± 3.69), Way Apo Buru (71.53 ± 7.71), Bestari (87.76 ± 12.69), Pepe (70.61 ± 10.69), and Situ Bagendit (81.81 ± 5.63) rice cultivars and all classified as high GI. However, Logawa (54.39 ± 1.49) cultivar was classified as low GI. Therefore, we have an urgent need to develop low GI rice cultivars via breeding technologies.

A STUDY OF THE GLYCEMIC INDEX OF THE MEDICAL FOOD NEO-MUNE

Objective: To study the glycemic index of a medical food Neo-Mune. Material and Methods: Ten healthy volunteers with normal pancreatic function were enrolled in this study. All eligible subjects were asked to return to the research center a week later to consume 50 grams of glucose solution and their plasma glucose levels were measured at 0 (baseline), 30, 60, 90 and 120 minutes after the glucose consumption. A week after that, the same cohort consumed 94.97 g Neo-Mune (advised carbohydrate provision of 50 grams) and again, their plasma glucose levels were recorded at 0, 30, 60, 90 and 120 minutes after consumption. The glycemic index (GI) was calculated from the area under the glucose response curve of Neo-Mune divided by the area under the glucose response curve of the glucose solution, multiplied by 100. Results: The plasma glucose levels reached their highest levels at 30 minutes post-consumption and decreased gradually in both cases. However, the plasma glucose levels were lower at 30 and 60 minutes post Neo-Mune consumption compared to those after the glucose solution consumption. The GI of Neo-Mune was identified as 42.12, which classifies it as a low-GI food. Conclusion:Neo-Mune, a low-GI food, is expected to show a low postprandial glycemic excursion after consumption.