Postprandial Glucose Excursions Research Articles

LBSUN307 A Randomized Controlled Pilot Study Of The Food Order Behavioral Intervention In Prediabetes

Abstract Background and Objectives Ordering the ingestion of carbohydrate-rich foods after protein/vegetables (carbohydrate-last food order) significantly reduced postprandial glucose and insulin excursions over 180 min in patients with prediabetes and type 2 diabetes, compared with the reverse food order (carbohydrate-first) in previous research. We implemented a 16-week food order behavioral intervention, assessing its feasibility and impacts on glucose tolerance (GT), HbA1c, and weight (wt) in adults with prediabetes. Methods Participants with overweight/obesity and prediabetes (HbA1c 5.7-6.4%) were randomized to receive either standard nutritional counseling (control group) or standard nutritional counseling plus carbohydrate-last food order counseling (FO group). Participants were instructed to maintain their usual level of exercise throughout the study; this was assessed by the Godin Leisure-Time Exercise questionnaire at baseline and wk 16. Participants in both groups received 4 in-person brief counseling sessions at 1-month intervals. Due to the Covid-19 pandemic, later participants received some or all of their counseling via telemedicine. Oral GT was tested at baseline and week 16. Feasibility was assessed via a questionnaire. Results Of the 45 randomized subjects, 39 completed the study (control 21, FO 18). Demographics and baseline variables including wt (190.8 lbs vs 191.1 lbs) and HbA1c (6% vs 6%) were similar between groups. Exercise levels did not differ between groups at baseline and wk 16. Within FO group, body wt declined (-3.6 ±5.7 lbs, p=0. 017; -1.8% ±2.8, p=0. 012), and there was a trend towards improvement in HbA1c (-0.1 ±0.2, p=0. 054). Control group wt changed (-2.6 ±6.8 lbs, p=0.102; -1.6% ±3.5, p=0. 048) without altering HbA1c (-0. 03 ±0.3, p=0.605). Changes in wt, HbA1c, and GT were not significantly different between groups. At week 16, 17 FO group subjects (94%) reported high intervention adherence, 13 (74%) reported it was easy to eat protein/vegetables before carbohydrates, and 14 (78%) reported they would continue eating protein/vegetables before carbohydrates. Conclusions Carbohydrate-last food order is a feasible behavioral strategy in individuals with prediabetes. More research with a larger sample size and longer duration is needed to delineate its clinical impact. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Evaluating Time in Range as an Outcome Measure for Vildagliptin 100 mg SR OD

Background: Vildagliptin, a dipeptidyl peptidase-4 inhibitor, has shown promising effects in improving glycemic control in patients with diabetes. Glycemic variability, characterized by fluctuations in blood glucose levels, is a common challenge in diabetes management. It has been associated with an increased risk of both acute and chronic complications. Clinical studies evaluating the effects of vildagliptin 50 mg bid have demonstrated its ability to reduce glycemic variability and improve the TIR. Vildagliptin has been shown to decrease postprandial glucose excursions and nocturnal glycemic fluctuations, leading to a smoother glycemic profile. Aims and Objectives: This pilot study highlights the relationship between vildagliptin 100 mg sustained release once daily (SR OD) therapy and its potential impact on reducing glycemic variability and promoting a better time in range (TIR) for patients with diabetes. Materials and Methods: In this study, patients were enrolled in a prospective, multicentric, and observational study to assess the real-world experience of vildagliptin 100 mg SR OD in terms of glycemic variability. Results and Conclusions: At the end of the pilot study period of 14 days, the results demonstrated that in real-life experience, vildagliptin 100 mg SR OD was associated with a clinically meaningful reduction in hemoglobin A1c, and a higher proportion of patients maintained their average blood glucose levels between 70 and 180 mg/dL for almost three-fourth of a day.

Metabolic syndrome associated with higher glycemic variability in type 1 diabetes: A multicenter cross-sectional study in china.

AimsThe comorbidity of metabolic syndrome (MetS) and type 1 diabetes mellitus (T1DM) is an obstacle to glucose control in patients with T1DM. We compared glycemic profiles using continuous glucose monitoring (CGM) systems in patients with T1DM with or without MetS.MethodsThis was a multicenter cross-sectional study of patients with T1DM (N = 207) with or without MetS. CGM data were collected from study enrollment until discharge during a 1-week study session. We analyzed baseline HbA1c, average glucose, estimated HbA1c, time in range (TIR), time above range (TAR), time below range (TBR), coefficient of variation (CV), postprandial glucose excursions (PPGE) and other glycemic variability (GV) metrics. Logistic regression was developed to investigate the association between MetS and CGM metrics.ResultsThe results showed higher average baseline HbA1c levels, and a higher percentage of patients with baseline HbA1c levels ≥7.5%, in the T1DM with MetS group. Furthermore, MetS was associated with GV, which indicated a higher CV in patients with T1DM with MetS. However, our results showed that TAR, TIR, TBR and other GV metrics were comparable between the two groups. The T1DM with MetS group also had a higher proportion of patients with high CV (≥ 36%) than the group without MetS. In multivariable logistic regression analysis, the presence of MetS was a risk factor for high CV (≥ 36%) in our study participants.ConclusionsT1DM patients with MetS in our study had better β-cell function. However, MetS was associated with worse glycemic control characterized by higher GV and HbA1c levels. Efforts should be expanded to improve treatment of MetS in patients with T1DM to achieve better glycemic control.

The increased prevalence of depression and anxiety in T2DM patients associated with blood glucose fluctuation and sleep quality

BackgroundCurrent evidence demonstrates that blood glucose fluctuation can be associated with depression and anxiety. The association among blood glucose fluctuation, traditional risk factors and emotional disorders in T2DM should be studied and clarified.MethodsA total of 182 diabetic patients including 81 patients with depression or anxiety and 101 patients without emotional disorder were enrolled into this study. Data were obtained through medical history and questionnaire survey. Data were analyzed using appropriate statistical methods.ResultsThe comparison results of basic information between the two groups showed that the differences of the proportion of female were statistically significant (p = 0.002).There was no statistical difference in laboratory examination indexes between the two groups, however, standard deviation of blood glucose (SDBG) and postprandial glucose excursion (PPGE) of the comorbidity group were significantly higher than that of control group (p = 0.032 and p = 0.037). The results of questionnaire survey showed that there were statistically significant differences in sleep quality, PSQI and dietary habit between the two groups (p < 0.001, p < 0.001 and p < 0.001). Stratified analysis results according to gender showed that the percentage of cognitive disorder, anxiety and depression in female group was significantly higher than that in male group (p = 0.001, p < 0.001 and p < 0.001). Mini-mental state examination (MMSE), self-rating anxiety scale (SAS) and patient health questionnaire (PHQ-9) score in female group were also higher than male group (p = 0.001, p < 0.001 and p < 0.001). Logistic regression analysis results showed that SDBG and sleep quality were associated with emotional disorders in T2DM (p = 0.040 and p < 0.001) and the OR values of these factors were 7.588 (1.097–52.069) and 4.428 (2.649–7.401).ConclusionsBlood glucose fluctuation and sleep quality are associated with the increased prevalence of depression and anxiety disorders in T2DM.

Continuous Glucose Monitoring System Profile of Women with Gestational Diabetes Mellitus Missed Using Isolated Fasting Plasma Glucose-Based Strategies Alternative to WHO 2013 Criteria: A Cross-Sectional Study.

The aim of the study was to evaluate the differences in the continuous glucose monitoring system (CGMS)-based glycemic parameters between women with normoglycemia and early gestational diabetes mellitus (GDM) identified on the basis of mild fasting plasma glucose elevation (FPG, 5.1-5.5mmol/L) and/or post-load plasma glucose elevation (PLG, 1-h ≥ 10.0mmol/L or 2-h ≥ 8.5mmol/L). This cross-sectional study included women with singleton pregnancy (8+0 to 19+6weeks of gestation) and normoglycemia or GDM per World Health Organization (WHO) 2013 criteria. We evaluated the glycemic parameters of clinical interest using blinded CGMS evaluation and reported them per standard methodology proposed by Hernandez et al. RESULTS: A total of 87 women (GDM, n = 38) were enrolled at 28.6 ± 4.5years. Among women with GDM, 10 (26.3%) had isolated mild FPG elevation (5.1-5.5mmol/L), 10 (26.3%) had isolated PLG elevation (1-h ≥ 10.0mmol/L or 2-h ≥ 8.5mmol/L), and 7 (18.4%) had a combination of both. The remaining 11 (28.9%) had elevated FPG (≥ 5.6mmol/L) with or without PLG elevation. Thus, when an isolated FPG cutoff ≥ 5.6mmol/L is used to diagnose GDM, 27 (71.0%) women would be perceived as normoglycemic. Such women had significantly higher CGMS parameters of clinical interest, such as 24-h mean glucose, fasting glucose, 1-h and 2-h postprandial glucose (PPG), 1-h PPG excursion, and peak PPG. An isolated FPG threshold, especially the higher cutoff ≥ 5.6mmol/L, can potentially miss a large proportion of women (nearly three-fourths) diagnosed with GDM per WHO 2013 criteria. Eventually, such women fare significantly differently from normoglycemic women in various CGMS parameters of clinical interest.

A potent physiological method to magnify and sustain soleus oxidative metabolism improves glucose and lipid regulation

SummarySlow oxidative muscle, most notably the soleus, is inherently well equipped with the molecular machinery for regulating blood-borne substrates. However, the entire human musculature accounts for only ∼15% of the body’s oxidative metabolism of glucose at the resting energy expenditure, despite being the body’s largest lean tissue mass. We found the human soleus muscle could raise local oxidative metabolism to high levels for hours without fatigue, during a type of soleus-dominant activity while sitting, even in unfit volunteers. Muscle biopsies revealed there was minimal glycogen use. Magnifying the otherwise negligible local energy expenditure with isolated contractions improved systemic VLDL-triglyceride and glucose homeostasis by a large magnitude, e.g., 52% less postprandial glucose excursion (∼50 mg/dL less between ∼1 and 2 h) with 60% less hyperinsulinemia. Targeting a small oxidative muscle mass (∼1% body mass) with local contractile activity is a potent method for improving systemic metabolic regulation while prolonging the benefits of oxidative metabolism.

Ultra rapid lispro improves postprandial glucose control versus lispro in combination with insulin glargine/degludec in adults with type 2 diabetes: a prospective, randomized, double-blind, phase 3 trial

Ultra rapid lispro (URLi) is a novel formulation of insulin lispro designed to more closely match the physiological insulin response to a meal, with the aim of improving postprandial glucose (PPG) control. We conducted a multinational, multicenter, randomized, double-blind, treat-to-target, 26-week, phase 3 trial to evaluate the efficacy and safety of URLi in adults with type 2 diabetes (T2D). After an 8-week lead-in period during which basal insulin glargine or degludec was optimized, adults with T2D were randomized (2:1) to prandial URLi (n = 395) or lispro (n = 200). The primary endpoint was non-inferiority of URLi versus lispro in glycated hemoglobin A1c (HbA1c) change from baseline to week 26. Multiplicity-adjusted analyses were performed to assess the superiority of URLi in 1- and 2-h PPG excursions during a mixed-meal tolerance test (MMTT) and HbA1c change at week 26. URLi showed non-inferiority for HbA1c change at week 26 versus lispro (least-squares mean [LSM] difference, 0.07%; 95% confidence interval: −0.07, 0.21). HbA1c was reduced by 0.56% and 0.63% with URLi and lispro, respectively, with no significant treatment difference (P = 0.321). URLi provided superior PPG excursion control versus lispro at 1 h (LSM difference: −14.6 mg/dL, P < 0.001) and 2 h (LSM difference: −21.8 mg/dL, P < 0.001) as well as other time points (30–240 min) during the MMTT. Incremental area under the glucose curve during the MMTT was also significantly lower with URLi versus lispro. The safety profiles were generally similar between treatment groups. In conclusion, URLi was superior to lispro for PPG control, with non-inferiority in HbA1c improvement, in adults with T2D.

Continuous Glucose Profiles in Healthy People With Fixed Meal Times and Under Everyday Life Conditions.

The increased use of continuous glucose monitoring (CGM) and automated insulin delivery systems raises the question about therapeutic targets for glucose profiles in people with diabetes. This study aimed to assess averaged pre- and postprandial glucose profiles in people without diabetes to provide guidance for normal glucose patterns in clinical practice. For that, number and timing of meal intake were predefined. To assess glucose traces in 36 participants without diabetes (mean age = 23.7 ± 5.7 years), CGM was performed for up to 14 days, starting with a run-in phase (first 3 days, excluded from analysis) followed by 4 days with fixed meal times at 8:00 am, 1:00 pm, and 6:00 pm and the remaining 7 days spent under everyday life conditions. Data from two simultaneously worn CGM sensors were averaged and adjusted to capillary plasma-equivalent glucose values. Glucose data were evaluated through descriptive statistics. Median glucose concentration on days with fixed meal times and under everyday life conditions was 95.0 mg/dL (91.6-99.1 mg/dL, interquartile range) and 98.1 mg/dL (93.7-100.8 mg/dL), respectively. On days with fixed meal times, mean premeal glucose was 92.8 ± 9.4 mg/dL, and mean peak postmeal glucose was 143.3 ± 23.5 mg/dL. By defining the time of meal intake, a clear pattern of distinct postprandial glucose excursions in participants without diabetes could be demonstrated and analyzed. The presented glucose profiles might be helpful as an estimate for adequate clinical targets in people with diabetes.

Changing Meal Sequence Affects Glucose Excursions in Gestational Diabetes Mellitus.

Studies on nutrient sequences during meals suggest that consuming carbohydrates last lowers postprandial glucose excursions more than consuming carbohydrates first. However, this phenomenon has not been studied in gestational diabetes mellitus (GDM). Ten women with GDM consumed the same caloric foods in different sequences over five successive days: (A) dish first, followed by carbohydrate and soup last; (B) carbohydrate first, followed by dish and soup last; (C) soup first, followed by dish and carbohydrate last; (D) three meals a day ad libitum; and (E) six meals a day as ad libitum. Continuous glucose monitoring (CGM) was used to assess diurnal glycemia. Decreases in mean glucose levels and the largest glucose levels in A were similar to group C. The peak glucose of breakfast and lunch in group B was more significant than in groups A and C. The B meal pattern showed more marked glycemic excursions than groups A and C. Increasing the number of meals reduced the peak glucose level and the glycemic excursions with the same total calories. Changing meal sequences or increasing the number of meals may reduce glycemic excursions in GDM. Our trial was registered retrospectively and the trial registration number is ChiCTR2200057044.

Effect of short‐term acute moderate‐intensity resistance exercise on blood glucose in older patients with type 2 diabetes mellitus and sarcopenia

To investigate the effects of short-term acute moderate-intensity resistance exercise on blood glucose in older patients with type2 diabetes mellitus and sarcopenia using ambulatory glucose monitoring technology. This is a prospective intervention of an own-controlled before-and-after cohort study. A total of 24 older type2 diabetes mellitus patients who met the enrollment criteria were selected, including 12 cases in the sarcopenia and 12 in the non-sarcopenia groups. First, they wore ambulatory glucose monitoring devices (Medtronic, Ipro2) and retained baseline data. Then they wore Ipro2 again and carried out two sessions of resistance exercise on alternate days. Blood glucose level, blood glucose fluctuation, and time in target range on the contrast and exercise days were compared and analyzed in both groups. The area under the curve of glucose level across 24 h and the mean blood glucose post exercise decreased (P <0.05) in the sarcopenia group. On the exercise day, the coefficient of variation of glucose, the largest amplitude of glycemic excursions, amplitude of postprandial glucose excursions and low blood glucose index decreased, whereas the time in target range increased (P < 0.05). Short-term acute moderate-intensity resistance exercise is an effective and safe exercise modality, which can reduce blood glucose levels, blood glucose fluctuations and the risk of hypoglycemia, as well as improve the time in target range for older patients with type2 diabetes mellitus and sarcopenia. Geriatr Gerontol Int 2022; 22: 653-659.

Reduction in Postprandial Peak Glucose With Increased Technosphere Insulin Dosage.

Technosphere Insulin (TI) is an ultra-rapid-acting inhaled insulin. This study assessed the mean peak two-hour postprandial glucose concentration with the initial TI dose (dose 1) calculated per the current label (United State Prescribing Information) compared with a ~2× higher dose (dose 2). Secondary objectives were to evaluate hypoglycemia within the two-hour postprandial period, evaluate change in forced expiratory volume in one second (FEV1) before and after the two-hour postprandial period, and monitor for other adverse events. Twenty patients with diabetes, on basal-bolus insulin therapy, received an initial dose 1 of TI followed by the higher dose 2, one to three days later. Subjects received an identical meal for both visits, and TI doses were administered immediately prior to the meal. The higher dose 2 provided significant reductions in mean postprandial glucose excursion (PPGE) in the two-hour postprandial period starting from 45 minutes (P = .008) to 120 minutes (P < .0001). Mean peak glucose was reduced from 228.6 to 179.3 mg/dL (P < .001) at two hours. Two hypoglycemic events (one level 1, one level 2) were observed in a single subject during the two-hour postprandial period with dose 2. There were no significant changes in FEV1 after either dose of TI. The higher dose 2 reduced PPGE versus the current label recommended dose 1 within the two-hour postprandial timeframe without any new safety concerns. When confirmed with a larger study, this higher TI dosing recommendation may help patients and clinicians minimize immediate postprandial hyperglycemia when titrating TI for prandial glucose control.

PLG-007 and Its Active Component Galactomannan-α Competitively Inhibit Enzymes That Hydrolyze Glucose Polymers.

PLG-007 is a developmental therapeutic compound that has been clinically shown to reduce the magnitude of postprandial glucose excursions and has the potential to be an adjunct treatment for diabetes and inflammatory-related diseases. The present investigation is aimed at understanding the molecular mechanism of action of PLG-007 and its galactomannan (GM) components GMα and GMβ (in a 1:4 mass ratio, respectively) on enzyme (i.e., α-amylase, maltase, and lactase) hydrolysis of glucose polymers using colorimetric assays and 13C HSQC NMR spectroscopy. The starch–iodine colorimetric assay indicated that GMα strongly inhibits α-amylase activity (~16-fold more potent than GMβ) and thus is the primary active component in PLG-007. 13C HSQC experiments, used to follow the α-amylase-mediated hydrolysis of starch and amylopectin, further demonstrate the α-amylase inhibitory effect of GMα via α-amylase-mediated hydrolysis of starch and amylopectin. Maltohexaose (MT6) was used to circumvent the relative kinetic complexity of starch/amylopectin degradation in Michaelis–Menten analyses. The Vmax, KM, and Ki parameters were determined using peak volume integrals from 13C HSQC NMR spectra. In the presence of PLG-007 with α-amylase and MT6, the increase in KM from 7.5 ± 0.6 × 10−3 M (control) to 21 ± 1.4 × 10−3 M, with no significant change in Vmax, indicates that PLG-007 is a competitive inhibitor of α-amylase. Using KM values, Ki was estimated to be 2.1 ± 0.9 × 10−6 M; however, the microscopic Ki value of GMα is expected to be larger as the binding stoichiometry is likely to be greater than 1:1. Colorimetric assays also demonstrated that GMα is a competitive inhibitor of the enzymes maltase and lactase. Overall, this study provides insight as to how PLG-007 (GMα) is likely to function in vivo.

Endogenous Glucose-Dependent Insulinotropic Polypeptide Contributes to Sitagliptin-Mediated Improvement in β-Cell Function in Patients With Type 2 Diabetes.

Dipeptidyl peptidase 4 (DPP-4) degrades the incretin hormones glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide (GIP). DPP-4 inhibitors improve glycemic control in type 2 diabetes, but the importance of protecting GIP from degradation for their clinical effects is unknown. We included 12 patients with type 2 diabetes (mean ± SD BMI 27 ± 2.6 kg/m2, HbA1c 7.1 ± 1.4% [54 ± 15 mmol/mol]) in this double-blind, placebo-controlled, crossover study to investigate the contribution of endogenous GIP to the effects of the DPP-4 inhibitor sitagliptin. Participants underwent two randomized, 13-day treatment courses of sitagliptin (100 mg/day) and placebo, respectively. At the end of each treatment period, we performed two mixed-meal tests with infusion of the GIP receptor antagonist GIP(3-30)NH2 (1,200 pmol/kg/min) or saline placebo. Sitagliptin lowered mean fasting plasma glucose by 1.1 mmol/L compared with placebo treatment. During placebo treatment, postprandial glucose excursions were increased during GIP(3-30)NH2 compared with saline (difference in area under the curve ± SEM 7.3 ± 2.8%) but were unchanged during sitagliptin treatment. Endogenous GIP improved β-cell function by 37 ± 12% during DPP-4 inhibition by sitagliptin. This was determined by the insulin secretion rate/plasma glucose ratio. We calculated an estimate of the absolute sitagliptin-mediated impact of GIP on β-cell function as the insulinogenic index during sitagliptin treatment plus saline infusion minus the insulinogenic index during sitagliptin plus GIP(3-30)NH2. This estimate was expressed relative to the maximal potential contribution of GIP to the effect of sitagliptin (100%), defined as the difference between the full sitagliptin treatment effect, including actions mediated by GIP (sitagliptin + saline), and the physiological response minus any contribution by GIP [placebo treatment + GIP(3-30)NH2]. We demonstrate insulinotropic and glucose-lowering effects of endogenous GIP in patients with type 2 diabetes and that endogenous GIP contributes to the improved β-cell function observed during DPP-4 inhibition.

Efficacy and Safety of Ultra-Rapid Lispro in Younger and Older Patients with Type 2 Diabetes: Randomized Double-Blind PRONTO-T2D Study.

IntroductionUltra-rapid lispro (URLi) is a new prandial insulin lispro formulation. In the PRONTO-T2D study, URLi, in a basal-bolus regimen with glargine or degludec, was non-inferior to lispro (Humalog®) for HbA1c reduction and superior for postprandial glucose (PPG) control. We evaluated the efficacy and safety of URLi compared to lispro in younger versus older patients in PRONTO-T2D.MethodsPRONTO-T2D was a phase 3, 26-week, double-blind, treat-to-target study in people with type 2 diabetes. In this sub-group analysis, we compared URLi to lispro on the change from baseline in HbA1c and rate of level 2 hypoglycemia (< 54 mg/dl) in patients aged < 65 (N = 406) and ≥ 65 years (N = 267).ResultsAt baseline, patients < 65 versus ≥ 65 years had mean age of 54.9 versus 69.2 years and duration of diabetes 14.6 versus 19.4 years. Mean HbA1c at screening and randomization was 8.35 and 7.34%, respectively, in patients < 65 years, and 8.21 and 7.23%, respectively, in patients ≥ 65 years. At endpoint, mean HbA1c with URLi versus lispro was 6.92 versus 6.90%, respectively, in patients < 65 years and 6.89 versus 6.79%, respectively, in patients ≥ 65 years. URLi significantly reduced 1- and 2-h PPG excursions with a standardized meal test in both age groups: between-treatment differences at 1-h postmeal for younger and older patients was – 9.8 and – 15.1 mg/dl, respectively; and at 2-h postmeal, – 18.7 and – 15.1 mg/dl, respectively, all p < 0.05. Severe and nocturnal hypoglycemia were similar between groups. The relative rate (URLi/Humalog) of level 2 hypoglycemia was lower in older versus younger patients, with a significant treatment-by-age interaction observed. No differential treatment effects were noted for insulin dose, weight, and fasting and maximum glucose after the meal test.ConclusionsURLi, in a basal-bolus regimen, resulted in endpoint HbA1c < 7% and significantly lower PPG excursions compared to lispro in both age groups, with reduced level 2 hypoglycemia in older versus younger patients.Trial registrationClinicalTrials.gov, NCT03214380.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01290-4.

Efficacy and safety of oral insulin versus placebo for patients with diabetes mellitus: A systematic review and meta-analysis.

Compliance to insulin injections is poor due to difficulty in subcutaneous administration. Hence, there is a need of an oral formulation of insulin. Oral insulin is currently under investigation. The present analysis aimed to evaluate oral insulin versus placebo for patients with diabetes mellitus (type-1 and type-2). Results from PUBMED and MEDLINE were searched and compiled from January 1, 2000 to January 9, 2020. Postprandial blood glucose excursions (2PPG), glycated hemoglobin (HbA1c), C-peptide levels, and immune antibody (IAA) levels were compared between the arms. In addition, time to diabetes and safety of oral insulin were discussed. Thirteen out of 1778 trials were included to the analysis. Oral insulin was found to induce significant reduction in mean 2PPG excursion (standardized mean difference [SMD]: -1.94, 95% CI: -3.20 to -0.68, I² = 91.81, P &lt; 0.005) and mean IAA levels (SMD:-0.49, 95% CI: -0.82 to -0.16, I² = 27.12, P &lt; 0.005) compared with placebo. Mean C-peptide levels were notably lower in the oral insulin arm. However, the difference was not statistically significant. No significant difference was observed in mean HbA1c levels. The rate of development of type-1 diabetes was not significantly influenced by oral insulin. No deaths or treatment-related serious adverse events were reported. Oral insulin provided significant benefits for acute maintenance of diabetes mellitus. It elicited lower immune response and was well tolerated. This new formulation has potential to augment the management of diabetes mellitus. More studies are required to assess its long-term effects.

Effects of soy protein isolate and soy peptide preload on gastric emptying rate and postprandial glycemic control in healthy humans

BackgroundThis study aims to compare the effects of soy protein isolate (SPI) and soy peptide (PEP) preload 30 min before a 75-g oral glucose tolerance test (OGTT) on the gastric emptying rate, plasma insulin, and blood glucose responses.MethodsNine healthy young subjects were evaluated on four occasions. The participants consumed a 200-ml solution containing either 20 g of SPI or PEP in experiment 1. In experiment 2, 30 min after consuming either 20 g of SPI or PEP solutions, an OGTT was performed to evaluate the individual glycemic response. The gastric emptying rate was measured by the 13C-sodium acetate breath test. Blood glucose and plasma insulin were measured before and after consuming either the SPI or PEP solutions and during the OGTT.ResultsIn experiment 1, plasma insulin levels were higher 30 min after consuming the PEP solution than after the SPI solution. PEP resulted in a faster gastric emptying rate than SPI. In experiment 2, just before performing the OGTT, the plasma insulin response was higher for PEP than for SPI. Fifteen minutes after starting the OGTT, the blood glucose response was lower after consuming PEP than after SPI. The gastric emptying rate tended to be faster after consuming PEP than after SPI (p = 0.08).ConclusionA PEP preload might be slightly more effective for the suppression of postprandial blood glucose excursion compared with SPI; thus, a PEP preload potentially induces an enhanced insulin response just before the OGTT.

Continuous glucose monitoring system profile of women diagnosed as gestational diabetes mellitus by International Association of Diabetes and Pregnancy Study Groups criteria and labeled as normoglycemic by alternate criteria in early pregnancy.

Aims/IntroductionWe aimed to evaluate and compare continuous glucose monitoring system (CGMS)‐based glycemic parameters in women in early pregnancy (<20 weeks of gestation) who were classified as: (i) gestational diabetes mellitus (GDM) by the International Association of Diabetes and Pregnancy Study Groups (IADPSG), but normoglycemia by alternate (UK National Institute for Health and Care Excellence, Canadian Diabetes Association and Diabetes in Pregnancy Study group of India) criteria; and (ii) normoglycemia by both (IADPSG and alternate) criteria.Material and MethodsIn this cross‐sectional study, eligible women underwent standard 75‐g oral glucose tolerance test, followed by the placement of a CGMS. Glycemia‐related parameters were calculated using the standard approach for CGMS data in pregnancy.ResultsWe enrolled 96 women at 14.0 ± 3.2 weeks of gestation. Of the women diagnosed as GDM by IADPSG criteria, 34.2%, 26.3% and 44.7% were classified as normoglycemic by UK National Institute for Health and Care Excellence, Canadian Diabetes Association and Diabetes in Pregnancy Study group of India criteria, respectively. Mean 1‐h postprandial glucose and time above range were significantly higher in women who were GDM by IADPSG, but normoglycemia by Canadian Diabetes Association criteria, compared with women with normoglycemia using both criteria. Similarly, mean 1‐h postprandial glucose, 2‐h postprandial glucose, peak postprandial glucose, 1‐h postprandial glucose excursion and time above range were significantly higher in women who were not identified as GDM by the UK National Institute for Health and Care Excellence criteria. Finally, women missed by the Diabetes in Pregnancy Study group of India criteria had significantly higher mean 1‐h postprandial glucose, 2‐h postprandial glucose, peak postprandial glucose, postprandial glucose excursion, 24‐h glucose and time above range parameters.ConclusionsMore than one‐quarter of women diagnosed as GDM by IADPSG criteria are not identified by alternate criteria. Such women are significantly different from normoglycemic women in terms of several CGMS‐based glycemic parameters of clinical significance.

What is the value of faster acting prandial insulin? Focus on ultra rapid lispro.

Rapid‐acting insulins (RAIs) have been instrumental in the management of diabetes because of their improved postprandial glucose (PPG) control compared with regular human insulin. However, their absorption rate and time action following subcutaneous administration still falls short of the normal physiological response to meal consumption, increasing the risk of early postmeal hyperglycaemia and late postmeal hypoglycaemia. Increased demand for faster acting insulins, which can quickly control PPG excursions without increasing the risk of late hypoglycaemia, led to the development of ultra‐rapid–acting insulins, including ultra‐rapid lispro (URLi). URLi is a novel formulation of insulin lispro with accelerated absorption driven by two excipients: treprostinil, which increases local vasodilation, and citrate, which increases local vascular permeability. Clinical pharmacology studies consistently showed an earlier onset and shorter duration of action with URLi compared with Lispro. In a head‐to‐head study with Faster aspart, Aspart and Lispro, URLi was absorbed faster, provided earlier insulin action, and more closely matched physiological glucose response than the other insulins tested. URLi's unique pharmacokinetic properties increase its potential for improved PPG control beyond that achieved with RAIs. Indeed, in pivotal phase 3 trials, URLi was superior to Lispro for PPG control both at 1 and 2 hours after a meal in type 1 and type 2 diabetes with multiple daily injections, and in type 1 diabetes with continuous subcutaneous insulin infusion. This was achieved without increasing the risk of hypoglycaemia. In this review, we focus on the clinical and pharmacological evidence for URLi in the treatment of diabetes and discuss the potential benefits and considerations with URLi compared with RAIs.

Additional insulin dosing for fat and protein in children with type 1 diabetes using multiple daily injections

High-fat high-protein (HFHP) meals are associated with post-prandial hyperglycemia in type 1 diabetes (T1D), administration of additional insulin for such meals is recommended in order to optimize glucose levels. Optimal timing of additional insulin for HFHP meals in children and young people receiving multiple daily injections (MDI) remains unclear. To investigate the glycemic impact of additional insulin doses given before or after eating a HFHP meal in children with T1D using MDI. A randomized, controlled three period crossover trial of 27 participants aged 13 years (6.1-17.7) at two Pediatric Diabetes centers was conducted. Additional rapid-acting insulin for the fat-protein content of a standardized HFHP meal was given at three time points calculated using an algorithm extrapolated from current evidence base and clinical recommendations. Post-prandial glucose (PPG) parameters were calculated for 420minutes using continuous glucose monitoring. The primary outcome was mean PPG excursion. Secondary outcomes included peak glucose, time to peak and hypoglycemia incidence. There was no difference in post-prandial glucose parameters when additional HFHP insulin was administered at mean glucose excursion (mmol/L) (SE): 1.9(0.7), 1.2(0.7), 2.5(0.7); p= 0.5); mean peak glucose (mmol/L)(SE): 10.9(0.9), 11.5(0.8), 11.5(0.9); p= 0.9; time to peak glucose (mins)(SE): 82.3(35.4), 113.6(30.9), 95.1(32.1); p= 0.8. Mild hypoglycemia was common (55%) in all groups (p= 0.97). We found no benefit in giving additional insulin as a split dose for HFHP meals in children using MDI, mild hypoglycemia was common. Future studies would benefit from refinement of the insulin dose algorithm.

108-LB: Ultrarapid Lispro (URLi) Improved Postprandial Glucose (PPG) Excursion vs. Humalog (HL) in Predominantly Chinese Adult Patients with Type 2 Diabetes (T2D)

URLi is a novel formulation of insulin lispro developed to better match physiological insulin response to a meal that demonstrates faster absorption and onset of action than HL. This study aimed to evaluate the efficacy and safety of URLi vs. HL in predominantly Chinese adult patients with T2D. It was a Phase 3, randomized, double-blind study, in which patients with T2D randomly received URLi (395 patients) or HL (200 patients) plus glargine or degludec for 26 weeks. The primary endpoint was the treatment difference in the change in HbA1c from baseline to Week 26 (noninferiority margin 0.4%) . The treatment differences in the 1- and 2-hour PPG excursions at Week 26 were assessed as the multiplicity-adjusted endpoints. URLi achieved noninferiority to HL on change in HbA1c with least squares mean difference (95% confidence interval) of 0.07% (-0.07, 0.21) . URLi was superior to HL in controlling 1-hour (4.8 mmol/L vs. 5.6 mmol/L, P &amp;lt;0.001) and 2-hour PPG excursions (6.2 mmol/L vs. 7.4 mmol/L, P &amp;lt;0.001) at Week 26. A greater decrease in daily mean 1- and 2-hour PPG excursions with URLi than HL from baseline to Week 26 was observed in the 10-point self-monitored blood glucose profile. Increase in the dose of bolus insulin from baseline to Week 26 was slightly higher with URLi than HL (0.21 U/kg/day vs. 0.18 U/kg/day, P=0.045) . During the 26-week treatment period, both groups showed similar and low rate and incidence of severe hypoglycemia and documented symptomatic hypoglycemia. The incidences of serious adverse events and treatment-emergent adverse events were comparable between both groups. URLi vs. HL in a basal-bolus regimen demonstrated noninferior glycemic control as assessed by HbA1c and superior control on PPG excursions in predominantly Chinese adult patients with T2D with a similar safety profile. Disclosure J. Zhou: n/a. S. Chen: None. J. Cheng: Employee; Eli Lilly and Company. L. Shen: Employee; Eli Lilly and Company. J. Zhu: Employee; Eli Lilly and Company. Y. Lou: None. Y. Bao: None. W. Jia: None. Funding Eli Lilly and Company