Effects of Resistant Starch Interventions on Metabolic Biomarkers in Pre-Diabetes and Diabetes Adults

Simple lifestyle changes can prevent or delay the onset of type 2 diabetes mellitus (T2DM). In addition to maintaining a physically active way of life, the diet has become one of the bases in managing TD2M. Due to many studies linking the ability of resistant starch (RS) to a substantial role in enhancing the nutritional quality of food and disease prevention, the challenge of incorporating RS into the diet and increasing its intake remains. Therefore, we conducted this review to assess the potential benefits of RS on metabolic biomarkers in pre-diabetes and diabetes adults based on available intervention studies over the last decade. Based on the conducted review, we observed that RS intake correlates directly to minimize possible effects through different mechanisms for better control of pre-diabetic and diabetic conditions. In most studies, significant changes were evident in the postprandial glucose and insulin incremental area under the curve (iAUC). Comparative evaluation of RS consumption and control groups also showed differences with inflammatory markers such as TNF-α, IL-1β, MCP-1, and E-selectin. Only RS2 and RS3 were extensively investigated and widely reported among the five reported RS types. However, a proper comparison and conclusion are deemed inappropriate considering the variations observed with the study duration, sample size, subjects and their metabolic conditions, intervention doses, and the intervention base products. In conclusion, this result provides interesting insights into the potential use of RS as part of a sustainable diet in diabetes management and should be further explored in terms of the mechanism involved.

Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial

<strong>Objective: </strong>We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin-receptor-1-b gene (<i>MTNR1B</i>).<strong> </strong> <p><strong>Research Design and Methods:</strong> In a Spanish natural late eating population, a randomized, cross-over study design was performed, following an 8-h fast. Each participant <strong>(n=845) </strong>underwent two evening 2-h 75g oral glucose tolerance tests (OGTT): an early condition scheduled 4 hours prior to habitual bedtime <strong>(“early dinner-timing”)</strong>, and a late condition scheduled 1 hour prior to habitual bedtime <strong>(“late dinner-timing”)</strong>, simulating an early and a late dinner timing, respectively.<strong> </strong>Differences in postprandial glucose and insulin responses were determined using incremental area under the curve (AUC) calculated by the trapezoidal method between <strong>early and late dinner-timing.</strong><strong></strong></p> <p><strong>Results:</strong> <strong>Melatonin serum levels were </strong>3.5-fold <strong>higher in the late <i>vs. </i>early condition, with late dinner-timing resulting in </strong>6.7% <strong>lower insulin</strong> <strong>area-under-the-curve (AUC) and </strong>8.3%<strong> higher glucose</strong> <strong>AUC. In the late condition<i> MTNR1B</i> G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in </strong>β-cell <strong>function (<i>P_int</i>AUCgluc=0.009, <i>P_int</i>CIR=0.022, <i>P_int</i>DI=0.018).</strong></p> <p><strong>Conclusions:</strong> <strong>Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impair glucose tolerance, especially in <i>MTNR1B</i> G-risk-allele carriers<i>, </i>attributable to insulin secretion defects.</strong></p>

Effect of linagliptin plus insulin in comparison to insulin alone on metabolic control and prognosis in hospitalized patients with SARS-CoV-2 infection

To evaluate the effect of the combination of linagliptin and insulin on metabolic control and prognosis in hospitalized patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and hyperglycemia. A parallel double-blind randomized clinical trial including hospitalized patients with SARS-CoV-2 infection and hyperglycemia, randomized to receive 5 mg linagliptin + insulin (LI group) or insulin alone (I group) was performed. The main outcomes were the need for assisted mechanical ventilation and glucose levels during hospitalization. Subjects were screened for eligibility at hospital admission if they were not with assisted mechanical ventilation and presented hyperglycemia, and a total of 73 patients with SARS-CoV-2 infection and hyperglycemia were randomized to the LI group (n = 35) or I group (n = 38). The average hospital stay was 12 ± 1 vs 10 ± 1 days for the I and LI groups, respectively (p = 0.343). There were no baseline clinical differences between the study groups, but the percentage of males was higher in the LI group (26 vs 18, p = 0.030). The improvements in fasting and postprandial glucose levels were better in the LI group that the I group (122 ± 7 vs 149 ± 10, p = 0.033; and 137 ± 7 vs 173 ± 12, p = 0.017, respectively), and insulin requirements tended to be lower in the LI group than the I group. Three patients in the LI group and 12 in the I group required assisted mechanical ventilation (HR 0.258, CI 95% 0.092–0.719, p = 0.009); 2 patients in the LI group and 6 in the I group died after a follow-up of 30 days (p = 0.139). No major side effects were observed. The combination of linagliptin and insulin in hospitalized patients with SARS-CoV-2 infection and hyperglycemia reduced the relative risk of assisted mechanical ventilation by 74% and improved better pre and postprandial glucose levels with lower insulin requirements, and no higher risk of hypoglycemia.This study is registered at clinicaltrials.gov, number NCT04542213 on 09/03/2020.

Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial

<strong>Objective: </strong>We tested whether the concurrence of food intake and elevated concentration of endogenous melatonin, as occurs in late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin-receptor-1-b gene (<i>MTNR1B</i>).<strong> </strong> <p><strong>Research Design and Methods:</strong> In a Spanish natural late eating population, a randomized, cross-over study design was performed, following an 8-h fast. Each participant <strong>(n=845) </strong>underwent two evening 2-h 75g oral glucose tolerance tests (OGTT): an early condition scheduled 4 hours prior to habitual bedtime <strong>(“early dinner-timing”)</strong>, and a late condition scheduled 1 hour prior to habitual bedtime <strong>(“late dinner-timing”)</strong>, simulating an early and a late dinner timing, respectively.<strong> </strong>Differences in postprandial glucose and insulin responses were determined using incremental area under the curve (AUC) calculated by the trapezoidal method between <strong>early and late dinner-timing.</strong><strong></strong></p> <p><strong>Results:</strong> <strong>Melatonin serum levels were </strong>3.5-fold <strong>higher in the late <i>vs. </i>early condition, with late dinner-timing resulting in </strong>6.7% <strong>lower insulin</strong> <strong>area-under-the-curve (AUC) and </strong>8.3%<strong> higher glucose</strong> <strong>AUC. In the late condition<i> MTNR1B</i> G-allele carriers had lower glucose tolerance than non-carriers. Genotype differences in glucose tolerance were attributed to reductions in </strong>β-cell <strong>function (<i>P_int</i>AUCgluc=0.009, <i>P_int</i>CIR=0.022, <i>P_int</i>DI=0.018).</strong></p> <p><strong>Conclusions:</strong> <strong>Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impair glucose tolerance, especially in <i>MTNR1B</i> G-risk-allele carriers<i>, </i>attributable to insulin secretion defects.</strong></p>

Changes in glycemic variability, gastric emptying and vascular endothelial function after switching from twice-daily to once-weekly exenatide in patients with type 2 diabetes: a subpopulation analysis of the twin-exenatide study

Background We investigated the changes in blood glucose fluctuation, gastric emptying, and vascular endothelial function by switching from an exenatide twice-daily formulation (BID) to a once-weekly formulation (QW) since the evaluation of postprandial glucose excursion and glycemic variability (GV) by continuous glucose monitoring (CGM) after switching was lacking. Methods Twenty-nine patients with type 2 diabetes treated with exenatide BID were included in this study and switched to exenatide QW for 24 weeks. GV assessed by CGM, gastric emptying (by 13 C-acetate breath test) and vascular endothelial function (by reactive hyperemia - peripheral arterial tonometry) were evaluated at baseline and 24 weeks after switching. Results HbA1c decreased significantly from the baseline to week 24, while postprandial glucose levels after breakfast and dinner significantly increased (both P <0.05). However, the increases in GV indices were modest and not statistically significant at week 24. Vascular endothelial function was also not significantly changed after switching (P >0.05). Gastric emptying was significantly accelerated at week 24 (Tmax 83.4 ± 12.1 min vs. 58.2 ± 16.4 min) (P <0.001) and correlated with increased postprandial glucose levels after breakfast and dinner (both P <0.05). Conclusions Despite the increase in postprandial glucose associated with accelerated gastric emptying after switching from exenatide BID to QW, change in GV was modest and no significant deterioration in vascular endothelial function was observed after switching. These results support the superiority of treatment with exenatide QW over exenatide BID in clinical practice; however, attention should be paid to the monitoring and management of postprandial glucose levels when selecting exenatide QW. Trial registration Clinical trial registry number; UMIN000016390 and jRCTs031180320. Approval date of Registry and the Registration: December 12, 2014.

Precision Nutrition Model Predicts Glucose Control of Overweight Females following the Consumption of Potatoes High in Resistant Starch

Individual glycemic responses following dietary intake result from complex physiological processes, and can be influenced by physical properties of foods, such as increased resistant starch (RS) from starch retrogradation. Predictive equations are needed to provide personalized dietary recommendations to reduce chronic disease development. Therefore, a precision nutrition model predicting the postprandial glucose response (PPGR) in overweight women following the consumption of potatoes was formulated. Thirty overweight women participated in this randomized crossover trial. Participants consumed 250 g of hot (9.2 g RS) or cold (13.7 g RS) potatoes on two separate occasions. Baseline characteristics included demographics, 10-day dietary records, body composition, and the relative abundance (RA) and α-diversity of gut microbiota. Elastic net regression using 5-fold cross-validation predicted PPGR after potato intake. Most participants (70%) had a favorable PPGR to the cold potato. The model explained 32.2% of the variance in PPGR with the equation: 547.65 × (0 [if cold, high-RS potato], ×1, if hot, low-RS potato]) + (BMI [kg/m2] × 40.66)—(insoluble fiber [g] × 49.35) + (Bacteroides [RA] × 8.69)—(Faecalibacterium [RA] × 73.49)—(Parabacteroides [RA] × 42.08) + (α-diversity × 110.87) + 292.52. This model improves the understanding of baseline characteristics that explain interpersonal variation in PPGR following potato intake and offers a tool to optimize dietary recommendations for a commonly consumed food.

A Deep Learning Framework for Automatic Meal Detection and Estimation in Artificial Pancreas Systems

Current artificial pancreas (AP) systems are hybrid closed-loop systems that require manual meal announcements to manage postprandial glucose control effectively. This poses a cognitive burden and challenge to users with T1D since this relies on frequent user engagement to maintain tight glucose control. In order to move towards fully automated closed-loop glucose control, we propose an algorithm based on a deep learning framework that performs multitask quantile regression, for both meal detection and carbohydrate estimation. Our proposed method is evaluated in silico on 10 adult subjects from the UVa/Padova simulator with a Bio-inspired Artificial Pancreas (BiAP) control algorithm over a 2 month period. Three different configurations of the AP are evaluated -BiAP without meal announcement (BiAP-NMA), BiAP with meal announcement (BiAP-MA), and BiAP with meal detection (BiAP-MD). We present results showing an improvement of BiAP-MD over BiAP-NMA, demonstrating 144.5 ± 6.8 mg/dL mean blood glucose level (−4.4 mg/dL, p< 0.01) and 77.8 ± 6.3% mean time between 70 and 180 mg/dL (+3.9%, p< 0.001). This improvement in control is realised without a significant increase in mean in hypoglycaemia (+0.1%, p= 0.4). In terms of detection of meals and snacks, the proposed method on average achieves 93% precision and 76% recall with a detection delay time of 38 ± 15 min (92% precision, 92% recall, and 37 min detection time for meals only). Furthermore, BiAP-MD handles hypoglycaemia better than BiAP-MA based on CVGA assessment with fewer control errors (10% vs. 20%). This study suggests that multitask quantile regression can improve the capability of AP systems for postprandial glucose control without increasing hypoglycaemia.

Investigation of the effects of animal and plant based milk on satiety and postprandial glucose levels

The aim of this study was to determine the short-term effects of animal and plant-based milk consumption on postprandial glycemia, toughness, food intake of healthy individuals. Cow milk and soymilk were used as the test drink and com-mercial fruit juice as the control group. In the study in which 19 healthy adult subjects participated, fast-ing blood glucose and post-prandial blood glucose ana-lysed, visual analog scale and appetite were ques-tioned. Then, 24-hour food comsumption records were taken and energy and mac-ronutrients were calculated and compared. While the highest energy intake was on the day that cow milk was consumed, no signifi-cant relationship was found between test groups in terms of energy and macronutrient intake (p>0.05). It was de-termined that the difference between fasting and post-prandial blood glucose was in the week in which the highest cow milk was con-sumed and this change was significant (p< 0.05). It was thought that the satiety ef-fect of cow milk may be higher than that of soy milk due to its animal protein and saturated fat content.

Utility of Continuous Glucose Monitoring vs. Meal Study in Detecting Hypoglycemia After Gastric Bypass

Context Gastric bypass (GB) increases postprandial glucose excursion, which in turn can predispose to the late complication of hypoglycemia. Diagnosis remains challenging and requires documentation of symptoms associated with low glucose, and relief of symptom when glucose is normalized (Whipple’s triad). Objective To compare the yield of mixed meal test (MMT) and continuous glucose monitoring system (CGMS) in detecting hypoglycemia after gastric bypass surgery (GB). Setting The study was conducted at General Clinical Research Unit, Cincinnati Children’s Hospital (Cincinnati, OH, United States). Methods Glucose profiles were evaluated in 15 patients with documented recurrent clinical hypoglycemia after GB, 8 matched asymptomatic GB subjects, and 9 healthy weight-matched non-operated controls using MMT in a control setting and CGMS under free-living conditions. Results Patients with prior GB had larger glucose variability during both MMT and CGMS when compared to non-surgical controls regardless of their hypoglycemic status. Sensitivity (71 vs. 47 %) and specificity (100 vs. 88 %) of MMT in detecting hypoglycemia was superior to CGMS. Conclusions Our findings indicate that a fixed carbohydrate ingestion during MMT is a more reliable test to diagnose GB-related hypoglycemia compared to CGMS during free-living state.

Comparative Evaluation of BGR-34 and Sitagliptin in Diabetic Subjects-Open Labelled Randomised Parallel Clinical Study

This article is mainly concerned with the simultaneous open model clinical study of the drug named sitagliptin, a potent hyperglycaemic drug against a novel entity of the natural origin BGR- 34 in diabetic subjects. This was a 3-month randomized, parallel, comparative study. One hundred subjects were planned to be included in the study. The patients were randomly divided into two groups and according to the appropriate sample size analysis, both groups consisted of 100 patients, following the inclusion and exclusion criteria. A total of 90 patients (both male and female) of the mean patient age 30-65 years with the type 2 diabetes were enrolled in the phase 4 of this study and then the data were analyzed on the basis of the different test which included HbA1c (glycated haemoglobin), RBS (random blood sugar), FBS (fasting blood sugar) and PPG (postprandial glucose) values. After completion of the data calibration, the results were analyzed and as a result 10-20% decreased values of HBA1C values accompanied with the RBS, FBS and PPG values were seen in the patients undergoing a 12-week course with BGR-34. Based on the results obtained in the present study, it can be concluded that BGR-34 is effective in reducing high blood sugar levels and this reflects that the BGR-34 therapy is more effective drug in the treatment of diabetes suggesting that it is better in efficacy, and reliability with little or no adverse effects.