Blood Glucose Excursions Research Articles

A Green Light-Activated Insulin Depot with Ultrafast In Vivo Efficiency in the Subcutaneous Space.

In this work, for the first time, we demonstrate light control of a therapeutic protein's release from a depot in the subcutaneous layer of the skin. The subcutaneous layer is a standard location for therapeutic protein depots due to its large size and ease of access, but prior attempts to utilize this space failed because insufficient light can reach this deeper layer. An analysis of existing biophysical literature suggested that an increase of photoactivation wavelength from 365 to 500 nm could allow an increase of depot irradiation in the subcutaneous by >100-fold. We therefore used a green light-activated thio-coumarin-based material and demonstrated robust release of a therapeutic, insulin, in response to skin illumination with an LED light source. We further demonstrated that this release is ultrafast, as fast or faster than any commercially used insulin, while maintaining the native insulin sequence. This release of insulin was then accompanied by a robust reduction in blood glucose, demonstrating the retention of bioactivity despite the synthetic processing required to generate the material. In addition, we observed that the material exhibits slow basal release of insulin, even in the absence of light, potentially through biochemical or photochemical unmasking of insulin. Thus, these materials can act much like the healthy pancreas does: releasing insulin at a slow basal rate and then, upon skin irradiation, releasing an ultrafast bolus of native insulin to reduce postprandial blood glucose excursions.

Immediate Impact of Switching from Dipeptidyl Peptidase4 (DPP4) Inhibitors to Low-Dose (0.3mg) Liraglutide on Glucose Profiles: A Retrospective Observational Study.

As treatment agents for diabetes, liraglutide is a long-acting glucagon-like peptide1 receptor agonist, and dipeptidyl peptidase4 (DPP4) inhibitors are widely used because of their safety and tolerability. Regular treatment with liraglutide has been reported to significantly reduce blood glucose levels, but the impact of low-dose (0.3mg) liraglutide on blood glucose levels immediately after treatment switching from a DPP4 inhibitor remains unknown. We conducted a single-arm, retrospective, observational study in 55 inpatients with type2 diabetes (T2D) to investigate the changes (Δ) in their blood glucose levels at six time points (6-point) from the day before (day-1) to the day after (day1) by switching the antidiabetic treatment from a DPP4 inhibitor to liraglutide 0.3mg (low-dose liraglutide) once daily. We also attempted to identify factors associated with the blood glucose-lowering effects of liraglutide. The median values of the changes in fasting, preprandial, and postprandial blood glucose levels and the fluctuations in the blood glucose levels expressed as the standard deviation of the 6-point blood glucose levels were significantly lower on day1 than on day-1 (P < 0.05, P < 0.0001, P < 0.0001, P < 0.01, respectively); there were no cases of severe hypoglycemia. The Δblood glucose levels were not associated with the baseline serum hemoglobin A1c values or with any markers of the insulin secreting capacity. There were no associations between the previously used blood glucose-lowering drug and the Δblood glucose levels. Switching from a DPP4 inhibitor to low-dose (0.3mg) liraglutide once daily significantly reduced the blood glucose levels and excursions of the blood glucose levels even from the very day after the treatment switch, with no serious adverse events.

Manipulation of Post-Prandial Hyperglycaemia in Type 2 Diabetes: An Update for Practitioners.

This review paper explores post-prandial glycemia in type 2 diabetes. Post-prandial glycemia is defined as the period of blood glucose excursion from immediately after the ingestion of food or drink to 4 to 6 hours after the end of the meal. Post-prandial hyperglycemia is an independent risk factor for cardiovascular disease with glucose "excursions" being more strongly associated with markers of oxidative stress than the fasting or pre-prandial glucose level. High blood glucose is a major promoter of enhanced free radical production and is associated with the onset and progression of type 2 diabetes. Oxidative stress impairs insulin action creating a vicious cycle where repeated post-prandial glucose spikes are key drivers in the pathogenesis of the vascular complications of type 2 diabetes, both microvascular and macrovascular. Some authors suggest post-prandial hyperglycemia is the major cause of death in type 2 diabetes. Proper management of post-prandial hyperglycemia could yield up to a 35% cut in overall cardiovascular events, and a 64% cut in myocardial infarction. The benefits of managing post-prandial hyperglycemia are similar in magnitude to those seen in type 2 diabetes patients receiving secondary prevention with statins - prevention which today is regarded as fundamental by all practitioners. Given all the evidence surrounding the impact of post-prandial glycemia on overall outcome, it is imperative that any considered strategy for the management of type 2 diabetes should include optimum dietary, pharma, and lifestyle interventions that address glucose excursion. Achieving a low post-prandial glucose response is key to prevention and progression of type 2 diabetes and cardiometabolic diseases. Further, such therapeutic interventions should be sustainable and must benefit patients in the short and long term with the minimum of intrusion and side effects. This paper reviews the current literature around dietary manipulation of post-prandial hyperglycemia, including novel approaches. A great deal of further work is required to optimize and standardize the dietary management of post-prandial glycemia in type 2 diabetes, including consideration of novel approaches that show great promise.

Glucose response to sugar challenge moderates the effect of insulin resistance on reinforcing value of sugar-sweetened yogurt

We have shown insulin resistance is associated with the choice of sugar-sweetened over monk fruit sweetened yogurt. This study extends this research by assessing the association between insulin resistance and reinforcing value for sugar versus monk fruit-sweetened yogurt, and testing the hypothesis that this effect is moderated by greater blood glucose response in people with insulin resistance. Eighteen people with overweight/obesity (BMI = 35.8 kg/m2, range 26.2–48.5) with varying degrees of insulin resistance (Homeostatic Model Assessment of Insulin Resistance (HOMA–IR) = 2.6, range of 0.6–8.0) had blood glucose measured for 2 h after a sugar challenge. Over six days, they consumed, in a double-blind fashion, novel flavored-colored sugar or monk fruit-sweetened yogurts, and the reinforcing value of sugar or monk fruit-sweetened yogurts and delay discounting (DD) were measured. HOMA-IR (r = 0.62, p = .006) and insulin (r = 0.51, p = .03) were related to the reinforcing value of sugar-sweetened, but not monk fruit-sweetened yogurt (r = −0.07, −0.10, respectively). The blood glucose area under the curve moderated the relationship between HOMA-IR and the reinforcing value of sugar-sweetened yogurt (p = .02). People with greater HOMA-IR and greater blood glucose excursions responded the most for sugar-sweetened yogurt. These results extend previous research and confirm the hypothesis that individual differences in response to sugar may activate brain reward centers and condition people to prefer high-sugar foods. DD was related to sugar reinforcement (r = −0.46, p = .03), consistent with the idea that those with high sugar reinforcement desire immediate gratification, and DD moderated the relationship between HOMA-IR and the reinforcing value of sugar-sweetened yogurt (p < .001). Research should test whether reducing insulin resistance would permit people with insulin resistance to choose lower-sugar foods.

Splitting Mealtime Insulin Doses for Mixed Fat and Protein Meals in Children and Adolescents with Type 1 Diabetes Using Multiple Daily Injection Regimen: A Randomized Cross-Over Trial

Aims. Assessment of the glycemic outcomes of increasing and splitting mealtime insulin doses for mixed fat and protein meals in pediatric patients with type 1 diabetes mellitus (T1DM) using multiple daily injection regimen and comparing the effects of regular insulin and fast-acting insulin on glycemic outcomes following those meals. Methods. This single-center, randomized, cross-over trial included 43 children and adolescents with T1DM randomly assigned to receive three interventional insulin doses for lunch meals over 3 consecutive days; Intervention A (100% insulin-to-carbohydrate ratio (ICR) dose given as premeal insulin lispro with an additional insulin sensitivity factor-calculated correction dose after 3 hr), Intervention B (130% ICR dose split into 60% premeal insulin lispro and 40% postmeal insulin lispro after 30 min), and Intervention C (130% ICR dose split into 60% premeal insulin lispro and 40% postmeal regular insulin after 30 min). The test meal consisted of two slices of pizza (weight: 150 g, carbohydrates: 40 g, fat: 15 g, protein: 20 g, and calories: 380 kcal). Postprandial blood glucose levels were monitored for 6 hr. Results. There were no significant differences in postprandial blood glucose excursions following the three interventions. However, Intervention C had a significantly lower late (3–6 hr) blood glucose area under the curve ( p = 0.01 ). Postprandial hypoglycemia developed in 12 participants (27.9%) following Interventions A and B and in 17 participants (39.5%) following Intervention C ( p = 0.32 ). Conclusions. Using regular insulin as a postmeal portion of increased and split insulin doses provided better late postprandial glycemic outcomes following mixed fat and protein meals. However, the amount of additional insulin used needs optimization to reduce the frequency of postprandial hypoglycemia. This trial is registered with NCT04783376.

Glucose variability and mood in people with type 1 diabetes using ecological momentary assessment

ObjectiveMood fluctuations related to blood glucose excursions are a commonly reported source of diabetes-distress, but research is scarce. We aimed to assess the relationship between real-time glucose variability and mood in adults with type 1 diabetes (T1D) using ecological momentary assessments. MethodsIn this prospective observational study, participants wore a masked continuous glucose monitor and received prompts on their smartphone 6 times a day to answer questions about their current mood (Profile Of Mood States (POMS)-SF (dimensions: Anxiety, Depressive symptoms, Anger, Fatigue, Vigor)) for 14 days. Mixed model analyses examined associations over time between daily Coefficient of Variation (CV) of blood glucose and mean and variability (CV) of POMS scores. Further, within-person differences in sleep and nocturnal hypoglycemia were explored. Results18 people with T1D (10 female, mean age 44.3 years) participated. A total of 264 out of 367 days (70.2%) could be included in the analyses. No overall significant associations were found between CV of blood glucose and mean and CV of POMS scores, however, nocturnal hypoglycemia moderated the associations between CV of blood glucose and POMS scales (mean Fatigue Estimate 1.998, p < .006, mean Vigor Estimate −3.308, p < .001; CV Anger Estimate 0.731p = 0.02, CV Vigor Estimate −0.525, p = .006). ConclusionWe found no overall relationship between real-time glycemic variability and mood per day. Further research into within-person differences such as sleep and nocturnal hypoglycemia is warranted.

1588-P: Translatable Modeling of Glucagon Actions in Human iPSC-Derived Hepatocytes Uniquely Predicts Differential Clinical Responses to Glucagon Analog Agonist Molecules

As the development of clinically efficacious glucagon receptor (GCGR) agonists for the treatment of metabolic diseases evolves, the challenge to identify physiologically relevant preclinical models that predict glucagon receptor actions in humans becomes ever more important. While many hepatocyte models are available, most fail to recapitulate fundamental metabolic regulatory responses to key physiologic stimuli including integration of glucagon and insulin actions that govern hepatic carbohydrate or lipid metabolism. We developed and optimized a human induced pluripotent stem cell (iPSC)-derived hepatocyte model to mimic physiologic insulin and glucagon signaling and counter-regulation of metabolic pathways. We leveraged the model to evaluate functional responses of different glucagon receptor agonist molecules to regulate carbohydrate and lipid metabolism. Unlike assays conducted in several other cell line and primary isolated hepatocyte systems, hepatic glucose output assays in the human IPSC hepatocyte model demonstrated substantial potency differences between two novel soluble glucagon analog agonists. These findings predicted differential dose-dependent blood glucose excursions in response to these agonists when administered in a single ascending dose study in healthy human volunteers. Modeling physiologic integration of insulin and glucagon signaling in a clinically translatable human iPSC hepatocyte model can advance understanding of the regulation of nutrient metabolism by glucagon receptor agonists in humans and support the development of novel therapeutic approaches to address metabolic disorders, including type 2 diabetes, obesity, and nonalcoholic fatty liver disease. Disclosure W.Roell: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Regmi: Employee; Eli Lilly and Company. C.T.Benson: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. T.Coskun: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.S.Moyers: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. J.Alsina-fernandez: Employee; Eli Lilly and Company. M.K.Thomas: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company.

EPS4.02 Earlier identification of cystic fibrosis diabetes in children with cystic fibrosis – real-world experience on the use of continuous (flash) glucose monitoring

Background: Annual screening for CF diabetes (CFD) is recommended from aged 10 years. A 2 hour blood glucose (BG) reading on OGTT of >11.1 mmol/l is diagnostic for CFD, however data on incidence of impaired glucose tolerance (IGT) are limited. Continuous glucose monitoring (CGM) alongside regular diet better defines daily BG excursions aiding interpretation of glycaemic control.

Negative energy balance hinders prosocial helping behavior

The internal state of an animal, including homeostatic requirements, modulates its behavior. Negative energy balance stimulates hunger, thus promoting a range of actions aimed at obtaining food. While these survival actions are well established, the influence of the energy status on prosocial behavior remains unexplored. We developed a paradigm to assess helping behavior in which a free mouse was faced with a conspecific trapped in a restrainer. We measured the willingness of the free mouse to liberate the confined mouse under diverse metabolic conditions. Around 42% of adlibitum-fed mice exhibited a helping behavior, as evidenced by the reduction in the latencies to release the trapped cagemate. This behavior was independent of subsequent social contact reward and was associated with changes in corticosterone indicative of emotional contagion. This decision-making process was coupled with reduced blood glucose excursions and higher Adenosine triphosphate (ATP):Adenosine diphosphate (ADP) ratios in the forebrain of helper mice, suggesting that it was a highly energy-demanding process. Interestingly, chronic (food restriction and type 2 diabetes) and acute (chemogenetic activation of hunger-promoting AgRP neurons) situations mimicking organismal negative energy balance and enhanced appetite attenuated helping behavior toward a distressed conspecific. To investigate similar effects in humans, we estimated the influence of glycated hemoglobin (a surrogate of long-term glycemic control) on prosocial behavior (namely charity donation) using the Understanding Society dataset. Our results evidenced that organismal energy status markedly influences helping behavior and that hypothalamic AgRP neurons are at the interface of metabolism and prosocial behavior.

The oral disposition index calculated from a meal tolerance test is a crucial indicator for evaluating differential normalization of postprandial glucose and triglyceride excursions in morbidly obese patients after laparoscopic sleeve gastrectomy.

To determine the normalization of postprandial blood glucose (PG) and triglyceride (TG) excursions in 30 morbidly obese patients with or without diabetes mellitus (DM) 1-year after they underwent a laparoscopic sleeve gastrectomy (LSG) vs. their pre-surgery data, we administered the 75-g oral glucose tolerance test (OGTT) and a meal tolerance test (MTT) using a 75-g glucose-equivalent carbohydrate- and fat-containing meal. The results were as follows; (i) Postoperative body-weight reduction was associated with DM remission and reduced multiple cardiometabolic risks. (ii) OGTT data showing postprandial hyper-insulinemic hypoglycemia in many post-surgery patients were associated with overdiagnosis of improved glucose tolerance. However, postoperative MTT data without hypoglycemia showed no improvement in the glucose tolerance vs. pre-surgery data. (iii) The disposition index (DI) i.e., [Matsuda index] × (Glucose-induced insulin secretion) was progressively worsened from normal glucose tolerance to DM patients after LSG. These post-surgery DI values measured by the MTT were correlated with 2h-plasma glucose levels and were not normalized in DM patients. (iv) The baseline, 2h-TG, and an increase in 2h-TG values above baseline were correlated with the insulin resistance index, DI, or HbA1c; These TG values were normalized post-LSG. In conclusion, the glucose tolerance curve measured by the MTT was not normalized in T2DM patients, which was associated with impaired normalization of the DI values in those patients 1-year after the LSG. However, the baseline TG and a fat-induced 2h-TG values were normalized postoperatively. The MTT can be used to assess normalization in postprandial glucose and TG excursions after LSG.

Study on Optimal Extraction and Hypoglycemic Effect of Quercetin.

Quercetin was extracted from Portulaca oleracea L. through biphasic acid hydrolysis to investigate its potential as a suppressor of dipeptidyl peptidase IV (DPP-IV) and its hypoglycemic effect in type 2 diabetic mice. The extraction procedure was optimized utilizing the response surface method (RSM) in a single-factor experimental setting. An extraction efficiency of 0.675% was achieved using the following optimized parameters: 0.064 mol/L vitriol, 1 : 109.155 solid-liquid ratio, and 21.408 min ultrasonication. Overall, findings indicate the effectiveness of quercetin extraction. A mouse model for type 2 diabetes was established to receive oral treatment with various quercetin concentrations for 8 weeks. Fasting blood glucose (FBG) and the DPP-IV activity in the serum were significantly reduced. The weight and insulin levels of the mice in the quercetin group were raised compared to those in the model group (P < 0.01). Quercetin dose-dependently inhibited postprandial blood glucose excursions, as demonstrated by the oral glucose tolerance test. These results confirmed that quercetin has hypoglycemic effects and considerably improves insulin sensitivity via DPP-IV targeting.

Design, synthesis and anti-diabetic activity of piperazine sulphonamide derivatives as dipeptidyl peptidase-4 inhibitors

Type II diabetes (T2DM) is considered one of the most prevalent metabolic disorders in the world. It is known as insulin resistance and persistent hyperglycemia. Over the past decade, inhibition of the enzymatic dipeptidyl peptidase-4 (DPP-4) has indeed been demonstrated to be an efficient and safe intervention for type 2 diabetes. In order to develop innovative DPP-4 inhibitors, several in silico techniques including 3D-QSAR, molecular docking, in-silico toxicity has been performed to confirm a total of 18 novel piperazine and pyridine derivatives to be synthesized from many designed molecules. These molecules have indeed been docked onto the protein surface of the DPP-4 enzyme, and ADMET characteristics have also been generated in silico. The compounds were then developed and analysed using FT-IR. Then, these compounds were investigated for DPP-4 inhibition in vitro. The most promising compound 8h showed 27.32% inhibition at 10μmol L-1 concentration over DPP-4 so selected for further in-vivo anti-diabetic evaluation. Compound 8h decreased blood glucose excursion in a dose-dependent manner during the OGTT and STZ-induced glucose models in normal Albino Wistar rats. Low-dose streptozotocin-induced type 2 diabetes in Albino Wistar rats treated chronically for 21 days with compound 8h resulted in a reduction in serum glucose levels. This highlighted that 8h is a moderately strong and specific blockbuster molecule that can be structurally modified to boost its effectiveness and overall pharmacological profile as a DPP-4 inhibitor.

Blood glucose response to running or cycling in individuals with type 1 diabetes: A systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to assess how running and cycling influence the magnitude of blood glucose (BG) excursions in individuals with type 1 diabetes. A systematic literature search was conducted in EMBASE, PubMed, Cochrane Central Register of Controlled Trials, and ISI Web of Knowledge for publications from January 1950 until February 2021. Parameters included for analysis were population (adults and adolescents), exercise type, intensity, duration and insulin preparation. The meta-analysis was performed to estimate the pooled mean with a 95% confidence interval (CI) of delta BG levels. In addition, sub-group and meta-regression analyses were performed to assess the influence of these parameters on delta BG. The database search identified 3192 articles of which 69 articles were included in the meta-analysis. Due to crossover designs within articles, 151 different results were included for analysis. Data from 1901 exercise tests of individuals with type 1 diabetes with a mean age of 29 ± 4 years were included. Overall, exercise tests BG decreased by -3.1 mmol/L [-3.4; -2.8] within a mean duration of 46 ± 21 min. The pooled mean decrease in BG for running was -4.1 mmol/L [-4.7; -2.4], whilst the pooled mean decrease in BG for cycling was -2.7 mmol/L [-3.0; -2.4] (p < 0.0001). Overall results can be found in Table S2. Running led to a larger decrease in BG in comparison to cycling. Active individuals with type 1 diabetes should be aware that current recommendations for glycaemic management need to be more specific to the mode of exercise.

The Impact of COVID-19 Lockdown on Glycemic Balance in Romanian Patients with Type 1 Diabetes Mellitus.

The COVID-19 pandemic has brought major changes not only at the economic and social level but especially in the medical system. To evaluate the impact of COVID-19 lockdown on the quality of glycemic control in Romanian patients with type 1 diabetes mellitus (T1DM). Our study group included 102 Romanian volunteers' patients with T1DM from both urban and rural areas. Data were collected during an interview, based on a structured questionnaire with multiple-choice questions about diabetes management during lockdown, how they interact with their diabetologist, how they accessed the treatment and what other factors influenced their diabetes management during the lockdown. Blood glucose levels were significantly higher in the MDII group as a consequence of delayed administration of insulin corrections due to inadequate insulin dosing (60% vs 31.81%; χ 2 = 5.51, p = 0.018). In addition, insulin pump users had improved response to stress and anxiety (ie, additional therapeutic safety being provided by use of insulin pump; in some devices, blood glucose being continuously monitored, leading to premature detection of important blood glucose excursions) compared to insulin pen users (χ 2 = 5.09, p = 0.024). In the context of hypoglycemia, we observed that in the pen MDII group, more users have administered an excess of insulin, compared with the pump users (80% vs 45.45%; χ 2 = 10.34; p = 0.001). A lower impact of COVID-19 lockdown on glycemic control was observed in patients with T1DM treated using insulin pumps compared to patients with T1DM who administered their insulin using insulin pens. Telemedicine and online consultations have brought significant improvements in diseases management. Stress, emotions, and anxiety were among the main reasons that led to increases in blood sugar levels, suggesting that the psychological impact may have long-term complications.

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.

Hepatocyte Rap1a contributes to obesity- and statin-associated hyperglycemia.

SUMMARYExcessive hepatic glucose production contributes to the development of hyperglycemia and is a key feature of type 2 diabetes. Here, we report that activation of hepatocyte Rap1a suppresses gluconeogenic gene expression and glucose production, whereas Rap1a silencing stimulates them. Rap1a activation is suppressed in obese mouse liver, and restoring its activity improves glucose intolerance. As Rap1a′s membrane localization and activation depends on its geranylgeranylation, which is inhibited by statins, we show that statin-treated hepatocytes and the human liver have lower active-Rap1a levels. Similar to Rap1a inhibition, statins stimulate hepatic gluconeogenesis and increase fasting blood glucose in obese mice. Geranylgeraniol treatment, which acts as the precursor for geranylgeranyl isoprenoids, restores Rap1a activity and improves statin-mediated glucose intolerance. Mechanistically, Rap1a activation induces actin polymerization, which suppresses gluconeogenesis by Akt-mediated FoxO1 inhibition. Thus, Rap1a regulates hepatic glucose homeostasis, and blocking its activity, via lowering geranylgeranyl isoprenoids, contributes to statin-induced glucose intolerance.

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.

The Implication of Time-in-Range for the Management of Diabetes in India: A Narrative Review

Introduction: In recent times, traditional self-monitoring of blood glucose (SMBG) using fingerstick capillary samples is moving to continuous glucose monitoring (CGM) due to inherent limitations of the traditional methods. CGM displays current glucose level, trends, rate of change, time-in-range (TIR), and glucose variability (GV) over a period of several days. It detects episodes of hyperglycemia and hypoglycemia, which allows immediate response to prevent these episodes. It also allows physicians to provide a personalized glycemic response to the patients. Materials and methods: Though CGM systems have been available for more than 20 years, their use is quite low. It is challenging for clinicians to invest time in learning and understanding the diverse reports of the various CGM devices. Moreover, there is a lack of consensus on the frequency of TIR measurement. Hence. a review of the literature was performed and existing guidelines from India and abroad were reviewed for a need for CGM and its frequency of measurements in DM patients. Results: TIR is inversely correlated to the risk of microvascular and macrovascular complications. CGM is recommended by expert clinician consensus and national and international medical organizations. For the patients use of CGMs involves cost. Besides, there is the discomfort and inconvenience of wearing the device. Hence, defining the implications of using CGM in practice is important. According to the 2020 recommendations by the Research Society for the Study of Diabetes in India (RSSDI) — Endocrine Society of India (ESI) and the 2019 recommendations by an expert group of endocrinologists and diabetologists, in the Indian context, CGM could be suggested for patients with Type 2 Diabetes who encounter severe hyperglycemia or hypoglycemia, repeated hypoglycemia, asymptomatic hypoglycemia, nocturnal hypoglycemia, refractory hyperglycemia, or large blood glucose excursions. Conclusions: The role of CGM to achieve better glycemic control and prevention of complications in T1D and T2D is well established. Significant education and awareness on CGM needs to be provided to physicians as well as patients with high GV and those on insulin therapy.

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.

The effects of macronutrients composition on hormones and substrates during a meal tolerance test in drugnaive and sitagliptin-treated individuals with type 2 diabetes: a randomized crossover study.

To evaluate the effect of sitagliptin treatment in early type 2 diabetes mellitus (T2DM) and the impact of different macronutrient compositions on hormones and substrates during meal tolerance tests (MTT). Half of the drug-naive patients with T2DM were randomly assigned for treatment with 100 mg of sitagliptin, q.d., or placebo for 4 weeks and then submitted to 3 consecutive MTT intercalated every 48 h. The MTTs differed in terms of macronutrient composition, with 70% of total energy from carbohydrates, proteins, or lipids. After 4 weeks of washout, a crossover treatment design was repeated. Both patients and researchers were blinded, and a repeated-measures ANOVA was employed for statistical analysis. Sitagliptin treatment reduced but did not normalize fasting and post-meal glucose values in the three MTTs, with lowered area-under-glucose-curve values varying from 7% to 15%. The sitagliptin treatment also improved the insulinogenic index (+86%) and the insulin/glucose (+25%), glucagon-like peptide-1/glucose (+46%) incremental area under the curves. Patients with early T2DM maintained the lowest glucose excursion after a protein- or lipid-rich meal without any major change in insulin, C-peptide, glucagon, or NEFA levels. We conclude that sitagliptin treatment is tolerable and contributes to better control of glucose homeostasis in early T2DM, irrespective of macronutrient composition. The blood glucose excursion during meal ingestion is minimal in protein- or fat-rich meals, which can be a positive ally for the management of T2DM. Clinical trial no: NCT00881543.