Postprandial Glycemic Excursions Research Articles

Clinical Consequences of Delayed Gastric Emptying With GLP-1 Receptor Agonists and Tirzepatide.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are established therapeutics for type 2 diabetes and obesity. Among other mechanisms, they slow gastric emptying and motility of the small intestine. This helps limiting postprandial glycemic excursions and reducing chylomicron formation and triglyceride absorption. Conversely, motility effects may have detrimental consequences, e.g., retained gastric contents at endoscopy or general anesthesia, potentially complicated by pulmonary aspiration, or bowel obstruction. We searched the PubMed database for studies involving GLP-1RA therapy and adverse gastrointestinal/biliary events. Retained gastric contents at the time of upper gastrointestinal endoscopy are found more frequently with GLP-1 RAs, but rarely are associated with pulmonary aspiration. Well-justified recommendations for the peri-procedural management of GLP-1RAs (e.g., whether to withhold these medications, and for how long) are compromised by limited evidence. Important aspects to be considered are (a) their long half-lives, (b) the capacity of GLP-1 receptor agonism to slow gastric emptying even at physiological GLP-1 concentrations, (c) tachyphylaxis observed with prolonged treatment, and (d) the limited effect on gastric emptying in individuals with slow gastric emptying before initiating treatment. Little information is available on the influence of diabetes mellitus itself (i.e., in the absence of GLP-1 RA treatment) on retained gastric contents and pulmonary aspiration. Prolonged fasting periods regarding solid meal components, point-of-care ultrasound examination for retained gastric content, and the use of prokinetic medications like erythromycin may prove helpful, and are an important area needing further study to increase patient safety for those treated with GLP-1 RAs.

Effect of Genistein on Starch Digestion In Vitro and Its Mechanism of Action.

The digestive properties of starch are crucial in determining postprandial glycaemic excursions. Genistein, an active phytoestrogen, has the potential to influence starch digestion rates. We investigated the way genistein affected the digestive properties of starch in vitro. We performed enzyme kinetics, fluorescence spectroscopy, molecular docking, and molecular dynamics (MD) simulations for analysing the inhibitory properties of genistein on starch digestive enzymes as well as clarifying relevant mechanism of action. Our findings demonstrated that, following the addition of 10% genistein, the contents of slowly digestible and resistant starches increased by 30.34% and 7.18%, respectively. Genistein inhibited α-amylase and α-glucosidase, with half maximal inhibitory concentrations of 0.69 ± 0.06 and 0.11 ± 0.04 mg/mL, respectively. Genistein exhibits a reversible and non-competitive inhibiting effect on α-amylase, while its inhibition on α-glucosidase is a reversible mixed manner type. Fluorescence spectroscopy indicated that the presence of genistein caused declining fluorescence intensity of the two digestive enzymes. Molecular docking and MD simulations showed that genistein binds spontaneously to α-amylase via hydrogen bonds, hydrophobic interactions, and π-stacking, whereas it binds with α-glucosidase via hydrogen bonds and hydrophobic interactions. These findings suggest the potential for developing genistein as a pharmacologic agent for regulating glycaemic excursions.

Glucose levels measured with continuous glucose monitoring in uncomplicated pregnancies

IntroductionTo characterize glucose levels during uncomplicated pregnancies, defined as pregnancy with a hemoglobin A1c <5.7% (<39 mmol/mol) in early pregnancy, and without a large-for-gestational-age birth, hypertensive disorders of pregnancy, or...

Impact of the timing of metformin administration on glycaemic and glucagon-like peptide-1 responses to intraduodenal glucose infusion in type 2 diabetes: a double-blind, randomised, placebo-controlled, crossover study

Aims/hypothesisMetformin lowers postprandial glycaemic excursions in individuals with type 2 diabetes by modulating gastrointestinal function, including the stimulation of glucagon-like peptide-1 (GLP-1). The impact of varying the timing of metformin administration on postprandial glucose metabolism is poorly defined. We evaluated the effects of metformin, administered at different intervals before an intraduodenal glucose infusion, on the subsequent glycaemic, insulinaemic and GLP-1 responses in metformin-treated type 2 diabetes.MethodsSixteen participants with type 2 diabetes that was relatively well-controlled by metformin monotherapy were studied on four separate days in a crossover design. On each day, participants were randomised to receive a bolus infusion of metformin (1000 mg in 50 ml 0.9% saline) via a nasoduodenal catheter at t = −60, −30 or 0 min (and saline at the other timepoints) or saline at all timepoints (control), followed by an intraduodenal glucose infusion of 12.56 kJ/min (3 kcal/min) at t = 0–60 min. The treatments were blinded to both participants and investigators involved in the study procedures. Plasma glucose, insulin and total GLP-1 levels were measured every 30 min between t = −60 min and t = 120 min.ResultsThere was a treatment-by-time interaction for metformin in reducing plasma glucose levels and increasing plasma GLP-1 and insulin levels (p<0.05 for each). The reduction in plasma glucose levels was greater when metformin was administered at t = −60 or −30 min vs t = 0 min (p<0.05 for each), and the increases in plasma GLP-1 levels were evident only when metformin was administered at t = −60 or −30 min (p<0.05 for each). Although metformin did not influence insulin sensitivity, it enhanced glucose-induced insulin secretion (p<0.05), and the increases in plasma insulin levels were comparable on the 3 days when metformin was given.Conclusions/interpretationIn well-controlled metformin-treated type 2 diabetes, glucose-lowering by metformin is greater when it is given before, rather than with, enteral glucose, and this is associated with a greater GLP-1 response. These observations suggest that administration of metformin before meals may optimise its effect in improving postprandial glycaemic control.Trial registrationwww.anzctr.org.au ACTRN12621000878875FundingThe study was not funded by a specific research grant.Graphical

Optimizing expression, purification, structural and functional assessments of a novel dimeric incretin (GLP-1cpGLP-1)

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that reduces postprandial glycemic excursions by enhancing insulin secretion. In this study, a new dimeric GLP-1 analogue (GLP-1cpGLP-1) was designed by inserting human insulin C-peptide (CP) in the middle of a dimer of [Gly8] GLP-1 (7–36). Then, the dimeric incretin (GLP-1cpGLP-1) was ligated to human αB-crystallin (αB-Cry) to create a hybrid protein, abbreviated as αB-GLP-1cpGLP-1. The constructed gene was well expressed in the bacterial host system. After specific chemical release from the hybrid protein, the dimeric incretin was purified by size exclusion chromatography (SEC). Finally, the RP-HPLC analysis indicated a purity of >99 % for the dimeric incretin. The secondary structure assessments by various spectroscopic methods, and in silico analysis suggested that the dimeric incretin has α-helical rich structure. The dynamic light scattering (DLS) analysis indicates that our dimeric incretin forms large oligomeric structures. This incretin analogue significantly reduced blood glucose levels in both healthy and diabetic mice while effectively triggering insulin release. The size exclusion HPLC also indicates the interaction of the new incretin analogue with human serum albumin, the main carrier protein in the bloodstream. Consistent with the results obtained from the biological activity assessments, this significant interaction indicates its potential as a viable therapeutic agent with a long-lasting effect. The results of our research represent a significant breakthrough in the successful design of an active incretin dimer capable of effectively controlling blood sugar levels and inducing insulin secretion in the realm of diabetes treatment.

Effects of low-GI biscuits as pre-loads or mid-meal snacks on post-prandial glycemic excursions in women with recent gestational diabetes: A protocol for a randomized crossover trial and an extended tailored intervention.

Increased post-prandial glycemic excursions contribute to the development of diabetes and have been observed in women with recent gestational diabetes mellitus (GDM) and with normal glucose tolerance at post-partum. As a convenient meal replacement, low-GI biscuits are helpful for improving glycemic excursions in patients with type 2 diabetes. However, it is unknown whether low-GI biscuits as pre-loads or mid-meal snacks have a better effect in diminishing post-prandial glycemic excursions from the individual level in women with recent GDM. Therefore, the aim of this trial is to tailor a better dietary strategy utilizing low-GI biscuits (Fitmeal) to improve post-prandial glycemic excursions through within-subject comparison in such a population and observe the long-term effect of a tailored dietary approach in glycemic control. We have designed a two-phase trial including a randomized, crossover, non-blinded trial in the first phase, followed by a 4-week tailored intervention in the second phase. A total of 52 post-partum women with recent GDM will be allocated into four meal plans: (1) Fitmeal pre-load 30 min before standard lunch meal (P+L), (2) Fitmeal as a mid-meal snack 2 h before standard lunch meal (S+L), (3) isocaloric standard control with co-ingestion of Fitmeal and standard lunch meal (CL) at the same time, and (4) placebo control with 200 ml of water taken 30 min before standard lunch meal (W + L), on four consecutive days. Acute post-prandial glycemic response (PGR) measured by continuous glucose monitoring (CGM) will be compared among the four meals. In the second phase, all participants will receive a 4-week tailored intervention using Fitmeal as pre-loads or mid-meal snacks based on within-subject PGR results from the first phase. Glycemic metrics, dietary behaviors, and psychosocial factors (e.g., quality of life, self-efficacy, perceived stress, and depression) will be examined at baseline and end-point. This trial is expected to optimize the use of low-GI biscuits as pre-loads or mid-meal snacks in improving individual post-prandial glycemic excursions among women with recent GDM. Furthermore, the findings of this study will provide novel information on how to deliver an effective dietary intervention at the individual level and guide future clinical practice of medical nutrition therapy for diabetes prevention. Chinese clinical trial registry, ChiCTR2200060923.

Study protocol: a randomised controlled proof-of-concept real-world study – does maximising time in range using hybrid closed loop insulin delivery and a low carbohydrate diet restore the glucagon response to hypoglycaemia in adults with type 1 diabetes?

IntroductionPeople with type 1 diabetes (T1D) develop an impaired glucagon response to hypoglycaemia within 5 years of diagnosis, increasing their risk of severe hypoglycaemia. It is not known whether eliminating...

Efficacy of insulin dosing algorithms for high-fat high-protein mixed meals to control postprandial glycemic excursions in people living with type 1 diabetes: A systematic review and meta-analysis.

Optimizing postprandial blood glucose (PPG) levels after mixed meals that contain high fat and protein remains a challenge in the treatment of type 1 diabetes. This study evaluated the efficacy of different algorithms used for dosing insulin based on counting units of high fat and high protein (HFHP) meals with the current conventional method of counting carbohydrates alone to control PPG excursions. The MEDLINE, EMBASE, and Cochrane electronic databases were searched, with the analysis restricted to randomized control trials (RCTs). The primary outcome was the PPG (mean and standard deviation) at 240 min. The pooled final estimate was the mean difference (MD) of the PPGs at 240 min using random effect models to account for heterogeneity. In total, 15 studies were identified and included in the systemic review, of which 12 were RCTs, and three studies were non-randomized trials. The pooled MD of the PPG at 240 min was in favor of additional insulin doses in HFHP meals compared to the carbohydrate counting alone. The statistically significant results favored the combined bolus (30:70) that split over 2h in insulin pump therapy with pooled MD of the PPG, 240 min of -24.65; 95% CI: -36.59, -8.41; and heterogeneity, 0%. Other statistically significant results favored the additional insulin added to insulin to carb ratio (ICR) of meal bolus (25-60% ICR) in multiple daily injections therapy with the pooled MD of PPG at 240 min, -21.71; 95% CI: -38.45, -4.73; and heterogeneity, 18%. Insulin treatment based on fat and protein content, in addition to carbohydrate counting, is more effective than the carbohydrate counting method alone; however, further research is warranted to determine the best equation for fat and protein counting, particularly in people with multiple daily injections.

Weight Management, Micronutrients, and Supplements in Diabetes

This year’s 39th International Symposium on Diabetes and Nutrition in Anavyssos, Greece, hosted a series of presentations and plenary lectures with a focus on the effects of weight loss, micronutrients, nutritional supplements, and alternative dietary patterns in the prevention and management of Type 2 diabetes (T2D) and cardiovascular risk reduction. Michael Lean discussed how diabetes remission can be achieved through weight loss using a low-energy diet (LED) or very low-energy diet (VLED), accompanied by continued long-term support from specialised healthcare professionals. Jeffrey Mechanick discussed the importance and impact of early intervention on T2D and cardiovascular disease (CVD). He emphasised that T2D should be seen not just at the point of disease, but on a spectrum from prediabetes to complications, with early interventions having significant impact on not only the progression of T2D, but also into the latter stages.Simin Liu presented an integrative multilevel framework for causal inference to personalise cardiometabolic health, highlighting recent work investigating the roles of dietary minerals, environment metals, and genomics in relation to cardiovascular disease and diabetes. Several of the presentations included discussion of specific interventions. Daniel West discussed the use of whey protein (WP) and how it can help control postprandial glycaemic excursions (PGE) in people with T2D controlled on oral antihyperglycaemic drugs. Following this, Andrea Hawkinson discussed how a new supplement, mulberry leaf (Morus alba) extract (MLE), can significantly lower postprandial glucose response, as well as early insulin response, highlighting the need for further studies to evaluate its efficacy in people with T2D. Philip Atherton showed studies providing evidence that protein and essential amino acid (EAA) supplementation can help support muscle mass, which is especially essential for older people with T2D and sarcopenia. Finally, Jose-María López-Pedrosa spoke about how a supplement containing slow digestible carbohydrates (SDC), arginine, lysine, and β-hydroxy-β-methylbutyric acid (HMB) can help preserve muscle mass, as well as improve insulin resistance, in a rat model of diabetes.

Diet consistency modification improves postprandial glycemic and gastroparesis symptoms.

Diabetic gastroparesis (DGP) is an autonomic neuropathy resulting from long-standing poorly controlled diabetes, and it is also linked to fluctuations in glycemic control due to variability on nutrient absorption. Considering the scarcity of information, the aim of this study was to identify the impact of modifications on diet consistency on post-prandial glucose variability using a continuous glucose monitoring (CGM) and its effect on the perception and severity of gastrointestinal symptoms. This proof-of-concept study was carried out in a cross-sectional cohort of six individuals with type 1 diabetes mellitus with confirmed diagnosis of DGP. Two types of diet were used to evaluate glycemic control and DGP symptoms, general consistency standard meal (SD) and modified consistency test diet (MD), associated with an application of rapid acting insulin at the time of food intake. Glycemic control was evaluated by CGM, and the Gastroparesis Cardinal Symptom Index (GCSI) was applied after meals. The CGM curve was different for MD + insulin and SD + insulin. There was a smaller increment of interstitial glucose with 2h after MD + insulin, returning almost to the basal level 4h later. Patients scored significantly lower GCSI after MD + insulin compared to the same index after they received SD + insulin. Moreover, there was a decrease in important clinical scores present in the index, like: "Not able to finish meal", "Loss of appetite" and "Stomach or belly feels larger". This study showed that a modified diet can improve postprandial glycemic excursion and the perception and severity of gastroparesis symptoms. The online version contains supplementary material available at 10.1007/s40200-022-01117-w.

Acute Flaxseed Intake Reduces Postprandial Glycemia in Subjects with Type 2 Diabetes: A Randomized Crossover Clinical Trial.

Background: Postprandial glycemic excursions are associated with impairment control of diabetes mellitus. Long-term consumption of flaxseed can lower blood glucose levels; however, its effects on the postprandial glycemic response remain unknown. Therefore, this study aimed to evaluate the acute effects of raw flaxseed consumption on the 2 h postprandial glycemic curve in men with type 2 diabetes mellitus (T2DM). Methods: This was a randomized crossover clinical trial. Nineteen men with T2DM were randomly assigned a standardized breakfast without (control) or with a previous intake of 15 g of ground raw golden flaxseed (flax). Glycemia was measured at fasting and postprandial at 15, 30, 45, 60, 90, and 120 min. Palatability markers (visual appeal, smell, and pleasantness of taste) and taste intensity (sweetness, saltiness, bitterness, sourness, and creaminess) were evaluated. Results: The peak glucose rise and the 2 h AUC glycemic response reduced in the flax group by 17% (p = 0.001) and 24% (p < 0.001), respectively. The glucose peak time, palatability, and taste parameters did not differ between the two groups. Conclusions: Ingestion of 15 g of ground raw golden flaxseed before breakfast decreases the 2 h postprandial glycemic response in men with T2DM.

The Effect of Two Different Insulin Formulations on Postprandial Hyperglycemia after High and Low Glycemic-Index Meal in Type 1 Diabetes.

Despite multiple pharmacological options, including rapid-acting insulin analogs, postprandial hyperglycemia is still highly prevalent in patients with type 1 and type 2 diabetes. We hypothesize that the new rapid-acting insulin formulation, the so-called faster-acting Aspart, may have a different effect in controlling postprandial hyperglycemic burden according to the quality of the meal compared to the traditional Aspart. Twenty-five patients with type 1 diabetes were consecutively recruited at the diabetes care center of the University Hospital affiliate of the Magna Græcia University of Catanzaro. Each patient performed four meal tests one week apart, two with a predefined high glycemic index (HGI) food and two with a low glycemic index (LGI) food using insulin Aspart once and Faster Aspart the other time. The 0–30 min, 0–60 min, and 0–120 min glucose Area Under the Curve (AUC) of postprandial glycemic excursion, calculated from continuous glucose monitoring data, were significantly lower with Faster Aspart administered before the HGI test meal as compared to Aspart. A significant difference in favor of Faster Aspart was also found when comparing the 0–60 min and 0–120 min AUC after the LGI meal. Faster Aspart may provide better postprandial glucose control than Aspart regardless of the glycemic index of the meal.

Influence of oral processing behaviour and bolus properties of brown rice and chickpeas on in vitro starch digestion and postprandial glycaemic response

PurposeOral processing behaviour may contribute to individual differences in glycaemic response to foods, especially in plant tissue where chewing behaviour can modulate release of starch from the cellular matrix. The aim of this study was to assess the impact of chewing time of two starch based foods (brown rice and chickpeas) on bolus properties, in vitro starch digestion and postprandial glycaemic excursion in healthy subjects.MethodsIn a cross-over trial participants (n = 26) consumed two carbohydrates-identical test meals (brown rice: 233 g; chickpeas: 323 g) with either long (brown rice: 41 s/bite; chickpeas: 37 s/bite) or short (brown rice: 23 s/bite; chickpeas: 20 s/bite) chewing time in duplicate while glycaemic responses were monitored using a continuous glucose monitoring device. Expectorated boli were collected, then bolus properties (number, mean area, saliva amylase activity) and in vitro starch digestion were determined.ResultsLonger chewing resulted in significantly (p < 0.05) more and smaller bolus particles, higher bolus saliva uptake and higher in vitro degree of intestinal starch hydrolysis (DH_Schewing time%) than shorter chewing for both foods (brown rice: DH_S%23 s = 84 ± 4% and DH_%S41s = 90 ± 6%; chickpeas: DH_S%20 s = 27 ± 3% and DH_%S37s = 34 ± 5%, p < 0.001). No significant effect of chewing time on glycaemic response (iAUC) (p > 0.05) was found for both meals. Brown rice showed significantly and considerably higher in vitro degree of intestinal starch hydrolysis and glycaemic response (iAUC) than chickpeas regardless of chewing time. No significant correlations were observed between bolus properties and in vitro starch hydrolysis or glycaemic response (p > 0.05).ConclusionDifferences in the innate structure of starch based foods (brown rice compared to chickpeas) have a larger effect on postprandial glucose response than differences in mastication behaviour although oral processing behaviour showed consistent effects on bolus properties and in vitro starch digestion.Trial registration ClinicalTrials.gov identifier: NCT04648397 (First posted: December 1, 2020).

Screening of Aqueous Extract of Persea americana Seeds for Alpha-Glucosidase Inhibitors.

Activity of α-glucosidase enzyme in the gastrointestinal tract has been implicated in postprandial hyperglycaemia. If not properly controlled, postprandial hyperglycaemia might progress to diabetes mellitus, a metabolic syndrome. Diabetes is associated with many complications such as retinopathy, heart attack, nephropathy, neuropathy, stroke, and lower limb amputation. Antidiabetic medications presently in use have little effect on postprandial glycaemic excursion and hence do not bring down the blood glucose level to baseline. This study extracted, fractionated, and screened the aqueous extract of Persea americana seeds for hypoglycaemic potential. Inhibitory effects of the fractions and subfractions of the extract on α-glucosidase activity were investigated. The most active subfraction was subjected to Fourier transform infrared (FTIR) and gas chromatography mass spectroscopy (GC-MS) analysis to elucidate the active components. The active subfraction showed a significant inhibition (p < 0.05) on α-glucosidase. The subfraction competitively inhibits α-glucosidase (with IC50 = 09.48 ± 0.58 μg/mL), though less potent than the standard drug, acarbose (IC50 = 06.45 ± 0.47 μg/mL). FTIR analysis of the subfraction showed the presence of carbonyl group, hydroxy group, carboxyl group, double bonds, methylene, and methyl groups. GC-MS analysis suggests the presence of cis-11,14-eicosadienoic acid, catechin, and chlorogenic acid as the active components. In conclusion, the components obtained from this study can be synthesised in the laboratory to further confirm their hypoglycaemic activity. The most active subfraction can be explored further to confirm its inhibitory activity against the enzyme and to determine its extent in the treatment of diabetes mellitus in vivo.

A Comparison of Postprandial Glucose Control in the Medtronic Advanced Hybrid Closed-Loop System Versus 670G.

Background: We recently reported that use of an "advanced" hybrid closed-loop system reduced hyperglycemia without increasing hypoglycemia compared to a first-generation system. The aim of this analysis was to evaluate whether this improved performance was specifically related to better mealtime glycemic control. Methods: We conducted a secondary analysis of postprandial glycemic control in an open-label, multinational, randomized crossover trial of 112 participants with type 1 diabetes, aged 14-29, of the Medtronic MiniMed™ 670G hybrid closed-loop system (670G) versus the Medtronic advanced hybrid closed-loop (AHCL) system, for 12 weeks each. We compared glycemic and insulin delivery metrics over a 3 h horizon across all meals to assess system performance and outcomes. Results: Overall meal size and premeal insulin on board were similar during run-in and between 670G and AHCL arms. Compared with 670G arm, premeal, peak, and mean glucose levels were numerically lower in the AHCL arm (167 ± 23, 231 ± 23, and 177 ± 20 mg/dL vs. 175 ± 23, 235 ± 23, and 180 ± 19 mg/dL, respectively), with a trend to lower hyperglycemia level 2 in AHCL arm. Adjusting for premeal glucose level, all postmeal outcomes between 670G and AHCL were statistically similar. Prandial insulin delivery also was similar in both treatment arms (21 ± 9 vs. 23 ± 10 U), with a shift in basal/bolus ratio from 28%/71% in 670G arm to 20%/80% in AHCL arm. Conclusions: Reduced hyperglycemia with AHCL compared to 670G was not related to early postprandial glycemic excursions after adjusting for premeal glucose level (<3 h after meal), but likely to later (>3 h) postprandial or overnight improvements. Further refinements to mealtime bolus algorithms and strategies may more optimally control prandial glycemic excursions.

Insulin analogs in the treatment of type II diabetes and future perspectives

The discovery of insulin by Banting and Best marked 100 years in 2021, and it was a life-saving treatment modality for type II diabetes mellitus (T2DM). Insulin is a natural hormone that has been used extensively in T2DM patients since its discovery. Currently, insulin analogs are also available in different formulations for T2DM management, overcoming the limitations of human insulin with better safety and side effect profiles. The insulin analogs like the rapid-acting analogs (Aspart, lispro, glulisine), the long-acting basal analogs (Glargine, detemir), the ultra-long acting (Insulin degludec), and the premixed insulin analog formulations (75% Neutral protamine lispro, 25% lispro; 50% neutral protamine lispro, 50% lispro; 70% protamine aspart, 30% aspart) have been prepared through genetic engineering while preserving the basic insulin profile. A large number of studies have demonstrated their clinical effects on glycated hemoglobin test (HbA1c) in achieving glycemic control and thereby lowering the microvascular and macrovascular complications of T2DM with less traditional side effects of regular human insulin, mainly the risk of hypoglycemia, postprandial glycemic excursions, and weight gain. This review explores the currently available insulin analogs, their clinical implications, pharmacokinetics (PK), pharmacodynamics (PD), safety profile, and cost-effectiveness. We also discuss the future developments in the management of T2DM, especially the scientific advancements surrounding the novel insulin formulations, including the biosimilar insulin, and the innovative insulin delivery methods, such as oral and inhaled insulin.

Pramlintide for post-bariatric hypoglycaemia.

The aim of this study was to examine the hypothesis that pramlintide would reduce hypoglycaemia by slowing gastric emptying and reducing postprandial glucagon secretion, thus limiting postprandial glycaemic excursions and insulin secretion, and thus to determine the efficacy of pramlintide on frequency and severity of hypoglycaemia in post-bariatric hypoglycaemia (PBH). Participants with PBH following gastric bypass were recruited from outpatient clinics at the Joslin Diabetes Center, Boston, Massachusetts for an open-label study of pramlintide efficacy over 8 weeks. Twenty-three participants were assessed for eligibility, 20 participants had at least one pramlintide dose, and 14 completed the study. A mixed-meal tolerance test (MMTT) was performed at baseline and after 8 weeks of subcutaneous pramlintide with a sequential dose increase to a maximum of 120 micrograms (mean 69 ± 32 mcg) three times daily. The primary endpoint was change in glucose excursions during the MMTT. Secondary measures included MMTT insulin response, satiety and dumping score, percentage time with sensor glucose (SG) <3.9 mM, and number of days with minimum SG <3 mM, during masked continuous glucose monitoring. There were no differences in MMTT glucose, glucagon or insulin between baseline and post treatment. We observed no significant change in satiety or dumping scores. The overall frequency of low SG values did not change, although there was substantial inter-individual variability. In PBH, pramlintide does not modulate glycaemic or insulin responses, satiety, or dumping scores during an MMTT and does not impact glycaemic excursions or decrease low SG levels in the outpatient setting.

Faster Aspart: a fast-acting insulin analog for an optimal glycemic control

The basal-bolus insulin regimen in the management of diabetes is essential to achieve the recommended glycosylated hemoglobin (HbA1c) to reduce the incidence or the progression of chronic complications. HbA1c is influenced by either fasting plasma glucose and post-prandial hyperglycemia. Faster Aspart is an insulin Aspart with two additional excipients, L-arginine and niacinamide, which provide a faster subcutaneous absorption, the earlier onset of appearance, and consequently the optimization of post-prandial glucose control. Faster Aspart has been widely investigated in the ‘‘onset’’ clinical trials, which show better post-prandial glycemic excursions and noninferiority compared to insulin Aspart with HbA1c reduction. Clinical evidence demonstrates that faster Aspart is a therapeutic option able to provide clinical benefits over the current rapid-acting insulin analogs in terms of improved meal-related glycaemic control in subjects with diabetes. KEY WORDS post-prandial hyperglycemia; cardiovascular disease; insulin treatment; faster-acting insulin; faster aspart.

Effects of the hemoglobin glycation index on hyperglycemia diagnosis: Results from the REACTION study

AimsThis study aimed to assess the effects of the hemoglobin glycation index (HGI) on hyperglycemia diagnosis and summarize the general characteristics of patients with a high-HGI phenotype. MethodsThe fasting plasma glucose and glycated hemoglobin (HbA1c) levels of participants (n = 47,648) were used to estimate a linear regression equation and determine the baseline HGI. Overall, 42,317 participants without a history of diabetes were included in the final analysis. The participants were divided into three groups according to the tertiles (low, moderate, and high) of baseline HGI. Proportions and variables were compared among the three HGI groups. A multivariate ordered logistic regression model was used to explore associations between related variables and the high-HGI phenotype. ResultsRegression analysis indicated that the high-HGI phenotype was positively associated with female sex, advanced age, obesity, increased low-density lipoprotein and triglyceride levels, decreased high-density lipoprotein cholesterol, and postprandial glycemic excursion levels (all P < 0.05). The prevalence of hyperglycemia increased from the low- to the high-HGI groups when using HbA1c for diagnosis. ConclusionsIndividuals with high HGI have similar clinical characteristics. Measuring HbA1c alone for diagnosis could lead to inappropriate diabetes management decisions in people with low or high HGI.

Role of High Energy Breakfast "Big Breakfast Diet" in Clock Gene Regulation of Postprandial Hyperglycemia and Weight Loss in Type 2 Diabetes.

Postprandial hyperglycemia (PPHG) is strongly linked with the future development of cardiovascular complications in type 2 diabetes (T2D). Hence, reducing postprandial glycemic excursions is essential in T2D treatment to slow progressive deficiency of β-cell function and prevent cardiovascular complications. Most of the metabolic processes involved in PPHG, i.e., β-cell secretory function, GLP-1 secretion, insulin sensitivity, muscular glucose uptake, and hepatic glucose production, are controlled by the circadian clock and display daily oscillation. Consequently, postprandial glycemia displays diurnal variation with a higher glycemic response after meals with the same carbohydrate content, consumed at dusk compared to the morning. T2D and meal timing schedule not synchronized with the circadian clock (i.e., skipping breakfast) are associated with disrupted clock gene expression and is linked to PPHG. In contrast, greater intake in the morning (i.e., high energy breakfast) than in the evening has a resetting effect on clock gene oscillations and beneficial effects on weight loss, appetite, and reduction of PPHG, independently of total energy intake. Therefore, resetting clock gene expression through a diet intervention consisting of meal timing aligned to the circadian clock, i.e., shifting most calories and carbohydrates to the early hours of the day, is a promising therapeutic approach to improve PPHG in T2D. This review will focus on recent studies, showing how a high-energy breakfast diet (Bdiet) has resetting and synchronizing actions on circadian clock genes expression, improving glucose metabolism, postprandial glycemic excursions along with weight loss in T2D.