Postprandial Hypoglycemia Research Articles

A lone spike in blood glucose can enhance the thrombo-inflammatory response in cortical venules

How transient hyperglycemia contributes to cerebro-vascular disease has been a challenge to study under controlled physiological conditions. We use amplified, ultrashort laser-pulses to physically disrupt brain-venule endothelium at targeted locations. This vessel disruption is performed in conjunction with transient hyperglycemia from a single injection of metabolically active D-glucose into healthy mice. The observed real-time responses to laser-induced disruption include rapid serum extravasation, platelet aggregation, and neutrophil recruitment. Thrombo-inflammation is pharmacologically ameliorated by a platelet inhibitor, by a scavenger of reactive oxygen species, and by a nitric oxide donor. As a control, vessel thrombo-inflammation is significantly reduced in mice injected with metabolically inert L-glucose. Venules in mice with diabetes show a similar response to laser-induced disruption and damage is reduced by restoration of normo-glycemia. Our approach provides a controlled method to probe synergies between transient metabolic and physical vascular perturbations and can reveal new aspects of brain pathophysiology.

Reactive hypoglycemia in binge eating disorder, food addiction, and the comorbid phenotype: unravelling the metabolic drive to disordered eating behaviours

BackgroundImpaired metabolic response such as blood glucose fast fluctuations may be hypothesized in binge eating disorder (BED) and food addiction (FA) by virtue of the repetitive consumption of highly processed food. Conversely, rapid changes in plasma glucose (i.e., hypoglycemia) may trigger craving for the same food products. The investigation of early glycemic disturbances in BED and FA could enhance the understanding of the metabolic mechanisms involved in the maintenance of the disorders. Present study investigated hypoglycemia events during a 5-h-long oral glucose tolerance test (OGTT) in people with BED, FA, and the comorbid phenotype. Further, the association between the severity of eating psychopathology and the variability in hypoglycaemia events was explored.MethodsTwo-hundred participants with high weight and no diabetes completed the extended OGTT and were screened for BED, FA, BED-FA, or no-BED/FA. The four groups were compared in hypoglycemia events, OGTT-derived measures, and eating psychopathology. The association between predictors (eating psychopathology), confounders (demographics, metabolic features), and the outcomes (hypoglycemia, early/late hypoglycemia, severe hypoglycemia, reactive hypoglycemia) was examined through logistic regression.ResultsHypoglycemia in general, and reactive hypoglycemia were highly frequent (79% and 28% of the sample, respectively). Hypoglycemia events (< 70 mg/dL) were equally experienced among groups, whilst severe hypoglycemia (< 54 mg/dL) was more frequent in BED at the late stage of OGTT (5 h; χ2 = 1.120, p = .011). The FA and BED groups exhibited significantly higher number of reactive hypoglycemia (χ2 = 13.898, p = .003), in different times by diagnosis (FA: 210′–240′; BED: at the 270′). FA severity was the only predictor of early and reactive hypoglycemia.ConclusionsPeople with BED or FA are prone to experiencing reactive hypoglycemia; FA severity may predict early and symptomatic hypoglycemia events. This can further reinforce disordered eating behaviours by promoting addictive responses, both biologically and behaviourally. These results inform professionals dealing with eating disorders about the need to refer patients for metabolic evaluation. On the other hand, clinicians dealing with obesity should screen for and address BED and FA in patients seeking care for weight loss.

Clinical evaluation of a decision support system for glucose infusion in hypoglycaemic clamp experiments.

To provide a preliminary evaluation of the accuracy and safety of Gluclas decision support system suggestions in a hypoglycaemic clamp study. This analysis was performed using data from 32 participants (four groups with different glucose-insulin regulation: post Roux-en-Y gastric bypass with and without postprandial hypoglycaemia syndrome, postsleeve gastrectomy and non-operated controls) undergoing Gluclas-assisted hypoglycaemic clamps (target: 2.5 mmol/L for 20 minutes at 150 minutes after oral glucose ingestion). Gluclas provided glucose infusion rate suggestions upon manual entry of blood glucose values (every 5 minutes), which were either followed or overruled by investigators after critical review. Accuracy and safety were evaluated by mean absolute error (MAE), mean absolute percentage error (MAPE), average glucose level, coefficient of variation (CV) and minimal glucose level during the 20-minute hypoglycaemic period. Investigators accepted 84% of suggestions, with a mean deviation of 30.33 mg/min. During the hypoglycaemic period, the MAE was 0.16 (0.12-0.24) (median [interquartile range]) mmol/L and the MAPE was 6.12% (4.80%-9.29%). CV was 4.90% (3.58%-7.27%), with 5% considered the threshold for sufficient quality. The minimal glucose level was 2.40 (2.30-2.50) mmol/L. Gluclas achieved sufficiently high accuracy with minimal safety risks in a population with differences in glucose-insulin dynamics, underscoring its applicability to various patient groups.

Transoral gastric outlet reduction for post-prandial hypoglycemia after Roux-en-Y gastric bypass.

Post-prandial hypoglycemia is an uncommon but disabling late complication of Roux-en-Y gastric bypass (RYGB). Most patients can be treated with dietary interventions and medications; however, some patients develop refractory hypoglycemia that may lead to multiple daily episodes and seizures. While RYGB reversal surgery is an effective treatment, complication rates are high, and patients inevitably experience weight regain. Transoral gastric outlet reduction (TORe) is a minimally invasive treatment that is effective for early and late dumping syndrome. However, prior studies have not distinguished the effectiveness of TORe specifically for patients with post-prandial hypoglycemia. This study aims to describe a single institution's experience of TORe for treating post-prandial hypoglycemia. This is a case series of patients with prior RYGB complicated by post-prandial hypoglycemia who underwent TORe from February 2020 to September 2021. Pre-procedural characteristics and post-procedural outcomes were obtained. Outcomes assessed included post-prandial hypoglycemia episodes, dumping syndrome symptoms, and weight change. A total of 11 patients underwent TORe from 2020 to 2021 for post-prandial hypoglycemia. Three (27%) patients had a history of seizures due to hypoglycemia. All had been advised on dietary changes, and ten patients (91%) were on medications for dumping. All patients reported a reduction in post-prandial hypoglycemic events as well as the majority of dumping syndrome symptoms during an average follow-up time of 409 ± 125days. Ten patients (91%) had experienced weight regain from their post-RYGB nadir weight. For these patients, the average total body weight loss 12months post-TORe was 12.4 ± 12%. There were no complications requiring hospitalization. One patient experienced post-TORe nausea and vomiting requiring dilation of the gastrojejunal anastomosis with resolution in symptoms. TORe is a safe and effective treatment for post-prandial hypoglycemia and weight regain after RYGB in patients with symptoms refractory to medications and dietary changes.

Insulin Resistance and Hypertension: Mechanisms Involved and Modifying Factors for Effective Glucose Control.

Factors such as aging, an unhealthy lifestyle with decreased physical activity, snacking, a standard Western diet, and smoking contribute to raising blood pressure to a dangerous level, increasing the risk of coronary artery disease and heart failure. Atherosclerosis, or aging of the blood vessels, is a physiological process that has accelerated in the last decades by the overconsumption of carbohydrates as the primary sources of caloric intake, resulting in increased triglycerides and VLDL-cholesterol and insulin spikes. Classically, medications ranging from beta blockers to angiotensin II blockers and even calcium channel blockers were used alone or in combination with lifestyle modifications as management tools in modern medicine to control arterial blood pressure. However, it is not easy to control blood pressure or the associated complications. A low-carbohydrate, high-fat (LCHF) diet can reduce glucose and insulin spikes, improve insulin sensitivity, and lessen atherosclerosis risk factors. We reviewed articles describing the etiology of insulin resistance (IR) and its impact on arterial blood pressure from databases including PubMed, PubMed Central, and Google Scholar. We discuss how the LCHF diet is beneficial to maintaining arterial blood pressure at normal levels, slowing down the progression of atherosclerosis, and reducing the use of antihypertensive medications. The mechanisms involved in IR associated with hypertension are also highlighted.

An Imbalance of Pathophysiologic Factors in Late Postprandial Hypoglycemia Post Bariatric Surgery: A Narrative Review.

With a rise in obesity and more patients opting for bariatric surgery, it becomes crucial to understand associated complications like postprandial hypoglycemia (PPH). After bariatric surgery, significant changes are seen in insulin sensitivity, beta cell function, glucagon-like peptide 1 (GLP-1) levels, the gut microbiome, and bile acid metabolism. And in a small subset of patients, exaggerated imbalances in these functional and metabolic processes lead to insulin-glucose mismatch and hypoglycemia. The main treatment for PPH involves dietary modifications. For those that do not respond, medications or surgical interventions are considered to reverse some of the imbalances. We present a few case reports of patients that safely tolerated GLP-1 agonists. However, larger randomized control trials are needed to further characterize PPH and understand its treatment.

Uncovering personalized glucose responses and circadian rhythms from multiple wearable biosensors with Bayesian dynamical modeling

Wearable biosensors and smartphone applications can measure physiological variables over multiple days in free-living conditions. We measure food and drink ingestion, glucose dynamics, physical activity, heart rate (HR), and heart rate variability (HRV) in 25 healthy participants over 14days. We develop a Bayesian inference framework to learn personal parameters that quantify circadian rhythms and physiological responses to external stressors. Modeling the effects of ingestion events on glucose levels reveals that slower glucose decay kinetics elicit larger postprandial glucose spikes, and we uncover a circadian baseline rhythm for glucose with high amplitudes in some individuals. Physical activity and circadian rhythms explain as much as 40%-65% of the HR variance, whereas the variance explained for HRV is more heterogeneous across individuals. A more complex model incorporating activity, HR, and HRV explains up to 15% of additional glucose variability, highlighting the relevance of integrating multiple biosensors to better predict glucose dynamics.

Association between pre-exercise food ingestion timing and reactive hypoglycemia: Insights from a large database of continuous glucose monitoring data

ABSTRACT Using a large database of continuous glucose monitoring (CGM) data, this study aimed to gain insights into the association between pre-exercise food ingestion timing and reactive hypoglycemia. A group of 6,761 users self-reported 48,799 pre-exercise food ingestion events and logged minute-by-minute CGM, which was used to detect reactive hypoglycemia (<70 mg/dL) in the first 30 min of exercise. A linear and a non-linear binomial logistic regression model was used to investigate the association between food ingestion timing and the probability of experiencing reactive hypoglycemia. An analysis of variance was conducted to compare the predictive ability of the models. On average, reactive hypoglycemia was detected in 8.34 ± 3.04% of the total events, with <15% of individuals experiencing hypoglycemia in >20% of their events. The majority of the reactive hypoglycemia events were found with pre-exercise food timing between ∼30 and ∼90 min, with a peak at ∼60 min. The superior accuracy (62.05 vs 45.1%) and F-score (0.75 vs 0.59) of the non-linear vs the linear model were statistically superior (P < 0.0001). These results support the notion of an unfavourable 30-to-90 min pre-exercise food ingestion time window which can significantly impact the likelihood of reactive hypoglycemia in some individuals.

Jointly Predicting Postprandial Hypoglycemia and Hyperglycemia Using Continuous Glucose Monitoring Data in Type 1 Diabetes.

The development of continuous glucose monitoring (CGM) systems has enabled people with type 1 diabetes mellitus (T1DM) to track their glucose trajectory in real-time and inspired research in personalised glucose prediction. In this paper, our aim is to predict postprandial abnormal-glycemia events. Different from prior research which focuses on hypoglycemia only, we make the first attempt to establish our problem as the joint prediction of hyperglycemia and hypoglycemia. On this basis, we propose a machine learning model that learns from the pattern of 1 hour past glucose and makes predictions for the two tasks simultaneously using a unified backbone. Key benefits of our methodology include 1) requiring only the CGM sequence as the input, thus making it more widely applicable than other counterparts using extra inputs such as the nutrition details, and 2) minimising the computational cost as the two tasks are unified into a single model. Our experiments on the openly available OhioT1DM dataset achieve state-of-the-art performance (Matthew's correlation coefficient of 0.61 for hyperglycemia and 0.48 for hypoglycemia). To encourage further study, we release our codes at https://github.com/r-cui/PostprandialHyperHypoPrediction under the MIT license.

The Relationship of Fruits and Fruit-Products Consumption with Glucose Homeostasis and Diabetes: A Comprehensive Update on the Current Clinical Literature

Type 2 diabetes mellitus is a major contributor to morbidity and mortality worldwide. This disease often leads to poor health outcomes, such as neuropathy and diabetic foot ulcers, and increased risk for comorbidities such as cardiovascular complications and renal disease. Lifestyle modifications including diet and physical activity interventions are often explored as prevention and management strategies for T2DM. It is well established that fruits are a rich source of fiber and a variety of phytochemicals, vitamins, minerals, and bioactive compounds that can help optimize human health. Unfortunately, many experts associate the consumption of fruit with a moderate to high glycemic index (GI), which leads to a spike in blood glucose and eventually elevated hemoglobin A1c (HbA1c). The purpose of this comprehensive review is to outline the current clinical literature on the relationship between fruit consumption and various indices of glucose metabolism. A variety of fruits have been clinically studied to determine this relationship, namely in the fresh form (e.g., berries, apples, watermelon, cherries, mangoes), dried fruits (raisins and dates), and juices (derived from cranberry, orange, grape, cherry, and pomegranate). Overall, intake of fruits and fruit-derived products is beneficial for healthy subjects and subjects with T2DM regarding their impact on glucose metabolism and other cardiometabolic markers (e.g., inflammatory responses, lipid profiles). Nonetheless, it is more advisable for diabetic patients to consume fresh or dried fruits rather than fruit-derived products. A special consideration needs to be attributed to both the amount of fruit intake with regards to their respective GI and glycemic load (GL), and when these fruits are consumed. Trials with more a comprehensive design and specific outcomes are required to reveal the mechanisms underlying the beneficial effects of fruit consumption on the T2DM population particularly.

The Effects of Elexacaftor, Tezacaftor, and Ivacaftor (ETI) on Blood Glucose in Patients With Cystic Fibrosis: A Systematic Review.

Cystic fibrosis (CF) is an autosomal recessive genetic disorder resulting from defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which in turn results in a multi-systemic disorder. There are numerous known CF alleles associated with different mutations of the CFTR gene, with the most common CF allele being a three-base-pair deletion known as ΔF508. One common manifestation of CF is glycemic dysregulation associated with decreased insulin secretion, often progressing into a distinct form of diabetes known as cystic fibrosis-related diabetes (CFRD). In the past decade, a class of drugs known as CFTR modulators has entered clinical practice. These drugs interact with the CFTR protein to restore its function, with different modulators (or combinations of modulators) suitable for patients with different CFTR mutations. Previous research has established that the modulator ivacaftor is effective in decreasing blood glucose and sometimes resolving CFRD in patients with certain CFTR mutations (class III mutations). However, early modulator therapies for individuals with the common ΔF508 mutation (e.g., a combination of the modulators lumacaftor and ivacaftor) have largely proven ineffective in improving glucose regulation. More recently, a combination therapy of three modulators, namely elexacaftor, tezacaftor, and ivacaftor (ETI), has entered clinical practice for patients with the ΔF508 mutation. However, it is not clear whether this therapy is effective in treating dysglycemia. We searched for studies of any design that examined the effects of ETI on measures of blood glucose. All available studies were observational studies comparing patients before and after initiating ETI therapy. Measures of daily-life blood glucose (those obtained with continuous glucose monitoring systems or by measuring glycated hemoglobin (HbA1c)) and post-prandial glucose spikes from oral glucose tolerance tests showed significant improvements in at least some studies. The majority of studies showed significant improvements from pre- to post-ETI in one or more blood glucose measures. While the interpretation of this evidence is complicated by the lack of randomized controlled trials, it appears that ETI therapy is associated with improved glucose regulation for at least some patients with the ΔF508 mutation.

Dumping Syndrome in Children: A Narrative Review.

Dumping syndrome (DS) is a typical side effect of stomach surgery, which includes cancer, non-cancer esophageal and gastric surgery, and bariatric surgery. It is marked by the fast evacuation of undigested food from the stomach into the small intestine, which causes a variety of symptoms. Early dumping symptoms include gastrointestinal symptoms such as stomach discomfort, diarrhea, and nausea, as well as vasomotor symptoms such as drowsiness and face flushing, and occur within the first hour following a meal. Late dumping symptoms appear one to three hours after a meal and are related to reactive hypoglycemia, resulting in hypoglycemia, sweating, palpitations, and confusion. Early dumping pathophysiology involves abnormalities in stomach structure and function, which result in rapid transit of stomach contents to the duodenum, insufficient digestion, and fluid transfers from the vascular compartment to the intestine. Late dumping occurs as a result of hyperinsulinemia caused by the fast passage of undigested foods to the gut. Symptom-based questionnaires and diagnostic testing such as plasma glucose measurement and stomach emptying studies can be used to confirm a diagnosis of DS. The primary approach to managing DS is dietary modifications, including eating smaller, more frequent meals and avoiding high glycemic index carbohydrates. Dietary supplements and medications may be used to slow down gastric emptying or control blood glucose levels. Pharmacological options include alpha-glycosidase inhibitors, somatostatin analogs, glucagon-like peptide-1 analogs, and sodium-glucose cotransporter inhibitors. In severe cases, refractory to conservative measures, surgical interventions may be considered. DS can arise in children following gastric surgery for obesity or corrective surgery for congenital abnormalities. It is frequently misdiagnosed and can have serious implications, such as hypoglycemia-related cognition deficits. Screening and early identification using glucose tolerance testing and continuous glucose monitoring (CGM) are critical in at-risk youngsters. Children's treatment techniques are similar to those used in adults, with dietary changes and medication therapies serving as the cornerstone of care. Overall, DS is a complex condition that requires a multidisciplinary approach to diagnosis and management. Further research is needed to improve understanding of its pathophysiology and optimize treatment strategies, particularly in children. This review aims to provide a well-rounded informative summary of the most recent literature on the under-recognized clinical and scientific aspects of DS among the children age group. It incorporates the quality of life, pathophysiology, diagnosis, prevalence, and treatment.

Patient-reported outcomes, weight loss, and remission of type 2 diabetes 3 years after gastric bypass and sleeve gastrectomy (Oseberg); a single-centre, randomised controlled trial

Little is known about the comparative effects of various bariatric procedures on patient-reported outcomes. We aimed to compare 3-year effects of gastric bypass and sleeve gastrectomy on patient-reported outcome measures in patients with obesity and type 2 diabetes. The Oseberg trial was a single-centre, parallel-group, randomised trial at Vestfold Hospital Trust, a public tertiary obesity centre in Tønsberg, Norway. Eligible patients were aged 18 years or older with previously verified BMI 35·0 kg/m2 or greater. Diabetes was diagnosed if glycated haemoglobin was at least 6·5% (48 mmol/mol) or by their use of anti-diabetic medications with glycated haemoglobin at least 6·1% (43 mmol/mol). Eligible patients were randomly assigned (1:1) to gastric bypass or sleeve gastrectomy. All patients received identical preoperative and postoperative treatment. Randomisation was done with a computerised random number generator and a block size of ten. Study personnel, patients, and the primary outcome assessor were blinded to allocations for 1 year. The prespecified secondary outcomes reported here were 3-year changes in several clinically important patient-reported outcomes, weight loss, and diabetes remission. Analyses were done in the intention to treat population. This trial is ongoing, closed to recruitment and is registered with ClinicalTrials.gov, NCT01778738. Between Oct 15, 2012 and Sept 1, 2017, 319 consecutive patients with type 2 diabetes scheduled for bariatric surgery were assessed for eligibility. 101 patients were not eligible (29 did not have type 2 diabetes according to inclusion criteria and 72 other exclusion criteria) and 93 declined to participate. 109 patients were enrolled and randomly assigned to sleeve gastrectomy (n=55) or gastric bypass (n=54). 72 (66%) of 109 patients were female and 37 (34%) were male. 104 (95%) of patients were White. 16 patients were lost to follow up and 93 (85%) patients completed the 3-year follow-up. Three additional patients were contacted by phone for registration of comorbidities Compared with sleeve gastrectomy, gastric bypass was associated with a greater improvement in weight-related quality of life (between group difference 9·4, 95% CI 3·3 to 15·5), less reflux symptoms (0·54, 0·17 to -0·90), greater total bodyweight loss (8% difference, 25% vs 17%), and a higher probability of diabetes remission (67% vs 33%, risk ratio 2·00; 95% CI 1·27 to 3·14). Five patients reported postprandial hypoglycaemia in the third year after gastric bypass versus none after sleeve-gastrectomy (p=0·059). Symptoms of abdominal pain, indigestion, diarrhoea, dumping syndrome, depression, binge eating, and appetitive drive did not differ between groups. At 3 years, gastric bypass was superior to sleeve gastrectomy in patients with type 2 diabetes and obesity regarding weight related quality of life, reflux symptoms, weight loss, and remission of diabetes, while symptoms of abdominal pain, indigestion, diarrhoea, dumping, depression and binge eating did not differ between groups. This new patient-reported knowledge can be used in the shared decision-making process to inform patients about similarities and differences between expected outcomes after the two surgical procedures. Morbid Obesity Centre, Vestfold Hospital Trust. For the Norwegian translation of the abstract see Supplementary Materials section.

Continuous glucose monitoring in a patient with insulinoma presenting with unawareness of postprandial hypoglycemia.

Unawareness of postprandial hypoglycemia for 5 years was identified in a 66-year-old man at a local clinic. The patient was referred to our hospital because of this first awareness of hypoglycemia (i.e. lightheadedness and impaired consciousness) developing after lunch. In a 75 g oral glucose tolerance test, the plasma glucose concentration was decreased to 32 mg/dL (1.8 mmol/L) at 150 min with relatively high concentrations of insulin (8.1 μU/mL), proinsulin (70.3 pmol/L), and C-peptide (4.63 ng/mL). In a prolonged fasting test, the plasma glucose concentration was decreased to 43 mg/dL (2.4 mmol/L) at 66 h with an insulin concentration of 1.4 μU/mL and a C-peptide concentration of 0.49 ng/mL. Computed tomography showed an 18 mm hyperenhancing tumor in the uncinate process of the pancreas. A selective arterial calcium stimulation test showed an elevated serum insulin concentration in the superior mesenteric artery. The patient was then diagnosed with insulinoma and received pancreaticoduodenectomy. Continuous glucose monitoring (CGM) using the Dexcom G6 system showed unawareness of hypoglycemia mainly during the daytime before surgery. When the sensor glucose value was reduced to 55 mg/dL (3.1 mmol/L), the Dexcom G6 system emitted an urgent low glucose alarm to the patient four times for 10 days. Two months after surgery, an overall increase in daily blood glucose concentrations and resolution of hypoglycemia were shown by CGM. We report a case of insulinoma with unawareness of postprandial hypoglycemia in the patient. The Dexcom G6 system was helpful for assessing preoperative hypoglycemia and for evaluating outcomes of treatment by surgery. Insulinoma occasionally leads to postprandial hypoglycemia. The CGM system is useful for revealing the presence of unnoticed hypoglycemia and for evaluating treatment outcomes after surgical resection. The Dexcom G6 system has an urgent low glucose alarm, making it particularly suitable for patients who are unaware of hypoglycemia.

Mixed Meal Tolerance Test Versus Continuous Glucose Monitoring for an Effective Diagnosis of Persistent Post-Bariatric Hypoglycemia.

Gastric bypass determines an increase in incretin secretion and glucose excursions throughout the day and may sometimes entail the development of severe post-bariatric hypoglycemia (PBH). However, there is no consensus on the gold standard method for its diagnosis. In this study, we evaluated the usefulness of a mixed meal tolerance test (MMTT) and continuous glucose monitoring (CGM) for the diagnosis of PBH, defined as glucose levels <54 mg/dL (3.0 mmol/L). We found that hypoglycemia occurred in 60% of patients after the MMTT and in 75% during CGM, and it was predominantly asymptomatic. The MMTT confirmed the diagnosis of PBH in 88.9%of patients in whom surgery had been performed more than three years ago, in comparison to 36.4% in cases with a shorter postsurgical duration. CGM diagnosed nocturnal asymptomatic hypoglycemia in 70% of patients, and daytime postprandial hypoglycemia in 25% of cases. The mean duration of asymptomatic hypoglycemia was more than 30 min a day. Patients with ≥2% of their CGM readings with hypoglycemia exhibited a higher degree of glucose variability than those with <1% of the time in hypoglycemia. Our results show that the MMTT may be a useful dynamic test to confirm the occurrence of hypoglycemia in a large number of patients with persistent and recurrent PBH during long-term follow-up after gastric bypass. CGM, on its part, helps identify hypoglycemia in the real-world setting, especially nocturnal asymptomatic hypoglycemia, bringing to light that PBH is not always postprandial.

254-OR: Effects of Roux-en-Y Gastric Bypass on Postprandial Glucose Turnover Assessed through the Single-Tracer Oral Minimal Model

Rearrangements of gastrointestinal anatomy after Roux-en-Y gastric bypass (RYGB) surgery alter postprandial glucose metabolism. However, the impact on different components of glucose homeostasis remain incompletely understood. Here, we aim to evaluate the effects of RYGB on postprandial glucose turnover, production (P) and disposal (D) glucose effectiveness (GEP, GED) and production and disposal sensitivity to insulin (SIP, SID). Ten RYGB (2M, age=39.2±3.1 y, BMI=28±1 kg/m2- mean±SE) subjects and 10 healthy controls (5M, age=36.4±3.2 y, BMI=26±1 kg/m2) ingested 60g of glucose (G) labelled with [6,6-2H2]-glucose. Plasma samples were frequently drawn to measure G, insulin (I) and tracer concentrations in the following 180 min. The Single-Tracer Oral Minimal Model was used to estimate meal glucose rate of appearance (Ra), endogenous glucose production (EGP), glucose disposal (Rd), GEP, GED, SIP and SID. Incremental area under the G curve (iAUC(G)) was not different in the two groups, while iAUC(I) was significantly higher in RYGB (8346±803 vs. 5451±602 μU/mL*min, p=0.011); iAUC(Ra) normalized to the G dose was significantly higher in the first 60 min after the meal (0.72±0.04 vs. 0.28±0.03, p&amp;lt;0.001) while, throughout the experiment, EGP suppression (EGPs) normalized to basal (EGPb) was significantly lower (0.31±0.06 vs. 0.55±0.05, p=0.006) and iAUC(Rd) normalized to basal (Rdb) was higher (3.46±0.10 vs. 2.82±0.08, p&amp;lt;0.001) in RYGB than controls. Model predicted SIP was significantly lower in RYGB than controls (2.0±0.5 vs. 5.1±1.2 10-4 dL/kg/min per μU/mL, p=0.033) while no differences were observed in GEP, GED and SID. We concluded that the abnormally high I concentration in RYGB was responsible for the higher iAUC(Rd) in the operated individuals, while the reduced SIP likely works as a protective mechanism against postprandial hypoglycaemia by reducing EGPs despite the high circulating I. Disclosure A.Brunasso: None. C.Dalla man: Research Support; Sanofi-Aventis Deutschland GmbH, Becton, Dickinson and Company. D.Herzig: None. L.Bally: Research Support; Dexcom, Inc., Ypsomed AG. M.Schiavon: None. Funding Italian Minister for Education (Law 232/2016); Swiss National Science Foundation (PCEGP3_186978)

106-LB: Postprandial Glucose Management among Adults Living with Type 1 Diabetes Using Single-Hormone and Dual-Hormone Automated Insulin Delivery Systems

Introduction: Despite the rapid advances of diabetes technologies, postprandial glucose management remains a challenge for people living with type 1 diabetes (pwT1D). We aim to assess the efficacy of single-hormone (SH) compared to dual-hormone (DH) automated insulin delivery (AID) systems in postprandial glucose management. Methods: Post-hoc analysis of a randomized controlled crossover inpatient trial including three standardized meals (taken at 8am, 12 pm, and 5pm) during a 24-hour period, comparing SH-AID and DH-AID among pwT1D. Data from meals of each participant was pooled. Primary outcome was time in range % (TIR%, 70 to 180 mg/dL), calculated by continuous glucose monitoring during the 4-hour postprandial period. Paired t-test was used to compare the two groups. Results: Eighteen adult participants were included (mean age [SD] 43 [14] years, mean duration of T1D 20 [11] years, mean HbA1c 7.6% [1.0], mean daily insulin intake 26.70 [11.04] units). Postprandial TIR% was similar between SH and DH-AID (66.4% vs 70.2%, p=0.443). Less time in postprandial hypoglycemia (&amp;lt;70 mg/dL) was observed in the DH-AID group compared to SH-AID (5.4% vs 11.9%, p=0.019). No difference was observed in postprandial time spent in hyperglycemia (&amp;gt;180 mg/dL), glycemic variability indices or insulin intake between the two groups. Conclusion: Compared with SH-AID, DH-AID reduces postprandial hypoglycemia, while other postprandial glucose metrics remain similar among adult pwT1D. Disclosure M. Lebbar: None. J. Molveau: None. V. Boudreau: None. R. Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. Z. Wu: Other Relationship; Eli Lilly and Company.

1586-P: Post-OGTT Low Blood Glucose in Individuals with Metabolic Syndrome, Metabolic Phenotypes, and Metabolic-Associated Fatty Liver Disease

Introduction: Post-prandial low blood glucose (LBG) is usually associated with late postprandial hyperinsulinemia in metabolic syndrome (MetS), but have not been well studied. Objectives: We aimed to 1) characterize insulin/glucose metabolism associated with LBG post 75g OGTT in a sample of individuals with MetS; and 2) assess the association between MAFLD (≥ 5% liver fat at MRI) and LBG. Methods: Plasma glucose, insulin and c-peptide concentrations were measured on OGTT over 180 mins. Insulin sensitivity and secretion were assessed with the Oral Minimal Model. During OGTT, we defined glucose ≤ 50 mg/dl as LBG, glucose &amp;gt; 70 mg/dl as no LBG and glucose 51-70 mg/dl as undefined status and were excluded from this analysis. Results: Of 82 participants, 50 were included and 15 (18 %) experienced LBG. Of the 33 participants who underwent MRI, 48% had MAFLD. Median age and BMI were 59 [IQR: 49-74] years and 28 [IQR: 26-31] kg/m2 respectively. Women represented 70% (n=35) of participants and experienced less LBG (p=0.0002) than men. Individuals experiencing LBG had higher insulin sensitivity (p=0.02), higher ß cell function (p=0.03), earlier glucose peaks (p&amp;lt;0.0001) and lower c-peptide peaks (p=0.007) than those without LBG. MAFLD was not associated with more LBG (p=0.7), but was associated with a different insulin curve. LBG+MAFLD status was associated with higher and later c-peptide and insulin levels compared to LBG without MAFLD status. Conclusion: In contrary to our hypothesis, individuals with MetS without MAFLD experiencing glucose ≤ 50 mg/dl during OGTT displayed a healthier metabolic profile. However, individuals with MAFLD experiencing a LBG during OGTT had a glucose phenotype similar to the late post-prandial hyperinsulinemic hypoglycemia often found in prediabetes state and associated with worst metabolic parameters. This suggests that MAFLD may be an important feature of MetS associated with a different post-OGTT glucose metabolism. Disclosure T.Gignac: None. A.Morissette: None. A.Agrinier: None. C.Gagnon: Advisory Panel; Novo Nordisk, Other Relationship; Ascendis Pharma A/S, Research Support; Novo Nordisk. M.Vohl: None. A.Marette: Advisory Panel; Valbiotis, Amancia, Plexus, Acasti. A.Carreau: Advisory Panel; Novartis, Consultant; Valbiotis, Speaker's Bureau; Novo Nordisk Canada Inc.

276-OR: Postprandial Hyper- and Hypoglycemia Are Related to Injection Time—An Insulclock Connected Insulin Cap–Based Real-World Study

Background: Reaching the optimal postprandial glucose dynamics is a daily challenge for people with T1D. The study aimed to analyze postprandial hyperglycemia excursion (PHE) and late postprandial hypoglycemia (LPH) risk according to insulin injection time. Methods: Real-world, retrospective study in T1D using multiple daily injection (MDI) insulin. Five hours of paired CGM and automatically tracked insulin injections were collected with the Insulclock® connected cap. Meal events were identified using the ROC detection methodology. Postprandial glucometrics and LPH (glucose &amp;lt;70 mg/dL 2-5 hours after a meal) were evaluated according to insulin injection time. Results: Meal glycemic excursions (n=2784) were analyzed in 82 people. In 63% insulin was injected after the meal started. The best balance between PHE control and LPH risk is obtained by injecting -15 to 0 minutes before meals. Higher PHE (glucose peak-baseline; mg/dL) was observed in delayed injections (mean±SD): Early (-45-15 min) (n=348) 101.8 ± 34.0; Optimal (-15-0 min)(n=612) 98.3± 29.8; Delayed (0-+45 min) (n=1528) 114.8±40,2 (n=348), (p &amp;lt;0.001). LPH risk also increased with delayed injections, n (%): Early 31 (8.9); Optimal 47 (7.7); Delayed 171 (11.2), (p 0.038). Conclusion: The correct timing of insulin injection is crucial to reduce postprandial hyper- and hypoglycemia. Disclosure F.Gomez-peralta: Advisory Panel; Abbott Diabetes, Insulcloud S.L., Speaker's Bureau; A. Menarini Diagnostics, Boehringer Ingelheim and Eli Lilly Alliance, Lilly Diabetes, Novartis, Novo Nordisk. C.Cerqueira: Employee; Insulcloud S.L. J.Pérez: Employee; Insulcloud S.L. L.Ruiz-valdepeñas: Employee; Insulcloud S.L., Stock/Shareholder; Insulcloud S.L. X.Valledor: Employee; Insulcloud S.L. A.Lopez-picado: Employee; Insulcloud S.L.. C.Abreu: Speaker's Bureau; Lilly, Novo Nordisk. E.Fernández-rubio: Speaker's Bureau; Lilly Diabetes, Novo Nordisk, AstraZeneca. P.Pujante alarcón: None. E.García: Advisory Panel; Airliquide, Speaker's Bureau; Abbott Diabetes, Dexcom, Inc., Boehringer Ingelheim and Eli Lilly Alliance, Novo Nordisk, Sanofi, Airliquide. S.Azriel: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk, Medtronic, Speaker's Bureau; Dexcom, Inc., Lilly Diabetes, AstraZeneca, Sanofi. R.Corcoy: Advisory Panel; Novo Nordisk, Other Relationship; Novo Nordisk, Lilly, Sanofi, Abbott, Speaker's Bureau; Sanofi, Roche Diabetes Care.

817-P: Late Postprandial Hypoglycemia Is Reduced with Ultrarapid Insulin—An Insulclock Connected Cap-Based Real-World Study

Background: Reaching optimal postprandial glucose dynamics is a daily challenge in T1D people. The study aimed to analyze the postprandial hyperglycemia excursion (PHE) and late postprandial hypoglycemia (LPH) risk according to time and type of insulin. Methods: Real-world (RW), retrospective study in T1D using multiple daily injection (MDI) insulin. Five hours of paired CGM and automatically tracked insulin injections collected with the connected cap Insulclock®. Meal events were identified using the ROC detection methodology. Postprandial glucometrics and LPH (glucose &amp;lt;70mg/dL 2-5 hours after a meal) were evaluated according to insulin injection time and type: rapid (RI) or ultrarapid analog-Fiasp®- (URI). Results: Meal glycemic excursions (n= 2488), RI: 1211, 48.7%; UR: 1277, 51.3%, in 82 people. In 63% insulin was injected after the meal started. URI use was associated with lower LPH risk URI vs RI, n(%): Early (-45-15 min): 20 (9,5) vs 11 (8,0); Optimal (-15-0 min): 18 (6,4) vs 29 (8,8); Delayed (0+45 min) 71 (9,1) vs 100 (13,4); (p 0.012). Lower PHE (Glucose peak-baseline; mg/dL) was observed with URI vs RI (mean±SD): Early: 102.23 ±32.19 vs 101.2 ±36.73; Optimal: 96.62 ±29.63 vs 99.89 ±29.93; Delayed 111.6 ±40.2 vs 118.13 ±43.3; (p &amp;lt;0.001). Conclusion: Ultrarapid analog use reduces postprandial hyper- and hypoglycemia, even in the case of delayed injections. Disclosure F.Gomez-peralta: Advisory Panel; Abbott Diabetes, Insulcloud S.L., Speaker's Bureau; A. Menarini Diagnostics, Boehringer Ingelheim and Eli Lilly Alliance, Lilly Diabetes, Novartis, Novo Nordisk. C.Cerqueira: Employee; Insulcloud S.L. J.Pérez: Employee; Insulcloud S.L. L.Ruiz-valdepeñas: Employee; Insulcloud S.L., Stock/Shareholder; Insulcloud S.L. X.Valledor: Employee; Insulcloud S.L. A.Lopez-picado: Employee; Insulcloud S.L.. C.Abreu: Speaker's Bureau; Lilly, Novo Nordisk. P.Pujante alarcón: None. E.Fernández-rubio: Speaker's Bureau; Lilly Diabetes, Novo Nordisk, AstraZeneca. E.García: Advisory Panel; Airliquide, Speaker's Bureau; Abbott Diabetes, Dexcom, Inc., Boehringer Ingelheim and Eli Lilly Alliance, Novo Nordisk, Sanofi, Airliquide. S.Azriel: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk, Medtronic, Speaker's Bureau; Dexcom, Inc., Lilly Diabetes, AstraZeneca, Sanofi. R.Corcoy: Advisory Panel; Novo Nordisk, Other Relationship; Novo Nordisk, Lilly, Sanofi, Abbott, Speaker's Bureau; Sanofi, Roche Diabetes Care.