Postprandial Hypoglycemia Research Articles

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 (<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 (>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 > 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<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 <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 <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 <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 <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.

623-P: Impact of a Low-Carbohydrate vs. Low-Fat Breakfast on Blood Glucose Control in Type 2 Diabetes

Postprandial hyperglycemia and glycemic variability are independent risk factors for cardiovascular disease and mortality in people living with type 2 diabetes (T2D). The highest glucose spike often occurs after the first morning meal, highlighting the major influence that breakfast has on overall glycemic control. We examined how advice and guidance to consume a low-carbohydrate (LC) versus standard dietary guidelines low-fat control (CTL) breakfast influenced glycemic control assessed by continuous glucose monitoring (CGM). Participants with T2D (N=121, 53% female, mean age 64 years) completed a remote 3-month parallel-group RCT comparing LC to CTL with 14-day CGM at the start and end of the intervention. Daily mean glucose, maximum glucose, area under the curve (AUC), mean amplitude of glycemic excursions, standard deviation (SD), and time above range (>10mmol/L) were all significantly lower, and time in range (3.9-10mmol/L) significantly higher, in the LC group versus CTL (all P<0.05). Post-breakfast mean and maximum glucose, SD and iAUC were also significantly lower in the LC group (all P<0.001). A low-carbohydrate breakfast appears to be a simple dietary strategy to improve several CGM metrics when compared to a typical dietary guidelines breakfast in persons living with T2D. Disclosure B.Oliveira: None. C.Chang: None. K.Falkenhain: None. K.Oetsch: None. M.E.Francois: None. J.P.Little: None. Funding Egg Nutrition Center; Egg Farmers of Canada

293-LB: Dorzagliatin, a Glucokinase Activator, Restores Glucose-Sensing in Type 2 Diabetic Human Islets

Introduction: Glucokinase (GK) has been considered a drug target for type 2 diabetes (T2D) to restore glucose sensing in beta cells. However, GK activators such as MK-0941 have had limited clinical success, causing hypoglycemia and other serious adverse events in terminated clinical trials. In contrast, the novel GK activator dorzagliatin, an approved therapy for T2D, showed sustained reduction in HbA1c in T2D patients and no serious adverse events. The purpose of the current study is to compare the effects of dorzagliatin with other GK activators, including MK-0941, on GK enzyme kinetics and the function of islets from T2D donors. Methods: Insulin secretion was assessed in islets from 8 T2D donors and 38 controls obtained through the Integrated Islet Distribution Program. Both glucose step and glucose ramp perifusion protocols were used to assess glucose-stimulated insulin secretion (GSIS). GK-GK activator binding was performed using molecular dynamics analysis. Publicly available data from the Human Pancreas Analysis Program were also used. Results: Unlike MK-0941 which strongly activates GK enzyme even at very low glucose levels, dorzagliatin activation of GK is glucose dose-dependent. This can be explained by molecular dynamics analysis showing dorzagliatin binds to GK with less affinity than MK-0941. T2D islets showed a right-shifted glucose threshold for GSIS and/or a reduction in the maximal rate of GSIS (Vmax) compared to controls in response to high glucose and IBMX, and dorzagliatin recovers both the threshold and Vmax. In contrast, MK-0941 induces a rapid and transient insulin spike at very low glucose concentrations but has a reduced response to high glucose. Conclusion: In isolated T2D islets, dorzagliatin recovers both the normal glucose threshold and Vmax and has a wider dose range compared to MK-0941. These findings may explain why MK-0941 causes hypoglycemia whereas dorzagliatin improves blood glucose without any serious adverse events in T2D patients. Disclosure J. Roman: None. Q. Zhu: Employee; Nanjing AscendRare Pharmaceutical Technology. Y. Yuan: Employee; Nanjing AscendRare Pharmaceutical Technology. C. Li: Employee; Hua Medicine, Nanjing AscendRare Pharmaceutical Technology. L. Chen: Employee; Hua Medicine. N. M. Doliba: None.

Subclinical Reactive Hypoglycemia with Low Glucose Effectiveness-Why We Cannot Stop Snacking despite Gaining Weight.

Obesity has grown worldwide owing to modern obesogenic lifestyles, including frequent snacking. Recently, we studied continuous glucose monitoring in obese/overweight men without diabetes and found that half of them exhibit glucose levels less than 70 mg/dL after a 75-g oral glucose load without notable hypoglycemic symptoms. Interestingly, people with "subclinical reactive hypoglycemia (SRH)" snack more frequently than those without it. Since the ingestion of sugary snacks or drinks could further induce SRH, a vicious cycle of "Snacking begets snacking via SRH" can be formed. Glucose effectiveness (Sg) is an insulin-independent mechanism that contributes to most of the whole-body glucose disposal after an oral glucose load in people without diabetes. Our recent data suggest that both higher and lower Sg are associated with SRH, while the latter but not the former is linked to snacking habits, obesity, and dysglycemia. The present review addresses the possible role of SRH in snacking habits in people with obesity/overweight, taking Sg into account. It is concluded that, for those with low Sg, SRH can be regarded as a link between snacking and obesity. Prevention of SRH by raising Sg might be key to controlling snacking habits and body weight.

Long-term follow-up of methimazole-associated insulin autoimmune syndrome: a rare case report

Insulin autoimmune syndrome (IAS) is a rare cause of hypoglycemia and is characterized by the presence of insulin autoantibodies and fasting or late postprandial hypoglycemia. The number of reports on the association of long-term follow-up of IAS in China is limited. We herein report a case of drug-induced IAS in a 44-year-old Chinese woman. She had been taking methimazole for Graves’ disease and had subsequently presented with recurrent hypoglycemic episodes. Laboratory assessments on admission revealed that her serum insulin level was significantly elevated (>1000 µIU/mL) and that she was positive for serum insulin autoantibody, leading to a diagnosis of IAS. Human leukocyte antigen DNA typing identified *04:06/*09:01:02, an immunogenetic determinant associated with IAS. After treatment with prednisone for 2 months, the hypoglycemic episodes disappeared, her serum insulin level gradually declined, and her insulin antibody levels became negative. Clinicians should be aware of the potential for methimazole to trigger autoimmune hypoglycemia in people with a genetic predisposition.

Rapid screening of sixty potato cultivars for starch profiles to address a consumer glycemic dilemma.

Potatoes are a dietary staple consumed by a significant portion of the world, providing valuable carbohydrates and vitamins. However, most commercially produced potatoes have a high content of highly branched amylopectin starch, which generally results in a high glycemic index (GI). Consumption of foods with high levels of amylopectin elicit a rapid spike in blood glucose levels, which is undesirable for individuals who are pre-diabetic, diabetic, or obese. Some cultivars of potatoes with lower amylopectin levels have previously been identified and are commercially available in niche markets in some countries, but they are relatively unavailable in the United States and Latin America. The high glycemic index of widely available potatoes presents a problematic "consumer's dilemma" for individuals and families that may not be able to afford a better-balanced, more favorable diet. Some native communities in the Andes (Bolivia, Chile, and Peru) reportedly embrace a tradition of providing low glycemic tubers to people with obesity or diabetes to help people mitigate what is now understood as the negative effects of high blood sugar and obesity. These cultivars are not widely available on a global market. This study examines 60 potato cultivars to identify potatoes with low amylopectin. Three independent analyses of potato starch were used: microscopic examination of granule structure, water absorption, and spectrophotometric analysis of iodine complexes to identify potato cultivars with low amylopectin Differences among cultivars tested were detected by all three types of analyses. The most promising cultivars are Huckleberry Gold, Muru, Multa, Green Mountain, and an October Blue x Colorado Rose cross. Further work is necessary to document the ability of these low amylopectin cultivars to reduce blood glucose spike levels in human subjects.

Post-prandial hypoglycaemia of unknown origin

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Debilitating post-prandial hypoglycaemia as a sole presentation of coeliac disease responding to gluten free diet and plasma exchange for autoimmune neuromyotonia

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1413680: Post-Bariatric Hypoglycemia (PBH) Refractory to Conventional Therapies: The Combined Effect of Very High Doses of Glucagon-Like Receptor Agonist (GLP1-RA) and a Low Dose of Sodium-Glucose Cotransporter-2 Inhibitor (SGLT2i)

As the number of bariatric surgeries in the United States plateaus at nearly 200,000, the prevalence of post-bariatric hypoglycemia (PBH) is escalating. Since the pathophysiology driving PBH is not fully understood, treatment for PBH can be challenging in the clinical practice. Most recently, the use of GLP1-RA or SGLT2i have been reported as monotherapy options for PBH. We are presenting the case of a patient without diabetes who failed conventional therapy for her persistent PBH and dumping syndrome but was successfully treated with very high doses of liraglutide and a low dose of empagliflozin. A 50-year-old Hispanic woman was referred to endocrinology with an 8-year history of recurrent syncope due to hypoglycemia. She was diagnosed with non-insulinoma pancreatogenic hypoglycemia complicated by PBH and dumping syndrome. She had a history of Roux-en-Y gastric bypass 10 years prior. Initially, she attempted diet modification, by eating less than 20 grams of carbohydrates per meal, with no improvement. Next, she trialed acarbose, which resulted in ongoing hypoglycemic events and gastrointestinal side effects. Intermittent-scanning Continuous Glucose Monitor (CGM) revealed 4% Target Below Range (TBR, <70 mg/dL) off of acarbose despite eating every 2 hours to avoid hypoglycemia. Her hypoglycemic events were confirmed with a glucometer. We started her on Octreotide 50 mcg sq twice daily (BID), which improved TBR to 1% but resulted in relentless constipation. To regulate her bowels, her Octreotide was adjusted to 25 mcg AM and 50 mcg PM, but her TBR increased to 3%. With the addition of Liraglutide 0.6 mg sq daily to Octreotide 50 mcg BID, her constipation was unbearable, and her TBR was 2%. She remained on Octreotide 50 mcg BID and Liraglutide was up-titrated to 1.2 mg daily (TBR 4%) and then 1.8mg daily (TBR 4%). Octreotide was discontinued. On liraglutide 2.4mg daily alone, she continued without nocturnal hypoglycemia. She noted improvement in both her gastrointestinal side effects and her post-prandial hypoglycemia (TBR 3%). The dose of Liraglutide was maximized to 3 mg daily. Her CGM was changed to real-time CGM, and her TBR was 2.4%. Empagliflozin 10 mg daily was added to Liraglutide 3 mg daily, and her hypoglycemia instantly, and completely resolved with a sustained TBR of 0%. Very high doses of Liraglutide combined with a low dose of empagliflozin corrected PBH to TBR 0% and resolved the dumping syndrome symptoms. This combination therapy should be considered in patients with PBH not responding to conventional anti-hypoglycemic monotherapies.

Unraveling, contributing factors to the severity of postprandial hypoglycemia after gastric bypass surgery.

Despite the increasing prevalence of postbariatric hypoglycemia (PBH), a late metabolic complication of bariatric surgery, our understanding of its diverse manifestations remains incomplete. To contrast parameters of glucose-insulin homeostasis in 2 distinct phenotypes of PBH (mild versus moderate hypoglycemia) based on nadir plasma glucose. University Hospital (Bern, Switzerland). Twenty-five subjects with PBH following gastric bypass surgery (age, 41 ± 12 years; body mass index, 28.1 ± 6.1kg/m2) received 75g of glucose with frequent blood sampling for glucose, insulin, C-peptide, and glucagon-like peptide 1 (GLP)-1. Based on nadir plasma glucose (</≥50mg/dL), subjects were grouped into level 1 (L1) and level 2 (L2) PBH groups. Beta-cell function (BCF), GLP-1 exposure (λ), beta-cell sensitivity to GLP-1 (π), potentiation of insulin secretion by GLP-1 (PI), first-pass hepatic insulin extraction (HE), insulin sensitivity (SI), and rate of glucose appearance (Ra) were calculated using an oral model of GLP-1 action coupled with the oral minimal model. Nadir glucose was 43.3 ± 6.0mg/dL (mean ± standard deviation) and 60.1 ± 9.1mg/dL in L2- and L1-PBH, respectively. Insulin exposure was significantly higher in L2 versus L1 (P = .004). Mathematical modeling revealed higher BCF in L2 versus L1 (34.3 versus 18.8 10-9∗min-1; P = .003). Despite an increased GLP-1 exposure in L2 compared to L1 PBH (50.7 versus 31.9pmol∗L-1∗min∗102; P = .021), no significant difference in PI was observed (P = .204). No significant differences were observed for HE, Ra, and SI. Our results suggest that higher insulin exposure in PBH patients with lower postprandial nadir glucose values mainly relate to a higher responsiveness to glucose, rather than GLP-1.

Feeding enhances fibronectin adherence of quiescent lymphocytes through non-canonical insulin signalling.

Nutritional availability during fasting and refeeding affects the temporal redistribution of lymphoid and myeloid immune cells among the circulating and tissue-resident pools. Conversely, nutritional imbalance and impaired glucose metabolism are associated with chronic inflammation, aberrant immunity and anomalous leukocyte trafficking. Despite being exposed to periodic alterations in blood insulin levels upon fasting and feeding, studies exploring the physiological effects of these hormonal changes on quiescent immune cell function and trafficking are scanty. Here, we report that oral glucose load in mice and healthy men enhances the adherence of circulating peripheral blood mononuclear cells (PBMCs) and lymphocytes to fibronectin. Adherence to fibronectin is also observed upon regular intake of breakfast following overnight fasting in healthy subjects. This glucose load-induced phenomenon is abrogated in streptozotocin-injected mice that lack insulin. Intra-vital microscopy in mice demonstrated that oral glucose feeding enhances the homing of PBMCs to injured blood vessels in vivo. Furthermore, employing flow cytometry, Western blotting and adhesion assays for PBMCs and Jurkat-T cells, we elucidate that insulin enhances fibronectin adherence of quiescent lymphocytes through non-canonical signalling involving insulin-like growth factor-1 receptor (IGF-1R) autophosphorylation, phospholipase C gamma-1 (PLCγ-1) Tyr783 phosphorylation and inside-out activation of β-integrins respectively. Our findings uncover the physiological relevance of post-prandial insulin spikes in regulating the adherence and trafficking of circulating quiescent T-cells through fibronectin-integrin interaction.

DISCORDANCE BETWEEN HBA1C AND FASTING PLASMA GLUCOSE IN REACTIVE HYPOGLYCEMIA: A CASE SERIES

Background: Reactive Hypoglycemia (post prandial hypoglycemia) refers to recurrent episodes of low blood glucose levels that occur hours after a meal – usually within 2-5 hours after eating. It is considered to be a prediabetic state. We looked at the data of 15 patients Aims and Objectives: diagnosed with reactive hypoglycemia based on the evidence of Continuous Glucose Monitoring, to determine the correlation of reactive hypoglycemia with HbA1c and Fasting Plasma Glucose. In this series we obs Results: erved a discordance between HbA1c and Fasting Plasma Glucose in patients with Reactive Hypoglycemia. In addition, there was also a subset of patients that demonstrated normal HbA1c and Fasting Plasma Glucose. As it has been observed that patients with suspecte Conclusion: d Reactive Hypoglycemia show varied discordance between HbA1c and Fasting Plasma Glucose, it is recommended to use Continuous Glucose Monitoring in the evaluation of all patients with a suspicion of Reactive Hypoglycemia

Ethnic Variability in Glucose and Insulin Response to Rice Among Healthy Overweight Adults: A Randomized Cross-Over Study.

The influence of ethnicity on postprandial glucose and insulin responses has been reported earlier and rice is a major contributor to the overall glycaemic load of Asian and Arab diets. This study aims to compare postprandial glycaemic and insulinaemic responses to rice among healthy overweight Asian, Arab and European participants. In a randomized crossover design, 47 healthy overweight participants (23 Asian, 16 Arab, and 8 European) consumed 75 grams of glucose beverage or ate 270 grams of cooked basmati rice (75 g of available carbohydrate) on two separate occasions, separated by a one 1-week washout period. Blood glucose and insulin levels were determined at fasting 0 (fasting), 30, 60, and 120 minutes and used to determine the incremental area under the curve (iAUC). The three groups were matched on body mass index and gender. Although no differences were noted statistically in most clinical features, a wide range of variation was noted in age, systolic, diastolic blood pressure. The fasting blood glucose and insulin levels were highest among Asians, followed by Arabs and Europeans (p < 0.01). According to the HOMA-IR test and the Matsuda index, Asians have a higher insulin resistance than Arabs or Europeans when consuming a glucose beverage (p < 0.001) and rice (p < 0.01). Postprandial glucose and insulin responses to glucose beverage did not differ between ethnic groups (p = 0.28; p = 0.10). Based on an unadjusted regression model, European participants had significantly lower iAUC-glucose (p = 0.02) and iAUC-insulin (p = 0.01) after rice consumption than Asian participants. In the adjusted model, the difference between the two groups remained for iAUC-insulin (p = 0.04) but not for iAUC-glucose (p = 0.07). Our study found that ethnic differences exist among healthy overweight adults in terms of insulin resistance, glycaemic response and insulinaemic response to rice. As a result of their high insulin resistance, Asian participants had a higher postprandial insulin spike than Europeans after eating rice. These findings could have substantial implications for nutrition recommendations based on ethnicity, particularly for Asians.

In vivo photoacoustic monitoring of vasoconstriction induced by acute hyperglycemia

Postprandial hyperglycemia, blood glucose spikes, induces endothelial dysfunction, increasing cardiovascular risks. Endothelial dysfunction leads to vasoconstriction, and observation of this phenomenon is important for understanding acute hyperglycemia. However, high-resolution imaging of microvessels during acute hyperglycemia has not been fully developed. Here, we demonstrate that photoacoustic microscopy can noninvasively monitor morphological changes in blood vessels of live animals’ extremities when blood glucose rises rapidly. As blood glucose level rose from 100 to 400 mg/dL following intraperitoneal glucose injection, heart/breath rate, and body temperature remained constant, but arterioles constricted by approximately –5.7 ± 1.1% within 20 min, and gradually recovered for another 40 min. In contrast, venular diameters remained within about 0.6 ± 1.5% during arteriolar constriction. Our results experimentally and statistically demonstrate that acute hyperglycemia produces transitory vasoconstriction in arterioles, with an opposite trend of change in blood glucose. These findings could help understanding vascular glucose homeostasis and the relationship between diabetes and cardiovascular diseases.

Serotonin alters the response to a glucose challenge in lactating cows.

Energy partitioning in lactating cows affects milk production, feed efficiency, and body reserves, with the latter having health implications for the transition into the following lactation. One molecule likely involved in the regulation of energy partitioning is serotonin. The objective of this experiment was to explore how increasing circulating serotonin, by intravenous infusion of the serotonin precursor 5-hydroxytryptophan (5-HTP), affects metabolic responses to a glucose challenge in midlactation cows as a means to manipulate energy partitioning. We intravenously infused Holstein cows with 5-HTP (1 mg/kg bodyweight dissolved in saline, n = 11) or saline alone as control (n = 9) over 1 h/day for 3 days. Cows were fasted overnight on day 2. On day 3, fasted cows were given an intravenous bolus of glucose (0.092 g/kg bodyweight). Blood samples were collected for the following 120 min for metabolic and hormonal analysis. Infusion of 5-HTP elevated circulating concentrations of serotonin and free fatty acids, reduced the concentration of insulin and amino acids, and did not affect the concentration of glucose and glucagon before the glucose challenge. Surrogate insulin sensitivity indices indicated improved insulin sensitivity in 5-HTP cows, but due to the unique metabolism of lactating ruminants, these index changes may instead reflect effects in insulin-independent glucose disposal, like milk synthesis. Challenging 5-HTP-treated cows with a glucose bolus reduced the insulin spike and blunted the decrease in free fatty acids, compared to saline cows, without changing glucose dynamics. Overall, these results suggest that serotonin stimulates insulin-independent glucose disposal, requiring less insulin to maintain normoglycemia.

Hypoglycemia post bariatric surgery: drugs with different mechanisms of action to treat a unique disorder.

Postprandial hypoglycemia (PPH) is a complex and multifactorial complication of bariatric surgery (BS). PPH may cause severe symptoms or be asymptomatic. The treatment of this condition requires dietary changes, but severe cases require drug therapy. The number of therapeutic options is limited and are often associated with adverse side effects. Different classes of drugs have been used and tested, but the resolution of PPH remains a challenge for physicians and patients. In this review, we gathered articles on PPH after BS from PubMed searches (2001 to 2022) and focused on the main drugs tested for the treatment of this condition, such as acarbose, somatostatin analogues, type 2 sodium-glucose cotransporter inhibitors, calcium channel blockers, and liraglutide. Avexitide and glucagon pump are two new therapeutic options that have been recently tested. For the search, the terms "postbariatric hypoglycemia," "bariatric surgery," and "late dumping syndrome" were used. PPH after BS is a frequent condition that should always be evaluated after BS. Treatment should be individualized and the available therapeutic options may be useful based on the condition's pathophysiology.

Acute PDE4 Inhibition Induces a Transient Increase in Blood Glucose in Mice.

cAMP-phosphodiesterase 4 (PDE4) inhibitors are currently approved for the treatment of inflammatory diseases. There is interest in expanding the therapeutic application of PDE4 inhibitors to metabolic disorders, as their chronic application induces weight loss in patients and animals and improves glucose handling in mouse models of obesity and diabetes. Unexpectedly, we have found that acute PDE4 inhibitor treatment induces a temporary increase, rather than a decrease, in blood glucose levels in mice. Blood glucose levels in postprandial mice increase rapidly upon drug injection, reaching a maximum after ~45 min, and returning to baseline within ~4 h. This transient blood glucose spike is replicated by several structurally distinct PDE4 inhibitors, suggesting that it is a class effect of PDE4 inhibitors. PDE4 inhibitor treatment does not reduce serum insulin levels, and the subsequent injection of insulin potently reduces PDE4 inhibitor-induced blood glucose levels, suggesting that the glycemic effects of PDE4 inhibition are independent of changes in insulin secretion and/or sensitivity. Conversely, PDE4 inhibitors induce a rapid reduction in skeletal muscle glycogen levels and potently inhibit the uptake of 2-deoxyglucose into muscle tissues. This suggests that reduced glucose uptake into muscle tissue is a significant contributor to the transient glycemic effects of PDE4 inhibitors in mice.