Postprandial Hypoglycemia Research Articles

Rare causes of hypoglycemia in adults

Hypoglycemia is defined by a low blood glucose level associated to clinical symptoms. Hypoglycemia may be related to treatment of diabetes, but also to drugs, alcohol, critical illness, cortisol insufficiency including hypopituitarism, insulinoma, bariatric or gastric surgery, pancreas transplantation or glucagon deficiency, or may be surreptitious. Some hypoglycemic episodes remain unexplained, and genetic, paraneoplastic and immune causes should be considered. Genetic causes may be related to endogenous hyperinsulinism and to inborn errors of metabolism (IEM). Endogenous hyperinsulinism is related to monogenic congenital hyperinsulinism, and especially to mutations of the glucokinase-activating gene or of insulin receptors, both characterised by postprandial hypoglycemia with major hyperinsulinism. In adulthood, IEM-related hypoglycemia can persist in a previously diagnosed childhood disease or may be a presenting sign. It is suggested by systemic involvement (rhabdomyolysis after fasting or exercising, heart disease, hepatomegaly), sometimes associated to a family history of hypoglycemia. The timing of hypoglycemic episodes with respect to the last meal also helps to orientate diagnosis. Fasting hypoglycemia may be related to type 0, I or III glycogen synthesis disorder, fatty acid oxidation or gluconeogenesis disorder. Postprandial hypoglycemia may be related to inherited fructose intolerance. Exercise-induced hyperinsulinism is mainly related to activating mutation of the SLC16A1 gene. Besides exceptional ectopic insulin secretion, paraneoplastic causes involve NICTH (Non-Islet-Cell Tumour Hypoglycemia), caused by Big-IGF2 secretion by a large tumour, with low blood levels of insulin, C-peptide and IGF1. Autoimmune causes involve antibodies against insulin (HIRATA syndrome), especially in case of Graves’ disease, or against the insulin receptor. Medical history, timing, and insulin level orientate the diagnosis.

Descripción de la experiencia en pacientes diagnosticados con insulinoma. Estudio multicéntrico en Medellín, Colombia

Objetivo: describir la experiencia de los pacientes con insulinoma, diagnosticados y tratados entre los años 2002 y 2017 en tres hospitales de la ciudad de Medellín, Colombia.
 Métodos: estudio descriptivo y retrospectivo de pacientes con criterios bioquímicos para hipoglucemia hiperinsulínica y confirmación histopatológica de insulinoma.
 Resultados: se estudiaron 19 casos, 10 eran mujeres (52,6 %), la edad media al diagnóstico fue 43 años (D.E 15,5). Hubo cuatro casos de insulinoma multifocal (21,1 %), tres asociados con NEM-1 (15,8 %) y dos malignos (10,6 %). Todos presentaron hipoglucemia en ayunas y 63,2 % posprandial. En la prueba de ayuno, el nadir de glucemia sucedió antes de 48 horas en todos los casos, en promedio 9 horas (D.E 8,0). El diagnóstico bioquímico fue realizado con hipoglucemia e insulina elevada en todos los casos, aunque el péptido C fue reportado en nueve pacientes (47,3 %) y las sulfonilureas en dos (11,1 %). La localización preoperatoria se hizo por imágenes en 12 individuos (68,5 %) y las pruebas invasivas fueron necesarias en seis (31,5 %). Las pruebas diagnósticas fueron positivas en un 83 % para resonancia, 50 % para ecografía endoscópica y prueba de estímulo intraarterial con calcio y 100 % para ecografía intraoperatoria. La cirugía se realizó en 18 casos (94,7 %). La mortalidad (15,8 %) fue derivada de complicaciones en el posoperatorio temprano; la curación se logró en todos los casos.
 Conclusiones: el insulinoma en nuestro medio tiene características demográficas y clínicas similares a otras series. Existen limitaciones locales para el acceso a los estudios bioquímicos y en el rendimiento diagnóstico de las pruebas de localización.

Postprandial Hypoglycemia in Patients after Gastric Bypass Surgery Is Mediated by Glucose-Induced IL-1β

Postprandial hypoglycemia is a disabling complication of the treatment of obesity by gastric bypass surgery. So far, no therapy exists, and the underlying mechanisms remain unclear. Here, we hypothesized that glucose-induced IL-1β leads to an exaggerated insulin response in this condition. Therefore, we conducted a placebo-controlled, randomized, double-blind, crossover study with the SGLT2-inhibitor empagliflozin and the IL-1 receptor antagonist anakinra (clinicaltrials.govNCT03200782; n= 12). Both drugs reduced postprandial insulin release and prevented hypoglycemia (symptomatic events requiring rescue glucose: placebo= 7/12, empagliflozin= 2/12, and anakinra= 2/12, pvallikelihood ratio test (LRT) = 0.013; nadir blood glucose for placebo= 2.4mmol/L, 95% CI2.18-2.62, empagliflozin= 2.69mmol/L, 95% CI 2.31-3.08, and anakinra= 2.99mmol/L, 95% CI 2.43-3.55, pvalLRT= 0.048). Moreover, analysis of monocytes exvivo revealed a hyper-reactive inflammatory state that has features of an exaggerated response to a meal. Our study proposes a role for glucose-induced IL-1β in postprandial hypoglycemia after gastric bypass surgery and suggests that SGLT2-inhibitors and IL-1 antagonism may improve this condition.

Spent coffee (Coffea arabica L.) grounds promote satiety and attenuate energy intake: A pilot study.

We evaluated the effects of acute intake of biscuits (B) containing either spent coffee grounds (SCG), (added with fructooligosaccharides; SC-FOS) or SCG antioxidant dietary fiber (SCF), on satiety, energy intake as well as gastrointestinal tolerance of healthy overweight volunteers. The addition of SCG and SCF to the biscuits (SC-FOS-B and SCF-B) increased their protein (11.4% and 12.2%), and total dietary fiber (8.4% and 11.8%) contents. TheSCF-B significantly increased satiety perception, impacting ad libitum energy intake compared to the traditional biscuits recipe (TB; no added fiber). Moreover, SC-FOS-B and SCF-B decreased (no-observed-adverse effect) the most frequently reported symptoms by the participants, demonstrating that doses up to 5g of SCF (per biscuit portion; 45g) are well tolerated. The use of SCF and SCG as functional ingredients represents a sustainable strategy for the coffee industry and also potentiates the reduction of overweight, one of the leading health problems among the population. PRACTICAL APPLICATIONS: The addition of SCF or SCG as food ingredients increases protein and the dietary fiber content of traditional biscuits. SCF can slow gastric emptying, modulate appetite and thus body weight. SCF attenuates carbohydrate digestion blunting post-prandial blood glucose spikes reducing the risk of type 2 diabetes. SCF can be used as a functional ingredient to formulate foods with health benefits.

Gain-of-function mutation in the voltage-gated potassium channel gene KCNQ1 and glucose-stimulated hypoinsulinemia - case report

BackgroundThe voltage-gated potassium channel Kv7.1 encoded by KCNQ1 is located in both cardiac myocytes and insulin producing beta cells. Loss-of-function mutations in KCNQ1 causes long QT syndrome along with glucose-stimulated hyperinsulinemia, increased C-peptide and postprandial hypoglycemia. The KCNE1 protein modulates Kv7.1 in cardiac myocytes, but is not expressed in beta cells. Gain-of-function mutations in KCNQ1 and KCNE1 shorten the action potential duration in cardiac myocytes, but their effect on beta cells and insulin secretion is unknown.Case presentationTwo patients with atrial fibrillation due to gain-of-function mutations in KCNQ1 (R670K) and KCNE1 (G60D) were BMI-, age-, and sex-matched to six control participants and underwent a 6-h oral glucose tolerance test (OGTT). During the OGTT, the KCNQ1 gain-of-function mutation carrier had 86% lower C-peptide response after glucose stimulation compared with matched control participants (iAUC360min = 34 pmol/l*min VS iAUC360min = 246 ± 71 pmol/l*min). The KCNE1 gain-of-function mutation carrier had normal C-peptide levels.ConclusionsThis case story presents a patient with a gain-of-function mutation KCNQ1 R670K with low glucose-stimulated C-peptide secretion, additionally suggesting involvement of the voltage-gated potassium channel KCNQ1 in glucose-stimulated insulin regulation.

Impact of Postprandial Hypoglycemia on Weight Loss After Bariatric Surgery.

Postprandial hypoglycemia (PPHG) is a well-known complication after bariatric surgery (BS). However, it is not known whether PPHG affects weight loss after BS. To assess the impact of PPHG on weight loss after BS in subjects without and with type 2 diabetes mellitus (T2D). Data from 338 subjects who had undergone gastric bypass (RYGB) or sleeve gastrectomy (LSG) and were followed up for at least 2years were analyzed. At each follow-up visit, the patient's anthropometric and biochemical characteristics were recorded and the Edinburgh Questionnaire was performed to evaluate the presence of PPHG symptoms. Before surgery: younger age and lower BMI predicted PPHG after BS (p = 0.02 and p = 0.0008, respectively). Also, the baseline OGTT indicated that subjects who developed PPHG had an earlier glucose peak and more often had low glucose levels at 2h compared with the no-PPHG group (p = 0.03 and p = 0.004, respectively). After surgery: Mild-to-moderate PPHG occurred equally after RYGB and LSG (38% vs 25%, p = ns when accounting for confounders), and in T2D who achieved remission and those who did not (29.5% vs 28.6%, ns). At the 2-year follow-up, occurrence of PPHG was independently associated with smaller weight loss (p = 0.0006). Mild-to-moderate PPHG is a frequent complication after bariatric surgery and results in smaller weight loss after 2years. Age, baseline BMI, and an earlier glucose peak during OGTT predict PPHG after bariatric surgery.

Post Prandial Hyperinsulnemic Hypoglycemia Thirteen Years after Gastric Bypass Surgery

As bariatric surgery for the treatment of obesity become popular, it is important to recognize its acute and chronic complicatons. Here, we report a case of a 39-year-old lady who presented to endocrine clinic with six months history of sever postprandial hypoglycemia thirteen years after Roux-en-Y-gastric bypass surgery. After confirmation of whipple’s triad, she underwent provocative meal test which revealed hyperinsulinemic hypoglycemia. She responded well to medical nutrition therapy and Acarbose. Since most of the reported cases of post bariatric hypoglycemia presented 1-5 years after their surgery, we report this rare case who presented 13 years after her surgery.

The continuing quest for better subcutaneously administered prandial insulins: a review of recent developments and potential clinical implications.

The class of rapid‐acting insulin analogues were introduced more than 20 years ago to control postprandial plasma glucose (PPG) excursions better than unmodified regular human insulin. Insulins, lispro, aspart and glulisine all achieved an earlier onset of action, greater peak effect and shorter duration of action resulting in lower PPG levels and a reduced risk of late postprandial hypoglycaemia. However, the subcutaneous absorption rate of these analogues still fails to match the physiological profile of insulin in the systemic circulation following a meal. Recent reformulations of aspart and lispro have generated a second generation of more rapid‐acting insulin analogue candidates, including fast‐acting aspart (faster aspart), ultra‐rapid lispro and BioChaperone Lispro. These modifications have the potential to mimic physiological prandial insulin secretion better with an even earlier onset of action with improved PPG control, shorter duration of effect and reduced risk of hypoglycaemia. Recent phase 3 trials in type 1 and type 2 diabetes show that faster aspart and ultra‐rapid lispro compared with conventional aspart and lispro, achieved fewer PPG excursions with a small increase in post‐meal hypoglycaemia but similar or marginally superior glycated haemoglobin levels, and suggest the need for parallel optimization of basal insulin replacement. Phase 1 trials for BioChaperone Lispro are equally encouraging with phase 3 trials yet to be initiated. Comparative analysis of the clinical and pharmacological evidence for these new prandial insulin candidates in the treatment of type 1 and type 2 diabetes is the main focus of this review.

Enzymatically elongated rice starches by amylosucrase from Deinococcus geothermalis lead to slow down the glucose generation rate at the mammalian α-glucosidase level

Amylosucrase (AS) catalyzes the transfer of a glucosyl unit from sucrose onto α-1,4-linked glucan polymers in starch. In this study, AS from Deinococcus geothermalis (DgAS) was applied to produce modified rice starches with slowly digestible properties. DgAS-treated waxy and normal rice starches showed significantly (p < 0.05) elevated degrees of polymerization, suggesting that the external chains were elongated. Additionally, the crystalline structures of starches changed from A- to B-type, and the temperature transition properties of enzymatically modified rice starches increased. The amounts of slowly digestible starch (SDS) increased remarkably (20.1% and 18.8%; waxy and normal rice starches, respectively), and the DgAS-treated rice starches were slowly hydrolyzed to glucose at the mammalian mucosal α-glucosidase level. Thus, DgAS-treated rice starches can be used to produce SDS-based ingredients that attenuate the glucose spike after glycemic food ingestion.

The Use of a Smart Bolus Calculator Informed by Real-time Insulin Sensitivity Assessments Reduces Postprandial Hypoglycemia Following an Aerobic Exercise Session in Individuals With Type 1 Diabetes.

Insulin dosing in type 1 diabetes (T1D) is oftentimes complicated by fluctuating insulin requirements driven by metabolic and psychobehavioral factors impacting individuals' insulin sensitivity (IS). In this context, smart bolus calculators that automatically tailor prandial insulin dosing to the metabolic state of a person can improve glucose management in T1D. Fifteen adults with T1D using continuous glucose monitors (CGMs) and insulin pumps completed two 24-h admissions in a hotel setting. During the admissions, participants engaged in an early afternoon 45-min aerobic exercise session, after which they received a standardized dinner meal. The dinner bolus was computed using a standard bolus calculator or smart bolus calculator informed by real-time IS estimates. Glucose control was assessed in the 4 h following dinner using CGMs and was compared between the two admissions. The IS-informed bolus calculator allowed for a reduction in postprandial hypoglycemia as quantified by the low blood glucose index (2.02 vs. 3.31, P = 0.006) and percent time <70 mg/dL (8.48% vs. 15.18%, P = 0.049), without increasing hyperglycemia (high blood glucose index: 3.13 vs. 2.09, P = 0.075; percent time >180 mg/dL: 13.24% vs. 10.42%, P = 0.5; percent time >250 mg/dL: 2.08% vs. 1.19%, P = 0.317). In addition, the number of hypoglycemia rescue treatments was reduced from 12 to 7 with the use of the system. The study shows that the proposed IS-informed bolus calculator is safe and feasible in adults with T1D, appropriately reducing postprandial hypoglycemia following an exercise-induced IS increase.

Innovative imaging of insulinoma: the end of sampling? A review.

Receptors for the incretin glucagon-like peptide-1 (GLP-1R) have been found overexpressed in selected types of human tumors and may, therefore, play an increasingly important role in endocrine gastrointestinal tumor management. In particular, virtually all benign insulinomas express GLP-1R in high density. Targeting GLP-1R with indium-111, technetium-99m or gallium-68-labeled exendin-4 offers a new approach that permits the successful localization of small benign insulinomas. It is likely that this new non-invasive technique has the potential to replace the invasive localization of insulinomas by selective arterial stimulation and venous sampling. In contrast to benign insulinomas, malignant insulin-secreting neuroendocrine tumors express GLP-1R in only one-third of the cases, while they more often express the somatostatin subtype 2 receptors. Importantly, one of the two receptors appears to be always overexpressed. In special cases of endogenous hyperinsulinemic hypoglycemia (EHH), that is, in the context of MEN-1 or adult nesidioblastosis GLP-1R imaging is useful whereas in postprandial hypoglycemia in the context of bariatric surgery, GLP-1R imaging is probably not helpful. This review focuses on the potential use of GLP-1R imaging in the differential diagnosis of EHH.

Utility of continuous glucose monitoring following gastrectomy.

Glucose fluctuation after gastrectomy represented by dumping syndrome is a well-known post-gastrectomy syndrome that negatively impacts patient quality of life. However, the current methods of post-gastrectomy glucose monitoring do not comprehensively capture the postoperative blood glucose fluctuations that characterize this. We used a continuous glucose monitoring (CGM) system to document the glycemic profiles of patients undergoing gastrectomy and compared these between patients undergoing distal gastrectomy (DG) and total gastrectomy (TG). To evaluate post-gastrectomy syndromes, including dumping syndrome, we used the Post-gastrectomy Syndrome Assessment Scale 37-item questionnaire. The glycemic profiles were also compared using this tool. We studied 57 patients who had undergone DG and 13 who had undergone TG between September 2017 and September 2019. Our results revealed larger diurnal glycemic variability and longer periods of nocturnal hypoglycemia after gastrectomy. The dumping score was worse in the TG than in the DG group (TG 2.4 ± 1.4 vs. DG 1.3 ± 1.2, P = 0.0061). Importantly, 30 of 57 DG patients (52.6%) and 5 of 13 TG patients (38.5%) experienced postprandial hypoglycemia following hyperglycemia without hypoglycemic symptoms. There was no correlation between the dumping symptom score and glycemic variability (ρ = 0.0545, P = 0.6662). CGM demonstrated diurnal glycemic variability and nocturnal hypoglycemia in patients undergoing gastrectomy. Because some hypoglycemic patients did not develop symptoms and glycemic variability was not necessarily associated with dumping symptom, dumping syndrome must only partially explain the postoperative glucose fluctuations.

Evidence for Relationship Between Early Dumping and Postprandial Hypoglycemia After Roux-en-Y Gastric Bypass.

Early dumping and post-bariatric hypoglycemia (PBH) are often addressed as two separate postprandial complications after Roux-en-Y gastric bypass (RYGB). The aim of the study was to evaluate the occurrence of early dumping in RYGB-operated individuals with PBH with and without treatment intervention. Eleven RYGB-operated women with documented PBH each underwent a baseline liquid mixed meal test (MMT) followed by five MMTs preceded by treatment with: acarbose 50mg for 1week, sitagliptin 100mg for 1week, verapamil 120mg for 1week, liraglutide 1.2mg for 3weeks, and pasireotide 300μg as a single dose. Repetitive venous blood sampling and continuous electrocardiogram recordings were performed at fasting and during a 3-h postprandial period. During the baseline MMT, there was a significant increase in HR (from 65 ± 2 to 90 ± 4bpm, p < 0.0001) within 30min after meal intake, while hypoglycemia occurred in the later postprandial period. The HR increase was accompanied by significant increases in serum albumin, plasma norepinephrine, blood glucose, serum insulin, and plasma GLP-1 concentrations. The postprandial HR changes were positively correlated with the changes in insulin and GLP-1 concentrations. Treatment with acarbose and pasireotide both reduced HR, plasma norepinephrine, and serum insulin, and pasireotide also decreased plasma GLP-1. RYGB-operated individuals with PBH also have large early postprandial HR increases, hemoconcentration, and sympathetic activation, consistent with early dumping. Moreover, hormone excursions associated with PBH appear to be related to measures of early dumping, suggesting a causal relationship between early dumping and PBH. NCT02527993.

Reactive hypoglycemia – an interdisciplinary approach of the disease of XXI Century

Reactive hypoglycemia is characterized by low blood glucose level in non-diabetic patients. It manifests as a syndrome of adrenergic and neuroglycopenic symptoms in the postprandial period, and their resolution occurs after consuming carbohydrates. The etiology of reactive hypoglycemia is not fully understood. It may occur in patients after gastrointestinal surgery due to too fast gastric emptying. Decreases in postprandial glucose are also observed in people with a pre-diabetes condition in which insulin secretion is disturbed. Hypoglycaemia can also be seen in patients with insulin resistance and hyperinsulinism. The aim of this study was to summarize existing knowledge about reactive hypoglycemia - etiology, diagnostic model and treatment.

Hyperinsulinemic Hypoglycemia after Bariatric Surgery.

Postprandial hyperinsulinemic hypoglycemia (PHH) is one of the serious complications after bariatric surgery, it can lead life-threatening neuroglycopenic symptoms, such as seizures, disorientation, impairment of version and loss of consciousness without any premonitory. The presentation, prevalence, diagnosis, pathology and treatment are reviewed in this summary.

Pediatric glucose regulation without pre-meal insulin boluses: an approach based on switched control and time-varying IOB constraints

Artificial pancreas (AP) systems have shown to improve glucose regulation in type 1 diabetes (T1D) patients. However, full closed-loop performance remains a challenge particularly in children and adolescents, since these age groups often present the worst glycemic control. In this work, a new algorithm based on switched control and time-varying insulin-on-board (IOB) constraints is presented (ARGAE). This method is a combination of ideas from the previously introduced Automatic Regulation of Glucose (ARG) algorithm, which features no pre-meal insulin boluses, and the Amplitude Enable (AE) mode, which allows the controller to act more aggressively at the beginning of meal intake without risking postprandial hypoglycemia. The proposed control strategy is evaluated in silico and its performance contrasted with the ARG algorithm in the pediatric population. Results show that the ARGAE presents improved performance compared to the ARG algorithm even in presence of misclassified meals. Thus, future in vivo testing will involve the AE configuration.

Continuous glucose monitoring reveals glycemic variability and hypoglycemia after vertical sleeve gastrectomy in rats

ObjectivePost–bariatric surgery hypoglycemia (PBH) is defined as the presence of neuroglycopenic symptoms accompanied by postprandial hypoglycemia in bariatric surgery patients. Recent clinical studies using continuous glucose monitoring (CGM) technology revealed that PBH is more frequently observed in vertical sleeve gastrectomy (VSG) patients than previously recognized. PBH cannot be alleviated by current medication. Therefore, a model system to investigate the mechanism and treatment is required. MethodsWe used CGM in a rat model of VSG and monitored the occurrence of glycemic variability and hypoglycemia in various meal conditions for 4 weeks after surgery. Another cohort of VSG rats with CGM was used to investigate whether the blockade of glucagon-like peptide-1 receptor (GLP-1R) signaling alleviates these symptoms. A mouse VSG model was used to investigate whether the impaired glucose counterregulatory system causes postprandial hypoglycemia. ResultsLike in humans, rats have increased glycemic variability and hypoglycemia after VSG. Postprandial hypoglycemia was specifically detected after liquid versus solid meals. Further, the blockade of GLP-1R signaling raises the glucose nadir but does not affect glycemic variability. ConclusionsRat bariatric surgery duplicates many features of human post–bariatric surgery hypoglycemia including postprandial hypoglycemia and glycemic variability, while blockade of GLP-1R signaling prevents hypoglycemia but not the variability.

Successful Medical Treatment of Hyperinsulinemic Hypoglycemia in the Adult: A Case Report and Brief Literature Review

Hyperinsulinemic hypoglycemia is characterized by inappropriate insulin secretion from the pancreatic beta cells causing low blood glucose levels. Nesidioblastosis is a very rare cause of hyperinsulinemic hypoglycemia in adults. Medical therapy can effectively improve disease symptoms. In 2014, a 45-year-old man presented with recurrent severe fasting and postprandial symptomatic hypoglycemia. The symptoms resolved after glucose ingestion. Fasting test was positive after only 4 h but imaging methods (abdominal computerized tomography, magnetic resonance imaging, endoscopic ultrasonography and octreotide scintigraphy) failed to identify pancreatic lesions. Hypoglycemia in face of endogenous hyperinsulinemia and lack of focal lesions in the pancreas in multiple imaging exams suggested the diagnosis of adult nesidioblastosis. The patient preferred conservative medical treatment in association with dietary recommendations. Nifedipine (30 mg/day) did not improve the glycemic profile and was poorly tolerated by the patient. Diazoxide 150 mg/day was started, with progressive increase to 400 mg/day over 6 weeks. Patient has been successfully treated with medical treatment for 5 years, with no events of severe hypoglycemia, no significant side effects and with marked improvement in quality of life. This clinical case demonstrates that adult hyperinsulinemic hypoglycemia can be effectively controlled with medical treatment, which is a viable alternative to pancreatic surgery. J Endocrinol Metab. 2019;9(6):199-202 doi: https://doi.org/10.14740/jem617

Stable Monomeric Insulin Formulations Enabled by Supramolecular PEGylation of Insulin Analogues.

Current "fast-acting" insulin analogues contain amino acid modifications meant to inhibit dimer formation and shift the equilibrium of association states toward the monomeric state. However, the insulin monomer is highly unstable and current formulation techniques require insulin to primarily exist as hexamers to prevent aggregation into inactive and immunogenic amyloids. Insulin formulation excipients have thus been traditionally selected to promote insulin association into the hexameric form to enhance formulation stability. This study exploits a novel excipient for the supramolecular PEGylation of insulin analogues, including aspart and lispro, to enhance the stability and maximize the prevalence of insulin monomers in formulation. Using multiple techniques, it is demonstrated that judicious choice of formulation excipients (tonicity agents and parenteral preservatives) enables insulin analogue formulations with 70-80% monomer and supramolecular PEGylation imbued stability under stressed aging for over 100 h without altering the insulin association state. Comparatively, commercial "fast-acting" formulations contain less than 1% monomer and remain stable for only 10 h under the same stressed aging conditions. This simple and effective formulation approach shows promise for next-generation ultrafast insulin formulations with a short duration of action that can reduce the risk of post-prandial hypoglycemia in the treatment of diabetes.

Patterns of postmeal insulin secretion in individuals with sulfonylurea-treated KCNJ11 neonatal diabetes show predominance of non-KATP-channel pathways

ObjectiveInsulin secretion in sulfonylurea-treated KCNJ11 permanent neonatal diabetes mellitus (PNDM) is thought to be mediated predominantly through amplifying non-KATP-channel pathways such as incretins. Affected individuals report symptoms of postprandial hypoglycemia...