Isomaltulose Enhances GLP-1 and PYY Secretion to a Mixed Meal in People With or Without Type 2 Diabetes as Compared to Saccharose.

SCOPE: Secretion of the gut hormones glucagon-like peptide (GLP-1) and peptide YY (PYY) are induced by nutrients reaching the lower small intestine which regulate insulin and glucagon release, inhibit appetite, and may improve ß-cell regeneration. The aim is to test the effect of a slowly digested isomaltulose (ISO) compared to the rapidly digested saccharose (SAC) as a snack given 1 h before a standardized mixed meal test (MMT) on GLP-1, PYY, glucose-dependent insulinotropic peptide (GIP), and metabolic responses in participants with or without type 2 diabetes (T2DM). METHODS AND RESULTS: Fifteen healthy volunteers and 15 patients with T2DM consumed either 50 g ISO or SAC 1 h preload of MMT on nonconsecutive days. Clinical parameters and incretin hormones are measured throughout the whole course of MMT. Administration of 50 g ISO as compared to SAC induced a significant increase in GLP-1, GIP, and PYY responses over 2 h after intake of a typical lunch in healthy controls. Patients with T2DM showed reduced overall responses of GLP-1 and delayed insulin release compared to controls while ISO significantly enhanced the GIP and almost tripled the PYY response compared to SAC. CONCLUSION: A snack containing ISO markedly enhances the release of the metabolically advantageous gut hormones PYY and GLP-1 and enhances GIP release in response to a subsequent complex meal.

The Regulation and Secretion of Glucagon in Response to Nutrient Composition: Unraveling Their Intricate Mechanisms.

Glucagon was initially regarded as a hyperglycemic substance; however, recent research has revealed its broader role in metabolism, encompassing effects on glucose, amino acids (AAs), and lipid metabolism. Notably, the interplay of glucagon with nutrient intake, particularly of AAs, and non-nutrient components is central to its secretion. Fasting and postprandial hyperglucagonemia have long been linked to the development and progression of type 2 diabetes (T2DM). However, recent studies have brought to light the positive impact of glucagon agonists on lipid metabolism and energy homeostasis. This review explores the multifaceted actions of glucagon, focusing on its regulation, signaling pathways, and effects on glucose, AAs, and lipid metabolism. The interplay between glucagon and other hormones, including insulin and incretins, is examined to provide a mechanistic understanding of its functions. Notably, the liver-α-cell axis, which involves glucagon and amino acids, emerges as a critical aspect of metabolic regulation. The dysregulation of glucagon secretion and its impact on conditions such as T2DM are discussed. The review highlights the potential therapeutic applications of targeting the glucagon pathway in the treatment of metabolic disorders.

Failure of internal fixation for ankle joint Charcot neuroarthropathy with beta(2)-microglobulin amyloidosis: a case report.

Charcot neuroarthropathy (CN) is a serious diabetic complication with a poor prognosis and a high rate of misdiagnosis. Furthermore, beta(2)-microglobulin amyloidosis (Abeta2M) makes the diagnosis and therapy more difficult and complex. This case report highlights the pathophysiology, clinical evaluation, treatment, and prevention of the major diabetic complications associated with CN and Abeta2M that cause poor quality of life, limit the patient's ability to walk independently, and are directly or indirectly linked with a high risk for lower limb amputation. Ankle CN was discovered in a 36-year-old single female with a history of type 1 diabetes mellitus and diabetic nephropathy. We performed early internal fixation. However, because she lived alone and needed hemodialysis three times a week, wearing a brace and non-weight-bearing were extremely inconvenient. Furthermore, she did not experience any pain and only some edema; thus, she proceeded to bear weight ahead of schedule without authorization. Due to the premature weight-bearing and poor compliance, the patient suffered severe bone resorption and infection and eventually had to undergo amputation. Abeta2M was suggested by bone pathological sections. We present a case of failed internal fixation of ankle CN with Abeta2M, emphasizing the importance of social factors and postoperative management.

Implication of sugar, protein and incretins in excessive glucagon secretion in type 2 diabetes after mixed meals.

AIMS: Amino acids powerfully release glucagon but their contribution to postprandial hyperglucagonemia in type 2 diabetes remains unclear. Exogenously applied GIP stimulates, while GLP-1 inhibits, glucagon secretion in humans. However, their role in mixed meals is unclear, which we therefore characterized. METHODS: In three experiments, participants with type 2 diabetes and obese controls randomly received different loads of sugars and/or proteins. In the first experiment, participants ingested the rapidly cleaved saccharose (SAC) or slowly cleaved isomaltulose (ISO) which is known to elicit opposite profiles of GIP and GLP-1 secretion. In the second one participants received test meals which contained saccharose or isomaltulose in combination with milk protein. The third set of participants underwent randomized oral protein tests with whey protein or casein. Incretins, glucagon, C-peptide, and insulin were profiled by specific immunological assays. RESULTS: 50 g of the sugars alone suppressed glucagon in controls but slightly less in type 2 diabetes patients. Participants with type 2 diabetes showed excessive glucagon responses within 15 min and lasting over 3 h, while the obese controls showed small initial and delayed greater glucagon responses to mixed meals. The release of GIP was significantly faster and greater with SAC compared to ISO, while GLP-1 showed an inverse pattern. The glucagon responses to whey or casein were only moderately increased in type 2 diabetes patients without a left shift of the dose response curve. CONCLUSIONS: The rapid hypersecretion of glucagon after mixed meals in type 2 diabetes patients compared to controls is unaffected by endogenous incretins. The defective suppression of glucagon by glucose combined with hypersecretion to protein is required for the exaggerated response. CLINICAL TRIALS NUMBERS: NCT03806920, NCT02219295, NCT04564391.

High Protein Diets Improve Liver Fat and Insulin Sensitivity by Prandial but Not Fasting Glucagon Secretion in Type 2 Diabetes.

Glucagon (GCGN) plays a key role in glucose and amino acid (AA) metabolism by increasing hepatic glucose output. AA strongly stimulate GCGN secretion which regulates hepatic AA degradation by ureagenesis. Although increased fasting GCGN levels cause hyperglycemia GCGN has beneficial actions by stimulating hepatic lipolysis and improving insulin sensitivity through alanine induced activation of AMPK. Indeed, stimulating prandial GCGN secretion by isocaloric high protein diets (HPDs) strongly reduces intrahepatic lipids (IHLs) and improves glucose metabolism in type 2 diabetes mellitus (T2DM). Therefore, the role of GCGN and circulating AAs in metabolic improvements in 31 patients with T2DM consuming HPD was investigated. Six weeks HPD strongly coordinated GCGN and AA levels with IHL and insulin sensitivity as shown by significant correlations compared to baseline. Reduction of IHL during the intervention by 42% significantly improved insulin sensitivity [homeostatic model assessment for insulin resistance (HOMA-IR) or hyperinsulinemic euglycemic clamps] but not fasting GCGN or AA levels. By contrast, GCGN secretion in mixed meal tolerance tests (MMTTs) decreased depending on IHL reduction together with a selective reduction of GCGN-regulated alanine levels indicating greater GCGN sensitivity. HPD aligned glucose metabolism with GCGN actions. Meal stimulated, but not fasting GCGN, was related to reduced liver fat and improved insulin sensitivity. This supports the concept of GCGN-induced hepatic lipolysis and alanine- and ureagenesis-induced activation of AMPK by HPD.

The effect of liraglutide on insulin allergy in a patient with glucocorticoid-induced diabetes and multiple sclerosis.

Glucocorticoid use may trigger secondary diabetes or exacerbate hyperglycemia in patients with diabetes mellitus (DM). Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used for the treatment of patients with type 2 diabetes. Few reports mention liraglutide as a treatment for steroid-induced DM (SIDM). Here, we report a patient with SIDM and multiple sclerosis, for whom switching to liraglutide combined with metformin therapy improved glucose levels and ameliorated the symptoms of insulin allergy. Liraglutide may be useful for treating SIDM with insulin allergy.

Admission Hemoglobin Is Prognostic for In-Hospital Mortality in Oldest-Old Patients with Acute Ischemic Stroke.

INTRODUCTION: Anemia is a common condition encountered in acute ischemic stroke, and only a few pieces of evidence has been produced suggesting its possible association with short-term mortality have been produced. The study sought to assess whether admission anemia status had any impact on short-term clinical outcome among oldest-old patients with acute ischemic stroke. MATERIALS AND METHODS: A retrospective review of Electronic Medical Recording System was performed in 2 tertiary hospitals. Data, from the oldest-old patients aged > = 80 years consecutively admitted with a diagnosis of acute ischemic stroke between January 1, 2015, and December 31, 2019, were analyzed. Admission hemoglobin was used as indicator for anemia and severity. Univariate and multivariate regression analyses were used to compare in-hospital mortality and length of in-hospital stay in different anemia statuses and normal hemoglobin patients. RESULTS: A total of 705 acute ischemic stroke patients were admitted, and 572 were included in the final analysis. Of included patients, 240 of them were anemic and 332 nonanemic patients. A statistical difference between the 2 groups was found in in-hospital mortality (p < 0.001). After adjustment for baseline characteristics, the odds ratio value of anemia for mortality were 3.91 (95% confidence intervals (CI) 1.60-9.61, p = 0.003) and 7.15 (95% CI: 1.46-34.90, p = 0.015) in moderate and severely anemic patients, respectively. Similarly, length of in-hospital stay was longer in anemic patients (21.64 ± 6.17 days) than in nonanemic patients (19.08 ± 5.48 days, p < 0.001). CONCLUSIONS: Increased severity of anemia may be an independent risk factor for increased in-hospital mortality and longer length of stay in oldest-old patients with acute ischemic stroke.

Yi-Qi-Jian-Pi-Xiao-Yu-Xie-Zhuo Formula Improves Muscle Atrophy via Modulating the IGF-1/PI3K/Akt Signaling Pathway in 5/6 Nephrectomized Rats.

The Yi-Qi-Jian-Pi-Xiao-Yu-Xie-Zhuo (YQJPXYXZ) formula has been used for treating chronic kidney disease (CKD) for many years with good efficiency based on the cumulative empirical experience of previous practitioners. Impairment of the IGF-1/PI3K/Akt signaling pathway plays an important role in mediating muscle wasting. This study aimed to observe effects of the YQJPXYXZ formula on muscle atrophy in CKD rats and investigate its possible mechanism on regulation of the IGF-1/PI3K/Akt signaling pathway. The 5/6 nephrectomized rats were randomly allocated into 3 groups: the CKD group, the KT (compound α-ketoacid tablets) group, and the YQJPXYXZ group. Besides, sham-operated rats were included as the sham group. All rats were treated for 12 weeks. Results showed that administration of the YQJPXYXZ formula prevented body weight loss and muscle fiber size decrease. Moreover, the YQJPXYXZ formula increased the IGF-1 level of serum and skeletal muscle in CKD rats and enhanced the phosphorylation level of Akt. Furthermore, the YQJPXYXZ formula decreased the Atrogin1 and MuRF1 mRNA and MuRF1 proteins. In conclusion, our data demonstrated that the YQJPXYXZ formula improves muscle wasting in CKD rats, which might be associated with the modulation of the IGF-1/PI3K/Akt signaling pathway and inhibition of the ubiquitin-proteasome system (UPS).

Surgical Outcomes of Articular Surface Crush Injury of Hawkins â ¢ Talus Neck and Medial Malleolus Fracture.

The present study was performed to evaluate the effects of the medial and anterolateral approach combined with internal fixation by double head compression screws and countersunk K-wires for Hawkins Ⅲ talus neck and medial malleolus fracture. Eleven patients with articular surface crush injury resulting in Hawkins Ⅲ talus neck fractures accompanied by medial malleolus fractures were reviewed. All patients underwent emergency operations. The fractures were fixed using double head compression screws and countersunk K-wires through combined medial and anterolateral approaches. FAOS, AOFAS ankle-hindfoot scale, and VAS questionnaire scores were recorded. In addition, ROM of the ankle and postoperative complications were assessed. All patients were followed up for a median of 52.45 ±â€…5.15 months. The multiple scales data of FAOS on the affected side were: pain score 89.14 ±â€…7.08; activities of daily living score 89.57 ±â€…8.88; quality-of-life score 89.20 ±â€…7.44; sports score 75.00 ±â€…15.49; and other symptoms score 84.74 ±â€…7.51. The mean overall AOFAS ankle-hindfoot score was 88.36 ±â€…6.39. The VAS score was 0.72 ±â€…0.65. Ankle motion included dorsiflexion (13.18°â€…±â€…9.02°) and plantar flexion (32.27°â€…±â€…12.34°). Subtalar joint motion included eversion (10.91°â€…±â€…7.01°) and inversion (11.36°â€…±â€…7.45°). All scores of the healthy side were higher than those of the affected side (p < .05). In addition to ROM of the ankle and subtalar joint and sports score, various indicators of recovery rate had scores > 80%. One patient developed skin necrosis, which healed after debridement and wound dressing. Late complications included subtalar and/or ankle traumatic arthritis in six patients, four of whom showed no obvious clinical symptoms. In conclusion, the method of emergency surgery and medial and anterolateral approach combined with countersunk K-wires to fix small bone fragments to restore the integrity of the articular surface is acceptable for Hawkins Ⅲ talus neck with medial malleolus fracture.

Membranous nephropathy with pulmonary cryptococcosis with improved 1-year follow-up results: A case report.

Cryptococcosis is frequently found in immunosuppressed patients. It is also a significant opportunistic infection in non-immunocompromised individuals. In this study, we present a rare case of membranous nephropathy (MN) with pulmonary cryptococcosis. A 33-year-old man with MN was referred to our hospital because of dyspnea and weakness for 1 week. Before the above symptoms occurred, the dose of Cyclosporin A was increased again for relapse of MN. Multiple massive or patchy high-density shadows were present on computed tomography of the lung. Initially the patient underwent empirical anti-bacterial therapy, which turned out to be ineffective. As the results of serum cryptococcal latex agglutination tests were positive, the administration of anti-fungal drugs was prescribed. The results of fungal culture and pathologic examination of the lung tissue revealed the findings consistent with Cryptococcus neoformans. The patient was successfully treated with voriconazole followed by fluconazole with satisfactory result. Therefore, in patients with chronic kidney disease, lung lesions with poor bactericidal effects of cephalosporins need further examination to make sure whether there is pulmonary cryptococcosis. Early diagnosis and treatment might contribute to good results. It is a problem worthy of consideration that whether immunosuppressive agents need to be discontinued or not during antifungal therapy.

"Out-in" position in the surgical treatment of three-column tibial plateau fractures: A technical note.

Three-column classification of tibial plateau fractures is based on computerized tomography (CT) images, and the patients with three-column fractures can be treated with posteromedial combined with anterolateral approach in the floating position. However, there are certain disadvantages to operating in a "floating position". Therefore, we proposed an "out-in" position for those fractures. The patient is placed in supine position on the operating table, and the healthy hip is elevated. For the posteromedial approach, the affected limb should be placed on a rectangular fluoroscopy table and kept in abduction and external rotation (out); for the anterolateral approach, the affected limb is retracted into the operating bed and kept in neutral position (in).This position has been shown to be highly effective for easy operation as well as intraoperative image monitoring. Furthermore, it highlights the advantage of anterior-posterior joint fracture reduction.

A Modified 2-Stage Treatment for AO/OTA 43-C1 Pilon Fractures Accompanied by Distal Fibular and Posterior Lip of the Distal Tibia Fracture.

The management of pilon fractures remains challenging owing to the high-energy axial loading mechanism that produces comminution of the articular surface, displacement of tibia metaphysis, and severe soft tissue injury. How to preserve the vitality of soft tissue and achieve anatomic reduction has become a timely issue. We report and evaluate the effect of a modified staging treatment for AO Foundation/Orthopaedic Trauma Association (AO/OTA) 43C1 pilon fracture accompanied by distal fibular and posterior lip of the distal tibia fracture. We performed a modified 2-stage treatment of type C1 pilon fracture with distal fibular and posterior malleolar fractures. In the first stage, the posterolateral incision was used for simultaneous reduction of fibula and posterior malleolus, and the tibia was fixed with an external fixator. In the second stage, the external fixator was removed, and the medial malleolus and tibia were fixed after the edema of soft tissue had subsided. The following data were collected: Foot and Ankle Outcome Score (FAOS), American Orthopaedic Foot & Ankle Society (AOFAS) score, Short Form 36 (SF-36) score, Burwell-Charnley fracture reduction score, and postoperative complications. Twenty-seven patients were monitored for an average of 31.70 ± 7.38 months. The Burwell-Charnley fracture reduction scores had anatomic and fair ratings of 92.59%. SF-36 physical component score was 42.94 ± 12.47 and mental component score was 48.73 ± 9.79. Score data from the multiple scales of FAOS included pain, 88.79 ± 8.59; activities of daily living, 91.89 ± 7.50; quality of life, 90.26 ± 10.52; sports, 87.93 ± 11.64; and symptoms, 85.32 ± 8.65. The AOFAS ankle-hindfoot scores were 87.30 ± 13.45. Complications were reported in 5 patients (18.52%). Our study provides a good alternative to the existing protocol for type C1 pilon fractures with distal fibular and posterior lip of the distal tibia fracture and effectively reduces soft tissue complications.

Gastric peroral endoscopic myotomy for gastroparesis: A systematic review of efficacy and safety / Miotomía endoscópica gástrica por vía oral para el tratamiento de la gastroparesia: revisión sistemática de su eficacia y seguridad

Introduction: To assess the efficacy and safety of gastric peroral endoscopic myotomy for the treatment of gastroparesis. Methods: PubMed, Embase, Cochrane Library and Web of Science databases were searched from their earliest records to May 2018. The evaluation of clinical efficacy and safety was based on gastric emptying scintigraphy normalization, the improvement in clinical symptoms and adverse event rate. R 3.5.0 software was used to calculate the pooled estimate rates by meta-analysis. The improvement rate of the Gastroparesis Cardinal Symptom Index score was analyzed at different follow-up times. Results: Fourteen studies with a total of 276 patients were included in this systematic review. The pooled gastric emptying scintigraphy normalization rate was 61.3% (95% CI, 51.5-70.8%) and clinical symptom improvement rate was 88.2% (95% CI, 83.6-93.1%). Intra-operative complications were found in about 3.2% (95% CI, 0.1-4.2%) of all included patients, and postoperative adverse events in 2.1% (95% CI, 0.3-4.8%). The mean Gastroparesis Cardinal Symptom Index score improvement rate was about 90.2% at one month follow-up, 83.3% at three months, 70.3% at six months, 52.4% at twelve months and 57.1% at eighteen months. Discussion: Our systematic review demonstrates that gastric peroral endoscopic myotomy is a safe and effective treatment for gastroparesis. Though the short-term outcomes are promising, prospective, randomized, controlled studies with large sample size and long-term follow-up are required to further confirm these results

Introducción: Evaluar la eficacia y seguridad de la miotomía endoscópica gástrica por vía oral para el tratamiento de la gastroparesia. Métodos: Se realizaron búsquedas en las bases de datos de PubMed, Embase, Cochrane Library y Web of Science desde sus primeros registros hasta mayo de 2018. La evaluación de la eficacia y la seguridad clínicas se basó en la normalización de la gammagrafía gástrica, la mejora de los síntomas clínicos y la tasa de episodios adversos. Se utilizó el software R 3.5.0 para calcular las tasas de estimación combinadas mediante un metaanálisis. La tasa de mejora de la puntuación del índice de síntomas cardinales de la gastroparesia se analizó en diferentes tiempos de seguimiento. Resultados: Catorce estudios con un total de 276 pacientes se incluyeron en esta revisión sistemática. La tasa de normalización combinada de la gammagrafía gástrica fue del 61,3% (IC 95% 51,5-70,8) y la tasa de mejoría de los síntomas clínicos fue del 88,2% (IC 95% 83,6-93,1). Se encontraron complicaciones intraoperatorias en, aproximadamente, el 3,2% (IC 95% 0,1-4,2) de todos los pacientes incluidos y los episodios adversos postoperatorios fueron del 2,1% (IC 95% 0,3-4,8%). La tasa de mejora de la puntuación del índice de síntomas cardinales de la gastroparesia media fue de alrededor del 90,2% a un mes de seguimiento, del 83,3% a los 3 meses, del 70,3% a los 6 meses, del 52,4% a los 12 meses y del 57,1% a los 18 meses. Discusión: Nuestra revisión sistemática demuestra que la miotomía endoscópica gástrica por vía oral es un tratamiento seguro y eficaz para la gastroparesia. Aunque los resultados a corto plazo son prometedores, se requieren estudios prospectivos de distribución aleatoria controlados con un tamaño de muestra grande y un seguimiento a largo plazo para continuar confirmando estos resultados

Gastric peroral endoscopic myotomy for gastroparesis: A systematic review of efficacy and safety.

INTRODUCTION: To assess the efficacy and safety of gastric peroral endoscopic myotomy for the treatment of gastroparesis. METHODS: PubMed, Embase, Cochrane Library and Web of Science databases were searched from their earliest records to May 2018. The evaluation of clinical efficacy and safety was based on gastric emptying scintigraphy normalization, the improvement in clinical symptoms and adverse event rate. R 3.5.0 software was used to calculate the pooled estimate rates by meta-analysis. The improvement rate of the Gastroparesis Cardinal Symptom Index score was analyzed at different follow-up times. RESULTS: Fourteen studies with a total of 276 patients were included in this systematic review. The pooled gastric emptying scintigraphy normalization rate was 61.3% (95% CI, 51.5-70.8%) and clinical symptom improvement rate was 88.2% (95% CI, 83.6-93.1%). Intra-operative complications were found in about 3.2% (95% CI, 0.1-4.2%) of all included patients, and postoperative adverse events in 2.1% (95% CI, 0.3-4.8%). The mean Gastroparesis Cardinal Symptom Index score improvement rate was about 90.2% at one month follow-up, 83.3% at three months, 70.3% at six months, 52.4% at twelve months and 57.1% at eighteen months. DISCUSSION: Our systematic review demonstrates that gastric peroral endoscopic myotomy is a safe and effective treatment for gastroparesis. Though the short-term outcomes are promising, prospective, randomized, controlled studies with large sample size and long-term follow-up are required to further confirm these results.