Differential effect of endogenous glucagon-like peptide-1 on prandial glucose counterregulatory response to hypoglycaemia in humans with and without bariatric surgery.

AIM: To determine the effect of endogenous glucagon-like peptide 1 (GLP-1) on prandial counterregulatory response to hypoglycaemia after gastric bypass (GB). MATERIALS AND METHODS: Glucose fluxes, and islet-cell and gut hormone responses before and after mixed-meal ingestion, were compared during a hyperinsulinaemic-hypoglycaemic (~3.2 mmol/L) clamp with and without a GLP-1 receptor (GLP-1R) antagonist exendin-(9-39) infusion in non-diabetic patients who had previously undergone GB compared to matched participants who had previously undergone sleeve gastrectomy (SG) and non-surgical controls. RESULTS: Exendin-(9-39) infusion raised prandial endogenous glucose production (EGP) response to insulin-induced hypoglycaemia in the GB group but had no consistent effect on EGP response among the SG group or non-surgical controls (p < 0.05 for interaction). The rates of systemic appearance of ingested glucose or prandial glucose utilization did not differ among the three groups or between studies with and without exendin-(9-39) infusion. Blockade of GLP-1R had no effect on insulin secretion or insulin action but enhanced prandial glucagon in all three groups. CONCLUSIONS: These results indicate that impaired post-meal glucose counterregulatory response to hypoglycaemia after GB is partly mediated by endogenous GLP-1, highlighting a novel pathogenic mechanism of GLP-1 in developing hypoglycaemia in this population.

The effect of level of injury on diabetes incidence and mortality after spinal cord injury - a longitudinal cohort study.

STUDY DESIGN: Retrospective longitudinal cohort study of veterans with SCI. OBJECTIVES: Spinal cord injury (SCI) is associated with an increased risk of developing diabetes mellitus (DM), likely due to body composition alterations and autonomic nervous system dysfunction. These factors are more pronounced in persons with tetraplegia (TP) versus paraplegia (PP). However, the effect of level of injury (LOI) on DM incidence is largely unknown. Therefore, the objective is to examine the effect of LOI on DM incidence in persons with SCI. SETTING: South Texas Veterans Health Care System. METHODS: We obtained electronic record data on age, sex, race/ethnicity, LOI and HbA1c concentration from January 1st 2001 through December 31st 2021. Cox proportional hazard regression analyses were used to assess the association between LOI, DM and all-cause mortality. RESULTS: Among 728 non-diabetic veterans with SCI (350 TP/ 378 PP, 52 ± 15 years, 690 male/38 female) 243 developed DM, of which 116 with TP and 127 with PP. Despite chronological variations between TP and PP, DM risk over the entire follow-up did not differ between the groups (hazard ratio (HR): 1.06, 95% CI: 0.82-1.38). Mortality was higher in TP versus PP (HR: 1.40, 95% CI: 1.09-1.78). However, developing DM did not increase the risk of death, regardless of LOI (HR: 1.07, 95% CI: 0.83-1.37). CONCLUSION: Despite chronological variations between both groups, the level of injury had minimal effect on long-term DM development in this cohort of veterans with SCI. Sponsorship NIH (DK105379; MS), RR&D SPiRE (I21RX003724-01A1; MT and SH).

C-reactive protein, D-dimer, erythrocyte sedimentation rate, and troponin in intensive care unit patients with COVID-19 in Iran.

Background: The coronavirus disease 2019 (COVID-19) pandemic in Iran has led to a lack of intensive care unit (ICU) facilities. This study examines C-reactive protein (CRP), D-dimer, erythrocyte sedimentation rate (ESR), and troponin in ICU patients with COVID-19 in comparison to COVID-19 patients admitted to the wards in Iran. Materials and Methods: In a case-control study, troponin, CRP, ESR, and D-dimer were compared in the case samples of 109 COVID-19 patients admitted to the ICU, and in the control group, 140 COVID-19 patients admitted to the wards. Results: The mean of CRP (P < 0.001) and D-dimer (P < 0.001) was higher, whereas troponin (P < 0.001) was lower in patients admitted to the ICU, but no significant difference was observed between the values of ESR (P = 0.292) in the two groups. Conclusion: This study showed that the values of CRP and D-dimer were higher in patients admitted to the ICU, but no significant difference was observed between the values of ESR in the two groups.

Altered Insulin Clearance after Gastric Bypass and Sleeve Gastrectomy in the Fasting and Prandial Conditions.

Background: The liver has the capacity to regulate glucose metabolism by altering the insulin clearance rate (ICR). The decreased fasting insulin concentrations and enhanced prandial hyperinsulinemia after Roux-en-Y gastric-bypass (GB) surgery and sleeve gastrectomy (SG) are well documented. Here, we investigated the effect of GB or SG on insulin kinetics in the fasting and fed states. Method: ICR was measured (i) during a mixed-meal test (MMT) in obese non-diabetic GB (n = 9) and SG (n = 7) subjects and (ii) during a MMT combined with a hyperinsulinemic hypoglycemic clamp in the same GB and SG subjects. Five BMI-matched and non-diabetic subjects served as age-matched non-operated controls (CN). Results: The enhanced ICR during the fasting state after GB and SC compared with CN (p < 0.05) was mainly attributed to augmented hepatic insulin clearance rather than non-liver organs. The dose-response slope of the total insulin extraction rate (InsExt) of exogenous insulin per circulatory insulin value was greater in the GB and SG subjects than in the CN subjects, despite the similar peripheral insulin sensitivity among the three groups. Compared to the SG or the CN subjects, the GB subjects had greater prandial insulin secretion (ISR), independent of glycemic levels. The larger post-meal ISR following GB compared with SG was associated with a greater InsExt until it reached a plateau, leading to a similar reduction in meal-induced ICR among the GB and SG subjects. Conclusions: GB and SG alter ICR in the presence or absence of meal stimulus. Further, altered ICR after bariatric surgery results from changes in hepatic insulin clearance and not from a change in peripheral insulin sensitivity.

Risk factors of the efficacy of hepatitis B vaccine in health-care workers.

BACKGROUND: Conventional hepatitis B virus vaccination fails to achieve efficient protection in about 5%-10% of the world population. Different factors influence the immunogenicity of hepatitis B vaccine. This study aimed to evaluate these factors in health-care workers. MATERIALS AND METHODS: This was a descriptive study which was implemented among 140 of medical and dental staff working as health-care workers who were low responder after vaccination entered the study. RESULTS: Age (>40 years), weight (body mass index >25), immunodeficiency diseases, (primary immune deficiency and immunosuppressant drugs), diabetes mellitus, and smoking were the important factors. CONCLUSION: In the high-risk group of hepatitis B disease, the risk factors of immunogenicity must be evaluated at vaccination and check titers of antibody after vaccination.

Beta-cell sensitivity to insulinotropic gut hormones is reduced after gastric bypass surgery.

OBJECTIVE: Postprandial hyperinsulinaemia after Roux-en Y gastric bypass (GB) has been attributed to rapid nutrient flux from the gut, and an enhanced incretin effect. However, it is unclear whether surgery changes islet cell responsiveness to regulatory factors. This study tested the hypothesis that ß-cell sensitivity to glucagon like-peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) is attenuated after GB. DESIGN: Ten non-diabetic subjects with GB, and 9 body mass index (BMI)-matched and age-matched non-surgical controls (CN) with normal glucose tolerance had blood glucose clamped at ~7.8 mM on three separate days. Stepwise incremental infusions of GLP-1 (15, 30, 60, 120 and 300 ng/LBkg/h), GIP (75, 150, 300, 600 and 1200 ng/LBkg/h) or saline were administered from 90 to 240 min and insulin secretion measured. RESULTS: GB subjects had similar fasting glucose levels but lower fasting insulin compared with CN, likely due to increased insulin clearance. The average insulin secretion rates (ISRs) to 7.8 mM glucose were ~30% lower in GB relative to CN subjects. However, incretin-stimulated ISRs, adjusted for insulin sensitivity and glucose-stimulated insulin secretion, were even more attenuated in the GB subjects, by threefold to fourfold (AUCISR(90-240 min) during GLP-1 and GIP: 47±8 and 44±12 nmol in GB and 116±16 and 161±44 in CN; p<0.01). CONCLUSION: After GB, the sensitivity of insulin secretion to both glucose and incretins is diminished.

Postprandial hypoglycemia after gastric bypass surgery: from pathogenesis to diagnosis and treatment.

PURPOSE OF REVIEW: The Roux-en-Y gastric bypass surgery (RYGB) improves glucose control in majority of patients with type 2 diabetes. However, a minority group of individuals develop a life-threatening complication of hyperinsulinemic hypoglycemia. The goal of this review is to identify underlying mechanisms by which RYGB cause hypoglycemia and describe pathogenesis-driven strategies to diagnose and treat this condition. RECENT FINDINGS: Gastric bypass leads to higher and earlier peak levels of glucose and lower nadir glucose after eating along with larger insulin and glucagon-like peptide 1 (GLP-1) secretion, resetting the balance between glucose appearance and clearance after this procedure. These weight-loss independent glycemic effects of RYGB have been attributed to changes in ingested glucose appearance as a result of rapid nutrient emptying from stomach pouch to the intestine and increased glucose clearance as a result of prandial hyperinsulinemia. The exaggerated effect of RYGB on postmeal glucose metabolism is a syndrome of postprandial hyperinsulinemic hypoglycemia manifesting in a group of individuals several years after this surgery. Affected patients have larger systemic appearance of ingested glucose and greater postmeal secretion of insulin and GLP-1 compared to those with history of RYGB without symptomatic hypoglycemia. Current evidence supporting a multifactorial model of glucose dysregulation among patients with hypoglycemia will be highlighted in this review. SUMMARY: Hypoglycemia after RYGB is a life-threatening condition and likely represents the extreme glycemic phenotype of this procedure. Diagnosis is challenging and treatment options are limited.

Role of vagal activation in postprandial glucose metabolism after gastric bypass in individuals with and without hypoglycaemia.

Patients who have undergone gastric bypass surgery (GB) have enhanced postprandial hyperinsulinaemia and a greater incretin effect is apparent. In the present study, we sought to determine the effect of vagal activation, a neural component of the enteroinsular axis, on postprandial glucose metabolism in patients with and without hypoglycaemia after GB. Seven patients with documented post-GB hypoglycaemia, seven asymptomatic patients without hypoglycaemia post-GB, and 10 weight-matched non-surgical controls with normal glucose tolerance were recruited. Blood glucose, and islet hormone and incretin secretion were compared during mixed meal tolerance tests (MMTs) with and without prior sham-feeding on two separate days. Sham feeding preceding the MMT caused a more rapid increase in prandial blood glucose levels but lowered overall glycaemia in all three groups (P < 0.05). Sham feeding had a similar effect to increase early (P < 0.05), but not overall, meal-induced insulin secretion in the three groups. Prandial glucagon concentrations were significantly greater in the GB groups, and sham feeding accentuated this response (P < 0.05). The effect of vagal activation on prandial glucose and islet-cell function is preserved in patients who have undergone GB, in those both with and without hypoglycaemia.

Beta-cell sensitivity to glucose is impaired after gastric bypass surgery.

AIMS: Patients who have undergone Roux-en-Y gastric bypass surgery (GB) have exaggerated postprandial insulin secretion, which has been attributed to increased meal glucose appearance and enhanced incretin effect. Here, we sought to determine ß-cell glucose sensitivity in the absence of meal stimulation and insulinotropic gut factors. MATERIALS AND METHODS: A total of 12 non-diabetic subjects with prior GB, and 7 matched non-surgical control subjects with normal glucose tolerance were studied. Blood glucose and insulin secretion rates were measured during a graded glucose infusion at increasing and then decreasing rates. Insulin sensitivity (SI ) and glucose effectiveness (SG ) were determined by the minimal model. RESULTS: GB subjects had SI comparable to that of control subjects. GB subjects had relative hyperglycaemia during the highest dose of glucose infusion associated with significantly reduced ß-cell glucose sensitivity throughout both step-up (GB: 34 ± 6, CN: 82 ± 9 pmol min-1 mM-1 L, P < .0001) and step-down (GB: 31 ± 6, CN: 74 ± 9 pmol min-1 mM-1 L, P < .0001) phases of the glucose infusion. GB subjects also had reduced SG (GB: 0.04 ± 0.00, CN: 0.07 ± 0.01 min-1 , P = .004). CONCLUSION: In the absence of enteric stimuli, ß-cell sensitivity to changes in glycaemia is blunted among individuals with GB, indicating a significant shift in a fundamental property of ß-cell function several years after surgery.

Study of the effect of Memantine therapy on the treatment of dyslexia in children.

BACKGROUND: Reading disorder (RD) is one of the important complaints in children with learning disorders (LD) that is prevalent in 4% of children in the United States. Treating this disorder includes education of reading practices and treating psychological disorders, and there are no exact medications prescribed in these children. Memantine has been effective in treating memory problems in Alzheimer Dementia, obsessive-compulsive disorder, autism disorder, and other psychological diseases. The aim of this study is to evaluate the effect of memantine in improving RD in children. MATERIALS AND METHODS: In this randomized clinical trial, 62 children, with RD in Pediatric Psychiatry Clinics of Noor and Ali-Asghar Hospital in Isfahan from 2015 to 2016, were participated. They were randomly assigned to two groups of equal number, one receiving education plus memantine and the other education plus placebo. RD was evaluated at the beginning, 1 and 3 months after intervention by Iranian standard reading and dyslexia test (Nama). RESULTS: Mean (standard deviation) age of participants was 7.55 (0.60) years. Most of the participants were boy (55%), most having parents in 36-45-year-old age group (52% and 48% for fathers and mothers, respectively), and also most parents in diploma and bachelor educational group (61% and 60% for fathers and mothers, respectively). There were statistical significant difference in trend of total score (P = 0.034), word chain (P < 0.001), rhyming (P < 0.001), text comprehension (P < 0.001), and letter fluency (P = 0.002), subscale between two groups. However, the difference of time trend between two groups was not significant in word reading (P = 0.14), word comprehension (P = 0.06), phoneme deletion (P = 0.12), reading nonwords (P = 0.32), and category fluency (P = 0.06). CONCLUSION: Adding memantine to educational practices is effective in improving RD in school-age children with LD.