Effect of hyperglycemia and empagliflozin on markers of cardiorenal injury and inflammation in patients with type 1 diabetes.

AIMS: To investigate the effect of hyperglycemia and empagliflozin on cardiorenal injury and inflammation in patients with uncomplicated type 1 diabetes (T1D). METHODS: Serum cardiac (sST2, Gal-3, cTnT), kidney injury (KIM-1, NGAL), inflammatory (sTNFR1, sTNFR2), and hemodynamic (NT-proBNP, EPO) markers were assessed post-hoc in two separate T1D cohorts. The glycemic clamp trial (NCT02344602) evaluated 49 adults with T1D and 27 controls under euglycemic and acute hyperglycemic conditions. The crossover BETWEEN trial (NCT02632747) investigated empagliflozin 25 mg plus ramipril for 4 weeks compared to placebo-ramipril for 4 weeks in 30 adults with T1D. RESULTS: In the glycemic clamp study, hyperglycemia acutely increased levels of NT-proBNP (p = 0.0003) and sTNFR2 (p = 0.003). BETWEEN participants treated with empagliflozin exhibited a paradoxical subacute rise in NT-proBNP (p = 0.0147) compared to placebo, independent of hematocrit. Individuals with higher baseline levels of sST2 and sTNFR1 had greater empagliflozin-associated reductions in systolic blood pressure and greater activation of renin-angiotensin-aldosterone system (RAAS) mediators, whereas those with higher baseline levels of KIM-1 and sTNFR1 had greater glomerular filtration rate (GFR) dip. CONCLUSION: The protective mechanisms of SGLT2 inhibition on blood pressure, RAAS activation, and renal hemodynamics are apparent in the subset of people with uncomplicated T1D with adverse cardiorenal and inflammatory markers.

High blood glucose variability may predict poor outcomes in patients with spontaneous cerebellar hemorrhage undergoing surgical operation: a retrospective study.

BACKGROUND: Elevated blood glucose (BG) variability has been reported as an independent risk factor for poor prognosis in a variety of diseases. This study aimed to investigate the association between BG variability and clinical outcomes in patients with spontaneous cerebellar hemorrhage (SCH) undergoing surgical operation. METHODS: This retrospective cohort study of the consecutive patients admitted to the department of Neurosurgery, the Affiliated Hospital of Qingdao University between January 2014 and June 2022 with the diagnosis of SCH underwent surgical intervention. BG analysis was continuously and routinely performed. BG variability was represented by the standard deviation (SD) of the serial measurements within the first 7 days. The general characteristics, imageological information, blood glucose level, and surgical information were reviewed and compared through medical records. RESULTS: A total of 115 patients (65 male and 50 female) were enrolled. Out of all 115 patients, the overall clinical outcomes according to the modified Rankin Scale (mRS) were poor (mRS 3-6) in 31 patients (26.96%) and good (mRS 0-2) in 84 patients (73.04%). Twelve of the 115 patients died during hospitalization, and the mortality rate was 10.43%. Multivariate logistic regression analysis showed that SD of BG (odds ratio (OR), 4.717; 95% confidence interval (CI), 1.054-21.115; P = 0.043), GCS (OR, 0.563; 95% CI, 0.330-0.958; P = 0.034), and hematoma volume (OR, 1.395; 95% CI, 1.118-1.748; P = 0.003) were significant predictors. The area under the ROC curve of SD of BG was 0.911 (95% CI, 0.850-0.973; P < 0.001) with a sensitivity and specificity of 90.3% and 83.3%, respectively, and the cut-off value was 1.736. CONCLUSIONS: High BG Variability is independently correlated with the 6-month poor outcomes in patients with SCH undergoing surgical operation.

Relationship between stress hyperglycemia ratio and prognosis in patients with aneurysmal subarachnoid hemorrhage: a two-center retrospective study.

Previous research have demonstrated that the stress hyperglycemia ratio (SHR) accurately reflects acute hyperglycemic states and correlates with adverse outcomes. This study aims to explore the relationship between SHR and the prognosis of patients with aneurysmal subarachnoid hemorrhage (aSAH). Patients with aSAH were categorized into four groups based on SHR tertiles. Functional outcomes were evaluated at 12 months using the modified Rankin Scale (mRS), with scores ranging from 0 to 2 indicating a good outcome and 3-6 indicating a poor outcome. The associations between SHR and functional outcomes were analyzed using logistic regression models and restricted cubic spline analysis. A total of 127 patients exhibited poor functional outcomes. Following comprehensive adjustments, those in the highest SHR tertile had a significantly increased risk of poor prognosis compared to those in the lowest tertile (odds ratio [OR], 4.12; 95% confidence interval [CI]: 1.87-9.06). Moreover, each unit increase in SHR was associated with a 7.51-fold increase in the risk of poor prognosis (OR, 7.51; 95% CI: 3.19-17.70). Further analysis using restricted cubic spline confirmed a linear correlation between SHR and poor prognosis (P for nonlinearity = 0.609). Similar patterns were observed across all studied subgroups. Elevated SHR significantly correlates with poor functional prognosis at one year in patients with aSAH, independent of their diabetes status.

A framework to classify gestational diabetes diagnosed by routine antenatal 75g glucose tolerance testing.

OBJECTIVE: To create an objective framework to classify gestational diabetes mellitus diagnosed by routine antenatal 75 g diabetes testing results to provide an alternative to current treatment-based classification. METHODS: A framework was created to classify gestational diabetes according to the severity of glycemic abnormalities after routine antenatal 75 g GTT (classes 1 through 4, determined by fasting and post-test glycemic abnormalities). A retrospective cohort chart review was used to correlate clinically how often diet therapy alone maintained glycemic targets throughout pregnancy in each class. Chi-square analysis was used to assess inter-class differences in the success of diet therapy alone maintaining glycemic targets throughout pregnancy. RESULTS: Seventy-four of 228 (33%), 35/228 (15%), 76/228 (33%), and 43/228 (19%) of the study population were classified as Class 1, 2, 3, or 4, respectively. Of eighty-nine patients who maintained glycemic targets throughout pregnancy with diet alone 51/89 (57%) were Class 1, 20/89 (22.5%) were Class 2, 11/89 (12.5%) were Class 3, and 7/89 (8%) were Class 4. Chi-square analysis showed statistically significant inter-class differences in the likelihood of diet therapy alone maintaining glycemic targets throughout pregnancy. CONCLUSION: In this framework classifying gestational diabetes according to the severity of glycemic abnormalities after routine antenatal 75 g GTT (an objective proxy for disease severity), the higher the assigned class, the less likely that diet therapy alone maintained glycemic targets throughout pregnancy (a clinical proxy for disease severity).

Non-enzymatic glycation and diabetic kidney disease.

Chronic diabetes leads to various complications including diabetic kidney disease (DKD). DKD is a major microvascular complication and the leading cause of morbidity and mortality in diabetic patients. Varying degrees of proteinuria and reduced glomerular filtration rate are the cardinal clinical manifestations of DKD that eventually progress into end-stage renal disease. Histopathologically, DKD is characterized by renal hypertrophy, mesangial expansion, podocyte injury, glomerulosclerosis, and tubulointerstitial fibrosis, ultimately leading to renal replacement therapy. Amongst the many mechanisms, hyperglycemia contributes to the pathogenesis of DKD via a mechanism known as non-enzymatic glycation (NEG). NEG is the irreversible conjugation of reducing sugars onto a free amino group of proteins by a series of events, resulting in the formation of initial Schiff's base and an Amadori product and to a variety of advanced glycation end products (AGEs). AGEs interact with cognate receptors and evoke aberrant signaling cascades that execute adverse events such as oxidative stress, inflammation, phenotypic switch, complement activation, and cell death in different kidney cells. Elevated levels of AGEs and their receptors were associated with clinical and morphological manifestations of DKD. In this chapter, we discussed the mechanism of AGEs accumulation, AGEs-induced cellular and molecular events in the kidney and their impact on the pathogenesis of DKD. We have also reflected upon the possible options to curtail the AGEs accumulation and approaches to prevent AGEs mediated adverse renal outcomes.

Glucose Fluctuations in Acute Ischemic Stroke.

INTRODUCTION: The Oxfordshire Community Stroke Project denotes four subtypes of ischemic stroke (total and partial anterior infarct, posterior, and lacunar). Hyperglycemia has been associated with a larger infarct size and poor prognosis. AIM: The purpose of the study was to investigate the correlation of glucose fluctuations with the Oxford sub-categories and patient outcomes using a blinded continuous glucose monitoring system. METHODS: This is a non-interventional prospective observational study. Stroke patients with symptoms onset in the last 24h, participated in the study. A glucose sensor was placed for 72 hours. Disability was assessed using the modified Rankin Scale. Stroke subtypes were compared with total mean glucose and time in range using ANOVA analysis. Multiple ordinal logistic regression was employed to analyze outcomes and survival. RESULTS: The sample consisted of 105 diabetic and non-diabetic patients. The overall mean glucose was 127.06 mg/dL and the time in range (70-140 mg/dL) was 70.98%. There was no significant difference between the stroke sub-categories and the total mean glucose. For every one-point increase in the time in range, we expect a 1.5% reduction in the odds of having a worse outcome. Patients with total anterior infarct are 2.31 times more likely to have a worse outcome than lacunar patients. CONCLUSION: The utilization of the Oxford classification may not be necessary for managing acute ischemic stroke glucose levels. Achieving glucose regulation and an increase in time in range can be attained through meticulous control, potentially extending life expectancy. Continuous glucose monitors may aid in achieving this objective.

Reduced cell-mediated immune response in hyperglycemic NOD mice following influenza vaccination.

Due to the higher risk of medical complications posed by influenza infection, patients with type 1 diabetes (T1D) are strongly recommended to receive the influenza vaccine. However, it remains unclear if hyperglycemia in patients with T1D affects vaccine-induced immune responses. In this study, we investigated the humoral and cellular immune responses of prediabetic and diabetic, nonobese diabetic (NOD) mice following influenza vaccination to determine the effects of hyperglycemia on influenza vaccine-induced responses. In diabetic NOD mice, vaccine-specific IgG and IgM levels, as well as IgG-producing cells, were comparable to those in prediabetic NOD mice. However, the diabetic NOD mice exhibited reduced percentages of memory T cells and activated T cells in the spleen, along with reduced number of vaccine-specific interferon (IFN)-γ-secreting cells. Thus, these findings suggest that in patients with T1D, hyperglycemia could lead to impaired cell-mediated immune responses following influenza vaccination.

Metformin is associated with reduced risk of mortality and morbidity in burn patients compared to insulin.

PURPOSE: The standard of care for burned patients experiencing hyperglycemia associated with the hypermetabolic response is insulin therapy. Insulin treatment predisposes burn patients to hypoglycemia, which increases morbidity and mortality. Metformin has been suggested as an alternative to insulin therapy for glycemic control in burn patients given its safety profile, but further research is warranted. This study investigated whether metformin use in burn patients is associated with improved glycemic control and morbidity/mortality outcomes compared to insulin use alone. MATERIALS AND METHODS: Using the TriNetX database, we conducted a retrospective study of burned patients who were administered insulin, metformin, or both within one week of injury. Demographic, comorbidity, and burn severity information were collected. Patients were categorized by treatment type, propensity score-matched, and compared for the following outcomes within 3 months: hyperglycemia, hypoglycemia, sepsis, lactic acidosis, and death. Statistical significance was set a priori at p ≤ 0.05. RESULTS: The insulin cohort was at increased risk for all outcomes (all p < 0.0001) compared to the metformin cohort, and an increased risk for sepsis, lactic acidosis, and death (all p ≤ 0.0002) compared to the insulin/metformin combination cohort. When compared to the metformin cohort, the combination cohort was at increased risk for all outcomes (all p ≤ 0.0107) except death. CONCLUSIONS: Treatment with metformin after burn is associated with a reduced risk of morbidity and mortality compared to insulin. The combination of insulin and metformin is no more effective in reducing the risk of hyperglycemia and hypoglycemia than insulin alone but is less effective than metformin alone.

Association between preoperative persistent hyperglycemia and postoperative delirium in geriatric hip fracture patients.

BACKGROUND: The management of preoperative blood glucose levels in reducing the incidence of postoperative delirium (POD) remains controversial. This study aims to investigate the impact of preoperative persistent hyperglycemia on POD in geriatric patients with hip fractures. METHODS: This retrospective cohort study analyzed medical records of patients who underwent hip fracture surgery at a tertiary medical institution between January 2013 and November 2023. Patients were categorized based on preoperative hyperglycemia (hyperglycemia defined as ≥ 6.1mmol/L), clinical classification of hyperglycemia, and percentile thresholds. Multivariate logistic regression and propensity score matching analysis (PSM) were employed to assess the association between different levels of preoperative glucose and POD. Subgroup analysis was conducted to explore potential interactions. RESULTS: A total of 1440 patients were included in this study, with an incidence rate of POD at 19.1% (275/1440). Utilizing multiple logistic analysis, we found that patients with hyperglycemia had a 1.65-fold increased risk of experiencing POD compared to those with normal preoperative glucose levels (95% CI: 1.17-2.32). Moreover, a significant upward trend was discerned in both the strength of association and the predicted probability of POD with higher preoperative glucose levels. PSM did not alter this trend, even after meticulous adjustments for potential confounding factors. Additionally, when treating preoperative glucose levels as a continuous variable, we observed a 6% increase in the risk of POD (95% CI: 1-12%) with each 1mmol/L elevation in preoperative glucose levels. CONCLUSIONS: There exists a clear linear dose-response relationship between preoperative blood glucose levels and the risk of POD. Higher preoperative hyperglycemia was associated with a greater risk of POD. CLINICAL TRIAL NUMBER: NCT06473324.

Infant of a diabetic mother: clinical presentation, diagnosis and treatment.

An infant of a diabetic mother is defined as a newborn born to a mother who has diabetes during pregnancy. The term diabetic mother refers to pregnant women with diabetes diagnosed either before (type 1 or 2 diabetes) or during pregnancy (gestational diabetes). Rising incidence of type 1 and type 2 diabetes in young women and increasing maternal age at conception account for the higher risk of birth complications and adverse maternal and infant outcomes. Infants of diabetic mothers (IDMs) because of mother's diabetes are prone to developing complications and the most common include: large birth weight and complications resulting from it (i.e. birth injuries, perinatal asphyxia), cardiovascular and respiratory insufficiency (poor tolerance of labor stress), neonatal hypoglycemia and it's complications, delayed lung maturity (fetal hyperinsulinism and the opposite function of insulin to cortisol), cardiomegaly and hypertrophy of the intraventricular septum (functional narrowing of the outflow of the left ventricle and cardiac failure), congenital malformations (most often of the central nervous system and heart). Less common complications in IDMs are: persistent pulmonary hypertension, hyperbilirubinemia, renal vein thrombosis, small left colon syndrome, intrauterine death, polycythemia, and a predisposition to obesity, insulin resistance and diabetes later in life. This article presents current knowledge about pathological conditions and the recommended management for IDMs.

Resurgence of orbital mucormycosis during COVID-19 pandemic: Study from a tertiary care center in Eastern India.

PURPOSE: A sudden surge of Mucormycosis cases during the second wave of Covid 19 was observed in certain parts of India. The reasons for this upsurge remain unknown. However its impact on the overall healthcare system was quite overwhelming. In this context this study was decided to estimate and assess the spectrum of orbital involvement in patients with Mucormycosis, to find its association with coexisting disease entities if any, and at the same time evaluate the therapeutic response to established treatment regimens. MATERIALS AND METHODS: This descriptive longitudinal study was conducted over a period of six months. Patients presenting with symptoms of Mucormycosis were jointly evaluated by a multi speciality team. After confirmation of diagnosis, patients were treated with intravenous Amphotericin B, surgical debridement of affected sinuses and orbital exenteration when indicated. They were followed up for three months after discharge. RESULTS: Forty-three patients were enrolled in this study. Thirty-seven (86.04%) were COVID positive. All of them had history of steroid exposure during COVID treatment. Ninety five percent of study participants had diabetes mellitus. Twenty-seven (62.79%) patients had orbital involvement. Most common clinical presentation was peri-orbital or facial pain and edema. Besides medical treatment, thirty-nine patients (90.69%) required sinus debridement and nine patients (20.9%) required orbital exenteration. Thirteen patients (30.23%) expired during the follow up period. With treatment disease regressed in twenty patients (46.51%). CONCLUSION: Diabetes and use of steroids to prevent anticipated cytokine storm may be the inciting factors for Orbital Mucormycosis in COVID patients. Early diagnosis, treatment and control of risk factors are keys for recovery and survival..

Stress hyperglycemia ratio and the clinical outcome of patients with heart failure: a meta-analysis.

Background: Stress hyperglycemia ratio (SHR) is a newly suggested measure of stress-induced hyperglycemia that combines both short-term and long-term glycemic conditions. The study aimed to explore the association between SHR and the incidence of adverse clinical events with heart failure (HF) through a meta-analysis. Methods: Cohort studies relevant to the aim of the meta-analysis were retrieved by search of electronic databases including PubMed, Web of Science, Embase, Wanfang, and CNKI. A random-effects model was used to combine the data by incorporating the influence of between-study heterogeneity. Results: Ten studies involving 15250 patients with HF were included. Pooled results showed that compared to patients with lower SHR at baseline, those with a higher SHR were associated with an increased risk of all-cause mortality during follow-up (risk ratio [RR]: 1.61, 95% confidence interval [CI]: 1.17 to 2.21, p = 0.003; I2 = 82%). Further meta-regression analysis suggests that different in the cutoff of SHR significantly modify the results (coefficient = 1.22, p = 0.02), and the subgroup analysis suggested a more remarkable association between SHR and all-cause mortality in studies with cutoff of SHR ≥ 1.05 than those with cutoff of SHR < 1.05 (RR: 2.29 versus 1.08, p for subgroup difference < 0.001). Subsequent meta-analyses also showed that a high SHR at baseline was related to the incidence of cardiovascular death (RR: 2.19, 95% CI: 1.55 to 3.09, p < 0.001; I2 = 0%), HF-rehospitalization (RR: 1.83, 95% CI: 1.44 to 2.33, p < 0.001; I2 = 0%), and major adverse cardiovascular events (RR: 1.54, 95% CI: 1.15 to 2.06, p = 0.004; I2 = 74%) during follow-up. Conclusion: A high SHR at baseline is associated with a poor clinical prognosis of patients with HF. Systematic review registration: https://inplasy.com, identifier INPLASY202430080.

The effects of stress hyperglycemia in diabetic and nondiabetic patients with large vessel occlusions undergoing mechanical thrombectomy.

INTRODUCTION: Diabetes and hyperglycemia are major risk factors that can increase infarction volume and contribute to poor functional status. Our study aim was to investigate the effect of stress hyperglycemia on various safety and efficacy outcomes in patients with large vessel occlusions (LVOs) undergoing mechanical thrombectomy (MT) with or without diabetes. METHODS: A retrospective analysis of consecutive LVO patient data treated with MT at a Comprehensive Stroke Center in the Mid-South was conducted. Adult patients with LVO on computed tomography angiography (CTA) and treated with MT within 24 h of symptom onset were included. The primary outcome was to determine if there was an association in collateral flow or infarct size in the setting of hyperglycemia. Secondary outcomes included National Institute of Health Sciences Score (NIHSS) and Modified Rankin Score (mRS). RESULTS: A total of 450 patients underwent MT, out of which 433 had baseline hemoglobin A1c recorded: mean age: 64 ± 15 years, 47% women, pretreatment NIHSS median 15 points (interquartile range 10-19), 323 (75%) with good collaterals grades >2 on multiphasic CTA, 326 (75%) were non-diabetic, and 107 (25%) were diabetic. Nondiabetics with stress hyperglycemia had a tendency toward higher pre-treatment NIHSS scores (mean 17.5 ± 7.6, P = 0.02) and at 24-h (12.9 ± 9.0, P = 0.02), poor collaterals (multiphasic CTA score ≥2; 21.4% vs. 34.5%, P = 0.02), larger infarct volumes (50.7 ± 63.6 vs. 24.4 ± 33.8 cc, P < 0.0001), and had poorer functional outcomes (good mRS 0-2 47.7% vs. good mRS 0-2 36.8%) when compared to nondiabetics without stress hyperglycemia. For every 1 mg/dL increase in admission blood glucose, there was a 0.3 cc increase in infarct volume (95% confidence intervals for ß =0.2-0.4; P < 0.0001) after adjusting for the final thrombolysis in cerebral infarction score. CONCLUSIONS: LVO patients with stress hyperglycemia without previously diagnosed diabetes had more severe strokes, developed larger infarct volumes, poorer collaterals, and had worse functional outcomes at 90 days post-MT. In addition, LVO patients with diabetes and stress hyperglycemia exhibited more passes during MT and worse functional outcomes.

Effects of preprandial versus postprandial nutritional insulin administration in the inpatient setting.

AIMS: Hospitalized patients can have inconsistent nutritional intake due to acute illness, changing diet, or unpredictable meal delivery. The aim of this study was to evaluate whether implementation of a hospital-wide policy shifting nutritional insulin administration from pre-meal to post-meal was associated with changes in glycemic control or length of stay (LOS). METHODS: This retrospective study performed at a community hospital evaluated adult inpatients receiving nutritional insulin across three time periods. pre-intervention, immediate post-intervention, and distant post-intervention. Outcomes included rates of hypoglycemia (glucose ≤ 70 mg/dL), moderate hypoglycemia (< 54 mg/dL), severe hypoglycemia (≤ 40 mg/dL), severe hyperglycemia (≥ 300 mg/dL), daily mean glucose level, and LOS. RESULTS: The number of patient-days analyzed across the cohorts were 1948, 1751, and 3244, respectively. After multivariate adjustment, risk of developing any hypoglycemia and severe hypoglycemia significantly decreased over time (p = 0.001 and p = 0.009, respectively). Daily mean glucose increased over time (194.6 ± 62.5 vs 196.8 ± 65.5 vs 199.3 ± 61.5 mg/dL; p = 0.003), but there were no significant differences among rates of severe hyperglycemia (p = 0.10) or LOS (p = 0.74). CONCLUSIONS: Implementing a hospital-wide shift to postprandial nutritional insulin administration significantly reduced hypoglycemia rates without increasing severe hyperglycemia. This suggests a promising strategy for improving patient safety, but further prospective randomized controlled trials are warranted to confirm these findings.

Risk factors at admission of in-hospital dysglycemia, mortality, and readmissions in patients with type 2 diabetes and pneumonia.

AIMS: In-hospital dysglycemia is associated with adverse outcomes. Identifying patients at risk of in-hospital dysglycemia early on admission may improve patient outcomes. METHODS: We analysed 117 inpatients admitted with pneumonia and type 2 diabetes monitored by continuous glucose monitoring. We assessed potential risk factors for in-hospital dysglycemia and adverse clinical outcomes. RESULTS: Time in range (3.9-10.0 mmol/l) decreased by 2.9 %-points [95 % CI 0.7-5.0] per 5 mmol/mol [2.6 %] increase in admission haemoglobin A1c, 16.2 %-points if admission diabetes therapy included insulin therapy [95 % CI 2.9-29.5], and 2.4 %-points [95 % CI 0.3-4.6] per increase in the Charlson Comorbidity Index (CCI) (integer, as a measure of severity and amount of comorbidities). Thirty-day readmission rate increased with an IRR of 1.24 [95 % CI 1.06-1.45] per increase in CCI. In-hospital mortality risk increased with an OR of 1.41 [95 % CI 1.07-1.87] per increase in Early Warning Score (EWS) (integer, as a measure of acute illness) at admission. CONCLUSIONS: Dysglycemia among hospitalised patients with pneumonia and type 2 diabetes was associated with high haemoglobin A1c, insulin treatment before admission, and the amount and severity of comorbidities (i.e., CCI). Thirty-day readmission rate increased with high CCI. The risk of in-hospital mortality increased with the degree of acute illness (i.e., high EWS) at admission. Clinical outcomes were independent of chronic glycemic status, i.e. HbA1c, and in-hospital glycemic status.

Psychosis Associated With Hyperglycemia in a Female Patient With Type 1 Diabetes Mellitus: A Case Report.

This paper presents the case of a 22-year-old woman who was hospitalized multiple times with episodes of psychosis co-occurring with hyperglycemia. Her psychosis was characterized by auditory hallucinations, visual hallucinations, and disorganized speech and behavior. The patient has a prior medical history of type 1 diabetes mellitus (T1DM) and Graves' disease and was non-adherent to diabetic diet and medications. The patient is a Somalian refugee who moved to the United States (US) a year ago. We explore the relatively unique observation of hyperglycemia-induced psychosis in the patient, specifically in the context of autoimmune disorders. We also discuss some of the complexities associated with the cultural aspects of mental health and diabetes management in refugee communities and their implications in clinical practice.

Insulin Dynamics and Pathophysiology in Youth-Onset Type 2 Diabetes.

Youth-onset type 2 diabetes (T2D) is increasing around the globe. The increased disease burden of youth-onset T2D portends substantial consequences for the health outcomes of young people and for health care systems. The pathophysiology of this condition is characterized by insulin resistance and initial insulin hypersecretion +/- an inherent insulin secretory defect, with progressive loss of stimulated insulin secretion leading to pancreatic ß-cell failure. Research studies focusing on youth-onset T2D have illuminated key differences for youth- versus adult-onset T2D, with youth having more profound insulin resistance and quicker progression to loss of sufficient insulin secretion to maintain euglycemia. Therapies targeted to improve both insulin resistance and, importantly, maintain sufficient insulin secretory function over the lifespan in youth-onset T2D are needed.

Low preoperative hemoglobin A1c level is a predictor of perioperative infectious complications after esophagectomy: A retrospective, single-center study.

This retrospective, single-center study aimed to evaluate the impact of blood glucose (BG) markers on perioperative complications after esophagectomy in a cohort of 176 patients. Study analyses included the correlation of daily maximum BG level and hemoglobin A1c (HbA1c) with clinicopathological factors. Maximum BG levels were significantly higher on postoperative day (POD) 0 than on PODs 2, 3, 5, and 7 (p < 0.05). Additionally, maximum BG levels on PODs 1, 2, and 7 were significantly higher in patients with preoperative HbA1c levels of ≥ 5.6% than in those with preoperative HbA1c levels of < 5.6% (p < 0.05 for all). The rates of any complications and infectious complications were higher in patients with preoperative HbA1c levels of < 5.6% than in those with preoperative HbA1c levels of ≥ 5.6% (p < 0.05 for both). A preoperative HbA1c level of < 5.6% was a significant predictor of infectious complications after esophagectomy by logistic regression analysis (p < 0.05). Maximum BG level after esophagectomy remained high in patients with high preoperative HbA1c levels, whereas a normal HbA1c level was an independent risk factor for infectious complications.

Protective effect of ellagic acid against high-glucose-induced injury in human umbilical venous endothelial cells.

Objective: There is escalating evidence suggesting the beneficial effects of ellagic acid (EA) on the cardiovascular system. The aim of the present study was to investigate the protective effect of EA in human umbilical vein endothelial cells (HUVECs) against high glucose (HG)- induced endothelial dysfunction and to study the potential roles of adropin and nitric oxide (NO) in this regard. Materials and Methods: The experimental groups consisted of normal and HG (30 mM, 48 hr)-treated HUVECs incubated without or with 5 or 10 µM of EA (6 groups of at least 6 replicates, each). The cell count and viability were studied. Moreover, the markers of the redox state, including malondialdehyde (MDA), the activities of superoxide dismutase (SOD) and catalase enzymes, and ferric reducing anti-oxidant power (FRAP), were assayed. The levels of adropin and eNOS gene expression were also studied using RT-qPCR. Results: A high concentration of glucose reduced cell count and caused lipid peroxidation, reduced anti-oxidant capacity of the cells, decreased NO levels, and downregulated the expression of NOS3 (encoding eNOS) and ENHO (encoding adropin) genes. Ellagic acid reversed all these effects. Conclusion: These results suggest a significant protective effect for EA against HG-induced injury in HUVECs. The improved redox state and upregulation of NOS3 and ENHO genes seem to play critical roles in this regard.

Microbiota based personalized nutrition improves hyperglycaemia and hypertension parameters and reduces inflammation: a prospective, open label, controlled, randomized, comparative, proof of concept study.

Background: Recent studies suggest that gut microbiota composition, abundance and diversity can influence many chronic diseases such as type 2 diabetes. Modulating gut microbiota through targeted nutrition can provide beneficial effects leading to the concept of personalized nutrition for health improvement. In this prospective clinical trial, we evaluated the impact of a microbiome-based targeted personalized diet on hyperglycaemic and hyperlipidaemic individuals. Specifically, BugSpeaks®-a microbiome profile test that profiles microbiota using next generation sequencing and provides personalized nutritional recommendation based on the individual microbiota profile was evaluated. Methods: A total of 30 participants with type 2 diabetes and hyperlipidaemia were recruited for this study. The microbiome profile of the 15 participants (test arm) was evaluated using whole genome shotgun metagenomics and personalized nutritional recommendations based on their microbiota profile were provided. The remaining 15 participants (control arm) were provided with diabetic nutritional guidance for 3 months. Clinical and anthropometric parameters such as HbA1c, systolic/diastolic pressure, c-reactive protein levels and microbiota composition were measured and compared during the study. Results: The test arm (microbiome-based nutrition) showed a statistically significant decrease in HbA1c level from 8.30 (95% confidence interval (CI), [7.74-8.85]) to 6.67 (95% CI [6.2-7.05]), p < 0.001 after 90 days. The test arm also showed a 5% decline in the systolic pressure whereas the control arm showed a 7% increase. Incidentally, a sub-cohort of the test arm of patients with >130 mm Hg systolic pressure showed a statistically significant decrease of systolic pressure by 14%. Interestingly, CRP level was also found to drop by 19.5%. Alpha diversity measures showed a significant increase in Shannon diversity measure (p < 0.05), after the microbiome-based personalized dietary intervention. The intervention led to a minimum two-fold (Log2 fold change increase in species like Phascolarctobacterium succinatutens, Bifidobacterium angulatum, and Levilactobacillus brevis which might have a beneficial role in the current context and a similar decrease in species like Alistipes finegoldii, and Sutterella faecalis which have been earlier shown to have some negative effects in the host. Overall, the study indicated a net positive impact of the microbiota based personalized dietary regime on the gut microbiome and correlated clinical parameters.