HYPERGLYCEMIA AS A PREDICTOR OF OUTCOME IN PAEDIATRIC SEVERE TRAUMATIC BRAIN INJURY PATIENTS UNDERWENT SURGERY: A SINGLE CENTER EXPERIENCE FROM EASTERN INDONESIA FROM 2017-2022.

OBJECTIVE: The aim: Traumatic Brain Injury (TBI) remains a significant health burden worldwide. This study aimed to describe, determine and recommendation concerning the impact of hyperglycemia on pediatric TBI. PATIENTS AND METHODS: Materials and methods: Paediatric trauma patients with severe TBI event were identified and admitted to our Dr. Soetomo General Hospital, Surabaya, the regional Trauma Center of East Java, Indonesia between calendar year of 2017 and 2022. Our institutions trauma database was utilized to select the patient included in this study. Patients with GCS ≤ 8 who underwent neurosurgical interventions were included to the study. Neurosurgical interventions are craniotomy for clot evacuation and decompressive craniectomy. We excluded patients with GCS > 8 and/or treated with conservative therapy (no surgery needed). Data collected for analysis as independent variables included patient age, admission GCS score and admission serum glucose score, mechanism of injury, type of intracranial lesion and type of surgery. Outcome of the patients included was examined at discharge which sub-grouped by Glasgow Outcomes Scale (GOS) score. Independent variables were entered into the logistic model in a stepwise fashion with a significant cutoff of p< 0,05. RESULTS: Results: Patients with worse neurological outcomes (GOS score 1-2) had a mean serum glucose value of over 200 mg/dL. Patients who died (GOS score of 1) had higher mean admission glucose values (226.44 ± 62,00) than the patients who had survived with a GOS score of 3 (139.80 ± 10.87), 4 (87), or 5 (134). Patients who resulted in a vegetative state (GOS score of 2) had higher mean admission serum glucose values than patients who were discharged with a GOS score of 5 (205.14 ± 36.17 vs. 134; p = 0.003). CONCLUSION: Conclusions: Hyperglycaemia in pediatric TBI patients that underwent neurosurgical intervention is associated with worse outcomes, even mortality. We believe that prospective evaluation of glucose normalization in the context of acute management of pediatric head injuries is both appropriate and necessary for the next study.

Antioxidant effect of enamel matrix derivative for early phase of periodontal tissue regeneration in diabetes.

BACKGROUND: Diabetes involves metabolic disorders in various tissues via hyperglycemia-induced oxidative stress. This study aimed to investigate the antioxidative effect of enamel matrix derivative (EMD) on periodontal regeneration in diabetes. METHODS: Twenty-two rats were equally divided into streptozotocin (STZ)-induced diabetes or control group. Two months after induction of hyperglycemia, systemic oxidative stress was measured using urinary 8-hydroxy-2'-deoxyguanosine. EMD or saline was applied into the intrabony defects created in the bilateral maxillary molar. mRNA expressions of inflammatory and oxidative stress markers were quantified (n = 6). Histometric analyses and immunohistochemistry of superoxide dismutase-1 (SOD-1) were performed 7 days postoperatively (n = 5). For in vitro experiments, the bone marrow-derived mesenchymal stem cells were isolated from rat femur and cultured in a high glucose (HG) or control medium. Reactive oxygen species (ROS) measurement and alizarin red staining were performed with/without EMD. RESULTS: Systemic oxidative stress was significantly higher in the diabetic group. The connective tissue attachment and cementum formation were significantly increased at EMD-treated sites in both diabetic and non-diabetic groups. The expression of nicotinamide adenine dinucleotide phosphate oxidase two and four was significantly lower at EMD-treated sites than at EMD-untreated sites in both diabetic and non-diabetic rats. Immunohistochemistry showed significantly higher SOD-1 expression at the EMD-treated site. In vitro, HG culture had significantly higher ROS production compared with control, which was downregulated by EMD. EMD treatment significantly recovered the impaired calcification in HG. CONCLUSION: EMD promoted early-phase wound healing and periodontal tissue regeneration in the surgically created bony defect of STZ-induced diabetic rat by suppressing hyperglycemia-induced oxidative stress.

Impact of poor glycemic control upon clinical outcomes after radical prostatectomy in localized prostate cancer.

To evaluate the clinical impact of preoperative glycemic status upon oncological and functional outcomes after radical prostatectomy in patients with localized prostate cancer, we analyzed the data of 2664 subjects who underwent radical prostatectomy with preoperative measurement of hemoglobin A1c within 6 months before surgery. The possible association between high hemoglobin A1c (≥ 6.5 ng/dL) and oncological/functional outcomes was evaluated. Among all subjects, 449 (16.9%) were categorized as the high hemoglobin A1c group and 2215 (83.1%) as the low hemoglobin A1c group. High hemoglobin A1c was associated with worse pathological outcomes including extra-capsular extension (HR 1.277, 95% CI 1.000-1.630, p = 0.050) and positive surgical margin (HR 1.302, 95% CI 1.012-1.674, p = 0.040) in multi-variate regression tests. Kaplan-Meier analysis showed statistically shorter biochemical recurrence-free survival in the high hemoglobin A1c group (p < 0.001), and subsequent multivariate Cox proportional analyses revealed that high hemoglobin A1c is an independent predictor for shorter BCR-free survival (HR 1.135, 95% CI 1.016-1.267, p = 0.024). Moreover, the high hemoglobin A1c group showed a significantly longer incontinence-free survival than the low hemoglobin A1c group (p = 0.001), and high preoperative hemoglobin A1c was also an independent predictor for longer incontinence-free survival in multivariate Cox analyses (HR 0.929, 95% CI 0.879-0.981, p = 0.008). The high preoperative hemoglobin A1c level was independently associated with worse oncological outcomes and also with inferior recovery of urinary continence after radical prostatectomy.

Pancreaticoduodenectomy model demonstrates a fundamental role of dysfunctional ß cells in predicting diabetes.

BACKGROUNDThe appearance of hyperglycemia is due to insulin resistance, functional deficits in the secretion of insulin, and a reduction of ß cell mass. There is a long-standing debate as to the relative contribution of these factors to clinically manifesting ß cell dysfunction. The aim of this study was to verify the acute effect of one of these factors, the reduction of ß cell mass, on the subsequent development of hyperglycemia.METHODSTo pursue this aim, nondiabetic patients, scheduled for identical pancreaticoduodenectomy surgery, underwent oral glucose tolerance tests (OGTT) and hyperglycemic clamp (HC) procedures, followed by arginine stimulation before and after surgery. Based on postsurgery OGTT, subjects were divided into 3 groups depending on glucose tolerance: normal glucose tolerance (post-NGT), impaired glucose tolerance (post-IGT), or having diabetes mellitus (post-DM).RESULTSAt baseline, the 3 groups showed similar fasting glucose and insulin levels; however, examining the various parameters, we found that reduced first-phase insulin secretion, reduced glucose sensitivity, and rate sensitivity were predictors of eventual postsurgery development of IGT and diabetes.CONCLUSIONDespite comparable functional mass and fasting glucose and insulin levels at baseline and the very same 50% mass reduction, only reduced first-phase insulin secretion and glucose sensitivity predicted the appearance of hyperglycemia. These functional alterations could be pivotal to the pathogenesis of type 2 diabetes (T2DM).TRIAL REGISTRATIONClinicalTrials.gov NCT02175459.FUNDINGUniversità Cattolica del Sacro Cuore; Italian Ministry of Education, University and Research; European Foundation for the Study of Diabetes.

Insulin resistance in bariatric surgery.

PURPOSE OF REVIEW: To give an updated review on the underlying mechanisms and clinical effects of improved glucose control after bariatric surgery. RECENT FINDINGS: The basic principles of the mechanism for the metabolic effects of bariatric surgery can be categorized into calorie restriction, deviation of nutrients, and reduced amounts of adipose tissue. Recent findings suggest the importance of early changes following deviation of nutrients to more distal parts of the small bowel resulting in altered release of gastrointestinal hormones, altered gut microbiota, and weight-reduction. In the long-term, loss of adipose tissue results in reduced inflammation and improved insulin sensitivity. From a clinical perspective these changes are associated with remission of diabetes in patients with morbid obesity and type 2 diabetes, prevention of diabetes in patients with insulin resistance without overt type 2 diabetes and prevention of both microvascular and macrovascular complications for all patients with morbid obesity. SUMMARY: At present, bariatric surgery remains the most effective treatment option to improve glucose control and long-term complications associated with hyperglycemia in patients with obesity.Although the mechanisms behind these metabolic effects remain only partially understood, further knowledge on these complex mechanisms may help identifying durable treatment options for morbid obesity and important metabolic comorbidities.

Bioinformatic analysis of peripheral blood RNA-sequencing sensitively detects the cause of late graft loss following overt hyperglycemia in pig-to-nonhuman primate islet xenotransplantation.

Clinical islet transplantation has recently been a promising treatment option for intractable type 1 diabetes patients. Although early graft loss has been well studied and controlled, the mechanisms of late graft loss largely remains obscure. Since long-term islet graft survival had not been achieved in islet xenotransplantation, it has been impossible to explore the mechanism of late islet graft loss. Fortunately, recent advances where consistent long-term survival (≥6 months) of adult porcine islet grafts was achieved in five independent, diabetic nonhuman primates (NHPs) enabled us to investigate on the late graft loss. Regardless of the conventional immune monitoring methods applied in the post-transplant period, the initiation of late graft loss could rarely be detected before the overt graft loss observed via uncontrolled blood glucose level. Thus, we retrospectively analyzed the gene expression profiles in 2 rhesus monkey recipients using peripheral blood RNA-sequencing (RNA-seq) data to find out the potential cause(s) of late graft loss. Bioinformatic analyses showed that highly relevant immunological pathways were activated in the animal which experienced late graft failure. Further connectivity analyses revealed that the activation of T cell signaling pathways was the most prominent, suggesting that T cell-mediated graft rejection could be the cause of the late-phase islet loss. Indeed, the porcine islets in the biopsied monkey liver samples were heavily infiltrated with CD3+ T cells. Furthermore, hypothesis test using a computational experiment reinforced our conclusion. Taken together, we suggest that bioinformatics analyses with peripheral blood RNA-seq could unveil the cause of insidious late islet graft loss.

Risk Factors of Intraoperative Dysglycemia in Elderly Surgical Patients.

BACKGROUNDː Dysglycemia is associated with adverse outcome including increased morbidity and mortality in surgical patients. Acute insulin resistance due to the surgical stress response is seen as a major cause of so-called stress hyperglycemia. However, understanding of factors determining blood glucose (BG) during surgery is limited. Therefore, we investigated risk factors contributing to intraoperative dysglycemia. METHODSː In this subgroup investigation of the BIOCOG study, we analyzed 87 patients of ≥ 65 years with tight intraoperative BG measurement every 20 min during elective surgery. Dysglycemia was defined as at least one intraoperative BG measurement outside the recommended target range of 80-150 mg/dL. Additionally, all postoperative BG measurements in the ICU were obtained. Multivariable logistic regression analysis adjusted for age, sex, American Society of Anesthesiologists (ASA) status, diabetes, type and duration of surgery, minimum Hemoglobin (Hb) and mean intraoperative norepinephrine use was performed to identify risk factors of intraoperative dysglycemia. RESULTSː 46 (52.9%) out of 87 patients developed intraoperative dysglycemia. 31.8% of all intraoperative BG measurements were detected outside the target range. Diabetes [OR 9.263 (95% CI 2.492, 34.433); p=0.001] and duration of surgery [OR 1.005 (1.000, 1.010); p=0.036] were independently associated with the development of intraoperative dysglycemia. Patients who experienced intraoperative dysglycemia had significantly elevated postoperative mean (p<0.001) and maximum BG levels (p=0.001). Length of ICU (p=0.007) as well as hospital stay (p=0.012) were longer in patients with dysglycemia. CONCLUSIONSː Diabetes and duration of surgery were confirmed as independent risk factors for intraoperative dysglycemia, which was associated with adverse outcome. These patients, therefore, might require intensified glycemic control. Increased awareness and management of intraoperative dysglycemia is warranted.

Islet Transplantation in Children.

PURPOSE OF REVIEW: Transplantation of the islets of Langerhans or the pancreas aims to restore blood sugar control. We review both forms of transplantation in children. RECENT FINDINGS: Allogenic islet transplantation typically in to the liver via the portal vein may be a potential alternative to pancreas transplantation in the future. Autologous islet transplantation after total pancreatectomy is effective for debilitating symptoms of recurrent and chronic pancreatitis. Chronic pancreatitis in children is most often related to genetic mutations but is otherwise similar to adults with eventual exocrine and endocrine failure. Removal of the pancreas ameliorates pain, and islet transplantation preserves endocrine function to the extent allowed by the damage sustained by the pancreas from chronic inflammation. Despite the complexity of the operative procedure, the outcome of total pancreatectomy and autologous islet transplantation in children has been excellent including quality of life.

Risk Factors for Relapse of Hyperglycemia after Laparoscopic Roux-en-Y Gastric Bypass in T2DM Obese Patients: a 5-Year Follow-Up of 24 Cases.

OBJECTIVES: To explore the risk factors for relapse of hyperglycemia in obese patients with type II diabetes mellitus (T2DM) who received laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. METHODS: A retrospective analysis was performed on all obese patients with T2DM who underwent a LRYGB during the period 2011-2013. Demographics, preoperative body mass index (BMI), preoperative glycated hemoglobin A1c (HbA1c), adherence to lifestyle intervention, preoperative medication of insulin, and the time interval between surgery and diagnosis of T2DM were investigated and compared. RESULTS: A total of 24 patients were included in our study. The median age was 45.5 years, the median BMI was 29.9 kg/m2, and the median HbA1c was 7.9%. Out of 24 patients, 54.2% (13/24) experienced a relapse of hyperglycemia. The 1-year, 3-year, and 5-year relapse rates were 4.2%, 12.5%, and 50.0%, respectively. The preoperative HbA1c level, C-peptide (2 h) level, and C-peptide (3 h) level were identified as independent variables for the relapse of hyperglycemia (8.11 ± 0.48 vs 7.72 ± 0.37 kg/m2, p = 0.036; 4.35 ± 1.46 vs 7.13 ± 4.10 ng/ml, p = 0.032; 3.76 ± 0.61 vs 5.99 ± 3.39 ng/ml, p = 0.029). Lifestyle intervention could reduce the hyperglycemia relapse rate (66.7 vs 41.7%) after LRYGB surgery. CONCLUSIONS: The preoperative HbA1c level and C-peptide level at surgery have an important significance in predicting the relapse of hyperglycemia after LRYGB surgery; lifestyle intervention is crucial for these patients.

DISORDERS OF CARBOHYDRATE METABOLISM IN PATIENTS WITH GASTRIC CANCER.

Object study carbohydrate metabolism state in patient with GC during the surgical treatment period, and the detection of factors that influence these kind of disorders. The results of investigations of 270 patients with GC were analyzed. The rest of patients were males - 193 (71.48%). 239 patients underwent different surgical involvements. The state of carbohydrate metabolism was evaluated based on the study of the level of glucose in blood serum and urine at various stages of surgical treatment. The results of carbohydrate metabolism in 270 patients with gastric cancer in the perioperative period are analyzed. Factors that have an effect on the changes in glucose and insulin levels in the blood and its appearance in the urine before the specific treatment, as well as at various periods of staying patients in the surgical department, was the duration of the anamnesis, advanced stages of the oncological process, complicated clinical course of the underlying disease.. It was established that surgical intervention itself, its extension, and also postoperative period have a direct negative effect on the disorders in carbohydrate metabolism. In 65.3% of cases operations were accompanied by hyperglycemia, and in 25.9% of cases glucosuria was detected. The duration of a surgical operation for more than two hours lead to an almost twofold increase in the incidence of cases of hyperglycemia, and tripled increase in glucosuria. Intensive correction of blood glucose level along with enteral feeding led to a decrease in levels of hyperglycemia and glucosuria. Complicated postoperative period did not lead to an increase in the incidence of carbohydrate metabolism disorders, but had an effect on the longer retention of elevated levels of glucose in the blood and urine.

Roux-en-Y Gastric Bypass Is More Effective than Sleeve Gastrectomy in Improving Postprandial Glycaemia and Lipaemia in Non-diabetic Morbidly Obese Patients: a Short-term Follow-up Analysis.

PURPOSE: We aimed to compare the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on postprandial glucose and lipid metabolism in addition to weight loss and fasting metabolic profile, in non-diabetic patients undergoing bariatric surgery. METHODS: Seventy-one patients were consecutively recruited and studied preoperatively, 3 and 6 months after surgery. Of these, 28 underwent RYGB (7 males, age 38 ± 9 years, BMI 46.9 ± 5.0 kg/m2), and 43 SG (9 males, age 38 ± 9 years, BMI 50.2 ± 7.0 kg/m2). A semi-liquid mixed meal was consumed, and blood samples were taken before, and every 30 min after meal ingestion up to 180 min postprandially, for measurement of glucose, insulin, and lipids. The overall postprandial response was assessed as area under the concentration-time curve (AUC). RESULTS: Baseline metabolic parameters were similar between RYGB and SG. Both groups experienced comparable weight loss, and a similar improvement in fasting glucose, insulin, and insulin resistance. Total and LDL cholesterol levels were lower at 6 months after RYGB compared to SG, while there was no difference in HDL cholesterol or triglycerides. Glucose AUC was lower after RYGB compared to SG at both 3 (p = 0.008) and 6 months (p = 0.016), without any difference in postprandial insulin response. Triglyceride AUC was also lower in RYGB vs. SG at 3 and 6 months (p ≤ 0.001). CONCLUSIONS: RYGB is superior to SG in improving postprandial glycaemia and lipaemia and cholesterol profile 6 months postoperatively in non-diabetic, severely obese patients. These findings imply procedure-specific effects, such as the malabsorptive nature of RYGB, and less likely a different incretin postoperative response.

Role of plasma glucose level on myocardial perfusion in ST-segment elevation myocardial infarction patients.

AIMS: Hyperglycemia is frequent in patients with ST elevation myocardial infarction (STEMI) and is associated with adverse outcome. Aim of our study was to evaluate the correlation between admission plasma glucose level (PGL) and coronary arteries flow velocity. METHODS: We enrolled 149 STEMI patients successfully treated with primary percutaneous coronary intervention (pPCI). The study population was divided into two groups based on PGL (< or >140 mg/dl) and on history of diabetes, and the groups compared in terms of corrected TIMI frame count (cTFC). RESULTS: Hyperglycemic patients had a significantly higher cTFC in both the culprit (p < 0.0001) and non-culprit vessel (p: 0.0002); diabetes history impairs as well cTFC of the culprit (p < 0.0001) and non-culprit vessel (p: 0.0001). Within the subpopulation of diabetic patients hyperglycemic ones showed higher cTFC in both the culprit (p 0.0013) and non-culprit vessel (p: 0.0006). Moreover in the whole population cTFC values of both arteries increase linearly with the increment of admission PGL. CONCLUSIONS: Admission PGL affects coronary flow of both culprit and non-culprit vessel. The impairment of coronary flow is also demonstrated in known diabetic patients, suggesting to consider hyperglycemia an additional risk factor. We finally demonstrated for the first time a positive linear relationship between PGL and cTFC.

Admission hyperglycemia and outcomes in large vessel occlusion strokes treated with mechanical thrombectomy.

BACKGROUND AND PURPOSE: Higher admission serum glucose levels have been associated with poor outcomes in patients with acute ischemic stroke (AIS) treated with IV thrombolysis. We sought to evaluate the association of admission serum glucose with early outcomes of patients with emergent large vessel occlusion (ELVO) treated with mechanical thrombectomy (MT). METHODS: Consecutive AIS patients due to ELVO treated with MT in three tertiary stroke centers were evaluated. The following outcomes were documented using standard definitions: symptomatic intracranial hemorrhage (sICH), complete reperfusion, mortality, functional independence (modified Rankin Scale (mRS) score of 0-2), and functional improvement (shift in mRS score) at 3 months. The association of admission serum glucose and admission hyperglycemia (>140 mg/dL) with outcomes was evaluated using univariable and multivariable binary and ordinal logistic regression models. RESULTS: 231 AIS patients with ELVO (mean age 62±14 years, 51% men, median admission National Institute of Health Stroke Scale score 16 points (IQR 12-21), median admission serum glucose 125 mg/dL (IQR 104-162)) were treated with MT. Admission hyperglycemia was associated with a lower likelihood of functional improvement (common OR 0.53; 95% CI 0.31 to 0.97; p=0.027) and higher odds of 3 month mortality (OR 2.76; 95% CI 1.40 to 5.44; p=0.004) in multivariable analyses adjusting for potential confounders. A 10 mg/dL increase in admission blood glucose was associated with a higher likelihood of sICH (OR 1.07; 95% CI 1.01 to 1.13; p=0.033) and 3 month mortality (OR 1.07; 95% CI 1.02 to 1.12; p=0.004) in multivariable models. There was no association between admission serum glucose or hyperglycemia and complete reperfusion. CONCLUSIONS: Higher admission serum glucose and admission hyperglycemia are independent predictors of adverse outcomes in ELVO patients treated with MT.

Insulin-Deficient Mouse ß-Cells Do Not Fully Mature but Can Be Remedied Through Insulin Replacement by Islet Transplantation.

Insulin receptor (IR) insufficiency in ß-cells leads to impaired insulin secretion and reduced ß-cell hyperplasia in response to hyperglycemia. Selective IR deficiency in ß-cells in later embryological development may lead to compensatory ß-cell hyperplasia. Although these findings suggest insulin signaling on the ß-cell is important for ß-cell function, they are confounded by loss of signaling by the insulinlike growth factors through the IR. To determine whether insulin itself is necessary for ß-cell development and maturation, we performed a characterization of pancreatic islets in mice with deletions of both nonallelic insulin genes (Ins1-/-Ins2-/-). We immunostained neonatal Ins1-/-Ins2-/- and Ins1+/+Ins2+/+ pancreata and performed quantitative polymerase chain reaction on isolated neonatal islets. Insulin-deficient islets had reduced expression of factors normally expressed in maturing ß-cells, including muscoloaponeurotic fibrosarcoma oncogene homolog A, homeodomain transcription factor 6.1, and glucose transporter 2. Ins1-/-Ins2-/-ß-cells expressed progenitor factors associated with stem cells or dedifferentiated ß-cells, including v-myc avian myolocytomatosis viral oncogene lung carcinoma derived and homeobox protein NANOG. We replaced insulin by injection or islet transplantation to keep mice alive into adulthood to determine whether insulin replacement was sufficient for the completed maturation of insulin-deficient ß-cells. Short-term insulin glargine (Lantus®) injections partially rescued the ß-cell phenotype, whereas long-term replacement of insulin by isogenic islet transplantation supported the formation of more mature ß-cells. Our findings suggest that tightly regulated glycemia, insulin species, or other islet factors are necessary for ß-cell maturation.

Elevated glycated hemoglobin level and hyperglycemia after aneurysmal subarachnoid hemorrhage.

OBJECTIVES: Elevated blood glucose is frequently detected early after aneurysmal subarachnoid hemorrhage (aSAH) and is considered a risk factor for poor neurological outcome. However it remains unclear whether hyperglycemia is caused by the SAH ictus or reflects a pre-existing hyperglycemic metabolism. In a prospective register we analysed glycated haemoglobin levels (HbA1c) in patients with aSAH and its influence on outcome. PATIENTS AND METHODS: Between July 2012 and July 2014, 87 patients with confirmed aSAH were included (NCT02081820). Within 72h HbA1c levels were assessed as a measure for hyperglycemic metabolism preceding aSAH. Blood glucose levels were recorded upon admission. Patient outcome was recorded after 6 months using modified Rankin scale (mRS). RESULTS: HbA1c levels did not correlate with initial neurological status (p=0.338, r=0.104). On the contrary, initial blood glucose levels correlated significantly with neurological status at admission (p=0.001, r=0.341). Additionally, HbA1c levels failed to show a significant influence on the occurrence of delayed cerebral ischemia (DCI) (p=0.400) or outcome after 6 months (p=0.790). CONCLUSION: A pre-existing hyperglycemic metabolism does not contribute to the severity of aSAH or influences the quality of neurological recovery. Hyperglycemia after aSAH correlates with initial neurological status and patient outcome and is potentially attributable to the metabolic changes induced by the brain injury after the hemorrhage.

Scaffold-supported Transplantation of Islets in the Epididymal Fat Pad of Diabetic Mice.

Islet transplantation has been clinically proven to be effective at treating type 1 diabetes. However, the current intrahepatic transplantation strategy may incur acute whole blood reactions and result in poor islet engraftment. Here, we report a robust protocol for the transplantation of islets at the extrahepatic transplantation site-the epididymal fat pad (EFP)-in a diabetic mouse model. A protocol to isolate and purify islets at high yields from C57BL/6J mice is described, as well as a transplantation method performed by seeding islets onto a decellularized scaffold (DCS) and implanting them at the EFP site in syngeneic C57BL/6J mice rendered diabetic by streptozotocin. The DCS graft containing 500 islets reversed the hyperglycemic condition within 10 days, while the free islets without DCS required at least 30 days. The normoglycemia was maintained for up to 3 months until the graft was explanted. In conclusion, DCS enhanced the engraftment of islets into the extrahepatic site of the EFP, which could easily be retrieved and might provide a reproducible and useful platform for investigating the scaffold materials, as well as other transplantation parameters required for a successful islet engraftment.

[Interpretation of the International Joint Statement on Metabolic Surgery in the Treatment Algorithm for Type 2 Diabetes].

Along with the soaring prevalence of obesity and type 2 diabetes mellitus (T2DM) globally, metabolic and bariatric surgery (MBS) has been rapidly developing into a major surgical subspecialty. However, the indications, benefits and potential risks of MBS are still controversial so far. In September 2015, the 2nd Diabetes Surgery Summit (DSS-II() was successfully convened, and later on an international joint statement on metabolic surgery in the treatment algorithm for T2DM was released based upon the consensus reached in DSS-II(, aiming to serve as a new global clinical guideline. The DSS-II( joint statement was initiated and endorsed by 5 leading international diabetes organizations, including American Diabetes Association (ADA), International Diabetes Federation (IDF), Chinese Diabetes Society (CDS), Diabetes India, as well as Diabetes UK, and was developed by an expert committee comprised of 48 international authorities as voting delegates. Up to the date of publication, the DSS-II( statement has been officially endorsed by 45 international professional associations/societies, including 30 non-surgical and 15 surgical organizations. In this statement, the following six aspects were recommended to differentiate MBS from traditional bariatric surgery: 1)The primary goal of MBS is to treat T2DM and to reduce the risk of T2DM complications; 2) In addition to a 50% or more of excess weight loss and normalization of glycemia, outcomes of diabetes complications should also be considered as clinical endpoints of MBS; 3) For patient selection, body mass index (BMI), T2DM treatment, as well as long-term risks versus benefits, including its effects on cardiovascular events (CVD), should all be considered; 4) T2DM and its complications, as well as pancreatic function reserve should be assessed pre-operatively; 5) Major surgical options include laparoscopic Roux-en-Y gastric bypass (LRYGB), laparoscopic sleeve gastrectomy (LSG), laparoscopic adjustable gastric banding (LAGB), and bilio-pancreatic diversion with duodenal switch(BPD-DS). BPD-DS has the best outcome in T2DM remission followed by LRYGB, LSG and LAGB; 6) Glycemic variation should be intensively monitored, and if needed, managed following surgery. Clinical follow-up should be conducted at least once every six months within two years after surgery. For patients achieving complete remission from T2DM, diabetes complications should still be monitored within five years after surgery with the same frequency and protocols as pre-operatively.

The stress hyperglycemia ratio, an index of relative hyperglycemia, as a predictor of clinical outcomes after percutaneous coronary intervention.

BACKGROUND: We aimed to investigate the outcome-predicting value of a novel index of stress hyperglycemia in coronary artery disease (CAD) patients who underwent percutaneous coronary intervention (PCI). METHODS: This was a retrospective observational study. Four-thousand-three-hundred-sixty-two subjects from the COACT registry were used to estimate the risk of major adverse cardiovascular and cerebrovascular events (MACCE), which are defined as composites of all-cause death, non-fatal myocardial infarction (MI) and non-fatal stroke. The stress hyperglycemia ratio (SHR) was calculated by dividing the random serum glucose at admission with the estimated average glucose derived from HbA1c. RESULTS: Over a median follow-up of 2.5years, 344 (7.9%), 43 (1.0%), and 89 (2.0%) cases of death, non-fatal MI, and non-fatal stroke occurred, respectively. Compared with the subjects in the lower three quartiles of SHR, the HR (95% CI) for the highest SHR quartile (Q4) group for MACCE was 1.31 (1.05, 1.64) in the total population and 1.45 (1.02, 2.06) in the non-diabetic population after adjusting for potential covariables. The risk of MACCE in the SHR Q4 group was significantly higher in patients presenting with ST-elevation MI (STEMI), which was not the case for patients presenting with other CAD types. The prognostic impact of SHR was more prominent for the 30-day MACCE. Similar results were observed in another cohort consisting of patients who only presented with acute MI. CONCLUSIONS: SHR is a useful predictive marker of MACCE after PCI, especially in non-diabetic patients with STEMI, which could be utilized to identify high-risk patients for adverse outcomes.

Diabetes Mellitus and Hyperglycemia and the Risk of Aseptic Loosening in Total Joint Arthroplasty.

BACKGROUND: It is unknown to what extent diabetes mellitus modifies the long-term risk of aseptic loosening in total hip arthroplasty (THA) and total knee arthroplasty (TKA). We examined the association between diabetes mellitus, perioperative hyperglycemia, and the likelihood of revisions for aseptic loosening. METHODS: We studied 16,085 primary THA and TKA procedures performed at a large tertiary care hospital between 2002 and 2009. All blood glucose values around the time of surgery (within 1 week) were retrieved. Subsequent revision surgeries and the reasons for revision were ascertained through the institutional joint registry. Multivariate Cox models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for aseptic loosening associated with diabetes mellitus and hyperglycemia adjusting for age, gender, body mass index, and surgery type. RESULTS: A total of 2911 (18%) surgeries had a diagnosis of diabetes mellitus at the time of surgery. Glucose testing was performed at least once in 7055 (44%) procedures within ±1 week of surgery. Although diabetic patients did not experience a higher risk of revision for aseptic loosening (HR, 0.87; 95% CI, 0.55-1.38), higher preoperative glucose values on the day before surgery were significantly associated with both the overall risk of revisions (HR, 2.80; 95% CI, 1.00-7.85) and revisions for aseptic loosening (HR, 4.95; 95% CI, 1.26-19.54). CONCLUSION: High preoperative hyperglycemia is a potential risk factor for aseptic loosening in THA and TKA.

Effect of the Diabetic State on Islet Engraftment and Function in a Large Animal Model of Islet-Kidney Transplantation.

In islet transplantation, in addition to immunologic and ischemic factors, the diabetic/hyperglycemic state of the recipient has been proposed, although not yet validated, as a possible cause of islet toxicity, contributing to islet loss during the engraftment period. Using a miniature swine model of islet transplantation, we have now assessed the effect of a persistent state of hyperglycemia on islet engraftment and subsequent function. An islet-kidney (IK) model previously described by our laboratory was utilized. Three experimental donor animals underwent total pancreatectomy and autologous islet transplantation underneath the renal capsule to prepare an IK at a load of ≤1,000 islet equivalents (IE)/kg donor weight, leading to a chronic diabetic state during the engraftment period (fasting blood glucose >250 mg/dL). Three control donor animals underwent partial pancreatectomy (sufficient to maintain normoglycemia during islet engraftment period) and IK preparation. As in vivo functional readout for islet engraftment, the IKs were transplanted across an immunologic minor or class I mismatch barrier into diabetic, nephrectomized recipients at an islet load of ∼4,500 IE/kg recipient weight. A 12-d course of cyclosporine was administered for tolerance induction. All experimental donors became diabetic and showed signs of end organ injury, while control donors maintained normoglycemia. All recipients of IK from both experimental and control donors achieved glycemic control over long-term follow-up, with reversal of diabetic nephropathy and with similar glucose tolerance tests. In this preclinical, large animal model, neither islet engraftment nor subsequent long-term islet function after transplantation appear to be affected by the diabetic state.