Calculated plasma osmolality at hospital admission correlates well with eGFR and D-Dimer, a simple outcome predictor and guiding tool for management of severe COVID-19 patients.

AIMS: To evaluate calculated total plasma osmolality as a marker of outcome prediction, fluid and metabolic balance, thrombotic risk in severe COVID-19 patients. METHODS: Retrospective data of RT-PCR confirmed hospitalized severe COVID-19 patients (total: n = 175 patients, including diabetic subset: n = 102) were analyzed. Clinically applicable cut-offs were derived using receiver operating characteristic (ROC) curve analysis for calculated total osmolality, eGFR, and D-dimer, and their correlations were studied. RESULTS: Among 175 severe COVID-19 patients, a significant association with mortality was seen with respect to calculated total osmolality (p < 0.001), eGFR (p < 0.001), and D-dimer (p < 0.001). In the total cohort, applicable cut-offs based on ROC curve in predicting outcome were, for total osmolality 299 mosm/kg (area under the curve (AUC)-0.773, odds ratio (OR)-1.09), eGFR 61.5 ml/min/m2 (AUC-0.789, OR-0.96), D-dimer 5.13 (AUC-0.814, OR-2.65) respectively. In diabetic subset, the cut-offs for total osmolality were 298 mosm/kg (AUC-0.794, OR-1.12), eGFR 44.9 ml/min/m2 (AUC-0.774, OR-0.96) and D-dimer 1.59 (AUC-0.769, OR-1.52) respectively. CONCLUSIONS: Applicable cut-offs for calculated total plasma osmolality, eGFR, and D-dimer predicts clinical outcome in severe COVID-19 with and without diabetes. Correlation studies validated calculated total osmolality as a marker of the combined effect of fluid and metabolic imbalance, compromised renal function and hypercoagulability.

Association between Hb A1c and Severity of COVID-19 Patients.

This study aimed to examine the relationship between Hb A1c levels and the clinical course of coronavirus-19 (COVID-19) patients. Sixty-six COVID-19(+) patients with high Hb A1c and 46 with average Hb A1c and 30 COVID-19(-) patients with average Hb A1c were included. Hb A1c levels and parameters examined in COVID-19(+) patients were compared between groups, and correlation analysis was performed between these parameters and Hb A1c levels. The effect of Hb A1c levels on intensive care unit (ICU) admission and mortality rate in COVID-19 patients was analyzed with the χ2 test. It was observed that hemoglobin (Hb) and arterial oxygen saturation (SaO2) levels of the COVID-19 (+) groups was lower than the COVID-19 (-) group, while ferritin, D-dimer, procalcitonin (PCT), and C-reactive protein (CRP) levels were higher. The COVID-19 (+) group with high Hb A1c had higher lactate dehydrogenase (LDH), PCT and D-dimer levels than the other two groups, while Hb, partial arterial oxygen pressure (PaO2) levels were lower. The Hb A1c levels of the COVID-19 (+) groups were positively correlated with absolute neutrophil count (ANC), LDH, PCT and (K+) levels, while negatively correlated with Hb and PaO2 levels. Hb A1c was found to be associated with the inflammation process, coagulation disorders and low PaO2 in COVID-19 patients. The COVID-19 patients with high Hb A1c levels had a higher mortality rate than other COVID-19 patients. Using Hb A1c measurements with other prognostic markers would contribute to the patient's risk of death assessment.

Wharton's Jelly Mesenchymal Stem Cell-Derived Extracellular Vesicles Reduce SARS-CoV2-Induced Inflammatory Cytokines Under High Glucose and Uremic Toxin Conditions.

Cytokine storm is recognized as one of the factors contributing to organ failures and mortality in patients with COVID-19. Due to chronic inflammation, COVID-19 patients with diabetes mellitus (DM) or renal disease (RD) have more severe symptoms and higher mortality. However, the factors that contribute to severe outcomes of COVID-19 patients with DM and RD have received little attention. In an effort to investigate potential treatments for COVID-19, recent research has focused on the immunomodulation functions of mesenchymal stem cells (MSCs). In this study, the correlation between DM and RD and the severity of COVID-19 was examined by a combined approach with a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that the odd of mortality in patients with both DM and RD was increased in comparison to those with a single comorbidity. In addition, in the experimental research, the data showed that high glucose and uremic toxins contributed to the induction of cytokine storm in human lung adenocarcinoma epithelial cells (Calu-3 cells) in response to SARS-CoV Peptide Pools. Of note, the incorporation of Wharton's jelly MSC-derived extracellular vesicles (WJ-EVs) into SARS-CoV peptide-induced Calu-3 resulted in a significant decrease in nuclear NF-κB p65 and the downregulation of the cytokine storm under high concentrations of glucose and uremic toxins. This clearly suggests the potential for WJ-EVs to reduce cytokine storm reactions in patients with both chronic inflammation diseases and viral infection.

A Serum Resistin and Multicytokine Inflammatory Pathway Is Linked With and Helps Predict All-cause Death in Diabetes.

CONTEXT: Type 2 diabetes (T2D) shows a high mortality rate, partly mediated by atherosclerotic plaque instability. Discovering novel biomarkers may help identify high-risk patients who would benefit from more aggressive and specific managements. We recently described a serum resistin and multicytokine inflammatory pathway (REMAP), including resistin, interleukin (IL)-1ß, IL-6, IL-8, and TNF-α, that is associated with cardiovascular disease. OBJECTIVE: We investigated whether REMAP is associated with and improves the prediction of mortality in T2D. METHODS: A REMAP score was investigated in 3 cohorts comprising 1528 patients with T2D (409 incident deaths) and in 59 patients who underwent carotid endarterectomy (CEA; 24 deaths). Plaques were classified as unstable/stable according to the modified American Heart Association atherosclerosis classification. RESULTS: REMAP was associated with all-cause mortality in each cohort and in all 1528 individuals (fully adjusted hazard ratio [HR] for 1 SD increase = 1.34, P < .001). In CEA patients, REMAP was associated with mortality (HR = 1.64, P = .04) and a modest change was observed when plaque stability was taken into account (HR = 1.58; P = .07). REMAP improved discrimination and reclassification measures of both Estimation of Mortality Risk in Type 2 Diabetic Patients and Risk Equations for Complications of Type 2 Diabetes, well-established prediction models of mortality in T2D (P < .05-< .001). CONCLUSION: REMAP is independently associated with and improves predict all-cause mortality in T2D; it can therefore be used to identify high-risk individuals to be targeted with more aggressive management. Whether REMAP can also identify patients who are more responsive to IL-6 and IL-1ß monoclonal antibodies that reduce cardiovascular burden and total mortality is an intriguing possibility to be tested.

Effects of platelet rich plasma on experimentally induced diabetic heart injury.

Diabetic heart is one of the common complications of diabetes mellitus. Platelet-rich plasma (PRP) is an autologous product rich in growth factors that can enhance tissue regeneration. This work was conducted to study the PRP ability to improve diabetes-inducing cardiac changes. Also, it sheds more light on the possible mechanisms through which PRP induces its effects. Rats were divided into; control, PRP, diabetic, and PRP-diabetic groups. Cardiac specimens were obtained and processed for biochemical, histological, and immunohistochemical study. The diabetic group exhibited a significant increase in cardiac oxidative stress, inflammation, and cardiac injury markers if compared with the control group. Additionally, the cardiac tissue showed variable morphological changes in the form of focal distortion and loss of cardiac myocytes. Distorted mitochondria and heterochromatic nuclei were observed in the cardiac muscle fibers. The mean number of charcoal-stained macrophages, and mean area fraction for collagen fibers, mean number of PCNA-immune positive cardiac muscle were significantly decrease in PRP- diabetic group. Collectively, the results showed that PRP treatment ameliorated most of all these previous changes. CONCLUSION: PRP ameliorated the diabetic cardiac injury via inhibition of oxidative stress and inflammation. It was confirmed by biochemical, histological, and immunohistochemical study. It could be concluded that PRP could be used as a potential therapy for diabetic heart.

DNA damage in leukocytes and serum nitrite concentration are negatively associated in type 1 diabetes.

Chronic hyperglycaemia leads to DNA damage in diabetes and might be associated with nitrosative stress. In this study, we aimed at assessing the level of DNA strand breaks in leukocytes, serum nitrite and nitrate in patients with type 1 diabetes and healthy controls and associations of these parameters with diabetes-related outcomes in a prospective study. The level of DNA damage was determined in 71 patients with type 1 diabetes and 57 healthy controls by comet assay and scored with arbitrary units (AU). The chemiluminescence method was used to measure nitrite and nitrate. Clinical information and data on consumption of alcohol, physical activity and smoking were collected. Progression of complications in patients with diabetes was assessed after a follow-up time of 4-5 years. We observed a higher level of DNA damage in leukocytes of patients with type 1 diabetes compared with healthy subjects [type 1 diabetes AU 50 (36-74.5); control AU 30 (24.1-43), P < 0.001]. According to regression, type 1 diabetes leads to a 2-fold increase in DNA damage. In the group of type 1 diabetes, DNA damage correlated positively with total cholesterol (R = 0.262, P = 0.028) and negatively with serum glucose level (R = -0.284; P = 0.018) and serum nitrite (R = -0.335; P = 0.008). DNA damage was not significantly associated with HbA1c, diabetes duration, complications and lifestyle factors. However, DNA damage > 57 AU was associated with statistically significantly lower serum nitrite and 1.52 higher risk of progression of complications of diabetes over the follow-up period. The latter result was not statistically significant due to insufficient study power [relative risk 1.52 (95% confidence interval = 0.68, 3.42, P = 0.31)]. Our results confirm that type 1 diabetes is associated with a higher level of DNA strand breaks in leukocytes when compared with the reference group and demonstrate the negative association between DNA damage and serum nitrite concentration.

Relationship between carotid intraplaque neovascularization and haemoglobin A1c in diabetic patients.

INTRODUCTION: We aimed to evaluate the characteristics of carotid artery plaques and the relationship between intraplaque neovascularization (IPN) and hemoglobin A1c (HbA1c) in patients of <60 years old with diabetes mellitus (DM) by comparison with diabetes ≥60 years of age. METHODS: One-hundred-and-one patients with DM were studied into two groups: those <60 and those ≥60 years of age. All the patients underwent standard carotid ultrasonography and contrast-enhanced ultrasonography, which we used to evaluate IPN. RESULTS: Diabetic complications were present in 41 of 50 patients (82 %) in the <60-year-old group, of whom 17 (34 %) had diabetes-related vascular complications. Of the 47 plaques in the <60-year-old group, six (13 %) had IPN Grade 0, 16 (34 %) had IPN Grade 1, and 25 (53 %) had IPN Grade 2. The AUC and RAUC of the plaque in the <60-year-old group were significantly higher than those of the ≥60-year-old group (P = 0.012 and 0.031, respectively). There were also differences in the AUC, RAUC and semi-quantitative grades between patients with and without diabetic macrovasculopathy and diabetic peripheral artery disease (all P < 0.05). The AUC, RAUC and semi-quantitative grading of IPN positively correlated with blood glucose and HbA1c (P < 0.05). CONCLUSION: IPN is more common in DM patients who are younger, and have higher blood glucose and HbA1c concentrations, and these plaques are more vulnerable.

Metformin attenuated histopathological ocular deteriorations in a streptozotocin-induced hyperglycemic rat model.

Diabetes mellitus (DM) often causes ocular disorders leading to vision loss. Metformin is commonly prescribed for type 2 diabetes. This study assessed the effect of metformin on hyperglycemic histopathological eye abnormalities and some possible pathways involved. Male rats were divided into 3 groups (N = 6), namely, healthy control, hyperglycemic non-treated control, and hyperglycemic rats treated with 200 mg/kg metformin. Two weeks after diabetes induction by an intraperitoneal streptozotocin (60 mg streptozotocin (STZ)/kg) injection, the rats develop ocular abnormalities, and metformin (200 mg/kg) treatment was administered daily. Rats underwent dilated retinal digital ophthalmoscope examination and graded for diabetic retinopathy. Rats were sacrificed at 12 weeks, and the cornea, lens, sclera, ciliary body, iris, conjunctiva, retinal, and optic nerve were examined histologically. Rats' fasting blood glucose and body weight were monitored. Serum tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), claudin-1, and glutathione/malondialdehyde ratios were analyzed. Metformin significantly attenuated diabetes-related histopathological ocular deteriorations in the cornea, lens, sclera, ciliary body, iris, conjunctiva, retina, and optic nerve partly by restoring serum TNF-α, VEGF, claudin-1, and glutathione/malondialdehyde ratios without significantly affecting the fasting blood glucose levels or body weight in these hyperglycemic rats. Metformin attenuated hyperglycemia-associated histopathological eye deteriorations, possibly partly by ameliorating vascular leakage, oxidative stress, inflammation, and neovascularization, without affecting the fasting blood glucose levels or body weights in these STZ-induced diabetic rats.

A preliminary evaluation of the circulating leptin/adiponectin ratio in dogs with pituitary-dependent hyperadrenocorticism and concurrent diabetes mellitus.

Leptin and adiponectin are thought to modulate insulin sensitivity and pancreatic ß-cell function, but there is limited information regarding the adipokine status of hyperglycemic dogs with hyperadrenocorticism. This study aimed to determine whether alterations in the leptin/adiponectin ratio, insulin sensitivity, and/or pancreatic ß-cell function are associated with diabetes mellitus (DM) in dogs with pituitary-dependent hyperadrenocorticism (PDH). A total of 48 client-owned dogs were included in this prospective observational study: 20 dogs with PDH (10 normoglycemic and 10 with DM), 15 dogs with DM, and 13 healthy dogs. The serum concentrations of leptin, adiponectin, resistin, interleukin (IL)-1ß, IL-6, IL-10, IL-18, and tumor necrosis factor (TNF)-α were measured, and homeostatic model assessment indices (HOMAs) were calculated and compared among the groups. Serum leptin was significantly higher in PDH dogs with and without DM than in healthy and DM dogs, and it was lower in DM dogs than in PDH dogs without DM. Serum adiponectin was significantly lower in PDH dogs with DM than in healthy and PDH dogs, and it was significantly lower in DM dogs than in healthy dogs. Serum IL-10 was significantly higher in PDH dogs with DM than in healthy and PDH dogs without DM. The leptin/adiponectin ratio was significantly higher in PDH dogs with DM than in normoglycemic PDH dogs. Serum IL-6 concentrations were significantly higher in DM dogs than in healthy dogs. Serum IL-1ß concentration was significantly higher in DM dogs than in healthy dogs and PDH dogs with DM and without DM. Serum TNF-α and IL-18 concentrations were not different among groups. The HOMAß-cell function was significantly lower in PDH dogs with DM than in normoglycemic PDH dogs, while HOMAinsulin sensitivity was significantly lower in PDH dogs with DM than in healthy dogs. These results suggest that adipokine dysregulation, a reduction in insulin sensitivity, and a further impairment in pancreatic ß-cell function might predispose PDH dogs to DM. Further longitudinal study will be necessary to confirm this result.

Assessment of pyloric sphincter distensibility and pressure in patients with diabetic gastroparesis.

BACKGROUND: Recent studies have shown that pyloric distensibility is altered in 30-50% of gastroparetic patients but the number of diabetic patients included in prior reports has been small. The aim of the present study was to assess pyloric sphincter measurements in diabetic patients with gastroparesis and to determine whether diabetes characteristics were correlated to pyloric disfunction. METHODS: Pyloric distensibility and pressure were measured using EndoFLIP® system in 46 patients with diabetic gastroparesis (DGP) and compared with 21 healthy volunteers (HV), and 33 patients with idiopathic gastroparesis (IGP). Altered pyloric distensibility was defined as the measurement below 10 mm2 /mmHg at 40 ml of inflation. In diabetic patients, blood glucose, glycated hemoglobin, duration, complications, and treatments were collected. KEY RESULTS: Mean pyloric distensibility at 40 ml of inflation was lower in DGP and IGP groups with, respectively, 10.8 ± 0.9 mm2 /mmHg and 14.8 ± 2.2 mm2 /mmHg in comparison with the HV group (25.2 ± 2.3 mm2 /mmHg; p < 0.005). 56.5% of patients had a decreased pyloric distensibility in the DGP group, 51.5% of patients in the IGP group, and 10% of patients in the HV group. No correlation was found between pyloric sphincter measurements and diabetes characteristics, including blood glucose, glycated hemoglobin, diabetes mellitus type, neuropathy, or GLP1 agonists intake. CONCLUSION AND INTERFERENCES: Pyloric sphincter distensibility and pressure were altered both in diabetic and idiopathic gastroparesis. Pyloric sphincter distensibility was not correlated to diabetes parameters.

Visit-to-visit variability of clinical risk markers in relation to long-term complications in type 1 diabetes.

BACKGROUND: Clinical characteristics such as HbA1c , systolic blood pressure (SBP), albuminuria and estimated glomerular filtration rate (eGFR) are important when treating type 1 diabetes. We investigated the variability in these measures as risk markers for micro- and macrovascular complications. METHODS: This prospective study included 1062 individuals with type 1 diabetes. Visit-to-visit variability of HbA1c , SBP, albuminuria and eGFR was calculated as the SD of the residuals in individual linear regression models using all available measures in a specified period of 3 years (VV). Endpoints included were as follows: cardiovascular events (CVE) defined as myocardial infarction, non-fatal stroke, or coronary or peripheral arterial intervention; end-stage kidney disease (ESKD) defined as eGFR <15 ml/min/1.73 m2 , chronic dialysis or kidney transplantation; eGFR decline ≥30%; and mortality. Adjustment included age, sex, cholesterol, HbA1c , SBP, body mass index, smoking, albuminuria, eGFR, and mean, intercept, slope of respective exposure variables and regression models. RESULTS: SBP VV was significantly associated with CVE (adjusted hazard ratio per 50% increase, (CI 95%); p: 1.21 [1.05-1.39]; p = 0.008), ESKD (1.51 [1.16-1.96]; p = 0.002) and mortality (1.25 [1.09-1.44]; p = 0.002). HbA1c VV was significantly associated with mortality (1.51 [1.30-1.75]; p < 0.001); albuminuria VV with eGFR decline (1.14 [1.08-1.20]; p = 0.024) and ESKD (1.14 [1.02-1.27]; p < 0.001), but neither CVE nor mortality. Adjusted eGFR VV was not associated with endpoints. CONCLUSION: In type 1 diabetes, higher variability of basic clinical risk markers adds important risk stratification information for the development of micro- and macrovascular complications.

Relationship between Perioperative Cardiovascular Events and Glycated Hemoglobin in Diabetic Patients Undergoing Noncardiac Surgery.

This retrospective nested case-control study is aimed at investigating the relationship between HbAlc and perioperative cardiovascular events (PCE) in patients with diabetes who underwent complex or moderately complex noncardiac surgery at the Second Affiliated Hospital of Xinjiang Medical University in 2013-2018. The patients were divided into four groups according to HbA1c ≤7%, 7.1%-7.9%, 8.0%-8.9%, and ≥9%. The occurrence of PCE among the groups was compared using univariable and multivariable analyses. Finally, 318 patients were included. There were 90 cases of PCE among the 318 patients; the occurrence rate of PCE was 28.3%. No death occurred. The occurrence rates of PCE in the HbA1c ≥ 8.0% - 8.9% and HbA1c ≥ 9.0% groups were 30.8% and 35.4%, respectively (P < 0.001 vs. the HbA1c 7.1%-7.9% group). The occurrence rate of PCE in the HbA1c ≤ 7% group was 25.9% (P > 0.05 vs. the HbA1c 7.1%-7.9% group). The multivariable logistic regression analysis showed that the course of diabetes (HbA1c stratification ≤7%, 7.1%-7.9%, 8.0%-8.9%, ≥9%, OR = 3.672, 95% CI: 1.552-8.687), HbA1c (OR = 1.895, 95% CI: 1.227-4.830), SBP (OR = 1.194, 95% CI: 1.015-2.023), and microalbuminuria (OR = 1.098, 95% CI: 1.005-1.023) was independently associated with PCE in diabetic patients. In conclusion, HbA1c levels are related to the incidence of PCE in diabetic patients undergoing complex or moderately complex noncardiac surgery.

Characteristics and outcomes of diabetic patients infected by the SARS-CoV-2.

Diabetes is considered a risk factor for complications due to COVID-19. In order to clarify this association, we are exploring the characteristics, the clinical signs, the outcomes and death in diabetic patients with COVID-19. In this retrospective observational study we are evaluating the demographic characteristics, the comorbidities of the patients, the clinical signs of the infection, the signs of clinical severity, the biological assessment at admission, the treatment, the outcomes and the deaths of 133 patients with COVID-19, of which 25 (19,4%) had diabetes. In the compared COVID-19 patients, with and without diabetes, the patients with diabetes were older, had higher blood pressure and more cardio-vascular diseases. Severe forms were more present in diabetic patients (56% versus 27.1%). Weight loss was higher in diabetic patients (6kg versus 3kg). Biologically, diabetic patients had higher levels of C-reactive protein (28 versus 5.8mg/l), procalcitonin (0.28 versus 0,13ng/l), ferritin (501 versus 140ng/ml), lactic dehydrogenase (268 versus 226IU/l) and of D. dimer (665 versus 444µg/l). Diabetic patients required more oxygen therapy (60% versus 26.9%), more mechanical ventilation (20% versus 8.3%) and more frequent admission to the intensive care unit (60% versus 27.8%). They presented more thromboembolic complications (12% versus 9%) but there were not significant differences in the other outcomes and in death rates. The excess of morbidity and mortality due to diabetes was still not fully clarified; the role of demographic factors, the interaction of mediations with ACE-2 receptors and the role of co-morbidities will all need to be studied in order to identify the patient at risk profile, i.e. who can develop severe forms of the diseases and more outcomes. The early identification of a possible hyper inflammation could be very valuable. More attention should be paid to patients with COVID-19 with diabetes because they are at a high risk of complications.

Circulating MiRNA-195-5p and -451a in Diabetic Patients with Transient and Acute Ischemic Stroke in the Emergency Department.

(1) Background: Circulating micro-RNAs (miRNAs) modulate the expression of molecules in diabetes. We evaluated the expression of serum miRNA-195-5p and -451a in diabetic patients with ischemic stroke and correlated them with two markers of brain tissue integrity. (2) Methods: Seventy-eight subjects with acute ischemic stroke (AIS) or transient ischemic attack (TIA) (40 with diabetes) were enrolled. Serum miRNA levels, brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor A (VEGF-A) were assessed at admission and 24 and 72 h after a post-ischemic stroke, and were compared to 20 controls. (3) Results: Both circulating miRNAs were two-fold up-regulated in diabetic AIS and TIA patients compared to non-diabetics. Their levels progressively decreased at 24 and 72 h in both AIS and TIA patients. Interestingly, in the non-diabetic TIA group, both circulating miRNAs, although higher than the controls, tended to achieve a complete decay after 72 h. Furthermore, miRNA-195-5p and miRNA-451a levels inversely correlated with both BDNF and VEGF-A serum levels. (4) Conclusions: These data show a different profile of both micro-RNAs in diabetic versus non-diabetic patients after acute ischemic stroke, suggesting their pivotal role in cerebrovascular ischemic attack.

Association of Glycemic Indices (Hyperglycemia, Glucose Variability, and Hypoglycemia) with Oxidative Stress and Diabetic Complications.

Oxidative stress (OS) is defined as a disturbance in the prooxidant-antioxidant balance of the cell, in favor of the former, which results in the antioxidant capacity of the cell to be overpowered. Excess reactive oxygen species (ROS) production is very harmful to cell constituents, especially proteins, lipids, and DNA, thus causing damage to the cell. Oxidative stress has been associated with a variety of pathologic conditions, including diabetes mellitus (DM), cancer, atherosclerosis, neurodegenerative diseases, rheumatoid arthritis, ischemia/reperfusion injury, obstructive sleep apnea, and accelerated aging. Regarding DM specifically, previous experimental and clinical studies have pointed to the fact that oxidative stress probably plays a major role in the pathogenesis and development of diabetic complications. It is postulated that hyperglycemia induces free radicals and impairs endogenous antioxidant defense systems through several different mechanisms. In particular, hyperglycemia promotes the creation of advanced glycation end-products (AGEs), the activation of protein kinase C (PKC), and the hyperactivity of hexosamine and sorbitol pathways, leading to the development of insulin resistance, impaired insulin secretion, and endothelial dysfunction, by inducing excessive ROS production and OS. Furthermore, glucose variability has been associated with OS as well, and recent evidence suggests that also hypoglycemia may be playing an important role in favoring diabetic vascular complications through OS, inflammation, prothrombotic events, and endothelial dysfunction. The association of these diabetic parameters (i.e., hyperglycemia, glucose variability, and hypoglycemia) with oxidative stress will be reviewed here.

Low serum trypsinogen levels in chronic pancreatitis: Correlation with parenchymal loss, exocrine pancreatic insufficiency, and diabetes but not CT-based cambridge severity scores for fibrosis.

BACKGROUND: Chronic pancreatitis (CP) is a complex inflammatory disorder of the pancreas affecting acinar cells, duct cells, islet cells and inflammatory cells including fibrosis-producing stellate cells. Serum trypsinogen is a biomarkers of acinar cell function. AIM: To define the degree of correlation between low trypsinogen levels as a marker of acinar cell function and variable features of CP. METHODS: Serum samples from previously ascertained and well phenotyped case and control subjects from the North American Pancreatitis Study II (NAPS2) were used to measure serum trypsinogen levels in a commercial laboratory. Control samples were used to define normal ranges and compared with levels in CP patients with defined features. RESULTS: A final cohort of 279 CP patients and 262 controls from the NAPS2 studies were evaluated. In controls trypsinogen had a mean of 34.96 ng/ml and SD = 11.99. Cut-off values for low trypsinogen ranged from <20 to 10 ng/ml and very low trypsinogen at <10 ng/ml. Compared to controls, CP was associated with very low trypsinogen levels (p < 0.0001). Within CP, very low trypsinogen levels correlated with parenchymal loss (pancreatic surgery [p < 0.05]; atrophy with calcifications, [p < 0.001]), EPI (p < 0.01, trend p < 0.001) and diabetes (trend p < 0.01) but not CT-based criteria for fibrosis (pancreatic duct dilation, irregularity, strictures). CONCLUSIONS: Very low serum trypsinogen levels correlate with measures of acinar cell loss including surgical resection, atrophic-calcific CP, diabetes and functional symptoms EPI but not duct morphology criteria. Serum trypsinogen levels correlate with decreased acinar cell function and therefore have biomarker utility clinical management.

Effect of diabetes mellitus and glycemic control on the prognosis of non-muscle invasive bladder cancer: a retrospective study.

BACKGROUND: Hyperglycemia is associated with series of process leading to oncogenesis. Evidence has shown that diabetes mellitus (DM) seems to be associated with poor prognosis in patients with bladder cancer. However, evidence on the effect of glycemic control on the outcomes of bladder cancer is still limited. In the current study, we aimed to investigate the effect of DM and glycemic control on the prognosis of bladder cancer. METHODS: We conducted a retrospective chart review of a prospective database from January 2012 to December 2017. Patients with newly diagnosed non-muscle invasive bladder cancer (NMIBC) were included. They were classified into the DM and non-DM groups. Prognosis including recurrence rate, progression rate, recurrence-free survival (RFS), and progression-free survival was compared between the two groups. Subgroup analysis of the DM subgroup, in which patients were classified by HbA1C level, was conducted to investigate the effect of glycemic control. RESULTS: A total of 287 patients were included in our study, with 61 patients in the DM group and 226 patients in the non-DM group. No statistically significant difference was found in the prognosis between the DM and non-DM groups. Subgroup analysis revealed higher recurrence rate (P = 0.037) and worse RFS (log-rank P = 0.019) in patients with HbA1C ≥ 7. CONCLUSIONS: DM is not a risk factor for recurrence and progression in patients with NMIBC. However, poor glycemic control is associated with poor prognosis in patients with both DM and NMIBC. Further prospective studies are needed to confirm current results.

Plasma circulating miR-23~27~24 clusters correlate with the immunometabolic derangement and predict C-peptide loss in children with type 1 diabetes.

AIMS/HYPOTHESIS: We aimed to analyse the association between plasma circulating microRNAs (miRNAs) and the immunometabolic profile in children with type 1 diabetes and to identify a composite signature of miRNAs/immunometabolic factors able to predict type 1 diabetes progression. METHODS: Plasma samples were obtained from children at diagnosis of type 1 diabetes (n = 88) and at 12 (n = 32) and 24 (n = 30) months after disease onset and from healthy control children with similar sex and age distribution (n = 47). We quantified 60 robustly expressed plasma circulating miRNAs by quantitative RT-PCR and nine plasma immunometabolic factors with a recognised role at the interface of metabolic and immune alterations in type 1 diabetes. Based on fasting C-peptide loss over time, children with type 1 diabetes were stratified into the following groups: those who had lost >90% of C-peptide compared with diagnosis level; those who had lost <10% of C-peptide; those showing an intermediate C-peptide loss. To evaluate the modulation of plasma circulating miRNAs during the course of type 1 diabetes, logistic regression models were implemented and the correlation between miRNAs and immunometabolic factors was also assessed. Results were then validated in an independent cohort of children with recent-onset type 1 diabetes (n = 18). The prognostic value of the identified plasma signature was tested by a neural network-based model. RESULTS: Plasma circulating miR-23~27~24 clusters (miR-23a-3p, miR-23b-3p, miR-24-3p, miR-27a-3p and miR-27b-3p) were upmodulated upon type 1 diabetes progression, showed positive correlation with osteoprotegerin (OPG) and were negatively correlated with soluble CD40 ligand, resistin, myeloperoxidase and soluble TNF receptor in children with type 1 diabetes but not in healthy children. The combination of plasma circulating miR-23a-3p, miR-23b-3p, miR-24-3p, miR-27b-3p and OPG, quantified at disease onset, showed a significant capability to predict the decline in insulin secretion 12 months after disease diagnosis in two independent cohorts of children with type 1 diabetes. CONCLUSIONS/INTERPRETATIONS: We have pinpointed a novel miR-23a-3p/miR-23b-3p/miR-24-3p/miR-27b-3p/OPG plasma signature that may be developed into a novel blood-based method to better stratify patients with type 1 diabetes and predict C-peptide loss.

Red Blood Cell Distribution Width is Associated with Glomerulonephritis in Diabetic Patients with Albuminuria.

BACKGROUND The aim of this study was to explore predictive factors to inform accurate diagnosis of glomerulonephritis (GNs) in patients with diabetes. MATERIAL AND METHODS Clinical characteristics and laboratory data were retrospectively analyzed from 200 patients with diabetes including 115 patients who had undergone a renal biopsy. Eligible patients were categorized into three groups: pure type 2 diabetes mellitus (T2DM), isolated diabetic nephropathy (DN), and GN. Odds ratios (ORs) were calculated to evaluate the contributions of predictive factors for GN. A receiver operating characteristic curve (ROC) was created to obtain cut-off values for predictive factors for GNs and investigate their corresponding predictive accuracy. RESULTS Red cell distribution width (RDW) was significantly higher in the GN group than in the DN group. Multivariate regression analysis revealed that baseline RDW level (OR=1.988, 95% CI=1.237~3.194, P=0.005) was an independent predictive factor for development of GNs. CONCLUSIONS Increased RDW levels are independently associated with a greater risk of GN in patients with diabetes who have albuminuria, and may be an additional valuable and noninvasive predictive tool for differentiating GNs and DN.

Preoperative Blood Glucose Level Predicts Postsurgical Gastroparesis Syndrome after Subtotal Gastrectomy: Development of an Individualized Usable Nomogram.

BACKGROUND: Postsurgical gastroparesis syndrome (PGS) after subtotal gastrectomy imposes significant social and economic burdens. We aimed to investigate the relationship between preoperative blood glucose level and PGS and develop a nomogram for individualized prediction. Patients and Methods. We retrospectively analyzed 633 patients with gastric cancer who underwent subtotal gastrectomy. Preoperative blood glucose levels were evaluated via receiver operating characteristic (ROC) curve analysis. Chi-squared tests and multivariable logistic regression analyses were used to develop a predictive model for PGS, presented as a nomogram, which was assessed for its clinical usefulness. RESULTS: Thirty-eight of 633 patients were diagnosed with PGS. Based on the ROC curve analysis, the preoperative blood glucose cutoff value for PGS was 6.25 mmol/L. The predictors of PGS included preoperative hyperglycemia (odds ratio (OR) 2.3, P = 0.03), body mass index (BMI; OR 0.21, P = 0.14 for BMI < 18.5 and OR 3.0, P = 0.004 for BMI > 24), and the anastomotic method (OR 7.3, P = 0.001 for Billroth II and OR 5.9, P = 0.15 for Roux-en-Y). The predictive model showed good discrimination ability, with a C-index of 0.710, and was clinically useful. CONCLUSIONS: Preoperative hyperglycemia effectively predicts PGS. We present a nomogram incorporating the preoperative blood glucose level, BMI, anastomotic method, and tumor size, for individualized prediction of PGS.