Renal ischemia-reperfusion injury (IRI) is a major contributor to acute kidney injury (AKI), leading to substantial morbidity and mortality. Spexin (SPX), a 14-amino acid endogenous peptide involved in metabolic regulation and immune modulation, has not yet been studied in the context of chronic treatment and renal IRI. This study evaluated the effects of exogenous SPX on renal function, histopathological changes, and molecular pathways in both IRI-induced injured and healthy kidneys. Twenty-eight male BALB/c mice were divided into four groups: control, SPX, IRI, and SPX+IRI. IRI was induced by 30 minutes of bilateral renal ischemia followed by 6 hours of reperfusion. Renal injury markers, histopathological changes, inflammatory mediators, apoptotic markers, and fibrosis-related proteins were analyzed. SPX significantly exacerbated IRI-induced kidney injury by activating the Wnt/β-catenin signaling pathway and promoting the upregulation of pro-inflammatory, pro-apoptotic, and pro-fibrotic mediators. It is noteworthy that SPX exerted more severe deleterious nephrotoxic effects in the healthy kidney compared to those observed in the IRI-induced injured kidney. These findings indicate that chronic treatment with SPX administration may have intrinsic pro-inflammatory, pro-apoptotic and fibrotic properties, raising concerns about its therapeutic potential. Further research is needed to clarify its physiological role and therapeutic implications in kidney diseases.
Animals ; Reperfusion Injury/chemically induced* ; Male ; Mice, Inbred BALB C ; Mice ; Acute Kidney Injury/metabolism* ; Kidney/blood supply* ; Peptide Hormones/adverse effects* ; Apoptosis/drug effects* ; Wnt Signaling Pathway/drug effects* ; Disease Models, Animal

A 2-year-old boy was admitted to Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine in Nov 30^th, 2018, due to polydipsia, polyphagia, polyuria accompanied with increased glucose levels for more than 2 weeks. He presented with symmetrical short stature [height 81 cm (－2.2 SD), weight 9.8 kg (－2.1 SD), body mass index 14.94 kg/m² (P₁₀-P₁₅)], and with no special facial or physical features. Laboratory results showed that the glycated hemoglobin A1c was 14%, the fasting C-peptide was 0.3 ng/mL, and the islet autoantibodies were all negative. Oral glucose tolerance test showed significant increases in both fasting and postprandial glucose, but partial islet functions remained (post-load C-peptide increased 1.43 times compared to baseline). A heterozygous variant c.1366C>T (p.R456C) was detected in GATA6 gene, thereby the boy was diagnosed with a specific type of diabetes mellitus. The boy had congenital heart disease and suffered from transient hyperosmolar hyperglycemia after a patent ductus arteriosus surgery at 11 months of age. Insulin replacement therapy was prescribed, but without regular follow-up thereafter. The latest follow-up was about 3.5 years after the diagnosis of diabetes when the child was 5 years and 11 months old, with the fasting blood glucose of 6.0-10.0 mmol/L, and the 2 h postprandial glucose of 17.0-20.0 mmol/L.
Male ; Child ; Humans ; Child, Preschool ; Infant ; Diabetes Mellitus, Type 2/complications* ; Mutation, Missense ; C-Peptide/genetics* ; China ; Insulin/genetics* ; Glucose ; Blood Glucose ; GATA6 Transcription Factor/genetics*

C-peptide immunoreactivity (CPR) levels for 180 minutes after ingestion of the test meals were compared. Ten patients with type 2 diabetes (age 52.5 ± 15.1 years, and 7 males and 3 females) were included in this study. The mean HbA1c level and body mass index were 8.8 ± 1.4%, and 29.7 ± 4.5 kg/m², respectively. Plasma glucose levels after ingestion of the WR diet or BR diet peaked at 60 minutes, which showed no significant differences between the two types of test meals. However, the incremental area under the curve (IAUC) of plasma glucose levels after ingestion of BR diet was significantly lower than that of WR diet. The serum CPR levels at 180 min and their IAUC over 180 minutes after ingestion of BR diet were significantly lower than those of WR diet. Conclusion: Increase in postprandial plasma glucose and insulin levels was suppressed by mixing high-β-glucan barley with WR in type 2 diabetic patients.]]>
Blood Glucose ; Body Mass Index ; C-Peptide ; Cardiopulmonary Resuscitation ; Diet ; Diet Therapy ; Eating ; Hordeum ; Humans ; Hyperglycemia ; Insulin ; Male ; Meals

BACKGROUND: An early identification of the risk groups might be beneficial in reducing morbidities in patients with gestational diabetes mellitus (GDM). Therefore, this study aimed to assess the biochemical predictors of glycemic conditions, in addition to fasting indices of glucose disposal, to predict the development of GDM in later stage and the need of glucose-lowering medication.METHODS: A total of 574 pregnant females (103 with GDM and 471 with normal glucose tolerance [NGT]) were included. A metabolic characterization was performed before 15+6 weeks of gestation by assessing fasting plasma glucose (FPG), fasting insulin (FI), fasting C-peptide (FCP), and glycosylated hemoglobin (HbA1c). Thereafter, the patients were followed-up until the delivery.RESULTS: Females with NGT had lower levels of FPG, FI, FCP, or HbA1c at the early stage of pregnancy, and therefore, showed an improved insulin action as compared to that in females who developed GDM. Higher fasting levels of FPG and FCP were associated with a higher risk of developing GDM. Moreover, the predictive accuracy of this metabolic profiling was also good to distinguish the patients who required glucose-lowering medications. Indices of glucose disposal based on C-peptide improved the predictive accuracy compared to that based on insulin. A modified quantitative insulin sensitivity check index (QUICKIc) showed the best differentiation in terms of predicting GDM (area under the receiver operating characteristics curve [ROC-AUC], 72.1%) or need for pharmacotherapy (ROC-AUC, 83.7%).CONCLUSION: Fasting measurements of glucose and C-peptide as well as the surrogate indices of glycemic condition could be used for stratifying pregnant females with higher risk of GDM at the beginning of pregnancy.
Blood Glucose ; C-Peptide ; Diabetes, Gestational ; Drug Therapy ; Fasting ; Female ; Glucose Metabolism Disorders ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Insulin ; Insulin Resistance ; Metabolic Diseases ; Metabolism ; Pregnancy ; ROC Curve

BACKGROUND: Conflicting results have been reported on the efficacy of insulin degludec/insulin aspart (IDegAsp) compared to basal insulin in type 2 diabetes. We investigated the effects of changing basal insulin to IDegAsp on glycemic control and sought to identify factors related to those effects.METHODS: In this retrospective study of patients from three referral hospitals, patients with type 2 diabetes using basal insulin with hemoglobin A1c (HbA1c) levels less than 11.0% were enrolled. Basal insulin was replaced with IDegAsp, and data were analyzed from 3 months before to 3 months after the replacement.RESULTS: Eighty patients were recruited (52.5% male; mean age, 67.0±9.8 years; mean duration of diabetes, 18.9±8.5 years; mean HbA1c, 8.7%±1.0%). HbA1c levels increased during 3 months of basal insulin use, but significantly decreased after changing to IDegAsp (8.28%±1.10%, P=0.0001). The reduction was significant at 6 months in 35 patients whose longer-term data were available. Patients with a measured fasting plasma glucose (m-FPG) lower than their predicted FPG (p-FPG) by regression from HbA1c showed a significant HbA1c reduction caused by the change to IDegAsp, even without a significantly increased insulin dose. However, patients whose m-FPG was higher than their p-FPG did not experience a significant HbA1c reduction, despite a significantly increased insulin dose. Furthermore, the HbA1c reduction caused by IDegAsp was significant in patients with low fasting C-peptide levels and high insulin doses.CONCLUSION: We observed a significant glucose-lowering effect by replacing basal insulin with IDegAsp, especially in patients with a lower m-FPG than p-FPG.
Adult ; Blood Glucose ; C-Peptide ; Diabetes Mellitus, Type 2 ; Fasting ; Humans ; Hyperglycemia ; Insulin ; Male ; Referral and Consultation ; Retrospective Studies

BACKGROUND: The Global Registry of Acute Coronary Events (GRACE) score is recommended by current ST-elevation myocardial infarction (STEMI) guidelines. But it has inherent defects. The present study aimed to investigate the more compatible risk stratification for Chinese patients with STEMI and to determine whether the addition of biomarkers to the Korea Acute Myocardial Infarction Registry (KAMIR) score could enhance its predictive value for long-term outcomes. METHODS: A total of 1093 consecutive STEMI patients were included and followed up 48.2 months. Homocysteine, hypersensitive C-reactive protein (hs-CRP), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were detected. The KAMIR score and the GRACE score were calculated. The performance between the KAMIR and the GRACE was compared. The predictive power of the KAMIR alone and combined with biomarkers were assessed by the receiver-operating characteristic (ROC) curve. RESULTS: The KAMIR demonstrated a better risk stratification and predictive ability than the GRACE (death: AUC = 0.802 vs. 0.721, P < 0.001; major adverse cardiovascular events (MACE): AUC = 0.683 vs. 0.656, P < 0.001). It showed that the biomarkers could independently predict death [homocysteine: HR = 1.019 (1.015-1.024), P < 0.001; hs-CRP: HR = 1.052 (1.000-1.104), P = 0.018; NT-pro BNP: HR = 1.142 (1.004-1.280), P = 0.021] and MACE [homocysteine: HR = 1.019 (1.015-1.024), P < 0.001; hs-CRP: HR = 1.012 (1.003-1.021), P = 0.020; NT-pro BNP: HR = 1.136 (1.104-1.168), P = 0.006]. When they were used in combination with the KAMIR, the area under the ROC curve (AUC) significantly increased for death [homocysteine: AUC = 0.802 vs. 0.890, Z = 5.982, P < 0.001; hs-CRP: AUC = 0.802 vs. 0.873, Z = 3.721, P < 0.001; NT-pro BNP: AUC = 0.802 vs. 0.871, Z = 2.187, P = 0.047; homocysteine, hs-CRP and NT-pro BNP: AUC = 0.802 vs. 0.940, Z = 6.177, P < 0.001] and MACE [homocysteine: AUC = 0.683 vs. 0.771, Z = 6.818, P < 0.001; hs-CRP: AUC = 0.683 vs. 0.712, Z = 2.022, P = 0.031; NT-pro BNP: AUC = 0.683 vs. 0.720, Z = 2.974, P = 0.003; homocysteine, hs-CRP and NT-pro BNP: AUC = 0.683 vs. 0.789, Z = 6.900, P < 0.001]. CONCLUSION The KAMIR is better than the GRACE in risk stratification and prognosis prediction in Chinese STEMI patients. A combination of above-mentioned biomarkers can develop a more predominant prediction for long-term outcomes.
Biomarkers ; blood ; C-Reactive Protein ; metabolism ; Humans ; Myocardial Infarction ; blood ; metabolism ; Natriuretic Peptide, Brain ; blood ; metabolism ; Peptide Fragments ; blood ; metabolism ; ROC Curve ; Registries ; Risk Factors ; ST Elevation Myocardial Infarction ; blood ; metabolism

The role of surgical intervention in patients with diabetic gastroparesis is unclear. We report a case of a 37-year-old man with a history of recurrent episodes of vomiting and long-standing type 2 diabetes mellitus. Esophagogastroduodenoscopy did not reveal any findings of reflux esophagitis or obstructive lesions. A gastric emptying time scan showed prolonged gastric emptying half-time (344 minutes) indicating delayed gastric emptying. Laboratory tests revealed elevated fasting serum glucose and glycosylated hemoglobin (HbA1c, 12.9%) and normal fasting C-peptide and insulin levels. We performed Roux-en-Y reconstruction after subtotal gastrectomy to treat gastroparesis and improve glycemic control, and the patient showed complete resolution of gastrointestinal symptoms postoperatively. Barium swallow test and gastric emptying time scan performed at follow-up revealed regular progression of barium and normal gastric emptying. Three months postoperatively, his fasting serum glucose level was within normal limits without the administration of insulin or oral antidiabetic drugs with a reduced HbA1c level (6.9%). Long-limb Roux-en-Y reconstruction after subtotal gastrectomy may be useful to treat severe diabetic gastroparesis by improving gastric emptying and glycemic control.
Adult ; Barium ; Blood Glucose ; C-Peptide ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Endoscopy, Digestive System ; Esophagitis, Peptic ; Fasting ; Follow-Up Studies ; Gastrectomy ; Gastric Emptying ; Gastroparesis ; Hemoglobin A, Glycosylated ; Humans ; Hypoglycemic Agents ; Insulin ; Vomiting

OBJECTIVE: To study the protective effect of vitamin A on residual pancreatic β cell function in children with type 1 diabetes mellitus (T1DM) and its mechanism. METHODS: A total of 46 children with T1DM (with a course of disease of 0.5-1 year) were randomly divided into an intervention group and a non-intervention group (n=23 each). The children in both groups were given insulin treatment, and those in the intervention group were also given vitamin A at a daily dose of 1 500-2 000 IU. A total of 25 healthy children were enrolled as the control group. The daily dose of insulin was calculated for the children with T1DM, and the serum levels of glycosylated hemoglobin (HbA1C), stimulated C-peptide, vitamin A, and interleukin-17 (IL-17) were measured before intervention and 3 months after intervention. RESULTS: Before vitamin A intervention, the intervention group and the non-intervention group had a significantly lower serum level of vitamin A and a significantly higher level of IL-17 than the control group (P<0.01). After 3 months of intervention, the intervention group had significantly lower serum IL-17 level and insulin dose and a significantly higher level of stimulated C-peptide than the non-intervention group (P<0.05). CONCLUSIONS Vitamin A may protect residual pancreatic β cell function, possibly by improving the abnormal secretion of IL-17 in children with T1DM.
Blood Glucose ; C-Peptide ; Diabetes Mellitus, Type 1 ; Glycated Hemoglobin A ; Humans ; Infant ; Insulin ; Insulin-Secreting Cells ; Vitamin A

PURPOSE: Hemophagocytic lymphohistiocytosis (HLH) is a hyperinflammatory syndrome with many causes, including Kawasaki disease (KD). The purpose of this study was to identify the laboratory tests needed to easily differentiate KD with HLH from incomplete KD alone. METHODS: We performed a retrospective study on patients diagnosed with incomplete KD and incomplete KD with HLH (HLH-KD) between January 2012 and March 2015. We compared 8 secondary HLH patients who were first diagnosed with incomplete KD with all 247 incomplete KD diagnosed patients during the study period. The complete blood count, erythrocyte sedimentation rate, platelet count, and serum total protein, albumin, triglyceride, C-reactive protein, N-terminal pro-brain natriuretic peptide (NT-proBNP), and ferritin levels were compared. Clinical characteristics and echocardiography findings were also compared between the 2 groups. RESULTS: The total duration of fever was longer in the HLH-KD group than in the KD group. White blood cell and platelet counts were higher in the KD group. Alanine aminotransferase, ferritin, and coronary artery diameter were increased in the HLH-KD group compared with those in the KD group. The median of NT-proBNP was significantly higher in the HLH-KD group than in the KD group at 889.0 (interquartile range [IQR], 384.5–1792.0) pg/mL vs. 233.0 (IQR, 107.0–544.0) pg/mL. CONCLUSION: The NT-proBNP level may be helpful in distinguishing incomplete KD from KD with HLH. The NT-proBNP level should be determined in KD patients with prolonged fever, in addition to the white blood cell count, platelet count, and ferritin level, to evaluate secondary HLH.
Alanine Transaminase ; Blood Cell Count ; Blood Sedimentation ; C-Reactive Protein ; Coronary Vessels ; Echocardiography ; Ferritins ; Fever ; Humans ; Leukocyte Count ; Leukocytes ; Lymphohistiocytosis, Hemophagocytic* ; Mucocutaneous Lymph Node Syndrome* ; Natriuretic Peptide, Brain ; Platelet Count ; Retrospective Studies ; Triglycerides

BACKGROUND: In Korea, the costs associated with self-monitoring of blood glucose (SMBG) for patients with type 2 diabetes mellitus (T2DM) under insulin treatment have been reimbursed since November 2015. We investigated whether this new reimbursement program for SMBG has improved the glycemic control in the beneficiaries of this policy. METHODS: Among all adult T2DM patients with ≥3 months of reimbursement (n=854), subjects without any changes in anti-hyperglycemic agents during the study period were selected. The improvement of glycosylated hemoglobin (HbA1c) was defined as an absolute reduction in HbA1c ≥0.6% or an HbA1c level at follow-up < 7%. RESULTS: HbA1c levels significantly decreased from 8.5%±1.3% to 8.2%±1.2% during the follow-up (P < 0.001) in all the study subjects (n=409). Among them, 35.5% (n=145) showed a significant improvement in HbA1c. Subjects covered under the Medical Aid system showed a higher prevalence of improvement in HbA1c than those with medical insurance (52.2% vs. 33.3%, respectively, P=0.012). In the improvement group, the baseline HbA1c (P < 0.001), fasting C-peptide (P=0.016), and daily dose of insulin/body weight (P=0.024) showed significant negative correlations with the degree of HbA1c change. Multivariate analysis showed that subjects in the Medical Aid system were about 2.5-fold more likely to improve in HbA1c compared to those with medical insurance (odds ratio, 2.459; 95% confidence interval, 1.138 to 5.314; P=0.022). CONCLUSION: The reimbursement for SMBG resulted in a significant improvement in HbA1c in T2DM subjects using insulin, which was more prominent in subjects with poor glucose control at baseline or covered under the Medical Aid system.
Adult ; Blood Glucose Self-Monitoring ; Blood Glucose ; C-Peptide ; Diabetes Mellitus, Type 2 ; Fasting ; Follow-Up Studies ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Insulin ; Insurance ; Insurance, Health, Reimbursement ; Korea ; Multivariate Analysis ; Prevalence