UNASSIGNED: Insulinoma is one of the causes of recurrent hypoglycemia, one of the chief complaints for emergency department admission. The gold standard in diagnosing insulinoma is a 72-hour fasting test which is inconvenient and inefficient as it requires hospitalization. Research has found that measurement of insulin and C-peptide during OGTT may help diagnose insulinoma. We aimed to assess the diagnostic value of OGTT in diagnosing insulinoma.
UNASSIGNED: The literature search was conducted on 19 August 2022 using several databases (MEDLINE, Scopus, Embase, and ScienceDirect). All studies that measured OGTT as diagnostic tools in diagnosing insulinoma and 72-hour fasting test as reference standard were included. The quality assessment of the selected studies was based on the Centre of Evidence-Based Medicine University of Oxford and the Quality Assessment of Diagnostic Accuracy-2 tool (QUADAS-2). Analysis of the included studies was performed qualitatively. This study was registered on PROSPERO (CRD42022360205).
UNASSIGNED: A total of two case-control studies (106 patients) were included, which were at risk of bias and low concern of applicability. Both studies demonstrated that the combination of insulin and C-peptide levels measured during OGTT had high specificity, sensitivity, positive predictive value, and negative predictive value in diagnosing insulinoma compared to the reference standard. A logistic regression model of 8.305 - (0.441 × insulin 2-h/0-h) - (1.679 × C-peptide 1-h/0-h) >0.351 has the highest diagnostic value in one study (AUC 0.97, Sensitivity 86.5%, Specificity 95.2%, PPV 94.1, NPV 88.9).
UNASSIGNED: The measurement of 0-h and 2-h insulin and C-peptide levels during 2-h OGTT was found in two small case-control studies with a total of 106 patients to have good sensitivity and specificity. However, due to these limitations, future research is still needed to validate the potential use of OGTT for the diagnosis of insulinoma.

OBJECTIVE: To provide updated efficacy and safety information for teplizumab in the treatment of Stage 3 type 1 diabetes mellitus (T1DM).
METHODS: The PubMed, Embase and Cochrane databases were searched for randomized controlled trials (RCTs) comparing teplizumab to placebo for T1DM that reported any of the following outcomes: (1) C-peptide area under the curve (AUC); (2) glycated haemoglobin (HbA1c) levels; (3) insulin requirements; and (4) adverse events. Heterogeneity was examined with I2 statistics. p values <0.05 were taken to indicate statistical significance. The continuous endpoints were compared through the pooled mean difference (MD) and binary endpoints were assessed using risk ratios, both with 95% confidence intervals (CIs). Statistical analyses were performed using Review Manager Web software.
RESULTS: Eight RCTs with 1052 patients (754 receiving teplizumab) were included. Teplizumab significantly increased the AUC of C-peptide levels at 6 (MD 0.10 nmol/L, 95% CI 0.05, 0.16), 12 (MD 0.13 nmol/L, 95% CI 0.06, 0.20), 18 (MD 0.18 nmol/L, 95% CI 0.09, 0.27) and 24 months (MD 0.16 nmol/L, 95% CI 0.02, 0.31), significantly reduced HbA1c levels at 6 (MD -0.57%, 95% CI -1.07, -0.08) and 12 months (MD -0.31%, 95% CI -0.59, -0.02), and significantly reduced insulin requirements at 6 (MD -0.12 U/kg, 95% CI -0.16, -0.08), 12 (MD -0.11 U/kg, 95% CI -0.15, -0.07), 18 (MD -0.17 U/kg, 95% CI -0.26, -0.09) and 24 months (MD -0.11 U/kg, 95% CI -0.22, -0.01).
CONCLUSIONS: Teplizumab increases AUC of C-peptide levels and decreases HbA1c levels and insulin use, without raising serious adverse event risk.

There are multiple disease-modifying immunotherapies showing the potential of preventing or delaying the progression of type 1 diabetes (T1D). We designed and performed this systematic review and meta-analysis to gain an overview of what a role immunotherapy plays in the treatment of T1D. We searched PubMed, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to December 2023. We included clinical trials of immunotherapy conducted in patients with T1D that reported the incidence of hypoglycemia or changes from baseline in at least one of following outcomes: 2 h and 4 h mixed-meal-stimulated C-peptide area under the curve (AUC), fasting C-peptide, daily insulin dosage, glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG). The results were computed as the weighted mean differences (WMDs) or odds ratios (ORs) and 95% confidence intervals (CIs) in random-effect model. In all, 34 clinical trials were included. When compared with control groups, 2 h C-peptide AUC was marginally higher in patient treated with nonantigen-based immunotherapies (WMD, 0.04nmol/L, 95% CI, 0.00-0.09 nmol/L, P=0.05), which was mainly driven by the effects of T cell-targeted therapy. A greater preservation in 4 h C-peptide AUC was observed in patients with nonantigen-based immunotherapies (WMD, 0.10nmol/L, 95% CI, 0.04-0.16 nmol/L, P=0.0007), which was mainly driven by the effects of tumor necrosis factor α (TNF-α) inhibitor and T cell-targeted therapy. After excluding small-sample trials, less daily insulin dosage was observed in patient treated with nonantigen-based immunotherapies when compared with control groups (WMD, -0.07units/kg/day, 95% CI, -0.11 to -0.03units/kg/day, P=0.0004). The use of antigen-based immunotherapies was also associated with a lower daily insulin dosage versus control groups (WMD, -0.11units/kg/day, 95% CI, -0.23 to -0.00units/kg/day, P=0.05). However, changes of HbA1c or FPG were comparable between nonantigen-based immunotherapies or antigen-based immunotherapies and control groups. The risk of hypoglycemia was not increased in patients treated with nonantigen-based immunotherapies or patients treated with antigen-based immunotherapies when compared with control groups. In conclusion, nonantigen-based immunotherapies were associated with a preservation of 2 h and 4 h C-peptide AUC in patients with T1D when compared with the controls, which was mainly driven by the effects of TNF-a inhibitor and T cell-targeted therapy. Both nonantigen-based immunotherapies and antigen-based immunotherapies tended to reduce the daily insulin dosage in patients with T1D when compared with the controls. However, they did not contribute to a substantial improvement in HbA1c or FPG. Both nonantigen-based immunotherapies and antigen-based immunotherapies were well tolerated with not increased risk of hypoglycemia in patients with T1D.

OBJECTIVE: Teplizumab has emerged as a potential disease-modifying drug in type 1 diabetes (T1D). This meta-analysis sought to summarize the therapeutic effect of teplizumab in newly diagnosed patients with T1D.
METHODS: Randomized controlled trials involving patients with T1D receiving teplizumab in the intervention arm and placebo (or no active intervention) in the control arm were searched throughout the electronic databases. The primary outcome was the change in area under the curve of C-peptide levels from baseline.
RESULTS: Seven reports from 6 studies involving 834 subjects met the inclusion criteria. Compared to teplizumab, greater reductions in area under the curve of C-peptide from the baseline values were observed in the control group after 6 months (mean difference [MD] 0.07 nmol/L [0.01, 0.13], P = .02), after 12 months (MD 0.07 nmol/L [0.04, 0.11], P = .0001), after 18 months (MD 0.10 nmol/L [0.06, 0.14], P < .00001), and after 24 months (MD 0.07 nmol/L [0.01, 0.14], P = .03) of interventions. Moreover, fewer patients treated with teplizumab had a decreased C-peptide response after 6 months (odds ratio [OR] 0.21), after 12 months (OR 0.17), after 18 months (OR 0.30), and after 24 months (OR 0.12) of treatment. The preservation of endogenous insulin production was supported by reduced use of exogenous insulin with maintenance of comparable glycemic control for up to 18 months post-treatment. Teplizumab imparted higher risks of grade 3 or higher adverse events, adverse events leading to study medication discontinuation, nausea, rash, and lymphopenia.
CONCLUSIONS: The results of the meta-analysis support teplizumab as a promising disease-modifying therapy for newly diagnosed T1D.

OBJECTIVE: To perform a systematic review of randomized controlled trials, evaluating the effect of probiotics, prebiotics or symbiotics supplementation on glycemic and inflammatory control in children with Type 1 Diabetes Mellitus (T1DM).
METHODS: The Medical Literature Analysis and Retrieval System Online (MEDLINE/PubMed), Clinical Trials, Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Scientific Electronic Library Online (SciELO) databases were searched. Randomized clinical trials of pediatric patients with DM1 using probiotics, prebiotics or symbiotics were included, regardless of year or language of publication. Studies that did not evaluate glycated hemoglobin (HbA1c) were excluded. Metabolic results (HbA1c, total insulin dose and C-peptide) and inflammatory control [interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ)] during probiotic supplementation or similar, related to modification of the intestinal microbiota, were analyzed. PROSPERO ID: CRD42022384485.
RESULTS: Five studies were selected for a systematic review. Regarding metabolic markers, only one of the articles that analyzed HbA1c showed a significant decrease (p=0.03) in the intervention group. One study identified a reduction in the total dose of insulin and increased C-peptide levels. Regarding the evaluation of inflammatory parameters (IL-10, TNF-α, INF-γ), there were no statistical relevant modifications.
CONCLUSIONS: Current data from the literature were not conclusive in identifying an improvement in glycemic control and did not observe changes in inflammatory parameters with the use of probiotics, prebiotics or symbiotics in pediatric patients with T1DM.

OBJECTIVE: Maturity-onset diabetes of the young type 13 (MODY13), a rare type of monogenic diabetes, is often misdiagnosed as type 1 or type 2 diabetes. To improve early diagnosis and precise treatment, we performed a systematic review and analysis of the literature about MODY13.
METHODS: PubMed, Cochrane, Embase, China National Knowledge Infrastructure (CNKI), Chinese BioMedical (CBM) Literature Database, and Wanfang Database were searched using the following search terms: \"MODY13,\" \"KCNJ11 maturity-onset diabetes of the young,\" \"KCNJ11-MODY,\" \"maturity-onset diabetes of the young type 13,\" and \"neonatal diabetes mellitus KCNJ11.\" The demography, clinical characteristics, and gene mutations of patients were expressed with descriptive statistical methods.
RESULTS: A total of 33 reports were included in this study, including 75 patients and 28 types of mutations. Thirty-six patients were male. The mean onset age was 25.20 ± 15.26 years. The averages of recorded body mass index, glycated hemoglobin (HbA1c), and fasting C-peptide were 23.45 ± 4.56kg/m2 , 10.07 ± 1.96%, and 0.31 ± 0.23nmol/L, respectively. Most of the mutation sites were located in the cytosolic region of N- and C-terminal domains of Kir6.2. Seven patients were reported to have diabetic chronic complications.
CONCLUSIONS: MODY13 was diagnosed later than other types of MODY and was associated with low fasting C-peptide. Mutation sites of MODY13 were mostly concentrated in N- and C-terminal intracellular domains. The majority of KCNJ11 gene mutations causing MODY 13 were from G to A. The incidence rates of chronic complications were lower than type 1 and type 2 diabetes.

Worldwide, diabetes and its complications have seriously affected people\'s quality of life and become a serious public health problem. C-peptide is not only an indicator of pancreatic β-cell function, but also a biologically active peptide that can bind to cell membrane surface signaling molecules and activate downstream signaling pathways to play antioxidant, anti-apoptotic and inflammatory roles, or regulate cellular transcription through internalization. It is complex how C-peptide is related to diabetic complications. Both deficiencies and overproduction can lead to complications, but their mechanisms of action may be different. C-peptide replacement therapy has shown beneficial effects on diabetic complications in animal models when C-peptide is deficient, but results from clinical trials have been unsatisfactory. The complex pattern of the relationship between C-peptide and diabetic chronic complications has not yet been fully understood. Future basic and clinical studies of C-peptide replacement therapies will need to focus on baseline levels of C-peptide in addition to more attention also needs to be paid to post-treatment C-peptide levels to explore the optimal range of fasting C-peptide and postprandial C-peptide maintenance.

OBJECTIVE: This meta-analysis aimed to assess the efficacy and safety of anti-CD3 monoclonal antibodies (mAbs) for type 1 diabetes.
METHODS: We searched PubMed, Embase and Cochrane until 23 February 2023 for randomized controlled trials that compared anti-CD3 mAbs with placebo in type 1 diabetes. The primary outcome was the area under the curve (AUC) of C-peptide, daily insulin dose or HbA1c.
RESULTS: Totally 12 trials that included 1870 participants were eligible for inclusion in the review. Compared with the control group, anti-CD3 mAbs increased AUC of C-peptide at 1 year (P = 0.0005, MD 0.14, 95% CI [0.06, 0.22], I2 = 94%), and 2 years (P = 0.0003, MD 0.20, 95% CI [0.09, 0.30], I2 = 88%). The use of anti-CD3 mAbs decreased insulin use at 1 year (P = 0.001, MD -0.09, 95% CI [-0.15, -0.04], I2 = 90%), and 2 years (P < 0.00001, MD -0.18, 95% CI [-0.25, -0.12], I2 = 86%). But there was no statistically significant effect on HbA1c levels. Vomiting, nausea, rash, pyrexia and headache were reported more frequently with anti-CD3 mAbs than with placebo. However, incidence of total adverse events and serious adverse events was similar when comparing anti-CD3 mAbs with placebo.
CONCLUSIONS: Our results suggest that anti-CD3 mAbs were a potential therapy for improving AUC of C-peptide and insulin use in type 1 diabetes.

Type 1 diabetes mellitus is widely recognized as a chronic autoimmune disease characterized by the pathogenic destruction of beta cells, resulting in the loss of endogenous insulin production. Insulin administration remains the primary therapy for symptomatic treatment. Recent studies showed that disease-modifying agents, such as anti-CD3 monoclonal antibodies, have shown promising outcomes in improving the management of the disease. In late 2022, teplizumab received approval from the US Food and Drug Administration (FDA) as the first disease-modifying agent for the treatment of type 1 diabetes. This review aims to evaluate the clinical evidence regarding the efficacy of anti-CD3 monoclonal antibodies in the prevention and treatment of type 1 diabetes.
A comprehensive search of PubMed, Google Scholar, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) was conducted up to December 2022 to identify relevant randomized controlled trials. Meta-analysis was performed using a random-effects model, and odds ratios with 95% confidence intervals (CIs) were calculated to quantify the effects. The Cochrane risk of bias tool was employed for quality assessment.
In total, 11 randomized controlled trials involving 1397 participants (908 participants in the intervention arm, 489 participants in the control arm) were included in this review. The mean age of participants was 15 years, and the mean follow-up time was 2.04 years. Teplizumab was the most commonly studied intervention. Compared with placebo, anti-CD3 monoclonal antibody treatment significantly increased the C-peptide concentration in the area under the curve at shorter timeframes (mean difference = 0.114, 95% CI: 0.069 to 0.159, p = .000). Furthermore, anti-CD3 monoclonal antibodies significantly reduced the patients\' insulin intake across all timeframes (mean difference = -0.123, 95% CI: -0.151 to -0.094, p < .001). However, no significant effect on glycated haemoglobin concentration was observed.
The findings of this review suggest that anti-CD3 monoclonal antibody treatment increases endogenous insulin production and improves the lifestyle of patients by reducing insulin dosage. Future studies should consider the limitations, including sample size, heterogeneity and duration of follow-up, to validate the generalizability of these findings further.

BACKGROUND: C-peptide is considered a peptide with active function in the body, which can affect people\'s health. However, the results of previous studies on the possible association of C-peptide with the risk of cardiometabolic disorders have not been fully understood. This systematic review and meta-analysis aimed to investigate the association between serum C-peptide level and the risk of cardiovascular disease (CVD) events.
METHODS: The various important databases, including PubMed, Scopus, and Web of Science, were searched comprehensively to November 2022 to identify the relevant studies. The HR(95% CI) or OR(95% CI) for observational studies were extracted and converted into log HR or log OR and their standard deviation(SD) was computed. A random-effects model with an inverse variance weighting method was conducted, to calculate the pooled effect size.
RESULTS: Sixteen observational studies, including one case-control study, eight cohort studies, and seven cross-sectional studies were included in the current meta-analysis. The sample size ranged from 90 to 7030, with an age range from 12 to 85 years. During the follow-up time (ranging from 5 to 17 years), 4852 CVD events occurred. Based on cohort and case-control studies, the pooled results showed no significant association between serum C-peptide with CVD events risk (RR = 1.02;95%CI:0.91-1.15, I2 = 34.7%; P-heterogeneity = 0.140). For cross-sectional studies, the pooled results indicated a positive association between serum C-peptide and the odds of CVD outcomes (OR = 1.35;95%CI:1.04-1.76, I2 = 83.6%; P-heterogeneity < 0.001).
CONCLUSIONS: The pooled results of the current study suggested that C-peptide level was not related to the risk of CVD events in cohort studies, however, the meta-analysis of cross-sectional studies showed a significant association between C-peptide and an increased risk of CVD events.