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Background: The TrialNet Oral Insulin (OI) prevention trial showed no overall treatment effect, using the diagnosis of type 1 diabetes as an endpoint. A significant delay in onset was only found in a high‐risk stratum (termed secondary stratum 1) of participants with low first‐phase insulin release (FPIR). Methods: Since trials with an endpoint of type 1 diabetes take years to complete, in this post hoc analysis, we assessed whether a novel combination of glucose and C‐peptide markers could identify a therapeutic benefit after 1 year of follow‐up (trial participants followed for a median 2.7 years). Results: Participants were relatives with multiple islet autoantibodies and low FPIR (n = 40). Glucose rose, and C‐peptide declined in the placebo group, whereas glucose rose minimally, and C‐peptide increased in the OI group. When glucose and C‐peptide were plotted on two‐dimensional grids using 30–120‐min oral glucose tolerance test (OGTT) time points, changes in ratios of their central points (centroid ratio) differed between groups (p = 0.037 adjusted for age, BMI, and baseline C‐peptide and glucose). Conclusions: These findings support a favorable early effect of OI on combined glucose and C‐peptide endpoints in high‐risk individuals, indicating metabolic benefit. With further study, these measures may allow for shorter trials compared to the standard endpoint of type 1 diabetes diagnosis. [ABSTRACT FROM AUTHOR]

Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R2 = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients' samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic. Molecular imaging holds promise for liver fibrosis grading but limited by a lack of effective biomarker. Here, the authors discover the grading potential of fibroblast activation protein alpha and design a responsive MRI nanoprobe that achieves fibrosis grading in mice models and clinical samples. [ABSTRACT FROM AUTHOR]

Introduction: Immunotherapy has a crucial role in the current treatment of multiple malignancies. Albeit described as rare, new onset autoimmune diabetes is a potentially life-threatening complication of programmed cell death-1 (PD-1) inhibitors, such as pembrolizumab, and its predisposing factors and pathological mechanism are yet to be clarified. Case Report: We present a case of a 72-year-old man with a high-grade bladder carcinoma undergoing pembrolizumab treatment. He had no personal or family history of diabetes mellitus but was diagnosed with primary hypothyroidism four months after starting pembrolizumab. Two years after starting pembrolizumab, he presented in the emergency department due to abdominal pain, anorexia, polydipsia, polyuria and vomiting over the preceding five days and he met criteria for severe diabetic ketoacidosis (DKA). Three days prior to his admission, he had received prednisolone therapy for suspected hypersensitivity related to a contrast-enhanced imaging that he performed. Management & Outcome: Prompt treatment for DKA was started, with transition to insulin basal-bolus therapy after DKA resolution, with progressive glycaemic stabilization. Further investigation revealed low C-peptide levels (0.07 ng/dL, with a fasting blood glucose of 288 mg/dL), HbA1c 9.2% and positive anti-IA2 antibodies, which allowed the diagnosis of new-onset autoimmune diabetes. Pembrolizumab was transiently suspended, and the patient resumed treatment after glycaemic profile optimization under multiple daily insulin administrations two months later. Discussion: This case highlights the importance of clinical suspicion and glycaemic monitoring as an integral part of treatment protocols in patients on pembrolizumab and other immune checkpoint inhibitors. Additional research and investigation into the underlying mechanisms of this condition are necessary to identify potential screening tests for individuals at higher risk of developing DM and to guide the implementation of management and preventive strategies for ketoacidosis complication. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The gut microbiome is implicated in the disease process leading to clinical type 1 diabetes, but less is known about potential changes in the gut microbiome after the diagnosis of type 1 diabetes and implications in glucose homeostasis. We aimed to analyse potential associations between the gut microbiome composition and clinical and laboratory data during a 2 year follow-up of people with newly diagnosed type 1 diabetes, recruited to the Innovative approaches to understanding and arresting type 1 diabetes (INNODIA) study. In addition, we analysed the microbiome composition in initially unaffected family members, who progressed to clinical type 1 diabetes during or after their follow-up for 4 years. Methods: We characterised the gut microbiome composition of 98 individuals with newly diagnosed type 1 diabetes (ND cohort) and 194 autoantibody-positive unaffected family members (UFM cohort), representing a subgroup of the INNODIA Natural History Study, using metagenomic sequencing. Participants from the ND cohort attended study visits within 6 weeks from the diagnosis and 3, 6, 12 and 24 months later for stool sample collection and laboratory tests (HbA1c, C-peptide, diabetes-associated autoantibodies). Participants from the UFM cohort were assessed at baseline and 6, 12, 18, 24 and 36 months later. Results: We observed a longitudinal increase in 21 bacterial species in the ND cohort but not in the UFM cohort. The relative abundance of Faecalibacterium prausnitzii was inversely associated with the HbA1c levels at diagnosis (p=0.0019). The rate of the subsequent disease progression in the ND cohort, as assessed by change in HbA1c, C-peptide levels and insulin dose, was associated with the abundance of several bacterial species. Individuals with rapid decrease in C-peptide levels in the ND cohort had the lowest gut microbiome diversity. Nineteen individuals who were diagnosed with type 1 diabetes in the UFM cohort had increased abundance of Sutterella sp. KLE1602 compared with the undiagnosed UFM individuals (p=1.2 × 10−4). Conclusions/interpretation: Our data revealed associations between the gut microbiome composition and the disease progression in individuals with recent-onset type 1 diabetes. Future mechanistic studies as well as animal studies and human trials are needed to further validate the significance and causality of these associations. [ABSTRACT FROM AUTHOR]

Purpose: Multiple daily injection (MDI) insulin therapy is an effective method of glycemic control and appropriate assignment to MDI therapy could minimize the risks of hypoglycemia and weight gain. The aim of the present study was to identify factors associated with indication for MDI therapy in type 2 diabetes (T2DM). Methods: We recruited 360 participants with T2DM that were admitted to the Endocrinology Department of Peking University People's Hospital between August 2017 and July 2018. They first underwent intensive insulin therapy, then were switched to an optimized, simpler insulin treatment that aimed to maintain fasting blood glucose between 4.4 and 7.2 mmol/L, without episodes of hypoglycemia. The baseline characteristics of groups administering either MDI or basal/premix insulin were compared and multivariable logistic regression analysis was used to determine the odds ratios (ORs) for factors associated with MDI therapy. Receiver operating characteristic (ROC) curves were then used to identify independent predictors of MDI insulin regimen efficacy. Results: The mean age of the participants was 57.6 ± 12.9 years, and diabetes duration was 14.2 ± 8.2 years. Two hundred and sixty-seven participants administered basal/premix insulin and 93 underwent MDI therapy, of whom 61.8% and 46.2% were male, respectively (p = 0.01). The duration of diabetes was significantly longer in the MDI group (13.1 ± 7.7 years vs. 17.3 ± 8.7 years; p < 0.01). Fasting plasma glucose (FPG) was higher in the MDI group than in the basal/premix group (8.3 [6.7, 11.3] mmol/L vs. 7.2 [5.7, 9.3] mmol/L; p < 0.01), while the postprandial C-peptide concentration (PCP) was significantly lower in the MDI group (2.6 [1.8, 3.5] ng/mL) compared to the basal/premix group (3.6 [2.5, 6.2] ng/mL, p < 0.01. Multivariable logistic regression analysis suggested that diabetes duration and FPG were positively associated with MDI therapy: OR (95% confidence interval [CI]) 1.06 (1.02, 1.10) and 1.12 (1.02, 1.24), respectively. In addition, PCP was negatively associated with MDI therapy (0.72 [0.60, 0.86]). ROC analysis suggested that a PCP of < 3.1 ng/mL predicted MDI therapy with 59.6% sensitivity and 72.1% specificity. Conclusion: The results of our study suggest that longer diabetes duration, higher FPG, and lower PCP were associated with necessity for MDI insulin regimen. These findings should assist with the personalization of insulin treatment. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate the association of fasting C-peptide and glucagon with diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2DM). Methods A comprehensive evaluation was conducted on 797 patients with T2DM to assess the various risk factors affecting DPN. The subjects were categorized into short duration and long duration group according to the duration of diabetes with a threshold of 10 years. Logistic regression analysis was employed to examine the association between DPN and islet function, as well as other parameters. Receiver operating characteristic curve analysis was performed to evaluate the predictive capability of glucagon. Results The fasting C-peptide levels were significantly lower in the DPN patients with short duration of diabetes, but lost significance in the long duration group. Conversely, a decreased level of glucagon was only observed in DPN patients with long duration of diabetes. For the group with long duration of diabetes, glucagon was the sole risk factor associated with DPN. The receiver operating characteristic curve analysis revealed that glucagon in the long duration group exhibited a moderate area under the curve of 0.706. Conclusions The serum glucagon levels in T2DM patients with DPN exhibited bidirectional changes based on the duration of diabetes. Decreased glucagon was associated with DPN in T2DM patients with long duration of diabetes. What is already known on this topic Diabetic peripheral neuropathy (DPN), a common complication of diabetes, significantly impairs the quality of life. Although increased level of serum glucagon in T2DM patients has been well documented, the impact of glucagon on T2DM patients with DPN remains unclear. What this study adds The serum glucagon levels in T2DM patients with DPN exhibited bidirectional changes based on the duration of diabetes. Decreased glucagon was associated with DPN in T2DM patients with long duration of diabetes. How this study might affect research, practice, or policy In clinical practice, patients with T2DM with a long duration of disease should pay attention to the occurrence and progression of DPN when using antidiabetic drugs target glucagon. [ABSTRACT FROM AUTHOR]

Background: Viral respiratory infections may precipitate type 1 diabetes (T1D). A possible association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, and the incidence of T1D is being determined. This study was carried out using Portuguese registries, aiming at examining temporal trends between COVID-19 and T1D. Methods: Hospital data, comparing the incidence before and during the COVID-19 pandemic, from children and young adults diagnosed with new-onset T1D, was acquired beginning in 2017 and until the end of 2022. Data was obtained from nine different Portuguese hospital units. The impact of the COVID-19 pandemic, beginning in March 2020, was assessed comparing the annual numbers of new-onset T1D cases. The annual median levels of glucose, glycated hemoglobin (HbA1c) and fasting C-peptide at T1D diagnosis were compared. The annual number of diabetic ketoacidosis (DKA) episodes among new T1D cases was also assessed at two centers. Results: In total, data from 574 newly diagnosed T1D patients was analyzed, including 530 (92.3%) children. The mean ages for child and adult patients were 9.1 (SD 4.4) and 32.8 (SD 13.6) years, respectively. 57.8% (331/573) were male, one patient had unknown sex. The overall median (25–75 percentiles) levels of glucose, HbA1c and fasting C-peptide at diagnosis were 454 mg/dL (356–568), 11.8% (10.1–13.4) and 0.50 µg/L (0.30–0.79), respectively. DKA at T1D diagnosis was present in 48.4% (76/157). For eight centers with complete 2018 to 2021 data (all calendar months), no overall significant increase in T1D cases was observed during the COVID-19 pandemic, i.e. 90 cases in 2018, 90 cases in 2019, 112 in 2020 and 100 in 2021 (P for trend = 0.36). Two of the centers, Faro (CHUA) and Dona Estefânia (CHULC) hospitals, did however see an increase in T1D from 2019 to 2020. No significant changes in glucose (P = 0.32), HbA1c (P = 0.68), fasting C-peptide (P = 0.20) or DKA frequency (P = 0.68) at the time of T1D diagnosis were observed over the entire study period. Conclusion: The T1D incidence did not increase significantly, when comparing the years before and during the COVID-19 pandemic, nor did key metabolic parameters or number of DKA episodes change. [ABSTRACT FROM AUTHOR]

Key Clinical Message: A comprehensive evaluation, including symptoms, medical history, C‐peptide levels, and anti‐GAD antibodies, is essential for distinguishing between diabetes' types, particularly in cases of diagnostic uncertainty. While obesity is often associated with T2DM, BMI should be viewed as a factor rather than a criterion for the exclusion of diabetes type. [ABSTRACT FROM AUTHOR]

Context Metabolic measures are frequently used to predict type 1 diabetes (T1D) and to understand effects of disease-modifying therapies. Objective Compare metabolic endpoints for their ability to detect preventive treatment effects and predict T1D. Methods Six-month changes in metabolic endpoints were assessed for (1) detecting treatment effects by comparing placebo and treatment arms from the randomized controlled teplizumab prevention trial, a multicenter clinical trial investigating 14-day intravenous teplizumab infusion and (2) predicting T1D in the TrialNet Pathway to Prevention natural history study. For each metabolic measure, t-Values from t tests for detecting a treatment effect were compared with chi-square values from proportional hazards regression for predicting T1D. Participants in the teplizumab prevention trial and participants in the Pathway to Prevention study selected with the same inclusion criteria used for the teplizumab trial were studied. Results Six-month changes in glucose-based endpoints predicted diabetes better than C-peptide–based endpoints, yet the latter were better at detecting a teplizumab effect. Combined measures of glucose and C-peptide were more balanced than measures of glucose alone or C-peptide alone for predicting diabetes and detecting a teplizumab effect. Conclusion The capacity of a metabolic endpoint to detect a treatment effect does not necessarily correspond to its accuracy for predicting T1D. However, combined glucose and C-peptide endpoints appear to be effective for both predicting diabetes and detecting a response to immunotherapy. These findings suggest that combined glucose and C-peptide endpoints should be incorporated into the design of future T1D prevention trials. [ABSTRACT FROM AUTHOR]

OBJECTIVE: We evaluated the effect of long-term intensive metabolic control with hybrid closed-loop (CL) on residual C-peptide secretion and glucose control compared with standard insulin therapy in youth with type 1 diabetes over 48 months. RESEARCH DESIGN AND METHODS: Following the 24-month primary phase of a multicenter, randomized, parallel trial of 96 newly diagnosed youth aged 10 to 16.9 years, participants were invited to an extension phase using treatment allocated at randomization. They continued with hybrid CL using the Cambridge algorithm or standard insulin therapy (control) until 48 months after diagnosis. Analysis was by intention-to-treat. RESULTS: At 24 months after diagnosis, 81 participants (mean ± SD age 14 ± 2 years) continued in the extension phase (47 CL, 34 control). There was no difference in fasting C-peptide corrected for fasting glucose at 48 months between groups (CL: 5 ± 9 vs. control: 6 ± 14 pmol/L per mmol/L; mean adjusted difference −2 [95% CI −7, 4; P = 0.54]). Central laboratory HbA1c remained lower in the CL group by 0.9% (10 mmol/mol [95% CI 0.2, 1.5; 3, 17 mmol/mol); P = 0.009). Time in target range of 3.9 to 10.0 mmol/L was 12 percentage points (95% CI 3, 20; P = 0.008) higher in the CL group compared with control. There were 11 severe hypoglycemic events (6 CL, 5 control) and 7 diabetic ketoacidosis events (3 CL, 4 control) during the extension phase. CONCLUSIONS: Improved glycemic control was sustained over 48 months after diagnosis with CL insulin delivery compared with standard therapy in youth with type 1 diabetes. This did not appear to confer a protective effect on residual C-peptide secretion. [ABSTRACT FROM AUTHOR]

Objective: We aimed to analyze the relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D (25(OH)D) in patients with type 2 diabetes mellitus. Methods: A total of 184 patients with T2DM who were hospitalized in the Department of Endocrinology of the ShiDong Clinical Hospital between January 2023 and June 2023 were selected. We compared review of anthropometric, biochemical, and inflammatory parameters and non-invasive scores between groups defined by ultrasound NAFLD severity grades.We determine the correlation between 25(OH)D and FLI and FIB-4 scores, respectively. Results: Statistically significant differences were seen between BMI, WC, C-peptide levels, FPG, ALT, serum 25(OH)D, TC, HDL, lumbar spine bone density, FLI, and FIB-4 in different degrees of NAFLD. Multivariate logistic regression analysis showed that 25(OH)D (OR = 1.26, p = 0.001), age (OR = 0.93, P < 0.001) and BMI (OR = 1.04, p = 0.007) were independent predictors of NAFLD in patients with T2DM. Conclusions: This study revealed the correlation between serum 25(OH)D levels and NAFLD in patients with T2DM. We also demonstrated that serum 25(OH)D levels were negatively correlated with FLI/FIB-4 levels in patients with T2DM with NAFLD, suggesting that vitamin D deficiency may promote hepatic fibrosis progression in T2DM with NAFLD. [ABSTRACT FROM AUTHOR]

Background: We evaluated changes in glycemic status, over 1 year, of coronavirus disease 2019 (COVID-19) survivors with dysglycemia in acute COVID-19. Methods: COVID-19 survivors who had dysglycemia (defined by glycosylated hemoglobin [HbA1c] 5.7% to 6.4% or random glucose ≥10.0 mmol/L) in acute COVID-19 were recruited from a major COVID-19 treatment center from September to October 2020. Matched non-COVID controls were recruited from community. The 75-g oral glucose tolerance test (OGTT) were performed at baseline (6 weeks after acute COVID-19) and 1 year after acute COVID-19, with HbA1c, insulin and C-peptide measurements. Progression in glycemic status was defined by progression from normoglycemia to prediabetes/diabetes, or prediabetes to diabetes. Results: Fifty-two COVID-19 survivors were recruited. Compared with non-COVID controls, they had higher C-peptide (P< 0.001) and trend towards higher homeostasis model assessment of insulin resistance (P=0.065). Forty-three COVID-19 survivors attended 1-year reassessment. HbA1c increased from 5.5%±0.3% to 5.7%±0.2% (P<0.001), with increases in glucose on OGTT at fasting (P=0.089), 30-minute (P=0.126), 1-hour (P=0.014), and 2-hour (P=0.165). At baseline, 19 subjects had normoglycemia, 23 had prediabetes, and one had diabetes. Over 1 year, 10 subjects (23.8%; of 42 non-diabetes subjects at baseline) had progression in glycemic status. C-peptide levels remained unchanged (P=0.835). Matsuda index decreased (P=0.007) and there was a trend of body mass index increase from 24.4±2.7 kg/m2 to 25.6±5.2 (P=0.083). Subjects with progression in glycemic status had more severe COVID-19 illness than non-progressors (P=0.030). Reassessment was not performed in the control group. Conclusion: Subjects who had dysglycemia in acute COVID-19 were characterized by insulin resistance. Over 1 year, a quarter had progression in glycemic status, especially those with more severe COVID-19. Importantly, there was no significant deterioration in insulin secretory capacity. [ABSTRACT FROM AUTHOR]

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Aims: To evaluate the correlation between C‐peptide index (CPI) at 2 h post‐meal and endogenous insulin secretory capacity and to develop clinical models to predict the possibility of withdrawal from insulin therapy in patients with type 2 diabetes. Method: This was a single‐centre retrospective study of patients with type 2 diabetes admitted to our hospital. Patients were divided into a withdrawal group (n = 72) and a non‐withdrawal group (n = 75) based on whether they were able to withdraw from insulin therapy at discharge, and the correlation between CPI at 2 h after meal and diabetes‐related parameters was evaluated. In addition, we created two clinical models to predict the possibility of withdrawal from insulin therapy using machine learning. Results: The glycated haemoglobin values of the study participants were 87.8 ± 22.6 mmol/mo. The CPI at 2 h post‐meal was 1.93 ± 1.28 in the non‐withdrawal group and 2.97 ± 2.07 in the withdrawal group (p < 0.001). CPI at 2 h post‐meal was an independent predictor of withdrawal from insulin therapy. In addition, CPI at 2 h post‐meal was a better predictor than fasting CPI. Six factors associated with insulin therapy withdrawal (age, duration of diabetes, creatinine, alanine aminotransferase, insulin therapy until hospitalization, and CPI at 2 h post‐meal) were used to generate two clinical models by machine learning. The accuracy of the generated clinical models ranged from 78.3% to 82.6%. Conclusion: The CPI at 2 h post‐meal is a clinically useful measure of endogenous insulin secretory capacity under non‐fasting conditions. [ABSTRACT FROM AUTHOR]

Aim: To provide updated efficacy and safety information for teplizumab in the treatment of Stage 3 type 1 diabetes mellitus (T1DM). Materials and 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). Conclusion: Teplizumab increases AUC of C‐peptide levels and decreases HbA1c levels and insulin use, without raising serious adverse event risk. [ABSTRACT FROM AUTHOR]

Background and Objective: The autoimmune mechanism in T1DM causes gradual loss of pancreatic β-cell, which progresses to hyperglycemia and ultimate reliance on consistent insulin therapy. T1DM has been the commonest type of diabetes in children and this study will help in refining indulgent towards the problem and its pathophysiology in our people. The objective was to find out the prevalence of C-peptide and antibody levels (anti GAD, ICA, IAA and IA2) in children and adolescents of Pakistan with T1DM. Methods: We conducted this cross-sectional study at Department of Pediatric Endocrinology, National Institute of Child Health, Karachi between August 2019 to February 2020 and included 98 children who had T1DM for more than one month. Subjects whose GFR was <30ml/min were omitted from the study. Among those registered subjects, C-peptide, human islet cell antibody (ICA), insulin auto antibodies (IAA) and anti-glutamic acid decarboxylase were assessed. Demographical and laboratorial facts were noted on a pre-constructed proforma. Results: There were 77(78.3%) cases who had level of C-peptide <0.8 and anti-GAD was found in 47(48%) subjects. 35(35.7%) cases found positive for IA2 .and 7(7.1%) patients had insulin auto antibodies positive while ICA was negative in total 98(100%) subjects. Conclusion: Children with T1 DM possessed increased levels of anti-GAD antibodies, insulin autoantibodies and anti (IA2) but islet cells antibodies were negligible in our population when checked at a point of time. C-peptide may be normal in some, but its level declines with long duration of diabetes in children. [ABSTRACT FROM AUTHOR]

Transient neonatal diabetes mellitus (TNDM) is a genetically heterogeneous form of neonatal diabetes characterized by hyperglycemia that remits during infancy with a tendency to recur in later life. This case report presents the history of a male infant with transient neonatal diabetes mellitus. The patient was treated with a continuous subcutaneous insulin infusion (CSII) and a continuous glucose monitoring (CGM) system until the age of 2 months, when the normoglycemia connected with a withdrawal of treatment was noted. The genetic test results excluded the majority of known mutations related to TNDM. This case report focuses on various genetic mutations and the clinical features connected with them that cause TNDM and highlights the difficulties in the diagnostic and therapeutic processes of this disease. CSII and CGM systems seem to be a safe and effective treatment option in TNDM and may be used in the therapy. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of the present study was to identify predictors of severe white matter hyperintensity (WMH) with obesity (SWO), and to build a prediction model for screening obese people with severe WMH without Nuclear Magnetic Resonance Imaging (MRI) examination. Patients subjects and methods: From September 2020 to October 2021, 650 patients with WMH were recruited consecutively. The subjects were divided into two groups, SWO group and non-SWO group. Univariate and Logistic regression analysis were was applied to explore the potential predictors of SWO. The Youden index method was adopted to determine the best cut-off value in the establishment of the prediction model of SWO. Each parameter had two options, low and high. The score table of the prediction model and nomogram based on the logistic regression were constructed. Of the 650 subjects, 487 subjects (75%) were randomly assigned to the training group and 163 subjects (25%) to the validation group. By resampling the area under the curve (AUC) of the subject's operating characteristics and calibration curves 1,000 times, nomogram performance was verified. A decision curve analysis (DCA) was used to evaluate the nomogram's clinical usefulness. By resampling the area under the curve (AUC) of the subject's operating characteristics and calibration curves 1,000 times, nomogram performance was verified. A decision curve analysis (DCA) was used to evaluate the nomogram's clinical usefulness. Results: Logistic regression demonstrated that hypertension, uric acid (UA), complement 3 (C3) and Interleukin 8 (IL-8) were independent risk factors for SWO. Hypertension, UA, C3, IL-8, folic acid (FA), fasting C-peptide (FCP) and eosinophil could be used to predict the occurrence of SWO in the prediction models, with a good diagnostic performance, Areas Under Curves (AUC) of Total score was 0.823 (95% CI: 0.760--0.885, p < 0.001), sensitivity of 60.0%, specificity of 91.4%. In the development group, the nomogram's AUC (C statistic) was 0.829 (95% CI: 0.760--0.899), while in the validation group, it was 0.835 (95% CI: 0.696, 0.975). In both the development and validation groups, the calibration curves following 1,000 bootstraps showed a satisfactory fit between the observed and predicted probabilities. DCA showed that the nomogram had great clinical utility. Conclusion: Hypertension, UA, C3, IL-8, FA, FCP and eosinophil models had the potential to predict the incidence of SWO. When the total score of the model exceeded 9 points, the risk of SWO would increase significantly, and the nomogram enabled visualization of the patient's WMH risk. The application prospect of our models mainly lied in the convenient screening of SWO without MRI examination in order to detect SWO and control the WMH hazards early. [ABSTRACT FROM AUTHOR]

Background: Laparoscopic sleeve gastrectomy (LSG) has emerged as a valuable treatment for various metabolic disorders, including metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with obesity. Consequently, there is a pressing need to develop noninvasive biomarkers for diagnosing and monitoring disease progression. Objectives: This study aimed to evaluate specific biomarkers, including Cytokeratin-18 (CK-18), C-peptide, monocyte to HDL cholesterol ratio (MHR), and MACK-3, in patients with obesity with MAFLD undergoing LSG. Design: A prospective cohort study on patients with obesity before and 6 months after the LSG procedure. Methods: 70 patients with obesity with confirmed MAFLD, determined by Transient Elastography (TE), were pre- and 6 months postoperatively tested. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), lipid profile, ghrelin, leptin, peptide YY, GLP-1, and liver fibrosis scores, including AST/ALT ratio (AAR), Fibrosis-4 index (FIB-4), and BARD Score were tested. Results: BMI significantly decreased in all participants, with a % excess weight loss of 62.0% ± 15.4%. TE measurements revealed a significant postoperative reduction from 100% to 87.1% (P =.006). All selected biomarkers showed significant postoperative improvement—a significant association of CK-18 with MAFLD markers, including AAR, FIB-4, and BARD score, were found. MACK-3 had positive associations with FIB-4. C-peptide and MHR showed no association with MAFLD markers. Furthermore, there was a positive correlation between CK-18 and MACK-3 tests and between C-peptide and CK-18 and MACK-3. Additionally, a receiver operating characteristic (ROC) curve was constructed, with CK-18 performing the best, with an estimated area under the curve of 0.863. Conclusion: Serum CK-18 outperformed other selected biomarkers in predicting and monitoring MAFLD in patients with obesity, suggesting its prospective utility in clinical practice. Further studies are needed to validate the accuracy of the MACK-3 test. Plain Language Summary: Effect on biomarkers in patients with fatty liver after weight loss surgery A sleeve gastrectomy is an operation when patient have obesity and need to lose weight. This operation help people with obesity who also have fatty liver disease that's not related to alcohol use. Researchers are looking for simple blood tests to track the disease. In this study, they checked how well 4 of these tests worked before and after the surgery in 70 people. They found that the patients lost a lot of weight and their liver health improved. One test, in particular, called CK-18, was really good at showing these changes. Another test, MACK-3, also showed promise, but more research is needed to be sure. The other 2 tests didn't seem to be linked to signs of fatty liver disease. This suggests that CK-18 could be a useful tool for doctors to see how patients are doing after this surgery [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Type 1 diabetes is an heterogenous condition. Characterising factors explaining differences in an individual's clinical course and treatment response will have important clinical and research implications. Our aim was to explore type 1 diabetes heterogeneity, as assessed by clinical characteristics, autoantibodies, beta cell function and glycaemic outcomes, during the first 12 months from diagnosis, and how it relates to age at diagnosis. Methods: Data were collected from the large INNODIA cohort of individuals (aged 1.0–45.0 years) newly diagnosed with type 1 diabetes, followed 3 monthly, to assess clinical characteristics, C-peptide, HbA1c and diabetes-associated antibodies, and their changes, during the first 12 months from diagnosis, across three age groups: <10 years; 10–17 years; and ≥18 years. Results: The study population included 649 individuals (57.3% male; age 12.1±8.3 years), 96.9% of whom were positive for one or more diabetes-related antibodies. Baseline (IQR) fasting C-peptide was 242.0 (139.0–382.0) pmol/l (AUC 749.3 [466.2–1106.1] pmol/l × min), with levels increasing with age (p<0.001). Over time, C-peptide remained lower in participants aged <10 years but it declined in all age groups. In parallel, glucose levels progressively increased. Lower baseline fasting C-peptide, BMI SD score and presence of diabetic ketoacidosis at diagnosis were associated with lower stimulated C-peptide over time. HbA1c decreased during the first 3 months (p<0.001), whereas insulin requirement increased from 3 months post diagnosis (p<0.001). Conclusions/interpretation: In this large cohort with newly diagnosed type 1 diabetes, we identified age-related differences in clinical and biochemical variables. Of note, C-peptide was lower in younger children but there were no main age differences in its rate of decline. [ABSTRACT FROM AUTHOR]

Objective: The relationships between carotid intima-media thickness (C-IMT) and β cell function and insulin resistance in patients with type 2 diabetes (T2D) have not been fully elucidated. This study is to investigate whether impaired glucose metabolism is etiologically associated with C-IMT in patients with T2D. Methods: The study group consisted of 490 (284 men, 206 women) participants. Venous blood specimens were obtained from all subjects for biochemical profiles after an >8-h overnight fast. C-IMT was measured as the distance between the luminal-intimal leading edge (I-line) and the medial-adventitial leading edge (M-line) on the far wall. Insulin resistance was estimated with the homeostasis model assessment of insulin resistance (HOMA-IR). The acute insulin response to arginine was calculated as the mean of the three plasma insulin levels obtained within 2, 4, and 6 min after the arginine bolus minus the pre-stimulus plasma insulin levels. Results: There was a graded increase in C-IMT values according to tertiles of HOMA-IR in men; the values of C-IMT were significantly decreased across the tertiles of acute insulin and C-peptide responses in women. Multivariate analysis revealed that HOMA-IR and age were positively associated with C-IMT among men participants, and acute insulin response and current smoking were the independent determinants of C-IMT in women. Conclusion: Early insulin response stimulated by arginine is independently associated with C-IMT in women T2D individuals, whereas insulin resistance is positively correlated with C-IMT in men T2D subjects. [ABSTRACT FROM AUTHOR]

Objective: MODY (maturity onset diabetes of the young) is a rare, monogenic, autosomal dominant form of diabetes occurring in young (< 25 years) individuals. It has a wide phenotypic variability and can be misdiagnosed as type 1 diabetes mellitus (T1DM). Appropriate detection of MODY has therapeutic and genetic implications. This study aimed to detect MODY among long standing, clinically diagnosed T1DM patients with preserved C-peptide levels. Methods: This was a hospital-based cross-sectional study from central South India which included 100 clinically diagnosed T1DM patients (according to ADA criteria), with a duration of > 3 years. MODY probability score, urinary C-peptide to creatinine ratio (UCPCR), and relevant biochemical investigations were performed. Targeted next-generation sequencing (NGS) for MODY-related genes (13 genes) was done for individuals with UCPCR > 0.2. Results: A UCPCR value of > 0.2 (suggestive of preserved endogenous insulin secretion) was observed in eight individuals. The mean HbA1c values were lower, and the MODY probability score was higher in individuals with preserved endogenous insulin (8.07% vs 9.53% and 2.8% vs 1.5%; p-value: 0.005 and 0.004 respectively). One of the eight individuals (12.5%) had a non-pathogenic gene variant in KLF11. Conclusion: In a South Indian cohort of T1DM with preserved C-peptide, we could not find any case of MODY through targeted NGS. UCPCR can be used as a screening tool to identify cases needing genetic testing for MODY. Larger studies utilizing whole exome sequencing should be conducted to know the actual prevalence of MODY among T1DM. [ABSTRACT FROM AUTHOR]

Background: The Korean Endocrine Hormone Reference Standard Data Center (KEHRS DC) has created reference standards (RSs) for endocrine hormones since 2020. This study is the first of its kind, wherein the KEHRS DC established RSs for serum Cpeptide levels in a healthy Korean population. Methods: Healthy Korean adults were recruited from May 2021 to September 2023. After excluding participants according to our criteria, serum samples were collected; each participant could then choose between fasting glucose only or fasting glucose plus an oral glucose tolerance test (OGTT). If their sample showed high glucose (=100 mg/dL) or hemoglobin A1c (HbA1c) (≥5.70%), their C-peptide levels were excluded from analyzing the RSs. Results: A total of 1,532 participants were recruited; however, only the data of 1,050 participants were analyzed after excluding those whose samples showed hyperglycemia or high HbA1c. Post-30-minute OGTT data from 342 subjects and post-120-minute OGTT data from 351 subjects were used. The means±2 standard deviations and expanded uncertainties of fasting, post-30-minute and 120-minute OGTT C-peptide levels were 1.26±0.82 and 0.34-3.18, 4.74±3.57 and 1.14-8.33, and 4.85±3.58 and 1.25-8.34 ng/mL, respectively. Serum C-peptide levels correlated with obesity, serum glucose levels, and HbA1c levels. Conclusion: The RSs for serum C-peptide levels established in this study are expected to be useful in both clinical and related fields. [ABSTRACT FROM AUTHOR]

Type 1 diabetes is a chronic autoimmune disease in which destruction of pancreatic β-cells causes life-threatening metabolic dysregulation. Numerous approaches are envisioned for new therapies, but limitations of current clinical outcome measures are significant disincentives to development efforts. C-peptide, a direct byproduct of proinsulin processing, is a quantitative biomarker of β-cell function that is not cleared by the liver and can be measured in the peripheral blood. Studies of quantitative measures of β-cell function have established a predictive relationship between stimulated C-peptide as a measure of β-cell function and clinical benefits. C-peptide levels at diagnosis are often high enough to afford glycemic control benefits associated with protection from end-organ complications of diabetes, and even lower levels offer protection from severe hypoglycemia in type 1 diabetes, as observed in large prospective cohort studies and interventional trials of islet transplantation. These observations support consideration of C-peptide not just as a biomarker of β-cell function but also as a specific, sensitive, feasible, and clinically meaningful outcome defining β-cell preservation or restoration for clinical trials of disease-modifying therapies. Regulatory acceptance of C-peptide as a validated surrogate for demonstration of efficacy would greatly facilitate development of disease-modifying therapies for type 1 diabetes. Article Highlights: Mixed-meal stimulated C-peptide level has been established as a biomarker of endogenous β-cell function and is used clinically to monitor disease progression in type 1 diabetes. Large prospective cohort studies and interventional trials of islet transplantation demonstrate the relationship between stimulated C-peptide levels and clinical benefits. A recent meta-analysis of interventional clinical trials aimed at preserving β-cell function in those recently diagnosed further supports stimulated C-peptide level as a validated surrogate end point for clinical trials of disease-modifying therapies in type 1 diabetes. [ABSTRACT FROM AUTHOR]

Maturity onset diabetes of the young (MODY) is characterized by noninsulin-dependent diabetes diagnosed before the age of 25 years with an autosomal dominant inheritance. Rare mutations in the hepatocyte nuclear factor-1-beta (HNF1B) gene produce a syndrome that resembles MODY. About half of patients diagnosed with MODY type 5 due to HNF1B variants, carry a whole gene deletion, known as 17q12 deletion syndrome. 17q12 deletion syndrome is a rare chromosomal anomaly and is typified by deletion of more than 15 genes, including HNF1B resulting in kidney abnormalities and renal cysts, a diabetes syndrome and neurodevelopmental or neuropsychiatric disorders. A 12-year-old girl was referred after high blood sugar was detected in the hospital where she presented with polyuria and polydipsia, which had persisted for one month. Her serum magnesium (Mg) level was low at 1.5 mg/dL (normal value 1.6-2.6) and glycated hemoglobin was 14% (normal value 3.6-5.8) concurrent with a c-peptide of 1.54 ng/mL (normal value 0.8-4). MODY5 was suspected but the NGS gene panel (ABCC8, BLK, CEL, GCK, HNF1A, HNF1B, HNF4A, INS, KCNJ11, KLF11, NEURODD1, PAX4, PDX1, RFX6, ZFP57, GLIS3, FOXP3, NEUROG3, G6PC2) did not identify any abnormality. During follow-up, her serum Mg remained low (1.2 mg/ dL) together with elevated urinary Mg excretion at 172.5 mg/day. An HNF1B variant was again suspected in a patient with chronic hypomagnesemia with normal basal C peptide level. Abdominal computed tomography and magnetic resonance imaging revealed a 43 mm diameter, cystic lesion in the head of the pancreas, with agenesis of the pancreatic neck, trunk and tail. Genetic testing using a microarray analysis was subsequently performed and a heterozygous deletion at 17q12, including HNF1B, was detected. In case of clinical suspicion of HNF1B variants, further genetic examination using other techniques such as MLPA and CGH array may be required to detect the variant. This is because deletions and duplications may not be detected using next generation screening panel techniques. [ABSTRACT FROM AUTHOR]

Background: Growth differentiation factor 15 (GDF15) is a mitokine, the role of which, total or H-specific, in modulating energy metabolism and homeostasis in obesity-related diseases, such as metabolic dysfunction associated steatotic liver disease (MASLD), has not been fully elucidated in adult humans. We aimed to investigate the fasting and stimulated levels of GDF15, total and H-specific, glucose-dependent insulinotropic polypeptide (GIP) and C-peptide, in two physiology interventional studies: one focusing on obesity, and the other on MASLD. Methods: Study 1 investigated individuals with normal weight or with obesity, undergoing a 3-h mixed meal test (MMT); and study 2, examined adults with MASLD and controls undergoing a 120-min oral glucose tolerance test (OGTT). Exploratory correlations of total and H-specific GDF15 with clinical, hormonal and metabolomic/lipidomic parameters were also performed. Results: In study 1, 15 individuals were included per weight group. Fasting and postprandial total and H-specific GDF15 were similar between groups, whereas GIP was markedly higher in leaner individuals and was upregulated following a MMT. Baseline and postprandial C-peptide were markedly elevated in people with obesity compared with lean subjects. GIP was higher in leaner individuals and was upregulated after a MMT, while C-peptide and its overall AUC after a MMT was markedly elevated in people with obesity compared with lean subjects. In study 2, 27 individuals were evaluated. Fasting total GDF15 was similar, but postprandial total GDF15 levels were significantly higher in MASLD patients compared to controls. GIP and C-peptide remained unaffected. The postprandial course of GDF15 was clustered among those of triglycerides and molecules of the alanine cycle, was robustly elevated under MASLD, and constituted the most notable differentiating molecule between healthy and MASLD status. We also present robust positive correlations of the incremental area under the curve of total and H-specific GDF15 with a plethora of lipid subspecies, which remained significant after adjusting for confounders. Conclusion: Serum GDF15 levels do not differ in relation to weight status in hyperlipidemic but otherwise metabolically healthy individuals. In contrast, GDF15 levels are significantly increased in MASLD patients at baseline and they remain significantly higher compared to healthy participants during OGTT, pointing to a role for GDF15 as a mitokine with important roles in the pathophysiology and possibly therapeutics of MASLD. Trial registration ClinicalTrials.gov NCT03986684, NCT04430946. [ABSTRACT FROM AUTHOR]

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = −0.27 and −0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations. [ABSTRACT FROM AUTHOR]

Objective To conduct a multicenter case series characterizing the clinical characteristics at presentation and pancreatic volume changes of patients with checkpoint inhibitor-associated autoimmune diabetes (CIADM). Research Design and Methods Electronic medical records were reviewed with 36 consecutive patients identified with CIADM, as defined by (1) previous immune checkpoint inhibitor (ICI) therapy, (2) new-onset hyperglycemia (blood glucose level ≥ 11.1 mmol/L and/or glycosylated hemoglobin ≥ 6.5%), and (3) insulin deficiency [C-peptide <0.4 nmol/L or diabetic ketoacidosis (DKA)] within 1 month of presentation. Pancreatic volume was available and measured using computed tomography volumetry for 17 patients with CIADM and 3 sets of control patients: 7 with ICI-related pancreatitis, 13 with asymptomatic ICI-related lipase elevation, and 11 ICI-treated controls for comparison. Results All patients had either anti-programmed cell death protein 1 or anti-programmed cell death ligand 1 therapy. Median time from ICI commencement to CIADM diagnosis was 15 weeks. At presentation, 25 (69%) had DKA, 27 (84%) had low C-peptide, and, by 1 month, 100% had low C-peptide. Traditional type 1 diabetes autoantibodies were positive in 15/35 (43%). Lipase was elevated in 13/27 (48%) at presentation. In 4 patients with longitudinal lipase testing, elevated levels peaked 1 month prior to CIADM diagnosis. Pancreatic volume was lower pre-ICI in CIADM patients compared with controls and demonstrated a mean decline of 41% from pretreatment to 6 months post-CIADM diagnosis. Conclusion Pronounced biochemical and radiologic changes occur during CIADM pathogenesis. Rapid loss of C-peptide is a distinct characteristic that can be used to aid diagnosis as autoantibodies are often negative. [ABSTRACT FROM AUTHOR]

Objective Zinc transporter 8 autoantibodies (ZNt8A) are 1 of the 4 main autoantibodies used for the diagnosis of type 1 diabetes (T1D), with glutamic acid decarboxylase autoantibodies (GADA), islet antigen-2 autoantibodies (IA-2A), and insulin autoantibodies (IAA). The objective of this study is to evaluate the diagnostic efficiency of these autoantibodies for the diagnosis of T1D in pediatric patients. Methods A retrospective analysis of patients under 16 years of age with suspected T1D was made between June 2020 and January 2021. A total of 80 patients were included in the study, with 1 sample per patient. Subjects were classified according to diagnosis. Results Of the subjects included in the study, 50 developed T1D. The diagnostic efficacy was IA-2A (cutoff ≥ 28 U/L) sensitivity 0.26 (95% CI: 0.14-0.38) and specificity 0.97 (95% CI: 0.79-1.0); GADA (cutoff ≥ 17 U/mL) sensitivity 0.40 (95% CI: 0.26-0.54) and specificity 0.87 (95% CI: 0.75-0.99); ZnT8A (cut off ≥ 15 U/L) sensitivity 0.62 (95% CI: 0.49-0.75) and specificity 0.97 (95% CI: 0.90-1.0). ZnT8A obtained the most significantly global diagnostic accuracy (0.75), and GADA with ZnT8A showed the highest correlation. Conclusion The results obtained indicate a higher efficiency of anti-ZnT8 autoantibodies for the diagnosis of T1D in pediatric patients. Clinical efficiency of diabetic autoantibodies is method and assay dependent and influences combined diagnostic strategies. [ABSTRACT FROM AUTHOR]

Investigation of biological systems often requires reconstruction of an unobservable continuous process from discrete time-series data sampled from a related process or processes. When the reconstructed process cannot be validated with experimental data, it is particularly important to quantify the uncertainty on the inferred process, and new methodologies are needed to support both the inference and uncertainty quantification. This work derives a novel statistical model that combines an established differential model of intra- and extravascular C-peptide dynamics with a Gaussian process model of insulin secretion rate (ISR) in order to provide clinical measures of betacell function with quantified uncertainty. These measures are computed from the ISR that is inferred from measured C-peptide data. The model is first validated using synthetic data, and then applied to oral glucose tolerance test (OGTT) data from youth participants with and without cystic fibrosis (CF). Because CF is characterized by scarring and fibrosis of the pancreas, impairment of beta-cell function, rather than reduced insulin sensitivity, is implicated in the early etiology of CF-related diabetes (CFRD). ISR-derived measures of beta-cell function show worsening beta-cell function from healthy control to CF to CFRD groups consistent with previous reports on dysglycemia in CF. However, the model additionally allows uncertainty in the data to be propagated to ISR and ISRderived measures of beta-cell function. These results provide insight into uncertainty in ISR-derived measures of beta cell function, characterize interindividual variability in CFRD etiology, and provide novel metrics to quantify the pathogenesis of CFRD. [ABSTRACT FROM AUTHOR]

This article explores the topic of Latent Autoimmune Diabetes in Adults (LADA), a form of diabetes that combines characteristics of both type 1 and type 2 diabetes. The article emphasizes the need for standardized diagnostic criteria and recommends autoantibody testing for newly diagnosed type 2 diabetes patients. The management of LADA is still uncertain, and further research is necessary to determine the most effective interventions. The article also acknowledges the variability in the progression and long-term outcomes of LADA patients. The authors call for more scientific research and international collaborations to address the unanswered questions surrounding LADA and ultimately benefit those affected by the condition. [Extracted from the article]

Aim: To compare the efficacy and safety of saxagliptin/dapagliflozin and insulin glargine in people with latent autoimmune diabetes in adults (LADA). Methods: In this phase 2b multicentre, open‐label, comparator‐controlled, parallel‐group, non‐inferiority study, we randomly assigned 33 people with LADA who had a fasting C‐peptide concentration ≥0.2 nmol/L (0.6 ng/mL) to receive 1‐year daily treatment with either the combination of saxagliptin (5 mg) plus dapagliflozin (10 mg) or insulin glargine (starting dose: 10 IU), both on top of metformin. The primary outcome was the 2‐h mixed meal‐stimulated C‐peptide area under the curve (AUC), measured 12 months after randomization. Secondary outcomes were glycated haemoglobin (HbA1c) levels, change in body mass index (BMI), and hypoglycaemic events. Results: In the modified intention‐to‐treat analysis, the primary outcome was similar in participants assigned to saxagliptin/dapagliflozin or to insulin glargine (median C‐peptide AUC: 152.0 ng*min/mL [95% confidence interval {CI} 68.2; 357.4] vs. 122.2 ng*min/mL [95% CI 84.3; 255.8]; p for noninferiority = 0.0087). Participants randomized to saxagliptin/dapagliflozin lost more weight than those randomized to insulin glargine (median BMI change at the end of the study: −0.4 kg/m2 [95% CI −1.6; −0.3] vs. +0.4 kg/m2 [95% CI −0.3; +1.1]; p = 0.0076). No differences in HbA1c or in the number of participants experiencing hypoglycaemic events were found. Conclusions: Saxagliptin/dapagliflozin was non‐inferior to glargine in terms of β‐cell function in this 12‐month, small, phase 2b study, enrolling people with LADA with still viable endogenous insulin production. Weight loss was greater with saxagliptin/dapagliflozin, with no differences in glycaemic control or hypoglycaemic risk. [ABSTRACT FROM AUTHOR]

C‐peptide, a byproduct of insulin synthesis believed to be biologically inert, is emerging as a multifunctional molecule. C‐peptide serves an anti‐inflammatory and anti‐atherogenic role in type 1 diabetes mellitus (T1DM) and early T2DM. C‐peptide protects endothelial cells by activating AMP‐activated protein kinase α, thus suppressing the activity of NAD(P)H oxidase activity and reducing reactive oxygen species (ROS) generation. It also prevents apoptosis by regulating hyperglycemia‐induced p53 upregulation and mitochondrial adaptor p66shc overactivation, as well as reducing caspase‐3 activity and promoting expression of B‐cell lymphoma‐2. Additionally, C‐peptide suppresses platelet‐derived growth factor (PDGF)‐beta receptor and p44/p42 mitogen‐activated protein (MAP) kinase phosphorylation to inhibit vascular smooth muscle cells (VSMC) proliferation. It also diminishes leukocyte adhesion by virtue of its capacity to abolish nuclear factor kappa B (NF‐kB) signaling, a major pro‐inflammatory cascade. Consequently, it is envisaged that supplementation of C‐peptide in T1DM might ameliorate or even prevent end‐organ damage. In marked contrast, C‐peptide increases monocyte recruitment and migration through phosphoinositide 3‐kinase (PI‐3 kinase)‐mediated pathways, induces lipid accumulation via peroxisome proliferator‐activated receptor γ upregulation, and stimulates VSMC proliferation and CD4+ lymphocyte migration through Src‐kinase and PI‐3K dependent pathways. Thus, it promotes atherosclerosis and microvascular damage in late T2DM. Indeed, C‐peptide is now contemplated as a potential biomarker for insulin resistance in T2DM and linked to increased coronary artery disease risk. This shift in the understanding of the pathophysiology of diabetes from being a single hormone deficiency to a dual hormone disorder warrants a careful consideration of the role of C‐peptide as a unique molecule with promising diagnostic, prognostic, and therapeutic applications. [ABSTRACT FROM AUTHOR]

Background: The prevalence of obesity has increased in patients with type 1 diabetes (T1D) and latent autoimmune diabetes of the adult (LADA), limiting the use of clinical features such as the body mass index for its differentiation with type 2 diabetes (T2D). Additionally, some patients with maturity-onset diabetes of the young (MODY) or LADA are misdiagnosed as having T2D. The evaluation of autoantibodies and genetic testing are not fully available. We aimed to evaluate the utility of a widely available and less expensive diagnostic tool such as C-peptide to differentiate between T1D, T2D, MODY, and LADA. Methods: Our study included 38 patients with T1D, 49 with T2D, 13 with MODY, and 61 with LADA. We recorded anthropometric measurements, biochemical profiles, and antidiabetic treatment and determined C-peptide, anti-GAD65, and anti-IA2 antibodies. Results: C-peptide concentration differed significantly among populations (T1D: 0.2 ng/mL; T2D: 2.4 ng/mL; MODY: 1.14 ng/mL; LADA: 1.87 ng/mL). Through a ROC curve, we observed that the C-peptide cut-off point of 0.95 ng/mL allows differentiation between T1D and T2D (sensitivity 82%, specificity 77%); 0.82 ng/mL between T1D and LADA (sensitivity 82%, specificity 77%); and 1.65 ng/mL between T2D and MODY (sensitivity 72%, specificity 72%). Conclusions: C-peptide is useful for the diagnostic differentiation of patients with type 1, type 2 diabetes, MODY, and LADA. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia, an age-related disorder characterized by loss of skeletal muscle mass and function, is recently recognized as a complication in elderly patients with type 2 diabetes mellitus (T2DM). Skeletal muscles play a crucial role in glycemic metabolism, utilizing around 80% of blood glucose. Accordingly, we aimed to explore the relationship between glucose metabolism and muscle mass in T2DM. Methods: We employed the AWGS 2019 criteria for diagnosing low muscle mass and 1999 World Health Organization (WHO) diabetes diagnostic standards. This study included data of 191 individuals aged 60 and above with T2DM of Shanghai Pudong Hospital from November 2021 to November 2022. Fasting C-peptide (FPCP), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG) and postprandial 2-hour C-peptide (PPCP), glycated hemoglobin A1c (HbA1c), glycated albumin (GA), serum lipids spectrum, renal and hepatic function, hemoglobin, and hormone were measured. Based on the findings of univariate analysis, logistic regression and receiver operating characteristic (ROC) curves were established. Results: Participants with low muscle mass had significantly lower alanine and aspartate aminotransferase, and both FPCP and PPCP levels (P < 0.05). Compared with those without low muscle mass, low muscle mass group had significantly higher FPG, HbA1c, GA levels (P < 0.05). Body fat (BF, OR = 1.181) was an independent risk factor for low muscle mass. PPCP (OR = 0.497), BMI (OR = 0.548), and female (OR = 0.050) were identified as protective factors for low skeletal muscle. The AUC of BMI was the highest, followed by the PPCP, gender and BF (0.810, 0.675, 0.647, and 0.639, respectively), and the AUC of the combination of the above four parameters reached 0.895. Conclusions: In this cross-sectional study, BMI, Female, and PPCP associated with T2DM were protective factors for low muscle mass. BF was associated with T2DM and risk factor for low muscle mass. [ABSTRACT FROM AUTHOR]

The classification of diabetes into type-1 (T1D) and type-2 (T2D) is a critical step in tailoring effective treatment strategies. This distinction relies on a nuanced evaluation of clinical and biochemical features. While age at diagnosis, autoimmune markers, and beta-cell function are among the crucial clinical parameters, biochemical indicators like C-peptide levels and antibody analyses play a pivotal role. This review comprehensively examines the utility of these features in accurately categorizing individuals into T1D and T2D subtypes, providing valuable insights for clinical practice. This scoping review systematically analyses 32 studies aimed at classifying T1D and T2D using various predictor variables. Clinical parameters including family history of diabetes, age at diagnosis, sex, history of insulin use, percent desirable weight or body mass index, waist, and blood pressure emerge as pivotal diagnostic tools. C-peptide measures, encompassing urinary C-peptide to creatinine ratio (UCPCR), and serum fasting and stimulated C-peptide levels further augment classification. Biochemical markers beyond C-peptide, such as serum level of adiponectin, triglycerides (TG), high-density lipoprotein–cholesterol (HDL-C), low-density lipoprotein (LDL-C), Total cholesterol, fasting and postprandial plasma glucose, and glycated hemoglobin (HbA1c), provide supplementary information for classification. Ketonuria and postglucagon or meal-stimulated C-peptide measurements contribute to nuanced classification, particularly in insulin-treated populations. Antibody analyses, particularly presence of GAD65, Zinc Transporter, and IA2 antibodies, highlight the autoimmune nature of T1D. In conclusion, this scoping review underscores the importance of a comprehensive approach that integrates clinical, biochemical, and immunological markers in accurately differentiating between T1D and T2D in clinical practice. [ABSTRACT FROM AUTHOR]

Purpose: Understanding factors that influence blood glucose levels in patients with type 2 diabetes mellitus (T2DM) is crucial for managing hyperglycemia. Currently, there is no standardized interpretation method for glucagon levels in oral glucose tolerance test (OGTT). This study aims to assess the relationship between the lowest glucagon/highest C-peptide ratio (Lglc/Hcp) in OGTT and glucose control levels in T2DM. Patients and Methods: Clinical data from 120 patients with T2DM were examined to compare the correlations of Lglc/Hcp and other pancreatic islet function-associated indices with fasting blood glucose (G0), glucose at 120 minutes in OGTT (G120), hemoglobin A1c (HbA1c), and the area under the glucose curve in OGTT (AUCglu). Additionally, the study investigated difference in Lglc/Hcp between patient groups based on the highest blood glucose levels (Hglu) in OGTT (Hglu ≥ 16.7 mmol/L vs Hglu < 16.7 mmol/L). Results: The generalized linear model suggested that Lglc/Hcp significantly correlated with G0 (B = 0.85, P < 0.001), G120(B = 1.46, P < 0.001), HbA1c (B = 0.67, P < 0.001), and AUCglu (B = 3.46, P < 0.001). This correlation surpassed C-peptide and glucagon-related parameters, even after adjusting for confounding factors. Furthermore, Lglc/Hcp was notably higher in patients with Hglu ≥ 16.7 mmol/L compared to those with Hglu < 16.7 mmol/L (Z = − 3.71, p < 0.001). Conclusion: Lglc/Hcp in OGTT closely relates to blood glucose control in patients with T2DM, potentially reflecting the overall pancreatic islet function in regulating glucose levels. Moreover, inhibiting glucagon secretion may be a crucial consideration for patients requiring insulin treatment. [ABSTRACT FROM AUTHOR]

Objective The perinatal period and in utero environment are important for fetal growth, development, and fetal programming. This study aimed to determine the effect of parental anthropometry and the maternal metabolic milieu on offspring adiposity at 2 years of age. Study Design This longitudinal birth cohort includes analysis of maternal (n = 337) and paternal (n = 219) anthropometry and maternal and fetal metabolic markers (n = 337), including glucose, homeostatic model of assessment (HOMA), C-peptide, and leptin from participants of the ROLO (the Randomized Control Trial of Low) pregnancy study, and their partners, to determine an association with offspring anthropometry at two years of age. Results Linear regression, when adjusted for confounders, indicated maternal and paternal anthropometry and was associated with offspring weight and length at 2 years of age. Maternal height was negatively associated with general adiposity in the total cohort of children (p = 0.002) and in female children (p = 0.006) and central adiposity in the total child cohort (p < 0.001). Paternal height was also negatively associated with general adiposity in all children (p = 0.002) and central adiposity in total (p = 0.023) and female children (p = 0.008). Maternal glucose, insulin resistance, and fetal C-peptide positively correlated with anthropometry in total, male, and female children. Conclusion Parental anthropometry in the perinatal period has a long-lasting effect on offspring anthropometry beyond the neonatal period. Maternal and fetal metabolic factors influence adiposity, and this extends beyond the perinatal period. Parental adiposity may play a significant role in early childhood adiposity and may be a target for interventions to decrease the risk of early childhood obesity. Key Points Parental height and weight were associated with offspring anthropometry and measures of offspring adiposity at 2 years of age. Maternal glucose, insulin resistance, and fetal C-peptide correlated with offspring anthropometry. Parental anthropometry has long-term effect on offspring adiposity and is seen at 2 years of age. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the prevalence and progression of fulminant type 1 diabetes (FT1D) in Qatar. Methods: This retrospective study analyzed consecutive index- diabetic ketoacidosis (DKA) admissions (2015–2020) among patients with new-onset T1D (NT1D) in Qatar. Results: Of the 242 patients, 2.5% fulfilled the FT1D diagnostic criteria. FT1D patients were younger (median-age 4-years vs.15-years in classic-T1D). Gender distribution in FT1D was equal, whereas the classic-T1D group showed a female predominance at 57.6% (n = 136). FT1D patients had a mean C-peptide of 0.11 ± 0.09 ng/ml, compared to 0.53 ± 0.45 ng/ml in classic-T1D. FT1D patients had a median length of stay (LOS) of 1 day (1-2.2) and a DKA duration of 11.25 h (11–15). The median (length of stay) LOS and DKA duration in classic-T1D patients were 2.5 days (1-3.9) and 15.4 h (11–23), respectively. The FT1D subset primarily consisted of moderate (83.3%) and severe 916.7%) DKA, whereas classic T1D had 25.4% mild, 60.6% moderate, and 14% severe DKA cases. FT1D was associated with a higher median white cell count (22.3 × 103/uL) at admission compared to classic T1D (10.6 × 103/uL). ICU admission was needed for 66.6% of FT1D patients, compared to 38.1% of classic-T1D patients. None of the patients in the FT1D group had mortality, while two died in the classic-T1D group. Conclusion: This is the first study establishing the existence of FT1D in ME, which presented distinctively from classic-T1D, exhibiting earlier age onset and higher critical care requirements. However, the clinical outcomes in patients with FT1D seem similar to classic T1D. [ABSTRACT FROM AUTHOR]

Background. A−β+ ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved β-cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at "T2D" onset and determined the prevalence and characteristics of pediatric A−β+ KPD within this cohort. Methods. We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the latter group, we identified patients with A−β+ KPD using criteria of the Rare and Atypical Diabetes Network (RADIANT) and defined its prevalence and characteristics. Results. Mean age at diagnosis was 13.7 ± 2.4 years: 63% female; 59% Hispanic, 29% African American, 9% non-Hispanic White, and 3% other. Fifty-six (7.8%) presented with DKA at diagnosis and lacked islet autoantibodies. Children presenting with DKA were older and had lower C-peptide and higher glucose concentrations than those without DKA. Twenty-five children with DKA (45%) met RADIANT A−β+ KPD criteria. They were predominantly male (64%), African American or Hispanic (96%), with substantial C-peptide (1.3 ± 0.7 ng/mL) at presentation with DKA and excellent long-term glycemic control (HbA1c 6.6% ± 1.9% at follow-up (median 1.3 years postdiagnosis)). Conclusions. In children with a clinical phenotype of T2D and DKA at diagnosis, approximately half meet criteria for A−β+ KPD. They manifest the key characteristics of obesity, preserved β-cell function, male predominance, and potential to discontinue insulin therapy, similar to adults with A−β+ KPD. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: The aim of this work was to describe the phenotype of adults presenting with a first episode of diabetic ketoacidosis (DKA) in Cape Town, South Africa, and identify predictors of insulin independence at 12 and 60 months after presentation. Methods: A prospective, descriptive cohort study of all individuals, 18 years or older, presenting for the first time with DKA to four public-sector hospitals of the Groote Schuur Academic Health Complex was performed. Clinical, biochemical and laboratory data including GAD antibody and C-peptide status were collected at baseline. Insulin was systematically weaned and stopped in individuals who achieved normoglycaemia within the months after DKA. Individuals were followed for 12 months and then annually until 5 years after initial presentation with ketoacidosis. Results: Eighty-eight individuals newly diagnosed with diabetes when presenting with DKA were included and followed for 5 years. The mean ± SD age was 35±10 years and the median (IQR) BMI at diagnosis was 28.5 (23.3–33.4) kg/m2. Overall, 46% were insulin independent 12 months after diagnosis and 26% remained insulin independent 5 years after presentation. Forty-one participants (47%) tested negative for anti-GAD and anti-IA-2 antibodies and had C-peptide levels >0.3 nmol/l; in this group, 68% were insulin independent at 12 months and 37% at 5 years after diagnosis. The presence of acanthosis nigricans was strongly associated with insulin independence (OR 27.1 [95% CI 7.2, 102.2]; p<0.001); a positive antibody status was associated with a lower likelihood of insulin independence at 12 months (OR 0.10 [95% CI 0.03, 0.36]; p<0.001). On multivariable analysis only acanthosis (OR 11.5 [95% CI 2.5, 53.2]; p=0.004) was predictive of insulin independence 5 years after diagnosis. Conclusions/interpretation: The predominant phenotype of adults presenting with a first episode of DKA in Cape Town, South Africa, was that of ketosis-prone type 2 diabetes. These individuals presented with obesity, acanthosis nigricans, negative antibodies and normal C-peptide and could potentially be weaned off insulin at follow-up. Classic type 1 diabetes (lower weight, antibody positivity, low or unrecordable C-peptide levels and long-term insulin dependence) was less common. The simple clinical sign of acanthosis nigricans is a strong predictor of insulin independence at 12 months and 5 years after initial presentation. [ABSTRACT FROM AUTHOR]

Objective: The number of admissions for severe diabetic ketoacidosis (DKA) in children with newly diagnosed type 1 diabetes (T1D) increased during the coronavirus disease 2019 pandemic. We aimed to investigate whether there has been a change in this situation in recent years. Materials and Methods: All children with T1D who were diagnosed in our tertiary hospital between 2019 and 2023 were included. Plasma insulin, C-peptide, hemoglobin A1c (HbA1c), and antibodies against thyroid peroxidase, thyroglobulin, insulin, islet cell, glutamic acid decarboxylase, tissue transglutaminase IgA, and endomysium IgA were measured. Results: The frequency of moderate–severe acidosis at admission, which increased after pandemic period compared to the pre-pandemic period, returns to its previous levels over time but still shows a statistical difference compared to the pre-pandemic period (P = .012). Age, blood gas pH and HCO3 level, C-peptide, HbA1c, and length of stay of children at the time of admission were compared year by year (years 2019-2023). No statistical differences were observed (P = .509, P = .181, P = .069, P = .469, P = .346, P = .946), respectively. A significant difference was observed in venous glucose (P < .001) and insulin (P = .001) according to years. Also, no significant difference was found about the degree of acidosis according to age (P = .334). Conclusion: Although the frequency of DKA in children with newly-diagnosed T1D increased in the first years of the pandemic, it has been decreasing over the years toward pre-pandemic levels. The frequency of DKA is still higher than the pre-pandemic period. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is an autoimmune disease initiated by genetic predisposition and environmental influences, which result in the specific destruction of insulin‐producing pancreatic β‐cells. Currently, there are over 1.6 million cases of T1D in the United States with a worldwide incidence rate that has been increasing since 1990. Here, we examined the effect of Cornus officinalis (CO), a well‐known ethnopharmacological agent, on a T1D model of the non‐obese diabetic (NOD) mouse. A measured dose of CO extract was delivered into 10‐week‐old NOD mice by oral gavage for 15 weeks. T1D incidence and hyperglycemia were significantly lower in the CO‐treated group as compared to the water gavage (WT) and a no handling or treatment control group (NHT) following treatment. T1D onset per group was 30%, 60% and 86% for the CO, WT and NHT groups, respectively. Circulating C‐peptide was higher, and pancreatic insulitis was decreased in non‐T1D CO‐treated mice. Our findings suggest that CO may have therapeutic potential as both a safe and effective interventional agent to slow early stage T1D progression. [ABSTRACT FROM AUTHOR]

Aims/Introduction: To evaluate the relative contributions of the area under the Cpeptide curve (AUCC) in diabetic retinopathy (DR) during an oral glucose tolerance test and C-peptide release test in patients with type 2 diabetes. Materials and Methods: We retrospectively analyzed the data of 969 patients. Their general characteristics were retrieved. A series of parameters for assessing pancreatic β-cells function, such as the AUCC for six time periods: 0-60 min (AUCC0-60), 0-120 min (AUCC0-120), 0-180 min (AUCC0-180), 60-120 min (AUCC60-120), 60-180 min (AUCC60-180) and 120-180 min (AUCC120-180); the area under the glucose-time curve for six time periods: 0-60 min (AUCG0-60), 0-120 min (AUCG0-120), 0-180 min (AUCG0-180), 60-120 min (AUCG60-120), 60-180 min (AUCG60-180) and 120-180 min (AUCG120-180) and their related indexes, were calculated through 0-180 min oral glucose tolerance test and C-peptide release test. We used univariate analysis to examine the potential factors affecting DR. Spearman's correlation was used to analyze the correlation between AUCC-related indexes and DR. The logistic regression model was used to investigate AUCC and its related indexes' contribution to incidence DR. A smooth curve fitting model was used to determine the correlation, non-linear relationship, and threshold effect between AUCC and DR. Results: Of the 969 patients with type 2 diabetes, 469 (48.40%) and 500 (51.60%) were classified as the DR group and non-DR group. Compared with the non-DR group, the DR patients had lower AUCC and AUCC/AUCG. Spearman's correlation analysis showed that AUCC-related indexes were all negatively correlated with DR. The logistic regression analysis determined that there were associations between AUCC and DR in the adjusted models. The odds ratio values of AUCC0-60, AUCC0-120, AUCC0-180, AUCC0-60/AUCG0-60, AUCC0-120/AUCG0-120, AUCC0-180/AUCG0-180, AUCC60-120, AUCC60-180, AUCC120-180, AUCC60-120/AUCG60-120, AUCC60-180/AUCG60-180 and AUCC120-180/AUCG120-180 were 0.817 (0.750, 0.890), 0.925 (0.895, 0.955), 0.951 (0.932, 0.970), 0.143 (0.060, 0.340), 0.194 (0.093, 0.406), 0.223 (0.116, 0.427), 0.886 (0.842, 0.933), 0.939 (0.915, 0.963), 0.887 (0.846, 0.930), 0.253 (0.133, 0.479), 0.282 (0.160, 0.497) and 0.355 (0.220, 0.573), respectively. AUCC showed a non-linear relationship with DR, with an inflection point. The inflection points of AUCC180/AUCG180, AUCC60-120, AUCC60-180, AUCC120-180, AUCC60-120/AUCG60-120, AUCC60-180/AUCG60-180, AUCC120-180/AUCG120-180 and DR were 17.51, 0.542, 6.6, 15.7, 8.23, 0.534, 0.593 and 0.808 (P < 0.0001). When the indexes related to the AUCC were less than the inflection point value, they were significantly negatively associated with DR. Conclusions: The indexes related to the AUCC for six time periods during an oral glucose tolerance test and C-peptide release test was closely associated with the incidence to DR in patients with type 2 diabetes. AUCC has the added advantage of being a cheap and convenient risk assessment over traditional ophthalmic screening. [ABSTRACT FROM AUTHOR]

The applicability of a UK‐validated genetic risk score (GRS) was assessed in 158 participants in the Fremantle Diabetes Study Phase II diagnosed between 20 and <40 years of age with type 1 or type 2 diabetes or latent autoimmune diabetes of adults (LADA). For type 1 versus type 2/LADA, the area under the receiver operating characteristic curve (AUC) was highest for serum C‐peptide (0.93) and lowest for the GRS (0.66). Adding age at diagnosis and body mass index to C‐peptide increased the AUC minimally (0.96). The GRS appears of modest diabetes diagnostic value in young Australians. [ABSTRACT FROM AUTHOR]

Medicinal plants used in the traditional system are the ideal therapeutic candidates for diabetes mellitus. In the present study, we aimed to identify the therapeutic potential of polyphenol from Acacia jacquemontii (AJ). In vitro, we study the characterization (HPLC) of AJ extracts, antioxidant, antidiabetic, and anti-inflammatory activities.In an in-vivo study, Wistar rats were grouped into normal control (NC), diabetic control (DC), glibenclamide (GL) treated, AJ n-hexane extract (AJHE) at a dose of 250 mg/kg, and AJ methanol extract (AJME) at a dose of 250 mg/kg treated groups. Glibenclamide was used as a reference drug and we evaluated the effect of AJ extracts on glycemic indicators. AJ extracts showed the presence of certain flavonoids and phenolic acids. From our results, a significant quantity of total flavonoid and total phenolic contents were observed. AJ extracts showed promising antioxidant effects (FRAP, OH radical scavenging activity), α-glucosidase (AJME: 53.2%, and AJHE: 59.2%), DPP-IV, LOX, and HYA inhibitory activities. AJ extracts significantly improved the biological markers including plasma insulin, HOMA-β, and serum C-peptide levels as well as normalized carbohydrate metabolizing enzyme levels in alloxanized diabetic rats. Histopathological examination demonstrated the hypoglycemic properties of AJ through the regeneration of β-cell in the pancreas. A. jacquemontii improved insulin signaling via up-regulation of genes i.e. ngn-3, Ins-1, Ins-2, and Pdx-1. The polyphenols in AJ are possibly the major contributors in in-vitro glucosidase, DPP-IV, LOX, and HYA inhibitory activities and maintenance of glucose homeostasis. [ABSTRACT FROM AUTHOR]

Aims: Determining diabetes type in children has become increasingly difficult due to an overlap in typical characteristics between type 1 diabetes (T1D) and type 2 diabetes (T2D). The Diabetes Study in Children of Diverse Ethnicity and Race (DISCOVER) programme is a National Institutes of Health (NIH)‐supported multicenter, prospective, observational study that enrols children and adolescents with non‐secondary diabetes. The primary aim of the study was to develop improved models to differentiate between T1D and T2D in diverse youth. Materials and Methods: The proposed models will evaluate the utility of three existing T1D genetic risk scores in combination with data on islet autoantibodies and other parameters typically available at the time of diabetes onset. Low non‐fasting serum C‐peptide (<0.6 nmol/L) between 3 and 10 years after diabetes diagnosis will be considered a biomarker for T1D as it reflects the loss of insulin secretion ability. Participating centres are enrolling youth (<19 years old) either with established diabetes (duration 3–10 years) for a cross‐sectional evaluation or with recent onset diabetes (duration 3 weeks–15 months) for the longitudinal observation with annual visits for 3 years. Cross‐sectional data will be used to develop models. Longitudinal data will be used to externally validate the best‐fitting model. Results: The results are expected to improve the ability to classify diabetes type in a large and growing subset of children who have an unclear form of diabetes at diagnosis. Conclusions: Accurate and timely classification of diabetes type will help establish the correct clinical management early in the course of the disease. [ABSTRACT FROM AUTHOR]

Background: Evidence of vitamin D status and cardiometabolic health in adults with type 2 diabetes mellitus (T2DM) is still limited. This study aimed to investigate the association between vitamin D status and cardiometabolic risk factors among adults with T2DM in Shenzhen, China. Methods: This cross-sectional study included 164 adults (aged =18 years) with T2DM who were hospitalized at Peking University Shenzhen Hospital from March 1, 2023, to May 31, 2023. Serum 25-hydroxyvitamin D [25(OH)D] concentration, the active marker of vitamin D, and three major cardiometabolic risk factors including blood pressure (BP), glucose metabolism-related indicators, and blood lipid profiles were collected. Vitamin D deficiency (VDD) was defined as 25(OH)D < 20 ng/mL. Correlation, Regression, and Logistic analysis were applied to verify the association among serum 25(OH)D concentration, VDD, and 11 cardiometabolic risk factors. Results: Median 25(OH)D concentration was 21.78 [interquartile range (IQR) =17.51-28.05] ng/mL. The prevalence of VDD was 40.24%. Serum 25(OH)D concentration was significantly negatively correlated with diastolic BP (DBP) and glycated hemoglobin A1c (HbA1c) rather than systolic BP, plasma glucose, plasma C-peptide, and blood lipid profiles among adults with T2DM in both correlation and linear regression analysis. Furthermore, the adjusted odd ratio for poor DBP control (=90 mmHg) of T2DM patients with VDD was 3.164 (95% confidence interval=1.303, 7.683; P=0.011) compared to those without VDD. Conclusion: In China, VDD was highly prevalent among adults with T2DM and associated with greater cardiovascular risk factors, especially with increased chances of uncontrolled DBP. These findings suggest that vitamin D levels should be monitored in T2DM patients, especially those with high DBP. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to determine the residual C-peptide level and to explore the clinical significance of preserved C-peptide secretion in glycemic control in Chinese individuals with type 1 diabetes (T1D). Research design and methods: A total of 534 participants with T1D were enrolled and divided into two groups, low--C-peptide group (fasting C-peptide ≤10 pmol/L) and preserved--C-peptide group (fasting C-peptide >10 pmol/L), and clinical factors were compared between the two groups. In 174 participants who were followed, factors associated with C-peptide loss were also identified by Cox regression. In addition, glucose metrics derived from intermittently scanned continuous glucose monitoring were compared between individuals with low C-peptide and those with preserved C-peptide in 178 participants. Results: The lack of preserved C-peptide was associated with longer diabetes duration, glutamic acid decarboxylase autoantibody, and higher daily insulin doses, after adjustment {OR, 1.10 [interquartile range (IQR), 1.06--1.14]; OR, 0.46 (IQR, 0.27--0.77); OR, 1.04 (IQR, 1.02--1.06)}. In the longitudinal analysis, the percentages of individuals with preserved C-peptide were 71.4%, 56.8%, 71.7%, 62.5%, and 22.2% over 5 years of follow-up. Preserved C-peptide was also associated with higher time in range after adjustment of diabetes duration [62.4 (IQR, 47.3--76.6) vs. 50.3 (IQR, 36.2--63.0) %, adjusted P = 0.003]. Conclusions: Our results indicate that a high proportion of Chinese patients with T1D had preserved C-peptide secretion. Meanwhile, residual C-peptide was associated with favorable glycemic control, suggesting the importance of research on adjunctive therapy to maintain b-cell function in T1D. [ABSTRACT FROM AUTHOR]

Context The impact of insulin, particularly exogenous hyperinsulinemia, on insulin secretion in humans is debated. Objective We assessed the effects of exogenous hyperinsulinemia on insulin secretion and whether the response is altered in insulin resistance associated with obesity. Methods Insulin secretion rates (ISRs) during euglycemic hyperinsulinemic clamp studies (52 volunteers) were calculated using a model that employs plasma C-peptide concentrations. One study involved a 2-step insulin clamp and the other study was a single step insulin clamp. For both studies the goal was to achieve plasma glucose concentrations of 95 mg/dL during the clamp irrespective of fasting glucose concentrations. The percent change in ISR from fasting to the end of the insulin clamp interval was the main outcome. Linear regression and analysis of covariance were used to test for the effects of insulin on ISR and to test for group differences. Results ISR was greater in obese volunteers (P <.001) under fasting and hyperinsulinemic clamp conditions. The change in plasma glucose from baseline to the end of the insulin clamp interval was highly correlated with the change in ISR (r = 0.61, P <.001). From baseline to the end of the clamp we observed a 27% (SD 20) suppression of ISR. The participants who underwent a 2-step insulin clamp had greater suppression of ISR during the second step than the first step (P <.001). The proportional suppression of ISR during euglycemic hyperinsulinemia was not different between nonobese and obese groups (P =.19). Conclusion Hyperinsulinemia suppresses endogenous insulin secretion and the relative change in insulin secretion produced by exogenous insulin did not differ between nonobese and obese people. [ABSTRACT FROM AUTHOR]