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C-peptide is an equimolar by-product of insulin biosynthesis. It is used clinically to assess insulin secretion and differentiate types of diabetes. However, the lack of standardization across assays limits its broader application. This study aimed to examine discrepancies between the leading C-peptide measurement methods used in clinical laboratories and propose a solution to reduce them based on a complete traceability chain.Two sets of serum samples were distributed to 10 manufacturers of C-peptide assays. The first set (A, n=20) was analyzed independently by each manufacturer, who then returned their results to us. Subsequently, we sent out the second set (B, n=20) along with the reference values for set A. For set B, each manufacturer provided both non-calibrated and recalibrated values for each sample. The recalibration was performed according to each manufacturer’s internal standard protocols. We assessed how recalibration affected agreement between methods and alignment with the reference method. Non-parametric statistical approaches, including Passing-Bablok regression, level of agreement, and standard deviation analysis, were applied to compare data from multiple perspectives.Despite most manufacturers using the same WHO C-peptide calibrator material, significant disagreement was observed between methods prior to recalibration. Recalibration with matrix-appropriate serum samples reduced the discordance among assays, bringing them closer to the reference method. Overall, recalibration reduced both systematic bias and individual assay disagreement.These findings underscore the importance of appropriate calibration schemes to improve agreement across C-peptide assays, enhancing the accuracy of C-peptide testing for clinical practice. [ABSTRACT FROM AUTHOR]

Background: Mass spectrometry (MS) methods exhibit higher accuracy and comparability in measuring serum C-peptide concentrations than immunoassays. We developed and validated a novel isotope dilution-ultraperformance liquid chromatography-tandem MS (IDUPLC-MS/MS) assay to measure serum C-peptide concentrations. Methods: Sample pretreatment involved solid-phase extraction, ion-exchange solid-phase extraction, and derivatization with 6-aminoquinolyl-N-hydroxysuccinimidylcarbamate (Cayman Chemical, Ann Arbor, Michigan, USA). We used an ExionLC UPLC system (Sciex, Framingham, MA, USA) and a Sciex Triple Quad 6500+ MS/MS system (Sciex) for electrospray ionization in positive-ion mode with multiple charge states of [M+3H]3+ and multiple reaction monitoring transitions. The total run time was 50 mins, and the flow rate was 0.20 mL/min. We evaluated the precision, trueness, linearity, lower limit of quantitation (LLOQ), carryover, and matrix effects. Method comparison with electrochemiluminescence immunoassay (ECLIA) was performed in 138 clinical specimens. Results: The intra- and inter-run precision coefficients of variation were <5% and the bias values for trueness were <4%, which were all acceptable. The verified linear interval was 0.050-15 ng/mL, and the LLOQ was 0.050 ng/mL. No significant carryover or matrix effects were observed. The correlation between this ID-UPLC-MS/MS method and ECLIA was good (R=0.995, slope=1.564); however, the ECLIA showed a positive bias (51.8%). Conclusions: The developed ID-UPLC-MS/MS assay shows acceptable performance in measuring serum C-peptide concentrations. This will be useful in situations requiring accurate measurement of serum C-peptide in clinical laboratories. [ABSTRACT FROM AUTHOR]

Objective: Diabetic peripheral neuropathy (DPN) is a chronic complication of diabetes that can potentially escalate into ulceration, amputation and other severe consequences. The aim of this study was to construct and validate a predictive nomogram model for assessing the risk of DPN development among diabetic patients, thereby facilitating the early identification of high-risk DPN individuals and mitigating the incidence of severe outcomes. Methods: 1185 patients were included in this study from June 2020 to June 2023. All patients underwent peripheral nerve function assessments, of which 801 were diagnosed with DPN. Patients were randomly divided into a training set (n =711) and a validation set (n = 474) with a ratio of 6:4. The least absolute shrinkage and selection operator (LASSO) logistic regression analysis was performed to identify independent risk factors and develop a simple nomogram. Subsequently, the discrimination and clinical value of the nomogram was extensively validated using receiver operating characteristic (ROC) curves, calibration curves and clinical decision curve analyses (DCA). Results: Following LASSO regression analysis, a nomogram model for predicting the risk of DPN was eventually established based on 7 factors: age (OR = 1.02, 95%CI: 1.01 - 1.03), hip circumference (HC, OR = 0.94, 95%CI: 0.92 – 0.97), fasting plasma glucose (FPG, OR = 1.06, 95%CI: 1.01 - 1.11), fasting C-peptide (FCP, OR = 0.66, 95%CI: 0.56 - 0.77), 2 hour postprandial C-peptide (PCP, OR = 0.78, 95%CI: 0.72 – 0.84), albumin (ALB, OR = 0.90, 95%CI: 0.87 – 0.94) and blood urea nitrogen (BUN, OR = 1.08, 95%CI: 1.01 - 1.17). The areas under the curves (AUC) of the nomogram were 0.703 (95% CI 0.664-0.743) and 0.704 (95% CI 0.652-0.756) in the training and validation sets, respectively. The Hosmer–Lemeshow test and calibration curves revealed high consistency between the predicted and actual results of the nomogram. DCA demonstrated that the nomogram was valuable in clinical practice. Conclusions: The DPN nomogram prediction model, containing 7 significant variables, has exhibited excellent performance. Its generalization to clinical practice could potentially help in the early detection and prompt intervention for high-risk DPN patients. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients. Methods: This was a retrospective study in which thirty-two overweight/obese patients with PCOS (n = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated. Results: ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease. Conclusion: ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients. [ABSTRACT FROM AUTHOR]

Background: Prior studies indicated the positive effects of probiotics on glycemic regulation in patients with gestational diabetes mellitus (GDM). Nonetheless, the results remain inconclusive. To address this, we conducted an umbrella meta-analysis to evaluate the impact of probiotics on glycemic indicators in GDM. Methods: A comprehensive search was conducted on the PubMed and Scopus databases to identify all relevant meta-analyses of randomized clinical trials published until July 2024. The outcomes included serum hemoglobin A1C (HbA1c), fasting blood insulin (FBI), fasting blood sugar (FBS), homeostatic model assessment for insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), homeostatic model assessment of beta cell function (HOMA-B), C-peptide, and oral glucose tolerance test (OGTT). Standardized mean difference (SMD) was used to test the effects. Results: In total, 27 studies, comprising 33,378 participants, were included in the analysis. Probiotics resulted in a significant decrease in FBS (SMD: -0.39, 95% CI: -0.56 to -0.23), especially when administered for ≤ 7 weeks. Significant reductions were also observed in FBI (SMD: -1.99, 95% CI: -2.41 to -1.58), HOMA-IR (SMD: -0.61, 95% CI: -0.72 to -0.50), and HOMA-B (SMD: -24.58, 95% CI: -30.59 to -18.56). Moreover, supplementation with probiotics significantly improved QUICKI (SMD: 0.007, 95% CI: 0.004 to 0.01). There was significant evidence of heterogeneity and publication bias. No significant effects were observed on 1-h OGTT, 2-h OGTT, HbA1c, and C-peptide. No dose-specific effect was observed. Conclusions: Supplementation with probiotics could improve glycemic control in women with GDM. The effects of probiotics on HOMA-IR, HOMA-B, and fasting insulin were clinically important, while, their effect on FBS was not clinically important. [ABSTRACT FROM AUTHOR]

Objective: There is a notable absence of extensive Chinese studies involving monogenic congenital hyperinsulinism (CHI). The purpose of this large retrospective Chinese cohort with monogenic CHI from a national children's medical center was to analyze the genetic and clinical characteristics. Methods: We compared clinical characteristics grouped by genotypes based on CHI‐targeted next‐generation sequencing (tNGS) and performed subgroup analyses by onset time. Results: Totally, 121 non‐consanguineous patients were enrolled. Among them, 79 patients (65.3%) had variants in ATP‐sensitive potassium channel (KATP) genes (62 heterozygotes and 17 compound heterozygotes), 35 (28.9%) in glutamate dehydrogenase 1 (GLUD1), and 7 (5.8%) in rare genes (hydroxyacyl‐CoA dehydrogenase [HADH], glucokinase [GCK], and hepatocyte nuclear factor 4 alpha [HNF4A]). Ten patients had ATP binding cassette subfamily C member 8 (ABCC8) variants (p.G111R), and 12 had GLUD1 variants (p.S498L), suggesting two potential founder variants. Three ABCC8 variants (p.G1478R, p.L580_S581insFASL, and p.S986 ∗) and two HNF4A variants (p.R63W and p.V382I) were previously reported to be associated with diabetes. Non‐surgical treatment was effective in 65.9% of patients with KATP variants, while in 100% of those with non‐KATP variants. For the subgroup of KATP variants, neonatal‐onset patients tended to present with mild symptoms (67.9% versus 19.3%), had a higher proportion of surgical intervention (24.5% versus 3.8%), and displayed higher levels of serum insulin and C‐peptide than non‐neonatal onset ones (p < 0.001). Conclusion: The absence of homozygous variants in KATP genes and a quite higher proportion of GLUD1 variants than previous cohorts, may explain a high response rate of non‐surgical treatment in this study. Surgery might be considered for neonatal‐onset children, especially when KATP variants were discovered but not for those carried variants reported to cause diabetes in later life. While expanding the genotypic spectrum, we also highlight the clinical significance of genetic screening. [ABSTRACT FROM AUTHOR]

Antigen-driven T-cell proliferation is often measured using fluorescent dye dilution assays, such as the CFSE-based proliferation assay. Dye dilution assays have been powerful tools to detect human CD4+ T-cell responses, particularly against autoantigens. However, it is not known how many cells within the proliferating population are specific for the stimulating antigen. Here we determined the frequency of CD4+ T cells specific for the stimulating antigen within the antigen-responsive population of CFSE-based proliferation assays. We compared CD4+ T-cell responses to a type 1 diabetes autoantigen (proinsulin C-peptide) and to a vaccine antigen (tetanus toxoid). The TCRs expressed by antigen-responsive CD4+ T cells were sequenced, and their antigen specificity was tested functionally by expressing them in a reporter T-cell line. Responses to C-peptide were weak, but detectable, in PBMC from individuals with T1D, whereas responses to tetanus toxoid were much stronger. The frequency of antigen-specific CD4+ T cells correlated with the strength of the response to antigen in the proliferation assay. However, antigen-specific CD4+ T cells were rare among antigen-responsive CD4+ T cells. For C-peptide, an average frequency of 7.5% (1%–11%, n = 4) of antigen-responsive CD4+ T cells were confirmed to be antigen specific. In the tetanus-toxoid-stimulated cultures, on average, 45% (16%–78%, n = 5) of the antigen-responsive CD4+ T cells were tetanus toxoid specific. These data show that antigen-specific CD4+ T cells are a minority of the cells that proliferate in response to antigen and have important implications for in vitro CD4+ T-cell proliferation assays. [ABSTRACT FROM AUTHOR]

Background: The prevalence of steatotic liver disease (SLD) in patients with type 2 diabetes (T2DM) exceeds 50%. This study aimed to investigate the clinical characteristics of SLD and liver fibrosis in Chinese patients with T2DM. Methods: Inpatients from 2021 to 2023 were included in the study. Fatty liver index (FLI) and fibrosis-4 (FIB-4) were calculated to assess hepatic steatosis and fibrosis respectively. Statistical analysis was completed by SPSS v25 and GraphPad Prism v8.0.1. Results: Of the 1466 participants, about one-third of the patients in T2DM-SLD group were diagnosed with liver fibrosis (LF), and the percentage of patients over 50 years old was 85.9%. Patients with SLD had higher levels of BMI, blood pressure, liver enzymes, fasting blood glucose (FBG), HbA1c, C-peptide, total cholesterol (TC) and triglyceride (TG) (P<0.05 for all). Patients with liver fibrosis had lower TC, TG, hemoglobin (Hb), erythrocyte count (RBC), leukocyte count (WBC) and platelet (PLT) levels (P<0.05 for all). Compared with simple T2DM and SLD-NLF (non-liver fibrosis) groups, for patients over 50 years old, the prevalence of coronary heart disease, stroke, tumor, and diabetic nephropathy was higher in patients with liver fibrosis. Liver fibrosis might be the risk factor of arterial stiffness, stroke, coronary heart disease and numbness based on multivariable logistic regression analysis. Conclusion: Hepatic steatosis and fibrosis were common in patients with T2DM. Liver fibrosis was relevant to many macrovascular and microvascular diabetic complications. [ABSTRACT FROM AUTHOR]

Loops in the axial channels of ClpAP and other AAA+ proteases bind a short peptide degron connected by a linker to the N- or C-terminal residue of a native protein to initiate degradation. ATP hydrolysis then powers pore-loop movements that translocate these segments through the channel until a native domain is pulled against the narrow channel entrance, creating an unfolding force. Substrate unfolding is thought to depend on strong contacts between pore loops and a subset of amino acids in the unstructured sequence directly preceding the folded domain. Here, we identify such contact sequences that promote grip for ClpAP and use ClpA structures to place these sequences within ClpA's two AAA+ rings. The positions and chemical nature of certain residues within an unstructured segment that are positioned to interact with the D2 ring have major positive effects on substrate unfolding, whereas segments located within the D1 ring have little consequence. Within the D2-bound segment, two short elements are critical for accelerating degradation; one is at the "top" of D2 and consists of at least two properly positioned nonslippery residues. In contrast, the second D2 element, which can be as short as one residue, is positioned to contact pore loops near the "bottom" of this ring. Comparison with similar studies for ClpXP reveals that positioning a wellgripped substrate sequence within the major unfoldase motor is more important than its proximity to the folded domain and that charged, polar, and hydrophobic residues all contribute favorable contacts to substrate grip. [ABSTRACT FROM AUTHOR]

Objective: Type 1 diabetes mellitus (T1DM) is a polygenic disease influenced by genetic, environmental, immunological factors.There are few studies regarding siblings with T1DM.We aimed to evaluate the presentation, diagnosis, follow-up, sociodemographic characteristics of sibling T1DM cases. Material and Methods: We retrospectively reviewed characteristics of sibling cases followed with T1DM between January 2005 and May 2017. Results: The prevalence of T1DM sibling diabetes in our clinic was 5.9%.We included 17 siblings (a total of 34 cases) who had diagnosis and follow-up data. One of the siblings was a twin.There were no statistically significant differences between the ages at diagnosis, presenting symptoms, duration of symptoms before diagnosis, glucose/C-peptide values at diagnosis, average HbA1c values in the first five years of follow-up, or hospitalization rates in the first five-years post-diagnosis between the first and second diagnosed siblings.Despite having a child diagnosed with T1DM, 23.6% of families had a second child diagnosed with diabetic ketoacidosis.Variations in antibody positivity were observed among siblings, there were no similarities between celiac disease, Hashimoto's thyroiditis.Vitamin D levels were significantly lower in siblings diagnosed secondarily. Conclusion: Our study is significant for being conducted at a reference center with a high number of diabetes patients under follow-up, for filling a gap in the literature with a detailed evaluation of sibling cases with T1DM.It serves as a comprehensive pilot study examining the manner, order of diagnosis, clinical, laboratory, and follow-up data of siblings with diabetes.There is a need for prospective studies with a larger number of sibling cases to further explore this topic. [ABSTRACT FROM AUTHOR]

Background • Non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions globally, particularly affecting individuals with type 2 diabetes mellitus (T2DM). Objective • Our study aims to elucidate the diagnostic value of fasting C-peptide in combination with insulin resistance for assessing hepatic fibrosis in patients with T2DM and comorbid NAFLD. Design • This was a retrospective study. Setting • The study was conducted at the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. Participants • The research involved 76 type 2 diabetes mellitus patients with nonalcoholic fatty liver disease, diagnosed at our hospital from April 2020 to October 2022. Patients were categorized into the non-progressive hepatic fibrosis group (n = 64) and progressive hepatic fibrosis group (n = 12) based on fibrosis-4 value. Interventions • General data, systolic/diastolic blood pressure, fasting plasma glucose, fasting C-peptide, fasting insulin, glycosylated hemoglobin, uric acid, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, aspartate transaminase, alanine transaminase, and γ-glutamyl transferase were collected. Insulin resistance was calculated using a designated formula. Primary Outcomes Measures • The predictive impact of fasting C-peptide in combination with insulin resistance was evaluated through receiver operating characteristic curves. Results • The age, body mass index, fasting C-peptide, fasting insulin, aspartate transaminase, and insulin resistance showed a significant increase in the progressive hepatic fibrosis group compared to the non-progressive group (P = .006, P = .014, P <.001, P < .001, P = .004, and P = .021). The combination's sensitivity demonstrated an elevation compared to fasting C-peptide or insulin resistance alone (P = .005). Conclusions • Fasting C-peptide in combination with insulin resistance proves to have a substantial predictive impact on hepatic fibrosis in type 2 diabetes mellitus patients with nonalcoholic fatty liver disease, holding valuable clinical diagnostic potential. [ABSTRACT FROM AUTHOR]

Background: Understanding how C-peptide levels in the umbilical cord can be used to predict when a diabetic mother's newborn will experience hypoglycemia is urgently needed. This study aimed to assess the role of umbilical cord C-peptide levels in the early prediction of hypoglycemia among neonates of diabetic mothers. Methods: We carried out this cross-sectional study on 52 singleton newborns born to diabetic mothersin the neonatal resuscitation room and obstetric operation room at Zagazig University Hospital. The umbilical cord C-peptide concentration was assessed via an enzyme-linked immunosorbent assay. Complete blood count, blood glucose level, insulin level, and glycated hemoglobin (HbA1C), were performed for neonates and mothers. Neonatal blood glucose was measured hourly three times. Results: A significant association was found between neonatal C-peptide levels and maternal premature rupture of membranes (p=0.013). Compared to normoglycemic neonates, hypoglycemic neonates had significantly higher C peptide levels (p<0.001). The best cut-off value of neonatal C-peptide for the prediction of neonatal hypoglycemia is =0.3685 ng/ml, with an area under the curve of 0.963, a sensitivity of 88.9%, a specificity of 88.4%, a positive predictive value of 61.5%, a negative predictive value of 97.4%, and accuracy of 88.5% (p<0.001). Conclusions: This study underscores the importance of monitoring umbilical cord C-peptide levels as a potential early predictor of neonatal hypoglycemia among infants born to diabetic mothers. [ABSTRACT FROM AUTHOR]

Aims/Hypotheses: To investigate the frequency and characteristics of partial remission in Swedish children with type 1 diabetes and whether the insulin delivery method, that is, continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDIs), affects incidence and duration of this period, 2007–2011. Factors that increase the proportion of subjects who enter partial remission and extend this period can improve long-term metabolic control and reduce the risk of severe hypoglycemia, improve quality of life, and, in the long run, reduce late complications. Methods: Longitudinal data from 2007 to 2020 were extracted from the Swedish National Quality Register (SWEDIABKIDS) with all reported newly diagnosed children. Data on C-peptide from the participants in the Better Diabetes Diagnosis study from 2007 to 2010 were used. The definition of partial remission was insulin dose–adjusted HbA1c: HbA1c (%) + [4 × total daily insulin dose (U/kg/day)] ≤9. Results: Of the 3887 patients, 56% were boys. More boys than girls were in partial remission throughout the follow-up period until 24 months after diabetes onset. Fewer children 0–6 years old had partial remission at 3 and 12 months but not at 24 months compared with older age-groups. A larger proportion of patients using CSII at 12 and 24 months remained in partial remission compared with those with MDI (37% vs. 33%, P = 0.02 and 31% vs. 27%, P = 0.01, respectively). The level of C-peptide was higher in the group with partial remission and mean HbA1c was lower (both P < 0.001). Partial remission at 12 months after diabetes onset was associated with CSII (odds ratio [OR]: 1.39, confidence interval [CI]:1.13, 1.71), shorter diabetes duration (OR: 0.80, CI: 0.76, 0.84), and male sex (OR: 1.23, CI: 1.04, 1.46). Conclusions/Interpretation: Insulin through MDI, longer duration of diabetes, and female sex were associated with lower frequency of partial remission. Use of CSII seems to contribute to longer partial remission among Swedish children with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Purpose: Alpelisib is a PI3K (Phosphoinositide 3-kinases) inhibitor used for breast cancer which develops hyperglycemia based on its action on glucose metabolism regulation. This study aims to identify potential risk factors predicting hyperglycemia development and the need for multiple treatments for hyperglycemia in patients receiving Alpelisib. Methods: Fourteen women diagnosed with metastatic hormone receptor-positive breast cancer carrying PI3K mutations who initiated treatment with Alpelisib were monitored through consultations in the Oncology and Endocrinology departments. Non-parametric ROC curves were generated to assess the need for three or more antidiabetic medications to achieve glycemic control. Results: The study population had a median age of 64 years (range:48–69) with a median body mass index (BMI) of 26.6 kg/m2 (range: 22.9–29.4). Overweight was observed in 35.7% of the participants and obesity in 21.4%. Fifty percent of the participants had prediabetes, and 85.7% developed hyperglycemia requiring pharmacological treatment, although none of them needed to discontinue treatment for this reason. Baseline C-peptide levels and BMI were associated with the number of antidiabetic drugs used (Spearman's Rho 0.553, p = 0.040; Spearman's Rho 0.581, p = 0.030, respectively). ROC curve analysis showed and area under the curve (AUC) of 0.819 for the variable risk profile (defined as baseline C-peptide >10.5 ng/ml and BMI > 27 kg/m2), whereas AUC values were 0.556 and 0.514 for HbA1c and baseline glucose, respectively, (p = 0.012). Conclusion: A joint follow-up by an Oncology department and a Diabetes Unit can prevent treatment discontinuation in patients under Alpelisib therapy. Baseline BMI and plasma C-peptide levels can predict an increased need for anti-hyperglycemic treatment. [ABSTRACT FROM AUTHOR]

Context: Congenital Hyperinsulinism (CHI) is associated with inappropriately high levels of C‐peptide in the context of hypoglycemia. Objective: We aimed to better clarify a diagnostic threshold value of C‐peptide for children presenting with CHI. Design: This was a retrospective case‐control analysis, examining all hypoglycemia screens, undertaken between 2009 and 2019 at a quaternary paediatrics unit. Plasma C‐peptide, insulin, free fatty acid (FFA) and B‐hydroxybutyrate (BHOB) concentrations in children diagnosed with CHI were compared with concentrations in children diagnosed with other conditions. Patients: All patients requiring hypoglycaemic screens at the quaternary children's hospital were analysed. Results: Median [C‐peptide] were statistically significantly different between CHI (147) and non‐CHI (72) patients, p < 0.05. The Youden Index indicated that a [C‐peptide] value of 291.5 pmol/L would give the greatest optimization of sensitivity (82%) and specificity (99%) for detecting CHI. Median [insulin] differed significantly between the cohorts with a level of 64 pmol/L for CHI patients compared with 0 pmol/L with non‐CHI patients (p < 0.01). Median [BOHB] was 0 μmol/L in CHI patients as compared with 2378 μmol/L for non‐CHI patients (p < 0.01). Median [FFA] levels were 1910 μmol/L in the non‐CHI cohort, compared with 0 in the CHI cohort (p < 0.01). Conclusions: This study suggests that a C‐peptide concentration greater than 291.5 pmol/L is diagnostic of CHI in children. C‐peptide appears to offer the greatest utility as a biochemical diagnostic test for CHI and could be prioritised for laboratory analysis. [ABSTRACT FROM AUTHOR]

Diabetes in the young has been traditionally defined as onset of diabetes below 35 years of age. In this age bracket, a variety of distinct types of diabetes might occur which poses a unique challenge in the diagnosis and management. Phenotypic features such as age of onset, presence of obesity and family history have traditionally been used in differentiating the various types of diabetes. With the increasing prevalence of obesity and T2DM in youth, these features have become less reliable in classifying diabetes in this age group. Along with detailed patient history and physical examination, biochemical parameters such as C-peptide and presence or absence of pancreatic autoantibodies (along with imaging studies for pancreatic pathology and genetic testing for monogenic forms of diabetes) are assuming greater importance in appropriate diagnosis and understanding the types of diabetes. C-peptide test which is a proxy for pancreatic beta cell function plays an important role in classifying type / subtypes of diabetes. When used appropriately it also helps in personalized approach to treatment and practice of Precision Diabetes.

الملخص: أهداف البحث: تعمل التمارين الرياضية على تحسين نسبة السكر في الدم بعد الأكل وحساسية الأنسولين لدى الأفراد المصابين بمرض السكري، ولكن تظل الكثافة المثلى لهذا التنظيم الأيضي غير واضحة. تهدف الدراسة الحالية إلى استكشاف تأثير كثافات التمارين المختلفة على مستويات الجلوكوز في الدم والأنسولين والببتيد سي لدى الأفراد المصابين بمرض السكري لتحديد الكثافة المثلى لتحسين هذه المؤشرات الأيضية. طريقة البحث: في هذه الدراسة المتقاطعة، شارك 25 فردا مصابا بمرض السكري في جلسات تمرين بأربع كثافات مختلفة بنسبة 50% و60% و70% و80% من أقصى معدل ضربات قلب متوقع باستخدام جهاز المشي. استمرت كل جلسة لمدة 30 دقيقة، بما في ذلك فترة إحماء لمدة 5 دقائق وفترة تهدئة لمدة 5 دقائق. تم جمع عينات الدم في أربع نقاط زمنية مميزة: أثناء الصيام، وقبل التمرين مباشرة، وبعد التمرين بـ 30 و60 دقيقة. تم تحليل هذه العينات لمعرفة مستويات الجلوكوز والأنسولين والببتيد سي. تم تقييم تأثيرات شدة التمرين على هذه المعلمات باستخدام تحليل التباين المتكرر، مع إجراء اختبارات لاحقة لتحديد الاختلافات المحددة بين الشدة. النتائج: كان متوسط أعمار المشاركين 34.88 عاما، ومتوسط طولهم 170 سم، ومؤشر كتلة الجسم 30.34 كجم/م2. لوحظ انخفاض كبير في مستويات الأنسولين والجلوكوز بعد التمرين بنسبة 70%. وعلى الرغم من ارتفاع مستويات الجلوكوز في الدم أثناء الصيام (110-115 مجم/ديسيلتر)، فقد لوحظ انخفاض كبير بعد 30 و60 دقيقة من التمرين. اقتربت مستويات الأنسولين من خط الأساس عند 70% من الشدة، من الصيام إلى 60 دقيقة بعد التمرين، مما يشير إلى استجابة إيجابية عند هذه الشدة. أظهرت مستويات الببتيد سي أيضًا تغييرات كبيرة، حيث جعل التمرين بنسبة 70% من الشدة أقرب إلى مستويات الصيام بعد 60 دقيقة من التمرين. الاستنتاجات: تسلط هذه الدراسة الضوء على أهمية شدة التمارين الرياضية في تحسين المعايير الأيضية لدى الأفراد المصابين بمرض السكري. وعلى وجه التحديد، كان 70% من الحد الأقصى لمعدل ضربات القلب المتوقع مفيدا، مما أدى إلى تحسين حساسية الأنسولين وتقليل خطر الإصابة بمرض السكري من مرحلة ما قبل السكري. Abstract: Objective: Exercise improves postprandial glycaemia and insulin sensitivity in individuals with prediabetes, but the optimal intensity for this metabolic regulation remains unclear. The current study aims to explore the impact of various exercise intensities on metabolic markers in prediabetic individuals to identify the optimal intensity for improving these indicators. Methods: In this crossover study, 25 prediabetic individuals participated in exercise sessions at 50 %, 60 %, 70 %, and 80 % intensities of their predicted maximum heart rate using a treadmill. Each session lasted for 30 min, including a 5-min warm-up and a 5-min cool-down period. Blood samples were collected at four distinct time points: during fasting, immediately before exercise, and 30 and 60 min post-exercise. These samples were analyzed for glucose, insulin, and C-peptide levels. The effects of exercise intensity on these parameters were evaluated using repeated measures ANOVA, with post hoc tests conducted to determine specific differences between the intensities. Results: The participants had an average age of 34.88 years, a mean height of 170 cm, and a BMI of 30.34 kg/m². A significant reduction in insulin and glucose levels post-exercise was observed at 70 % intensity (p ≤ 0.001). Despite high fasting blood glucose levels (110–115 mg/dL), significant reductions were noted at 30 and 60 min post-exercise (p ≤ 0.001). Insulin levels approached near baseline at 70 % intensity, from fasting (26.74 ± 20.83) to 60 min post-exercise (28.47 ± 20.79), indicating a positive response at this intensity. C-peptide levels also showed significant changes, with the 70 % intensity exercise bringing them closest to fasting levels by 60 min post-exercise. Conclusion: This study highlights the importance of exercise intensities in enhancing metabolic parameters in prediabetic individuals. Specifically, 70 % of the predicted maximum heart rate was beneficial, optimizing insulin sensitivity and potentially reducing the risk of progressing from prediabetes to diabetes.

Abstract Background In order to investigate microvascular complications in metabolic diseases, we aimed to investigate cerebral and peripheral microcirculation in relation to peripheral neuropathy and laboratory biomarkers in type 2 diabetes mellitus (T2DM) and obesity. Methods Based on the degree of neuropathy (NP), study participants (40 T2DM and 30 obese individuals) were classified into no-NP, mild-NP and severe-NP subgroups. After the injection of Technetium-99 m hexamethylpropylene amine oxime, both T2DM and obese participants underwent single-photon emission computed tomography/computed tomography ([99mTc]Tc-HMPAO SPECT/CT) and SPECT-only examinations to assess lower limb and brain perfusion; respectively. Peripheral nerve function was evaluated with a neurometer and glycaemic markers were measured from plasma in both groups. Results Compared to the obese individuals, lower extremity perfusion was significantly reduced in the diabetic subjects (p

Type 1 diabetes (T1D) is a chronic disease characterized by the immune-mediated destruction of the pancreatic beta cells responsible for insulin production. The secreted insulin and C-peptide are equimolar. Due to its longer half-life, C-peptide has become a safer means of assessing the pancreatic reserve. C-peptide levels were evaluated in a population of patients with T1D, focusing on the relationship between this variable and other factors. In addition, the influence of C-peptide on metabolic control and microvascular complications was investigated. This cross-sectional study included 95 patients who had been diagnosed with T1D at least five years earlier. These patients were evaluated using a clinical demographic survey, anthropometric data, laboratory tests, and fundoscopy. This study showed that 29.5% of patients had residual insulin secretion, which correlated directly with their age at diagnosis. No statistically significant differences in metabolic control or microvascular complications were observed between the C-peptide level groups. In addition, our results indicate that ancestry does not influence the persistence of residual C-peptide function in our highly mixed population. It is recommended that future research consider incorporating new variables, such as HLA and pancreatic autoimmunity, as factors that may influence residual β-cell function. [ABSTRACT FROM AUTHOR]

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]

Copyright of Journal of Taibah University Medical Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Fulminant type 1 diabetes (FT1D) is a rapidly progressive form of diabetes in which the endogenous capacity to secrete insulin is depleted. The onset is unpredictable with conventional FT1D, and a few reports have tracked C-peptide in patients with conventional FT1D pre-onset. In this report, we present two typical cases of conventional FT1D where C-peptide was monitored from the onset of precursor symptoms to the development of diabetic ketoacidosis (DKA). Furthermore, we conducted a literature review and provide a detailed description of the process of C-peptide depletion in conventional FT1D. Case 1 involved a 72-year-old woman who initially presented with fever and fatigue. Case 2 involved a 45-year-old woman with fever, abdominal pain, and acute pancreatitis. In both cases, DKA developed five days after initial symptoms. A noteworthy observation in both cases was the drastic drop in C-peptide, which was detectable at initial presentation but depleted by the time of DKA diagnosis. These cases emphasize the importance of close follow-up of plasma glucose and serum C-peptide in cases presenting with infection and pancreatitis. Our literature review revealed that in conventional FT1D, endogenous insulin secretion becomes deficient in an average of 5.3 days. Regardless of any concomitant acute pancreatitis and/or pancreas enlargement, the period until endogenous insulin secretion became deficient showed no substantial variation. This result supports the concept that progression of conventional FT1D is more rapid than that of immune checkpoint inhibitor-related FT1D, which deplete insulin secretion in approximately 2 weeks. [ABSTRACT FROM AUTHOR]

Diabetes in the young has been traditionally defined as onset of diabetes below 35 years of age. In this age bracket, a variety of distinct types of diabetes might occur which poses a unique challenge in the diagnosis and management. Phenotypic features such as age of onset, presence of obesity and family history have traditionally been used in differentiating the various types of diabetes. With the increasing prevalence of obesity and T2DM in youth, these features have become less reliable in classifying diabetes in this age group. Along with detailed patient history and physical examination, biochemical parameters such as C-peptide and presence or absence of pancreatic autoantibodies (along with imaging studies for pancreatic pathology and genetic testing for monogenic forms of diabetes) are assuming greater importance in appropriate diagnosis and understanding the types of diabetes. C-peptide test which is a proxy for pancreatic beta cell function plays an important role in classifying type / subtypes of diabetes. When used appropriately it also helps in personalized approach to treatment and practice of Precision Diabetes. [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]

Magnesium (Mg) is the second most frequent intracellular cation in humans with critical role in insulin metabolism and glucoregulation. It is an antioxidant and acts as a cofactor for several enzymes. Evaluate serum Mg levels Iraqi women with PCOS and assess its relationship with Cpeptide and BMI. This is a case control study that included 80 women with PCOS and 80 healthy volunteers (as control group) in the age range between 18-45 years old. C-peptide was measured using ELISA technique, while Mg was measured using a spectrophotometric technique. Serum C-peptide levels were significantly higher in PCOS patients compared to the control group. In PCOS patients, serum magnesium concentration was significantly lower compared to the control group. This experiment found no correlation between Mg, C-peptide, or BMI. The ROC analysis area under the curves for Mg and C-peptide were 0.803 and 0.875, respectively. These figures demonstrate analysis method reliability. PCOS patients had lower blood magnesium and higher C-peptide levels. No statistically significant relationship was found between these factors. Due to the low magnesium levels in PCOS women's serum. The correlation between lower serum magnesium and higher C-peptide levels in PCOS patients was not significant. Lower serum magnesium levels in women with PCOS need further study and treatment to determine its role and association with PCOS. [ABSTRACT FROM AUTHOR]

Childhood and adolescence are the times when T1DM develops more frequently than adults. This study investigated the relationship between Adiponectin levels and some clinical variables in Iraqi adolescents with T1DM. The study included 90 subjects. Two groups were created for this study based on the initial mutant cell's lineage.: 45 Adolescence of Type I diabetes mellitus ranging in age (12-17 years) and control group 45 Participants in this study were matched for age and sex and appeared healthy. There was a highly substantial increase of rise weight, height, FBS, PPBS, TG, and HOMA-IR in T1DM adolescents in comparison to groups under control. There is a significant increase in BMI, TC and insulin level IR in T1DM Adolescence in contrast to groups under control. There was an appositive correlation between Adiponectin level and weight, BMI, and Insulin level and a highly positive correlation coefficient with FBS. PPBS, TC, TG, AIC, HOMA-IR while negative correlation with LDL in adolescent T1DM patients. We conclude that the decrease in adiponectin in patients with type 1 diabetes and adolescent children is an indicator of the appearance of many early diabetes complications in them, and this is considered a risk indicator for many diseases and thus leads to metabolic dysfunction in diabetic patients. [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]

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]

Copyright of Magazine of Al-Kufa University for Biology is the property of Republic of Iraq Ministry of Higher Education & Scientific Research (MOHESR) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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]

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]

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]

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]

IntroductionExercise is vital in preventing and treating obesity. Despite its importance, the understanding of how exercise influences childhood obesity at the biochemical level is limited. In this study, we explore the effects of a 16-week exercise program (EP) on body composition, physical fitness, and the blood levels of hormones related to obesity.MethodsSixteen boys with obesity (n = 16) and seventeen boys without obesity (n = 17) took part in an EP comprising sports games and aerobic and resistance exercises. We examined alterations in body composition and physical fitness. In addition, we measured circulating hormone levels, including C-peptide, resistin, insulin-like growth factor 1 (IGF-1), and growth hormone (GH), in the blood.ResultsBody fat percentage (BFP) decreased from 37.61% at pre-EP to 29.16% at post-EP in the obese group, but not in the non-obese group. The EP decreased C-peptide (4.58 ng/mL vs. 2.96 ng/mL, p < 0.001) and resistin levels (14.05 ng/mL vs. 11.06 ng/mL, p < 0.001) in the obese group. After the EP, significant improvement in IGF-1 (non-obese: 265.56 ng/mL vs. 311.81 ng/mL, p < 0.001; obese: 224.74 ng/mL vs. 272.89 ng/mL, p < 0.001) and GH levels (non-obese: 3.91 ng/mL vs. 4.80 ng/mL, p < 0.05; obese: 1.76 ng/mL vs. 2.51 ng/mL, p < 0.05) were observed in both groups. Lower C-peptide levels were associated with BFP (r = 0.447, p = 0.009) and muscle mass (r = −0.385, p = 0.02), whereas enhanced IGF-1 levels correlated with increased muscle strength (r = 0.343, p = 0.05) and cardiovascular fitness (r = 0.347, p = 0.04). Multiple linear regression analysis revealed that cardiovascular fitness variability and BFP in the obese group were determined by C-peptide (β = −0.054, p < 0.001) and IGF-1 levels (β = −2.936, p < 0.05), respectively.DiscussionExercise may induce positive effects on improvements in body composition and physical fitness, as well as on blood levels of metabolic biochemicals such as C-peptide and IGF-1, in adolescent boys with obesity.

ObjectiveDiabetic peripheral neuropathy (DPN) is a chronic complication of diabetes that can potentially escalate into ulceration, amputation and other severe consequences. The aim of this study was to construct and validate a predictive nomogram model for assessing the risk of DPN development among diabetic patients, thereby facilitating the early identification of high-risk DPN individuals and mitigating the incidence of severe outcomes.Methods1185 patients were included in this study from June 2020 to June 2023. All patients underwent peripheral nerve function assessments, of which 801 were diagnosed with DPN. Patients were randomly divided into a training set (n =711) and a validation set (n = 474) with a ratio of 6:4. The least absolute shrinkage and selection operator (LASSO) logistic regression analysis was performed to identify independent risk factors and develop a simple nomogram. Subsequently, the discrimination and clinical value of the nomogram was extensively validated using receiver operating characteristic (ROC) curves, calibration curves and clinical decision curve analyses (DCA).ResultsFollowing LASSO regression analysis, a nomogram model for predicting the risk of DPN was eventually established based on 7 factors: age (OR = 1.02, 95%CI: 1.01 - 1.03), hip circumference (HC, OR = 0.94, 95%CI: 0.92 – 0.97), fasting plasma glucose (FPG, OR = 1.06, 95%CI: 1.01 - 1.11), fasting C-peptide (FCP, OR = 0.66, 95%CI: 0.56 - 0.77), 2 hour postprandial C-peptide (PCP, OR = 0.78, 95%CI: 0.72 – 0.84), albumin (ALB, OR = 0.90, 95%CI: 0.87 – 0.94) and blood urea nitrogen (BUN, OR = 1.08, 95%CI: 1.01 - 1.17). The areas under the curves (AUC) of the nomogram were 0.703 (95% CI 0.664-0.743) and 0.704 (95% CI 0.652-0.756) in the training and validation sets, respectively. The Hosmer–Lemeshow test and calibration curves revealed high consistency between the predicted and actual results of the nomogram. DCA demonstrated that the nomogram was valuable in clinical practice.ConclusionsThe DPN nomogram prediction model, containing 7 significant variables, has exhibited excellent performance. Its generalization to clinical practice could potentially help in the early detection and prompt intervention for high-risk DPN patients.

Objective To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients.Methods This was a retrospective study in which thirty-two overweight/obese patients with PCOS (n = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated.Results ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease.Conclusion ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients.

Metformin is the first-line treatment for type 2 diabetes (T2D) in youth but with limited sustained glycemic response. To identify common variants associated with metformin response, we used a genome-wide approach in 506 youth from the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study and examined the relationship between T2D partitioned polygenic scores (pPS), glycemic traits, and metformin response in these youth. Several variants met a suggestive threshold (P < 1 × 10-6), though none including published adult variants reached genome-wide significance. We pursued replication of top nine variants in three cohorts, and rs76195229 in ATRNL1 was associated with worse metformin response in the Metformin Genetics Consortium (n = 7,812), though statistically not being significant after Bonferroni correction (P = 0.06). A higher β-cell pPS was associated with a lower insulinogenic index (P = 0.02) and C-peptide (P = 0.047) at baseline and higher pPS related to two insulin resistance processes were associated with increased C-peptide at baseline (P = 0.04,0.02). Although pPS were not associated with changes in glycemic traits or metformin response, our results indicate a trend in the association of the β-cell pPS with reduced β-cell function over time. Our data show initial evidence for genetic variation associated with metformin response in youth with T2D.

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

Background:Diabetic neuropathy affects significant individuals worldwide and is considered a chronic complication of diabetes. However, the exact mechanisms underlying the development of diabetic neuropathy are still not fully understood. Objectives:This study investigated the involvement of vitamin D2, PTH, and C-peptide in the onset of diabetic neuropathy. Materials and Methods:This study included 120 diabetic patients and 30 healthy controls. Diabetic patients were divided into group 1 with neuropathy (N = 80) and group 2 without neuropathy (N = 40). The following data were incorporated: sex, age, diabetes duration, and BMI. Biochemical evaluations involved HbA1C, C-peptide, PTH, and vitamin D2. Results:The study’s population had a 52.2 ± 13.9 years mean age. Patients had 9.8 years average diabetes duration, were mostly overweight, and were poorly controlled (mean HbA1C = 8.8). Vitamin D2 was insufficient, particularly in diabetics, and C-peptide measures were markedly low. There were differences in the three parameters between diabetes and controls. Potential relationships among the parameters were detected namely, higher HbA1C, elder, lower vitamin D2, besides higher C-peptide and vitamin D2 levels. ROC-curve metrics for vitamin D2, PTH, and C-peptide, revealed varied diagnostic potential. All parameters were unable to distinguish between patients with or without neuropathy from healthy subjects. Conclusion:The study highlights the importance of glycemic control, insulin production, PTH, and vitamin D2 levels in the context of diabetic neuropathy. While these biomarkers show associations with neuropathy risk, their diagnostic potential is still limited. The associations between age, HbA1C levels, PTH, C-peptide levels, and vitamin D2 levels provide valuable insights into potential contributors to neuropathy risk.

Abstract Impaired insulin secretory capacity is associated with high glycemic variability in patients with type 2 diabetes (T2DM). However, there are no existing reports on the association between insulin secretory capacity and time in range (TIR). This retrospective study involved 330 T2DM admitted for diabetes education who underwent intermittently scanned continuous glucose monitoring (isCGM) and had their fasting serum C-peptide immunoreactivity (S-CPR) measured within 5 days of admission. The baseline characteristics were as follows: age, 60.2 years; glycated hemoglobin (HbA1c), 9.2%; S-CPR, 2.2 ng/mL; S-CPR index (S-CPR [ng/mL]/fasting plasma glucose [mg/dL] × 100), 1.6; and TIR, 60.3%. TIR correlated significantly with the S-CPR index, which was confirmed by multivariate analysis that included various factors such as HbA1c. Receiver operating characteristic (ROC) analysis showed that 1.88 was the optimal S-CPR index level to predict TIR ≥ 70%. In addition to HbA1c and biguanide use, the S-CPR index was a significant factor associated with TIR > 70%. S-CPR index values of ≥ 1.88 also correlated significantly with TIR > 70%. In conclusion, insulin secretory capacity is associated with TIR in Japanese T2DM, suggesting that the S-CPR index might be a potentially useful biomarker insulin secretory capacity, in association with TIR. Trial registration UMIN0000254333.

Tong Zhang,1– 3,&ast; Han Wu,1,2,&ast; Chenling Qiu,1,2 Mingxin Wang,1,2 Haiting Wang,1,2 Shunhua Zhu,1,4 Yinhai Xu,2 Qingli Huang,1,4 Shibao Li1,2 1Medical Technology School of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 2Department of Laboratory Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, 221000, People’s Republic of China; 3Chuzhou Center for Disease Control and Prevention, Chuzhou City, Anhui, 239000, People’s Republic of China; 4Public Experimental Research Center of Xuzhou Medical University, Xuzhou City, Jiangsu, 221004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingli Huang; Shibao Li, Email qlhuang@xzhmu.edu.cn; sdjnshlb@xzhmu.edu.cnIntroduction: Insulin and C-peptide played crucial roles as clinical indicators for diabetes and certain liver diseases. However, there has been limited research on the simultaneous detection of insulin and C-peptide in trace serum. It is necessary to develop a novel method with high sensitivity and specificity for detecting insulin and C-peptide simultaneously.Methods: A core-shell-satellites hierarchical structured nanocomposite was fabricated as SERS biosensor using a simple wet-chemical method, employing 4-MBA and DTNB for recognition and antibodies for specific capture. Gold nanorods (Au NRs) were modified with Raman reporter molecules and silver nanoparticles (Ag NPs), creating SERS tags with high sensitivity for detecting insulin and C-peptide. Antibody-modified commercial carboxylated magnetic bead@antibody served as the capture probes. Target materials were captured by probes and combined with SERS tags, forming a “sandwich” composite structure for subsequent detection.Results: Under optimized conditions, the nanocomposite fabricated could be used to detect simultaneously for insulin and C-peptide with the detection limit of 4.29 × 10− 5 pM and 1.76 × 10− 10 nM in serum. The insulin concentration (4.29 × 10− 5– 4.29 pM) showed a strong linear correlation with the SERS intensity at 1075 cm− 1, with high recoveries (96.4– 105.3%) and low RSD (0.8%– 10.0%) in detecting human serum samples. Meanwhile, the C-peptide concentration (1.76 × 10− 10– 1.76 × 10− 3 nM) also showed a specific linear correlation with the SERS intensity at 1333 cm− 1, with recoveries 85.4%– 105.0% and RSD 1.7%– 10.8%.Conclusion: This breakthrough provided a novel, sensitive, convenient and stable approach for clinical diagnosis of diabetes and certain liver diseases. Overall, our findings presented a significant contribution to the field of biomedical research, opening up new possibilities for improved diagnosis and monitoring of diabetes and liver diseases.Keywords: surface-enhanced Raman scattering, SERS, nanocomposites, insulin, C-peptide

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 C-peptide 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 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.