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The connecting peptide (C-peptide) is a hormone with promising health benefits in ameliorating diabetes-related complications, yet mechanisms remain elusive. Emerging studies point to a possible dependence of peptide activity on bioavailable metals, particularly Cu(II) and Zn(II). However, little is known about the chemical nature of the interactions, hindering advances in its therapeutic applications. This work uncovers the Cu(II)-binding site in C-peptide that may be key to understanding its metal-dependent function. A combination of spectroscopic studies reveal that Cu(II) and Zn(II) bind to C-peptide at specific residues in the N-terminal region of the peptide and that Cu(II) is able to displace Zn(II) for C-peptide binding. The data point to a Cu(II)-binding site consisting of 1N3O square-planar coordination that is entropically driven. Furthermore, the entire random coil peptide sequence is needed for specific metal binding as mutations and truncations reshuffle the coordinating residues. These results expand our understanding of how metals influence hormone activity and facilitate the discovery and validation of both new and established paradigms in peptide biology.

AimsLittle information is published on diabetes in young people in Bangladesh. We aimed to investigate the demographic, clinical, and biochemical features, and HLA-DRB1 alleles in new cases of diabetes affecting Bangladeshi children and adolescents

AbstractType 2 diabetes (T2DM) is a common comorbidity in COVID-19 patients, which could favor disease progression. Our study aimed to evaluate the impact of some glycemic biomarkers on characteristic features of COVID-19. Electronic medical records of patients consecutively admitted to a COVID-19 ward were analyzed. Demographic and anthropometric as well as clinical and laboratory parameters were obtained. T2DM was present in 47% of the patients, with 22.58% of diabetic patients being newly diagnosed at admission. The most important predictors of severe COVID-19 were age (OR 1.214 [1.078-1.366], p = 0.001), creatinine levels (OR 1.018 [1.003-1.034], p = 0.017), glucose above 7.0 mmol/L at admission (OR 7.800 [2.232-27.255], p = 0.001) and HbA1c ≥ 6.5% (OR 4.840 [1.428-16.405], p = 0.011) irrespective of the presence of DM. C-peptide levels correlated positively with age, creatinine level, the severity of hypoxia and ferritin levels of patients (p

Background: Prior to year 2000, the majority of pancreas transplants (PTx) were performed as simultaneous pancreas-kidney transplants (SPKTs) in Caucasian adults with end stage renal failure secondary to type 1 diabetes mellitus (T1DM) who were middle-aged. In the new millennium, improving outcomes have led to expanded recipient selection that includes patients with a type 2 diabetes mellitus (T2DM) phenotype, which excessively affects minority populations. Methods: Using PubMed® to identify appropriate citations, we performed a literature review of PTx in minorities and in patients with a T2DM phenotype. Results: Mid-term outcomes with SPKT in patients with uremia and circulating C-peptide levels (T2DMphenotype) are comparable to those patients with T1DM although there may exist a selection bias in the former group. Excellent outcomes with SPKT suggests that the pathophysiology of T2DM is heterogeneous with elements consisting of both insulin deficiency and resistance related to beta-cell failure. As a result, increasing endogenous insulin (Cp) production following PTx may lead to freedom checking blood sugars or taking insulin, better metabolic counter-regulation, and improvements in quality of life and life expectancy compared to other available treatment options. Experience with solitary PTx for T2DM or in minorities is limited but largely mirrors the trends reported in SPKT. Conclusions: PTx is a viable treatment option in patients with pancreas endocrine failure who are selected appropriately regardless of diabetes type or recipient race. This review will summarize data that unconventional patient populations with insulin-requiring diabetes may gain value from PTx with an emphasis on contemporary experiences and appropriate selection in minorities in the new millennium.

Abstract Background Recent literature reported the biological role of C-peptide, but this role is still controversial and unclear. The primary aim of this study was to investigate associations between C-peptide and cardiovascular biomarkers as well as events. Methods A total of 55636 participants who had a health examination from 2017 to 2021 were included. Of them, 6727 participants visited the hospital at least twice. Cardiovascular biomarkers like high-sensitivity C-reactive protein (hs-CRP) and high-sensitivity cardiac troponin T (hs-cTnT) were measured and their relationships with fasting C-peptide were evaluated for all participants. Cardiovascular events were obtained during the last visit and their associations with C-peptide were evaluated for those participants who visited the hospital at least twice. Results Among the included participants, 11.1% had a previous type 2 diabetes mellitus (T2DM). In the participants without previous T2DM, the relationships between fasting C-peptide and hs-CRP and hs-cTnT were negative if the value of fasting C-peptide was

Abstract Objective To assess the correlation between the insulin-based and C-peptide based HOMA-IR in the general population without diabetes in sub-Saharan Africa as well as to identify factors associated with IR. Results This was a cross-sectional study in urban settings in Yaoundé, Cameroon. We included 84 people with a body mass index (BMI) ≥ 18.5 Kg/m² and without diabetes (females: 72.6%; mean age: 37 years). IR was assessed using the following formulae: HOMA-IRINS = fasting insulin (mU/ml) x fasting plasma glucose (FPG) (mmol/L)/ 22.5; HOMA-IRCP1 = fasting C-peptide (mU/ml) x FPG (mmol/L)/ 22.5; and HOMA-IRCP2 = 1.5 + (FPG (mg/dl) x fasting C-peptide (ng/ml))/ 2800. Correlation (rho) between HOMA-IRINS and C-peptide based HOMA-IR was investigated using the Spearman rank test. The median (25th -75th percentiles) HOMA-IRINS, HOMA-IRCP1, and HOMA-IRCP2 were: 1.94 (1.36–3.50), 0.18 (0.11–0.27) and 9.91 (6.81–14.52), respectively. There was no correlation between the insulin-based and C-peptide-based HOMA-IR indices: rho = 0.043, p = 0.697. IR (HOMA-IRINS ≥ 2.8) was associated with obesity: A BMI ≥ 30 Kg/m² (adjusted odds ratio (aOR): 16.9, 95% confidence intervals (CI): 3.1–92.5) and being a student (aOR: 8.9, 95%CI: 2.1–38.2) were associated with IR.

Abstract Background C-peptide offers potential as a marker to indicate childhood metabolic outcomes. Measuring C-peptide concentration might have better future utility in the risk stratification of neonates born to overweight or diabetic mothers. Prior research has tried to bring this matter into the light; however, the clinical significance of these associations is still far from reach. Here we sought to investigate the associations between fetomaternal metabolic variables and umbilical cord blood C-peptide concentration. Methods For the present study, 858 pregnant women were randomly selected from among a sub-group of 35,430 Iranian pregnant women who participated in a randomized community non-inferiority trial of gestational diabetes mellitus (GDM) screening. Their umbilical cord (UC) blood C-peptide concentrations were measured, and the pregnancy variables of macrosomia/large for gestational age (LGA) and primary cesarean section (CS) delivery were assessed. The variation of C-peptide concentrations among GDM and macrosomia status was plotted. Due to the skewed distribution of C-peptide concentration in the sample, median regression analysis was used to identify potential factors related to UC C-peptide concentration. Results In the univariate model, positive GDM status was associated with a 0.3 (95% CI: 0.06 − 0.54, p = 0.01) increase in the median coefficient of UC blood C-peptide concentration. Moreover, one unit (kg) increase in the birth weight was associated with a 0.25 (95% CI: 0.03 − 0.47, p = 0.03) increase in the median coefficient of UC blood C-peptide concentration. In the multivariate model, after adjusting for maternal age, maternal BMI, and macrosomia status, the positive status of GDM and macrosomia were significantly associated with an increase in the median coefficient of UC blood C-peptide concentration (Coef.= 0.27, 95% CI: 0.13 − 0.42, p

Abstract Aims/Introduction This study aimed to identify the clinical factors affecting postoperative residual pancreatic β‐cell function, as assessed by the C‐peptide index (CPI), and to investigate the association between perioperative CPI and the status of diabetes management after pancreatectomy. Materials and Methods The associations between perioperative CPI and clinical background, including surgical procedures of pancreatectomy, were analyzed in 47 patients who underwent pancreatectomy, and were assessed for pre‐and postoperative CPI. The association between perioperative CPI and glycemic control after pancreatectomy was investigated. Results The low postoperative CPI group (CPI

Background: High altitude exposure triggers a series of physiological changes to maintain homeostasis. Although longer-term (days to years) acclimatization processes are well studied, less is known about the physiological changes upon rapid ascent. We took advantage of Peru’s geography to measure the first physiological changes following rapid transport from a low to a high-altitude environment among lowlanders. Methods: Blood glucose, insulin, C-peptide, and salivary cortisol among healthy lowland Peruvians were measured before and after glucose ingestion at 40 m and upon arrival at 3470 m. Resting heart rate, blood oxygen saturation, and blood pressure were also monitored. Results: At high altitude, we find a significant ( pp Conclusions: Although many overlapping environmental and physiological factors are present in the high-altitude environment, the first steps of acclimatization in this population appear to be caused by increased energy expenditure and glucose metabolism to maintain oxygen homeostasis until the longer-term acclimatization mechanisms become more significant.

Abstract Background The number of dialysis patients with diabetes is currently increasing in Japan and a similar proportion worldwide. It was suggested that approximately 20% of these patients had hypoglycemia after dialysis session and most of these hypoglycemia were unconscious. Furthermore, it was suggested that glucose variabilities induced by hemodialysis may be related to insulin and insulin-counter hormones, such as glucagon, adrenocorticotropic hormone (ACTH), and cortisol and growth hormone, but conclusive evidence has not still been obtained. Methods We investigated in detail the glucose and hormonal profiles in 7 patients with type 2 diabetes on hemodialysis (all male, HbA1c 6.8 ± 2.1%, glycated albumin 24.7 ± 10.2%). All participants were attached continuous glucose monitoring (iPro2®). Blood glucose level, C-peptide immunoreactivity, plasma glucagon, ACTH, cortisol and growth hormone were measured by 7 points blood tests at before breakfast, after breakfast (predialysis), 2 h and 4 h after starting dialysis, after lunch and before/after dinner on the dialysis day and 6 points at before/after each meal on the non-dialysis day, and these relationship with blood glucose dynamics were examined. The meal contents were set to the indicated energy amount, and the same menu was served daily for breakfast, lunch, and dinner on dialysis and non-dialysis days of this study period. In addition, the start time of lunch on non-dialysis day was the same as the start time of lunch on the dialysis day. Results Serum C-peptide level was significantly increased by taking breakfast and lunch on the hemodialysis day, significantly decreased during hemodialysis, and was significantly lower before and after lunch on the hemodialysis day than on the non-hemodialysis day. Plasma glucagon level significantly decreased during hemodialysis and that before lunch on hemodialysis day was significantly lower than on non-hemodialysis day. ACTH, cortisol, and growth hormone did not show any changes related to hemodialysis. Conclusions It was suggested that C-peptide and glucagon play an important role in hemodialysis-related glycemic variabilities in patients with type 2 diabetic hemodialysis. Trial registration UMIN Clinical Trial Registry (Registration Number UMIN000018707 ). Registered 18 August 2015, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&language=J&recptno=R000021647 .

This study aims to demonstrate that proteolytic enzymes released as a result of hemolysis decrease the small peptide hormones, whereas N-phenyl maleimide (NPM) can be used to prevent hemolysis interference.

Introduction: The measurement of insulin and C-peptide provides a valuable tool for the clinical evaluation of hypoglycemia. In research, these biomarkers are used together to better understand hyperinsulinemia, hepatic insulin clearance, and beta cell function. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is an attractive approach for the analysis of insulin and C-peptide because the platform is specific, can avoid certain limitations of immunoassays, and can be multiplexed. Previously described LC-MS/MS methods for the simultaneous quantification of insulin and C-peptide measure the intact analytes and most have relied on immunoaffinity enrichment. These approaches can be limited in terms of sensitivity and interference from auto-antibodies, respectively. We have developed a novel method that does not require antibodies and uses proteolytic digestion to yield readily ionizable proteotypic peptides that enables the sensitive, specific, and simultaneous quantitation of insulin and C-peptide. Methods: Serum samples were precipitated with acetonitrile. Analytes were enriched using solid phase extraction and then digested with endoproteinase Glu-C. Surrogate peptides for insulin and C-peptide were analyzed using targeted LC-MS/MS. Results: Inter-day imprecision was below 20 %CV and linearity was observed down to the lower limit of quantitation for both analytes (insulin = 0.09 ng/mL, C-peptide = 0.06 ng/mL). Comparison to a commercially available insulin immunoassay (Beckman Coulter UniCel DxI 600 Access) revealed a 30% bias between methods. Conclusion: A novel LC-MS/MS method for the simultaneous analysis of insulin and C-peptide using Glu-C digestion was developed and evaluated. A detailed standard operating procedure is provided to help facilitate implementation in other laboratories.

Abstract Objective To examine the association of early-pregnancy serum C-peptide with incident gestational diabetes mellitus (GDM) and the predictive ability of maternal C-peptide for GDM. Methods A nested case–control study of 332 GDM cases and 664 controls was established based on the Tongji-Shuangliu Birth Cohort. The GDM cases and controls were matched at 1:2 on maternal age (± 3 years) and gestational age (± 4 weeks). Multivariable conditional logistic regression was applied to assess the association of C-peptide with risk of GDM. Partial Spearman’s correlation coefficients were estimated for the correlations between C-peptide and multiple metabolic biomarkers. C-statistics were calculated to assess the predictive ability of early-pregnancy C-peptide for GDM. Results Of 996 pregnant women, median maternal age was 28.0 years old and median gestational age was 11.0 weeks. After adjustment for potential confounders, the odds ratio of GDM comparing the extreme quartiles of C-peptide was 2.28 (95% confidence interval, 1.43, 3.62; P for trend

We evaluated the clinical impact, in daily clinical practice, of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) therapies in patients with type 2 diabetes. Data from 500 unselected consecutive patients were retrospectively analyzed. Only those with a full assessment at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment with SGLT2i or GLP1RA were included in the study (n = 167). At baseline, patients had a high mean body weight (BW), abdominal circumference (AC), body mass index (BMI), and HOMA index. Despite normal C-peptide values, 39 patients were being treated with insulin (up to 120 IU/day). During therapy, a progressive improvement in BW, BMI, and AC was observed with both the molecules. Fasting glucose and glycated Hb decrease was already significant at T3 in all patients, while the HOMA index selectively improved with SGLT2i therapy. Renal function parameters remained stable regardless of the drug used. Finally, SGLT2i reduced serum uric acid and improved the lipid profile, while GLP1RA reduced serum levels of liver enzymes. Both the therapeutic regimens allowed a significant reduction or complete suspension of unnecessary insulin therapies. Our real life data confirm the results obtained from randomized clinical trials and should be taken as a warning against inappropriate use of insulin in patients with preserved β-cell function.

Abstract Background Abnormal thyroid hormone levels have been reported in type 2, but the relationship between thyroid hormone levels and glycaemic indices: fasting plasma glucose (FPG), C-peptide (C-pep) and glycated haemoglobin (HbAlc), used in the management of type 2 is not well defined. This cross-sectional study examined the relationship between thyroid hormones and glycaemic indices in type 2. Results Positive correlations were observed between FPG and HbAlc in hypothyroid (r = 0.382, P = 0.011) and hyperthyroid group (r = 0.295, P = 0.012). FPG correlated with C-pep in hyperthyroid diabetics (r = 0.481, P

Background: Persistence of β cell-function in Type 1 diabetes (T1D) is associated with glycaemia stability and lower prevalence of microvascular complications. We aimed to assess the prevalence of residual C- peptide secretion in long-term Brazilian childhood onset T1D receiving usual diabetes care and its association to clinical, metabolic variables and microvascular complications. Methods: A cross-sectional observational study with 138 T1D adults with ≥ 3 years from the diagnosis by routine diabetes care. Clinical, metabolic variables and microvascular complications were compared between positive ultra-sensitive fasting serum C-peptide (FCP +) and negative (FCP-) participants. Results: T1D studied had ≥ 3 yrs. of diagnosis and 60% had FCP > 1.15 pmol/L. FCP + T1D were older at diagnosis (10 vs 8 y.o; p = 0.03) and had less duration of diabetes (11 vs 15 y.o; p = 0.002). There was no association between the FCP + and other clinical and metabolic variable but there was inversely association with microalbuminuria (28.6% vs 13.4%, p = 0.03), regardless of HbA1c. FCP > 47 pmol/L were associated with nephropathy protection but were not related to others microvascular complications. Conclusion: Residual insulin secretion is present in 60% of T1D with ≥ 3 years of diagnosis in routine diabetes care. FCP + was positively associated with age of diagnosis and negatively with duration of disease and microalbuminuria, regardless of HbA1c. [ABSTRACT FROM AUTHOR]

Background: The conclusion between Connecting peptide (C-peptide) and diabetic chronic complication was controversial. The purpose of this study is to explore the possible association between average C-peptide with diabetic retinopathy (DR) progression in Chinese patients with type 2 diabetes. Methods: This is a retro-prospective study. 622 patients with type 2 diabetes were included. DR was evaluated using non-mydriatic fundus photography and DR progression was defined as any deterioration of either eye. Fasting and postprandial c-peptide levels were assayed at baseline and follow-up period. Differences between continuous variables were compared using the Mann–Whitney U test; and categorical variables were analyzed by the chi-square test. Correlation between parameters and 30-minute postprandial C-peptide were determined by Spearman correlation test. The relationship between C-peptide and DR progression was evaluated by multivariable binary logistic regression. Two-tailed P-values < 0.05 were regarded as statistically significant. Results: DR was present in 162 (26.0%) patients at baseline, and 26.4% of patients were found progression of DR at follow-up. Patients with progression of DR had lower average levels of 30-minute postprandial C-peptide (2.01 ng/ml vs. 2.6 ng/ml, p = 0.015) and 120-minute postprandial C-peptide (3.17 ng/ml vs. 3.92 ng/ml, p < 0.029), as well as average increment of 30-minute (0.41 ng/ml vs. 0.64 ng/ml, p = 0.015) and 120-minute postprandial C-peptide (1.48 ng/ml vs. 1.93 ng/ml, p < 0.017), than those without DR aggravation. Multivariate logistic regression analysis determined that 30-minute postprandial C-peptide and its increment were related to reduced odds ratios for DR progression (odds ratios [OR] = 0.83 and 0.74, respectively). Conclusion: Our results suggest that the Average 30-minute post-prandial C-peptide and increment were negatively correlated with DR progression, which further demonstrates the importance to preserve β-cell residual function in the prevention for DR progression. Trial registration: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Components of metabolic syndrome can be observed in patients with primary hyperparathyroidism (PHPT). The link between these disorders remains unclear due to the lack of relevant experimental models and the heterogeneity of examined groups. The effect of surgery on metabolic abnormalities is also controversial. We conducted a comprehensive assessment of metabolic parameters in young patients with PHPT. Methods: One-center prospective comparative study was carried out. The participants underwent a complex biochemical and hormonal examination, a hyperinsulinemic euglycemic and hyperglycemic clamps, a bioelectrical impedance analysis of the body composition before and 13 months after parathyroidectomy compared to sex-, age- and body mass index matched healthy volunteers. Results: 45.8% of patients (n = 24) had excessive visceral fat. Insulin resistance was detected in 54.2% of cases. PHPT patients had higher serum triglycerides, lower M-value and higher C-peptide and insulin levels in both phases of insulin secretion compared to the control group (p < 0.05 for all parameters). There were tendencies to decreased fasting glucose (p = 0.031), uric acid (p = 0.044) and insulin levels of the second secretion phase (p = 0.039) after surgery, but no statistically significant changes of lipid profile and M-value as well as body composition were revealed. We obtained negative correlations between percent body fat and osteocalcin and magnesium levels in patients before surgery. Conclusion: PHPT is associated with insulin resistance that is the main risk factor of serious metabolic disorders. Surgery may potentially improve carbohydrate and purine metabolism. [ABSTRACT FROM AUTHOR]

C-peptide is an increasingly used and established marker for beta cell function by assessing endogenous insulin secretion. Accurate and comparable C-peptide measurements are needed in clinical practice and research studies. For example, to calculate HOMA-indices, the C-peptide/glucose ratio, and the classification of recently published novel subgroups of diabetes and prediabetes have used C-peptide measurements. Although the process for standardization of C-peptide measurements is advanced, its full implementation is still missing; therefore, the current status of the comparability of C-peptide measurements using different immunoassays is unclear. Here we compared five widely used C-peptide immunoassays on different analyzers (Abbott ALINITY i, DiaSorin Liaison XL, Roche Cobas e411, Siemens Healthineers ADVIA Centaur XPT, and Immulite 2000 XPi) using serum samples covering the clinically relevant C-peptide concentration range. Although all investigated immunoassays are traceable to the international reference reagent for C-peptide (NIBSC code: 84/510), results of C-peptide measurements showed significant differences between analyzers in the entire concentration range, especially with increasing C-peptide concentrations. The mean bias was largest (36.6%) between results of the immunoassays by Roche and Siemens Healthineers (ADVIA Centaur XPT), and both assays revealed large discrepancies compared to immunoassays by Abbott, DiaSorin, and Siemens Healthineers (Immulite 2000 XPi). In contrast, the three latter assays showed similar C-peptide results (mean bias: 2.3% to 4.2%). Consequently, C-peptide discrepancies might affect clinical diagnosis and the interpretation of study results. Therefore, there is an urgent need to implement and finalize the standardization process of C-peptide measurements to improve patient care and the comparability of research studies. [ABSTRACT FROM AUTHOR]

Immunoassays employed to measure C-peptide in rat serum neither have high sensitivity nor good range. Hence, the aim of this work was to develop a sensitive and specific user friendly immunoradiometric assay (IRMA) utilizing in-house magnetizable cellulose particles for quantification of C-peptide in rat serum. For development of IRMA, detector antibody (M1*) was prepared by chloramine-T method using 125I and capture antibody (SM2) was prepared by carbonyldiimidazole (CDI) activation method. The matched pair M1*-SM2 yielded an assay with adequate sensitivity (0.24 ng/ml) and range (0–20 ng/ml). C-peptide concentrations in rat serum samples (n = 30) analyzed using the developed assay ranged between 0.3 and 0.54 ng/ml. The reported C-peptide range can be used as a reference in impending diabetic research carried out using rat models. [ABSTRACT FROM AUTHOR]

Aim/hypothesis: The risk of progressing from autoantibody positivity to type 1 diabetes is inversely related to age. Separately, whether age influences patterns of C-peptide loss or changes in insulin sensitivity in autoantibody-positive individuals who progress to stage 3 type 1 diabetes is unclear. Methods: Beta cell function and insulin sensitivity were determined by modelling of OGTTs performed in 658 autoantibody-positive participants followed longitudinally in the Diabetes Prevention Trial–Type 1 (DPT-1). In this secondary analysis of DPT-1 data, time trajectories of beta cell function and insulin sensitivity were analysed in participants who progressed to type 1 diabetes (progressors) to address the impact of age on patterns of metabolic progression to diabetes. Results: Among the entire DPT-1 cohort, the highest discriminant age for type 1 diabetes risk was 14 years, with participants aged <14 years being twice as likely to progress to type 1 diabetes as those aged ≥14 years. At study entry, beta cell glucose sensitivity was impaired to a similar extent in progressors aged <14 years and progressors aged ≥14 years. From study entry to stage 3 type 1 diabetes onset, beta cell glucose sensitivity and insulin sensitivity declined in both progressor groups. However, there were no significant differences in the yearly rate of decline in either glucose sensitivity (−13.7 [21.2] vs −11.9 [21.5] pmol min−1 m−2 [mmol/l]−1, median [IQR], p=0.52) or insulin sensitivity (−22 [37] vs −14 [40] ml min−1 m−2, median [IQR], p=0.07) between progressors aged <14 years and progressors aged ≥14 years. Conclusions/interpretation: Our data indicate that during progression to stage 3 type 1 diabetes, rates of change in declining glucose and insulin sensitivity are not significantly different between progressors aged <14 years and progressors aged ≥14 years. These data suggest there is a predictable course of declining metabolic function during the progression to type 1 diabetes that is not influenced by age. [ABSTRACT FROM AUTHOR]

Insulin autoimmune syndrome (IAS) is a rare endocrine disorder characterized by recurrent episodes of severe hypoglycemia, markedly elevated serum insulin, and positive insulin autoantibodies. In recent years, various countries have reported it one after another. It can be seen that we must pay attention to this disease. The diagnosis of IAS is challenging, requiring a careful workup aimed at excluding other causes of hyperinsulinemic hypoglycemia. High levels of insulin autoantibodies are found in patients, and C-peptide is not parallel to insulin, which could be diagnostic. IAS is a self-limiting disease with a good prognosis. Its treatment mainly includes symptomatic supportive treatment, such as adjusting the diet and using acarbose and other drugs to delay the absorption of glucose to prevent hypoglycemia. For patients with severe symptoms, available treatments may include drugs that reduce pancreatic insulin secretion (such as somatostatin and diazoxide), immunosuppressants (glucocorticoids, zaprin, and rituximab), and even plasma exchange to remove autoantibodies from the body. This review provides a comprehensive analysis of the epidemiology, pathogenesis, clinical manifestations, diagnosis and identification, and monitoring and treatment management of IAS. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is caused by retinal vascular dysfunction and neurodegeneration. Intraocular delivery of C-peptide has been shown to be beneficial against hyperglycemia-induced microvascular leakage in the retina of diabetes; however, the effect of C-peptide on diabetes-induced retinal neurodegeneration remains unknown. Moreover, extraocular C-peptide replacement therapy against DR to avoid various adverse effects caused by intravitreal injections has not been studied. Here, we demonstrate that systemic C-peptide supplementation using osmotic pumps or biopolymer-conjugated C-peptide hydrogels ameliorates neurodegeneration by inhibiting vascular endothelial growth factor-induced pathological events, but not hyperglycemia-induced vascular endothelial growth factor expression, in the retinas of diabetic mice. C-peptide inhibited hyperglycemia-induced activation of macroglial and microglial cells, downregulation of glutamate aspartate transporter 1 expression, neuronal apoptosis, and histopathological changes by a mechanism involving reactive oxygen species generation in the retinas of diabetic mice, but transglutaminase 2, which is involved in retinal vascular leakage, is not associated with these pathological events. Overall, our findings suggest that systemic C-peptide supplementation alleviates hyperglycemia-induced retinal neurodegeneration by inhibiting a pathological mechanism, involving reactive oxygen species, but not transglutaminase 2, in diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Diagnosis of endogenous hyperinsulinism relies on the occurrence of a hypoglycemia, concomitant with inadequate high insulin and C-peptide levels. However, diagnostic cutoffs are not consensual among the different learned societies. The objective of this work was to propose optimized cutoffs for these three parameters for the diagnosis of endogenous hyperinsulinism. Methods: All the patients having performed a fasting trial in Cochin Hospital Endocrinology Department between February 2012 and August 2022 were included. The results of glycemia, insulin and C-peptide levels during fasting trial were collected and analyzed. Results: One hundred and fifty-nine patients were included: 26 with endogenous hyperinsulinism and 133 without endogenous hyperinsulinism. ROC analysis of glycemia nadir during fasting trial identified the value of 2.3 mmol/L as the optimal cutoff, ensuring a sensitivity of 100% associated with a specificity of 81%. ROC analysis of insulin and C-peptide levels concomitant with hypoglycemia <2.3 mmol/L showed very good diagnostic performances of both parameters with respective cutoffs of 3.1 mUI/L (=21.5 pmol/L; sensitivity=96%; specificity=92%) and 0.30 nmol/L (sensitivity=96%; specificity=100%). Insulin to glycemia ratio as well as C-peptide to glycemia ratio (in pmol/mmol) at the time of glycemia nadir did not show better diagnostic performances than C-peptide alone. Conclusion: A C-peptide level 0.3 nmol/L concomitant with a hypoglycemia <2.3 mmol/L appears as the best criterion to make the diagnosis of endogenous hyperinsulinism. Insulin level can be underestimated on hemolyzed blood samples, frequently observed in fasting trial, and thus shows lower diagnostic performances. [ABSTRACT FROM AUTHOR]

Aims: This study aims to evaluate the stability of C‐peptide over time and to compare fasting C‐peptide and C‐peptide response after mixed‐meal tolerance test (MMTT) at T90 or T120 with C‐peptide area under the curve (AUC) in long‐standing type 1 diabetes. Methods: We included 607 type 1 diabetes individuals with diabetes duration >5 years. C‐peptide concentrations (ultrasensitive assay) were collected in the fasting state, and in a subpopulation after MMTT (T0, just prior to, T30‐T60‐T90‐T120, 30–120 min after ingestion of mixed‐meal) (n = 168). Fasting C‐peptide concentrations (in n = 535) at Year 0 and Year 1 were compared. The clinical determinants associated with residual C‐peptide secretion and the correspondence of C‐peptide at MMTT T90 / T120 and total AUC were assessed. Results: A total of 153 participants (25%) had detectable fasting serum C‐peptide (i.e ≥ 3.8 pmol/L). Fasting C‐peptide was significantly lower at Year 1 (p < 0.001, effect size = −0.16). Participants with higher fasting C‐peptide had a higher age at diagnosis and shorter disease duration and were less frequently insulin pump users. Overall, 109 of 168 (65%) participants had both non‐detectable fasting and post‐meal serum C‐peptide concentrations. The T90 and T120 C‐peptide values at MMTT were concordant with total AUC. In 17 (10%) individuals, C‐peptide was only detectable at MMTT and not in the fasting state. Conclusions: Stimulated C‐peptide was detectable in an additional 10% of individuals compared with fasting in individuals with >5 years of diabetes duration. T90 and T120 MMTT measurements showed good concordance with the MMTT total AUC. Overall, there was a decrease of C‐peptide at 1‐year follow‐up. [ABSTRACT FROM AUTHOR]

The study aimed to determine the relationship between glucose, C-peptide, brain-derived neurotrophic factor (BDNF), and leptin between mother and fetus and neonatal weight. Methods: In the prospective observational cohort study, we included 66 women with type-1 diabetes mellitus (T1DM). According to the z-score for neonatal weight, patients were divided into healthy-weight neonates (n = 42) and overweight neonates (n = 24). The maternal blood samples were taken during pregnancy and cesarean section when the umbilical vein blood sample was also withdrawn. The maternal vein sera were analyzed for fasting glucose, C-reactive protein (CRP), leptin, BDNF, TSH, FT3, and FT4. The umbilical vein sera were analyzed for glucose, C-peptide, leptin, TSH, thyroid-stimulating protein (FT3), free thyroxine (FT4), and BDNF concentration. The neonatologist measured the skinfold thickness on the third day of neonatal life. Results: A strong correlation was confirmed between maternal and umbilical vein glucose concentration and maternal glucose and C-peptide in umbilical vein blood. A negative correlation was found between the concentration of BDNF in the umbilical vein and glucose in maternal blood. A strong correlation was seen between BMI and maternal blood leptin concentration, neonatal fat body mass, and umbilical vein blood leptin concentration. Higher BMI elevated BDNF, and TSH increase the odds for overweight neonates in the first trimester of pregnancy. Maternal higher leptin concentration in the first trimester decrease the odds of overweight neonates. Conclusions: Maternal glucose concentrations affect the fetus's glucose, C-peptide, and BDNF concentrations. Leptin levels increase in maternal blood due to increased body mass index, and in the neonate, fat body mass is responsible for increased leptin concentrations. [ABSTRACT FROM AUTHOR]

Auxin efflux through plasma-membrane-integral PIN-FORMED (PIN) carriers is essential for plant tissue organization and tightly regulated. For instance, a molecular rheostat critically controls PIN-mediated auxin transport in developing protophloem sieve elements of Arabidopsis roots. Plasma-membrane-association of the rheostat proteins, BREVIS RADIX (BRX) and PROTEIN KINASE ASSOCIATED WITH BRX (PAX), is reinforced by interaction with PHOSPHATIDYLINOSITOL-4-PHOSPHATE-5-KINASE (PIP5K). Genetic evidence suggests that BRX dampens autocrine signaling of CLAVATA3/EMBRYO SURROUNDING REGION-RELATED 45 (CLE45) peptide via its receptor BARELY ANY MERISTEM 3 (BAM3). How excess CLE45-BAM3 signaling interferes with protophloem development and whether it does so directly or indirectly remains unclear. Here we show that rheostat polarity is independent of PIN polarity, but interdependent with PIP5K. Catalytically inactive PIP5K confers rheostat polarity without reinforcing its localization, revealing a possible PIP5K scaffolding function. Moreover, PIP5K and PAX cooperatively control local PIN abundance. We further find that CLE45-BAM3 signaling branches via RLCK-VII/PBS1-LIKE (PBL) cytoplasmic kinases to destabilize rheostat localization. Our data thus reveal antagonism between CLE45-BAM3-PBL signaling and PIP5K that converges on auxin efflux regulation through dynamic control of PAX polarity. Because second-site bam3 mutation suppresses root as well as shoot phenotypes of pip5k mutants, CLE peptide signaling likely modulates phosphoinositide-dependent processes in various developmental contexts. In this paper the authors demonstrate that auxin efflux in the phloem vascular tissue of plants is determined by antagonism between CLE peptide signaling pathways and phosphoinositide kinases. [ABSTRACT FROM AUTHOR]

Background: Type 1 diabetes mellitus (T1DM) is a common chronic systemic disease that threatens the health of children worldwide. Diabetic ketoacidosis (DKA) is the most severe acute complication of diabetes and can lead to death. This study aimed to explore the epidemiological features, clinical manifestations, and risk factors for DKA in children and adolescents newly diagnosed with T1DM in the Department of Endocrinology of the Children's Hospital of Henan Province. Methods: Medical records of 683 children and adolescents newly diagnosed with T1DM in our center from March 2014 to November 2021 were retrospectively analyzed. The data included the general condition, laboratory indexes, and clinical symptoms. The patients were divided into three groups according to age: Group I, 0–3 years; Group II, 4–9 years; and Group III, 10–18 years. Results: The incidence of DKA was 62.96% and was highest in Group I. Group I had the lowest C-peptide and hemoglobin A1c, but the highest blood glucose at first diagnosis, and 25-hydroxyvitamin D3 levels, hospitalization lengths, and medical costs. 25.5% of the children were delayed in diagnosis. Logistic regression analysis showed that elevated HbA1c levels and hyperglycemia were independent risk factors for DKA. On the other hand, C-peptide and 25- hydroxyvitamin D were protective factors for DKA. Conclusions: The incidence of DKA among children and adolescents in the Henan Province is very high. Moreover, DKA can be easily delayed in diagnosis. Newly diagnosed infants with T1DM are more likely to present with DKA, suffer more severe metabolic disorders, endure longer hospital stays, and accrue higher medical costs. [ABSTRACT FROM AUTHOR]

Background: Until date, diabetes during pregnancy has been linked to an increased risk of maternal, fetal, and neonatal morbidity and mortality. Infants of diabetic mothers (IDM) frequently have difficulties related to fetal hyperglycemia and hyperinsulinemia caused by maternal hyperglycemia. Because insulin breakdown is accelerated in the presence of mild hemolysis, cord serum C-peptide levels are utilized as an indicator of fetal beta-cell function rather than insulin levels. Objective: To study the relationship between umbilical cord C-peptide and risk of hypoglycemia in infants of diabetic mothers. Patients and Methods: This Cross-sectional study was conducted on 50 infants of diabetic mothers. Infants who developed hypoglycemia in first 24-hour age were considered as cases and infants who did not develop hypoglycemia during the first 24 hours were considered as controls in Neonatal Unit of Benha university hospitals in cooperation with the Department of Obstetrics and Gynecology, during the period from January 2022 to July 2022. Result: The infants were divided into two groups: Hypoglycemia group (Cases group): included 31 infants of diabetic mothers who developed hypoglycemia in first 24-hour age. normoglycemic group (Control group): included 19 infants who did not develop hypoglycemia during the first 24 hours. Conclusion: In this study, we discovered a substantial rise in UC C-peptide levels in hypoglycemic babies as compared to the control group, indicating that C-peptide might be utilized as an early predictor of hypoglycemia in IDMs. [ABSTRACT FROM AUTHOR]

Background. IDM/LADA is late-manifesting immune-mediated diabetes diagnosed in patients over 30 years of age. It is estimated to account for 5–10% of diabetes cases in adults. Objectives. The aim of the study was to identify the parameters implying the diagnosis of immune-mediated diabetes among adults with new-onset diabetes. Material and methods. Study included patients 30–50 years of age with new-onset diabetes, hospitalised between 2014 and 2019 in the Diabetology Department. Medical history, hyperglycaemia symptoms, comorbidities, anthropometric measurements and laboratory tests were analysed. The exclusion criterion was a history of pancreatitis. Results. We analysed a group of 182 patients (mean age 38.1 ± 5.1). IDM/LADA was diagnosed in 78 (43%) patients. In the subgroup of subjects 30–35 years of age, IDM/LADA patients constituted 50.08%, whereas in the 36–50 years of age group, this constituted 38.65% of all the patients. The IDM/LADA patients were younger, had a lower body mass and BMI, noticed symptoms of diabetes before hospitalisation and more often had other autoimmune disorders. Thier C-peptide concentrations were nearly three times lower, while T2DM patients had a higher concentration of total cholesterol and triglycerides and more frequently had arterial hypertension (all p < 0.05). Testing for one antibody (GADA) allows one to diagnose 83% of IDM/LADA cases. Furthermore, determination of both GADA and ICA resulted in diagnosing autoimmune diabetes in 97% of all the patients. Conclusions. With a measurement of C-peptide concentration and GADA detection, we could diagnose IDM/LADA with 89% sensitivity. Moreover, the inclusion of clinical features increased the sensitivity up to 93.5%. Considering the age criterion, there was no significant difference between the groups of patients with IDM/LADA. [ABSTRACT FROM AUTHOR]

In clinical practice, the distinction between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) can be challenging, leaving patients with "ambiguous" diabetes type. Insulin-treated patients (n=115) previously diagnosed with T2DM had to be re-classified based on clinical phenotype and laboratory results, and were operationally defined as having an ambiguous diabetes type. They were compared against patients with definite T1DM and T2DM regarding 12 clinical and laboratory features typically different between diabetes types. Characteristics of patients with ambiguous diabetes type, representing approximately 6% of all patients with T1DM or T2DM seen at our specialized clinic, fell in between those of patients with definite T1DM and T2DM, both regarding individual features and with respect to a novel classification based on multi-variable regression analysis (P<0.0001). In conclusion, a substantial proportion of diabetes patients in a tertiary care centre presented with an "ambiguous" diabetes type. Their clinical characteristics fall in between those of definite T1DM or T2DM patients. [ABSTRACT FROM AUTHOR]

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Objectives: The aim of the presented word was to assess the diagnostic accuracy of serum Nesfatin-1 in type 2 diabetes mellitus and its relationship with C-peptide level in obese and non-obese type-2 diabetic women of Iraqi population. Methods: (A case-control study was performed on 50 type 2 diabetic patients admitted in Al-Hussein Teaching Hospital and Al-Hassan center of diabetes and endocrinology unit/Kerbala health directorate -- Iraq and another 50 control individuals, during the period from April, 2022 -- Jan. 2023). The T2DM groups were divided into two groups 25 obese and 25 non-obese; also the control group was divided into 25 obese and 25 non-obese as apparently healthy groups. The ELISA Kit was used to measure serum Nesfatin-1 and C-peptide, and random serum glucose was measured by enzymatic colorimetric method, and lipid profile test were measured through spectrophotometric technique, instead of HbA1c% was determined using HPLC method. Results: The results observed indicated that Nesfatin-1 levels shown a non-significant decrease in all of type 2 diabetic groups as compared with apparently healthy control group, while the C-peptide were significantly decreased in type 2 diabetic patients when compared with apparently control group. In addition, the random blood glucose and HbA1c% were shown significant elevation in type 2 diabetic patients as compared with apparently healthy control groups. The observed data indicated that Nesfatin-1 and C-peptide levels when comparing between type 2 diabetic patients and control in obese groups shown a risk factors depending upon the odd ratio observed (OR = 1.064 (1.011-1.119), 1.0200 (0.992-1.08)) respectively, but only Nesfatin-1 was shown to be significant. In BMI the levels of Nesfatin-1 and C-peptide, as shown the Nesfatin-1 was significant in obese groups, while the C-peptide as shown significant in normal weight groups. The optimal diagnostic points for Nesfatin-1 were (sensitivity = 98%, specificity = 90%) at a level (Cut-off points) = 39.13, while C-Peptide levels: (sensitivity = 98%, specificity = 94%) at a level (Cut-off points) = 15.99. Both markers have P-values of the AUC were <0.001 and statistically significant. Conclusion: Accordingly, it was concluded that a significant relationship between circulating Nesfatin-1 levels and type 2 diabetes. Nesfatin-1 appears to be able to contribute to the treatment of obesity and diabetes because of its anorexigenic and antihyperglycemic effects. In addition, C-peptide is a known biomarker of insulin resistance and beta-cell function. High specificity and sensitivity analyzed results were obtained by ROC analysis for both markers in T2DM. [ABSTRACT FROM AUTHOR]

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Gestational diabetes mellitus (GDM) is characterized by diminished glucose tolerance that manifests during pregnancy. Leptin, a vital adipokine governing several physiological processes, including insulin sensitivity, plays a pivotal role. Insulin resistance stands as the principal factor underlying the development of GDM. This study aims to assess and compare serum leptin levels and various insulin resistance (IR) models between GDM cases and normoglycemic pregnant women. Furthermore, we seek to determine whether leptin and IR models hold predictive value for GDM.A cross-sectional study was conducted, enrolling one hundred GDM cases and one hundred normoglycemic pregnant women. Fasting blood samples were collected for the analysis of serum leptin, insulin, and C-peptide using ELISA. Appropriate statistical analyses were performed employing GraphPad InStat 3.Fasting Cpeptide levels were significantly higher in GDM cases (p=0.0014). Conversely, fasting serum insulin and leptin levels exhibited no significant differences in GDM patients (p=0.6968 and p=0.213, respectively). Comparative analysis of IR models between cases and controls revealed significantly lower HOMA B cell and HOMA 1% B cell (insulin-based) values, along with significantly higher HOMA B cell and HOMA 1% B cell (C-peptide-based) values in cases (p<0.0001). In summary, our findings suggest that leptin levels were not significantly altered in GDM, while C-peptide and C-peptide-based insulin resistance models were elevated. Both leptin and various insulin resistance models did not emerge as reliable markers for predicting GDM. [ABSTRACT FROM AUTHOR]

Objectives: To estimate vitamin D levels in children with type 1 diabetes, and to evaluate its role in the pathogenesis and progress of the disease. Method: The cross-sectional study was conducted at the Paediatric Department of Kafrelsheikh University Hospital, Egypt, from November 2019 to August 2021, and comprised children of either gender aged 3-18 years who were either inpatients or visiting the paediatric outpatient clinic. The subjects were enrolled into 3 groups. Those with newly diagnosed type 1 diabetes were in group A, those with established type 1 diabetes were in group B, and healthy children matched for age and gender and randomly selected were in the control group C. Glycated haemoglobin, serum fasting C-peptide, and serum vitamin D levels were evaluated using quantitative colorimetric determination, an automated analyser, and enzyme-linked immunosorbent assay, respectively. Data was analysed using SPSS 25. Results: Of the 80 subjects, 30(37.5%) were in group A; 17(56.7%) boys and 13(43.3%) girls with mean age 7.77±2.95 years. In group B, there were 30(37.5%) subjects; 14(46.7%) boys and 16(53.3%) girls with mean age 9.6±3.62 years. There were 20(25%) subjects in group C; 10(50%) boys and as many girls with mean age 8.38±2.68 years (p>0.05). Glycated haemoglobin, serum fasting C-peptide and serum vitamin D was significantly different between the control group and the treatment groups (p

Abstract Background Elevated C‐peptide has been suggested as a risk factor for coronary artery disease (CAD). Elevated urinary C‐peptide to creatinine ratio (UCPCR) as an alternative measurement is shown to be related to insulin secretion dysfunction; however, data regarding UCPCR predictive value for CAD in diabetes mellitus (DM) are scarce. Therefore, we aimed to assess the UCPCR association with CAD in type 1 DM (T1DM) patients. Methods 279 patients previously diagnosed with T1DM included and categorized into two groups of CAD (n = 84) and without‐CAD (n = 195). Furthermore, each group was divided into obese (body mass index (BMI) ≥ 30) and non‐obese (BMI

IntroductionThe prevalence of obesity in general pediatric population increases without sparing children with T1D. We intended to find factors associated with the possibility of preserving endogenous insulin secretion in individuals with long-standing T1D. At onset, higher BMI is associated with higher C-peptide level, which may indicate to be one of the favorable factors involved in preserving residual β-cell function. The study determines the influence of BMI on C-peptide secretion in children newly diagnosed with T1D in two years observation.MethodsWe assessed the possible relationship between selected pro- and anti-inflammatory cytokines, body mass at recognition and β-cell function status. 153 pediatric patients with newly diagnosed T1D were divided into quartiles according to BMI-SDS index. We separated a group consisted of patients with BMI-SDS >1. Participants were followed up for two years and examined for changes in body weight, HbA1c, and insulin requirement. C-peptide was assessed at baseline and after two years. We evaluated the patients’ levels of selected inflammatory cytokines at baseline.ResultsSubjects with higher BMI-SDS presented higher serum C-peptide levels and lower insulin requirements at diagnosis than children with lower body weight. The two-year follow-up showed that C-peptide levels of obese patients dropped more rapidly than in children with BMI-SDS within normal limits. The group with BMI-SDS >1 showed the greatest decrease in C-peptide level. Despite statistically insignificant differences in HbA1c at diagnosis between the study groups, in the fourth quartile and BMI-SDS >1 groups, HbA1c as well as insulin requirements increased after two years. The levels of cytokines varied the most between BMI-SDS 1 groups and were significantly higher within BMI-SDS >1 group.DiscussionHigher BMI, associated with enhanced levels of inflammatory cytokines, relates to preservation of C-peptide at T1D recognition in children but is not beneficial in the long term. A decrease in C-peptide levels combined with an increase in insulin requirements and in HbA1c among patients with high BMI occur, which may indicate a negative effect of excessive body weight on the long term preservation of residual β-cell function. The process seems to be mediated by inflammatory cytokines.

Neprilysin inhibition might similarly block degradation of C-peptides in the kidney and thus increase the urinary C-peptide level. gl In conclusion, ARNI is in wide use for treatment of HF and hypertension, both of which are frequently observed in individuals with diabetes. As urine C-peptide levels are substantially elevated in comparison with serum C-peptide levels, the effect of sacubitril/valsartan on urine C-peptide levels would be independent of GLP-1-mediated enhancement of insulin secretion. Keywords: Angiotensin receptor-neprilysin inhibitor; C-peptide; Neprilysin EN Angiotensin receptor-neprilysin inhibitor C-peptide Neprilysin 1038 1040 3 08/25/23 20230901 NES 230901 The possible mechanism of increased urinary C-peptide due to neprilysin inhibitors is investigated. [Extracted from the article]

Hyaluronan (HA), an extracellular matrix glycosaminoglycan, is implicated in the pathogenesis of both type 1 diabetes (T1D) as well as type 2 diabetes (T2D) and has been postulated to be increased in these diseases due to hyperglycemia. We have examined the serum and tissue distribution of HA in human subjects with T1D and T2D and in mouse models of these diseases and evaluated the relationship between HA levels and glycemic control. We found that serum HA levels are increased in T2D but not T1D independently of hemoglobin-A1c, C-peptide, body mass index, or time since diabetes diagnosis. HA is likewise increased in skeletal muscle in T2D subjects relative to non-diabetic controls. Analogous increases in serum and muscle HA are seen in diabetic db/db mice (T2D), but not in diabetic DORmO mice (T1D). Diabetes induced by the β-cell toxin streptozotozin (STZ) lead to an increase in blood glucose but not to an increase in serum HA. These data indicate that HA levels are increased in multiple tissue compartments in T2D but not T1D independently of glycemic control. Given that T2D but not T1D is associated with systemic inflammation, these patterns are consistent with inflammatory factors and not hyperglycemia driving increased HA. Serum HA may have value as a biomarker of systemic inflammation in T2D.

A three-arm, randomized, double-masked, placebo-controlled phase 2b trial performed by the Type 1 Diabetes TrialNet Study Group previously demonstrated that low-dose anti-thymocyte globulin (ATG) (2.5 mg/kg) preserved β-cell function and reduced HbA1c for 1 year in new-onset type 1 diabetes. Subjects (N = 89) were randomized to 1) ATG and pegylated granulocyte colony-stimulating factor (GCSF), 2) ATG alone, or 3) placebo. Herein, we report 2-year area under the curve (AUC) C-peptide and HbA1c, prespecified secondary end points, and potential immunologic correlates. The 2-year mean mixed-meal tolerance test-stimulated AUC C-peptide, analyzed by ANCOVA adjusting for baseline C-peptide, age, and sex (n = 82) with significance defined as one-sided P < 0.025, was significantly higher in subjects treated with ATG versus placebo (P = 0.00005) but not ATG/GCSF versus placebo (P = 0.032). HbA1c was significantly reduced at 2 years in subjects treated with ATG (P = 0.011) and ATG/GCSF (P = 0.022) versus placebo. Flow cytometry analyses demonstrated reduced circulating CD4:CD8 ratio, increased regulatory T-cell:conventional CD4 T-cell ratios, and increased PD-1+CD4+ T cells following low-dose ATG and ATG/GCSF. Low-dose ATG partially preserved β-cell function and reduced HbA1c 2 years after therapy in new-onset type 1 diabetes. Future studies should determine whether low-dose ATG might prevent or delay the onset of type 1 diabetes.

ObjectiveTo determine the association of insulin sensitivity and metabolic status with declining cognition in HIV-infected individuals.MethodsWe conducted targeted clinical and metabolic measures in longitudinal plasma samples obtained from HIV-infected patients enrolled in the Central Nervous System HIV Anti-Retroviral Therapy Effects Research Study (CHARTER). Findings were validated with plasma samples from the Multicenter AIDS Cohort Study (MACS). Patients were grouped according to longitudinally and serially assessed cognitive performance as having stably normal or declining cognition.ResultsPatients with declining cognition exhibited baseline hyperinsulinemia and elevated plasma c-peptide levels with normal c-peptide/insulin ratios, suggesting that insulin production was increased, but insulin clearance was normal. The association of hyperinsulinemia with worsening cognition was further supported by low high-density lipoprotein (HDL), high low-density lipoprotein/HDL ratio, and elevated cholesterol/HDL ratio compared to patients with stably normal cognition.ConclusionsThese findings suggest that hyperinsulinemia and impaired insulin sensitivity are associated with cognitive decline in antiretroviral therapy-treated HIV-infected patients.

Published information on diabetes in Pakistani youth is limited. We aimed to investigate the demographic, clinical, and biochemical features, and HLA-DRB1 alleles in new cases of diabetes affecting children and adolescents

Background: Surgery is a stress which stimulates the increase of counter regulatory hormones. Pre-operative prolonged fasting increases stress further. Although a pre-operative carbohydrate (CHO) drink has been variably reported to yield benefit in reducing the perioperative stress and is being used frequently for elective surgeries, some recent reports also reports that preoperative CHO loading did not result in increase or decrease in the post-operative complication rates when compared with placebo or fasting group. Aims and Objectives: The present study was designed to determine the stress response in the postoperative period at 24 h in terms of changes in the levels of cortisol and other biomarkers. Materials and Methods: This randomized, parallel group, and double-blind study was conducted in 75 patients aged 18–65 years, of American Society of Anesthesiologists Physical Status Classes I and II, scheduled for elective lumbar spine surgery under general anesthesia. The patients were randomly allocated to receive 300 ml plain water at 9 pm on the day before surgery and 2 h before operation (Group C, control, n=25), or 300 ml plain water at 9 pm on the day before surgery and solution containing 75 grams of glucose dissolved in 300 ml water in the morning 2 h before surgery (Group CHO-1, n=25), or to receive 75 grams of glucose dissolved in 300 ml water at 9 pm in the night before the surgery and again in the morning at 2 h before surgery (Group CHO-2, n=25). In all the three groups, the levels of insulin (C-peptide), lactate, glucose, and cortisol were determined preoperatively (before the induction of anesthesia) and 24 h postoperatively. Results: There was considerable difference between post-operative blood cortisol level among the three groups (583.9 vs. 462.3 vs. 389.6 nMol/L, Control vs., CHO load once or twice, respectively, P

Abstract Background Type 1 diabetes (T1D) places an extraordinary burden on individuals and their families, as well as on the healthcare system. Despite recent advances in glucose sensors and insulin pump technology, only a minority of patients meet their glucose targets and face the risk of both acute and long-term complications, some of which are life-threatening. The JAK-STAT pathway is critical for the immune-mediated pancreatic beta cell destruction in T1D. Our pre-clinical data show that inhibitors of JAK1/JAK2 prevent diabetes and reverse newly diagnosed diabetes in the T1D non-obese diabetic mouse model. The goal of this study is to determine if the JAK1/JAK2 inhibitor baricitinib impairs type 1 diabetes autoimmunity and preserves beta cell function. Methods This will be as a multicentre, two-arm, double-blind, placebo-controlled randomized trial in individuals aged 10–30 years with recent-onset T1D. Eighty-three participants will be randomized in a 2:1 ratio within 100 days of diagnosis to receive either baricitinib 4mg/day or placebo for 48 weeks and then monitored for a further 48 weeks after stopping study drug. The primary outcome is the plasma C-peptide 2h area under the curve following ingestion of a mixed meal. Secondary outcomes include HbA1c, insulin dose, continuous glucose profile and adverse events. Mechanistic assessments will characterize general and diabetes-specific immune responses. Discussion This study will determine if baricitinib slows the progressive, immune-mediated loss of beta cell function that occurs after clinical presentation of T1D. Preservation of beta cell function would be expected to improve glucose control and prevent diabetes complications, and justify additional trials of baricitinib combined with other therapies and of its use in at-risk populations to prevent T1D. Trial registration ANZCTR ACTRN12620000239965 . Registered on 26 February 2020. ClinicalTrials.gov NCT04774224. Registered on 01 March 2021

Abstract Background The INNODIA consortium has established a pan-European infrastructure using validated centres to prospectively evaluate clinical data from individuals with newly diagnosed type 1 diabetes combined with centralised collection of clinical samples to determine rates of decline in beta-cell function and identify novel biomarkers, which could be used for future stratification of phase 2 clinical trials. Methods In this context, we have developed a Master Protocol, based on the “backbone” of the INNODIA natural history study, which we believe could improve the delivery of phase 2 studies exploring the use of single or combinations of Investigational Medicinal Products (IMPs), designed to prevent or reverse declines in beta-cell function in individuals with newly diagnosed type 1 diabetes. Although many IMPs have demonstrated potential efficacy in phase 2 studies, few subsequent phase 3 studies have confirmed these benefits. Currently, phase 2 drug development for this indication is limited by poor evaluation of drug dosage and lack of mechanistic data to understand variable responses to the IMPs. Identification of biomarkers which might permit more robust stratification of participants at baseline has been slow. Discussion The Master Protocol provides (1) standardised assessment of efficacy and safety, (2) comparable collection of mechanistic data, (3) the opportunity to include adaptive designs and the use of shared control groups in the evaluation of combination therapies, and (4) benefits of greater understanding of endpoint variation to ensure more robust sample size calculations and future baseline stratification using existing and novel biomarkers.

BACKGROUND: Type 1 diabetes mellitus (T1DM) is characterized by the development of absolute insulin deficiency. In some patients residual insulin secretion may persist for a long time. C-peptide is a widely used to measure the pancreatic beta cells function, in clinical practice and in research studies.AIM: To assess C-peptide levels and presence of islets autoantibodies (Ab) in children with different duration of T1DM and to identify factors associated with the preserved secretion.MATERIALS AND METHODS: Single-center cross-sectional study including data from 703 cases of children with T1DM, examined in the Endocrinology Research Center in 2016-2020, who was underwent a study of C-peptide levels and was positive for one or more islets antibodies (ZnT8, IA-2, GAD, ICA, IAA). There were 3 groups of patients: 1st — T1DM duration 5 years.RESULTS: The median of the fasting C-peptide level in the 1st group was 0.6 ng/ml [0.27; 1.09]; in the 2nd group — 0.2 ng/ml [0.01; 0.8]; in the 3rd group — 0.01 ng/ml [0.01; 0.037]. The preserved secretion of C-peptide (> 0.6 ng/ml) was determined in 51.4% in the 1st group, in 31.4% — in the 2nd group and in 11.4% in the 3rd group. In patients with obesity during the first year from the T1DM diagnosis C-peptide levels above 1.1 ng/ml was determined significantly more often (65.2%), as well as at the period of 1 to 5 years of the disease (35.7%), compared with children with normal BMI (18.5% and 14.5%, respectively) or overweight (15.7% and 19%, respectively), p