BACKGROUND Type 2 diabetes mellitus(T2DM),driven by insulin resistance and β cell dysfunction,necessitates reliable assessment of β cell function.C-peptide(CP)measurement,a stable marker of endogenous insulin secret...BACKGROUND Type 2 diabetes mellitus(T2DM),driven by insulin resistance and β cell dysfunction,necessitates reliable assessment of β cell function.C-peptide(CP)measurement,a stable marker of endogenous insulin secretion,is useful for this clinically as it avoids interference from exogenous insulin.While fasting CP(FCP)and postprandial CP(PCP),along with glucose-adjusted indices and ratios,such as FCP/fasting plasma glucose(FPG),2 hours postprandial CP(2hCP)/postprandial blood glucose(PBG)and CP ratio,are used,their comparative efficacy in reflectingβcell function remains unclear.Hemoglobin A1c(HbA1c),a key glycemic control indicator,theoretically linksβcell function to complications,but limited studies have explored the associations between diverse CP indices,HbA1c,and diabetic microvascular complications.AIM To investigate the relationships between different CP indices and HbA1c as well as diabetic microvascular complications in T2DM.METHODS T2DM patients admitted to Department of Endocrinology at Beijing Hospital between July 1,2021 and December 31,2021 were included in the study.Clinical and laboratory data were collected,including CP levels,glucose levels,HbA1c levels and diabetic microvascular complications.Statistical analysis was performed using Statistical Package for the Social Sciences 24.0.RESULTS A total of 453 patients were included in the final analysis.Adjusted by confounding factors,CP ratio and CP/blood glucose(BG)ratio were not relevant to HbA1c,but FCP,2hCP,delta CP,FCP/FPG,2hCP/PBG and delta CP/BG were still negatively correlated to HbA1c,of which 2hCP/PBG showed the strongest negative correlation(r=-0.485,P<0.001).Independent of HbA1c and other confounding factors,2hCP,2hCP/PBG,delta CP and delta CP/BG were protective factors of diabetic retinopathy while 2hCP,delta CP and FCP/FPG were protective factors of diabetic peripheral neuropathy.CONCLUSION This study indicates that higher levels of CP indices suggest better glucose control and a lower prevalence of diabetic microvascular complications,and PCP indices,particularly 2hCP/PBG,were more relevant to HbA1c and diabetic microvascular complications than FCP indices.These results suggest CP-related indices could be useful biomarkers for diabetes management,warranting further research.展开更多
AIM To determine whether fasting C-peptide is an independent predictor for non-alcoholic fatty liver disease(NAFLD) in United States population.METHODS Using the National Health and Nutrition Examination Survey(NHANES...AIM To determine whether fasting C-peptide is an independent predictor for non-alcoholic fatty liver disease(NAFLD) in United States population.METHODS Using the National Health and Nutrition Examination Survey(NHANES) 1988-1994, NAFLD participants aged 20 or greater without any other liver diseases were included in this study. Excessive alcohol intake is defined as > 2 drinks per day for males and > 1 drink per day for females. C-peptide and 27 other factors known to be associated with NAFLD(e.g., age, gender, body mass index, waist circumference, race/ethnicity, liver chemistries, and other diabetes tests) were tested in both univariate and multivariate level using logistic regression with a P-value 0.05.RESULTS Of 18825 participants aged ≥ 20, 3235 participants(n = 3235) met inclusion criteria. There were 23 factors associated with NAFLD by univariate analysis. 9 factors, ranked by the highest change in pseudo R2, were found to be significant predictors of NAFLD in multivariate model: waist circumference, fasting C-peptide, natural log of alanine aminotransferase(ALT), total protein, beingMexican American, natural log of glycated hemoglobin, triglyceride level, being non-Hispanic white, and ferritin level. CONCLUSION Together with waist circumference and ALT, fasting C-peptide is among three most important predictors of NAFLD in United States population in the NHANES data set. Further study is needed to validate the clinical utility of fasting C-peptide in diagnosis or monitoring insulin resistance in NAFLD patients.展开更多
With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications a...With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications along with the aging of the population, increase in adult obesity rate, and other risk factors. Diabetic en- cephalopathy is one of the severe microvascular complications of diabetes, characterized by impaired cogni- tive functions, and electrophysiological, neurochemical, and structural abnormalities. It may involve direct neuronal damage caused by intracellular glucose. However, the pathogenesis of this disease is complex and its diagnosis is not very clear. Previous researches have suggested that chronic metabolic alterations, vascular changes, and neuronal apoptosis may play important roles in neuronai loss and damaged cognitive functions. Multiple factors are responsible for neuronal apoptosis, such as disturbed insulin growth factor （IGF） system, hyperglycemia, and the aging process. Recent data suggest that insulin/C-peptide deficiency may exert a primary and key effect in diabetic encephalopathy. Administration of C-peptide partially improves the condition of the IGF system in the brain and prevents neuronal apoptosis in the hippocampus of diabetic patients. Those findings provide a basis for application of C-peptide as a potentially effective therapy for diabetes and diabetic encephalopathy.展开更多
Diabetes is associated with several complications such as retinopathy, nephropathy, neuropathy and cardiovascular diseases. Currently, insulin is the main used medication for management of insulin-dependentdiabetes me...Diabetes is associated with several complications such as retinopathy, nephropathy, neuropathy and cardiovascular diseases. Currently, insulin is the main used medication for management of insulin-dependentdiabetes mellitus(type-1 diabetes). In this metabolic syndrome, in addition to decrease of endogenous insulin, the plasma level of connecting peptide(C-peptide) is also reduced due to beta cell destruction. Studies in the past decade have shown that C-peptide is much more than a byproduct of insulin biosynthesis and possess different biological activities. Therefore, it may be possible that C-peptide deficiency be involved, at least in part, in the development of different complications of diabetes. It has been shown that a small level of remaining C-peptide is associated with significant metabolic benefit. The purpose of this review is to describe beneficial effects of C-peptide replacement on pathological features associated with insulin-dependent diabetes. Also, experimental and clinical findings on the effects of C-peptide on wholebody glucose utilization, adipose tissue metabolism and tissues blood flow are summarized and discussed. The hypoglycemic, antilipolytic and vasodilator effects of C-peptide suggest that it may contribute to fine-tuning of the tissues metabolism under different physiologic or pathologic conditions. Therefore, C-peptide replacement together with the classic insulin therapy may prevent, retard, or ameliorate diabetic complications in patients with type-1 diabetes.展开更多
Objective: In this study, we assessed the level of fasting C-peptide as a predictor of β-cell function and insulin resistance in patients with Type 2 diabetes mellitus (T2DM), Gezira State-Sudan. Methods: In this cro...Objective: In this study, we assessed the level of fasting C-peptide as a predictor of β-cell function and insulin resistance in patients with Type 2 diabetes mellitus (T2DM), Gezira State-Sudan. Methods: In this cross-sectional study, 100 T2DM patients attending the Diabetic patients care Centre were recruited, thirty five patients were males and sixty five were females, the mean age of the patients was 50.29 ± 0.456 years, and body mass index (BMI) was 26.54 ± 0.437. We estimated β-cell function using fasting C-peptide levels;homeostatic model assessment for β-cell function (HOMA-B) and insulin resistance (HOMA-IR) were calculated from C-peptide and fasting blood glucose (FBG). Results: C-peptide was significantly and positively correlated with HOMA-B and HOMA-IR. FBG also showed significant negative correlation with HOMA-B, but was positively and significantly correlated with HOMA-IR. HbA1c was negatively and significantly correlated with HOMA-B. Patients with low C-peptide levels had increased FBG and HbA1c level, while patients with high C-peptide levels were having high HOMA-IR and HOMA-B. Conclusions: Fasting C-peptide is a useful marker of pancreatic β-cell function, and its circulating levels could be used to evaluate insulin secretion and insulin resistance. Moreover, HOMA-IR is an effective index to achieve glycemic control by appropriate pharmacologic treatment of T2DM.展开更多
Gestational diabetes is typically diagnosed in the late second or third trimester of pregnancy.It is one of the most common metabolic disorders among expectant mothers,with potential serious short-and long-term compli...Gestational diabetes is typically diagnosed in the late second or third trimester of pregnancy.It is one of the most common metabolic disorders among expectant mothers,with potential serious short-and long-term complications for both maternal and offspring health.C-peptide is secreted from pancreatic beta-cells into circulation in equimolar amounts with insulin.It is a useful biomarker to estimate the beta-cell function because it undergoes negligible hepatic clearance and consequently it has a longer half-life compared to insulin.Pregnancy induces increased insulin resistance due to physiological changes in hormonal and metabolic homeostasis.Inadequate compensation by islet beta-cells results in hyperglycemia.The standard oral glucose tolerance test at 24-28 wk of gestation sets the diagnosis.Accumulated evidence from prospective studies indicates a link between early pregnancy C-peptide levels and the risk of subsequent gestational diabetes.Elevated C-peptide levels and surrogate glycemic indices at the beginning of pregnancy could prompt appropriate strategies for secondary prevention.展开更多
Background: Increased glomerular filtration rate (GFR) commonly develops in early diabetes and is closely correlated with the development of diabetic nephropathy. Objective: The aim was to study the relationship betwe...Background: Increased glomerular filtration rate (GFR) commonly develops in early diabetes and is closely correlated with the development of diabetic nephropathy. Objective: The aim was to study the relationship between GFR, C-peptide level and other parameters at diagnosis of Type 1 diabetes. Methods: We determined GFR, Cpeptide level, glycated hemoglobin (HbA1c), body mass index (BMI) SDS and loss of weight at diagnosis of Type 1 diabetes in 495 children (231 females). Linear and multiple regression analysis was used to test for the associations between GFR and other parameters. Results: In the 495 patients, GFR median (interquartile range) was increased vs normal values (p = 0.0001). GFR was significantly negatively correlated with age (p < 0.001) and C-peptide level (p = 0.001), and positively correlated with weight loss (p = 0.02). The multiple regression analysis showed that age (p = 0.001) and C-peptide level (p = 0.05) were independently and negatively related to GFR. Conclusions: This study shows that, at onset of Type 1 diabetes, higher the GFR, younger the age and lower the C-peptide level are. The role of this hyperfiltration in the development of later nephropathy and the putative preventive effect of C-peptide administration need to be evaluated.展开更多
As a product in the process of insulin synthesis, C-peptide’s physiological function is still not very clear. Recent studies have shown that C-peptide has many potential cell targets and has biological effects on a v...As a product in the process of insulin synthesis, C-peptide’s physiological function is still not very clear. Recent studies have shown that C-peptide has many potential cell targets and has biological effects on a variety of tissue systems in humans and other animals. In this paper, the effects of C-peptide on diabetic complications, reproductive endocrine system, blood system, tissue repair, and neoplastic diseases were reviewed to provide references for further clarification of c-peptide related problems.展开更多
Background: Measuring fasting C-peptide (FCP) and antibodies against Glutamic acid decarboxylase (GADA) and Islet cell antibodies (ICA) are not so commonly explored in children and young adults. Objectives: To assess ...Background: Measuring fasting C-peptide (FCP) and antibodies against Glutamic acid decarboxylase (GADA) and Islet cell antibodies (ICA) are not so commonly explored in children and young adults. Objectives: To assess the levels of FCP, GADA and ICA in subjects below the age of 25 years with DM and compare their levels to differentiate between Autoimmune and Non-Autoimmune Type 1 DM. Methodology: Blood samples of 93 subjects diagnosed with DM, reporting to the tertiary care hospital, were analysed for ICA, GADA and FCP. Receiver operating characteristics (ROC) curves were analysed to check the ability of autoimmune markers, BMI and C-peptide to differentiate between Autoimmune (Ai) and Non-Autoimmune (NonAi) diabetes. Results: 30/93 (32.2%) were positive for anti-GAD ab and/or ICA and categorised as Autoimmune (Ai), the most common antibody being, anti-GAD ab (80%) in them. The level of FCP among Ai compared to NonAi, was significantly low (p 20.75 nmol/l) as a very dependable test for diagnosing Ai, Type 1 DM, in children and young adults. Its sensitivity and specificity are in the range of 86.2% and 96.8% respectively. Low level of C-peptide (Conclusion: This study revealed predominant positivity for anti-GAD ab (80%) among Ai+ patients. ROC analysis shows GADA above 20.75 nmol/l and Fasting C-peptide < 0.36 nmol/l as a good indicator for diagnosing Ai in children and young adults.展开更多
Objective: to explore the role of serum C-peptide index and glycosylated hemoglobin index in the diagnosis of diseased diabetes patients. Methods: eighty patients with suspected diabetes were selected from our hospita...Objective: to explore the role of serum C-peptide index and glycosylated hemoglobin index in the diagnosis of diseased diabetes patients. Methods: eighty patients with suspected diabetes were selected from our hospital, and the selected time range was from August 2021 to August 2022. They were set as the observation group. Eighty patients with physical examination were collected at the same time, and they were set as the control group. The clinical comprehensive diagnosis results and the positive detection rate of serum C-peptide index and glycosylated egg white index were observed. The gold standard was clinical comprehensive diagnosis, To evaluate the efficacy of relying on serum C-peptide index and glycosylated protein index in patients with suspected diabetes. The measurement values of serum C-peptide index level, glycosylated hemoglobin index level and blood glucose index level of the patients diagnosed as diabetes in the observation group and the subjects included in the control group were analyzed. Results: among the 80 patients suspected of diabetes in the observation group, 68 were diagnosed as diabetes according to the clinical comprehensive diagnosis results, accounting for 85.00%. The diagnosis was carried out only according to the serum C-peptide index, and 57 cases were positive, accounting for 71.25%. The diagnosis was carried out only according to the glycosylated hemoglobin index, and 56 cases were positive, accounting for 70.00%. The combined diagnosis of the two indexes showed that 67 cases were positive, accounting for 83.75%, which was significantly higher than the other two groups (P < 0.05). The method of joint test of serum C-peptide index item and glycosylated hemoglobin index item was used to carry out the diagnosis of patients with suspected diabetes. The sensitivity index, specificity index and accuracy index were significantly higher than those of the two indicators used alone, of which, the sensitivity and accuracy were significantly different (P < 0.05). After testing the body serum C-peptide index of patients diagnosed as diabetes in the observation group, its value was lower than that of the control group, and after testing the glycosylated hemoglobin index and blood glucose index, its value was higher than that of the control group (P < 0.05). Conclusion: for patients with diabetes, attention should be paid to the joint test of serum C-peptide index and glycosylated hemoglobin index. The diagnostic efficacy is high and the value is significant.展开更多
Background Food composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The...Background Food composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The aim of this study was to explore the fast response of C-peptide, glucagon-like peptide-1 （GLP-1）, ghrelin and endomorphin-1 （EM-1） to the eastern and western style meals in patients with type 2 diabetes mellitus. Methods The study enrolled 57 patients with type 2 diabetes （20 men and 37 women, mean age （67.05±8.26） years）. Eastern style meal （meal A） and western style meal （meal B） were designed to produce the fullness effect. C-peptide, GLP-1, ghrelin and EM-1 were assessed before （0 hour） and after （2 hours） each diet. Results The delta （2h-0h） of C- peptide in meal A was significantly lower than that in meal B （P=0.0004）. C-peptide, GLP-1, ghrelin and EM-1 were obviously higher before meal B than those before meal A （P 〈0.0001, 〈0.0001, =0.001, =0.0004 respectively）. Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A （P=0.0005, 0.0079 respectively）. Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B （rA0h=0.7838, rB05=0.9368, rA25=0.7615, rB2h=0.9409, r A（2h-0h）=0.7531, rB（2h 05）=0.9980, respectively, P 〈0.0001）. Conclusion Western style meal （high fat and protein food） could make more response of C-peptide than eastern style meal, and could stimulate more gut hormones （GLP-1, ghrelin） and brain peptide （EM-1） at the first phase of digestion.展开更多
Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,im...Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.展开更多
BACKGROUND Adult-onset diabetes is most often considered to be type 2 diabetes.However,other types of diabetes can develop in adults,including exocrine pancreas diseaseassociated diabetes,also called type 3c diabetes....BACKGROUND Adult-onset diabetes is most often considered to be type 2 diabetes.However,other types of diabetes can develop in adults,including exocrine pancreas diseaseassociated diabetes,also called type 3c diabetes.Differential diagnosis between these types of diabetes still remains a diagnostic challenge.AIM To define anthropometric and laboratory markers that will allow for early diagnosis of pancreatic disease-associated diabetes.METHODS The study group included 44 patients with pancreatogenic diabetes(26 with pancreatic cancer and 18 with chronic pancreatitis),while the control group consisted of 35 patients with type 2 diabetes.We analyzed several parameters,including sex,age,body mass index(BMI),fasting plasma glucose,fasting Cpeptide and insulin with homeostasis model assessment of insulin resistance(HOMA-IR)index calculation,adrenomedullin,adiponectin and creatinine levels with epidermal growth factor receptor(eGFR)calculation.We also developed an equation,termed type 3c diabetes index,which utilized BMI,fasting insulin and adrenomedullin levels,and eGFR to better identify patients with type 3c diabetes.RESULTS Compared to patients with type 2 diabetes,patients with pancreatogenic diabetes had significantly lower BMI(25.11±4.87 kg/m^(2) vs 30.83±5.21 kg/m^(2)),fasting C-peptide(0.81±0.42 nmol/L vs 1.71±0.80 nmol/L),insulin(76.81±63.34 pmol/L vs 233.19±164.51 pmol/L)and HOMA-IR index,despite similar fasting plasma glucose levels.Patients with pancreatogenic diabetes also had lower adrenomedullin levels(0.41±0.25 ng/mL vs 0.63±0.38 ng/mL)but higher adiponectin levels(13.08±7.20μg/mL vs 8.28±4.01μg/mL)and eGFR levels(100.53±21.60 mL/min/1.73 m^(2) vs 85.14±19.24 mL/min/1.73 m^(2)).Finally,patients with pancreatogenic diabetes had significantly lower Type 3c diabetes index values.CONCLUSION Patients with pancreatogenic diabetes differ from patients with type 2 diabetes in anthropometric and laboratory parameters.The type 3c diabetes index had the highest discriminating value,above any single parameter.展开更多
Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin...Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin cell receptors (type II DM). Type I DM usually presents with florid manifestations contrary to a slowly-progressive type II. Patients and methods: Over the past 10 years, we encountered 9 obese patients with controlled insulin-requiring type II DM for years, at a dose of 62 ± 5 units/day, who developed sudden and severe insulin resistance (IR) that required 210 ± 25 units daily. All patients had very high levels of anti-Glutamic Acid Decarboxylase (GAD) antibodies. Despite a lack of previous testing for anti-GAD antibodies, they were treated, with Cyclosporin A (Cy), as an autoimmune disorder superimposed on their type II MD. Initially all patients were treated with 100 mg, of Cy, twice daily aiming at an initial trough level of 100 - 150 ng/ml. Three months later, the dose was reduced to 50 mg twice daily for a total of 2 years. Results: Amelioration of IR was achieved by 1 month with a reduction of daily insulin requirement to 123 ± 16 units that further decreased to 76 ± 11 by the end of the 3rd month. Such improvement persisted for 2 years and >1 year after Cy discontinuation. Moreover, a decline in insulin requirements was associated with a parallel decrease in anti-GAD antibody levels and an increase in C-peptide insulin without kidney disease. Conclusion: Anti-GAD antibodies can induce acute IR in type II DM, and this phenomenon can be treated safely and effectively with Cy.展开更多
BACKGROUND Insulin therapy plays a crucial role in managing diabetes.Regulatory guidelines mandate assessing the pharmacokinetics(PK)and pharmacodynamics(PD)of new insulin formulations with euglycemic clamp techniques...BACKGROUND Insulin therapy plays a crucial role in managing diabetes.Regulatory guidelines mandate assessing the pharmacokinetics(PK)and pharmacodynamics(PD)of new insulin formulations with euglycemic clamp techniques before entry into the market.Typically,blood glucose(BG)levels are maintained at 5%below baseline to suppress endogenous insulin secretion in healthy volunteers.However,in scenarios where BG baseline is relatively low,maintaining it at 5%below baseline can increase hypoglycemic risk.Consequently,we adjusted to maintain it at 2.5%below a baseline of<4.00 mmol/L.It remains uncertain whether this adjustment impacts endogenous insulin inhibition or the PD of study insulin.AIM To evaluate and compare the PD and C-peptide status using two different target BG setting methods.METHODS Data came from euglycemic clamp trials assessing the PK/PD of insulin aspart(IAsp)in healthy participants.Target BG was set at 2.5%below baseline for those with a basal BG of<4.00 mmol/L(group A),and at 5%below baseline for others(group B).The area under the curve(AUC)of IAsp(AUC_(IAsp,0-8 h))and GIR from 0 to 8 hours(AUCGIR,0-8 h)was used to characterize the PK and PD of IAsp,respectively.The C-peptide reduction and PK/PD of IAsp were compared between the two groups.RESULTS Out of 135 subjects,15 were assigned to group A and 120 to group B;however,group B exhibited higher basal Cpeptide(1.59±0.36 vs 1.32±0.42 ng/mL,P=0.006).Following propensity score matching to adjust for basal Cpeptide differences,71 subjects(15 in group A and 56 in group B)were analyzed.No significant differences were observed in demographics,IAsp dosage,or clamp quality.Group B showed significantly higher baseline(4.35±0.21 vs 3.91±0.09 mmol/L,P<0.001),target(4.13±0.20 vs 3.81±0.08 mmol/L,P<0.001),and clamped(4.10±0.17 vs 3.80±0.06 mmol/L,P<0.001)BG levels.Both groups exhibited comparable C-peptide suppression(32.5%±10.0%vs 35.6%±12.1%,P=0.370)and similar IAsp activity(AUCGIR,0-8 h:1433±400 vs 1440±397 mg/kg,P=0.952)under nearly equivalent IAsp exposure(AUC_(IAsp,0-8 h):566±51 vs 571±85 ng/mL×h,P=0.840).CONCLUSION Maintaining BG at 2.5%below a baseline of<4.00 mmol/L did not compromise the endogenous insulin suppression nor alter the observed pharmacodynamic effects of the study insulin.展开更多
Roux-en-Y gastric bypass surgery（RYGB） has been demonstrated to be successful for treating type-II diabetes2mellitus（T2DM） patients with a body mass index（BMI）,30 kg/m,but reports of RYGB for T2 DM patients with...Roux-en-Y gastric bypass surgery（RYGB） has been demonstrated to be successful for treating type-II diabetes2mellitus（T2DM） patients with a body mass index（BMI）,30 kg/m,but reports of RYGB for T2 DM patients with22 a BMI,28 kg/mare lacking.T2 DM patients with a BMI,28 kg/mwere prospectively recruited to participate in this study in four hospitals.The endpoint was T2 DM remission（defined by fasting blood glucose（FBG） level,110 mg/d L and hemoglobin（Hb）A1c level,6.0% at 12 months postoperatively）.Predictors of remission were investigated by univariate and multivariate analyses.Eighty-six patients were assessed.Eighty-five patients underwent RYGB,with one conversion to open surgery.We compared the values of various variables before and after2 surgery.The mean BMI decreased from 24.68±2.12 to 21.72±2.43 kg/m（P,0.001）.Fifty-eight（67.4%） patients were not treated by drugs or insulin after surgery,and 20 patients（23.3%） had complete remission of T2 DM at12 months after surgery with an acceptable number of complications.The mean Hb A1 c level in the remission group was significantly lower than that in the non-remission group.Patients with a higher weight,lower Hb A1 c level,higher C-peptide level,and higher FBG level were more likely to have T2 DM remission in multivariate2 analyses.In conclusion,RYGB was effective and safe for treating T2 DM patients with a BMI,28 kg/m.Complete remission can be predicted by cases having a higher weight,lower Hb A1 c level,higher C-peptide level,and higher FBG level.展开更多
Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with typ...Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with type 2 diabetes （T2D） were recruited in this study. T2D patients were divided into two groups according to therapy： 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra- venous injection of 1 mg of ghicagon. Results Both fasting and 6-minute post-ghicagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients （0. 76±0. 36 ng/mL vs. 1.81±0. 78 ng/mL, P 〈 0.05 ; 0.88±0.42 ng/mL vs. 3.68±0. 98 ng/mL, P 〈 0. 05 ）. In T1D patients, the C-peptide level after injection of ghicagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy （2.45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P 〈 0.05 ; 5.26±1.24 ng/mL vs. 2.15±0.76 ng/mL, P 〈 0.05 ）. The serum C-peptide level after ghicagon stimulation was positively correlated with C-peptide levels at fasting in all three groups （ r = 0.76, P 〈 0.05 ）. Conclusions The 6-minute ghicagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.展开更多
Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T...Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.展开更多
Aim: To investigate the clinical characteristics of diabetic patients with a low-titer positive for the anti-glutamic acid decarboxylase 65 antibody (GAD antibody). Methods: The subjects were 420 diabetic inpatients. ...Aim: To investigate the clinical characteristics of diabetic patients with a low-titer positive for the anti-glutamic acid decarboxylase 65 antibody (GAD antibody). Methods: The subjects were 420 diabetic inpatients. The endogenous insulin secretion was estimated on the basis of the C-peptide immunoreactivity from a 24 h urine collection (uCPR). Clinical variables were compared between patients negative for the GAD antibody (GAD antibody titer < 1.5 U/mL), a low-titer positive GAD antibody (1.5 U/mL ≤ GAD antibody titer < 10 U/mL) and a high-titer positive GAD antibody (10 U/mL ≤ GAD antibody titer). Results: The low and high-titer positive GAD antibodies were found in 25 and 10 patients, respectively. The uCPR was significantly lower in both the patients with a low (37 ± 33 ug/24h) and high-titer (39 ± 27 ug/24h) positive GAD antibodies than in those negative for GAD antibodies (71 ± 52 ug/24h). The uCPR level was significantly lower in the low-titer positive GAD antibody group (29 ± 22 ug/24h) than in the negative group (67 ± 55 ug/24h) among the patients not taking insulin secretagogues. The difference disappeared in the subjects taking insulin secreagogues. In the stepwise multiple regression analysis, a low-titer positive GAD antibody was independently associated with the uCPR level. Conclusions: Endogenous insulin secretion is reduced in diabetic patients positive for GAD antibodies, even if the titer is low. Earlier initiation of insulin therapy might therefore protect the pancreatic β-cell function in diabetic patients with a low-titer positive GAD antibody.展开更多
Clinically, determination of insulin resistance is important for diabetic patients. We evaluated the relationship among 20/(fasting C-peptide × fasting plasma glucose), HOMA-IR and QUICKI indices in type 2 diabet...Clinically, determination of insulin resistance is important for diabetic patients. We evaluated the relationship among 20/(fasting C-peptide × fasting plasma glucose), HOMA-IR and QUICKI indices in type 2 diabetic patients. The study included 40 patients with type 2 diabetes. Patients divided into three groups based on their medication: metformin, metformin + glibenclamide and metformin + glitazone. Fasting blood sugar, and lipid profile were measured by enzymatic method, serum insulin, and C-peptide were measured by ELISA method. Insulin resistance was calculated by using of 20/(fasting C-peptide × fasting plasma glucose), HOMA-IR and QUICKI indices. There was no significant relationship between 20/(fasting C-peptide × fasting plasma glucose) index and other parameters in all studied groups except QUICKI in metformin group showed a significant correlation with 20/(fasting C-peptide × fasting plasma glucose) index (r = 0.56 and p = 0.03). There was a significant correlation between HOMA-IR and QUICKI indices in all studied groups. There was no significant relationship between 20/(fasting C-peptide × fasting plasma glucose) index with other clinical parameters. On the other hand, our data strongly suggested a significant correlation between HOMA-IR and QUICKI indices in studied subjects with type 2 diabetes.展开更多
基金Supported by National High Level Hospital Clinical Research Funding,No.BJ-2022-145China Endocrinology and Metabolism Young Scientific Talent Research Project,No.2021-N-03.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM),driven by insulin resistance and β cell dysfunction,necessitates reliable assessment of β cell function.C-peptide(CP)measurement,a stable marker of endogenous insulin secretion,is useful for this clinically as it avoids interference from exogenous insulin.While fasting CP(FCP)and postprandial CP(PCP),along with glucose-adjusted indices and ratios,such as FCP/fasting plasma glucose(FPG),2 hours postprandial CP(2hCP)/postprandial blood glucose(PBG)and CP ratio,are used,their comparative efficacy in reflectingβcell function remains unclear.Hemoglobin A1c(HbA1c),a key glycemic control indicator,theoretically linksβcell function to complications,but limited studies have explored the associations between diverse CP indices,HbA1c,and diabetic microvascular complications.AIM To investigate the relationships between different CP indices and HbA1c as well as diabetic microvascular complications in T2DM.METHODS T2DM patients admitted to Department of Endocrinology at Beijing Hospital between July 1,2021 and December 31,2021 were included in the study.Clinical and laboratory data were collected,including CP levels,glucose levels,HbA1c levels and diabetic microvascular complications.Statistical analysis was performed using Statistical Package for the Social Sciences 24.0.RESULTS A total of 453 patients were included in the final analysis.Adjusted by confounding factors,CP ratio and CP/blood glucose(BG)ratio were not relevant to HbA1c,but FCP,2hCP,delta CP,FCP/FPG,2hCP/PBG and delta CP/BG were still negatively correlated to HbA1c,of which 2hCP/PBG showed the strongest negative correlation(r=-0.485,P<0.001).Independent of HbA1c and other confounding factors,2hCP,2hCP/PBG,delta CP and delta CP/BG were protective factors of diabetic retinopathy while 2hCP,delta CP and FCP/FPG were protective factors of diabetic peripheral neuropathy.CONCLUSION This study indicates that higher levels of CP indices suggest better glucose control and a lower prevalence of diabetic microvascular complications,and PCP indices,particularly 2hCP/PBG,were more relevant to HbA1c and diabetic microvascular complications than FCP indices.These results suggest CP-related indices could be useful biomarkers for diabetes management,warranting further research.
文摘AIM To determine whether fasting C-peptide is an independent predictor for non-alcoholic fatty liver disease(NAFLD) in United States population.METHODS Using the National Health and Nutrition Examination Survey(NHANES) 1988-1994, NAFLD participants aged 20 or greater without any other liver diseases were included in this study. Excessive alcohol intake is defined as > 2 drinks per day for males and > 1 drink per day for females. C-peptide and 27 other factors known to be associated with NAFLD(e.g., age, gender, body mass index, waist circumference, race/ethnicity, liver chemistries, and other diabetes tests) were tested in both univariate and multivariate level using logistic regression with a P-value 0.05.RESULTS Of 18825 participants aged ≥ 20, 3235 participants(n = 3235) met inclusion criteria. There were 23 factors associated with NAFLD by univariate analysis. 9 factors, ranked by the highest change in pseudo R2, were found to be significant predictors of NAFLD in multivariate model: waist circumference, fasting C-peptide, natural log of alanine aminotransferase(ALT), total protein, beingMexican American, natural log of glycated hemoglobin, triglyceride level, being non-Hispanic white, and ferritin level. CONCLUSION Together with waist circumference and ALT, fasting C-peptide is among three most important predictors of NAFLD in United States population in the NHANES data set. Further study is needed to validate the clinical utility of fasting C-peptide in diagnosis or monitoring insulin resistance in NAFLD patients.
文摘With the changes of life style, diabetes and its complications have become a major cause of morbidity and mortality. It is reasonable to anticipate a continued rise in the incidence of diabetes and its complications along with the aging of the population, increase in adult obesity rate, and other risk factors. Diabetic en- cephalopathy is one of the severe microvascular complications of diabetes, characterized by impaired cogni- tive functions, and electrophysiological, neurochemical, and structural abnormalities. It may involve direct neuronal damage caused by intracellular glucose. However, the pathogenesis of this disease is complex and its diagnosis is not very clear. Previous researches have suggested that chronic metabolic alterations, vascular changes, and neuronal apoptosis may play important roles in neuronai loss and damaged cognitive functions. Multiple factors are responsible for neuronal apoptosis, such as disturbed insulin growth factor （IGF） system, hyperglycemia, and the aging process. Recent data suggest that insulin/C-peptide deficiency may exert a primary and key effect in diabetic encephalopathy. Administration of C-peptide partially improves the condition of the IGF system in the brain and prevents neuronal apoptosis in the hippocampus of diabetic patients. Those findings provide a basis for application of C-peptide as a potentially effective therapy for diabetes and diabetic encephalopathy.
基金Supported by Mashhad University of Medical Sciences
文摘Diabetes is associated with several complications such as retinopathy, nephropathy, neuropathy and cardiovascular diseases. Currently, insulin is the main used medication for management of insulin-dependentdiabetes mellitus(type-1 diabetes). In this metabolic syndrome, in addition to decrease of endogenous insulin, the plasma level of connecting peptide(C-peptide) is also reduced due to beta cell destruction. Studies in the past decade have shown that C-peptide is much more than a byproduct of insulin biosynthesis and possess different biological activities. Therefore, it may be possible that C-peptide deficiency be involved, at least in part, in the development of different complications of diabetes. It has been shown that a small level of remaining C-peptide is associated with significant metabolic benefit. The purpose of this review is to describe beneficial effects of C-peptide replacement on pathological features associated with insulin-dependent diabetes. Also, experimental and clinical findings on the effects of C-peptide on wholebody glucose utilization, adipose tissue metabolism and tissues blood flow are summarized and discussed. The hypoglycemic, antilipolytic and vasodilator effects of C-peptide suggest that it may contribute to fine-tuning of the tissues metabolism under different physiologic or pathologic conditions. Therefore, C-peptide replacement together with the classic insulin therapy may prevent, retard, or ameliorate diabetic complications in patients with type-1 diabetes.
文摘Objective: In this study, we assessed the level of fasting C-peptide as a predictor of β-cell function and insulin resistance in patients with Type 2 diabetes mellitus (T2DM), Gezira State-Sudan. Methods: In this cross-sectional study, 100 T2DM patients attending the Diabetic patients care Centre were recruited, thirty five patients were males and sixty five were females, the mean age of the patients was 50.29 ± 0.456 years, and body mass index (BMI) was 26.54 ± 0.437. We estimated β-cell function using fasting C-peptide levels;homeostatic model assessment for β-cell function (HOMA-B) and insulin resistance (HOMA-IR) were calculated from C-peptide and fasting blood glucose (FBG). Results: C-peptide was significantly and positively correlated with HOMA-B and HOMA-IR. FBG also showed significant negative correlation with HOMA-B, but was positively and significantly correlated with HOMA-IR. HbA1c was negatively and significantly correlated with HOMA-B. Patients with low C-peptide levels had increased FBG and HbA1c level, while patients with high C-peptide levels were having high HOMA-IR and HOMA-B. Conclusions: Fasting C-peptide is a useful marker of pancreatic β-cell function, and its circulating levels could be used to evaluate insulin secretion and insulin resistance. Moreover, HOMA-IR is an effective index to achieve glycemic control by appropriate pharmacologic treatment of T2DM.
文摘Gestational diabetes is typically diagnosed in the late second or third trimester of pregnancy.It is one of the most common metabolic disorders among expectant mothers,with potential serious short-and long-term complications for both maternal and offspring health.C-peptide is secreted from pancreatic beta-cells into circulation in equimolar amounts with insulin.It is a useful biomarker to estimate the beta-cell function because it undergoes negligible hepatic clearance and consequently it has a longer half-life compared to insulin.Pregnancy induces increased insulin resistance due to physiological changes in hormonal and metabolic homeostasis.Inadequate compensation by islet beta-cells results in hyperglycemia.The standard oral glucose tolerance test at 24-28 wk of gestation sets the diagnosis.Accumulated evidence from prospective studies indicates a link between early pregnancy C-peptide levels and the risk of subsequent gestational diabetes.Elevated C-peptide levels and surrogate glycemic indices at the beginning of pregnancy could prompt appropriate strategies for secondary prevention.
文摘Background: Increased glomerular filtration rate (GFR) commonly develops in early diabetes and is closely correlated with the development of diabetic nephropathy. Objective: The aim was to study the relationship between GFR, C-peptide level and other parameters at diagnosis of Type 1 diabetes. Methods: We determined GFR, Cpeptide level, glycated hemoglobin (HbA1c), body mass index (BMI) SDS and loss of weight at diagnosis of Type 1 diabetes in 495 children (231 females). Linear and multiple regression analysis was used to test for the associations between GFR and other parameters. Results: In the 495 patients, GFR median (interquartile range) was increased vs normal values (p = 0.0001). GFR was significantly negatively correlated with age (p < 0.001) and C-peptide level (p = 0.001), and positively correlated with weight loss (p = 0.02). The multiple regression analysis showed that age (p = 0.001) and C-peptide level (p = 0.05) were independently and negatively related to GFR. Conclusions: This study shows that, at onset of Type 1 diabetes, higher the GFR, younger the age and lower the C-peptide level are. The role of this hyperfiltration in the development of later nephropathy and the putative preventive effect of C-peptide administration need to be evaluated.
文摘As a product in the process of insulin synthesis, C-peptide’s physiological function is still not very clear. Recent studies have shown that C-peptide has many potential cell targets and has biological effects on a variety of tissue systems in humans and other animals. In this paper, the effects of C-peptide on diabetic complications, reproductive endocrine system, blood system, tissue repair, and neoplastic diseases were reviewed to provide references for further clarification of c-peptide related problems.
文摘Background: Measuring fasting C-peptide (FCP) and antibodies against Glutamic acid decarboxylase (GADA) and Islet cell antibodies (ICA) are not so commonly explored in children and young adults. Objectives: To assess the levels of FCP, GADA and ICA in subjects below the age of 25 years with DM and compare their levels to differentiate between Autoimmune and Non-Autoimmune Type 1 DM. Methodology: Blood samples of 93 subjects diagnosed with DM, reporting to the tertiary care hospital, were analysed for ICA, GADA and FCP. Receiver operating characteristics (ROC) curves were analysed to check the ability of autoimmune markers, BMI and C-peptide to differentiate between Autoimmune (Ai) and Non-Autoimmune (NonAi) diabetes. Results: 30/93 (32.2%) were positive for anti-GAD ab and/or ICA and categorised as Autoimmune (Ai), the most common antibody being, anti-GAD ab (80%) in them. The level of FCP among Ai compared to NonAi, was significantly low (p 20.75 nmol/l) as a very dependable test for diagnosing Ai, Type 1 DM, in children and young adults. Its sensitivity and specificity are in the range of 86.2% and 96.8% respectively. Low level of C-peptide (Conclusion: This study revealed predominant positivity for anti-GAD ab (80%) among Ai+ patients. ROC analysis shows GADA above 20.75 nmol/l and Fasting C-peptide < 0.36 nmol/l as a good indicator for diagnosing Ai in children and young adults.
文摘Objective: to explore the role of serum C-peptide index and glycosylated hemoglobin index in the diagnosis of diseased diabetes patients. Methods: eighty patients with suspected diabetes were selected from our hospital, and the selected time range was from August 2021 to August 2022. They were set as the observation group. Eighty patients with physical examination were collected at the same time, and they were set as the control group. The clinical comprehensive diagnosis results and the positive detection rate of serum C-peptide index and glycosylated egg white index were observed. The gold standard was clinical comprehensive diagnosis, To evaluate the efficacy of relying on serum C-peptide index and glycosylated protein index in patients with suspected diabetes. The measurement values of serum C-peptide index level, glycosylated hemoglobin index level and blood glucose index level of the patients diagnosed as diabetes in the observation group and the subjects included in the control group were analyzed. Results: among the 80 patients suspected of diabetes in the observation group, 68 were diagnosed as diabetes according to the clinical comprehensive diagnosis results, accounting for 85.00%. The diagnosis was carried out only according to the serum C-peptide index, and 57 cases were positive, accounting for 71.25%. The diagnosis was carried out only according to the glycosylated hemoglobin index, and 56 cases were positive, accounting for 70.00%. The combined diagnosis of the two indexes showed that 67 cases were positive, accounting for 83.75%, which was significantly higher than the other two groups (P < 0.05). The method of joint test of serum C-peptide index item and glycosylated hemoglobin index item was used to carry out the diagnosis of patients with suspected diabetes. The sensitivity index, specificity index and accuracy index were significantly higher than those of the two indicators used alone, of which, the sensitivity and accuracy were significantly different (P < 0.05). After testing the body serum C-peptide index of patients diagnosed as diabetes in the observation group, its value was lower than that of the control group, and after testing the glycosylated hemoglobin index and blood glucose index, its value was higher than that of the control group (P < 0.05). Conclusion: for patients with diabetes, attention should be paid to the joint test of serum C-peptide index and glycosylated hemoglobin index. The diagnostic efficacy is high and the value is significant.
基金This work was supported by a grant from the National Natural Science Foundation of China （No. 81070677）. Conflict of interest： None.
文摘Background Food composition and style is changing dramatically now, which causes inappropriate secretion of hormones from brain, gastrointestinal and endo-pancreas, may be related to unbalance of glucose in blood. The aim of this study was to explore the fast response of C-peptide, glucagon-like peptide-1 （GLP-1）, ghrelin and endomorphin-1 （EM-1） to the eastern and western style meals in patients with type 2 diabetes mellitus. Methods The study enrolled 57 patients with type 2 diabetes （20 men and 37 women, mean age （67.05±8.26） years）. Eastern style meal （meal A） and western style meal （meal B） were designed to produce the fullness effect. C-peptide, GLP-1, ghrelin and EM-1 were assessed before （0 hour） and after （2 hours） each diet. Results The delta （2h-0h） of C- peptide in meal A was significantly lower than that in meal B （P=0.0004）. C-peptide, GLP-1, ghrelin and EM-1 were obviously higher before meal B than those before meal A （P 〈0.0001, 〈0.0001, =0.001, =0.0004 respectively）. Blood glucose 2 hours and 3 hours after meal B were higher than those after meal A （P=0.0005, 0.0079 respectively）. Correlations between GLP-1 and ghrelin were strongly positive before both meals and 2 hours after both meals and also in relation to the delta of meal A and meal B （rA0h=0.7838, rB05=0.9368, rA25=0.7615, rB2h=0.9409, r A（2h-0h）=0.7531, rB（2h 05）=0.9980, respectively, P 〈0.0001）. Conclusion Western style meal （high fat and protein food） could make more response of C-peptide than eastern style meal, and could stimulate more gut hormones （GLP-1, ghrelin） and brain peptide （EM-1） at the first phase of digestion.
文摘Use of immunomodulating agents to prevent the progression of autoimmuneβ-cell damage leading to type 1 diabetes mellitus(T1DM)is an interesting area for research.These include non-specific anti-inflammatory agents,immunologic vaccination and anti-inflammatory agents targeting specific immune cells or cytokines.Teplizumab is an anti-CD3-molecule that binds to and leads to the disappearance of the CD3/TCR complex and rendering the T cell anergic to its target antigen.Preclinical and clinical trials have demonstrated its efficacy in reducing the decline in serum C-peptide levels and the need for insulin therapy if used early in the disease process of T1DM.The benefits have been apparent as early as six months to as long as seven years after therapy.It has recently been approved by the Food and Drug Administration to delay the onset of clinical(stage 3)type 1 diabetes in children above 8 years of age.In their recent metaanalysis published in the World Journal of Diabetes,Ma et al found that those in the teplizumab treatment group have a greater likelihood of reduction in insulin use,change in C-peptide response,and better glycemic control compared to the control group with a good safety profile.However,all the included randomized control trials have been conducted in high-income countries.High cost of therapy and unknown utility of the molecule in stage 3 disease limit its widespread use.
文摘BACKGROUND Adult-onset diabetes is most often considered to be type 2 diabetes.However,other types of diabetes can develop in adults,including exocrine pancreas diseaseassociated diabetes,also called type 3c diabetes.Differential diagnosis between these types of diabetes still remains a diagnostic challenge.AIM To define anthropometric and laboratory markers that will allow for early diagnosis of pancreatic disease-associated diabetes.METHODS The study group included 44 patients with pancreatogenic diabetes(26 with pancreatic cancer and 18 with chronic pancreatitis),while the control group consisted of 35 patients with type 2 diabetes.We analyzed several parameters,including sex,age,body mass index(BMI),fasting plasma glucose,fasting Cpeptide and insulin with homeostasis model assessment of insulin resistance(HOMA-IR)index calculation,adrenomedullin,adiponectin and creatinine levels with epidermal growth factor receptor(eGFR)calculation.We also developed an equation,termed type 3c diabetes index,which utilized BMI,fasting insulin and adrenomedullin levels,and eGFR to better identify patients with type 3c diabetes.RESULTS Compared to patients with type 2 diabetes,patients with pancreatogenic diabetes had significantly lower BMI(25.11±4.87 kg/m^(2) vs 30.83±5.21 kg/m^(2)),fasting C-peptide(0.81±0.42 nmol/L vs 1.71±0.80 nmol/L),insulin(76.81±63.34 pmol/L vs 233.19±164.51 pmol/L)and HOMA-IR index,despite similar fasting plasma glucose levels.Patients with pancreatogenic diabetes also had lower adrenomedullin levels(0.41±0.25 ng/mL vs 0.63±0.38 ng/mL)but higher adiponectin levels(13.08±7.20μg/mL vs 8.28±4.01μg/mL)and eGFR levels(100.53±21.60 mL/min/1.73 m^(2) vs 85.14±19.24 mL/min/1.73 m^(2)).Finally,patients with pancreatogenic diabetes had significantly lower Type 3c diabetes index values.CONCLUSION Patients with pancreatogenic diabetes differ from patients with type 2 diabetes in anthropometric and laboratory parameters.The type 3c diabetes index had the highest discriminating value,above any single parameter.
文摘Background: Diabetes mellitus (DM) is a disease characterized by hyperglycemia due to (a) insulin-insufficiency (type I DM), or (b) impaired glucose cell-entry (insulin resistance) due to the downregulation of insulin cell receptors (type II DM). Type I DM usually presents with florid manifestations contrary to a slowly-progressive type II. Patients and methods: Over the past 10 years, we encountered 9 obese patients with controlled insulin-requiring type II DM for years, at a dose of 62 ± 5 units/day, who developed sudden and severe insulin resistance (IR) that required 210 ± 25 units daily. All patients had very high levels of anti-Glutamic Acid Decarboxylase (GAD) antibodies. Despite a lack of previous testing for anti-GAD antibodies, they were treated, with Cyclosporin A (Cy), as an autoimmune disorder superimposed on their type II MD. Initially all patients were treated with 100 mg, of Cy, twice daily aiming at an initial trough level of 100 - 150 ng/ml. Three months later, the dose was reduced to 50 mg twice daily for a total of 2 years. Results: Amelioration of IR was achieved by 1 month with a reduction of daily insulin requirement to 123 ± 16 units that further decreased to 76 ± 11 by the end of the 3rd month. Such improvement persisted for 2 years and >1 year after Cy discontinuation. Moreover, a decline in insulin requirements was associated with a parallel decrease in anti-GAD antibody levels and an increase in C-peptide insulin without kidney disease. Conclusion: Anti-GAD antibodies can induce acute IR in type II DM, and this phenomenon can be treated safely and effectively with Cy.
基金This retrospective analysis incorporated data from two clinical trials(CTR20220854 and CTR20222843)sponsored by Chongqing Chenan Biopharmaceutical Co.,Ltd.and Jiangsu Hengrui Pharmaceuticals Co.,Ltd.However,these sponsors did not partake in the study design,data interpretation,or manuscript preparation.
文摘BACKGROUND Insulin therapy plays a crucial role in managing diabetes.Regulatory guidelines mandate assessing the pharmacokinetics(PK)and pharmacodynamics(PD)of new insulin formulations with euglycemic clamp techniques before entry into the market.Typically,blood glucose(BG)levels are maintained at 5%below baseline to suppress endogenous insulin secretion in healthy volunteers.However,in scenarios where BG baseline is relatively low,maintaining it at 5%below baseline can increase hypoglycemic risk.Consequently,we adjusted to maintain it at 2.5%below a baseline of<4.00 mmol/L.It remains uncertain whether this adjustment impacts endogenous insulin inhibition or the PD of study insulin.AIM To evaluate and compare the PD and C-peptide status using two different target BG setting methods.METHODS Data came from euglycemic clamp trials assessing the PK/PD of insulin aspart(IAsp)in healthy participants.Target BG was set at 2.5%below baseline for those with a basal BG of<4.00 mmol/L(group A),and at 5%below baseline for others(group B).The area under the curve(AUC)of IAsp(AUC_(IAsp,0-8 h))and GIR from 0 to 8 hours(AUCGIR,0-8 h)was used to characterize the PK and PD of IAsp,respectively.The C-peptide reduction and PK/PD of IAsp were compared between the two groups.RESULTS Out of 135 subjects,15 were assigned to group A and 120 to group B;however,group B exhibited higher basal Cpeptide(1.59±0.36 vs 1.32±0.42 ng/mL,P=0.006).Following propensity score matching to adjust for basal Cpeptide differences,71 subjects(15 in group A and 56 in group B)were analyzed.No significant differences were observed in demographics,IAsp dosage,or clamp quality.Group B showed significantly higher baseline(4.35±0.21 vs 3.91±0.09 mmol/L,P<0.001),target(4.13±0.20 vs 3.81±0.08 mmol/L,P<0.001),and clamped(4.10±0.17 vs 3.80±0.06 mmol/L,P<0.001)BG levels.Both groups exhibited comparable C-peptide suppression(32.5%±10.0%vs 35.6%±12.1%,P=0.370)and similar IAsp activity(AUCGIR,0-8 h:1433±400 vs 1440±397 mg/kg,P=0.952)under nearly equivalent IAsp exposure(AUC_(IAsp,0-8 h):566±51 vs 571±85 ng/mL×h,P=0.840).CONCLUSION Maintaining BG at 2.5%below a baseline of<4.00 mmol/L did not compromise the endogenous insulin suppression nor alter the observed pharmacodynamic effects of the study insulin.
文摘Roux-en-Y gastric bypass surgery（RYGB） has been demonstrated to be successful for treating type-II diabetes2mellitus（T2DM） patients with a body mass index（BMI）,30 kg/m,but reports of RYGB for T2 DM patients with22 a BMI,28 kg/mare lacking.T2 DM patients with a BMI,28 kg/mwere prospectively recruited to participate in this study in four hospitals.The endpoint was T2 DM remission（defined by fasting blood glucose（FBG） level,110 mg/d L and hemoglobin（Hb）A1c level,6.0% at 12 months postoperatively）.Predictors of remission were investigated by univariate and multivariate analyses.Eighty-six patients were assessed.Eighty-five patients underwent RYGB,with one conversion to open surgery.We compared the values of various variables before and after2 surgery.The mean BMI decreased from 24.68±2.12 to 21.72±2.43 kg/m（P,0.001）.Fifty-eight（67.4%） patients were not treated by drugs or insulin after surgery,and 20 patients（23.3%） had complete remission of T2 DM at12 months after surgery with an acceptable number of complications.The mean Hb A1 c level in the remission group was significantly lower than that in the non-remission group.Patients with a higher weight,lower Hb A1 c level,higher C-peptide level,and higher FBG level were more likely to have T2 DM remission in multivariate2 analyses.In conclusion,RYGB was effective and safe for treating T2 DM patients with a BMI,28 kg/m.Complete remission can be predicted by cases having a higher weight,lower Hb A1 c level,higher C-peptide level,and higher FBG level.
文摘Objective To evaluate islet β cell response to intravenous glucagon （ a non-glucose secretagogue） stimulation in diabetes mellitus. Methods Nineteen patients with type 1 diabetes （T1 D） and 131 patients with type 2 diabetes （T2D） were recruited in this study. T2D patients were divided into two groups according to therapy： 36 cases treated with insulin and 95 cases treated with diet or oral therapy. The serum C-peptide levels were determined at fasting and six minutes after intra- venous injection of 1 mg of ghicagon. Results Both fasting and 6-minute post-ghicagon-stimulated C-peptide levels in T1D patients were significantly lower than those of T2D patients （0. 76±0. 36 ng/mL vs. 1.81±0. 78 ng/mL, P 〈 0.05 ; 0.88±0.42 ng/mL vs. 3.68±0. 98 ng/mL, P 〈 0. 05 ）. In T1D patients, the C-peptide level after injection of ghicagon was similar to the fasting level. In T2D, patients treated with diet or oral drug had a significantly greater fasting and stimulated C-peptide level than those patients received insulin therapy （2.45±0. 93 ng/mL vs. 1.61±0. 68 ng/mL, P 〈 0.05 ; 5.26±1.24 ng/mL vs. 2.15±0.76 ng/mL, P 〈 0.05 ）. The serum C-peptide level after ghicagon stimulation was positively correlated with C-peptide levels at fasting in all three groups （ r = 0.76, P 〈 0.05 ）. Conclusions The 6-minute ghicagon test is valuable in assessing the function of islet β cell in patients with diabetes mellitus. It is helpful for diagnosis and treatment of diabetes mellitus.
基金supported by the National Natural Science Foundation of China(No.82120108008,No.91857117)the Project of Biobank(No.YBKA201909)from Shanghai Ninth People’s Hospital,Shanghai Jiaotong University School of Medicinea grant from Shanghai Jiaotong University School of Medicine(No.19XJ11007).
文摘Objective Isletαcells input is essential for insulin secretion fromβcells.The present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)patients.Methods A total of 4670 T2D patients from seven communities in Shanghai,China were enrolled.The anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were measured.Results The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels increased.Next,the population was divided into two groups:abdominal obesity and non-abdominal obesity groups.After adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity group.There was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity group.In the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p levels.In the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal obesity.The 25(OH)D influenced C-p in part by influencing glucagon.The effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.
文摘Aim: To investigate the clinical characteristics of diabetic patients with a low-titer positive for the anti-glutamic acid decarboxylase 65 antibody (GAD antibody). Methods: The subjects were 420 diabetic inpatients. The endogenous insulin secretion was estimated on the basis of the C-peptide immunoreactivity from a 24 h urine collection (uCPR). Clinical variables were compared between patients negative for the GAD antibody (GAD antibody titer < 1.5 U/mL), a low-titer positive GAD antibody (1.5 U/mL ≤ GAD antibody titer < 10 U/mL) and a high-titer positive GAD antibody (10 U/mL ≤ GAD antibody titer). Results: The low and high-titer positive GAD antibodies were found in 25 and 10 patients, respectively. The uCPR was significantly lower in both the patients with a low (37 ± 33 ug/24h) and high-titer (39 ± 27 ug/24h) positive GAD antibodies than in those negative for GAD antibodies (71 ± 52 ug/24h). The uCPR level was significantly lower in the low-titer positive GAD antibody group (29 ± 22 ug/24h) than in the negative group (67 ± 55 ug/24h) among the patients not taking insulin secretagogues. The difference disappeared in the subjects taking insulin secreagogues. In the stepwise multiple regression analysis, a low-titer positive GAD antibody was independently associated with the uCPR level. Conclusions: Endogenous insulin secretion is reduced in diabetic patients positive for GAD antibodies, even if the titer is low. Earlier initiation of insulin therapy might therefore protect the pancreatic β-cell function in diabetic patients with a low-titer positive GAD antibody.
文摘Clinically, determination of insulin resistance is important for diabetic patients. We evaluated the relationship among 20/(fasting C-peptide × fasting plasma glucose), HOMA-IR and QUICKI indices in type 2 diabetic patients. The study included 40 patients with type 2 diabetes. Patients divided into three groups based on their medication: metformin, metformin + glibenclamide and metformin + glitazone. Fasting blood sugar, and lipid profile were measured by enzymatic method, serum insulin, and C-peptide were measured by ELISA method. Insulin resistance was calculated by using of 20/(fasting C-peptide × fasting plasma glucose), HOMA-IR and QUICKI indices. There was no significant relationship between 20/(fasting C-peptide × fasting plasma glucose) index and other parameters in all studied groups except QUICKI in metformin group showed a significant correlation with 20/(fasting C-peptide × fasting plasma glucose) index (r = 0.56 and p = 0.03). There was a significant correlation between HOMA-IR and QUICKI indices in all studied groups. There was no significant relationship between 20/(fasting C-peptide × fasting plasma glucose) index with other clinical parameters. On the other hand, our data strongly suggested a significant correlation between HOMA-IR and QUICKI indices in studied subjects with type 2 diabetes.
