Determination Of C-peptide Research Articles

IDF23-0329 Serum C-Peptide determination and prediction of Diabetic Retinopathy in Type 2 Diabetes Mellitus from South India

IDF23-0329 Serum C-Peptide determination and prediction of Diabetic Retinopathy in Type 2 Diabetes Mellitus from South India

Significance of standard and speckle-tracking echocardiography for early diagnosis of asymptomatic left ventricular dysfunction in type 2 diabetes

Aim. To study the relationship between echocardiographic parameters of left ventricular (LV) function and carbohydrate metabolism indicators, as well as to evaluate value of speckle-tracking echocardiography (STE) in the early diagnosis of subclinical LV dysfunction in type 2 diabetes (T2D) in individuals without clinical manifestations of cardiovascular disease (CVD).Material and methods. The study included 120 people of both sexes aged 45 to 75 years. Patients were divided into three following groups: 1 — with T2D (n=53), 2 — with prediabetes (n=20), 3 — control, without carbohydrate metabolism disorders (n=47). All participants underwent transthoracic two-dimensional echocardiography with an assessment of standard systolic and diastolic parameters, as well as quantitative STE indicators. In addition, all participants underwent laboratory diagnostics of carbohydrate metabolism disorders, which included the determination of blood fasting glucose, glycated hemoglobin (HbA1c), insulin, and C-peptide, as well as insulin resistance index estimation.Results. In patients with T2D, in comparison with the control group, diastolic function parameters were significantly different as follows: a lower value of early to late diastolic transmitral flow velocity (E/A) ratio, the ratio of early transmitral flow velocity to early diastolic mitral annulus velocity (E/e'), mitral annular velocity (e') and higher isovolumic relaxation time (IVRT), as well as early diastolic flow deceleration time (DT). According to multivariate analysis, not only T2D, but also prediabetes was an independent predictor of diastolic dysfunction. The Simpson's LV ejection fraction was preserved in all study participants. In patients with T2D, in comparison with the control, according to STE, a decrease in global longitudinal strain (GLS), an increase in apical rotation, and also LV twist were revealed. In a multivariate regression analysis, the HbA1c level had an inverse relationship with GLS and was an independent predictor of its decrease, and the T2D duration was a significant predictor of twisting changes, apical and basal rotation. At the same time, GLS and LV twist had a high sensitivity in determining the decrease in E/A, e'/a', e', as well as the increase in IVRT.Conclusion. In patients with T2D without CVD manifestations, sub-clinical signs of diastolic dysfunction were revealed, such as delayed LV relaxation; systolic dysfunction with preserved ejection fraction was manifested by a decrease in GLS, as well as an increase in apical rotation and LV twisting, identified by STE. The severity of asymptomatic LV systolic-diastolic dysfunction was associated with the severity of glucose metabolism disorders and T2D duration.

A homogeneous enzyme-free ratiometric immunoassay for the determination of C-peptide

In this study, a homogeneous enzyme-free ratiometric (HOMO- EF-RA) immunoassay was developed for the sensitive detection of C-peptide. In the immunoassay, there have been a miscible detection system by mixing with the fluorescent quantum dots conjugated antigen (QD-Ag conjugates) and the dylight dye conjugated antibody (DL-Ab conjugates). When connecting between Ag-QD conjugate and Ab-DL conjugate by specific recognition, the system emitted fluorescence resonant energy transfer (FRET). The target C-peptide can inhibit the connection and FRET formation between QD-Ag conjugates and DL-Ab conjugates, thus changing the dual fluorescence. By measuring the ratio dual fluorescence changes of the system, the content of C-peptide was evaluated without any enzyme used and multiple incubation and washing steps. This immunoassay realized the highly sensitive (as low as 0.12 ng mL−1), selective and rapid (as less as 6 min) detection of C-peptide. Furthermore, the simple and convenient immunoassay was applied successfully to the determination of C-peptide in real serum samples.

C-peptide determination in the diagnosis of type of diabetes and its management: A clinical perspective.

Impaired beta‐cell function is a recognized cornerstone of diabetes pathophysiology. Estimates of insulin secretory capacity are useful to inform clinical practice, helping to classify types of diabetes, complication risk stratification and to guide treatment decisions. Because C‐peptide secretion mirrors beta‐cell function, it has emerged as a valuable clinical biomarker, mainly in autoimmune diabetes and especially in adult‐onset diabetes. Nonetheless, the lack of robust evidence about the clinical utility of C‐peptide measurement in type 2 diabetes, where insulin resistance is a major confounder, limits its use in such cases. Furthermore, problems remain in the standardization of the assay for C‐peptide, raising concerns about comparability of measurements between different laboratories. To approach the heterogeneity and complexity of diabetes, reliable, simple and inexpensive clinical markers are required that can inform clinicians about probable pathophysiology and disease progression, and so enable personalization of management and therapy. This review summarizes the current evidence base about the potential value of C‐peptide in the management of the two most prevalent forms of diabetes (type 2 diabetes and autoimmune diabetes) to address how its measurement may assist daily clinical practice and to highlight current limitations and areas of uncertainties to be covered by future research.

Exposure Levels and Contributing Factors of Various Arsenic Species and Their Health Effects on Korean Adults.

Arsenic is a human carcinogen. Data on urinary arsenic species analyses of Koreans are limited. This study evaluated the arsenic exposure level, contributing factors, and health effects in Korean adults. Dietary intake information and urine samples were obtained from 2044 participants. Arsenic exposure was assessed based on urinary concentrations of arsenic species, such as inorganic arsenic, As(III) and As(V), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and arsenobetaine (AsB), using high-performance liquid chromatography with inductively coupled plasma mass spectrometry, followed by determination of biomarkers, malondialdehyde and c-peptide. The geometric mean concentrations were 30.9 μg/L for the sum of inorganic arsenic and their metabolites, and 84.7 μg/L for the total sum of arsenic measured. Urinary concentrations of arsenic species were influenced by age, inhabitant area (inland or coastal), and seafood intake, which was positively correlated with inorganic arsenic, DMA, and AsB. Rice intake was positively correlated with inorganic arsenic and its metabolites but not with AsB. Additionally, malondialdehyde and c-peptide levels were significantly associated with urinary concentrations of various arsenic species. Seafood and rice are major sources of organic/inorganic arsenic exposure in Korean adults; however, it is necessary to evaluate whether their overconsumption could have a potentially detrimental effect on human health.

Longitudinal progression of diabetes mellitus in Wolfram syndrome: The Washington University Wolfram Research Clinic experience.

(1) Describe the progression of diabetes mellitus over time in an observational study of Wolfram syndrome, a rare, genetic, neurodegenerative disorder, which often includes diabetes mellitus and is typically diagnosed during childhood or adolescence. (2) Determine whether C-peptide could be used as a marker of diabetes progression in interventional trials for Wolfram syndrome. N=44 (25F/19M) participants with genetically confirmed Wolfram syndrome attended the Washington University Wolfram Research Clinic annually from 2010 to 2019. Medical history, physical examinations, blood sampling, and questionnaires were used to collect data about diabetes mellitus and other components of Wolfram syndrome. Beta-cell function was assessed by determination of C-peptide during a mixed meal tolerance test. Random coefficients models evaluated the rate of progression of C-peptide over time, and power analyses were used to estimate the number of subjects needed to detect a change in C-peptide decline during an intervention trial. 93.2% of patients had diabetes mellitus. Mean HbA1c across all study visits was 7.9%. C-peptide significantly decreased with increasing duration of diabetes mellitus (p< 0.0001); an optimal break point in C-peptide decline was identified to occur between 0.1 and 2.3 years after diabetes mellitus diagnosis. Twenty patients per group (active vs. control) were estimated to be needed to detect a 60% slowing of C-peptide decline during the first 2.3 years following diabetes diagnosis. C-peptide declines over time in Wolfram syndrome and could potentially be used as a marker of diabetes progression in interventional studies for Wolfram syndrome, especially within the first 2 years after diabetes diagnosis.

Proinsulin to C-Peptide Ratio in the First Year After Diagnosis of Type 1 Diabetes.

The proinsulin to C-peptide (PI:C) ratio is reputedly a biomarker of β-cell endoplasmic reticulum (ER) stress. This study examined the natural history of the PI:C ratio and its correlation with residual β-cell function in childhood new-onset type 1 diabetes (T1D). Over the first year of T1D, the temporal trend in fasting and nutrient-stimulated PI data is limited. PI was a secondary pre-planned analysis of our 1-year, randomized, double-blind, placebo-controlled gamma aminobutyric acid (GABA) trial in new-onset T1D. Of the 99 participants in the primary study, aged 4 to 18 years, 30 were placebo. This study only involved the 30 placebo patients; all were enrolled within 5 weeks of T1D diagnosis. A liquid mixed meal tolerance test was administered at baseline and 5 and 12 months for determination of C-peptide, PI, glucose, and hemoglobin A1C. Both the fasting (P = 0.0003) and stimulated (P = 0.00008) PI:C ratios increased from baseline to 12 months, indicating escalating β-cell ER stress. The baseline fasting PI correlated with the fasting change in C-peptide at 12 months (P = 0.004) with a higher PI correlating with greater decline in C-peptide. Patients with an insulin-adjusted A1C >9% (hence, not in remission) had higher fasting PI:C ratios. Younger age at diagnosis correlated with a higher PI:C ratio (P = 0.04). Children with new-onset T1D undergo progressive β-cell ER stress and aberrant proinsulin processing, as evidenced by increasing PI:C ratios. Moreover, the PI:C ratio reflects more aggressive β-cell onslaught with younger age, as well as diminished glycemic control.

Glutamic Acid Decarboxylase and Islet Cell Cytoplasmic Autoantibodies Positivity in Latent Autoimmune Diabetes of Adults: Need for Early Insulinisation

Introduction: Latent Autoimmune Diabetes of Adults (LADA) remains a poorly understood disease at both the clinical and research level and usually misdiagnosed as Type 2 Diabetes Mellitus (T2DM) and treated with Oral Hypoglycaemic Agents (OHA). This might lead to accelerated b-cell destruction leading to early insulin-dependency in these patients. Screening of T2DM and determination of C-peptide and insulin antibodies helps to differentiate this disease from LADA. Early insulinisation of these patients prevents b-cell destruction and preserves residual b cell function. Aim: To screen type 2 diabetic patients for potential LADA subjects based on LADA clinical risk score and to confirm them as LADA based on Glutamic Acid Decarboxylase (GADA) positivity and Islet Cell Cytoplasmic Autoantibodies (ICA) positivity. Materials and Methods: The hospital based cross-sectional study was done on 945 T2DM patients attending Out Patient Department (OPD) of Rajarajeswari Medical College and Hospital, Bengaluru, Karnataka, India from March 2017 to May 2019. Patients were screened using LADA clinical risk score and potential LADA subjects were identified and tested for C-peptide, GAD and IC Antibodies to confirm LADA. C-Peptide and GAD antibodies were measured by ELISA method. IC antibodies were observed using immunoflorescence microscopy. Inferential Statistics (Chi-square test, Z test, t-test) by using SPSS V20 and MS Excel was used. Results: Out of 945 T2DM patients, 188 patients (20%) were considered as potential LADA subjects based on LADA clinical risk score. All 188 subjects were tested for C-peptide, GAD and IC antibodies. 36% (68 subjects) of them had low C-peptide levels. Among them four subjects (6%) had high GADA titer confirming them as LADA subjects. Three (4%) of the subjects had low GADA titer, remaining 61 subjects did not show antibody positivity. Only one of them had both IC antibody positivity out of four subjects with high GADA titer. Remaining 64% (120 subjects) had normal C-peptide levels and antibody negative. Conclusion: Using 5-point LADA clinical risk score 20% were identified as potential LADA subjects out of 945 T2DM subjects. 6% of the potential LADA subjects had high GADA titer confirming them as LADA, who may be benefited by early insulinisation.

Insights into the physiology of C-peptide.

Current knowledge suggests a complex role of C-peptide in human physiology, but its mechanism of action is only partially understood. The effects of C-peptide appear to be variable depending on the target tissue, physiological environment, its combination with other bioactive molecules such as insulin, or depending on its concentration. It is apparent that C-peptide has therapeutic potential for the treatment of vascular and nervous damage caused by type 1 or late type 2 diabetes mellitus. The question remains whether the effect is mediated by the receptor, the existence of which is still uncertain, or whether an alternative non-receptor-mediated mechanism is responsible. The Institute of Endocrinology in Prague has been paying much attention to the issue of C-peptide and its metabolic effect since the 1980s. The RIA methodology of human C-peptide determination was introduced here and transferred to commercial production. By long-term monitoring of C-peptide oGTT-derived indices, the Institute has contributed to elucidating the pathophysiology of glucose tolerance disorders. This review summarizes the current knowledge of C-peptide physiology and highlights the contributions of the Institute of Endocrinology to this issue.

MON-623 Pattern of C-Peptide Response to Oral Glucose Tolerance Test: Interest and Cut-Off Values

Introduction: Oral glucose tolerance test (OGTT) allows classification of subjects in 3 groups, depending on glycaemia 120 minutes after 75g glucose ingestion: normal (glycaemia < 1.4 g/L), glucose intolerant (1.4-2 g/L) and diabetic (>2g/L). Five insulin profiles following OGTT associated with different incidence rates of diabetes over 10 years of follow-up have also previously been described (Kraft J et al, Laboratory Medicine, 1975; Hayashi T et al, Diabetes Care.2013). Insulin measurement is very sensible to hemolysis and can advantageously be replaced by C-peptide determination. However, little is known about C-peptide reference values and response to OGTT.Material and Methods: 128 patients were included to evaluate glyceamia (COBASe801® ROCHE Diagnostics, France), insulin and C-peptide (LiaisonXL®, Diasorin, France) responses to OGTT.Results: According to Hayashi classification, 23 (18%) patients of the whole cohort harbored a physiological insulin response corresponding to profile I (peak of insulin during OGTT at 30 min and higher insulin level at 60 vs. 120 min). Others presented 5 pathological profiles: 14 (11%) patients were classified in profile II (peak of insulin at 30 min and lower or equal insulin level at 60 vs. 120 min), 56 (44%) in profile III (peak of insulin at 60 min), 26 (20%) in profile IV (peak of insulin at 120 min and lower insulin level at 30 vs. 60 min), and finally 9 (7%) in profile V (peak of insulin at 120 min and higher or equal insulin level at 30 vs. 60 min). Only 4 different mean C-peptide profiles emerged from the subgroups previously defined by insulin profile, mean C-peptide profile being substantially similar to mean insulin profile. The only major difference relied on a similar C-peptide profile corresponding to a growing curve from T0 to T120 in both patients with insulin profile IV and V. Mean and 95% confidence interval of C-peptide value at the different times of OGTT were also calculated in the subgroup of patients with both normal glycemic and insulin (pattern I) responses to propose reference values: respectively T0: 0.53 (0.26-0.77); T30: 2.2 (1.24-3.29); T60: 2.26 (1.36-3.68); T120: 1.88 (0.84-2.62) nmol/L. Conclusion: C-peptide response to OGTT profile seems to give globally the same information as insulin profile and should therefore also be predictive of the risk type 2 diabetes in case of hemolyzed samples. The slight differences observed between insulin and C-peptide profiles can be explained by their different metabolic pathways, insulin being quickly degraded in the liver and C-peptide undergoing a longer renal elimination. This work also allows us to propose for the first-time reference values for C-peptide at the different times of OGTT using Liaison XL®.

MON-184 Hypoglycemia During Mixed Meal Tolerance Testing and Early Glucose Dysregulation in Cystic Fibrosis

Post-prandial and oral glucose tolerance test (OGTT)-related hypoglycemia is common in cystic fibrosis (CF). The mechanisms underlying this “reactive” hypoglycemia are unclear. We hypothesized that late hypoglycemia would be associated with higher peak plasma glucose, impaired early-phase insulin secretion compared to PI-NGT, and augmentation of late insulin secretion. To understand these relationships, we performed standardized mixed-meal tolerance tests (MMTT) with timed blood sampling for determination of plasma glucose, insulin and C-peptide in non-diabetic adolescents and young adults with pancreatic insufficient CF (PI-CF). Glucose tolerance was defined by OGTT as: normal (NGT; 1-hour glucose <155 and 2-hour glucose <140mg/dL, n=13), or abnormal (AGT; 1-hour glucose ≥155 or 2-hour glucose ≥140 mg/dL and <200 mg/dL, n=21). Hypoglycemia was defined as plasma glucose <70mg/dL during MMTT and used to assign subjects to exposure groups for analysis. Insulin secretory rates (ISRs) were derived by parametric deconvolution of C-peptide kinetics using a two-compartment model. Glucose and ISR incremental areas under curve (Glc-AUC; ISR-AUC) were calculated. Peak plasma glucose and ISR-AUCinterval were compared between hypoglycemia groups [hypo(+) vs hypo(-)] using Student’s t-test and Mann Whitney U Tests, respectively. Linear regression was performed to explore whether ISR AUC was different in hypo(+) vs hypo(-) after adjustment for Glc-AUC. 34 subjects with PI-CF were evaluated. Participants were 50% female, aged 25±8.7 years, with FEV-1 % predicted 81±19, HbA1c 5.5±0.4%, and BMI z-score 0.17±1. Hypoglycemia occurred in 9 subjects (2 NGT, 7 AGT) at 163±30 min following the start of the meal. No group differences in gender, age, lung function, HbA1c, or BMI z-score were found. Peak plasma glucose was higher in hypo(+) vs hypo(-) (215±21 vs 168±33 mg/dL, p=0.0004). Moreover, early-phase ISR-AUC15-45 min was lower in hypo(+) vs hypo(-) PI-NGT (609±190 vs 1313±850 µU/mL, p=0.03), including the 2 NGT-hypo(+): 430mg/dL and 548mg/dL, respectively. ISR-AUC120-180 min was not different in hypo(+) than hypo(-) PI-AGT (2528 ±1723 vs 2219±1072 µU/mL, p=0.85); however, glc-AUC120-180 min was lower in hypo(+) than hypo(-) PI-AGT (-785±1288mg·min/dL vs 750±1115 mg·min/dL, p=0.015). After adjusting for glc-AUC over this interval, hypo(+) tended to have higher late insulin secretion than hypo(-) PI-AGT (p=0.089). Meal-related hypoglycemia in CF is common and not only seen following the glucose load of an OGTT. Hypoglycemia is associated with early glucose dysregulation (higher peak plasma glucose), loss of early-phase insulin secretion (lower ISR AUC15-45 min), and possible late compensatory hyperinsulinemia (higher ISR AUC120-180 min relative to glucose). Whether hypoglycemia may predict progression to CFRD in individuals with PI-CF requires further study.

Unusual high blood glucose in ketoacidosis as first presentation of type 1 diabetes mellitus

SummaryDiabetic ketoacidosis is a life-threatening complication of diabetes mellitus. It usually occurs in patients with type 1 diabetes where it is typically associated with only moderately increased blood glucose. Here, we report the case of a 52-year-old female patient who was admitted to the emergency unit with severely altered mental status but stable vital signs. Laboratory results on admission revealed very high blood glucose (1687 mg/dL/93.6 mmol/L) and severe acidosis (pH <7) with proof of ketone bodies in serum and urine. Past history revealed a paranoid schizophrenia diagnosed 10 years ago and for which the patient was treated with risperidone for many years. Acute treatment with intravenous fluids, intravenous insulin infusion and sodium bicarbonate improved the symptoms. Further laboratory investigations confirmed diagnosis of autoimmune type 1 diabetes. After normalization of blood glucose levels, the patient could soon be discharged with a subcutaneous insulin therapy.Learning points:Diabetic ketoacidosis as first manifestation of type 1 diabetes can occur with markedly elevated blood glucose concentrations in elder patients.Atypical antipsychotics are associated with hyperglycemia and an increased risk of new-onset diabetes.First report of risperidone-associated diabetic ketoacidosis in new-onset type 1 diabetes.Patients treated with atypical antipsychotics require special care and regular laboratory examinations to detect hyperglycemia and diabetic ketoacidosis.In cases when the diagnosis is in doubt, blood gas analysis as well as determination of C-peptide and islet autoantibodies can help to establish the definite diabetes type.

Early Diagnosis of Diabetes Using Stochastic Sensors

Diabetes is one of the most frequent diseases, affecting 1 in 12 persons worldwide according to International Diabetes Federation, therefore improved methods of monitoring and screening are needed. Stochastic sensors represent a promising candidate in early diagnosis due to their capacity to perform qualitative and quantitative analysis of multiple biomarkers. For the determination of C-peptide, insulin, proinsulin, leptin, adiponectin and CRP the immunoassay techniques are routinely used in clinical practice, requiring diferite detection kits, therefore one of the main advantage in using this method consists in determining in one run all the analytes. In this paper, stochastic microsensors based on new carbon materials were proposed for the assay of diabetes related biomarkers like: proinsulin, insulin, C-peptide, leptin, adiponectin, Zn, pyruvic and lactic acids and CRP in biological fluids like urine and serum samples.

English

This study was designed to demonstrate the relationship between 25-hydroxy vitamin D (25(OH)D) levels and insulin resistance (IR) in normal pregnancy and in gestational diabetes mellitus (GDM). The study included 103 pregnant women classified into two main groups: normal pregnant (n= 48) and GDM (n= 55). Further classification for each group was carried out based on 25(OH)D status (deficient, insufficient and sufficient). Serum were used for determination of fasting blood glucose (FBG), fasting insulin (FI), C-peptide, cholesterol, triacylglycerol (TAG), total Ca, 25(OH)D and parathyroid hormone (PTH). IR markers were calculated including glucose/insulin ratio (G/I), fasting insulin resistance index (FIRI), and homeostasis model assessment of insulin resistance (HOMA-IR), Log HOMA-IR, HOMAA1-% B, and HOMA β cell. Results indicated significantly increased FBG, FI, C-peptide, FIRI, HOMA-IR, Log HOMA-IR and HOMA β cell, cholesterol and TAG in GDM compared to control group. Mean values of 25(OH)D did not show significant variations between the two groups. In control group, no significant correlations were obtained between 25(OH)D and any tested parameters, however, in GDM 25(OH)D showed significant correlations with FBG and Log HOMA-IR. Results also revealed increased prevalence of 25(OH)D deficiency among healthy pregnancy and GDM (~69 and 67%, respectively) groups. Furthermore, deficient GDM had significantly higher FBG, IR markers, cholesterol and TAG compared to matched deficient normal pregnancy. Improving 25(OH)D status had significantly normalizes IR and lipid parameters, indicating that 25(OH)D may be associated with elevated IR that accompany GDM. Key words: Gestational diabetes mellitus, vitamin D, insulin resistance, calcium homeostasis.

Purity Measurement of Human C-Peptide by High Performance Liquid Chromatography and Quantitative Nuclear Magnetic Resonance

Purity determination of human C-peptide (hCP) with metrological traceability is fundamental to accurate and comparable clinical analysis of hCP. Based on high performance liquid chromatography and quantitative nuclear magnetic resonance (qNMR) with a purified hCP, a method was reported to determine the purity of an hCP sample used in an intercomparison. The composition of deuterium solvent for qNMR was optimized to improve the separation of the β-proton of an aspartic acid residue in the sequence of hCP, which were used for NMR integration. The calculated mean and uncertainty (77.86 ± 3.85%) are consistent with the results (80.18 ± 0.62%) of different methods reported by many metrological laboratories. This method extended the application of qNMR to peptides with high molecular weight of about 3020.

Simultaneous determination of insulin, DesB30 insulin, proinsulin, and C-peptide in human plasma samples by liquid chromatography coupled to high resolution mass spectrometry

The endocrine pancreatic processes comprising the main actions of insulin, proinsulin, and C-peptide, represent a well-investigated system in the human organism because of the widespread epidemic of diabetes mellitus. Besides their medical relevance, insulin and its related compounds have further been of particular interest also to forensic science and doping controls, and in all disciplines, a specific and sensitive determination of the target analytes is critical for accurate result interpretation. In the present study, a method was developed allowing for the simultaneous determination of human insulin (and its synthetic analogues), the degradation product DesB30 human insulin, proinsulin, and C-peptide in plasma samples (100 µL) by liquid chromatography coupled to high resolution mass spectrometry. Immunoaffinity extraction employing magnetic nanoparticles and two monoclonal antibodies for insulin and C-peptide were used in combination with two internal standards. The assay was validated for quantitative result evaluation considering the parameters specificity, linearity (0–10 ng/mL), limit of detection (~0.05 ng/mL), precision at high and low levels (6–25%), accuracy at high and low levels (85–127%), recovery (33–44%), ion suppression, and stability. Furthermore, the method was applied to samples from healthy athletes, patients with diabetes mellitus (type II) with and without treatment with insulin, and patients being treated for diabetes mellitus (type I). The results enable a thorough interpretation of the data with respect to endocrine, forensic and doping control samples.

Effects of saxagliptin add-on therapy to insulin on blood glycemic fluctuations in patients with type 2 diabetes: A randomized, control, open-labeled trial.

Background:To investigate whether saxagliptin add-on therapy to continuous subcutaneous insulin infusion (CSII) further improve blood glycemic control than CSII therapy in patients with newly diagnosed type 2 diabetes (T2D).Methods:This was a single-center, randomized, control, open-labeled trial. Newly diagnosed T2D patients were recruited between February 2014 and December 2015. Subjects were divided into saxagliptin add-on therapy to CSII group (n = 31) and CSII therapy group (n = 38). The treatment was maintained for 4 weeks. Oral glucose tolerance test was performed at baseline. Serum samples were obtained before and 30 and 120 minutes after oral administration for glucose, insulin, and C-peptide determination. Continuous glucose monitoring (CGM) was performed before and endpoint.Results:A total of 69 subjects were admitted. After 4-week therapy, CGM data showed that patients with saxagliptin add-on therapy exhibited further improvement of mean amplitude glycemic excursion (MAGE), the incremental area under curve of plasma glucose >7.8 and 10 mmol/L compared with that of control group. In addition, the hourly mean blood glucose concentrations, especially between 0000 and 0600 in patient with saxagliptin add-on therapy, were significantly lower compared with that of the control patients. Furthermore, patients in saxagliptin add-on group needed lower insulin dose to maintain euglycemic control. In addition, severe hypoglycemic episode was not observed from any group.Conclusion:Saxagliptin add-on therapy to insulin had the ability of further improve blood glycemic controlling, with lower insulin dose required by patients with T2D to maintain euglycemic controlling.

Posttransplantation diabetes mellitus in patients after kidney transplantation - Incidence and risk factors

Transplantation (NTX) associated ischemia-reperfusion-mechanisms and the predisposition for insulin resistance are discussed as causes of a posttransplantation diabetes mellitus (PTDM). Furthermore, immunosuppressants can have a damaging effect on insulin secretion. 55 metabolically healthy patients with an endstage renal disease (age 52 ± 14 years, body mass index 27 ± 5 kg / m(2), blood pressure 137 ± 15/82 ± 11 mmHg) were included in a prospectively cohort study. These patients were transplanted between 2009 and 2011 (82 % of the NTX patients). Baseline examination was performed before NTX. Within the 2nd week as well as 6 and 12 months after transplantation an oral glucose tolerance test (oGGT), 3 and 9 months after NTX a glucagon test took place. In these connections the determination of plasma glucose, C-peptide and insulin was performed. Study endpoints were: graft failure, impaired glucose tolerance (iGT), PTDM, patient's death. Over a follow-up-period of 1 year post NTX iGT / PTDM occurred in 31 % and graft failure in 13 %. In comparison with the healthy control group patients with iGT / PTDM were older (59 ± 8 vs. 48 ± 14ys, p = 0.001), overweight (BMI 29 ± 4 vs. 26 ± 5 kg / m(2), p = 0.038), showed an indication of an insulin resistance before NTX (HOMA 4.0 ± 2.9 vs. 2.4 ± 1.4, p = 0.013; C-peptide 10.1 ± 5.2 vs. 7.1 ± 3.6 ng / ml, p = 0.014; insulin 14.6 ± 9.4 vs. 10.6 ± 5.5mU / l, p = 0.045) and higher HbA1c levels (5.6 ± 0.5 vs. 5.4 ± 0.4 %, p = 0.032). Age (p = 0.001), fasting plasma glucose (p = 0.042), the glucose levels of oGTT immediately after transplantation were shown as prognostically relevant (fasting glucose: p = 0.027; 1 h: p = 0.014; 2 h: p = 0.002). An isolated defective secretion as a result of a toxic damage to the β-cells by immunosuppressants couldn't be shown in any of the patients with iGT / PTDM. 4 % of the patients died in the first year after NTX. In 31 % a disorder of glucose metabolism was found as a frequent complication after NTX. The HOMA index was found to be a meaningful marker for an existing insulin resistance. The fasting glucose before and an oGTT in the first weeks after NTX showed itself as clinically valid laboratory parameters for a risk assessment.

Diabetes induction by total pancreatectomy in minipigs with simultaneous splenectomy: a feasible approach for advanced diabetes research.

Safe and reliable diabetes models are a key prerequisite for advanced preclinical studies on diabetes. Chemical induction is the standard model of diabetes in rodents and also widely used in large animal models of non-human primates and minipigs. However, uncertain efficacy, the potential of beta-cell regeneration, and relevant side effects are debatable aspects particularly in large animals. Therefore, we aimed to evaluate a surgical approach of total pancreatectomy combined with splenectomy for diabetes induction in an exploratory study in Goettingen minipigs. Total pancreatectomy was performed in Goettingen minipigs (n = 4) under general anesthesia and endotracheal intubation. Prior to surgery, a central venous line was established for drug application and blood sampling. After median laparotomy, splenectomy was performed and the lobular pancreas was carefully dissected with particular attention to the duodenal vascular arcade. Close monitoring of blood glucose was initiated immediately after surgery by standard glucometer measurement or continuous glucose monitoring systems (CGMS). Exogenous insulin was given by multiple daily subcutaneous (s.c.) injections or via insulin pump systems (CSII). Complete endogenous insulin deficiency was confirmed by intravenous glucose tolerance test (ivGTT) and measurement of c-peptide. For establishing a suitable regimen for diabetes management, the animals were followed for 4-6 weeks. Following pancreatectomy and splenectomy, the animals showed a quick recovery from surgery and initial analgetic medication and volume substitution could be terminated within 24 h. A rapid increase in blood glucose was observed immediately following pancreatectomy necessitating insulin therapy. The induced exocrine insufficiency did not cause any clinical symptoms. Complete insulin deficiency could be confirmed in all animals by determination of negative c-peptide during glucose challenge. The two regimen of insulin treatment (multiple daily injections (MDI) and continuous subcutaneous insulin infusion (CSII)) were both feasible with respect to acceptable glycemic control whereas CSII was considerably advantageous in comfort and popularity for both animals and care takers. Surgical pancreatectomy in combination with splenectomy to facilitate access to the pancreas is a feasible model for efficient diabetes induction in minipigs. The procedure itself and postoperative animal care could be performed without complications in this exploratory study. Nevertheless, this approach requires well-equipped infrastructure, experienced and skilled surgeons and anesthesiologists and dedicated animal care takers. The impact of total pancreatectomy in combination with splenectomy on the digestive and immune system must be considered in the design and definition of end points of experimental diabetes and transplantation studies.

Diabetes associated with dominant insulin gene mutations: outcome of 24-month, sensor-augmented insulin pump treatment.

Diabetes associated with dominant insulin gene mutations: outcome of 24-month, sensor-augmented insulin pump treatment.