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We present a case of hypoglycemia in a young patient without diabetes mellitus who presented initially with enlarging neck mass and weight loss, and was found to have aggressive melanoma with metastasis to multiple organs and diffuse lymphadenopathy. He had presented to the emergency room two times with neuroglycopenic symptoms that required admission and intravenous dextrose continuously. Evaluation of hypoglycemia included C-peptide, insulin levels, insulin-like growth factor (IGF) -I and -II, and ß- hydroxybutyrate. Insulin levels were suppressed appropriately during hypoglycemia, however, IGF-II:IGF-I ratio was high, suggesting non-islet tumour induced hypoglycemia. The presence of IGF-II produced by large tumors results in a low hepatic glucose output and increased uptake by skeletal muscle, resulting in hypoglycemia especially in a patient with extremely low appetite such as our patient. Treating the culprit malignancy leads to resolution of hypoglycemia, but corticosteroids have been used to suppress IGF-II levels and alleviate symptoms.

We present a case of a 73-year-old woman who developed recurrent hypoglycaemia during a prolonged hospital stay following a mechanical fall. She had a complex history of insulin-treated diabetes mellitus, hypothyroidism, diffuse systemic cutaneous sclerosis, Raynaud’s disease, previous breast cancer, Barrett’s oesophagus and previous partial gastrectomy for a benign mass. Hypoglycaemia persisted despite weaning of insulin. She had no clinical features of adrenal or pituitary insufficiency with an acceptable cortisol on stopping prednisolone and had an optimal thyroid replacement. A 72-hour fast elicited hypoglycaemia with corresponding low insulin level. Although the C-peptide was detectable, there were no clinical, biochemical or radiological features suggestive of insulinoma. Reactive hypoglycaemia post partial gastrectomy was ruled out based on limited relation of the hypoglycaemia to meals and the low insulin levels. Hydroxychloroquine (HCQ)-induced hypoglycaemia was considered based on previous case reports and the recent literature, with a successful resolution of hypoglycaemia on discontinuation of HCQ.

A 20-year-old woman was referred to the diabetes clinic with type 2 diabetes diagnosed at the age of 19. Her body mass index was 31.4 kg/m2, HbA1C was 76 mmol/mol, GAD antibodies were negative with a detectable C-peptide. She had a characteristic facial appearance with widespread eyes, posterior hairline suggesting a facial gestalt and abnormal dentition. She also had hypothyroidism, mild intellectual disability, primary amenorrhoea and patent ductus arteriosus. Karyotyping reported normal 46XX karyotype. Genetic testing revealed a pathogenic variant in the gene encoding the HIST1H1E protein which confirmed her diagnosis of HIST1H1E syndrome. Type 2 diabetes has not been reported in previous cases of HIST1H1E and so this is the first reported case of type 2 diabetes with HIST1H1E syndrome.

Twelve years following gastric bypass surgery, a cachectic 69-year-old woman presented with both fasting and postprandial hypoglycaemia. Postprandial symptoms were relieved by dietary modification and acarbose, as is common in such cases. During a supervised fast, symptomatic hypoglycaemia occurred. Concurrent laboratory testing showed suppression of plasma insulin, c-peptide, proinsulin and insulin-like growth factor II. However, beta-hydroxybutyrate was also low, surprising given insulin deficiency. Elevated plasma free fatty acid (FFA) concentrations suggested that lipolysis was not impaired, making cachexia/malnutrition a less likely cause of hypoglycaemia. The apparent diagnosis was failure to counter-regulate—subsequent plasma carnitine measurements showed carnitine deficiency which presumably prevented FFA transport across mitochondrial membranes for ketogenesis. Repletion with high-dose oral carnitine supplements effected resolution of fasting hypoglycaemia.

Background Nitrite stimulates insulin secretion from pancreatic β-cells; however, the underlying mechanisms have not been completely addressed. The aim of this study is to determine effect of nitrite on gene expression of SNARE proteins involved in insulin secretion from isolated pancreatic islets in Type 2 diabetic Wistar rats. Material and methods Three groups of rats were studied (n = 10/group): Control, diabetes, and diabetes + nitrite, which treated with sodium nitrite (50 mg/L) for 8 weeks. Type 2 diabetes was induced using a low-dose of streptozotocin (25 mg/kg) combined with high-fat diet. At the end of the study, pancreatic islets were isolated and mRNA expressions of interested genes were measured; in addition, protein expression of proinsulin and C-peptide in pancreatic tissue was assessed using immunofluorescence staining. Results Compared with controls, in the isolated pancreatic islets of Type 2 diabetic rats, mRNA expression of glucokinase (59%), syntaxin1A (49%), SNAP25 (70%), Munc18b (48%), insulin1 (56%), and insulin2 (52%) as well as protein expression of proinsulin and C-peptide were lower. In diabetic rats, nitrite administration significantly increased gene expression of glucokinase, synaptotagmin III, syntaxin1A, SNAP25, Munc18b, and insulin genes as well as increased protein expression of proinsulin and C-peptide. Conclusions Stimulatory effect of nitrite on insulin secretion in Type 2 diabetic rats is at least in part due to increased gene expression of molecules involved in glucose sensing (glucokinase), calcium sensing (synaptotagmin III), and exocytosis of insulin vesicles (syntaxin1A, SNAP25, and Munc18b) as well as increased expression of insulin genes.

Real-time continuous glucose monitoring (RT-CGM) is superior to blood glucose monitoring (BGM) for adults with insulin-treated type 2 diabetes (T2D); however, the utility of C-peptide levels for predicting the magnitude of the glycemic benefits is controversial. Data were from a subset of 147 participants in the MOBILE study (NCT03566693) who were treated with basal-only insulin and who had baseline C-peptide levels ≥0.5 ng/mL. Participants were randomized to treatment with either RT-CGM (n=100) or BGM (n=47). Between-group differences in HbA1c and time in range (TIR) changes were assessed. The between-group difference in HbA1c favored the RT-CGM group (by 0.58 percentage points, P=0.004 at 3 months and by 0.42 percentage points, P=0.04 at 8 months). TIR was 16% higher, and time >180 mg/dL was 16% lower, in the RT-CGM group at 8 months (P=0.002 for each). In T2D managed with basal insulin, RT-CGM benefits occur for those with residual insulin secretory capacity.

To explore the association between retinal neurodegeneration and metabolic parameters in progressive dysglycemia.A cross-sectional study was performed on 68 participants: normal glucose tolerance (n = 23), prediabetes (n = 25), and Type 2 diabetes without diabetic retinopathy (n = 20). Anthropometric assessment and laboratory sampling for HbA1c, fasting glucose, insulin, c-peptide, lipid profile, renal function, and albumin-to-creatinine ratio were conducted. Central and pericentral macular thicknesses on spectral domain optical coherence tomography were compared with systemic parameters.Baseline demographic characteristics were similar across all groups. Cuzick's trend test revealed progressive full-thickness macular thinning with increasing dysglycemia across all three groups (P = 0.015). The urinary albumin-to-creatinine ratio was significantly correlated with full-thickness superior (R = -0.435; P = 0.0002), inferior (R = -0.409; P = 0.0005), temporal (R = -0.429; P = 0.003), and nasal (R = -0.493; P0.0001) pericentral macular thinning, after post hoc Bonferroni adjustment. There was no association between macular thinning and waist circumference, body mass index, blood pressure, lipid profile, or insulin resistance.Progressive dysglycemia is associated with macular thinning before the onset of visible retinopathy and occurs alongside microalbuminuria. Retinal neurodegenerative changes may help identify those most at risk from dysglycemic end-organ damage.

Background: Mesenchymal stem cells (MSCs) from human adipose tissue and bone marrow have a great potential for use in cell therapy due to their ease of isolation, expansion, and differentiation. Our intention was to isolate and promote in vitro expansion and differentiation of MSCs from human adipose and bone marrow tissue into cells with a pancreatic endocrine phenotype and to compare the potency of these cells together.Methods and Results: MSCs were pre-induced with nicotinamide, mercaptoethanol, B-27 and b-FGF in L-DMEM for 2 days and re-induced again in supplemented H-DMEM for another 3 days. Expression of five genes in differentiated beta cells was evaluated by Real-time PCR and western blotting and the potency of insulin release in response to glucose stimulation was evaluated by insulin and C-peptide ELISA kit.Quantitative RT-PCR results showed up-regulation of four genes in differentiated beta-islet cells (Insulin, Ngn-3, Pax-4 and Pdx-1) compared with the control. Western blot analysis showed that MSCs cells mainly produced proinsulin and insulin after differentiation but nestin was more expressed in pre-differentiated stem cells. Glucose and insulin secretion assay showed that insulin levels and C-peptide secretion were significantly increased in response to 10 mM glucose.Conclusions: Our study showed that both adipose and bone marrow stem cells could differentiate into functional beta-islet cells but it seems that adipose stem cells could be a better choice for treatment of diabetes mellitus according to their more safety and potency.

The UK islet allotransplant program is nationally funded to deliver one or two transplants over 12 months to individuals with type 1 diabetes and recurrent severe hypoglycemia. Analyses were undertaken 10 years after program inception to evaluate associations between transplanted mass; single versus two transplants; time between two transplants and graft survival (stimulated C-peptide >50 pmol/L) and function. In total, 84 islet transplant recipients were studied. Uninterrupted graft survival over 12 months was attained in 23 (68%) single and 47 (94%) (p = .002) two transplant recipients (separated by [median (IQR)] 6 (3–8) months). 64% recipients of one or two transplants with uninterrupted function at 12 months sustained graft function at 6 years. Total transplanted mass was associated with Mixed Meal Tolerance Test stimulated C-peptide at 12 months (p < .01). Despite 1.9-fold greater transplanted mass in recipients of two versus one islet infusion (12 218 [9291–15 417] vs. 6442 [5156–7639] IEQ/kg; p < .0001), stimulated C-peptide was not significantly higher. Shorter time between transplants was associated with greater insulin dose reduction at 12 months (beta −0.35; p = .02). Graft survival over the first 12 months was greater in recipients of two versus one islet transplant in the UK program, although function at 1 and 6 years was comparable. Minimizing the interval between 2 islet infusions may maximize cumulative impact on graft function.

Melatonin (Mel) and its receptors are promising for glycaemic control in patients with type 2 diabetes mellitus (T2DM) and its complications, but there is significant heterogeneity among studies. This study aims to investigate the effects of Mel receptor agonist Neu-P11 on glucose metabolism, immunity, and islet function in T2DM rats.In this study, SD rats were treated with a high-fat diet and streptozotocin (STZ) to establish a T2DM model. The glucose oxidase method was used to measure blood glucose levels. Glucose and insulin tolerance tests were used to assess glucose metabolism. Haematoxylin-eosin staining was used to observe pancreatic tissue injury. The apoptosis of isletβ cells was analysed by TUNEL and insulin staining. Reactive oxygen species (ROS) levels and immune cell expression were analysed by flow cytometry. IF was used to analyse the activation of microglia. The immunoglobulins: IgA, IgG, IgM, tumour necrosis factorα (TNF-α), interleukins IL-10 and IL-1β, interferonγ (IFN-γ), C-peptide, and insulin levels were determined by ELISA. The expression of CD11b, CD86, cleaved caspase 3, p21, and P16 proteins were analysed by western blot.The results showed that the blood glucose level increased, insulin resistance occurred, spleen coefficient and ROS levels increased, humoral immunity in peripheral blood decreased, and inflammation increased in the model group compared to the control group. After Mel and Neu-P11 treatment, the blood glucose level decreased significantly, insulin sensitivity improved, spleen coefficient and ROS levels decreased, humoral immunity in peripheral blood was enhanced, and inflammation improved in T2DM rats. Brain functional analysis of T2DM rats showed that microglia cells were activated, TNF-α and IL-β levels were increased, and IL-10 levels were decreased. Mel and Neu-P11 treatment reversed these indexes. Functional analysis of islets in T2DM rats showed that islet structure inflammation was impaired, isletβ cells were apoptotic, p21 and p16 protein expressions were increased, and blood C-peptide and insulin were decreased. Mel and Neu-P11 treatment restored the function of pancreatic b cells and improved the damage of pancreatic tissue.Melatonin and its receptor Neu-P11 can reduce the blood glucose level, enhance humoral and cellular immunity, inhibit microglia activation and inflammation, and repair isletβ cell function, and this improve the characterization of T2DM-related diseases.

OBJECTIVE 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. METHODS N=44 (25F/19M) participants with genetically-confirmed Wolfram syndrome attended the Washington University Wolfram Research Clinic annually from 2010-2019. 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. RESULTS 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

OBJECTIVE We assessed whether Index60, a composite measure of fasting C-peptide, 60-min C-peptide, and 60-min glucose, could improve the metabolic staging of type 1 diabetes for progression to clinical disease (stage 3) among autoantibody-positive (Ab+) individuals with normal 2-h glucose values ( RESEARCH DESIGN AND METHODS We analyzed 3,058 Type 1 Diabetes TrialNet Pathway to Prevention participants with 2-h glucose RESULTS HI-IND60 and HI-BOTH were younger, with greater frequency of more than two Ab+, and lower C-peptide levels, than either HI-2HGLU or LO-BOTH (all P < 0.001). The cumulative incidence for stage 3 was greater for HI-IND60 and HI-BOTH than for either HI-2HGLU or LO-BOTH (all P < 0.001). Those with Index60 values above the median were younger and had higher frequency of two or more Ab+ (P < 0.001) and DR3-DQ2/DR4-DQ8 prevalence (P < 0.001) and lower area under the curve (AUC) C-peptide levels (P < 0.001) than those below. Those above the 2-h glucose median had higher AUC C-peptide levels (P < 0.001), but otherwise did not differ from those below. CONCLUSIONS Index60 identifies individuals with characteristics of type 1 diabetes at appreciable risk for progression who would otherwise be missed by 2-h glucose staging criteria.

Formal stimulation tests for β-cell secretory reserve, like glucagon stimulation test (GST) or mixed meal tolerance test, are cumbersome, hence, difficult to use in clinical practice. C-peptide response at 2-h following usual meal, measured simultaneously with plasma glucose, may be used as an alternative. We compared C-peptide at 2-h post usual meal (uCP) with C-peptide at 6 min in GST (gCP), and C–peptide at 90 min following standardized mixed meal (Sustacal®) (sCP) in 112 participants, of which 64.3% had T2DM, 12.5% had T1DM, and the remaining 23.2% had other forms of diabetes (LADA, FCPD, MODY, PNDM). Correlations between uCP & gCP and uCP & sCP were assessed in different groups and subgroups. We found either very strong or moderately strong correlation in each categories except in T2DM treated with OAD, where gCP showed fair correlation with uCP. In the receiver operating characteristic (ROC) curves of uCP to define insulin dependence (gCP and sCP thresholds of

To compare advanced glycation end-products (AGE, RAGE) and 3-nitrotyrosine (3-HT) in patients with DM 1 after successful simultaneous pancreas-kidney transplantation (SPK) and kidney transplantation alone (KTA). To assess relationship between levels of AGE, RAGE, 3-HT and renal transplant (RT) function, carbohydrate and mineral metabolism.The study included 58 patients who received kidney transplantation in end-stage renal disease (ESRD). 36 patients received SPK. There were performed routine laboratory, examination of AGE, RAGE, 3-NT, parathyroid hormone (PTH), 25(OH)vitamin D, calcium, phosphorus, FGF23, osteoprotegerin (OPG), and fetuin-A levels.All patients after SPK reached normoglycemia (HbA1c 5.7 [5.3; 6.1] %; C-peptide 3.24 [2.29; 4.40] ng/ml) with the achievement of significant difference vs patients after KTA. Arterial hypertension (AH) was more frequent in recipients of SPK before transplantation than after (p=0.008). AH also persisted in greater number of cases in patients after KTA than after SPK. Patients after SPK had higher AGE (р=0.0003) and lower RAGE (р=0.000003) levels. OPG in patients after SPK was significantly higher (р=0.04). The correlation analysis revealed significant positive correlation between 3-HT and OPG (p0.05; r=0.30), RAGE and eGFR (r=-0.52), HbA1c (r=0.48), duration of AH (r=0.34), AGE with HbA1c (r=0.51).The results of the "metabolic memory" markers analysis may indicate their contribution to the persistence of the metabolic consequences of CKD and DM 1 after achievement of normoglycemia and renal function restoration and their possible participation in development of recurrent nephropathy, vascular calcification, and bone disorders.Цель. Сравнить состояние конечных продуктов гликирования (AGE, RAGE) и 3-нитротирозина (3-НТ) у пациентов с сахарным диабетом 1-го типа после успешной сочетанной трансплантации почки и поджелудочной железы (СТПиПЖ), изолированной трансплантации почки (ИТП). Оценить взаимосвязь уровней AGE, RAGE, 3-НТ с функцией ренального трансплантата, состоянием углеводного и минерального обмена. Материалы и методы. В исследование включили 58 пациентов после трансплантации почки по поводу терминальной стадии хронической болезни почек (36 реципиентов после СТПиПЖ). Всем больным проводились клинико-лабораторное обследование, определение уровней AGE, RAGE, 3-НТ, паратгормона, 25(ОН)витамина D, FGF23, остеопротегерина (ОПГ) и фетуина А. Результаты. У пациентов после СТПиПЖ наблюдалась нормогликемия (гликированный гемоглобин HbA1c 5,7 [5,3; 6,1] %; С-пептид 3,24 [2,29; 4,40] нг/мл) с достижением значимой разницы при сравнении с больными после ИТП. Артериальная гипертензия (АГ) значимо чаще наблюдалась у реципиентов СТПиПЖ до трансплантации, чем после (р=0,008), у больных после ИТП АГ также сохранялась чаще, чем у пациентов после СТПиПЖ. Соответственно, больные после СТПиПЖ гораздо реже нуждались в антигипертензивной терапии (р=0,001). Уровень AGE был значимо выше (р=0,0003), RAGE значимо ниже (р=0,000003) у пациентов после СТПиПЖ, ОПГ значимо больше у реципиентов СТПиПЖ (р=0,04). Обнаружена положительная корреляция 3-НТ с ОПГ (p0,05; r=0,30), RAGE с расчетной скоростью клубочковой фильтрации (r=-0,52), HbA1c (r=0,48), длительностью АГ (r=0,34), AGE с HbA1c (r=0,51). Заключение. Результаты анализа маркеров метаболической памяти могут отражать их вклад в персистенцию метаболических последствий хронической болезни почек и сахарного диабета 1-го типа после достижения нормогликемии и восстановления почечной функции после СТПиПЖ, участие в развитии возвратной нефропатии, сосудистой кальцификации и костных нарушений.

Background/Aim: Epicardial fat tissue (EFT) is considered a cardiovascular risk factor independent from visceral adiposity, obesity, hypertension, and diabetes. Fasting serum C-peptide is a known marker of endogenous insulin secretion and beta cell function. Our aim was to evaluate C- peptide levels in patients with metabolic syndrome (MetS) in relation to the EFT thickness. Methods: Forty-five subjects with MetS without a history of coronary artery disease and 25 healthy volunteers were enrolled this prospective case-control study. We examined the laboratory values, including C peptide, insulin, and HOMA-IR after 8 hours of fasting. EFT thickness was measured by two-dimensional transthoracic echocardiography. Results: The serum C peptide levels were significantly higher in patients with metabolic syndrome compared to the healthy controls [3.41(1.98) ng/ml vs 2.07 (1.39), P

Background: Both Type 1 and Type 2 diabetes can cause neuropathy, which is a frequent and severe consequence. C-peptide depletion may be partly related to in the occurrence of certain diabetic complications. It has been demonstrated that even a little amount of residual C-peptide has a considerable metabolic advantage. Objective: The study’s objective was to predict the relation of plasma C-peptide levels in patients with diabetic neuropathy, and its effect on Na-K ATPase activity. Design and Methods: In this case-control study, 150 individuals have been included: 80 patients with diabetic neuropathy, 40 diabetics without neuropathy and 30 non-diabetic subjects as a control. Patients in the first group were carefully chosen based on their clinical symptoms and nerve conduction studies results. The assessment of plasma C-peptide was done by ELISA, Na-K ATPase enzyme activity by spectrophotometer, and HbA1C by HPLC. Results: Mean plasma C-peptide level and Erythrocyte Na-K ATPase activity were substantially lower in neuropathy type 2 DM patients compared to diabetes without neuropathy and control (p= 0.002, 0.000 respectively). The negative correlation between C-peptide with HbA1c, and diabetes period were all negligible (p= 0.447,0.098), Even though there was a notable negative correlation with age (p= 0.03). On the other hand, the relationship linking C-peptide and Na-K ATPase enzyme activity was shown to be insignificant (p=0.69). Conclusions: Diabetic neuropathy is related to a low C-peptide level. The association between C-peptide and Na-K ATPase enzyme activity, on the other hand, was shown to be insignificant. C-peptide HbA1c, and duration of diabetes all had minor negative associations. How to cite this article:Al-Rikabi EH, Yasser OM, Mousa MJ. Assessment of the Effect of C-Peptide Level on Na-K ATPase Activity In Individuals with Type II Diabetic Peripheral Neuropathy. J Commun Dis. 2021;53(3):213-219. DOI: https://doi.org/10.24321/0019.5138.202159

Aims/Hypothesis We aimed to evaluate hematopoietic stem cells (HSC) and very small embryonic-like stem cells (VSEL) mobilization to establish their role in residual beta cell function maintenance and partial remission occurrence in children newly diagnosed with type 1 diabetes. Methods We recruited 59 type 1 diabetic patients (aged 6–18 years) monitored for 2 years, and 31 healthy children as a control group. HSC and VSEL levels were assessed at disease onset in PBMC isolated from whole peripheral blood with the use of flow cytometry. An assessment of beta cell function was based on C-peptide secretion. Studied groups were stratified on the basis of VSEL, HSC and/or C-peptide median levels in regard to beta cell function and partial remission. Results Patients with higher stimulated C-peptide secretion at disease onset demonstrated lower levels of HSC (p Conclusions These clinical observations indicate a possible significant role of HSC and VSEL in maintaining residual beta cell function in type 1 diabetic patients. Graphical Abstract

Objective: The beta-cell stress hypothesis suggests that increased insulin demand contributes to the development of type 1 diabetes. In the TRIGR trial we set out to assess the profile of plasma glucose and HbA1c before the diagnosis of clinical diabetes compared to nondiabetic children. Research Design and Methods: A cohort of children (N = 2159) with an affected first-degree relative and increased HLA risk were recruited 2002-2007 and followed until 2017. To study the relationship between plasma glucose/HbA1c and the development of autoantibodies or clinical disease Kaplan-Meir curves were developed. Mixed models were constructed for plasma glucose and HbA1c separately. Results: A family history of type 2 diabetes was related to an increase in plasma glucose (p < 0.001). An increase in glucose from the previous sample predicted clinical diabetes (p < 0.001) but not autoantibodies. An increase of HbA1c of 20% or 30% from the previous sample predicted the development of any autoantibody (p < 0.003 resp < 0.001) and the development of diabetes (p < 0.002 resp < 0.001. Participants without autoantibodies had lower HbA1c (mean 5.18%, STD 0.24; mean 33.08 mmol/mol, STD 2.85) than those who progressed to clinical disease (5.31%, 0.42; 34.46 mmol/mol, 4.68; p < 0.001) but higher than those who developed any autoantibody (5.10%, 0.30; 32.21 mmol/mol, 3.49; p < 0.001), or multiple autoantibodies (5.11%, 0.35; 32.26 mmol/mol, 3.92; p < 0.003). Conclusions: A pronounced increase in plasma glucose and HbA1c precedes development of clinical diabetes, while the association between plasma glucose or HbA1c and development of autoantibodies is complex. Increased insulin demand may contribute to development of type 1 diabetes. Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [HD040364, HD042444, HD051997]; Special Statutory Funding Program for Type 1 Diabetes Research; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR); Juvenile Diabetes Research Foundation InternationalJuvenile Diabetes Research Foundation; Academy of FinlandAcademy of FinlandEuropean Commission; Commission of the European CommunitiesEuropean Commission [QLK1-2002-00372]; EFSD/JDRF/Novo Nordisk Focused Research Grant

Aims/Introduction The benefits of once‐daily insulin degludec/aspart (IDegAsp) compared with basal insulin in type 2 diabetes patients have not been established. Materials and Methods This was a retrospective observational study. From a basal insulin cohort from three referral hospitals, patients were enrolled who initiated once‐daily IDegAsp. A control group maintaining basal insulin was selected by propensity score matching. Glycated hemoglobin (HbA1c) changes over a period of 6 months and associated clinical factors were evaluated. Results The IDegAsp group and the control group comprised of 87 patients, respectively. Baseline HbA1c was comparable between the two groups (8.7 ± 0.9 vs 8.6 ± 0.9%, mean and standard deviation). After 6 months with matched insulin doses, HbA1c in the IDegAsp group was lower than that in the control group (8.1 ± 1.0 vs 8.4 ± 1.1%, P = 0.029). Among baseline variables, fasting plasma glucose (FPG) and fasting C‐peptide in the IDegAsp were lower than that in the control (FPG 124.2 ± 38.4 vs 148.0 ± 50.6 mg/dL, P, Once‐daily insulin degludec/aspart was more effective in glycated hemoglobin reduction than basal insulin, especially in patients showing a lower ratio of fasting plasma glucose‐to‐estimated average glucose. This indicates that marked postprandial hyperglycemia was tied to the efficacy of once‐daily insulin degludec/aspart compared with basal insulin.

Aim: To search for risk factors that could predict progression in latent autoimmune diabetes in adults (LADA) and compare them with those for type 2 diabetes. Materials and Methods: This study included 175 participants with LADA (autoanti-body positive, without insulin treatment ≥1 year after diagnosis) and 2331 partici-pants with type 2 diabetes (autoantibody negative, without insulin treatment ≥1 yearafter diagnosis) from the HUNT2 and HUNT3 surveys. We used Cox regressionmodels and receiver operating characteristic curve analysis to identify predictive fac-tors for progression to insulin dependency within 10 years. Results: Low C-peptide levels (

Human C-peptide is secreted in equimolar amounts with insulin by pancreatic beta-cells. Measurement of C-peptide plays an important role in the diagnosis and treatment of diabetes where it is used to evaluate the function of islet cells. However, C-peptide measurement results across different laboratories vary considerably and there is an urgent need to improve comparability between laboratories. As it is sensitive and specific, isotope dilution-liquid chromatography-tandem mass spectrometry (ID-LC-MS/MS) has made a major contribution and will continue to play a significant role in the standardization of C-peptide measurement. Here, we reviewed the application of ID-LC-MS/MS in C-peptide measurement by discussing the biochemical properties of C-peptide, common sample preparation procedures, and the sensitivity problems often encountered with ID-LC-MS/MS C-peptide measurement. Collectively, these factors are crucial for the development of ID-LC-MS/MS methods for C-peptide measurement. We also discussed the advantages, disadvantages, and progress of implementing ID-LC-MS/MS as a routine measurement tool for C-peptide in clinical laboratories. Finally, we summarized the existing reference system and the status of C-peptide measurement in clinical laboratories to convey the necessity of improving the comparability of C-peptide measurement in clinical laboratories using ID-LC-MS/MS.

Objective The proinsulin to C-peptide (PI:C) ratio is reputedly a biomarker of β-cell endoplasmic reticulum (ER) stress. Objective 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. Methods 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. Results 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). Conclusion 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.

Background Studies in animal models and humans with type 1 diabetes mellitus (T1DM) have shown that probiotic supplementation leads to decreased pro-inflammatory cytokines (responsible for damaging β-cells of the pancreas), improved gut barrier function, and induction of immune tolerance. Objective To study the effect of supplementation of probiotics in children with T1DM on glycemic control, insulin dose, and plasma C-peptide levels. Methods A single-centered, double-blinded, and randomized placebo-controlled pilot trial was conducted in children (2–12 years) with new-onset T1DM. Ninety-six children were randomized and allocated to Placebo or Intervention groups. The intervention included high dose (112.5 billion viable lyophilized bacteria per capsule) multi-strain probiotic De Simone formulation (manufactured by Danisco-Dupont) sold as Visbiome® in India. The probiotic was supplemented for 3 months and HbA1c, fasting C-peptide, blood sugar records, and insulin dose was recorded at baseline and 3 months. Results A total of 90 patients (45 in each group) were analyzed for outcome parameters. We found a significant decrease in HbA1c (5.1 vs. 3.8; p = 0.021) and a significant decline in total and bolus insulin dose (U/kg/day; p = 0.037 and 0.018, respectively) in the intervention group when compared with the placebo group. A significantly higher (p = 0.023) number of children achieved remission in the treatment group. We did not notice adverse effects in either of the study groups. Conclusion Children with newly diagnosed T1DM managed with standard treatment along with probiotics showed better glycemic control and a decrease in insulin requirements; however, more extensive studies are further warranted.

Aims/hypothesis Metabolic effects of intermittent unhealthy lifestyle in young adults are poorly studied. We investigated the gluco-metabolic and hepatic effects of participation in Roskilde Festival (1 week of binge drinking and junk food consumption) in young, healthy males. Methods Fourteen festival participants (FP) were studied before, during and after 1 week’s participation in Roskilde Festival. Fourteen matched controls (CTRL) who did not participate in Roskilde Festival or change their lifestyle in other ways were investigated along a similar timeline. Results The FP group consumed more alcohol compared to their standard living conditions (2.0 ± 3.9 vs 16.3 ± 8.3 units/day, P < 0.001). CTRLs did not change their alcohol consumption. AUC for glucose during OGTT did not change in either group. C-peptide responses increased in the FP group (206 ± 24 vs 236 ± 17 min × nmol/L, P = 0.052) and the Matsuda index of insulin sensitivity decreased (6.2 ± 2.4 vs 4.7 ± 1.4, P = 0.054). AUC for glucagon during oral glucose tolerance test (OGTT) increased in the FP group (1037 ± 90 vs 1562 ± 195 min × pmol/L, P = 0.003) together with fasting fibroblast growth factor 21 (FGF21) (62 ± 30 vs 132 ± 72 pmol/L, P < 0.001), growth differentiation factor 15 (GDF5) (276 ± 78 vs 330 ± 83 pg/mL, P = 0.009) and aspartate aminotransferase (AST) levels (37.6 ± 6.8 vs 42.4 ± 11 U/L, P = 0.043). Four participants (29%) developed ultrasound-detectable steatosis and a mean strain elastography-assessed liver stiffness increased (P = 0.026) in the FP group. Conclusions/Interpretation Participation in Roskilde Festival did not affect oral glucose tolerance but was associated with a reduction in insulin sensitivity, increases in glucagon, FGF21, GDF15 and AST and lead to increased liver stiffness and, in 29% of the participants, ultrasound-detectable hepatic steatosis.

Context Patients with nonalcoholic fatty liver disease (NAFLD) are characterized by insulin resistance and hyperinsulinism. However, insulin resistance measurements have not been shown to be good diagnostic tools to predict NAFLD in prior studies. Objective We aimed to assess a newly validated method to measure intact molecules of insulin by mass spectrometry to predict NAFLD. Methods Patients underwent a 2-hour oral glucose tolerance test (OGTT), a liver magnetic resonance spectroscopy (1H-MRS), and a percutaneous liver biopsy if they had a diagnosis of NAFLD. Mass spectrometry was used to measure intact molecules of insulin and C-peptide. Results A total of 180 patients were recruited (67% male; 52 ± 11 years of age; body mass index [BMI] 33.2 ± 5.7 kg/m2; 46% with diabetes and 65% with NAFLD). Intact fasting insulin was higher in patients with NAFLD, irrespective of diabetes status. Patients with NAFLD without diabetes showed ~4-fold increase in insulin secretion during the OGTT compared with all other subgroups (P = 0.008). Fasting intact insulin measurements predicted NAFLD in patients without diabetes (area under the receiver operating characteristic curve [AUC] of 0.90 [0.84-0.96]). This was significantly better than measuring insulin by radioimmunoassay (AUC 0.80 [0.71-0.89]; P = 0.007). Intact fasting insulin was better than other clinical variables (eg, aspartate transaminase, triglycerides, high-density lipoprotein, glucose, HbA1c, and BMI) to predict NAFLD. When combined with alanine transaminase (ALT) (intact insulin × ALT), it detected NAFLD with AUC 0.94 (0.89-0.99) and positive and negative predictive values of 93% and 88%, respectively. This newly described approach was significantly better than previously validated noninvasive scores such as NAFLD-LFS (P = 0.009), HSI (P < 0.001), and TyG index (P = 0.039). Conclusion In patients without diabetes, accurate measurement of fasting intact insulin levels by mass spectrometry constitutes an easy and noninvasive strategy to predict presence of NAFLD.

Type 2 Diabetes Mellitus (Non Insulin Dependent Diabetes Mellitus -NIDDM) is a chronic metabolic disorder most prevalent in India with microvascular complications. Several studies were underway to identify biomarkers to detect complications associated with increasing duration of disease. The present study was done to understand the role of Connecting peptide (C-peptide) in pathogenesis of microvascular changes and it’s correlation to dyslipidemia of T2DM. The study was done at Government General Hospital, Guntur. In this study 61 known T2 DM patients and 51 age sex matched controls were selected. Their fasting blood samples were analysed for FBS, HbA1C, Urea, Creatinine, Total Cholesterol, High Density Lipoprotein Cholesterol and C-peptide. Dyslipidemia was not observed in Diabetic patients compared to controls (TC, HDLC & NonHDL p = 0.363, 0.294 & 0.336 respectively). HbA1C and C-peptide showed significant correlation between cases and controls (P = 9%. (ANOVA p = 9%. We conclude that C-peptide would be a good marker to assess degree of function of pancreas and predictor of atherogenic complication in longstanding NIDDM. Keywords: Type 2 Diabetes Mellitus, C-peptide, HbA1c, Atherogenesis.

It were examined 262 patients, among which there were 121 patients with low-progressive autoimmune diabetes of adults (LADA), 60 patients with type 1 diabetes mellitus (DM) and 81 patients with diagnosed type 2 DM. It was performed comparative analysis of C-peptide level and indicators of insulin resistance (IR) in patients in the monitoring groups. It was installed the authentic reduction of C-peptide level in the blood of LADA patients and type 1 DM patients compared with type 2 DM patients. It wasn’t established in the absence of significant differences on this index between LADA patients and type 1 DM patients, despite on a significant reduction in C-peptide in patients LADA compared with controls, significant differences in this case. According to the results of calculating several coefficients, that are recommended for the determination of IR, it was confirmed the presence of this state in patients LADA. At the same time indicators of IR in LADA patients were significantly lower than in type 2 DM patients. These data indicate that the disorders of carbohydrate metabolism in LADA patients are caused by the decrease in the insulin secretion in pancreas β-cells, and also by the presence of IR.

The urinary C-peptide/creatinine ratio (UCPCR) is low in patients with type 1 diabetes mellitus, but it has not been well characterized in patients with type 2 diabetes mellitus (T2DM). We aimed to measure the UCPCRs in patients with T2DM and explore the relationships among UCPCR, insulin resistance (IR), and chronic vascular complications of diabetes.A cross-sectional study was performed of 1299 Chinese hospitalized patients with T2DM. Binary logistic regression was used to evaluate the relationships between the chronic vascular complications of diabetes and UCPCR. K-means analysis was used to allocate participants to subgroups with five to six variables (age at diagnosis, body mass index [BMI], glycosylated hemoglobin, homoeostasis model assessment 2-estimated beta-cell function (HOMA2-B), and HOMA2-insulin resistance (HOMA2-IR), with or without UCPCR).UCPCR positively correlated with HOMA2-IR (r = 0.448, P .001). After adjustment for sex, age, duration of diabetes, and other cardiovascular risk factors, UCPCR was positively associated with diabetic kidney disease (DKD) (odds ratio [OR] = 1.198, 95% CI 1.019-1.408, P = .029) and coronary heart disease (CHD) (OR = 1.312, 95% CI 1.079-1.594, P = .006). When UCPCR was added, cluster analysis using the six variables identified five subgroups of T2DM, characterized by differing age at diagnosis, BMI, beta-cell function, IR, and prevalence of vascular complications.UCPCR is positively associated with IR, DKD, and CHD and represents a promising biomarker that could refine the classification of T2DM.背景: 1型糖尿病患者尿C肽/肌酐比值水平低。但尿C肽/肌酐比值在2型糖尿病患者中并没有被充分评估, 本研究拟测定2型糖尿病患者的尿C肽/肌酐比值水平, 探讨尿C肽/肌酐比值与胰岛素抵抗及糖尿病慢性血管并发症的相关性, 并评估尿C肽/肌酐比值改善2型糖尿病精准分型的可能性。 方法: 本研究共纳入北京大学人民医院内分泌科住院2型糖尿病患者1299名。采集所有患者的临床资料, 测定其空腹尿C肽/肌酐比, 通过二元Logistic回归分析尿C肽/肌酐比值与糖尿病血管并发症的相关性。并分别用传统的五个变量[诊断年龄, 体重指数, 糖化血红蛋白, 改良稳态模型计算的β细胞功能指数(HOMA2-B)及胰岛素抵抗指数(HOMR2-IR)]和加入尿C肽/肌酐比值后的六个变量, 通过相同的k-means聚类算法对2型糖尿病患者进行聚类分组, 比较不同亚组的临床特点。 结果: 尿C肽/肌酐比值与HOMA2-IR水平 (r=0.448, P0.001)正相关。在调整了性别, 年龄, 病程及其他心血管疾病危险因素后, 尿C肽/肌酐比值水平与糖尿病肾病 [比值比(OR) =1.198, 95%CI (1.019, 1.408), P=0.029]及冠状动脉粥样硬化性心脏病的发生风险呈正相关 [OR=1.312, 95%CI (1.079, 1.594), P=0.006]。在五个传统临床变量基础上, 加入尿C肽/肌酐比值后再进行聚类分型, 可以清晰地将患者分为五组:两组具有早发糖尿病特征[早发胰岛素缺乏型糖尿病(n=350)和早发胰岛素抵抗型糖尿病(n=176)], 两组具有晚发糖尿病特征[晚发胰岛素缺乏型糖尿病(n=318)和晚发胰岛素抵抗型糖尿病(n=133)]及轻型糖尿病(n=299)。各组间诊断年龄, 体重指数, 胰岛β细胞功能, 胰岛素抵抗水平以及糖尿病血管并发症比例显著不同。 结论: 尿C肽/肌酐比值与胰岛素抵抗水平及糖尿病肾病, 冠状动脉粥样硬化性心脏病发生风险正相关。在传统临床变量基础上引入尿C肽/肌酐比值, 可以改善2型糖尿病的精准分型。.

Background Serum fatty acid-binding protein 4 (FABP4), as an intracellular lipid chaperone and adipokine, was reported to be related to the incidence of type 2 diabetes (T2D) and diabetic complications, but its association with pancreatic islet β-cell and α-cell functions has not been fully elucidated. So the present study was to investigate the serum FABP4 levels and responses of islet β-cells and α-cells in patients with T2D. Methods 115 patients with T2D and 89 healthy controls (HC), who received serum FABP4 levels test, were recruited to participate in this study. Moreover, 75-g oral glucose tolerance test (OGTT) was performed in T2D patients to evaluate islet β-cell and α-cell functions. Systemic insulin sensitivity and overall insulin secretion of islet β-cell function were assessed by Matsuda index using C peptide (ISIM-cp) and ratio of the area under the C peptide curve to the glucose curve (AUCcp/glu) during OGTT, respectively. Fasting glucagon (Gluca0min) and postchallenge glucagon assessed by the area under the glucagon curve (AUCgluca) were determined during OGTT to evaluate islet α-cell function. And other various clinical variables were also measured in all participants. Skewed variables were natural log-transformed (ln), such as lnFABP4. Results The serum FABP4 levels in T2D patients were significantly higher than those in HC (p M-cp (r = − 0.332, p cp/glu (r = 0.324, p 0min (r = 0.200, p = 0.040) and lnAUCgluca (r = 0.311, p M-cp (β = − 0.296, t = − 2.900, p = 0.005), lnAUCcp/glu (β = 0.223, t = 2.038, p = 0.046), lnGluca0min (β = 0.272, t = 2.330, p = 0.024) and lnAUCgluca (β = 0.341, t = 3.065, p = 0.004), respectively. Conclusion Increased serum FABP4 levels were closely associated with blunted insulin sensitivity, increased insulin secretion, and elevated fasting and postchallenge glucagon levels in patients with T2D.

Aims/Introduction Recent studies have suggested C‐X‐C motif chemokine ligand 14 (CXCL14), secreted from adipose tissue, to play an important role in the pathogenesis of metabolic syndrome. However, the clinical significance of CXCL14 in humans has not been elucidated. This study aimed to assess correlations between serum CXCL14 levels and clinical parameters in patients with type 2 diabetes mellitus. Materials and Methods In total, 176 individuals with type 2 diabetes mellitus were recruited. Serum CXCL14 concentrations were determined by enzyme‐linked immunosorbent assay. We examined the associations of serum CXCL14 levels with laboratory values, abdominal computed tomography image information, surrogate markers used for evaluating the pathological states of diabetes, obesity and atherosclerosis. Results Serum CXCL14 levels correlated positively with body mass index, waist circumference, subcutaneous and visceral fat areas, and serum alanine transaminase, uric acid, total cholesterol, low‐density lipoprotein cholesterol, triglycerides and C‐peptide (CPR) levels. In contrast, CXCL14 levels correlated inversely with age, pulse wave velocity and serum adiponectin levels. Multiple linear regression analysis showed serum levels of CPR (β = 0.227, P = 0.038) and the fatty liver index (β = 0.205, P = 0.049) to be the only parameters showing independent statistically significant associations with serum CXCL14 levels. Conclusions Serum CXCL14 levels were independently associated with serum CPR and fatty liver index in patients with type 2 diabetes mellitus. In these patients, a high serum CPR concentration might reflect insulin resistance rather than β‐cell function, because CXCL14 showed simple correlations with obesity‐related parameters. Collectively, these data suggested that serum CXCL14 levels in type 2 diabetes patients might be useful predictors of elevated serum CPR and hepatic steatosis.

BACKGROUND In preclinical studies, bitter compounds, including quinine, stimulate secretion of glucoregulatory hormones [e.g., glucagon-like peptide-1 (GLP-1)] and slow gastric emptying, both key determinants of postprandial glycemia. A greater density of bitter-taste receptors has been reported in the duodenum than the stomach. Thus, intraduodenal (ID) delivery may be more effective in stimulating GI functions to lower postprandial glucose. OBJECTIVE We compared effects of intragastric (IG) and ID quinine [as quinine hydrochloride (QHCl)] administration on the plasma glucose response to a mixed-nutrient drink and relations with gastric emptying, plasma C-peptide (reflecting insulin secretion), and GLP-1. METHODS Fourteen healthy men [mean ± SD age: 25 ± 3 y; BMI (in kg/m2): 22.5 ± 0.5] received, on 4 separate occasions, in double-blind, randomly assigned order, 600 mg QHCl or control, IG or ID, 60 min (IG conditions) or 30 min (IG conditions) before a mixed-nutrient drink. Plasma glucose (primary outcome) and hormones were measured before, and for 2 h following, the drink. Gastric emptying of the drink was measured using a 13C-acetate breath test. Data were analyzed using repeated-measures 2-way ANOVAs (factors: treatment and route of administration) to evaluate effects of QHCl alone and 3-way ANOVAs (factors: treatment, route-of-administration, and time) for responses to the drink. RESULTS After QHCl alone, there were effects of treatment, but not route of administration, on C-peptide, GLP-1, and glucose (P

Meal ingestion elicits a variety of neuronal, physiological and hormonal responses that differ in healthy, obese or diabetic individuals. The mixed meal tolerance test (MMTT) is a well-established method to evaluate pancreatic β-cell reserve and glucose homeostasis in both preclinical and clinical research in response to calorically defined meal. Nonhuman primates (NHPs) are highly valuable for diabetic research as they can naturally develop type 2 diabetes mellitus (T2DM) in a way similar to the onset and progression of human T2DM. The purpose of this study was to investigate the reproducibility and effects of a MMTT containing acetaminophen on plasma glucose, insulin, C-peptide, incretin hormones, lipids, acetaminophen appearance (a surrogate marker for gastric emptying) in 16 conscious obese cynomolgus monkeys (Macaca fascicularis). Plasma insulin, C-peptide, TG, aGLP-1, tGIP, PYY and acetaminophen significantly increased after meal/acetaminophen administration. A subsequent study in 6 animals showed that the changes of plasma glucose, insulin, C-peptide, lipids and acetaminophen were reproducible. There were no significant differences in responses to the MMTT among the obese NHPs with (n = 11) or without (n = 5) hyperglycemia. Our results demonstrate that mixed meal administration induces significant secretion of several incretins which are critical for maintaining glucose homeostasis. In addition, the responses to the MMTTs are reproducible in NHPs, which is important when the MMTT is used for evaluating post-meal glucose homeostasis in research.

The aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood ( 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n = 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p p p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration (> 20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend

Since its discovery in 1994, leptin continues to have new potential physiological roles uncovered, including a role in the regulation of blood flow. Leptin's role in regulating blood flow is not completely understood. Red blood cell (RBC)-derived ATP is a recognized stimulus of blood flow, and multiple studies suggest that C-peptide, a hormone secreted in equimolar amounts with insulin from the pancreatic β-cells, can stimulate that release when delivered by albumin and in combination with Zn2+. Here, we report leptin delivers C-peptide and Zn2+ to RBCs in a saturable and specific manner. We labeled leptin with technetium-99 m (99mTc) to perform binding studies while using albumin to block the specific binding of 99mTc-leptin in the presence or absence of C-peptide. Our results suggest that leptin has a saturable and specific binding site on the RBC ((Kd = 1.79 ± 0.46) × 10-7 M) that is statistically equal to the binding affinity in the presence of 20 nM C-peptide ((Kd = 2.05 ± 0.20) × 10-7 M). While the binding affinity between leptin and the RBC did not change with C-peptide, the moles of bound leptin did increase with C-peptide, suggesting a separate binding site on the cell for a leptin/C-peptide complex. The RBC-derived ATP increased in the presence of a leptin/C-peptide/Zn2+ addition, in a concentration-dependent manner. Control RBCs ATP release increased (71 ± 5.6%) in the presence of C-peptide and Zn2+, which increased further to (94 ± 5.6%) in the presence of Zn2+, C-peptide, and leptin.

Background Dysimmunity plays a key role in diabetes, especially type 1 diabetes mellitus. Islet-specific autoantibodies (ISAs) have been used as diagnostic markers for different phenotypic classifications of diabetes. This study was aimed to explore the relationships between ISA titers and the clinical characteristics of diabetic patients. Methods A total of 509 diabetic patients admitted to Department of Endocrinology and Metabolism at the Affiliated Hospital of Nantong University were recruited. Anthropometric parameters, serum biochemical index, glycosylated hemoglobin, urinary microalbumin/creatinine ratio, ISAs, fat mass, and islet β-cell function were measured. Multiple linear regression analysis was performed to identify relationships between ISA titers and clinical characteristics. Results Compared with autoantibody negative group, blood pressure, weight, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), visceral fat mass, fasting C-peptide (FCP), 120 minutes C-peptide (120minCP) and area under C-peptide curve (AUCCP) of patients in either autoantibody positive or glutamate decarboxylase antibody (GADA) positive group were lower. Body mass index (BMI), waist circumference, triglycerides (TGs), body fat mass of patients in either autoantibody positive group were lower than autoantibody negative group. GADA titer negatively correlated with TC, LDL-C, FCP, 120minCP, and AUCCP. The islet cell antibody and insulin autoantibody titers both negatively correlated with body weight, BMI, TC, TG, and LDL-C. After adjusting confounders, multiple linear regression analysis showed that LDL-C and FCP negatively correlated with GADA titer. Conclusion Diabetic patients with a high ISA titer, especially GADA titer, have worse islet β-cell function, but less abdominal obesity and fewer features of the metabolic syndrome.

Background/Objectives Different infant formulas, varying in protein type and quantity, are available for infants who are not breastfed or are partially breastfed. Postprandial insulinemic and glycemic responses to intact vs partially hydrolyzed protein in infant formula are unclear. To compare the effect of different forms (partially hydrolyzed vs non-hydrolyzed) and levels of protein in infant formula compared with a human milk reference subgroup on insulin response in adults. Subjects/Methods In a randomized, double-blinded, cross-over study, 35 healthy adults consumed 600 ml of three different infant formulas: Intact protein-based formula (INTACT) (1.87 g protein/100 kcal; whey/casein ratio of 70/30; 63 kcal/100 ml), partially hydrolyzed whey-based formula (PHw) (1.96 g protein/100 kcal; 100% whey; 63 kcal/100 ml), a high-protein partially hydrolyzed whey-based formula (HPPHw) (2.79 g protein/100 kcal; 100%whey; 73 kcal/100 ml) and a subgroup also consumed human milk (HM) (n = 11). Lipid and carbohydrate (lactose) contents were similar (5.1–5.5 and 10.5–11.6 g/100 kcal, respectively). Venous blood samples were taken after overnight fasting and at different intervals for 180 min post-drink for insulin, glucose, blood lipids, GLP-1, glucagon, and C-peptide. Results Twenty-nine subjects (eight consuming HM) adhered to the protocol. INTACT and PHw groups had similar postprandial insulinemia and glycaemia (Cmax and iAUC) that were not different from those of the HM subgroup. HPPHw resulted in higher postprandial insulin responses (iAUC) relative to all other groups (p p p = 0.002 for the comparison with INTACT, PHw, HM, respectively). HPPHw resulted in a higher glucose response compared to INTACT and PHw (iAUC: p = 0.003, p = 0.001, respectively), but was not different from HM (p = 0.41). Conclusion This study in adults demonstrates similar postprandial insulinemia and glycaemia between INTACT and PHw, close to that of HM, but lower than HPPHw, which had a higher protein content compared to the other test milks. The findings remain to be confirmed in infants. Clinical trial registration This study is registered at clinicaltrials.gov, identifier NCT04332510.

One century after the discovery of insulin, the French Health regulations have just authorized the reimbursement for islet transplantation. Intraportal islet allotransplantation from a pancreatic donor is indicated in patients with type 1 diabetes (T1D) complicated with lability or hypoglycemia unawareness, or in case of a functioning kidney graft; islet auto-transplantation may be indicated after pancreatic surgery.Compared with insulin even administered in closed-loop pumps, the specificity of islet allotransplantation is the restoration of C-peptide secretion. Long-term insulin-independence is observed when the engrafted islet mass is sufficient, at the cost of immunosuppression. Fewer low-glucose events and less glucose variability, are observed even with minimal functional islet graft, after islet transplantation as at onset of T1D, when a residual C-peptide secretion is maintained, an objective currently approached with less aggressive immuno-modulating therapies than in the past. Therefore, restoration or preservation of endogen insulin secretion is an important goal, allowing to maintain a long-term glucose balance with more than 70% of time in range 3.9-10mmol/L and less than 3% of time3.9mmol/L, thus reducing the occurrence of diabetic complications. In the clinical setting, - the preservation of C-peptide at early stage of T1D, - the use of technological ressources (multi-injections, sensors, insulin pump, closed-loop systems) at later stages, - and islet transplantation when hypoglycemia awareness becomes impaired are complementary for a personalized care all along the life of T1D patients.

Since the beginning of our pancreas transplant programme, plasma C-peptide was routinely measured daily during the postoperative period. We aimed to evaluate the clinical interest of the C-peptide in the follow-up of pancreas transplantation with a particular look on early graft failure. From 2000 to 2016, 384 pancreas transplantations were evaluated. We collected and compared C-peptide, glycaemia and adjusted C-peptide (aCP; calculated based on C-peptide, glycaemia and creatininaemia) in patients with and without pancreas failure within 30 days after surgery. Variations of glycaemia, C-peptide and aCP between the day before and the day of failure were also recorded. The difference of aCP was significant during the first week after transplantation between patients with thrombosis and those with functional allograft: 63.2 vs. 26.7 on day 1, P = 0.0003; 61.4 vs. 26.7 on day 3, P

BACKGROUND The potential of a ketone monoester (β-hydroxybutyrate; KEβHB) supplement to rapidly mimic a state of nutritional ketosis offers a new therapeutic possibility for diabetes prevention and management. While KEβHB supplementation has a glucose-lowering effect in adults with obesity, its impact on glucose control in other insulin-resistant states is unknown. OBJECTIVES The primary objective was to investigate the effect of KEβHB-supplemented drink on plasma glucose in adults with prediabetes. The secondary objective was to determine its impact on plasma glucoregulatory peptides. METHODS This randomized controlled trial [called CETUS (Cross-over randomizEd Trial of β-hydroxybUtyrate in prediabeteS)] included 18 adults [67% men, mean age = 55 y, mean BMI (kg/m2) = 28.4] with prediabetes (glycated hemoglobin between 5.7% and 6.4% and/or fasting plasma glucose between 100 and 125 mg/dL). Participants were randomly assigned to receive KEβHB-supplemented and placebo drinks in a crossover sequence (washout period of 7-10 d between the drinks). Blood samples were collected from 0 to 150 min, at intervals of 30 min. Paired-samples t tests were used to investigate the change in the outcome variables [β-hydroxybutyrate (βHB), glucose, and glucoregulatory peptides] after both drinks. Repeated measures analyses were conducted to determine the change in concentrations of the prespecified outcomes over time. RESULTS Blood βHB concentrations increased to 3.5 mmol/L within 30 minutes after KEβHB supplementation. Plasma glucose AUC was significantly lower after KEβHB supplementation than after the placebo [mean difference (95% CI): -59 (-85.3, -32.3) mmol/L × min]. Compared with the placebo, KEβHB supplementation led to significantly greater AUCs for plasma insulin [0.237 (0.044, 0.429) nmol/L × min], C-peptide [0.259 (0.114, 0.403) nmol/L × min], and glucose-dependent insulinotropic peptide [0.243 (0.085, 0.401) nmol/L × min], with no significant differences in the AUCs for amylin, glucagon, and glucagon-like peptide 1. CONCLUSIONS Ingestion of the KEβHB-supplemented drink acutely increased the blood βHB concentrations and lowered the plasma glucose concentrations in adults with prediabetes. Further research is needed to investigate the dynamics of repeated ingestions of a KEβHB supplement by individuals with prediabetes, with a view to preventing new-onset diabetes. This trial was registered at www.clinicaltrials.gov as NCT03889210.

In humans, food intake and glucose infusion have been reported to increase subcutaneous blood flow. Since local blood flow influences the rate of insulin absorption from the subcutaneous tissue, we hypothesised that an increase in blood glucose levels-occurring as the result of glucose infusion or food intake-could modulate the pharmacokinetic properties of subcutaneously administered insulin. The pharmacokinetic profile of insulin aspart was assessed in 29 domestic pigs that were examined in a fed and fasted state or included in hyperinsulinaemic clamp studies of 4 vs. 10 mmol/L glucose prior to subcutaneous (30 nmol) or intravenous (0.1 nmol/kg) insulin administration. Results showed that food intake compared to fasting accelerated absorption and decreased clearance of insulin aspart (P < 0.05). Furthermore, higher c-peptide but also glucagon levels were observed in fed compared to fasted pigs (P < 0.05). The pharmacokinetic profile of insulin aspart did not differ between pigs clamped at 4 vs. 10 mmol/L glucose. Hence, food intake rather than blood glucose levels within normal range modulates the pharmacokinetic properties of insulin aspart upon subcutaneous and intravenous administration in pigs.

Xu Wu, Yashan Li, Baohua Man, Dexuan Li The Third People’s Hospital of Yunnan Province, Department of Clinical Laboratory, Kunming, 650200, People’s Republic of ChinaCorrespondence: Dexuan LiDepartment of Clinical Laboratory, The Third People’s Hospital of Yunnan Province, No. 292 Beijing Road, Kunming, 650200, People’s Republic of ChinaEmail 147347278@qq.comPurpose: The pancreatic islet specific microRNA-375 (miR-375) is overexpressed in type 2 diabetes mellitus (T2DM) patients suppressing the glucose-induced insulin secretion. Thus, miR-375 may serve as a biomarker for the early prediction of T2DM among high-risk individuals. We conducted this clinical study to assess the significance of miR-375 among type 2 diabetes mellitus (T2DM) patients and their first-degree relatives.Patients and Methods: We included 56 Han Chinese individuals (N: NGT = 21, T2DM = 10, FD-NGT =13 and FD-T2DM = 12) who received medical health check-ups from January 2018 to September 2018 at The Third Hospital of Yunnan Province, China. They were categorized as normal glucose tolerance (NGT), T2DM, first-degree relatives with normal glucose tolerance (FD-NGT) and first-degree relatives with T2DM (FD-T2DM). OGTT, C-peptide and Insulin tests were performed to confirm the diagnosis. The miR-375 levels were determined by Quantitative real-time RT-PCR (qRT-PCR).Results: The OGTT test showed a significant difference in T2DM and FD-T2DM groups compared with NGT and FD-NGT (p< 0.05). Similar results were observed during C-peptide and insulin tests. Interestingly, the 2-hour insulin test showed FD-NGT group having a significantly higher mean ± standard error of (64.240 ± 12.775) compared to NGT (28.836 ± 10.875). Assessment of miR-375 expression levels in 4 groups showed a significant up-regulation in T2DM and FD-T2DM compared with NGT and FD-NGT groups. A slight increase in miRNA expression was observed in FD-NGT compared with NGT group but was not statistically significant.Conclusion: The OGTT, C-peptide and insulin tests revealed a statistically significant difference in T2DM and FD-T2DM compared with NGT and FD-NGT groups. A significantly higher miR-375 expression was also observed in T2DM and FD-T2DM groups compared with NGT and FD-NGT and thus, miR-375 may serve as a stable biomarker for the early prediction of T2DM among high-risk individuals.Keywords: C-peptide, insulin, microRNA-375, OGTT, type 2 diabetes mellitus

Summary Background & aims Seaweed including brown seaweeds with rich bioactive components may be efficacious for a glycaemic management strategy and appetite control. We investigated the effects of two brown edible seaweeds, Laminaria digitata (LD) and Undaria pinnatifida (UP), on postprandial glucose metabolism and appetite following a starch load in a human meal study. Methods Twenty healthy subjects were enrolled in a randomized, 3-way, blinded cross-over trial. The study was registered under ClinicalTrials.gov Identifier no. NCT00123456. At each test day, the subjects received one of three meals comprising 30 g of starch with 5 g of LD or UP or an energy-adjusted control meal containing pea protein. Fasting and postprandial blood glucose, insulin, C-peptide and glucagon-like peptide-1 (GLP-1) concentrations were measured. Subjective appetite sensations were scored using visual analogue scales (VAS). Results Linear mixed model (LMM) analysis showed a lower blood glucose, insulin and C-peptide response following the intake of LD and UP, after correction for body weight. Participants weighing ≤ 63 kg had a reduced glucose response compared to control meal between 40 and 90 min both following LD and UP meals. Furthermore, LMM analysis for C-peptide showed a significantly lower response after intake of LD. Compared to the control meal, GLP-1 response was higher after the LD meal, both before and after the body weight adjustment. The VAS scores showed a decreased appetite sensation after intake of the seaweeds. Ad-libitum food intake was not different three hours after the seaweed meals compared to control. Conclusions Concomitant ingestion of brown seaweeds may help improving postprandial glycaemic and appetite control in healthy and normal weight adults, depending on the dose per body weight. Clinical trial registry number Clinicaltrials.gov (ID# NCT02608372 ).

Aims/Hypothesis Studies in permanent neonatal diabetes suggest that sulphonylureas lower blood glucose without causing hypoglycemia, in part by augmenting the incretin effect. This mechanism has not previously been attributed to sulphonylureas in patients with type 2 diabetes (T2DM). We therefore aimed to evaluate the impact of low-dose gliclazide on beta-cell function and incretin action in patients with T2DM. Methods Paired oral glucose tolerance tests and isoglycemic infusions were performed to evaluate the difference in the classical incretin effect in the presence and absence of low-dose gliclazide in 16 subjects with T2DM (hemoglobin A1c Results A single dose of 20 mg gliclazide reduced mean glucose during the oral glucose tolerance test from 12.01 ± 0.56 to 10.82 ± 0.5mmol/l [P = 0.0006; mean ± standard error of the mean (SEM)]. The classical incretin effect was augmented by 20 mg gliclazide, from 35.5% (lower quartile 27.3, upper quartile 61.2) to 54.99% (34.8, 72.8; P = 0.049). Gliclazide increased beta-cell glucose sensitivity by 46% [control 22.61 ± 3.94, gliclazide 33.11 ± 7.83 (P = 0.01)] as well as late-phase incretin potentiation [control 0.92 ± 0.05, gliclazide 1.285 ± 0.14 (P = 0.038)]. Conclusions/Interpretation Low-dose gliclazide reduces plasma glucose in response to oral glucose load, with concomitant augmentation of the classical incretin effect. Beta-cell modeling shows that low plasma concentrations of gliclazide potentiate late-phase insulin secretion and increase glucose sensitivity by 50%. Further studies are merited to explore whether low-dose gliclazide, by enhancing incretin action, could effectively lower blood glucose without risk of hypoglycemia.

Summary Background and objective Foods for Special Medical Purposes (FSMPs) are formulated to support the nutritional needs of subjects with impaired capacity to ingest, digest or absorb ordinary food or nutrients. Polglumyt® is a proprietary highly purified, high quality glycogen obtained from mussels. Here we report the results of a single-center, single dose, open label, single arm study carried out to investigate acceptance (i.e. gastrointestinal tolerance and palatability), metabolic profile and safety of a low osmolarity, high-density energy Polglumyt®-based drink (the investigational product, IP) as a novel FSMP. Methods Twelve healthy subjects received a single oral administration of the IP under fasting conditions. The study endpoints were: changes in gastrointestinal system tolerability at 3 h, 6 h and 24 h after IP intake; IP palatability evaluation; metabolic evaluation through the kinetic profile of circulating glucose, insulin and C-peptide from 0 h to 6 h after IP intake and changes from baseline in circulating triglycerides at 3 h and 6 h after IP intake. Results The IP showed a good gastrointestinal tolerability and an acceptable palatability. The IP did not affect the physiological glycemic profile and the triglycerides levels 6 h after the intake. The IP was well tolerated by study subjects, with no or minor adverse events. Conclusions The study results encourage additional clinical investigations on the IP as a novel FSMP in patients with impaired digestion or gastrointestinal absorption, unable to assume an ordinary diet, e.g. patients undergoing invasive gastrointestinal surgery, elderly or oncological patients, even with certain metabolic disorders.

Previously, we demonstrated low-dose anti-thymocyte globulin (ATG) and granulocyte colony stimulating factor (GCSF) immunotherapy preserved C-peptide for two years in a pilot study of subjects with established type 1 diabetes (n=25). Herein, we evaluated the long-term outcomes of ATG/GCSF in study participants with five years of available follow-up data (n=15). The primary endpoint was area under the curve (AUC) C-peptide during a two-hour mixed-meal tolerance test (MMTT). After five years, there were no statistically significant differences in AUC C-peptide when comparing subjects who received ATG/GCSF versus placebo (p = 0.41). A modeling framework based on mean trajectories in C-peptide AUC over five years, accounting for differing trends between groups, was applied to re-categorize responders (n=9) and non-responders (n=7). ATG/GCSF reponders demonstrated nearly unchanged HbA1c over five years [mean (95% CI) adjusted change = 0.29% (-0.69%, 1.27%)], but the study was not powered for comparisons against non-responders 1.75% (-0.57%, 4.06%) and placebo 1.44% (0.21%, 2.66%). These data underscore the importance of long-term follow up in previous and ongoing phase 2 trials of low-dose ATG in recent-onset type 1 diabetes.

Objective Pulsatile insulin secretion is impaired in diseases such as type 2 diabetes that are characterized by insulin resistance. This has led to the suggestion that changes in insulin pulsatility directly impair insulin signaling. We sought to examine the effects of pulse characteristics on insulin action in humans, hypothesizing that a decrease in pulse amplitude or frequency is associated with impaired hepatic insulin action. Methods We studied 29 nondiabetic subjects on two occasions. On 1 occasion, hepatic and peripheral insulin action was measured using a euglycemic clamp. The deuterated water method was used to estimate the contribution of gluconeogenesis to endogenous glucose production. On a separate study day, we utilized nonparametric stochastic deconvolution of frequently sampled peripheral C-peptide concentrations during fasting to reconstruct portal insulin secretion. In addition to measuring basal and pulsatile insulin secretion, we used approximate entropy to measure orderliness and Fourier transform to measure the average, and the dispersion of, insulin pulse frequencies. Results In univariate analysis, basal insulin secretion (R2 = 0.16) and insulin pulse amplitude (R2 = 0.09) correlated weakly with insulin-induced suppression of gluconeogenesis. However, after adjustment for age, sex, and weight, these associations were no longer significant. The other pulse characteristics also did not correlate with the ability of insulin to suppress endogenous glucose production (and gluconeogenesis) or to stimulate glucose disappearance. Conclusions Overall, our data demonstrate that insulin pulse characteristics, considered independently of other factors, do not correlate with measures of hepatic and peripheral insulin sensitivity in nondiabetic humans.

Background: The ability to measure insulin secretion from pancreatic beta cells and monitor glucose-insulin physiology is vital to current health needs. C-peptide has been used successfully as a surrogate for plasma insulin concentration. Quantifying the expected variability of modelled insulin secretion will improve confidence in model estimates. Methods: Forty-three healthy adult males of Māori or Pacific peoples ancestry living in New Zealand participated in an frequently sampled, intravenous glucose tolerance test (FS-IVGTT) with an average age of 29 years and a BMI of 33 kg/m2. A 2-compartment model framework and standardized kinetic parameters were used to estimate endogenous pancreatic insulin secretion from plasma C-peptide measurements. Monte Carlo analysis (N = 10 000) was then used to independently vary parameters within ±2 standard deviations of the mean of each variable and the 5th and 95th percentiles determined the bounds of the expected range of insulin secretion. Cumulative distribution functions (CDFs) were calculated for each subject for area under the curve (AUC) total, AUC Phase 1, and AUC Phase 2. Normalizing each AUC by the participant’s median value over all N = 10 000 iterations quantifies the expected model-based variability in AUC. Results: Larger variation is found in subjects with a BMI > 30 kg/m2, where the interquartile range is 34.3% compared to subjects with a BMI ≤ 30 kg/m2 where the interquartile range is 24.7%. Conclusions: Use of C-peptide measurements using a 2-compartment model and standardized kinetic parameters, one can expect ~±15% variation in modelled insulin secretion estimates. The variation should be considered when applying this insulin secretion estimation method to clinical diagnostic thresholds and interpretation of model-based analyses such as insulin sensitivity.

Background Until now, diabetes during pregnancy has been associated with a high risk of maternal, fetal, and neonatal morbidities and mortalities. The main aim of this study was to evaluate the risk factors of hypoglycemia in infants of diabetic mothers (IDMs) and to study the relationship between umbilical cord (UC) C peptide levels and the risk of developing hypoglycemia. Material and methods UC blood C-peptide and serial serum blood glucose measurements were done for all included singleton newborns born to diabetic mothers during the study period. Maternal and neonatal data such as gestational age, maternal age, maternal weight, types of diabetics and its control, maternal glycated hemoglobin (HbA1C), birth weight, Apgar score, and neonatal complete blood picture were collected. Results In total, 83 IDMs met the inclusion criteria. Fifty-four (65.06%) developed hypoglycemia and 29 (34.94%) remained normoglycemic. However, there were no significant differences between hypoglycemic and normoglycemic IDMs in terms of types of maternal diabetics (P value = 0.41), its duration (P value = 0.43). The hypoglycemia peak occurred within the first 3 h of life, with 33.11 ± 8.84 mg/dl for the hypoglycemia group and 54.10 ± 6.66 mg/dl for the normoglycemic group (P value P-value P value = 0.005). Conclusion Poor diabetes control, especially in the last trimester, is associated with neonatal hypoglycemia. Increased UC C-peptide levels could be used as an early indicator for the risk of developing neonatal hypoglycemia and a predictor for babies need neonatal admission.

Mesenchymal stem cells (MSCs) possess regenerative and immunomodulatory properties and can control the immune dysregulation that leads to β-cell destruction. Stem-cell transplantation could thus manage insulin-dependent diabetes mellitus (IDDM) in dogs. In this pilot study, we aimed to assess canine adipose tissue-derived MSCs (cAT-MSCs) transplantation as a treatment for canine diabetes mellitus. This study included four dogs with over a year of insulin treatment for IDDM, following diagnosis at the Veterinary Medicine Teaching Hospital of Seoul National University. Allogenic cAT-MSCs were infused intravenously three or five times monthly to dogs with IDDM. Blood and urine samples were obtained monthly. General clinical symptoms, including changes in body weight, vitality, appetite, and water intake were assessed. Three of the four owners observed improvement of vitality after stem cell treatment. Two of the four dogs showed improvement in appetite and body weight, polyuria, and polydipsia. C-peptide has increased by about 5-15% in three of the cases, and fructosamine and HbA1c levels have improved in two of the cases. Hyperlipidemia was resolved in two of the dogs, and there was no concurrent bacterial cystitis in any of the dogs. C-peptide secretion and lipid metabolism are associated with diabetic complications. Improvement in these parameters following the treatment suggests that cAT-MSC transplantation in dogs with IDDM might help to improve their insulin secretory capacity and prevent diabetic complications.

Introduction: Diabetes mellitus is the commonest endocrine disorder in population. This clinical syndrome is due to either absolute or relative insulin deciency. Currently number of diabetics worldwide is 422 million. In India the projected increase is from 20 to 62 million, The term diabetes is derived from Greek words Dia meaning “through”, and Bainein meaning “to go”. This disease causes loss of weight as if the body mass is passed through urine. It is a disease known from ancient times. Charaka in his treatise, elaborated this disorder as “Madhumeha” (meaning sweet urine) around 400 BC. Aim & Objective: The level of fasting insulin and serum c-peptide in individual with high BMI /sedentary life style; newly diagnosed cases of hypertension / type2 DM; and old cases of diabetes mellitus. Raised level of serum insulin and c-peptide as a cause of progressive diabetes which can lead to cardiovascular complications and help to prepare patient. Materials And Methods: It is an observational cross sectional study done in the diabetic outpatient clinic of our hospital. 60 diabetic patients were evaluated for fasting plasma glucose level, post prandial glucose level, Glycosalated haemoglobin HbA1c, fasting Insulin and fasting C-peptide level. Results And Analysis: From the above table it was inferred that there is very strong positive correlation of HbA1c with C-PEPTIDE and INSULIN ( r > 0.7 and p value = .000 ). From the table it is inferred that there is a very strong positive correlation of INSULIN with C-PEPTIDE ( r > 0.7 and p value =.000 ). From table it is inferred that C-PEPTIDE has a strong negative correlation with SBPand DBP. (r value > 0.7 and p = .000 ). From table it is inferred that INSULIN has a strong negative correlation with SBPand DBP. ( r value > 0.7 and p =.000). Summary & Conclusion: The level of serum insulin and c-peptide is found to be higher in “newly diagnosed” cases than that of “old diagnosed” cases and this can be explained by the fact that treatment modies the course of disease and slows its progression. With passage of duration, hypertension starts to build up in established cases of diabetes. C-peptide and serum insulin testing should be done in patients with poor blood glucose control to decide treatment modalities and to create awareness about lifestyle modications and education to Prevent progression of prediabetic stage to diabetic and further to its complicated stage.