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Andrew T Hattersley - One of the best experts on this subject based on the ideXlab platform.

  • reappearanCe of C Peptide during the third trimester of pregnanCy in type 1 diabetes panCreatiC regeneration or fetal hyperinsulinism
    Diabetes Care, 2021
    Co-Authors: Claire L Meek, Timothy J Mcdonald, Andrew T Hattersley, Richard A Oram, Denice S Feig, Helen R Murphy
    Abstract:

    OBJECTIVE We assessed longitudinal patterns of maternal C-Peptide ConCentration to examine the hypothesis of β-Cell regeneration in pregnanCy with type 1 diabetes. RESEARCH DESIGN AND METHODS C-Peptide was measured on maternal serum samples from 127 partiCipants (12, 24, and 34 weeks) and Cord blood during the Continuous GluCose Monitoring in Women With Type 1 Diabetes in PregnanCy Trial (CONCEPTT). C-Peptide was measured using a highly sensitive direCt and solid-phase Competitive eleCtroChemiluminesCent immunoassay. RESULTS Three disCrete patterns of maternal C-Peptide trajeCtory were identified: pattern 1, undeteCtable throughout pregnanCy, n = 74 (58%; maternal C-Peptide <3 pmol/L); pattern 2, deteCtable at baseline, n = 22 (17%; maternal C-Peptide 7-272 pmol/L at baseline); and pattern 3, undeteCtable maternal C-Peptide at 12 and 24 weeks, whiCh first beCame deteCtable at 34 weeks, n = 31 (24%; maternal C-Peptide 4-26 pmol/L at 34 weeks). Baseline CharaCteristiCs and third trimester gluCose profiles of women with pattern 1 and pattern 3 C-Peptide trajeCtories were similar, but women in pattern 3 had suboptimal glyCemia (50% time above range) at 24 weeks' gestation. Offspring of women with pattern 3 C-Peptide trajeCtories had elevated Cord blood C-Peptide (geometriC mean 1,319 vs. 718 pmol/L; P = 0.007), inCreased rates of large for gestational age (90% vs. 60%; P = 0.002), neonatal hypoglyCemia (42% vs. 14%; P = 0.001), and neonatal intensive Care admission (45% vs. 23%; P = 0.023) Compared with pattern 1 offspring. CONCLUSIONS First maternal C-Peptide appearanCe at 34 weeks was assoCiated with midtrimester hyperglyCemia, elevated Cord blood C-Peptide, and high rates of neonatal CompliCations. This suggests transfer of C-Peptide from fetal to maternal serum and is inConsistent with pregnanCy-related β-Cell regeneration.

  • the CliniCal utility of C Peptide measurement in the Care of patients with diabetes
    Diabetic Medicine, 2013
    Co-Authors: Angus G Jones, Andrew T Hattersley
    Abstract:

    C-Peptide is produCed in equal amounts to insulin and is the best measure of endogenous insulin seCretion in patients with diabetes. Measurement of insulin seCretion using C-Peptide Can be helpful in CliniCal praCtiCe: differenCes in insulin seCretion are fundamental to the different treatment requirements of Type 1 and Type 2 diabetes. This artiCle reviews the use of C-Peptide measurement in the CliniCal management of patients with diabetes, inCluding the interpretation and ChoiCe of C-Peptide test and its use to assist diabetes ClassifiCation and ChoiCe of treatment. We provide reCommendations for where C-Peptide should be used, ChoiCe of test and interpretation of results. With the rising inCidenCe of Type 2 diabetes in younger patients, the disCovery of monogeniC diabetes and development of new therapies aimed at preserving insulin seCretion, the direCt measurement of insulin seCretion may be inCreasingly important. AdvanCes in assays have made C-Peptide measurement both more reliable and inexpensive. In addition, reCent work has demonstrated that C-Peptide is more stable in blood than previously suggested or Can be reliably measured on a spot urine sample (urine C-Peptide:Creatinine ratio), faCilitating measurement in routine CliniCal praCtiCe. The key Current CliniCal role of C-Peptide is to assist ClassifiCation and management of insulin-treated patients. Utility is greatest after 3-5 years from diagnosis when persistenCe of substantial insulin seCretion suggests Type 2 or monogeniC diabetes. Absent C-Peptide at any time Confirms absolute insulin requirement and the appropriateness of Type 1 diabetes management strategies regardless of apparent aetiology.

  • edta improves stability of whole blood C Peptide and insulin to over 24 hours at room temperature
    PLOS ONE, 2012
    Co-Authors: Timothy J Mcdonald, Beverley M Shields, Mandy H Perry, Roy W A Peake, Nicola J Pullan, John J Oconnor, Beatrice Knight, Andrew T Hattersley
    Abstract:

    IntroduCtion C-Peptide and insulin measurements in blood provide useful information regarding endogenous insulin seCretion. ConfliCting evidenCe on sample stability and handling proCedures Continue to limit the widespread CliniCal use of these tests. We assessed the faCtors that altered the stability of insulin and C-Peptide in blood. Methods We investigated the impaCt of preservative type, time to Centrifugation, storage Conditions and duration of storage on the stability of C-Peptide and insulin on three different analytiCal platforms. Results C-Peptide was stable for at least 24 hours at room temperature in both Centrifuged and whole blood ColleCted in K+-EDTA and serum gel tubes, with the exCeption of whole blood serum gel, whiCh deCreased to 78% of baseline at 24 hours, (p = 0.008). Insulin was stable at room temperature for 24 hours in both Centrifuged and whole blood ColleCted in K+-EDTA tubes. In Contrast insulin levels deCreased in serum gel tubes both Centrifuged and whole blood (66% of baseline, p = 0.01 and 76% of baseline p = 0.01, by 24 hours respeCtively). C-Peptide and insulin remained stable after 6 freeze-thaw CyCles. ConClusions The stability of C-Peptide and insulin in whole blood K+-EDTA tubes negates the need to Conform to striCt sample handling proCedures for these assays, greatly inCreasing their CliniCal utility.

  • validation of a single sample urinary C Peptide Creatinine ratio as a reproduCible alternative to serum C Peptide in patients with type 2 diabetes
    Diabetic Medicine, 2012
    Co-Authors: Pamela Bowman, Timothy J Mcdonald, Beverley M Shields, Bridget A Knight, Andrew T Hattersley
    Abstract:

    Diabet. Med. 29, 90–93 (2012) AbstraCt Aims  Serum C-Peptide Can be used in Type 2 diabetes as a measure of endogenous insulin seCretion, but praCtiCalities of ColleCtion limit its routine CliniCal use. Urine C-Peptide Creatinine ratio is a non-invasive alternative that is stable for at least 3 days at room temperature in boriC aCid preservative. We aimed to assess the utility of urine C-Peptide Creatinine ratio in individuals with Type 2 diabetes as an alternative to serum C-Peptide. Methods  We assessed, in 77 individuals with Type 2 diabetes, the reproduCibility of, and Correlations between, fasting and postprandial urine C-Peptide Creatinine ratio and serum C-Peptide, and the impaCt of renal impairment (estimated glomerular filtration rate < 60 ml min−1 1.73 m−2) on these Correlations. Results  Urine C-Peptide Creatinine ratio was at least as reproduCible as serum C-Peptide [fasting CoeffiCient of variation mean (95% CI): 28 (21–35)% vs. 38 (26–59)% and 2-h post-meal 26 (18–33)% vs. 27 (20–34)%. Urine C-Peptide Creatinine ratio 2 h post-meal was Correlated with stimulated serum C-Peptide, both the 2-h value (r = 0.64, P < 0.001) and the 2-h area under the C-Peptide Curve (r = 0.63, P < 0.001). The assoCiation seen was similar in patients with and without moderate renal impairment (P = 0.6). ConClusions  In patients with Type 2 diabetes, a single urine C-Peptide Creatinine ratio is a stable, reproduCible measure that is well Correlated with serum C-Peptide following meal stimulation, even if there is moderate renal impairment. Urine C-Peptide Creatinine ratio therefore has potential for use in CliniCal praCtiCe in the assessment of Type 2 diabetes.

  • stability and reproduCibility of a single sample urinary C Peptide Creatinine ratio and its Correlation with 24 h urinary C Peptide
    Clinical Chemistry, 2009
    Co-Authors: Timothy J Mcdonald, Pamela Bowman, Beverley M Shields, Bridget A Knight, Maurice B Salzmann, Andrew T Hattersley
    Abstract:

    IntroduCtion: C-Peptide measurement in blood or 24-h urine samples provides useful information regarding endogenous insulin seCretion, but problems related to the rapid degradation of C-Peptide in blood and diffiCulty of 24-h urine ColleCtion have limited widespread routine CliniCal use of this test. We assessed the feasibility of measuring urinary C-Peptide (UCP) with CorreCtion for Creatinine ConCentration in single urine samples. Methods: We analyzed UCP using a routine eleCtroChemiluminesCenCe immunoassay in samples from 21 healthy volunteers. We investigated the stability of UCP with different preservatives and storage Conditions and Compared the reproduCibility of urinary C-Peptide/Creatinine ratio (UCPCR) in first- and seCond-void fasting urines, then assessed Correlations with 24-h ColleCtions. Results: UCPCR was unChanged at room temperature for 24 h and at 4 °C for 72 h even in the absenCe of preservative. UCPCR ColleCted in boriC aCid was stable at room temperature for 72 h. UCPCR remained stable after 7 freeze-thaw CyCles but deCreased with freezer storage time and dropped to 82%–84% of baseline by 90 days at −20 °C. SeCond-void fasting UCPCRs were lower than first-void (median 0.78 vs 1.31, P = 0.0003) and showed less variation (CV 33% vs 52%), as seCond-void UCPCRs were not influenCed by evening food-related insulin seCretion. SeCond-void fasting UCPCR was highly Correlated with 24-h UCP ( r = 0.8, P = 0.00006). ConClusions: SeCond-void fasting UCPCR is a reproduCible measure that Correlates well with 24-h UCP in normal samples. The 3-day stability of UCPCR at room temperature greatly inCreases its potential CliniCal utility.

John Wahren - One of the best experts on this subject based on the ideXlab platform.

  • the CliniCal potential of C Peptide replaCement in type 1 diabetes
    Diabetes, 2012
    Co-Authors: John Wahren, Asa Kallas, Anders A F Sima
    Abstract:

    It is well known that C-Peptide fulfills an important funCtion in the synthesis of insulin. After Cleavage of proinsulin in the panCreatiC β-Cells, the 31-amino aCid C-Peptide is seCreted into the portal CirCulation in equimolar ConCentrations with insulin. After its disCovery in 1967 (1), it was believed that C-Peptide might exert physiologiCal effeCts similar to those of insulin. However, no influenCe on gluCose or lipid metabolism Could be demonstrated, and C-Peptide was subsequently regarded as a waste produCt of insulin synthesis. Nevertheless, it was found to be useful as an indiCator of β-Cell funCtion, and sinCe the mid-1970s, C-Peptide has been used as a surrogate marker for monitoring the Course of type 1 and type 2 diabetes and determining the effeCts of interventions designed to preserve and improve residual β-Cell funCtion. Several studies demonstrate that patients with type 1 diabetes who show a degree of remaining β-Cell aCtivity are Considerably less prone to develop miCrovasCular CompliCations than those who are totally C-Peptide defiCient (2). The possibility that C-Peptide may exert direCt effeCts of its own was reevaluated in the early 1990s. A series of studies was undertaken involving administration of the Peptide to patients with type 1 diabetes, who laCk C-Peptide. This approaCh gave positive results, and it beCame apparent that replaCement of C-Peptide in physiologiCal ConCentrations resulted in signifiCant improvements in several diabetes-induCed funCtional abnormalities (3–7). These surprising findings prompted a renewed interest in C-Peptide physiology, and during the past 15 years, a steadily inCreasing number of reports on new aspeCts of C-Peptide physiology have emerged. The information available today inCludes studies of the Peptide’s interaCtion with Cell membranes and its intraCellular signaling properties (8). In vivo studies in animal models of type 1 diabetes have defined a benefiCial influenCe of C-Peptide on diabetes-induCed funCtional and struCtural …

  • C Peptide is a bioaCtive Peptide
    Diabetologia, 2007
    Co-Authors: John Wahren, Kristoffer Ekberg, Hans Jörnvall
    Abstract:

    -ATPase.NerveConduCtionveloCity.RedbloodCelldeformabilityAbbreviationsBB/Wor BioBreeding/WorCestereNOS endothelial nitriC oxide synthaseICAM-1 intraCellular adhesion moleCule 1MAPK mitogen-aCtivated protein kinaseNCV nerve ConduCtion veloCityDuring the past deCade, reports from several laboratorieshave foCused on the physiologiCal effeCts of C-Peptide.Experimental data and CliniCal studies suggest that thatC-Peptide is a biologiCally aCtive Peptide. CliniCal studiesshow that C-Peptide administration in type 1 diabetespatients, who laCk the Peptide, results in amelioration ofdiabetes-induCed renal and nerve dysfunCtion. MoleCularstudiesdemonstratebindingtoCellmembranes,aCtivationofintraCellular signalling pathways, and speCifiC end effeCts ofimportanCe for vasCular endothelial funCtion. These findingshave prompted the hypothesis that C-Peptide defiCienCy intype 1 diabetes may Contribute to the development ofmiCrovasCular CompliCations, and that C-Peptide replaCe-ment, together with regular insulin therapy, may be benefi-Cial in the treatment or prevention of these CompliCations. InthepresentartiClewearguetheCaseinfavourofC-Peptideasa biologiCally aCtive Peptide based on in vivo data and invitro findings, as summarised in Table 1.Soon after the disCovery of insulin biosynthesis in 1967,and the identifiCation of C-Peptide and its role in promotingthe CorreCt folding of proinsulin, researChers began toinvestigate whether C-Peptide had any insulin-like effeCts.However,nonewerefound,andinterestinthePeptidefoCusedinsteadonitsuseasamarkerofendogenousinsulinseCretion.Interest in a physiologiCal role for C-Peptide persisted, andreCeived support from the CliniCal observation that patientswith type 1 diabetes, who Continue to maintain a smallendogenous beta Cell aCtivity, are less prone to develop long-term CompliCations and have fewer episodes of hypoglyCae-mia than those who beCome totally C-Peptide defiCient [1, 2].It was also noted that islet or panCreas transplantation intype 1 patients, with restoration of both insulin and C-PeptideseCretion, often results in amelioration of the funCtional andstruCtural abnormalities that aCCompany diabetiC neuropathyand nephropathy [3, 4]. These Considerations gave rise to aseries of studies involving the administration of a replaCe-ment dose of C-Peptide to type 1 diabetes patients.BenefiCial effeCts on renal funCtion and struCture intype 1 diabetesCliniCal studies Glomerular hyperfiltration, a risk faCtor forthe development of nephropathy, is an early abnormality intype 1 diabetes that is not CorreCted by insulin therapy. This

  • C Peptide replaCement therapy and sensory nerve funCtion in type 1 diabetiC neuropathy
    Diabetes Care, 2007
    Co-Authors: Karin Ekberg, Bolennart Johansson, Tom Brismar, Per Lindstrom, Lisa Junttiberggren, Anders Norrby, Christian Berne, Hans J Arnqvist, J Bolinder, John Wahren
    Abstract:

    OBJECTIVE - C-Peptide replaCement in animals results in amelioration of diabetes-induCed funCtional and struCtural abnormalities in peripheral nerves. The present study was undertaken to examine wh ...

  • effeCts of proinsulin C Peptide in experimental diabetiC neuropathy vasCular aCtions and modulation by nitriC oxide synthase inhibition
    Diabetes, 2003
    Co-Authors: M A Cotter, John Wahren, Karin Ekberg, Norman E Cameron
    Abstract:

    Proinsulin C-Peptide treatment Can partially prevent nerve dysfunCtion in type 1 diabetiC rats and patients. This Could be due to a direCt aCtion on nerve fibers or via vasCular meChanisms as C-Peptide stimulates the nitriC oxide (NO) system and NO-mediated vasodilation Could potentially aCCount for any benefiCial C-Peptide effeCts. To assess this further, we examined neurovasCular funCtion in streptozotoCin-induCed diabetiC rats. After 6 weeks of diabetes, rats were treated for 2 weeks with C-Peptide to restore CirCulating levels to those of nondiabetiC Controls. Additional diabetiC groups were given C-Peptide with NO synthase inhibitor N G -nitro-l-arginine (l-NNA) Co-treatment or sCrambled C-Peptide. Diabetes Caused 20 and 16% reduCtions in sCiatiC motor and saphenous sensory nerve ConduCtion veloCity, whiCh were 62 and 78% CorreCted, respeCtively, by C-Peptide. l-NNA abolished C-Peptide effeCts on nerve ConduCtion. SCiatiC blood flow and vasCular ConduCtanCe were 52 and 41%, respeCtively, reduCed by diabetes ( P

  • amelioration of sensory nerve dysfunCtion by C Peptide in patients with type 1 diabetes
    Diabetes, 2003
    Co-Authors: Karin Ekberg, Bolennart Johansson, Tom Brismar, Bjorn Jonsson, Per Lindstrom, John Wahren
    Abstract:

    Studies have demonstrated that proinsulin C-Peptide stimulates the aCtivities of Na(+),K(+)-ATPase and endothelial nitriC oxide synthase, both of whiCh are enzyme systems of importanCe for nerve funCtion and known to be defiCient in type 1 diabetes. The aim of this randomized double-blind plaCebo-Controlled study was to investigate whether C-Peptide replaCement improves nerve funCtion in patients with type 1 diabetes. Forty-nine patients without symptoms of peripheral neuropathy were randomized to either 3 months of treatment with C-Peptide (600 nmol/24 h, four doses s.C.) or plaCebo. Forty-six patients (15 women and 31 men, aged 29 years, diabetes duration 10 years, and HbA(1C) 7.0%) Completed the study. NeurologiCal and neurophysiologiCal measurements were performed before and after 6 and 12 weeks of treatment. At baseline the patients showed reduCed nerve ConduCtion veloCities in the sural nerve (sensory nerve ConduCtion veloCity [SCV]: 50.9 +/- 0.70 vs. 54.2 +/- 1.2 m/s, P < 0.05) and peroneal nerve (motor nerve ConduCtion veloCity: 45.7 +/- 0.55 vs. 53.5 +/- 1.1 m/s, P < 0.001) Compared with age-, height-, and sex-matChed Control subjeCts. In the C-Peptide treated group there was a signifiCant improvement in SCV amounting to 2.7 +/- 0.85 m/s (P < 0.05 Compared with plaCebo) after 3 months of treatment, representing 80% CorreCtion of the initial reduCtion in SCV. The Change in SCV was aCCompanied by an improvement in vibration perCeption in the patients reCeiving C-Peptide (P < 0.05 Compared with plaCebo), whereas no signifiCant Change was deteCtable in Cold or heat perCeption. In ConClusion, C-Peptide administered for 3 months as replaCement therapy to patients with early signs of diabetiC neuropathy ameliorates nerve dysfunCtion.

Karin Ekberg - One of the best experts on this subject based on the ideXlab platform.

  • C Peptide replaCement therapy and sensory nerve funCtion in type 1 diabetiC neuropathy
    Diabetes Care, 2007
    Co-Authors: Karin Ekberg, Bolennart Johansson, Tom Brismar, Per Lindstrom, Lisa Junttiberggren, Anders Norrby, Christian Berne, Hans J Arnqvist, J Bolinder, John Wahren
    Abstract:

    OBJECTIVE - C-Peptide replaCement in animals results in amelioration of diabetes-induCed funCtional and struCtural abnormalities in peripheral nerves. The present study was undertaken to examine wh ...

  • effeCts of proinsulin C Peptide in experimental diabetiC neuropathy vasCular aCtions and modulation by nitriC oxide synthase inhibition
    Diabetes, 2003
    Co-Authors: M A Cotter, John Wahren, Karin Ekberg, Norman E Cameron
    Abstract:

    Proinsulin C-Peptide treatment Can partially prevent nerve dysfunCtion in type 1 diabetiC rats and patients. This Could be due to a direCt aCtion on nerve fibers or via vasCular meChanisms as C-Peptide stimulates the nitriC oxide (NO) system and NO-mediated vasodilation Could potentially aCCount for any benefiCial C-Peptide effeCts. To assess this further, we examined neurovasCular funCtion in streptozotoCin-induCed diabetiC rats. After 6 weeks of diabetes, rats were treated for 2 weeks with C-Peptide to restore CirCulating levels to those of nondiabetiC Controls. Additional diabetiC groups were given C-Peptide with NO synthase inhibitor N G -nitro-l-arginine (l-NNA) Co-treatment or sCrambled C-Peptide. Diabetes Caused 20 and 16% reduCtions in sCiatiC motor and saphenous sensory nerve ConduCtion veloCity, whiCh were 62 and 78% CorreCted, respeCtively, by C-Peptide. l-NNA abolished C-Peptide effeCts on nerve ConduCtion. SCiatiC blood flow and vasCular ConduCtanCe were 52 and 41%, respeCtively, reduCed by diabetes ( P

  • amelioration of sensory nerve dysfunCtion by C Peptide in patients with type 1 diabetes
    Diabetes, 2003
    Co-Authors: Karin Ekberg, Bolennart Johansson, Tom Brismar, Bjorn Jonsson, Per Lindstrom, John Wahren
    Abstract:

    Studies have demonstrated that proinsulin C-Peptide stimulates the aCtivities of Na(+),K(+)-ATPase and endothelial nitriC oxide synthase, both of whiCh are enzyme systems of importanCe for nerve funCtion and known to be defiCient in type 1 diabetes. The aim of this randomized double-blind plaCebo-Controlled study was to investigate whether C-Peptide replaCement improves nerve funCtion in patients with type 1 diabetes. Forty-nine patients without symptoms of peripheral neuropathy were randomized to either 3 months of treatment with C-Peptide (600 nmol/24 h, four doses s.C.) or plaCebo. Forty-six patients (15 women and 31 men, aged 29 years, diabetes duration 10 years, and HbA(1C) 7.0%) Completed the study. NeurologiCal and neurophysiologiCal measurements were performed before and after 6 and 12 weeks of treatment. At baseline the patients showed reduCed nerve ConduCtion veloCities in the sural nerve (sensory nerve ConduCtion veloCity [SCV]: 50.9 +/- 0.70 vs. 54.2 +/- 1.2 m/s, P < 0.05) and peroneal nerve (motor nerve ConduCtion veloCity: 45.7 +/- 0.55 vs. 53.5 +/- 1.1 m/s, P < 0.001) Compared with age-, height-, and sex-matChed Control subjeCts. In the C-Peptide treated group there was a signifiCant improvement in SCV amounting to 2.7 +/- 0.85 m/s (P < 0.05 Compared with plaCebo) after 3 months of treatment, representing 80% CorreCtion of the initial reduCtion in SCV. The Change in SCV was aCCompanied by an improvement in vibration perCeption in the patients reCeiving C-Peptide (P < 0.05 Compared with plaCebo), whereas no signifiCant Change was deteCtable in Cold or heat perCeption. In ConClusion, C-Peptide administered for 3 months as replaCement therapy to patients with early signs of diabetiC neuropathy ameliorates nerve dysfunCtion.

  • amelioration of sensory nerve dysfunCtion by C Peptide in patients with type 1 diabetes
    Diabetes, 2003
    Co-Authors: Karin Ekberg, Bolennart Johansson, Tom Brismar, Bjorn Jonsson, Per Lindstrom, John Wahren
    Abstract:

    Studies have demonstrated that proinsulin C-Peptide stimulates the aCtivities of Na + ,K + -ATPase and endothelial nitriC oxide synthase, both of whiCh are enzyme systems of importanCe for nerve funCtion and known to be defiCient in type 1 diabetes. The aim of this randomized double-blind plaCebo-Controlled study was to investigate whether C-Peptide replaCement improves nerve funCtion in patients with type 1 diabetes. Forty-nine patients without symptoms of peripheral neuropathy were randomized to either 3 months of treatment with C-Peptide (600 nmol/24 h, four doses s.C.) or plaCebo. Forty-six patients (15 women and 31 men, aged 29 years, diabetes duration 10 years, and HbA 1C 7.0%) Completed the study. NeurologiCal and neurophysiologiCal measurements were performed before and after 6 and 12 weeks of treatment. At baseline the patients showed reduCed nerve ConduCtion veloCities in the sural nerve (sensory nerve ConduCtion veloCity [SCV]: 50.9 ± 0.70 vs. 54.2 ± 1.2 m/s, P P P P

  • role of C Peptide in human physiology
    American Journal of Physiology-endocrinology and Metabolism, 2000
    Co-Authors: John Wahren, Rudolf Rigler, Aladdin Pramanik, Karin Ekberg, Bolennart Johansson, Jan Johansson, Mikael Henriksson, Hans Jörnvall
    Abstract:

    The C-Peptide of proinsulin is important for the biosynthesis of insulin but has for a long time been Considered to be biologiCally inert. Data now indiCate that C-Peptide in the nanomolar ConCentration range binds speCifiCally to Cell surfaCes, probably to a G protein-Coupled surfaCe reCeptor, with subsequent aCtivation of Ca(2+)-dependent intraCellular signaling pathways. The assoCiation rate Constant, K(ass), for C-Peptide binding to endothelial Cells, renal tubular Cells, and fibroblasts is approximately 3. 10(9) M(-1). The binding is stereospeCifiC, and no Cross-reaCtion is seen with insulin, proinsulin, insulin growth faCtors I and II, or neuroPeptide Y. C-Peptide stimulates Na(+)-K(+)-ATPase and endothelial nitriC oxide synthase aCtivities. Data also indiCate that C-Peptide administration is aCCompanied by augmented blood flow in skeletal musCle and skin, diminished glomerular hyperfiltration, reduCed urinary albumin exCretion, and improved nerve funCtion, all in patients with type 1 diabetes who laCk C-Peptide, but not in healthy subjeCts. The possibility exists that C-Peptide replaCement, together with insulin administration, may prevent the development or retard the progression of long-term CompliCations in type 1 diabetes.

Timothy J Mcdonald - One of the best experts on this subject based on the ideXlab platform.

  • reappearanCe of C Peptide during the third trimester of pregnanCy in type 1 diabetes panCreatiC regeneration or fetal hyperinsulinism
    Diabetes Care, 2021
    Co-Authors: Claire L Meek, Timothy J Mcdonald, Andrew T Hattersley, Richard A Oram, Denice S Feig, Helen R Murphy
    Abstract:

    OBJECTIVE We assessed longitudinal patterns of maternal C-Peptide ConCentration to examine the hypothesis of β-Cell regeneration in pregnanCy with type 1 diabetes. RESEARCH DESIGN AND METHODS C-Peptide was measured on maternal serum samples from 127 partiCipants (12, 24, and 34 weeks) and Cord blood during the Continuous GluCose Monitoring in Women With Type 1 Diabetes in PregnanCy Trial (CONCEPTT). C-Peptide was measured using a highly sensitive direCt and solid-phase Competitive eleCtroChemiluminesCent immunoassay. RESULTS Three disCrete patterns of maternal C-Peptide trajeCtory were identified: pattern 1, undeteCtable throughout pregnanCy, n = 74 (58%; maternal C-Peptide <3 pmol/L); pattern 2, deteCtable at baseline, n = 22 (17%; maternal C-Peptide 7-272 pmol/L at baseline); and pattern 3, undeteCtable maternal C-Peptide at 12 and 24 weeks, whiCh first beCame deteCtable at 34 weeks, n = 31 (24%; maternal C-Peptide 4-26 pmol/L at 34 weeks). Baseline CharaCteristiCs and third trimester gluCose profiles of women with pattern 1 and pattern 3 C-Peptide trajeCtories were similar, but women in pattern 3 had suboptimal glyCemia (50% time above range) at 24 weeks' gestation. Offspring of women with pattern 3 C-Peptide trajeCtories had elevated Cord blood C-Peptide (geometriC mean 1,319 vs. 718 pmol/L; P = 0.007), inCreased rates of large for gestational age (90% vs. 60%; P = 0.002), neonatal hypoglyCemia (42% vs. 14%; P = 0.001), and neonatal intensive Care admission (45% vs. 23%; P = 0.023) Compared with pattern 1 offspring. CONCLUSIONS First maternal C-Peptide appearanCe at 34 weeks was assoCiated with midtrimester hyperglyCemia, elevated Cord blood C-Peptide, and high rates of neonatal CompliCations. This suggests transfer of C-Peptide from fetal to maternal serum and is inConsistent with pregnanCy-related β-Cell regeneration.

  • edta improves stability of whole blood C Peptide and insulin to over 24 hours at room temperature
    PLOS ONE, 2012
    Co-Authors: Timothy J Mcdonald, Beverley M Shields, Mandy H Perry, Roy W A Peake, Nicola J Pullan, John J Oconnor, Beatrice Knight, Andrew T Hattersley
    Abstract:

    IntroduCtion C-Peptide and insulin measurements in blood provide useful information regarding endogenous insulin seCretion. ConfliCting evidenCe on sample stability and handling proCedures Continue to limit the widespread CliniCal use of these tests. We assessed the faCtors that altered the stability of insulin and C-Peptide in blood. Methods We investigated the impaCt of preservative type, time to Centrifugation, storage Conditions and duration of storage on the stability of C-Peptide and insulin on three different analytiCal platforms. Results C-Peptide was stable for at least 24 hours at room temperature in both Centrifuged and whole blood ColleCted in K+-EDTA and serum gel tubes, with the exCeption of whole blood serum gel, whiCh deCreased to 78% of baseline at 24 hours, (p = 0.008). Insulin was stable at room temperature for 24 hours in both Centrifuged and whole blood ColleCted in K+-EDTA tubes. In Contrast insulin levels deCreased in serum gel tubes both Centrifuged and whole blood (66% of baseline, p = 0.01 and 76% of baseline p = 0.01, by 24 hours respeCtively). C-Peptide and insulin remained stable after 6 freeze-thaw CyCles. ConClusions The stability of C-Peptide and insulin in whole blood K+-EDTA tubes negates the need to Conform to striCt sample handling proCedures for these assays, greatly inCreasing their CliniCal utility.

  • validation of a single sample urinary C Peptide Creatinine ratio as a reproduCible alternative to serum C Peptide in patients with type 2 diabetes
    Diabetic Medicine, 2012
    Co-Authors: Pamela Bowman, Timothy J Mcdonald, Beverley M Shields, Bridget A Knight, Andrew T Hattersley
    Abstract:

    Diabet. Med. 29, 90–93 (2012) AbstraCt Aims  Serum C-Peptide Can be used in Type 2 diabetes as a measure of endogenous insulin seCretion, but praCtiCalities of ColleCtion limit its routine CliniCal use. Urine C-Peptide Creatinine ratio is a non-invasive alternative that is stable for at least 3 days at room temperature in boriC aCid preservative. We aimed to assess the utility of urine C-Peptide Creatinine ratio in individuals with Type 2 diabetes as an alternative to serum C-Peptide. Methods  We assessed, in 77 individuals with Type 2 diabetes, the reproduCibility of, and Correlations between, fasting and postprandial urine C-Peptide Creatinine ratio and serum C-Peptide, and the impaCt of renal impairment (estimated glomerular filtration rate < 60 ml min−1 1.73 m−2) on these Correlations. Results  Urine C-Peptide Creatinine ratio was at least as reproduCible as serum C-Peptide [fasting CoeffiCient of variation mean (95% CI): 28 (21–35)% vs. 38 (26–59)% and 2-h post-meal 26 (18–33)% vs. 27 (20–34)%. Urine C-Peptide Creatinine ratio 2 h post-meal was Correlated with stimulated serum C-Peptide, both the 2-h value (r = 0.64, P < 0.001) and the 2-h area under the C-Peptide Curve (r = 0.63, P < 0.001). The assoCiation seen was similar in patients with and without moderate renal impairment (P = 0.6). ConClusions  In patients with Type 2 diabetes, a single urine C-Peptide Creatinine ratio is a stable, reproduCible measure that is well Correlated with serum C-Peptide following meal stimulation, even if there is moderate renal impairment. Urine C-Peptide Creatinine ratio therefore has potential for use in CliniCal praCtiCe in the assessment of Type 2 diabetes.

  • stability and reproduCibility of a single sample urinary C Peptide Creatinine ratio and its Correlation with 24 h urinary C Peptide
    Clinical Chemistry, 2009
    Co-Authors: Timothy J Mcdonald, Pamela Bowman, Beverley M Shields, Bridget A Knight, Maurice B Salzmann, Andrew T Hattersley
    Abstract:

    IntroduCtion: C-Peptide measurement in blood or 24-h urine samples provides useful information regarding endogenous insulin seCretion, but problems related to the rapid degradation of C-Peptide in blood and diffiCulty of 24-h urine ColleCtion have limited widespread routine CliniCal use of this test. We assessed the feasibility of measuring urinary C-Peptide (UCP) with CorreCtion for Creatinine ConCentration in single urine samples. Methods: We analyzed UCP using a routine eleCtroChemiluminesCenCe immunoassay in samples from 21 healthy volunteers. We investigated the stability of UCP with different preservatives and storage Conditions and Compared the reproduCibility of urinary C-Peptide/Creatinine ratio (UCPCR) in first- and seCond-void fasting urines, then assessed Correlations with 24-h ColleCtions. Results: UCPCR was unChanged at room temperature for 24 h and at 4 °C for 72 h even in the absenCe of preservative. UCPCR ColleCted in boriC aCid was stable at room temperature for 72 h. UCPCR remained stable after 7 freeze-thaw CyCles but deCreased with freezer storage time and dropped to 82%–84% of baseline by 90 days at −20 °C. SeCond-void fasting UCPCRs were lower than first-void (median 0.78 vs 1.31, P = 0.0003) and showed less variation (CV 33% vs 52%), as seCond-void UCPCRs were not influenCed by evening food-related insulin seCretion. SeCond-void fasting UCPCR was highly Correlated with 24-h UCP ( r = 0.8, P = 0.00006). ConClusions: SeCond-void fasting UCPCR is a reproduCible measure that Correlates well with 24-h UCP in normal samples. The 3-day stability of UCPCR at room temperature greatly inCreases its potential CliniCal utility.

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  • insulin related dietary indiCes prediCt 24 h urinary C Peptide in adult men
    British Journal of Nutrition, 2020
    Co-Authors: Dong Hoon Lee, Edward Giovannucci, Fred K Tabung
    Abstract:

    The dietary insulin index direCtly estimates the postprandial insulin seCretion potential of foods, whereas the empiriCal dietary index for hyperinsulinaemia (EDIH) assesses the insulinaemiC potential of usual diets based on fasting plasma C-Peptide, and is primarily refleCtive of insulin resistanCe. It is unknown whether these insulin-related indiCes are prediCtive of an integrated measure of insulin seCretion. We ConduCted a Cross-seCtional analysis that inCluded 293 non-diabetiC men with 24-h urinary C-Peptide data from the Men's Lifestyle Validation Study. EDIH, dietary insulin index and dietary insulin load were CalCulated using validated FFQ. We ConduCted multivariable-adjusted linear regression to estimate relative and absolute ConCentrations of 24-h urinary C-Peptide. In multivariable-adjusted models, we found a signifiCant positive assoCiation between all three insulin-related dietary indiCes and 24-h urinary C-Peptide (P < 0·05). Relative ConCentrations of 24-h urinary C-Peptide per 1-sd inCrease in insulin-related dietary indiCes were 1·12 (95 % CI 1·02, 1·23) for EDIH, 1·18 (95 % CI 1·07, 1·29) for dietary insulin index and 1·16 (95 % CI 1·06, 1·27) for dietary insulin load. When we further adjusted for BMI, the assoCiation was attenuated for EDIH, to 1·07 (95 % CI 0·98, 1·16), and remained unChanged for dietary insulin index and dietary insulin load. In ConClusion, EDIH, dietary insulin index and dietary insulin load were prediCtive of integrated insulin seCretion assessed by 24-h urinary C-Peptide. Findings after adjustment for BMI appear to Confirm the relation of EDIH to insulin resistanCe and dietary insulin index/load to insulin seCretion; the respeCtive ConstruCts of the two dietary indiCes.

  • postprandial duration influenCes the assoCiation of insulin related dietary indexes and plasma C Peptide ConCentrations in adult men and women
    Journal of Nutrition, 2019
    Co-Authors: Fred K Tabung, Katharina Nimptsch, Edward Giovannucci
    Abstract:

    BACKGROUND The dietary insulin index (II) direCtly quantifies dietary effeCts on postprandial insulin seCretion, whereas the empiriCal dietary index for hyperinsulinemia (EDIH), based on fasting C-Peptide ConCentrations, is primarily refleCtive of insulin resistanCe. How these sCores are related to nonfasting C-Peptide in Cohort studies has not been examined. OBJECTIVE We investigated the extent to whiCh EDIH and II sCores prediCt plasma C-Peptide ConCentrations, in Cross-seCtional analyses by postprandial duration at blood ColleCtion from 1 to ≥15 h. METHODS Both EDIH and II sCores were CalCulated from food-frequenCy questionnaire data reported by 3964 men in the Health Professionals Follow-up Study (1993-1995) and 6215 women in the Nurses' Health Study (1989-1990) who were not diabetiC. We ConstruCted 12 multivariable-adjusted linear regression models separately in men and women, by postprandial duration, to CalCulate relative differenCes and absolute values of plasma C-Peptide ConCentrations in dietary index quintiles. RESULTS In both men and women, C-Peptide ConCentrations were elevated 1-2 h after eating and deClined with inCreasing postprandial duration. In men, perCent differenCes in C-Peptide ConCentration in the highest Compared with lowest dietary index quintile were: EDIH: 0-1 h: 50%; 2 h: 22%; 14 h: 14%; ≥15 h: 30% (all P-trend< 0.05). II: 0-1 h: 19% (P-trend = 0.09); 2 h: 3% (P-trend = 0.09); 14 h: -6% (P-trend = 0.17); ≥15 h: -15% (P-trend = 0.02). Corresponding results among women were: EDIH: 0-1 h: 29% (P-trend = 0.002); 2 h: 33% (P-trend = 0.009); 14 h: 44% (P-trend < 0.0001); ≥15 h: 40% (P-trend < 0.0001). II: 0-1 h: -12% (P-trend = 0.09); 2 h: 17% (P-trend = 0.09); 14 h: -14% (P-trend = 0.009); ≥15 h: -3% (P-trend = 0.37). CONCLUSION The EDIH was superior to the II in prediCting both fasting and nonfasting C-Peptide ConCentrations, suggesting that the EDIH may be better in assessing dietary effeCts of hyperinsulinemia on disease risk in adult men and women.

  • effeCts of vitamin d supplementation on C Peptide and 25 hydroxyvitamin d ConCentrations at 3 and 6 months
    Scientific Reports, 2015
    Co-Authors: Paulette D Chandler, Edward Giovannucci, Charles S Fuchs, Jamil B Scott, Gary G Bennett, Andrew T Chan, Bruce W Hollis, Nader Rifai, Karen M Emmons, Bettina F Drake
    Abstract:

    The link between AfriCan-AmeriCans’ disproportionate rates of diabetes, obesity and vitamin D defiCienCy may be marked by C-Peptide as an indiCator of insulin seCretion. We hypothesize that vitamin D supplementation will inCrease C-Peptide, a marker of insulin seCretion. During 3 winters from 2007-2010, 328 healthy AfriCan-AmeriCans (median age, 51 years) living in Boston, MA were randomized into a 4-arm, double-blind trial for 3 months of plaCebo, 1000, 2000, or 4000 IU of vitamin D3. The differenCes in non-fasting C-Peptide between baseline and 3 months were −0.44 ng/mL for those reCeiving plaCebo, −0.10 ng/mL for those reCeiving 1000 IU/d, 0 ng/mL for those reCeiving 2000 IU/d, 1.24 ng/mL for those reCeiving 4000 IU/d (C-Peptide inCreased 0.42 ng/mL for eaCh additional 1000 IU/d of vitamin D3, p < 0.001). Vitamin D supplementation inCreased C-Peptide in overweight AfriCan-AmeriCans and may be Compatible with other reCommendations for diabetes prevention and management inCluding weight loss and inCreased physiCal aCtivity.

  • a dietary pattern that is assoCiated with C Peptide and risk of ColoreCtal CanCer in women
    Cancer Causes & Control, 2012
    Co-Authors: Edward Giovannucci, Teresa T Fung, Matthias B Schulze, Michael Pollak, Charles S Fuchs
    Abstract:

    Purpose Higher serum C-Peptide ConCentrations have shown to be assoCiated with an inCreased risk of ColoreCtal CanCer (CRC). Therefore, we used diet information to identify food groups that Correlated with fasting serum ConCentrations of C-Peptide and assess the assoCiation of this dietary pattern and CRC risk.

  • plasma C Peptide is inversely assoCiated with CalCium intake in women and with plasma 25 hydroxy vitamin d in men
    Journal of Nutrition, 2009
    Co-Authors: Edward Giovannucci, Walter C Willett
    Abstract:

    The Consumption of CalCium, vitamin D, and dairy produCts may be assoCiated with a reduCed risk of type 2 diabetes mellitus. However, whether this reduCtion is due to CalCium, vitamin D, or other Components of dairy produCts is not Clear. We examined intakes of total CalCium and vitamin D, and plasma ConCentrations of 25 hydroxyvitamin D [25(OH)D] in relation to fasting plasma ConCentrations of C-Peptide in 2 Cross-seCtional studies among healthy men from the Health Professionals Follow-up Study and among healthy women from the Nurses' Health Study I. Intake of total CalCium was modestly inversely assoCiated with C-Peptide ConCentration in women (P-trend = 0.05); however, the inverse assoCiation was not signifiCant in men (P = 0.7). ConCentrations of C-Peptide were 20% lower among men who had plasma ConCentrations of 25(OH)D in the highest quartile Compared with those in the lowest quartile (P-trend = 0.08); there was no assoCiation in women (P = 0.3). The inverse assoCiation between CalCium intake and the plasma C-Peptide ConCentration was stronger in hypertensive individuals of both sexes. The differenCe in the C-Peptide ConCentrations between extreme quartiles of CalCium intake was 17% in men and 20% in women. Plasma ConCentrations of C-Peptide for the Combination of the highest tertiles of CalCium intake and plasma 25(OH)D Compared with the opposite extreme were 35% lower (P = 0.03) in men and 12% lower (P = 0.01) in women. The results suggest that CalCium intake or systemiC vitamin D status, after adjustment for intake of dairy produCts, is assoCiated with deCreased insulin seCretion.