Urinary C-Peptide: A Useful Tool for Evaluating the Endogenous Insulin Reserve in Cohort and Longitudinal Studies of Diabetes in Childhood

Author(s):  
C E de Beaufort ◽  
N C den Boer ◽  
G J Bruining ◽  
G A M Eilers ◽  
R van Strik ◽  
...  

Increasing research into the remission phase of type I diabetes mellitus stresses the importance of a non-traumatic and reliable method for the evaluation of endogenous insulin production. We compared 24-h urinary C-peptide excretion (UCE) with plasma C-peptide values before and after stimulation with 1 mg glucagon in 24 type I diabetic children. Fasting plasma C-peptide values and stimulated plasma C-peptide values showed a linear correlation with 24 h UCE. Mean plasma C-peptide levels correlated inversely with the exogenous insulin dose. A slightly better correlation was found between the exogenous insulin dose and 24 h UCE. Control data of 24 h UCE were obtained from healthy siblings. A linear correlation with age was found up to 10 years of age above which UCE values seem to reach a plateau. This effect of age, as well as the frequency of sampling was taken into account in the derivation of 95% reference intervals for UCE. The measurement of 24 h UCE appears to be a useful parameter to assess endogenous insulin production in diabetic children, provided that age is taken into account.

Author(s):  
A J Krentz ◽  
P J Hale ◽  
E C Albutt ◽  
M Nattrass

A case of factitious remission of type I diabetes in an adolescent girl is reported. The clue to diagnosis came from an inconsistency between clinic blood glucose levels and the corresponding values of glycosylated haemoglobin. Investigations of 24 h hormone and metabolite profiles demonstrated discrepancies between insulin dose, endogenous insulin production and free insulin levels which provided confirmatory evidence of surreptitious self-administration of insulin by the patient.


1999 ◽  
Vol 97 (2) ◽  
pp. 149-156 ◽  
Author(s):  
Flemming WOLLESEN ◽  
Lars BERGLUND ◽  
Christian BERNE

Insulin stimulates endothelin-1 (ET-1) expression in a dose-response relationship, and ET-1 effects on vascular wall structure are similar to the long-term complications of diabetes. We therefore determined whether the plasma ET-1 concentration in patients with diabetes is associated with their total insulin exposure to see if plasma ET-1 might be a link between insulin exposure and long-term complications of diabetes. We studied 69 patients with Type I and 40 patients with Type II diabetes mellitus in equally tight glycaemic control for 2 years in a cross-sectional design. We measured basal and glucagon-stimulated plasma C-peptide, abdominal sagittal diameter, skinfold thickness, glomerular filtration rate, albumin excretion rate and standard clinical characteristics. Mean HbA1c was 6.4% in Type I and 6.3% in Type II diabetes. Patients with an albumin excretion rate > 300 μg/min were excluded. Adjusted mean plasma ET-1 was 4.11 (S.E.M. 0.39) pg/ml in 21 normal subjects, 3.47 (0.19) pg/ml in Type I diabetes and 4.84 (0.26) pg/ml in Type II diabetes (P = 0.0001). In all patients with measurable plasma C-peptide, plasma ET-1 was associated with basal plasma C-peptide (r = 0.5018, P < 0.0001), with stimulated plasma C-peptide (r = 0.5379, P < 0.0001), and with total daily insulin dose (r = 0.2219, P = 0.00851). Abdominal obesity, metabolic abnormalities, blood pressure and glomerular filtration rate were not associated with plasma ET-1, when corrected for C-peptide and daily insulin dose. Our study shows that the plasma concentration of ET-1 is closely associated with insulin secretion and insulin dose in patients with diabetes. Plasma ET-1 is higher in Type II diabetes than in Type I diabetes. Increased insulin exposure in patients with diabetes may have long-term effects on vascular wall structure through its stimulation of ET-1 expression.


1993 ◽  
Vol 39 (6) ◽  
pp. 11-14
Author(s):  
M. M. Shagaeva ◽  
I. A. Sobenin ◽  
L. S. Slavina ◽  
A. N. Orekhov

The task of this research was to study exogenous insulin effect on blood serum atherogenic potential in patients with type I diabetes mellitus. Under study were relationship between blood serum atherogenic potential in diabetics and daily insulin dose and duration of therapy, as well as exogenous insulin effect on the major atherosclerotic manifestations in tissue cultures, such as intracellular cholesterol content in cultured cells and labeled thymidine incorporation in cellular nuclei DNA. Blood serum atherogenicity did not correlate with insulin dose and duration of insulin therapy both in adult patients and children. Insulin prescription to newly detected patients with type I condition did not influence blood serum atherogenic potential. Exogenic insulin did not influence the major atherosclerotic manifestations at the cellular level, namely, on intracellular cholesterol content in cultured cells and these cells proliferative activity; it had no influence on blood serum atherogenic potential of the patients with type I condition.


2005 ◽  
Vol 11 ◽  
pp. 17
Author(s):  
Stanley Andrew Tan ◽  
Marilyn Kay Wilson ◽  
John Stephan Pasztor ◽  
Linda Giles Tan

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2082
Author(s):  
Josip Delmis ◽  
Marina Ivanisevic ◽  
Marina Horvaticek

Type 1 diabetes (T1DM) is an autoimmune disease characterized by the gradual loss of β-cell function and insulin secretion. In pregnant women with T1DM, endogenous insulin production is absent or minimal, and exogenous insulin is required to control glycemia and prevent ketoacidosis. During pregnancy, there is a partial decrease in the activity of the immune system, and there is a suppression of autoimmune diseases. These changes in pregnant women with T1DM are reflected by Langerhans islet enlargement and improved function compared to pre-pregnancy conditions. N-3 polyunsaturated fatty acids (n-3 PUFA) have a protective effect, affect β-cell preservation, and increase endogenous insulin production. Increased endogenous insulin production results in reduced daily insulin doses, better metabolic control, and adverse effects of insulin therapy, primarily hypoglycemia. Hypoglycemia affects most pregnant women with T1DM and is several times more common than that outside of pregnancy. Strict glycemic control improves the outcome of pregnancy but increases the risk of hypoglycemia and causes maternal complications, including coma and convulsions. The suppression of the immune system during pregnancy increases the concentration of C-peptide in women with T1DM, and n-3 PUFA supplements serve as the additional support for a rise in C-peptide levels through its anti-inflammatory action.


Author(s):  
T. A. Stewart ◽  
D. Liggitt ◽  
S. Pitts ◽  
L. Martin ◽  
M. Siegel ◽  
...  

Insulin-dependant (Type I) diabetes mellitus (IDDM) is a metabolic disorder resulting from the lack of endogenous insulin secretion. The disease is thought to result from the autoimmune mediated destruction of the insulin producing ß cells within the islets of Langerhans. The disease process is probably triggered by environmental agents, e.g. virus or chemical toxins on a background of genetic susceptibility associated with particular alleles within the major histocompatiblity complex (MHC). The relation between IDDM and the MHC locus has been reinforced by the demonstration of both class I and class II MHC proteins on the surface of ß cells from newly diagnosed patients as well as mounting evidence that IDDM has an autoimmune pathogenesis. In 1984, a series of observations were used to advance a hypothesis, in which it was suggested that aberrant expression of class II MHC molecules, perhaps induced by gamma-interferon (IFN γ) could present self antigens and initiate an autoimmune disease. We have tested some aspects of this model and demonstrated that expression of IFN γ by pancreatic ß cells can initiate an inflammatory destruction of both the islets and pancreas and does lead to IDDM.


PEDIATRICS ◽  
1987 ◽  
Vol 79 (5) ◽  
pp. 756-759
Author(s):  
John I. Malone ◽  
Saul Lowitt ◽  
John A. Duncan ◽  
Shirish C. Shah

Hematuria of unknown origin occurs in 30% of patients with diabetic nephropathy. In nondiabetic persons, hematuria may be caused by hypercalciuria with or without nephrolithiasis. Eight children with type I diabetes mellitus, hematuria, and hypercalciuria were observed in our clinic during a 1-year period. Two of these also had evidence of renal papillary necrosis. To assess the importance of hypercalciuria in the pathogenesis of hematuria in children with diabetes mellitus, we measured urinary calcium excretion in a large population of such patients. The calcium to creatinine ratio in the urine of diabetic children (0.21 ± 0.01) was greater than that of nondiabetic children (0.12 ± 0.01). A calcium to creatinine ratio of 0.28 was established as the upper limit of normal in our nondiabetic population, and 27% of the diabetic children were hypercalciuric on this basis. The diabetic children with hypercalciuria also had hyperphosphaturia and a urinary CaHPO4.2H2O molar ion product three times that found in the nondiabetic control population. These data suggest that many children with diabetes are at risk for renal damage due to hypercalciuria. Because hypercalciuria is more common in diabetic than nondiabetic children, it may play a previously unrecognized role in the renal disease associated with diabetes mellitus.


2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Lawrence S. Gazda ◽  
Horatiu V. Vinerean ◽  
Melissa A. Laramore ◽  
Richard D. Hall ◽  
Joseph W. Carraway ◽  
...  

We have previously described the use of a double coated agarose-agarose porcine islet macrobead for the treatment of type I diabetes mellitus. In the current study, the long-term viral safety of macrobead implantation into pancreatectomized diabetic dogs treated with pravastatin (n=3) was assessed while 2 dogs served as nonimplanted controls. A more gradual return to preimplant insulin requirements occurred after a 2nd implant procedure (days 148, 189, and >652) when compared to a first macrobead implantation (days 9, 21, and 21) in all macrobead implanted animals. In all three implanted dogs, porcine C-peptide was detected in the blood for at least 10 days following the first implant and for at least 26 days following the second implant. C-peptide was also present in the peritoneal fluid of all three implanted dogs at 6 months after 2nd implant and in 2 of 3 dogs at necropsy. Prescreening results of islet macrobeads and culture media prior to transplantation were negative for 13 viruses. No evidence of PERV or other viral transmission was found throughout the study. This study demonstrates that the long-term (2.4 years) implantation of agarose-agarose encapsulated porcine islets is a safe procedure in a large animal model of type I diabetes mellitus.


2017 ◽  
Vol 33 (S1) ◽  
pp. 166-167
Author(s):  
Danni Chen ◽  
Kun Xiong ◽  
Di Xue

INTRODUCTION:Despite several therapeutic options existing for the patients with type I diabetes, the patients are still at high risk for severe acute and chronic complications (1). Pancreatic islet transplantation is a promising therapy to achieve good glycemic control with no or little additional insulin (2). This study was to evaluate the effectiveness, safety, economics and social ethics of islet transplantation (IT) for the patients with type I diabetes.METHODS:We searched PubMed, Cochrane Library, CNKI and CBM to retrieve eligible literatures. The values of H1bAc before and after transplantation, the rates of insulin independence and functional islet graft at the last follow-up, and the insulin dose per patient-day were analyzed. Descriptive statistics, t tests and random effects meta-analyses were used in the study.RESULTS:Totally 21 original papers with 488 cases from 9 different countries were reviewed and analyzed. The studies showed that the H1bAc was decreased from 7.7 percent (95 percent Confidence Interval, CI: 7.4, 8.1) before IT to 6.2 percent (95 percent CI: 5.9, 6.4) after IT. At the last follow-up, the rate of insulin independence was 48.96 percent (95 percent CI: 31.32, 66.73) and the rate of functional islet graft was 65.79 percent (95 percent CI: 47.06, 82.21). The daily insulin requirement dropped from 0.52U/kg/d to 0.21 U/kg/d. The main adverse events of islet transplantation were bleeding (7.01 percent) and the complications related to immunosuppression therapy (6.37 percent), but they were less than those of whole pancreas transplantation.Another study with a 20-year follow-up also showed that the cost-effectiveness of islet transplantation (USD47,800 per QALY) was better than that of insulin therapy (USD71,000 per QALY). In spite of the better evidences of islet transplantation, the insufficient organ donation and issues of cell purification and immunological rejection limited islet transplantation's widespread utilization (1).CONCLUSIONS:The islet transplantation therapy for the patients with type I diabetes has a potential to achieve insulin independence and better cost-effectiveness, and is relatively safe. But there are some obstacles for its wide utilization.


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