Dataset Information

Continuous glucose monitoring after islet transplantation in type 1 diabetes: an excellent graft function (?-score greater than 7) Is required to abrogate hyperglycemia, whereas a minimal function is necessary to suppress severe hypoglycemia (?-score greater than 3).

ABSTRACT: For the last 10 yr, continuous glucose monitoring (CGM) has brought up new insights into the accuracy of blood glucose analysis.Our objective was to determine how islet graft function was able to influence the various components of dysglycemia after islet transplantation (IT).We conducted a single-arm open-labeled study with a 3-yr follow-up in a referral center (ClinicalTrial.gov identifiers NCT00446264 and NCT01123187).Twenty-three consecutive patients with type 1 diabetes (14 islet alone, nine islet after kidney) received IT within 3 months using the Edmonton protocol.INTERVENTION included 72-h CGM before and 3, 6, 9, 12, 24, and 36 months after transplantation.Graft function was estimated via ?-score, a previously validated index (range 0-8) based on treatment requirements, C-peptide, blood glucose, and glycated hemoglobin.At the 3-yr visit, graft function persisted in 19 patients (82%), and 10 (43%) remained insulin independent. Glycated hemoglobin decreased in the whole cohort from 8.3% (7.3-9.0%) at baseline to 6.7% (5.9-7.7%) at 3 yr [median (interquartile range), P < 0.01]. Mean glucose, glucose sd, and time spent with glycemia above 10 mmol/liter (hyperglycemia) and below 3 mmol/liter (hypoglycemia) were significantly lower after IT (P < 0.05 vs. baseline). The four CGM outcomes were related to ?-score (P < 0.001). However, partial function (?-score >3) was sufficient to abrogate hypoglycemia; suboptimal function (?-score >5) was necessary to significantly improve mean glucose, glucose sd, and hyperglycemia; and optimal function (? score >7) was necessary to normalize them.The four components of dysglycemia were not equally affected by the degree of islet graft function, which could have important implications for future development of ?-cell replacement. A ?-score above 3 dramatically reduced the occurrence of hypoglycemia.

SUBMITTER: Vantyghem MC

PROVIDER: S-EPMC3485599 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Continuous glucose monitoring after islet transplantation in type 1 diabetes: an excellent graft function (β-score greater than 7) Is required to abrogate hyperglycemia, whereas a minimal function is necessary to suppress severe hypoglycemia (β-score greater than 3).

Vantyghem Marie-Christine MC Raverdy Violeta V Balavoine Anne-Sophie AS Defrance Frédérique F Caiazzo Robert R Arnalsteen Laurent L Gmyr Valéry V Hazzan Marc M Noël Christian C Kerr-Conte Julie J Pattou Francois F

The Journal of clinical endocrinology and metabolism 20120920 11

<h4>Context</h4>For the last 10 yr, continuous glucose monitoring (CGM) has brought up new insights into the accuracy of blood glucose analysis.<h4>Objective</h4>Our objective was to determine how islet graft function was able to influence the various components of dysglycemia after islet transplantation (IT).<h4>Design and setting</h4>We conducted a single-arm open-labeled study with a 3-yr follow-up in a referral center (ClinicalTrial.gov identifiers NCT00446264 and NCT01123187).<h4>Patients</ ...[more]

PMID: 22996144

Similar Datasets

Project description:To determine the predictive value of the presence of maternal islet beta-cell autoantibodies with respect to neonatal outcomes.A total of 311 pregnant women with abnormal 75 g oral glucose tolerance test (OGTT) results were enrolled in this study. Maternal glutamic acid decarboxylase autoantibodies (GADA), islet cell autoantibodies (ICA) and insulin autoantibodies (IAA) were tested in fasting blood both on the day following the routine OGTT and before delivery. The birth weight, Apgar score, blood glucose and outcomes of each neonate were later evaluated and recorded.1. In this study, 33.9% of the pregnant women with gestational hyperglycemia had detectable levels of one or more types of anti-islet cell antibodies in the third trimester. The proportion of women who produced GADA and/or ICA was significantly higher in the group of women with gestational hyperglycemia than in the control group (P<0.05). The groups similarly differed in the proportion of women who tested positive for any anti-islet cell antibody (P<0.05). 2. Of the patients in our study, those who produced GADA exhibited an increase in uterine and umbilical arterial pulsatility indexes (PIs) during the third trimesters compared with the control group (P˂0.05). Additionally, an increased frequency of fetal growth restriction (FGR) was observed in the infants of women who produced IAA during pregnancy compared with those without autoantibodies (P˂0.05). 3. The rate of newborn admission to the neonatal intensive care unit (NICU) was significantly associated with the presence of maternal ICA during the third trimester (OR, 6.36; 95% CI, 1.22-33.26). 4. The incidence of neonatal asphyxia was associated with the presence of maternal GADA in both the second (OR, 10.44; 95% CI, 1.46-74.92) and the third (OR, 8.33; 95% CI, 1.45-47.82) trimesters.Approximately one-third of the women with gestational hyperglycemia produced anti-islet cell antibodies. The incidence of FGR was higher in women with gestational hyperglycemia who produced IAA than in those without autoantibodies. Maternal ICA production in the third trimester was a risk factor for the subsequent admission of newborns to the NICU. Furthermore, the presence of maternal GADA placed the neonate at increased risk for asphyxia.

Project description:Type 1 diabetes is a complex disease characterized by the lack of endogenous insulin secreted from the pancreatic β-cells. Although β-cell targeted autoimmune processes and β-cell dysfunction are known to occur in type 1 diabetes, a complete understanding of the cell-to-cell interactions that support pancreatic function is still lacking. To characterize the pancreatic endocrine compartment, we studied pancreata from healthy adult donors and investigated a single cell surface adhesion molecule, desmoglein-2 (DSG2). Genetically-modified mice lacking Dsg2 were examined for islet cell mass, insulin production, responses to glucose, susceptibility to a streptozotocin-induced mouse model of hyperglycaemia, and ability to cure diabetes in a syngeneic transplantation model. Herein, we have identified DSG2 as a previously unrecognized adhesion molecule that supports β-cells. Furthermore, we reveal that DSG2 is within the top 10 percent of all genes expressed by human pancreatic islets and is expressed by the insulin-producing β-cells but not the somatostatin-producing δ-cells. In a Dsg2 loss-of-function mice (Dsg2lo/lo), we observed a significant reduction in the number of pancreatic islets and islet size, and consequently, there was less total insulin content per islet cluster. Dsg2lo/lo mice also exhibited a reduction in blood vessel barrier integrity, an increased incidence of streptozotocin-induced diabetes, and islets isolated from Dsg2lo/lo mice were more susceptible to cytokine-induced β-cell apoptosis. Following transplantation into diabetic mice, islets isolated from Dsg2lo/lo mice were less effective than their wildtype counterparts at curing diabetes. In vitro assays using the Beta-TC-6 murine β-cell line suggest that DSG2 supports the actin cytoskeleton as well as the release of cytokines and chemokines. Taken together, our study suggests that DSG2 is an under-appreciated regulator of β-cell function in pancreatic islets and that a better understanding of this adhesion molecule may provide new opportunities to combat type 1 diabetes.

Dataset Information

Continuous glucose monitoring after islet transplantation in type 1 diabetes: an excellent graft function (?-score greater than 7) Is required to abrogate hyperglycemia, whereas a minimal function is necessary to suppress severe hypoglycemia (?-score greater than 3).

Publications

Continuous glucose monitoring after islet transplantation in type 1 diabetes: an excellent graft function (β-score greater than 7) Is required to abrogate hyperglycemia, whereas a minimal function is necessary to suppress severe hypoglycemia (β-score greater than 3).

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets