Assessment of the Severity of Hypoglycemia and Glycemic Lability in Type 1 Diabetic Subjects Undergoing Islet Transplantation

Abstract

Currently, the major indications for solitary islet transplantation are recurrent severe hypoglycemia and labile glucose control. Quantifying these problems remains subjective. We have developed a scoring system for both hypoglycemia and glycemic lability, established normative data, and used them in patients who have undergone islet transplantation. A composite hypoglycemic score (HYPO score) was devised based on the frequency, severity, and degree of unawareness of the hypoglycemia. In addition, using 4 weeks of glucose records, a lability index (LI) was calculated based on the change in glucose levels over time and compared with a clinical assessment of glycemic lability. A mean amplitude of glycemic excursions (MAGE) was also calculated based on 2 consecutive days of seven readings each day. These scores were determined in 100 randomly selected subjects with type 1 diabetes from our general clinic to serve as a control group and in patients before and after islet transplantation. The mean age of the control diabetic subjects was 38.4 ؎ 1.3 years (؎SE), with a duration of diabetes of 21.5 ؎ 1.1 years. The median HYPO score in the control subjects was 143 (25th to 75th interquartile range: 46 -423). The LI in the diabetic control subjects was 223 (25th to 75th interquartile range: 130 -329 mmol/l 2 /h ⅐ week ؊1 ). The LI correlated much more closely than the MAGE with the clinical assessment of lability. A HYPO score of >1,047 (90th percentile) or an LI >433 mmol/l 2 / h ⅐ week ؊1 (90th percentile) indicated serious problems with hypoglycemia or glycemic lability, respectively. The islet transplant patients (n ‫؍‬ 51) were 42.1 ؎ 1.4 years old, with a duration of diabetes of 25.7 ؎ 1.4 years. Islet transplant patients had a mean HYPO score of 1,234 ؎ 184 pretransplant, which was significantly higher than that of the control subjects (P < 0.001), which became negligible posttransplantation with the elimination of hypoglycemia. The median LI pretransplant was 497 mmol/l 2 /h ⅐ week ؊1 (25th to 75th interquartile range: 330 -692), significantly higher than that of control subjects (P < 0.001), and fell to 40 (25th to 75th interquartile range: 14 -83) within a month after the final transplant. In those who had lost graft function, the LI rose again. The HYPO score and LI provide measures of the extent of problems with hypoglycemia and glycemic lability, respectively, complement the clinical assessment of the problems with glucose control before islet transplantation, and will allow comparison of selection of subjects for transplants between centers. Diabetes 53:955-962, 2004 P atients with type 1 diabetes have to balance the risks of long-term hyperglycemia and its consequences versus the acute risk of hypoglycemia. The Diabetes Control and Complications Trial has confirmed that achieving strict glycemic control is worthwhile but comes with the price of a threefold increased risk of severe hypoglycemia (1). In addition to long-term consequences (2), such hypoglycemia comes with costs in the short term as evidenced...

Assessment of glycemic lability and severity of hypoglycemia in Korean patients with type 1 diabetes

“…The modified LI and the average daily risk range (ADRR) showed higher concordance with other glycemic lability indexes than did the LI or mean amplitude of glycemic excursions (MAGE). The results showed that the hypoglycemic indexes in this study population were lower than the results from Ryan et al Furthermore, the ADRR or modified LI were better measures for high risk of severe lability than were the LI and MAGE.Key words: Glycemic lability, Type 1 diabetes mellitus, Hypoglycemia center comparison as well as to establish standards for pancreas or islet transplantation [7]. Several indexes have been proposed for glycemic lability and hypoglycemia.…”

“…The LI measures the severity of glycemic lability and complements the clinical assessment of patients before islet transplantation [7,12]. The LI is calculated based on the change in glucose level over a four-week period; however, the LI can change depending on the frequency of glucose measurements [13].…”

“…Key words: Glycemic lability, Type 1 diabetes mellitus, Hypoglycemia center comparison as well as to establish standards for pancreas or islet transplantation [7]. Several indexes have been proposed for glycemic lability and hypoglycemia.…”

Islet Cell Hormonal Responses to Hypoglycemia After Human Islet Transplantation for Type 1 Diabetes

“…Recent work from Edmonton, Alberta, clearly demonstrates that intrahepatic transplantation of isolated pancreatic islets can eliminate the development of severe hypoglycemic episodes in patients with type 1 diabetes (2). Islet transplantation may abolish hypoglycemia by reducing exogenous insulin requirements, but whether improvement in glucose counterregulatory mechanisms against hypoglycemia also contributes has not been fully studied.…”

Quelles cellules souches pour une réparation du pancréas endocrine ?

“…Chez les premiers patients, durant la première année qui a suivi la greffe, la glycémie s'est normalisée, leur permettant d'éviter le recours à l'insuline. Toutefois, cinq années plus tard, seuls 10 % des patients greffés sont restés indépendants d'un apport d'insuline exogène [3]. Ces données encourageantes ont entraîné la mise en place d'importants programmes de greffes d'îlots dans le monde.…”