Assessment of glycemic control after islet transplantation using the continuous glucose monitor in insulin-independent versus insulin-requiring type 1 diabetes subjects.

BACKGROUND: The aim of this study was to assess and compare glycemic control using the continuous glucose monitor (CGMS, Medtronic Minimed, Northridge, CA) in type 1 diabetes mellitus (T1DM) subjects who are insulin-independent versus those who require insulin after islet transplantation alone (ITA). METHODS: Glycemic control was assessed using 72-h CGMS in eight T1DM subjects who were insulin-independent after ITA (ITA-II), eight T1DM subjects who were C-peptide-positive but insulin-requiring after ITA (ITA-IR), and eight non-transplanted (NT) T1DM subjects. RESULTS: Standard deviation of glucose values was not significantly different between ITA-II and ITA-IR subjects (ITA-II, 1.2 +/- 0.1 mM; ITA-IR, 2.0 +/- 0.3 mM; P = 0.072). Both ITA groups were more stable than NT subjects (NT, 3.3 +/- 0.3 mM; P = 0.001 vs. ITA). Mean high glucose values were significantly lower in ITA subjects compared with NT subjects (ITA-II, 10.5 +/- 0.6 mM; ITA-IR, 13.0 +/- 1.0 mM; NT, 16.1 +/- 1.1 mM; P = 0.002). Mean average glucose values were not significantly different among all groups (ITA-I, 6.7 +/- 0.2 mM; ITA-IR, 7.8 +/- 0.3 mM; NT, 7.7 +/- 0.6 mM; P = 0.198). Mean low glucose values were significantly higher in both ITA groups compared with NT subjects (ITA-II, 4.5 +/- 0.2 mM; ITA-IR, 4.3 +/- 0.3 mM; NT, 3.0 +/- 0.2 mM; P = 0.003). Duration of hypoglycemic excursions (<3.0 mM) was markedly reduced in both ITA groups (ITA-II, 0%; ITA-IR, 2.4 +/- 0.2%; NT, 11.8 +/- 4.2%). Glycated hemoglobin was not significantly different between ITA groups (ITA-II, 6.4 +/- 0.2%; ITA-IR, 6.5 +/- 0.3%) and was significantly higher in NT subjects (8.3 +/- 0.2%; P < 0.001 vs. ITA). CONCLUSIONS: CGMS monitoring demonstrates that glycemic lability and hypoglycemia are significantly reduced in C-peptide-positive islet transplant recipients, whether or not supplementary, exogenous insulin is used, compared with non-transplanted T1DM subjects.

Beta-score: an assessment of beta-cell function after islet transplantation.

OBJECTIVE: Success after islet transplantation can be defined in terms of insulin independence, C-peptide secretion, or glycemic control. These measures are interdependent and all need to be considered in evaluating beta-cell function after islet transplantation. For the current study, a composite beta-score was developed that provides an integrated measure of beta-cell function success after islet transplantation. RESEARCH DESIGN AND METHODS: The proposed scoring system gave 2 points each for normal fasting glucose, HbA(1c), stimulated C-peptide, and absence of insulin or oral hypoglycemic agent use. No points were awarded if the fasting glucose was in the diabetic range, the HbA(1c) was >6.9%, C-peptide secretion was absent on stimulation, or daily insulin use was in excess of 0.24 units/kg. One point was given for intermediate values. The score ranged from 0 to 8 and was correlated with the glucose value 90 min after a standard mixed meal challenge (n = 218) in 57 subjects before and after islet transplantation. The score was also used to follow subjects for up to 5 years after islet transplantation. RESULTS: The beta-score correlated well with the plasma glucose level 90 min after a mixed meal challenge (r = -0.849, P < 0.001). On follow-up, the beta-score rose after the first transplant and was maintained up to 5 years, demonstrating continuing function of the transplanted beta-cells. CONCLUSIONS: The beta-score provides a simple clinical scoring system that encompasses glycemic control, diabetes therapy, and endogenous insulin secretion that correlates well with physiological measures of beta-cell function. On this basis, it is suitable as an overall measure of beta-cell transplant function. The beta-score gives an integrated measure of beta-cell function as a continuum that may be more useful than simply assessing the presence or absence of insulin independence.

Assessment of diet quality in pregnant women using the Healthy Eating Index.

The objectives of this pilot study were to examine the diets of pregnant women and healthy women of childbearing age, to quantify their diets using the US Department of Agriculture Healthy Eating Index (HEI), and to assess the validity of the HEI in pregnancy in terms of macronutrients and micronutrients. Dietary information was prospectively collected from nonpregnant women and pregnant women at 20 to 38 weeks' gestation using 4-day food records. Diet records were analyzed for nutrient content using computer software and for overall quality using the HEI. Differences between the groups were analyzed statistically using the Student's t test, descriptive statistics, and chi 2 analysis. The macronutrient composition of the diets and the number of food group servings were similar in both groups. The HEI scores for control (nonpregnant) and pregnant women were similar, 72.6+/-1.52 and 75.0+/-0.99, respectively, of a maximum possible score of 100. Pregnant women did not meet daily recommended intakes of micronutrients of concern in pregnancy (calcium, iron, folate) through dietary means. Dietary counseling and nutritional supplements (particularly iron and folate) may be necessary. The HEI was useful in providing a composite measure of dietary intake, but did not discern the need for vitamin and mineral supplements during pregnancy.

Islet graft assessment in the Edmonton Protocol: implications for predicting long-term clinical outcome.

The success of the Edmonton Protocol for islet transplantation has provided new hope in the treatment of type 1 diabetes. This study reports on the assessment of 83 human islet grafts transplanted using the Edmonton Protocol since 1999. Cellular composition, as assessed by immunohistochemistry, showed a lower islet purity (approximately 40%) than has been reported in previous studies using dithizone staining to quantitate islet equivalents. Furthermore, grafts were found to contain substantial populations of exocrine and ductal tissue. Total cellular insulin transplanted was 8,097.6 +/- 3,164.4 microg/patient, and was significantly lower in bottom gradient layer grafts than top gradient layer or whole/combined grafts (P < 0.0005). A static incubation test for islet function gave a stimulation index of 3-4, although this measure did not correlate with posttransplant metabolic outcome. Furthermore, we confirmed a previously reported trend in which donor age affects islet yield and purity. It is important to note that a significant positive correlation was observed between the number of islet progenitor (ductal-epithelial) cells transplanted and long-term metabolic success as assessed an by intravenous glucose tolerance test at approximately 2 years posttransplant. In summary, careful assessment of islet graft composition is needed in a clinical transplantation program to accurately estimate islet purity and assess the contribution of other cell types present, such as islet progenitor cells.

Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation.

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.week(-1)). The LI correlated much more closely than the MAGE with the clinical assessment of lability. A HYPO score of > or = 1,047 (90th percentile) or an LI > or = 433 mmol/l(2)/h.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.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.