Correlation Between Hemoglobin Glycation Index Measured by Continuous Glucose Monitoring With Complications in Type 1 Diabetes.

OBJECTIVE: HbA1C is the "gold standard" parameter to evaluate glycemic control in diabetes; however, its correlation with mean glucose is not always perfect. The objective of this study was to correlate continuous glucose monitoring (CGM)-derived hemoglobin glycation index (HGI) with microvascular complications. METHODS: We conducted a cross-sectional study including permanent users of CGM with type 1 diabetes mellitus or latent autoimmune diabetes of the adult. HGI was estimated, and presence of microvascular complications was compared in subgroups with high or low HGI. A logistic regression analysis to assess the contribution of high HGI to chronic kidney disease (CKD) was performed. RESULTS: In total, 52 participants who were aged 39.7 ± 14.7 years, with 73.1% women and 15.5 years (IQR, 7.5-29 years) since diagnosis, were included; 32.7% recorded diabetic retinopathy, 25% CKD, and 19.2% neuropathy. The median HbA1C was 7.6% (60 mmol/mol) and glucose management indicator (GMI) 7.0% (53 mmol/mol). The average HGI was 0.55% ± 0.66%. The measured HbA1C was higher in the group with high HGI (8.1% [65 mmol/mol] vs 6.9% [52 mmol/mol]; P < .001), whereas GMI (7.0% [53 mmol/mol] vs 7.0% [53 mmol/mol]; P = .495) and mean glucose were similar in both groups (153 mg/dL vs 153 mg/dL; P = .564). In the high HGI group, higher occurrence of CKD (P = .016) and neuropathy were observed (P = .025). High HGI was associated with increased risk of CKD (odds ratio [OR]: 5.05; 95% CI: 1.02-24.8; P = .04) after adjusting for time since diagnosis (OR: 1.09; 95% CI: 1.02-1.16; P = .008). CONCLUSION: High HGI measured by CGM may be a useful marker for increased risk of microvascular diabetic complications.

Recommendations on the use of the flash continuous glucose monitoring system in hospitalized patients with diabetes in Latin America.

BACKGROUND: Continuous glucose monitoring can improve glycemic control for hospitalized patients with diabetes, according to current evidence. However, there is a lack of consensus-established recommendations for the management of hospitalized patients with diabetes using flash continuous glucose monitoring system (fCGM) in Latin America. Therefore, this expert consensus exercise aimed to establish guidelines on the implementation of fCGM in the management of hospitalized patients with diabetes in Latin America. METHODS: The modified Delphi method was applied on a panel of nine specialists, establishing consensus at 80%. A twenty-two-question instrument was developed to establish recommendations on the use of fCGM in hospitalized patients living with diabetes. RESULTS: Based on consensus, experts recommend the use of fCGM in hospitalized patients with diabetes starting at admission or whenever hyperglycemia (> 180 mg/dl) is confirmed and continue monitoring throughout the entire hospital stay. The recommended frequency of fCGM scans varies depending on the patient's age and diabetes type: ten scans per day for pediatric patients with type 1 and 2 diabetes, adult patients with type 1 diabetes and pregnant patients, and seven scans for adult patients with type 2 diabetes. Different hospital services can benefit from fCGM, including the emergency room, internal medicine departments, intensive care units, surgery rooms, and surgery wards. CONCLUSIONS: The use of fCGM is recommended for patients with diabetes starting at the time of admission in hospitals in Latin America, whenever the necessary resources (devices, education, personnel) are available.

Type 2 diabetes in latin America: recommendations on the flash glucose monitoring system.

OBJECTIVE: To establish recommendations through the consensus of a Latin American experts panel on the use of the flash glucose monitoring system (fCGM) in people living with type 2 diabetes mellitus (T2DM) regarding the benefits and challenges of using the fCGM. METHODS: An executive committee of experts was created, comprised by a panel of fifteen physicians, including endocrinologists and internal medicine physicians, with expertise in management of adult patients with T2DM. The experts were from various countries: Colombia, Chile, Peru, Mexico, Argentina, and Brazil. The modified Delphi method was used, considering a consensus level of at least 80% of the participants. A seventeen-item instrument was developed to establish recommendations on the use of fCGM in patients with T2DM in Latin American. RESULTS: The number of glucose scans recommended per day with the fCGM for patients managed with oral antidiabetic drugs or basal insulin was a median of 6 scans per day, and for those managed with multiple insulin doses, a median of 10 scans per day was recommended. Additionally, a holistic and individualized management approach was recommended, taking into account new treatment directions and identifying patients who would benefit from the use of the fCGM. CONCLUSION: Continuous use of the fCGM is recommended for people living with T2DM, regardless of their type of treatment. These metrics must be evaluated individually for each patient profile.

Prevalence of obesity in people with and without type 1 diabetes across Belgium, Kuwait, and Mexico: an IMI2 SOPHIA study.

Background: Individuals with type 1 diabetes (T1D) are traditionally perceived as lean, but recent evidence suggests an increasing trend of obesity. To provide global estimates, this study explored the prevalence of obesity among adults with and without T1D across three distinct global regions. Methods: An observational, cross-sectional study was performed utilizing data from T1D registries and national health surveys to assess the prevalence of obesity (BMI ≥ 30 kg/m2) and the prevalence of overweight and obesity (BMI ≥ 25 kg/m2) across Belgium, Kuwait, and Mexico. Demographic and clinical characteristics of adults with and without T1D were assessed. Prevalence estimates were calculated through a binomial generalized linear mixed-effects model adjusting for age, sex, HbA1c, and survey year. As a sensitivity analysis, propensity score matching was performed for confounder adjustment of age and sex. Findings: The study encompassed 3594 individuals with T1D (from 2003 to 2022) and 9898 without T1D (from 2014 to 2021). After model adjustment for confounders (age, sex, HbA1c% and data-collection year), individual obesity prevalence was lower in individuals with T1D in Kuwait and Mexico than among those without type 1 diabetes (Kuwait: 22% (CI: 18-26%) vs. 44% (CI: 41-48%); Mexico: 5% (CI: 3-7%) vs. 40% (CI: 38-42%)). In contrast, individuals with T1D in Belgium showed a more comparable proportions to those without T1D (12% (CI: 9-16%) vs. 16% (CI:11-22%)). Interpretation: Our data reveal that obesity is prevalent among people with T1D. These findings underscore the need for targeted strategies in T1D care that address the growing concern of obesity. Funding: This manuscript is part of the Stratification of Obesity Phenotypes to Optimize Future Obesity Therapy (SOPHIA) project (www.imisophia.eu). SOPHIA has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No. 875534. This Joint Undertaking support from the European Union's Horizon 2020 research and innovation program and EFPIA and type 1 diabetes Exchange, Breakthrough T1D, and Obesity Action Coalition.

Obesity in people living with type 1 diabetes.

Although type 1 diabetes is traditionally considered a disease of lean people, overweight and obesity are becoming increasingly more common in individuals with type 1 diabetes. Non-physiological insulin replacement that causes peripheral hyperinsulinaemia, insulin profiles that do not match basal and mealtime insulin needs, defensive snacking to avoid hypoglycaemia, or a combination of these, are believed to affect body composition and drive excessive accumulation of body fat in people with type 1 diabetes. The consequences of overweight or obesity in people with type 1 diabetes are of particular concern, as they increase the risk of both diabetes-related and obesity-related complications, including cardiovascular disease, stroke, and various types of cancer. In this Review, we summarise the current understanding of the aetiology and consequences of excessive bodyweight in people with type 1 diabetes and highlight the need to optimise future prevention and treatment strategies in this population.

Glycemic control, treatment and complications in patients with type 1 diabetes amongst healthcare settings in Mexico.

AIMS: Type 1 diabetes (T1D) is a growing chronic disease. Evidence of whether the healthcare setting affects management and glycemic control is scarce. We evaluate outcomes in patients with T1D in private and public healthcare settings in Mexico, registered in the National T1D Registry in Mexico (RENACED-DT1). METHODS: Biochemical parameters, diabetes education, and treatment were analyzed considering the data registered in the last visit. Development of chronic complications was determined during follow-up. RESULTS: We included 1,603 patients; 71.5% (n = 1,146) registered in the public system, and 28.5% (n = 457) in a private institution. Patients in the public setting had higher HbA1c (8.6%, IQR: 7.3%-10.5% vs 7.7%, IQR: 7.0%-8.8%; p < 0.001). Indicators of diabetes education, glucose monitoring, and use of insulin-pumps were lower in the public setting. Patients in the public setting were at higher risk of diabetic chronic kidney disease, retinopathy, and neuropathy. Diabetes knowledge was a mediator between type of healthcare setting and the likelihood of achieving glycemic control. CONCLUSIONS: Patients registered in public healthcare settings have an adverse metabolic profile and higher risk of complications. Social factors need to be addressed in order to implement multidisciplinary measures focused on diabetes education for patients with T1D in Mexico.

The use of exenatide in islet transplant recipients with chronic allograft dysfunction: safety, efficacy, and metabolic effects.

BACKGROUND: A current limitation of islet transplantation is reduced long-term graft function. The glucagon-like peptide-1 receptor agonist, exenatide (Byetta, Amylin Pharmaceuticals, CA) has properties that could improve existing islet function, prevent further loss of islet mass and possibly even stimulate islet regeneration. METHODS: This prospective study evaluated the safety, efficacy, and metabolic effects of exenatide in subjects with type 1 diabetes mellitus and islet allograft dysfunction requiring exogenous insulin. RESULTS: Sixteen subjects commenced exenatide, 12 continue (follow-up 214+/-57 days; range 108-287), four (25%) discontinued medication because of side effects. At 6 months, exogenous insulin was significantly reduced with stable glycemic control (0.15+/-0.02 vs. 0.11+/-0.025 U/kg per day; P<0.0001); three subjects discontinued insulin from 4, 5, and 9 U/day, respectively, two sustained insulin independence with A1c reduction below graft dysfunction criteria. Postprandial capillary blood glucose was significantly decreased (129.4+/-3.8 vs. 118.7+/-4.6 mg/dL; P<0.001), C-peptide and C-peptide-to-glucose ratio increased significantly by 5th and 6th months of treatment (ratio, 1.09+/-0.15 vs. 1.52+/-0.18; P<0.05). Weight loss more than 3 kg occurred in 8 of 12 (67%) subjects. Stimulation testing demonstrated improved glucose disposal and C-peptide secretion (glucose area under the curve 52,332+/-3,219 vs. 42,072+/-1,965; P=0.002 mg x min x dL, mixed meal stimulation index 0.50+/-0.06 vs. 0.66+/-0.09; P=0.03 pmol x mL), with marked suppression of glucagon secretion and progressive increase in amylin secretion. Side effects were more frequent and severe compared with published reports in type 2 diabetes, tolerated doses were lower. CONCLUSIONS: Exenatide was tolerated in this patient population after appropriate dose titration and there appeared to be gradual but sustained positive effects on glycemic control and islet graft function.

Nutritional status and behavior in subjects with type 1 diabetes, before and after islet transplantation.

BACKGROUND: To investigate whether changes of nutritional status and behavior are associated with islet transplantation (ITx) and to assess their possible mechanisms. METHODS: In this observational study, 52 subjects with type 1 diabetes, 30 of whom received ITx, underwent nutritional assessments. The study consisted of questionnaires complemented by a dietary intake recording, anthropometric measurements, and body composition analysis. Laboratory tests were also reviewed as part of the follow up. RESULTS: After ITx, significant reductions in body weight (3.7 kg; P<0.0001), body mass index (1.39 kg/m2; P<0.0001), waist circumference (3.96 cm; P=0.006), and fat weight (3.28 kg; P<0.01) were observed. The average consumption of carbohydrate and protein were also lower than pretransplant, together with some micronutrients (vitamins B12 and B6, zinc, and phosphorus). Insulin administration and changes in A1C were not associated with a significant change in anthropometric measurements. Subjects on exenatide after ITx showed significantly lower weight and body mass index than those not taking exenatide. CONCLUSIONS: ITx is associated with modifications in nutritional behavior and status. Drugs and health conditions are likely to be at least in part responsible for these changes, but a voluntary modification of eating habits by the patients also plays a role. Strict monitoring of nutritional parameters, counseling by experts in nutrition, and multivitamin/mineral supplement after ITx could be of benefit to the patients.

Improved metabolic control and quality of life in seven patients with type 1 diabetes following islet after kidney transplantation.

BACKGROUND: The beneficial effects of glycemic control on both survival and function of transplanted kidneys in patients with type 1 diabetes mellitus (T1DM) and end-stage renal disease (ESRD) have been recognized. METHODS: Herein, we present the clinical outcome of a single-center pilot trial of islet after kidney (IAK) transplantation in seven patients with T1DM. The immunosuppression protocol for the kidney graft was converted to sirolimus+tacrolimus regimen 6 months before islet transplantation to exclude negative effects on kidney graft function. Primary endpoint was achievement of insulin independence after transplantation. Clinical outcome, metabolic control, severe hypoglycemia, kidney function, Quality of Life (QOL) psychometric measures, and adverse events were monitored. RESULTS: Seven patients showed graft function with improved metabolic control (A1c, fasting glycemia, and metabolic tests) after IAK (14,779+/-3,800 IEQ/kg). One-year insulin independence was 30% with persistent graft function in 86% (C-peptide-positive). A1c reduction was 1.95+/-0.31% from baseline (P<0.0001). No episodes of severe hypoglycemia were observed, even after resuming insulin. The direct consequence of these benefits was a significant improvement in diabetes QOL. Adverse events included procedure-related pleural effusion (n=2), cholecystitis (n=1), and additional immunosuppression-related, all resolved without sequelae. Kidney function (by estimated glomerular filtration rate) remained stable during follow-up in six of seven patients. CONCLUSIONS: Islet transplantation represents a feasible therapeutic option for patients with T1DM bearing a stable kidney allograft. Insulin independence at 1 year is lower than what reported in islet transplant alone. Nevertheless, clear benefits in terms of optimal metabolic control and absence of severe hypoglycemia are invariably present.

Allosensitization of islet allograft recipients.

BACKGROUND: The immune monitoring of islet transplant recipients includes the assessment of panel reactive antibodies (PRA). A negative association of PRA+ with allogeneic solid organ graft survival has been recognized, but scattered data is available for islet transplantation. METHODS: We performed a retrospective analysis of PRA status in 66 patients with type 1 diabetes mellitus recipient of islet allografts between 1985 and 2006. RESULTS: Pretransplant PRA+ was observed in 10 subjects in the old trials and associated with kidney transplantation and/or pregnancies. Thirteen subjects displayed PRA+ at follow-up, eight of whom were de novo. Overall, PRA+ did not correlate with islet graft outcome: long-term graft survival was observed in the presence of basal or persistent PRA+ and graft dysfunction occurred also in the absence of PRA+. Loss of graft function was associated with PRA+ after lowering of immunosuppression or after infection episodes. Loss of C-peptide did not affect kidney graft function even in simultaneous islet-kidney transplant recipients. Mostly, PRA remained negative under adequate immunosuppression. Patients whose immunosuppression was discontinued invariably developed PRA+. CONCLUSIONS: Monitoring of PRA under immunosuppression may have little clinical value under adequate immunosuppression in islet transplant recipients. The implications of allosensitization after discontinuation of immunosuppression need to be evaluated to define the real clinical impact in this patient population.

Resolution of severe atopic dermatitis after tacrolimus withdrawal.

Tacrolimus is an immunosuppressive agent used in solid organ and islet transplantation. Its topical form has shown benefit in the treatment of inflammatory skin conditions. Although tacrolimus has a wide spectrum of side effects, dermatological complications related to systemic tacrolimus therapy are limited in the literature. Atopic dermatitis (AD) is a chronic pruritic cutaneous condition that usually begins in infancy and is characterized by an increased Th2 response. We report the case of a patient with type 1 diabetes mellitus (T1DM) and history of AD latent for 10 years who developed severe dermatitis and alopecia 5 months after undergoing allogeneic islet transplantation and initiating a steroid-free immunosuppressive regimen with sirolimus and tacrolimus maintenance. After exclusion of other possible causes for the progression and exacerbation of the clinical presentation of AD, discontinuation of tacrolimus and introduction of mycophenolate mofetil resulted in full remission of the symptoms. The beneficial effects of tacrolimus withdrawal suggest a cause-effect relationship between this adverse event and the utilization of the drug. Islet graft function remained stable after modification of the therapeutic regimen (stable glycemic control and unchanged C-peptide).

Negative impact of new-onset diabetes mellitus on patient and graft survival after liver transplantation: Long-term follow up.

BACKGROUND: Little is known about the long-term consequences of new-onset diabetes mellitus (NODM) after liver transplantation (LTX). METHODS: In a chart review between 1996 and 2004, we evaluated its incidence and possible effect on patient and graft survival. Inclusion criteria were: adult primary LTX; deceased donor LTX without combined organs; and dual immunosuppression with tacrolimus and corticosteroid. Patients who died within six months after LTX were excluded. For analytical purposes, each patient was classified into one of four groups: 1) preLTX diabetes mellitus (DM): established DM before LTX; 2) sustained NODM: NODM sustained > or =6 months; 3) transitory NODM: NODM temporarily existed > or =1 and <6 months; and 4) normal: no DM either pre- or postLTX. Patients who had NODM <1 month due to high-dose steroid (e.g., either immediate postLTX or rejection treatment) were considered as normal. Patient and graft survival was examined using Kaplan-Meier methodology. RESULTS: In all, 778 patients met the inclusion/exclusion criteria: preLTX DM 159 (20.4%), sustained NODM 284 (36.5%), transitory NODM 108 (13.9%), and normal 227 (29.2%). Median follow-up was 57.2 months. There was a significant difference in patient (P = 0.012) and graft survival (P = 0.004) among the groups, with sustained NODM showing the poorest patient and graft survivals. Sustained NODM patients had a significantly higher rate of death due to infection, as well as graft failure due to chronic rejection and late onset hepatic artery thrombosis. CONCLUSION: NODM is a frequent complication with poor patient and graft survival after LTX.

Immunosuppression and procedure-related complications in 26 patients with type 1 diabetes mellitus receiving allogeneic islet cell transplantation.

BACKGROUND: The success of sirolimus and low-dose tacrolimus in islet cell transplantation has influenced many transplant centers to utilize this novel regimen. The long-term safety and tolerability of this steroid-free immunosuppressive protocol for allogeneic islet transplantation has yet to be determined. METHODS: We transplanted 26 adult patients with long standing type 1 diabetes mellitus between April 2000 and June 2004. Immunosuppression consisted of induction with daclizumab and maintenance therapy with tacrolimus and sirolimus. Adverse events (AEs) in patients were followed and graded using the Common Terminology Criteria for Adverse Events, version 3.0 (National Cancer Institute). RESULTS: To date, the majority of patients were able to remain on the immunosuppression combination for up to 22+/-11 months. Four patients were successfully converted to Mycophenolate Mofetil due to tacrolimus-related toxicity. Withdrawal from immunosuppression was decided in four patients due to hypereosinophilic syndrome, parvovirus infection, aspiration pneumonia, and severe depression, respectively. Six patients required filgrastim therapy for neutropenia. Transient elevation of liver enzymes was observed in most patients early after islet infusion. Increased LDL in 20 patients required medical treatment. CONCLUSION: There was a varying range of AEs, most of them mild and self-limiting; however, some required urgent medical attention. The majority of patients were able to tolerate and remain on this effective regimen. To date, no deaths, cytomegalovirus disease, graft-versus-host disease, or posttransplant lymphoproliferative disease has been observed.

Early metabolic markers of islet allograft dysfunction.

BACKGROUND: Islet transplantation can restore normoglycemia to patients with unstable type 1 diabetes mellitus, but long-term insulin independence is usually not sustained. Identification of predictor(s) of islet allograft dysfunction (IGD) might allow for early intervention(s) to preserve functional islet mass. METHODS: Fourteen islet transplantation recipients with long-term history of type 1 diabetes mellitus underwent metabolic testing by mixed meal tolerance test, intravenous glucose tolerance test, and arginine stimulation test every 3 months postislet transplant completion. Metabolic responses were compared between subjects who maintained insulin independence at 18 months (group 1; n=5) and those who restarted insulin within 18 months (group 2; n=9). Data were analyzed before development of islet graft dysfunction and while insulin independent. RESULTS: The 90-min glucose, time-to-peak C-peptide, and area under the curve for glucose were consistently higher in group 2 and increased as a function of time. At 12 months, acute insulin release to glucose in group 2 was markedly reduced as compared with baseline (5.62+/-1.21 microIU/mL, n=4 vs. 16.14+/-3.69 microIU/mL, n=8), whereas it remained stable in group 1 (22.36+/-4.98 microIU/mL, n=5 vs. 27.70+/-2.83 microIU/mL, n=5). Acute insulin release to glucose, acute C-peptide release to glucose (ACpRg), and mixed meal stimulation index were significantly decreased and time-to-peak C-peptide, 90-min glucose, and area under the curve for glucose were significantly increased when measured at time points preceding intervals where IGD occurred compared with intervals where there was no IGD. CONCLUSIONS: The intravenous glucose tolerance test and mixed meal tolerance test may be useful in the prediction of IGD and should be essential components of the metabolic testing of islet transplant recipients.

Stable renal function after islet transplantation: importance of patient selection and aggressive clinical management.

BACKGROUND: Proteinuria development and decrease in glomerular filtration rate (GFR) have been observed after successful islet transplantation. The aim of this study was to determine clinical, laboratory, and immunosuppressant-related factors associated with kidney dysfunction in islet transplant recipients. METHODS: A retrospective cohort study was conducted in 35 subjects submitted to pancreatic islet transplantation for treatment of unstable type 1 diabetes mellitus. Demographic, anthropometrical, and laboratory data, as well as immunosuppressive and antihypertensive therapy were recorded. Kidney function was assessed by albuminuria and estimated GFR (eGFR), calculated by modification of diet in renal disease formula. RESULTS: Age was the only independent risk factor for low eGFR (<60 mL/min/1.73 m2) (odds ratio [OR]=1.78 [1.22-2.61]). Low-density lipoprotein cholesterol (OR=2.90 [1.37-6.12]) and previous microalbuminuria (OR=6.42 [1.42-29.11]) were risk factors for transient macroalbuminuria. Interestingly, tacrolimus was a protective factor for macroalbuminuria (OR=0.12 [0.06-0.26]). Six of 30 (20%) normoalbuminuric subjects at baseline progressed to microalbuminuria. No subject developed sustained macroalbuminuria. Surprisingly, overall eGFR remained stable during follow-up (before transplant: 74.0+/-2.0; during immunosuppressive therapy: 75.4+/-2.8; and after withdrawal: 76.3+/-5.3 mL/min/1.73 m2; P>0.05). Even subjects with low eGFR and microalbuminuria at baseline (n=10) maintained stable values posttransplantation (61.13+/-3.25 mL/min/1.73 m2 vs. 63.32+/-4.36 mL/min/1.73 m2, P=0.500). CONCLUSIONS: Kidney function remained stable after islet transplantation alone. The unchanged kidney function found in this sample may be attributed to healthier kidney status at baseline and possibly to prompt treatment of modifiable risk factors. Aggressive treatment of risk factors for nephropathy, such as blood pressure, low-density lipoprotein cholesterol, and careful tacrolimus levels monitorization, should be part of islet transplant recipient care.

Long-term metabolic and hormonal effects of exenatide on islet transplant recipients with allograft dysfunction.

The initial success of islet transplantation (ITx) is followed by graft dysfunction (GDF) and insulin reintroduction. Exenatide, a GLP-1 agonist, increases insulin and decreases glucagon secretion and has potential for beta-cell regeneration. To improve functional islet mass, exenatide treatment was given to ITx recipients with GDF. The objective of this study was to assess metabolic and hormonal effects of exenatide in GDF. In this prospective, single-arm, nonrandomized study, 11 type 1 diabetes recipients of ITx with GDF had HbA1c, weight, insulin requirements, and 5-h mixed meal tolerance test (MMTT; with/without exenatide given before test) at baseline, 3, 6, and 12 months after initiating exenatide treatment. Baseline MMTT showed postprandial hyperglycemia and hyperglucagonemia. Daily exenatide treatment resulted in improved glucose, increased amylin/insulin ratio, and decreased proinsulin/insulin ratio as assessed by MMTT. Glucagon responses remained unchanged. Exenatide administration 1 h before MMTT showed decreased glucagon and glucose at 0 min and attenuation in their postprandial rise. Time-to-peak glucose was delayed, followed by insulin, proinsulin, amylin, and C-peptide, indicating glucose-driven insulin secretion. Five subjects completed 12-month follow-up. Glucose and glucagon suppression responses after MMTT with exenatide were no longer observed. Retrospective 3-month analysis of these subjects revealed higher and sustained glucagon levels that did not suppress as profoundly with exenatide administration, associated with higher glucose levels and increased C-peptide responses. In conclusion, Exenatide suppresses the abnormal postprandial hyperglucagonemia and hyperglycemia observed in GDF. Changes in amylin and proinsulin secretion may reflect more efficient insulin processing. Different degrees of responsiveness to exenatide were identified. These may help guide the clinical management of ITx recipients.

Impact of islet transplantation on glycemic control as evidenced by a continuous glucose monitoring system.

BACKGROUND: This study evaluated the effects of islet allotransplantation (ITx) on metabolic control utilizing a continuous glucose monitoring system (CGMS) and assessed its effectiveness as an indicator and predictor of graft dysfunction (GD). METHODS: Glycemic control was assessed in 25 patients with type 1 diabetes mellitus (T1DM); 12 ITx recipients and 13 controls. Mean interstitial glucose, standard deviation (SD), glucose variability, and percentage of time in hyperglycemia (%GT >140 mg/dl), hypoglycemia (%GT <54 mg/dl), and normoglycemia (%GT 54-140 mg/dl) were measured in 72-hour time periods from CGMS recordings in the control group at baseline and in the ITx group at 3, 6, 9, 12, 15, and 18 months after ITx completion and were analyzed as predictors and indicators of GD. Hemoglobin A1c (HbA1c), 90-minute glucose after a mixed meal tolerance test, fasting C-peptide/glucose ratio, and insulin requirements were followed. RESULTS: Compared to the control group, the percentage of time in hypoglycemia was significantly lower in the ITx group at all time points; time in normoglycemia was increased at all times except at 15 months; and time in hyperglycemia was significantly lower at 6, 9, 12, and 18 months. Mean glucose and glucose variability were significantly lower in the ITx group at all times except at 3 and 15 months, whereas HbA1c and 90-minute glucose were significantly lower in the ITx group at all time points. Mean glucose, SD, glucose variability, and %GT >140 mg/dl were significant as indicators but not as predictors of GD. CONCLUSIONS: The CGMS demonstrated the benefits of ITx in T1DM, with improvements in glycemic control apparent up to 18 months after transplant. CGMS measures were found to be indicators of GD.