Analyzing breath samples of hypoglycemic events in type 1 diabetes patients: towards developing an alternative to diabetes alert dogs.

Diabetes is a disease that involves dysregulation of metabolic processes. Patients with type 1 diabetes (T1D) require insulin injections and measured food intake to maintain clinical stability, manually tracking their results by measuring blood glucose levels. Low blood glucose levels, hypoglycemia, can be extremely dangerous and can result in seizures, coma, or even death. Canines trained as diabetes alert dogs (DADs) have demonstrated the ability to detect hypoglycemia from breath, which led us to hypothesize that hypoglycemia, a metabolic dysregulation leading to low blood glucose levels, could be identified through analyzing volatile organic compounds (VOCs) contained within breath. We hoped to replicate the canines' detection ability and success by analytically using gas chromatography/mass spectrometry of VOCs in 128 breath samples collected from 52 youths with T1D at two different diabetes camps. We used different tests for significance including Ranksum, Student's T-test, and difference between means, and found a subset of 56 traces of potential metabolites. Principle component and linear discriminant analysis (LDA) confirmed a hypoglycemic signature likely resides within this group. Supervised machine learning combined with LDA narrowed the list of likely components to seven. The technique of leave one out cross validation demonstrated the model thus developed has a sensitivity of 91% (95% confidence interval (CI) [57.1, 94.7]) and a specificity of 84% (95% CI [73.0, 92.7]) at identifying hypoglycemia. Confidence intervals were obtained by bootstrapping. These results demonstrate that it is possible to differentiate breath samples obtained during hypoglycemic events from all other breath samples by analytical means and could lead to developing a simple analytical monitoring device as an alternative to using DADs.

Inflammatory bowel disease among patients with psoriasis treated with ixekizumab: A presentation of adjudicated data from an integrated database of 7 randomized controlled and uncontrolled trials.

BACKGROUND: Inflammatory bowel disease (IBD) occurs more frequently in patients with psoriasis. The 2 diseases have significant genetic overlap, but the pathogenesis underlying their co-occurrence is unknown. OBJECTIVE: We sought to report adjudicated IBD cases (Crohn's disease [CD] and ulcerative colitis [UC]) in patients exposed to ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A. METHODS: Adverse events (AEs) integrated from 7 randomized controlled and uncontrolled trials were analyzed for the controlled induction period, controlled maintenance period, and all ixekizumab-treated patients. Suspected IBD cases were reviewed by blinded external experts using internationally recognized criteria (Registre Epidemiologique des Maladies de l'Appareil Digestif registry). RESULTS: In all, 4209 patients (6480 patient-exposure years) were exposed to ixekizumab. Suspected CD (N = 12) or UC (N = 17) AEs were reported; 19 were adjudicated as definite/probable IBD (CD, N = 7, incidence rate = 1.1/1000 patient-exposure years; UC, N = 12, incidence rate = 1.9/1000 patient-exposure years). Among these, 3 occurred during induction (CD, N = 1; UC, N = 2) and 7 during maintenance (CD, N = 4; UC, N = 3). Twelve of 16 patients with reported IBD history have not had an IBD treatment-emergent AE/serious AE to date. LIMITATIONS: Clinical review (adjudication) was not prespecified. AE data collected post-hoc may have been limited by length of time from occurrence. CONCLUSION: From an integrated database of 7 ixekizumab psoriasis trials, CD and UC cases were uncommon (<1%).

Dogs Can Be Successfully Trained to Alert to Hypoglycemia Samples from Patients with Type 1 Diabetes.

INTRODUCTION: Hypoglycemia (Hypo) is the most common side effect of insulin therapy in people with type 1 diabetes (T1D). Over time, patients with T1D become unaware of signs and symptoms of Hypo. Hypo unawareness leads to morbidity and mortality. Diabetes alert dogs (DADs) represent a unique way to help patients with Hypo unawareness. Our group has previously presented data in abstract form which demonstrates the sensitivity and specificity of DADS. The purpose of our current study is to expand evaluation of DAD sensitivity and specificity using a method that reduces the possibility of trainer bias. METHODS: We evaluated 6 dogs aging 1-10 years old who had received an average of 6 months of training for Hypo alert using positive training methods. Perspiration samples were collected from patients during Hypo (BG 46-65 mg/dL) and normoglycemia (BG 85-136 mg/dl) and were used in training. These samples were placed in glass vials which were then placed into 7 steel cans (1 Hypo, 2 normal, 4 blank) randomly placed by roll of a dice. The dogs alerted by either sitting in front of, or pushing, the can containing the Hypo sample. Dogs were rewarded for appropriate recognition of the Hypo samples using a food treat via a remote control dispenser. The results were videotaped and statistically evaluated for sensitivity (proportion of lows correctly alerted, "true positive rate") and specificity (proportion of blanks + normal samples not alerted, "true negative rate") calculated after pooling data across all trials for all dogs. RESULTS: All DADs displayed statistically significant (p value <0.05) greater sensitivity (min 50.0%-max 87.5%) to detect the Hypo sample than the expected random correct alert of 14%. Specificity ranged from a min of 89.6% to a max of 97.9% (expected rate is not defined in this scenario). CONCLUSIONS: Our results suggest that properly trained DADs can successfully recognize and alert to Hypo in an in vitro setting using smell alone.

Durability of glycemic control with insulin lispro mix 75/25 versus insulin glargine for older patients with type 2 diabetes.

BACKGROUND AND AIMS: Few studies have evaluated long-term durability of glycemic control in older patients. The aim of this study was to compare durability of glycemic control of twice-daily insulin lispro mix 75/25 (LM75/25; 75 % insulin lispro protamine suspension, 25 % insulin lispro) and once-daily insulin glargine (GL) added to oral antihyperglycemic medications in older patients (≥65 years of age). METHODS: Patients were participants in the maintenance phase of the DURABLE trial. During the initiation phase, patients with type 2 diabetes were randomized to LM75/25 or GL. After 6 months, patients with hemoglobin A1c (HbA1c) ≤7.0 % advanced to the 24-month maintenance phase. The primary objective was between-group comparison of duration of maintaining the HbA1c goal in older patients (≥65 years of age). A similar analysis was conducted for older patients achieving HbA1c ≤6.5 % in the initiation phase. RESULTS: Median time of maintaining HbA1c goal was longer in LM75/25 versus GL (19.6 versus 15.4 months, p = 0.007) and more LM75/25 patients maintained goal versus GL (49.2 versus 30.4 %; p = 0.003). HbA1c reduction from baseline was greater in LM75/25 versus GL (-1.56 ± 0.10 versus -1.24 ± 0.11 %; p = 0.003). Post-meal glucose was significantly lower in LM75/25 versus GL (158.86 ± 3.42 versus 171.67 ± 4.51 mg/dL; p = 0.017). No differences were observed in overall and severe hypoglycemia. LM75/25 patients had higher daily insulin doses (0.41 ± 0.02 versus 0.32 ± 0.02 units/kg/day; p < 0.001) and more weight gain (5.47 ± 0.49 versus 3.10 ± 0.53 kg; p = 0.001). Similar results were generally obtained in older patients with HbA1c ≤6.5 %. CONCLUSIONS: In our evaluation of older patients from a larger trial, LM75/25 appeared to provide longer durability of glycemic control, as well as a greater number of patients maintaining HbA1c goal versus GL.

Ethnic differences in glycemic markers in patients with type 2 diabetes.

OBJECTIVE: Recent studies have reported hemoglobin A1c (HbA1c) differences across ethnic groups that could limit its use in clinical practice. The authors of the A1C-Derived Average Glucose study have advocated to report HbA1c in estimated average glucose (AG) equivalents. The aim of this study was to assess the relationships between HbA1c and the mean of three 7-point self-monitored blood glucose (BG) profiles, and to assess whether estimated AG is an accurate measure of glycemia in different ethnic groups. RESEARCH DESIGN AND METHODS: We evaluated 1,879 participants with type 2 diabetes in the DURABLE trial who were 30 to 80 years of age, from 11 countries, and, according to self-reported ethnic origin, were Caucasian, of African descent (black), Asian, or Hispanic. We performed logistic regression of the relationship between the mean self-monitored BG and HbA1c, and estimated AG, according to ethnic background. RESULTS: Baseline mean (SD) HbA1c was 9.0% (1.3) (75 [SD, 14] mmol/mol), and mean self-monitored BG was 12.1 mmol/L (3.1) (217 [SD, 55] mg/dL). In the clinically relevant HbA1c range of 7.0-9.0% (53-75 mmol/mol), non-Caucasian ethnic groups had 0.2-0.5% (2-6 mmol/mol) higher HbA1c compared with Caucasians for a given BG level. At the mean self-monitored BG levels≤11.6 mmol/L, estimated AG overestimated the actual average BG; at levels>11.6 mmol/L, estimated AG underestimated the actual BG levels. CONCLUSIONS: For a given degree of glycemia, HbA1c levels vary among different ethnic groups. Ethnicity needs to be taken into account when using HbA1c to assess glycemic control or to set glycemic targets. Estimated AG is not a reliable marker for mean glycemia and therefore is of limited clinical value.

Understanding heterogeneity in response to antidiabetes treatment: a post hoc analysis using SIDES, a subgroup identification algorithm.

BACKGROUND: Treatment response in patients with type 2 diabetes mellitus (T2DM) varies because of different genotypic and phenotypic characteristics. Results of clinical trials are based largely on aggregated estimates of treatment effect rather than individualized outcomes. This research assessed heterogeneity and differential treatment response using the subgroup identification based on differential effect search (SIDES) algorithm with data from a large multinational study. METHODS: This was a retrospective analysis of the DURABLE trial, a randomized, open-label, two-arm, parallel study. The trial enrolled 2091 insulin-naïve T2DM patients aged 30 to 80 years. Patients received twice-daily insulin lispro mix 75/25 (LM75/25) or once-daily insulin glargine (insulin glargine). The SIDES methodology was used to find subgroups where the treatment effect was substantially different from what was observed in the full population of the clinical trial. A subgroup identification tool implementing the SIDES algorithm was used to examine data for 1092 patients (584 LM75/25 and 508 insulin glargine), achieving at-goal 12- or 24-week glycated hemoglobin A1c (A1C) (≤7.0%). RESULTS: The overall at-goal population treatment difference (A1C reduction) was not clinically meaningful, but a clinically meaningful difference was observed (A1C reduction 2.31% ± 0.06% LM75/25 versus 2.01% ± 0.07% insulin glargine; p = .001) in patients with a baseline fasting insulin level >11.4 µIU/ml and age ≤56 years. CONCLUSION: The observation that younger patients with higher levels of fasting insulin may benefit from a regimen that includes short-acting insulin targeting postprandial glycemia helps explain the heterogeneity in response and warrants further investigation.

Impact of race/ethnicity on efficacy and safety of two starter insulin regimens in patients with type 2 diabetes: a posthoc analysis of the DURABLE trial.

OBJECTIVE: To explore the impact of race/ethnicity on efficacy and safety of twice-daily insulin lispro mix 75/25 (LM75/25; 75% lispro protamine suspension, 25% insulin lispro) and once daily insulin glargine (GL). DESIGN, SETTING, PATIENTS: More than 2,000 Patients with type 2 diabetes enrolled in the 24-week initiation phase of the DURABLE Trial. MAIN OUTCOME MEASURES: Efficacy and safety variables at endpoint, including hemoglobin A1c (HbA1c), self-monitored plasma glucose (SMPG), and hypoglycemia, in each racial/ethnic group were compared to Caucasians within treatment groups. RESULTS: Asian patients had less (LM75/25: -1.46%, P < .01; GL: -1.25%, P < .01) and Hispanic patients had greater (LM75/25: -2.17%) HbA1c reduction from baseline vs Caucasian patients (LM75/25: -1.84%; GL: -1.78%). Fewer Asian (LM75/25: 20%, P < .001; GL: 22%, P < .001) and Hispanic patients (LM75/25: 40%, P < .01) reached HbA1c target (< 7%) vs Caucasian patients (LM75/25: 53%; GL: 44%). Fasting plasma glucose was similar among groups, postprandial glucose (PPG) with GL was lower for African patients post-breakfast and post-dinner and higher for Asian patients post-lunch. Only PPG with LM75/25 was lower for Hispanic patients post-breakfast. Weight gain was lower in Asian patients (LM75/ 25). Insulin dose was higher for Asian (LM75/25 and GL) and lower for African patients (GL). Hypoglycemia rate was lower for Asian (LM75/25 and GL) and Hispanic patients (LM75/25). CONCLUSIONS: There were significant efficacy and safety differences among racial/ethnic groups in the DURABLE trial. These differences may be important in designing insulin based treatment plans.

Health literacy and willingness to use online health information by teens with asthma and diabetes.

OBJECTIVE: This study measured health literacy in a population of teens in treatment for asthma or diabetes and tested the association between health literacy and willingness to use online health resources. MATERIALS AND METHODS: About 180 patients aged 13-18 years treated for asthma or diabetes in specialty care clinics completed assessments of demographic characteristics, health literacy, and Internet access and use. Teens were provided a resource page listing selected publically available health-related Web sites and asked about perceived ease of use, perceived usefulness, and intent to use the listed Web sites. The relationship between demographic characteristics, health literacy, and online health information use was tested using chi-squared or Fisher's exact test. Predictors of intent to use resource page Web sites were assessed using bivariate and multivariate ordinal logistic regression. RESULTS: About 92% of participants had adequate health literacy. Over 50% of participants had previously searched online for health information. Older age was the only significant predictor of health information search. Most teens (79%) reported intent to use at least one Web site from the resource page at least occasionally within the next 3 months. Higher health literacy (odds ratio [OR]=6.24, p<0.01) and stronger perceived usefulness (OR=1.74, p=0.01) were associated with greater intent for regular use, after controlling for demographic and Internet access variables. CONCLUSIONS: Teens with lower health literacy searched online for health information as often as peers with higher literacy, but were less likely to express the intent to use recommended sites. Belief in the usefulness of a Web site is the strongest attitudinal predictor of intended future use.

European cystic fibrosis bone mineralisation guidelines.

Patients with cystic fibrosis (CF) are at risk of developing low bone mineral density (BMD) and fragility fractures. This paper presents consensus statements that summarise current knowledge of the epidemiology and pathophysiology of CF-related skeletal deficits and provides guidance on its assessment, prevention and treatment. The statements were validated using a modified Delphi methodology.

Total body and spinal bone mineral density across Tanner stage in perinatally HIV-infected and uninfected children and youth in PACTG 1045.

OBJECTIVE: To characterize total body bone mineral content (BMC) and total body and spinal bone mineral density (BMD) in perinatally HIV-infected and uninfected children/youth across puberty. DESIGN: HIV-infected (7-24 years) were randomly selected from six strata based on Tanner stage/protease inhibitor use. HIV-uninfected were frequency-matched by Tanner group and sociodemographic background to the HIV-infected. METHODS: Dual-energy X-ray absorptiometry (DXA) measured BMC and BMD. Linear regression models tested differences in bone outcomes by HIV and the interaction of HIV by Tanner group (1-2, 3-4, 5). Models were performed separately by sex and adjusted for DXA scanner, race/ethnicity, height, age and lean body mass. RESULTS: HIV-infected (N = 236) and uninfected (N = 143) were comparable on sex and race/ethnicity. HIV-infected were slightly older (median 12.6 versus 11.9 years). In adjusted models, HIV-infected males had significantly lower total body BMC and total body and spinal BMD at Tanner 5, lower BMC at Tanner 3-4 and similar BMC and BMD at Tanner 1-2, compared to HIV-uninfected males. HIV-infected and uninfected girls did not differ significantly on any bone outcome, but there was a marginally significant interaction of HIV and Tanner group for spinal BMD. Kaletra/ritonavir was associated with lower BMC and total body BMD and nevirapine was associated with higher spinal BMD in a model with all HIV-infected. CONCLUSIONS: Perinatally HIV-infected males showed more evidence of lower bone density especially in the final stage of pubertal development than HIV-infected girls and they may be at increased risk for bone disease during adulthood.

Pharmacotherapy of diabetes in cystic fibrosis patients.

IMPORTANCE OF THE FIELD: Cystic fibrosis-related diabetes (CFRD) is a unique type of diabetes. In this article I review the pathophysiology of CFRD to gain insight as to why these patients have clinical features of both type 1 and 2 diabetes (DM). The reader will also learn that, although CFRD is different from type 1 and 2 DM, the development of diabetes-induced complications is similar to other types of DM. These complications can include retinopathy, nephropathy and neuropathy resulting from uncontrolled hyperglycemia; however, hyperglycemia and/or insulin deficiency in people with CFRD may exacerbate underlying CF problems, such as decreased pulmonary function and weight loss. AREAS COVERED IN THIS REVIEW: Review medical therapy of CFRD including the over-riding goal of maintaining blood glucose levels in a range as close to normal as possible. The other important goal for diabetes management is to prevent diabetes complications and to encourage psychological wellbeing of the patient. However, as reviewed in this article, the underlying medical condition of people with CF and the basic metabolic differences caused by the disease often provide challenges in maintaining optimal diabetes control. WHAT THE READER WILL GAIN: The reader will gain an understanding of how CFRD physically affects the patient with CF and the various pharmacologic therapies available for treatment of this type of diabetes. Furthermore they will gain insight into areas where more research is needed. TAKE HOME MESSAGE: Cystic fibrosis-related diabetes is unique to CF and thus deserves disease specific medical therapy.

Obesity and dyslipidemia in behaviorally HIV-infected young women: Adolescent Trials Network study 021.

BACKGROUND: The goal of this study was to determine the nature and prevalence of abnormalities in lipids, glucose metabolism, and body composition in behaviorally human immunodeficiency virus (HIV)-infected young women and the relationship of these abnormalities to different classes of antiretroviral therapy regimens. METHODS: We conducted a cross-sectional, multicenter study involving 173 behaviorally HIV-infected women aged 14-24 years and 61 HIV-seronegative control subjects. HIV-infected women were categorized as follows: antiretroviral therapy naive (n=85), receiving a regimen containing a nonnucleoside reverse-transcriptase inhibitor (NNRTI; n=33), receiving a regimen containing a protease inhibitor (PI; n=36), or receiving a regimen not containing an NNRTI or a PI (n=19). Measurements included fasting lipid levels, glucose and insulin levels before and 2 hours after an oral glucose challenge, high-sensitivity C-reactive protein (hsCRP) levels, anthropometry, fat distribution (measured by dual energy X-ray absorptiometry), and antiretroviral therapy and medical histories. Race-adjusted results were compared across groups and within HIV-infected groups. RESULTS: The median age of participants was 20 years. Of HIV-infected subjects, 77% were African American, 35% smoked cigarettes, and 32% reported exercising regularly. More than 40% had a body mass index > or =25. Triglycerides; total, high-density lipoprotein (HDL), and non-HDL cholesterol; and hsCRP levels differed significantly among groups, with higher levels being most common among those receiving antiretroviral therapy. Indices of glucose metabolism did not differ among groups. In general, cholesterol levels, hsCRP levels, and indices of glucose metabolism worsened as body mass index increased. CONCLUSIONS: Obesity, dyslipidemia, and inflammation were prominent among HIV-infected adolescent women and, coupled with other risk factors, may accelerate the lifetime risk of cardiovascular disease and other adverse events. These results underscore the need for a multifaceted approach to addressing risk reduction in this population.

Insulin-like growth factor-I levels predict weight, height and protein catabolism in children and adolescents with cystic fibrosis.

Multiple reports have demonstrated the benefit of growth hormone (GH) treatment in children with cystic fibrosis (CF) and previous studies have demonstrated low to normal insulin-like growth factor-I (IGF-I) levels in these patients. Most biological effects of GH are mediated by IGF-I; however, the relationship between height, weight and rate of growth has not been systematically studied in CF. We conducted a retrospective analysis of 52 patients (including control volunteers with CF) who had participated in previous studies of GH treatment to determine the relationship between levels of IGF-I and growth in children with CF. In a subset of these patients, we also evaluated the relationship between protein catabolism and IGF-I. Baseline IGF-I levels and IGF-I z-scores were correlated with same day measures of height, weight, height and weight z-scores. In a subset of patients, IGF-I levels were also correlated with leucine rate of appearance (a measure of protein catabolism). IGF-I levels were obtained every six months during our studies and were correlated with same day height, weight and protein turnover. Height and weight velocity were calculated every six months from study baseline and were correlated with IGF-I levels. In all patients, whether treated with GH or controls, we found a positive linear correlation between IGF-I levels and height (r = 0.66, p < 0.0001) and weight (r = 0.61, p < 0.0001), as well as height and weight velocity. There was also a strong relationship between leucine rate of appearance and IGF-I. These results suggest a strong correlation between IGF-I and height, weight and protein catabolism and emphasize the need to normalize IGF-I levels in children with cystic fibrosis.

Effect of ingested interferon-alpha on beta-cell function in children with new-onset type 1 diabetes.

OBJECTIVE: To evaluate the safety and efficacy of ingested human recombinant interferon-alpha (hrIFN-alpha) for preservation of beta-cell function in young patients with recent-onset type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects aged 3-25 years in whom type 1 diabetes was diagnosed within 6 weeks of enrollment were randomly assigned to receive ingested hrIFN-alpha at 5,000 or 30,000 units or placebo once daily for 1 year. The primary outcome was change in C-peptide secretion after a mixed meal. RESULTS: Individuals in the placebo group (n = 30) lost 56 +/- 29% of their C-peptide secretion from 0 to 12 months, expressed as area under the curve (AUC) in response to a mixed meal. In contrast, children treated with hrIFN-alpha lost 29 +/- 54 and 48 +/- 35% (for 5,000 [n = 27] and 30,000 units [n = 31], respectively, P = 0.028, ANOVA adjusted for age, baseline C-peptide AUC, and study site). Bonferroni post hoc analyses for placebo versus 5,000 units and placebo versus 30,000 units demonstrated that the overall trend was determined by the 5,000-unit treatment group. Adverse events occurred at similar rates in all treatment groups. CONCLUSIONS: Ingested hrIFN-alpha was safe at the doses used. Patients in the 5,000-unit hrIFN-alpha treatment group maintained more beta-cell function 1 year after study enrollment than individuals in the placebo group, whereas this effect was not observed in patients who received 30,000 units hrIFN-alpha. Further studies of low-dose ingested hrIFN-alpha in new-onset type 1 diabetes are needed to confirm this effect.

Morphologic and metabolic abnormalities in vertically HIV-infected children and youth.

OBJECTIVE: To compare the distribution of lipid and glucose abnormalities and altered fat distribution among vertically HIV-infected patients and controls. DESIGN: Cross-sectional multicenter study on HIV-infected (HIV-positive) patients, 7-24 years of age, stratified by Tanner stage and protease inhibitor use (protease inhibitor, n = 161 and non- protease inhibitor, n = 79) and seronegative controls (HIV-negative, n = 146). METHODS: Measurements included fasting lipids, glucose, insulin, 2-h oral glucose tolerance test, dual-energy X-ray absorptiometry, anthropometry, and antiretroviral therapy and medical histories. Multiple linear regression models were used to compare distributions between HIV-positive and HIV-negative groups. RESULTS: Both HIV-positive groups had long exposures to antiretroviral therapy. Protease inhibitor and nonprotease inhibitor groups had similar current CD4 cell count and HIV-1 RNA, but the protease inhibitor group had lower nadir CD4 cell count, higher peak HIV-1 RNA, and more advanced Centers for Disease Control disease stage. In adjusted analyses, both HIV-positive groups had significantly lower mean Z scores for height, weight, BMI, and total and limb fat than the HIV-negative group. Mean triglycerides were significantly higher and high-density lipoprotein cholesterol lower in both HIV-positive groups relative to the HIV-negative group. The protease inhibitor group also had significantly higher mean total, low-density lipoprotein, and non-high density lipoprotein cholesterol. Mean fasting insulin was higher in both HIV-positive groups, and 2-h glucose and insulin were higher in the protease inhibitor group. Ritonavir was associated with increasing dyslipidemia and altered glucose metabolism. CONCLUSION: In a large group of vertically HIV-infected children and youth with extensive antiretroviral therapy exposure, height, weight, and total and limb fat were lower than in controls. There was a high prevalence of lipid abnormalities among those on protease inhibitors and evidence of developing insulin resistance, factors that may accelerate lifetime risk for cardiovascular disease.

Use of the insulin pump in treat cystic fibrosis related diabetes.

OBJECTIVES: This study was conducted to determine efficacy and tolerability of the continued subcutaneous insulin infusion (CSII) via an insulin pump for treatment of Cystic Fibrosis Related Diabetes (CFRD). We also tested the hypothesis that CSII would improve body weight, blood sugar control, lean body mass, whole body protein turnover, hepatic glucose production (HGP). METHODS: We recruited 9 CF patients with established diabetes and placed them on insulin pump therapy for six months. Each subject kept daily blood sugar records before and during pump use. Prior to the pump placement and at the end of six months, each patient underwent the following measurements: 1) whole body protein turnover using the stable isotope [1-(13)C] leucine; 2) DEXA scan for measurement of lean body mass; 3) anthropometric measurements; 4) Hemoglobin A1c. Patient data was compared to baseline data and the mean change from baseline was analyzed. RESULTS: There was significant improvement in both fasting and post-prandial blood glucose levels, body weight, HbA1C, and lean mass. Protein catabolism as measured by leucine rate of appearance was significantly lower, as was hepatic glucose production. No patient developed hypoglycemia during the study. CONCLUSIONS: This study demonstrates that CSII is safe and effective for treatment of CFRD and that metabolic benefits are also present.