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Improved Health-Related Quality of Life in a Phase 3 Islet Transplantation Trial in Type 1 Diabetes Complicated by Severe Hypoglycemia.

ABSTRACT: OBJECTIVE:Attaining glycemic targets without severe hypoglycemic events (SHEs) is a challenging treatment goal for patients with type 1 diabetes complicated by impaired awareness of hypoglycemia (IAH). The CIT Consortium Protocol 07 (CIT-07) trial showed islet transplantation to be an effective treatment for subjects with IAH and intractable SHEs. We evaluated health-related quality of life (HRQOL), functional health status, and health utility before and after pancreatic islet transplantation in CIT-07 trial participants. RESEARCH DESIGN AND METHODS:Four surveys, the Diabetes Distress Scale (DDS), the Hypoglycemic Fear Survey (HFS), the Short Form 36 Health Survey (SF-36), and the EuroQoL 5 Dimensions (EQ-5D), were administered repeatedly before and after islet transplantation. Summary statistics and longitudinal modeling were used to describe changes in survey scores from baseline and to characterize change in relation to a minimally important difference (MID) threshold of half an SD. RESULTS:Improvements in condition-specific HRQOL met the MID threshold. Reductions from baseline in the DDS total score and its four DDS subscales (all P ? 0.0013) and in the HFS total score and its two subscales (all P < 0.0001) were observed across all time points. Improvements were observed after both 1 and 2 years for the EQ-5D visual analog scale (both P < 0.0001). CONCLUSIONS:In CIT-07, 87.5% of the subjects achieved the primary end point of freedom from SHE along with glycemic control (HbA1c <7% [<53 mmol/mol]) at 1 year post-initial islet transplantation. The same subjects reported consistent, statistically significant, and clinically meaningful improvements in condition-specific HRQOL as well as self-assessments of overall health.

SUBMITTER: Foster ED

PROVIDER: S-EPMC5911786 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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Improved Health-Related Quality of Life in a Phase 3 Islet Transplantation Trial in Type 1 Diabetes Complicated by Severe Hypoglycemia.

Foster Eric D ED Bridges Nancy D ND Feurer Irene D ID Eggerman Thomas L TL Hunsicker Lawrence G LG Alejandro Rodolfo R

Diabetes care 20180321 5

<h4>Objective</h4>Attaining glycemic targets without severe hypoglycemic events (SHEs) is a challenging treatment goal for patients with type 1 diabetes complicated by impaired awareness of hypoglycemia (IAH). The CIT Consortium Protocol 07 (CIT-07) trial showed islet transplantation to be an effective treatment for subjects with IAH and intractable SHEs. We evaluated health-related quality of life (HRQOL), functional health status, and health utility before and after pancreatic islet transplant ...[more]

PMID: 29563196

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Project description:OBJECTIVE:Impaired awareness of hypoglycemia (IAH) and severe hypoglycemic events (SHEs) cause substantial morbidity and mortality in patients with type 1 diabetes (T1D). Current therapies are effective in preventing SHEs in 50-80% of patients with IAH and SHEs, leaving a substantial number of patients at risk. We evaluated the effectiveness and safety of a standardized human pancreatic islet product in subjects in whom IAH and SHEs persisted despite medical treatment. RESEARCH DESIGN AND METHODS:This multicenter, single-arm, phase 3 study of the investigational product purified human pancreatic islets (PHPI) was conducted at eight centers in North America. Forty-eight adults with T1D for >5 years, absent stimulated C-peptide, and documented IAH and SHEs despite expert care were enrolled. Each received immunosuppression and one or more transplants of PHPI, manufactured on-site under good manufacturing practice conditions using a common batch record and standardized lot release criteria and test methods. The primary end point was the achievement of HbA1c <7.0% (53 mmol/mol) at day 365 and freedom from SHEs from day 28 to day 365 after the first transplant. RESULTS:The primary end point was successfully met by 87.5% of subjects at 1 year and by 71% at 2 years. The median HbA1c level was 5.6% (38 mmol/mol) at both 1 and 2 years. Hypoglycemia awareness was restored, with highly significant improvements in Clarke and HYPO scores (P > 0.0001). No study-related deaths or disabilities occurred. Five of the enrollees (10.4%) experienced bleeds requiring transfusions (corresponding to 5 of 75 procedures), and two enrollees (4.1%) had infections attributed to immunosuppression. Glomerular filtration rate decreased significantly on immunosuppression, and donor-specific antibodies developed in two patients. CONCLUSIONS:Transplanted PHPI provided glycemic control, restoration of hypoglycemia awareness, and protection from SHEs in subjects with intractable IAH and SHEs. Safety events occurred related to the infusion procedure and immunosuppression, including bleeding and decreased renal function. Islet transplantation should be considered for patients with T1D and IAH in whom other, less invasive current treatments have been ineffective in preventing SHEs.

Project description:Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases. Patients are generally advised lifestyle changes with antihyperglycemic agents prescribed. The major drawback of prescribing antihyperglycemic agents is the risk of hypoglycemia which subsequently impacts on health-related quality of life (HRQoL). This study is aimed at examining association between previous history of hypoglycemia and HRQoL. The study was a multicenter cross-sectional study, conducted from February 2013 to March 2015 at 5 tertiary care hospitals in Thailand (Srinagarind, Phramongkutklao, Ramathibodi, King Chulalongkorn Memorial, and Siriraj hospitals). The study population were males or females diagnosed with type 2 DM according to ADA criteria, 30 years of age or older, who had been treated with sulfonylurea (SU) monotherapy or SU and metformin combination for at least 6 months. Prespecified medical factors were extracted from medical records 12 months prior to patients' enrolment. The experience of hypoglycemia questionnaire was used to collect and measure severity of hypoglycemia experienced during the previous 6 months. HRQoL was assessed using the 3-level version of EuroQol-5-dimension (EQ-5D-3L) and visual analogue scale (EQ-VAS) questionnaires. Of 659 eligible patients surveyed, 202 patients (30.65%) had experienced symptoms of hypoglycemia. HRQoL was significantly lower among patients reporting at least one of hypoglycemic symptoms, measured by EQ-VAS scores (mean ± SD; 73.66 ± 13.18, 73.56 ± 15.10, or 68.93 ± 14.76 vs. 77.01 ± 13.02, one-way ANOVA; p = 0.006) and EQ-5D-3L index scores (0.62 ± 0.47, 0.68 ± 0.38, or 0.58 ± 0.51 vs. 0.79 ± 0.31, one-way ANOVA; p < 0.001) for mild, moderate, or severe/very severe hypoglycemic patients compared with patients without hypoglycemic symptoms. After adjusting for confounding factors in a multiple linear regression model, patients with hypoglycemic symptoms either mild, moderate, or severe/very severe demonstrated significantly higher impairment for EQ-VAS and EQ-5D indexes than those who did not experience hypoglycemic symptoms. In conclusion, our study showed decreased HRQoL determined by EQ-5D and EQ-VAS in patients reporting symptoms of hypoglycemia compared with patients not reporting hypoglycemic symptoms, relative to severity of hypoglycemia.

Project description:ImportanceIntensive glucose-lowering treatment among patients with non-insulin-requiring type 2 diabetes may increase the risk of hypoglycemia.ObjectivesTo estimate the prevalence of intensive treatment and the association between intensive treatment, clinical complexity, and incidence of severe hypoglycemia among adults with type 2 diabetes who are not using insulin.Design, setting, and participantsRetrospective analysis of administrative, pharmacy, and laboratory data from the OptumLabs Data Warehouse from January 1, 2001, through December 31, 2013. The study included nonpregnant adults 18 years or older with type 2 diabetes who achieved and maintained a hemoglobin A1c (HbA1c) level less than 7.0% without use of insulin and had no episodes of severe hypoglycemia or hyperglycemia in the prior 12 months.Main outcomes and measuresRisk-adjusted probability of intensive treatment and incident severe hypoglycemia, stratified by patient clinical complexity. Intensive treatment was defined as use of more glucose-lowering medications than recommended by practice guidelines at specific index HbA1c levels. Severe hypoglycemia was ascertained by ambulatory, emergency department, and hospital claims for hypoglycemia during the 2 years after the index HbA1c test. Patients were categorized as having high vs low clinical complexity if they were 75 years or older, had dementia or end-stage renal disease, or had 3 or more serious chronic conditions.ResultsOf 31 542 eligible patients (median age, 58 years; interquartile range, 51-65 years; 15 483 women [49.1%]; 18 188 white [57.7%]), 3910 (12.4%) had clinical complexity. The risk-adjusted probability of intensive treatment was 25.7% (95% CI, 25.1%-26.2%) in patients with low clinical complexity and 20.8% (95% CI, 19.4%-22.2%) in patients with high clinical complexity. In patients with low clinical complexity, the risk-adjusted probability of severe hypoglycemia during the subsequent 2 years was 1.02% (95% CI, 0.87%-1.17%) with standard treatment and 1.30% (95% CI, 0.98%-1.62%) with intensive treatment (absolute difference, 0.28%; 95% CI, -0.10% to 0.66%). In patients with high clinical complexity, intensive treatment significantly increased the risk-adjusted probability of severe hypoglycemia from 1.74% (95% CI, 1.28%-2.20%) with standard treatment to 3.04% (95% CI, 1.91%-4.18%) with intensive treatment (absolute difference, 1.30%; 95% CI, 0.10%-2.50%).Conclusions and relevanceMore than 20% of patients with type 2 diabetes received intensive treatment that may be unnecessary. Among patients with high clinical complexity, intensive treatment nearly doubles the risk of severe hypoglycemia.

Dataset Information

Improved Health-Related Quality of Life in a Phase 3 Islet Transplantation Trial in Type 1 Diabetes Complicated by Severe Hypoglycemia.

Publications

Improved Health-Related Quality of Life in a Phase 3 Islet Transplantation Trial in Type 1 Diabetes Complicated by Severe Hypoglycemia.

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