Ruth S. Weinstock

Continuous glucose monitoring and intensive treatment of type 1 diabetes

BACKGROUND The value of continuous glucose monitoring in the management of type 1 diabetes mellitus has not been determined. METHODS In a multicenter clinical trial, we randomly assigned 322 adults and children who were already receiving intensive therapy for type 1 diabetes to a group with continuous glucose monitoring or to a control group performing home monitoring with a blood glucose meter. All the patients were stratified into three groups according to age and had a glycated hemoglobin level of 7.0 to 10.0%. The primary outcome was the change in the glycated hemoglobin level at 26 weeks. RESULTS The changes in glycated hemoglobin levels in the two study groups varied markedly according to age group (P=0.003), with a significant difference among patients 25 years of age or older that favored the continuous-monitoring group (mean difference in change, -0.53%; 95% confidence interval [CI], -0.71 to -0.35; P<0.001). The between-group difference was not significant among those who were 15 to 24 years of age (mean difference, 0.08; 95% CI, -0.17 to 0.33; P=0.52) or among those who were 8 to 14 years of age (mean difference, -0.13; 95% CI, -0.38 to 0.11; P=0.29). Secondary glycated hemoglobin outcomes were better in the continuous-monitoring group than in the control group among the oldest and youngest patients but not among those who were 15 to 24 years of age. The use of continuous glucose monitoring averaged 6.0 or more days per week for 83% of patients 25 years of age or older, 30% of those 15 to 24 years of age, and 50% of those 8 to 14 years of age. The rate of severe hypoglycemia was low and did not differ between the two study groups; however, the trial was not powered to detect such a difference. CONCLUSIONS Continuous glucose monitoring can be associated with improved glycemic control in adults with type 1 diabetes. Further work is needed to identify barriers to effectiveness of continuous monitoring in children and adolescents. (ClinicalTrials.gov number, NCT00406133.)

A Randomized Trial Comparing Telemedicine Case Management with Usual Care in Older, Ethnically Diverse, Medically Underserved Patients with Diabetes Mellitus

BACKGROUND Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions who experience barriers to access to care or a high burden of illness. METHODS The authors conducted a randomized, controlled trial comparing telemedicine case management to usual care, with blinding of those obtaining outcome data, in 1,665 Medicare recipients with diabetes, aged 55 years or greater, and living in federally designated medically underserved areas of New York State. The primary endpoints were HgbA1c, blood pressure, and low-density lipoprotein (LDL) cholesterol levels. RESULTS In the intervention group (n = 844), mean HgbA1c improved over one year from 7.35% to 6.97% and from 8.35% to 7.42% in the subgroup with baseline HgbA1c > or =7% (n = 353). In the usual care group (n = 821) mean HgbA1c improved over one year from 7.42% to 7.17%. Adjusted net reductions (one-year minus baseline mean values in each group, compared between groups) favoring the intervention were as follows: HgbA1c, 0.18% (p = 0.006), systolic and diastolic blood pressure, 3.4 (p = 0.001) and 1.9 mm Hg (p < 0.001), and LDL cholesterol, 9.5 mg/dL (p < 0.001). In the subgroup with baseline HgbA1c > or =7%, net adjusted reduction in HgbA1c favoring the intervention group was 0.32% (p = 0.002). Mean LDL cholesterol level in the intervention group at one year was 95.7 mg/dL. The intervention effects were similar in magnitude in the subgroups living in New York City and upstate New York. CONCLUSION Telemedicine case management improved glycemic control, blood pressure levels, and total and LDL cholesterol levels at one year of follow-up.

A Randomized Trial Comparing Telemedicine Case Management with Usual Care in Older, Ethnically Diverse, Medically Underserved Patients with Diabetes Mellitus: 5 Year Results of the IDEATel Study

CONTEXT Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions and lower access to care. OBJECTIVES To examine the effectiveness of a telemedicine intervention to achieve clinical management goals in older, ethnically diverse, medically underserved patients with diabetes. DESIGN, Setting, and Patients A randomized controlled trial was conducted, comparing telemedicine case management to usual care, with blinded outcome evaluation, in 1,665 Medicare recipients with diabetes, aged >/= 55 years, residing in federally designated medically underserved areas of New York State. Interventions Home telemedicine unit with nurse case management versus usual care. Main Outcome Measures The primary endpoints assessed over 5 years of follow-up were hemoglobin A1c (HgbA1c), low density lipoprotein (LDL) cholesterol, and blood pressure levels. RESULTS Intention-to-treat mixed models showed that telemedicine achieved net overall reductions over five years of follow-up in the primary endpoints (HgbA1c, p = 0.001; LDL, p < 0.001; systolic and diastolic blood pressure, p = 0.024; p < 0.001). Estimated differences (95% CI) in year 5 were 0.29 (0.12, 0.46)% for HgbA1c, 3.84 (-0.08, 7.77) mg/dL for LDL cholesterol, and 4.32 (1.93, 6.72) mm Hg for systolic and 2.64 (1.53, 3.74) mm Hg for diastolic blood pressure. There were 176 deaths in the intervention group and 169 in the usual care group (hazard ratio 1.01 [0.82, 1.24]). CONCLUSIONS Telemedicine case management resulted in net improvements in HgbA1c, LDL-cholesterol and blood pressure levels over 5 years in medically underserved Medicare beneficiaries. Mortality was not different between the groups, although power was limited. Trial Registration http://clinicaltrials.gov Identifier: NCT00271739.

Usability in the real world: assessing medical information technologies in patient's homes

OBJECTIVE This paper presents an approach to usability evaluation of computer-based health care systems designed for patient use in their homes. Although such devices are becoming more prevalent, there is very little known about their usability. DESIGN The theoretical foundations for the methods are discussed. The approach incorporates a cognitive walkthrough usability evaluation and new methods for usability testing that can be conducted in patients homes. The method was applied to the IDEATel intervention, a multi-institution randomized controlled trial of the feasibility, acceptability, and clinical utility of a home-based telemedicine system for diabetic Medicare population. The usability study was designed to assess barriers to optimal use of the system. The focus was both on dimensions of the interface and on dimensions of patient skills and competency. The usability field research involved testing 25 patients in their homes using the system. The analysis included a range of video-analytic methods of varying levels of granularity. RESULTS The usability evaluation revealed aspects of the interface that were sub-optimal and impeded the performance of certain tasks. It also found a range of patient-related factors such as numeracy and psychomotor skills that constituted barriers to productive use. CONCLUSIONS A multifaceted usability approach provided important insight regarding use of technology by an elderly chronic-care patient population and more generally, for understanding how home health initiatives can more effectively use such technology.

Columbia University's Informatics for Diabetes Education and Telemedicine (IDEATel) Project: rationale and design.

The Columbia University Informatics for Diabetes Education and Telemedicine (IDEATel) Project is a four-year demonstration project funded by the Centers for Medicare and Medicaid Services with the overall goals of evaluating the feasibility, acceptability, effectiveness, and cost-effectiveness of telemedicine in the management of older patients with diabetes. The study is designed as a randomized controlled trial and is being conducted by a state-wide consortium in New York. Eligibility requires that participants have diabetes, are Medicare beneficiaries, and reside in federally designated medically underserved areas. A total of 1,500 participants will be randomized, half in New York City and half in other areas of the state. Intervention participants receive a home telemedicine unit that provides synchronous videoconferencing with a project-based nurse, electronic transmission of home fingerstick glucose and blood pressure data, and Web access to a project Web site. End points include glycosylated hemoglobin, blood pressure, and lipid levels; patient satisfaction; health care service utilization; and costs. The project is intended to provide data to help inform regulatory and reimbursement policies for electronically delivered health care services.

Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: The TODAY clinical trial

OBJECTIVE Among adolescents with type 2 diabetes, there is limited information regarding incidence and progression of hypertension and microalbuminuria. Hypertension and microalbuminuria assessments made during the TODAY clinical trial were analyzed for effect of treatment, glycemic control, sex, and race/ethnicity. RESEARCH DESIGN AND METHODS A cohort of 699 adolescents, 10–17 years of age, <2 years duration of type 2 diabetes, BMI ≥85%, HbA1c ≤8% on metformin therapy, controlled blood pressure (BP), and calculated creatinine clearance >70 mL/min, were randomized to metformin, metformin plus rosiglitazone, or metformin plus intensive lifestyle intervention. Primary study outcome was loss of glycemic control for 6 months or sustained metabolic decompensation requiring insulin. Hypertension and microalbuminuria were managed aggressively with standardized therapy to maintain BP <130/80 or <95th percentile for age, sex, and height and microalbuminuria <30 μg/mg. RESULTS In this cohort, 319 (45.6%) reached primary study outcome, and 11.6% were hypertensive at baseline and 33.8% by end of study (average follow-up 3.9 years). Male sex and higher BMI significantly increased the risk for hypertension. Microalbuminuria was found in 6.3% at baseline and rose to 16.6% by end of study. Diagnosis of microalbuminuria was not significantly different between treatment arms, sex, or race/ethnicity, but higher levels of HbA1c were significantly related to risk of developing microalbuminuria. CONCLUSIONS Prevalence of hypertension and microalbuminuria increased over time among adolescents with type 2 diabetes regardless of diabetes treatment. The greatest risk for hypertension was male sex and higher BMI. The risk for microalbuminuria was more closely related to glycemic control.

Efficacy and Safety of Dulaglutide Versus Sitagliptin After 52 Weeks in Type 2 Diabetes in a Randomized Controlled Trial (AWARD-5)

OBJECTIVE To compare the efficacy and safety of two doses of once-weekly dulaglutide, a glucagon-like peptide 1 receptor agonist, to sitagliptin in uncontrolled, metformin-treated patients with type 2 diabetes. The primary objective was to compare (for noninferiority and then superiority) dulaglutide 1.5 mg versus sitagliptin in change from baseline in glycosylated hemoglobin A1c (HbA1c) at 52 weeks. RESEARCH DESIGN AND METHODS This multicenter, adaptive, double-blind, parallel-arm study randomized patients (N = 1,098; mean baseline age 54 years; HbA1c 8.1% [65 mmol/mol]; weight 86.4 kg; diabetes duration 7 years) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, sitagliptin 100 mg, or placebo (placebo-controlled period up to 26 weeks). The treatment period lasted 104 weeks, with 52-week primary end point data presented. RESULTS The mean HbA1c changes to 52 weeks were (least squares mean ± SE): −1.10 ± 0.06% (−12.0 ± 0.7 mmol/mol), −0.87 ± 0.06% (9.5 ± 0.7 mmol/mol), and −0.39 ± 0.06% (4.3 ± 0.7 mmol/mol) for dulaglutide 1.5 mg, dulaglutide 0.75 mg, and sitagliptin, respectively. Both dulaglutide doses were superior to sitagliptin (P < 0.001, both comparisons). No events of severe hypoglycemia were reported. Mean weight changes to 52 weeks were greater with dulaglutide 1.5 mg (−3.03 ± 0.22 kg) and dulaglutide 0.75 mg (−2.60 ± 0.23 kg) compared with sitagliptin (−1.53 ± 0.22 kg) (P < 0.001, both comparisons). The most common gastrointestinal treatment-emergent adverse events in dulaglutide 1.5- and 0.75-mg arms were nausea, diarrhea, and vomiting. CONCLUSIONS Both dulaglutide doses demonstrated superior glycemic control versus sitagliptin at 52 weeks with an acceptable tolerability and safety profile.

Severe hypoglycemia and diabetic ketoacidosis in adults with type 1 diabetes: results from the T1D Exchange clinic registry.

CONTEXT Few studies have assessed factors associated with severe hypoglycemia (SH) and diabetic ketoacidosis (DKA) in adults with type 1 diabetes (T1D). OBJECTIVE Our objective was to determine frequency of and factors associated with the occurrence of SH and DKA in adults with T1D. DESIGN AND SETTING We conducted a cross-sectional analysis from the T1D Exchange clinic registry at 70 U.S. endocrinology centers. PATIENTS Analysis included 7012 participants in the T1D Exchange clinic registry aged 26 to 93 years old with T1D for ≥2 years. RESULTS Higher frequencies of SH and DKA were associated with lower socioeconomic status (P < .001). SH was strongly associated with diabetes duration (P < .001), with 18.6% of those with diabetes ≥40 years having an event in the past 12 months. SH frequency was lowest in those with hemoglobin A1c (HbA1c) levels of 7.0% (53 mmol/mol) to 7.5% (58 mmol/mol), being higher in those with HbA1c levels <7.0% (<53 mmol/mol) or >7.5% (>58 mmol/mol). DKA frequency increased with higher HbA1c levels (P < .001), with 21.0% of those with HbA1c ≥10.0% (≥86 mmol/mol) having an event in the past 12 months. CONCLUSIONS SH and DKA are more common in those with lower socioeconomic status. DKA, most common in those with HbA1c ≥10.0% (≥86 mmol/mol), should be largely preventable. In contrast, SH, most frequent with diabetes ≥40 years duration, cannot be abolished given the limitation of current therapies. To reduce SH in adults with longstanding diabetes, consideration should be given to modifying HbA1c goals, particularly in patients with very low HbA1c levels.

Reliability and validity of the Appraisal of Diabetes Scale

The present research evaluated the psychometric properties of a brief self-report instrument designed to assess appraisal of diabetes. Two hundred male subjects completed the Appraisal of Diabetes Scale (ADS) and provided blood samples that were subsequently assayed to provide an index of glycemic control (i.e., glycosylated hemoglobin). Subjects also completed either (a) additional measures of diabetes-related health beliefs, diabetic daily hassles, perceived stress, diabetic adherence, and psychiatric symptoms or (b) the ADS on two additional occasions. Results indicated that the ADS is an internally consistent and stable measure of diabetes-related appraisal. The validity of the measure was supported by correlational analyses which documented the relationship between the ADS and several related self-report measures.

Ezetimibe/Simvastatin vs Atorvastatin in Patients With Type 2 Diabetes Mellitus and Hypercholesterolemia: The VYTAL Study

OBJECTIVE To compare the efficacy and safety of the recommended usual starting and next highest doses of ezetimibe/ simvastatin and atorvastatin in patients with type 2 diabetes mellitus and hypercholesterolemia. PATIENTS AND METHODS This double-blind, multicenter study (June 22 to December 7, 2005) consisted of adult patients randomized to the recommended usual starting (ezetimibe/simvastatin, 10/20 mg/d, vs atorvastatin, 10 or 20 mg/d) or next highest (ezetimibe/simvastatin, 10/40 mg/d, vs atorvastatin, 40 mg/d) doses. Efficacy end points included percent changes from baseline in low-density lipoprotein cholesterol (LDL-C) levels (primary) and proportion of patients attaining LDL-C levels less than 70 mg/dL (secondary). RESULTS A total of 1229 patients participated in the study. Significantly greater mean reductions were found in LDL-C levels with ezetimibe/simvastatin, 10/20 mg/d (-53.6%; 95% confidence interval [CI], -55.4% to -51.8%), than with atorvastatin, 10 mg/d (-38.3%; 95% CI, -40.1% to -36.5%; P < .001) or 20 mg/d (-44.6%; 95% CI, -46.4% to -42.8%; P < .001), and with ezetimibe/simvastatin, 10/40 mg/d (-57.6%; 95% CI, -59.4% to -55.8%), vs atorvastatin, 40 mg/d (-50.9%; 95% CI, -52.7% to -49.1%; P < .001). Ezetimibe/simvastatin was also superior to atorvastatin in attainment of LDL-C levels less than 70 mg/dL (P < .001 for all dose comparisons). Significantly better improvements with ezetimibe/simvastatin than with atorvastatin (P < or = .001) were observed for total cholesterol, high-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol. Ezetimibe/ simvastatin, 10/20 mg/d, reduced high-sensitivity C-reactive protein and triglyceride levels significantly more than atorvastatin, 10 mg/d (P = .02), with comparable reductions at other doses. Incidences of clinical adverse events, including serious drug-related and prespecified gastrointestinal-, gallbladder-, and hepatitis-related allergic reactions or rash events, and laboratory adverse events, including repeated elevation of hepatic transaminases or creatine kinase levels, were similar for both treatments. CONCLUSION Ezetimibe/simvastatin provided additional lipid-modifying benefits over atorvastatin monotherapy at the recommended usual starting and next highest doses in patients with type 2 diabetes. Both treatments were generally well tolerated.