Risa P. Hayes

Diabetes in Japan: a review of disease burden and approaches to treatment

In recent years there has been rapid growth in diabetes in Japan which now is one of the nations most affected by the worldwide diabetes epidemic. Diabetes has been identified as a healthcare priority by the Ministry of Health, Labour and Welfare (MHLW). Type 1 diabetes is rare in Japan, and type 2 diabetes predominates in both adults and children. The growth in diabetes is due to increases in the number of people with type 2 diabetes associated with increased longevity and lifestyle changes. Approximately 13.5% of the Japanese population now has either type 2 diabetes or impaired glucose tolerance. This high prevalence of type 2 diabetes is associated with a significant economic burden, with diabetes accounting for up to 6% of the total healthcare budget. The costs of diabetes are increased in patients with co‐morbidities such as hypertension and hyperlipidaemia and in patients who develop complications, of which retinopathy has the highest cost. Costs increase with increasing number of complications. Current guidelines from the Japan Diabetes Society (JDS) recommend a target HbA1c of 6.5% for glycaemic control. This is achieved in approximately one third of patients with type 2 diabetes, and Japanese patients typically have lower HbA1c than patients in Western countries (e.g. US, UK). Japanese patients with type 2 diabetes have better adherence with diet and exercise recommendations than their peers in Western countries. Sulfonylureas have been the most widely prescribed first‐line treatment for type 2 diabetes, although there is increasing use of combination therapy and of insulin. Copyright

Patient-reported outcomes in a trial of exenatide and insulin glargine for the treatment of type 2 diabetes.

BackgroundPatient-reported measures can be used to examine whether drug differences other than clinical efficacy have an impact on outcomes that may be important to patients. Although exenatide and insulin glargine appear to have similar efficacy for treatment of type 2 diabetes, there are several differences between the two treatments that could influence outcomes from the patients perspective. The purpose of the current study was to examine whether the two drugs were comparable as assessed by patient-reported outcomes using data from a clinical trial in which these injectable medications were added to pre-existing oral treatment regimens.MethodsPatients were randomized to either twice daily exenatide or once daily insulin glargine during a 26-week international trial. At baseline and endpoint, five patient-reported outcome measures were administered: the Vitality Scale of the SF-36, The Diabetes Symptom Checklist – Revised (DSC-R), the EuroQol EQ-5D, the Treatment Flexibility Scale (TFS), and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). Change from baseline to endpoint was analyzed within each treatment group. Group differences were examined with General linear models (GLMs), controlling for country and baseline scores.ResultsA total of 549 patients with type 2 diabetes were enrolled in the trial, and current analyses were conducted with data from the 455 per protocol patients (228 exenatide and 227 insulin glargine). The sample was primarily Caucasian (79.6%), with slightly more men (55.2%) than women, and with a mean age of 58.5 years. Paired t-tests found that both treatment groups demonstrated statistically significant baseline to endpoint change on several of the health outcomes instruments including the DSC-R, DTSQ, and the SF-36 Vitality subscale. GLMs found no statistically significant differences between groups in change on the health outcomes instruments.ConclusionThis analysis found that both exenatide and insulin glargine were associated with significant improvements in patient-reported outcomes when added to oral medications among patients with type 2 diabetes. Despite an additional daily injection and a higher rate of gastrointestinal adverse events, treatment satisfaction in the exenatide group was comparable to that of the glargine group, possibly because of weight reduction observed in patients treated with exenatide.

Construct validation of patient global impression of severity (PGI-S) and improvement (PGI-I) questionnaires in the treatment of men with lower urinary tract symptoms secondary to benign prostatic hyperplasia

BackgroundLower urinary tract symptoms (LUTS) in aging men are often associated with benign prostatic hyperplasia (BPH). While regulatory evaluations of treatment benefit require an assessment of specific symptoms, a simpler approach to measuring patients’ perceptions of severity and symptom change may be particularly useful for clinical practice. The aim of this study was to provide evidence of the validity of the 1-item Patient Global Impression of Severity (PGI-S) and Improvement (PGI-I) questionnaires for use as outcome measures in the treatment of BPH-LUTS.MethodsThis was a secondary analysis of data from 4 randomized placebo-controlled 12-week trials evaluating tadalafil for the treatment of BPH-LUTS (N=1694). Visit 2 (V2 [beginning of a 4-week placebo lead-in period]) and endpoint assessments included International Prostate Symptom Score (IPSS), IPSS Quality of Life Index (IPSS-QoL), BPH Impact Index (BII), and peak urine flow (Qmax). PGI-S was only administered at V2 and PGI-I only at endpoint. Associations between the PGI-S or the PGI-I and the other assessments were analyzed by calculating Spearman rank correlation coefficients and performing analysis of variance (ANOVA).ResultsSpearman correlation coefficients were 0.43, 0.43, 0.53, and −0.09, between the PGI-S and IPSS, IPSS-QoL, BII, and Qmax baseline results (all P<0.001). Similar results were seen across race, ethnicity, and baseline severity (moderate LUTS versus severe LUTS). IPSS, IPSS-QoL, BII baseline scores (P <0.001) and Qmax values (P=0.003) were significantly different among the 4 PGI-S severity levels. Spearman correlation coefficients were 0.56, 0.53, 0.47 and −0.15 between the PGI-I and change in IPSS, IPSS-QoL, BII scores, and Qmax values from baseline to endpoint (all P<0.001). Similar results were seen across race, ethnicity, and baseline severity. Change in IPSS, IPSS-QoL, BII scores, and Qmax values (P<0.001) were significantly different among the PGI-I levels (i.e., patient perception of change in urinary symptoms).ConclusionsThis study demonstrated patients’ overall perceptions of their severity and change in BPH-LUTS can be captured in a way that is simple, valid, and easily administered in a research setting or clinical practice. Clinical parameters are weakly associated with patients’ perception of urinary symptoms, emphasizing the importance of a patient-reported assessment in the evaluation of BPH-LUTS treatment benefit.

The Improving Primary Care of African Americans with Diabetes (IPCAAD) project: rationale and design

African Americans have an increased burden of both diabetes and diabetes complications. Since many patients have high glucose levels novel interventions are needed, especially for urban patients with limited resources. In the Grady Diabetes Clinic in Atlanta, a stepped care strategy improves metabolic control. However, most diabetes patients do not receive specialized care. We will attempt to translate diabetes clinic approaches to the primary care setting by implementing a novel partnership between specialists and generalists. We hypothesize that endocrinologist-supported strategies aimed at providers will result in effective diabetes management in primary care sites, and the Improving Primary Care of African Americans with Diabetes project will test this hypothesis in a major randomized, controlled trial involving over 2000 patients. Physicians in Grady Medical Clinic units will receive (1) usual care, (2) computerized reminders that recommend individualized changes in therapy and/or (3) directed discussion by endocrinologists providing feedback on performance. We will measure outcomes related to both microvascular disease (HbA1c, which reflects average glucose levels over an approximately 2-month period) and macrovascular disease (blood pressure and lipids) and assess provider performance as well. We will compare two readily generalizable program interventions that should delineate approaches effective in a primary care setting as needed to improve care and prevent complications in urban African Americans with type 2 diabetes.

Reliability and validity of an instrument for assessing patients’ perceptions about medications for diabetes: the PAM-D

PurposeTo evaluate the reliability and validity of the Perceptions About Medications for Diabetes (PAM-D) instrument.MethodsThe item pool was generated from a literature review and 18 focus groups of Type 2 diabetes patients. Surveys were mailed to 1,000 low-income diabetes patients; 362 were returned; 65 of 100 re-test surveys were returned.ResultsThis paper uses data from 343 Type 2 respondents. Mean age and age diagnosed were 59 and 48, respectively; 72% female; 52% African American; 51% were taking oral antihyperglycemic agents [OHA] monotherapy, 18% insulin monotherapy, and 28% insulin plus OHA. The initial 66 items were reduced to 37 across nine scales: scheduling flexibility, portability convenience, regimen inconvenience, medication effectiveness, difficulty remembering medications, gastrointestinal, hypoglycemia-related, and weight/edema physical side effects, and emotional side effects. Scale reliabilities ranged from 0.71 to 0.92 (coefficient alpha) and from 0.54 to 0.83 (test–retest coefficient, 37–81-day interval); factor loadings ranged from 0.35 to 0.86 (median, 0.67); significant scale differences across medication groups (insulin, OHA, insulin plus OHA) were consistent with a priori hypotheses.ConclusionsThe PAM-D has substantial reliability and validity in a low-income, inner-city population of Type 2 diabetes patients and may be valuable for understanding multidimensional perceptions driving patients’ treatment preferences.

Effect of inhaled insulin on patient-reported outcomes and treatment preference in patients with type 1 diabetes*

ABSTRACT Objective: To compare patient-reported outcomes and treatment preference between preprandial inhaled insulin and preprandial subcutaneous (SC) insulin in the context of a clinical trial of crossover design with a primary objective of comparing HbA1c between groups. Research design and methods: Multi-center, randomized, open-label, two-arm crossover trial conducted in the US and Canada with two 12-week periods comparing preference between preprandial human insulin inhalation powder (HIIP; AIR† inhaled insulin) and preprandial SC insulin (regular human insulin or insulin lispro) in patients with type 1 diabetes. Patients received HIIP plus insulin glargine during period 1 and SC insulin plus insulin glargine during period 2, or the reverse sequence. Main outcome measures: SF-36 Vitality Subscale, Diabetes Symptom Checklist-Revised subscales, Diabetes Treatment Satisfaction Questionnaire, Insulin Delivery System Questionnaire, HIIP-specific questionnaire, preference question. Results: Of 137 patients entered, 119 completed the study (54% female, mean age 40.9 ± 12.4 years, mean HbA1C 8.1 ± 1.0%). Patients had significantly greater treatment satisfaction and more positive evaluation of their insulin delivery system (easier to control blood sugar, less lifestyle impact) with HIIP than with SC insulin (all p < 0.01). Patients preferring HIIP (80%) were significantly more confident about ( p = 0.005) and comfortable with ( p = 0.003) using the system than those preferring SC insulin. Results may not be generalizable to all patients with type 1 diabetes. Conclusions: Some patients desire alternatives to insulin injection. In this study 80% preferred HIIP to injected insulin. Other patients feel more comfortable with familiar insulin delivery. Healthcare providers should help patients find insulin delivery that corresponds to individual preferences.

Diabetes in Urban African Americans: Assessment of Diabetes-Specific Locus of Control in Patients With Type 2 Diabetes:

PURPOSE This study was conducted to examine the applicability and relationship to glycemic control of the Diabetes Locus of Control (DLC) Scales in a low-literacy, economically deprived, African American population with type 2 diabetes. METHODS The DLC Scales were administered orally to African American patients with type 2 diabetes who had been referred to the diabetes unit of a large urban public hospital. Reliability, interscale correlations, and associations with patient characteristics were compared with those originally obtained for a better educated, predominately Caucasian population. RESULTS The structure and correlates of the DLC Scales in the African American population were more similar than different from those originally obtained from a primarily well-educated, Caucasian population. However, comprehension of some items was difficult for up to 10% of the low-literacy population. A significant relationship was found between belief in chance and both glycemic control at the 6-month follow-up and the change in glycemic control over time. CONCLUSIONS Although the DLC Scales operate similarly in an urban African American population with limited education, further modification is needed to enhance the prediction of glycemic control and provide direction for developing targeted interventions.

Comparison of prandial AIR inhaled insulin alone to intensified insulin glargine alone and to AIR insulin plus intensified insulin glargine in patients with type 2 diabetes previously treated with once-daily insulin glargine.

BACKGROUND Patients with type 2 diabetes often initiate insulin with once-daily basal insulin. Over time, many patients intensify their insulin regimens in an attempt to attain and sustain glycemic targets. This study compares three intensification approaches: changing insulin glargine to preprandial AIR inhaled insulin (developed by Alkermes, Inc. [Cambridge, MA] and Eli Lilly and Company [Indianapolis, IN]; AIR is a registered trademark of Alkermes, Inc.), intensifying glargine via validated titration algorithms (IG), or adding AIR insulin while intensifying glargine (AIR + IG). METHODS Five hundred sixty patients with hemoglobin A(1c) (A1C) of 7.5-10.5%, on one or more antihyperglycemic medications, and on once-daily insulin glargine for > or =4 months were randomly allocated to one of the three treatments lasting 52 weeks. The primary objective assessed between-group differences in A1C mean change from baseline to 24 weeks using last-observation-carried-forward (LOCF) in the intent-to-treat population. RESULTS At 24 weeks, A1C was reduced from a mean baseline of 8.5% to 7.7%, 7.9%, and 7.5% for the AIR, IG, and AIR + IG groups, respectively. AIR produced 0.20% greater A1C decrease than IG (least-squares mean difference = -0.20%; 95% confidence interval [CI], -0.39, -0.02). AIR + IG had a 0.35% greater A1C decrease versus IG (95% CI, -0.57, -0.13). The -0.15% difference between AIR + IG versus AIR was not significant (P < 0.198). More hypoglycemia categorized as severe occurred with AIR alone versus IG alone at LOCF end points. More nocturnal hypoglycemia occurred with IG alone versus AIR alone and AIR + IG. CONCLUSIONS Preprandial inhaled insulin provides an alternative for patients not optimized on insulin glargine alone. Glycemic control, hypoglycemic risk, delivery preference, and regimen complexity must be considered when selecting insulin initiation and optimization regimens.

Assessing the effect of weight and weight loss in obese persons with type 2 diabetes

The objective of this study was to assess specific areas of life in which obesity affects individuals with type 2 diabetes mellitus (T2DM), and changes that obese persons with T2DM experience with weight loss of varying degrees. Thirty in-depth interviews were conducted in persons identified as: age ≥40 years, diagnosed with T2DM for ≥2 years, on oral antihyperglycemic medications >3 months, BMI 30–35 kg/m2, having attempted to lose weight in the last 2 years. Participants (60% female, mean age 53 years, 53% Caucasian, mean BMI 32.2 kg/m2) agreed that 5% weight loss, while not reflective of an ultimate goal, would be meaningful and important; benefits were expected to accrue in physical functioning, self-confidence, blood glucose levels, and motivation to keep losing weight. Participants reported the greatest effect of weight loss on energy, physical activity, mobility, pain, and clothes/appearance. Participants reported weight affecting mood, with feelings of depression and frustration most commonly described. This research indicates that weight loss is likely to affect health-related quality of life in obese individuals with T2DM. Given the purported weight loss benefits of many emerging diabetic medications, it will be important to include measures of weight-related quality of life in future clinical trials of these agents.

Exploration of oncologists’ attitudes toward and perceived value of patient-reported outcomes

PurposeTo understand oncologists’ attitudes toward patient-reported outcome (PRO) measures and to learn how PRO data influence their clinical decision-making.MethodsTwenty practicing oncologists participated in 1 of 4 semi-structured focus groups.ResultsMost oncologists had no experience with PRO measures, but were able to identify several concepts appropriate for patient-reported assessment. Participants agreed that clinical measures such as performance status were more meaningful to them, but acknowledged that PRO measures were more appropriate for assessing patient symptoms and treatment response. All oncologists believed that clinical efficacy and toxicity data were of primary importance, but that PROs become increasingly important when multiple treatments are available, in advanced or incurable disease, and in palliative care. Several issues prevented oncologists from being able to draw meaningful conclusions from PRO data: lack of familiarity with PRO measures, being presented with too much data to process, lack of clarity around a meaningful change in PRO measure scores, and lack of standardization in the use of PRO measures.ConclusionsOncologists indicated that PRO data are most influential in advanced or incurable disease and in palliative care. Improving the interpretability of PRO measures could increase the usefulness of PRO data in treatment decision-making.