Impact and Feasibility of Personalized Decision Support for Older Patients with Diabetes: A Pilot Randomized Trial.

BACKGROUND: Diabetes guidelines recommend individualizing glycemic goals (A1C) for older patients. The aim of this study was to assess a personalized Web-based decision support tool. METHODS: We randomized physicians and their patients with type 2 diabetes (≥65 years of age) to a support tool or educational pamphlet (75:25 patients). Prior to a visit, intervention patients interacted with the tool, which provided personalized risk predictions and elicited treatment preferences. Main outcomes included 1) patient-doctor communication, 2) decisional conflict, 3) changes in goals, and 4) intervention acceptability. RESULTS: We did not find significant differences in proportions of patients who had an A1C discussion (91% intervention v. 76% control; P = 0.19). Intervention patients had larger declines in the informed subscale of decisional conflict (-20 v. 0, respectively; P = 0.04). There were no significant differences in proportions of patients with changes in goals (49% v. 28%, respectively; P = 0.08). Most intervention patients reported that the tool was easy to use (91%) and helped them to communicate (84%). A limitation was that this was a pilot trial at one academic institution. CONCLUSIONS: Web-based decision support tools may be a practical approach to facilitating the personalization of goals for chronic conditions. TRIAL REGISTRATION: NCT02169999 ( https://clinicaltrials.gov/show/NCT02169999 ).

Cost-effectiveness of MODY genetic testing: translating genomic advances into practical health applications.

OBJECTIVE To evaluate the cost-effectiveness of a genetic testing policy for HNF1A-, HNF4A-, and GCK-MODY in a hypothetical cohort of type 2 diabetic patients 25-40 years old with a MODY prevalence of 2%. RESEARCH DESIGN AND METHODS We used a simulation model of type 2 diabetes complications based on UK Prospective Diabetes Study data, modified to account for the natural history of disease by genetic subtype to compare a policy of genetic testing at diabetes diagnosis versus a policy of no testing. Under the screening policy, successful sulfonylurea treatment of HNF1A-MODY and HNF4A-MODY was modeled to produce a glycosylated hemoglobin reduction of -1.5% compared with usual care. GCK-MODY received no therapy. Main outcome measures were costs and quality-adjusted life years (QALYs) based on lifetime risk of complications and treatments, expressed as the incremental cost-effectiveness ratio (ICER) (USD/QALY). RESULTS The testing policy yielded an average gain of 0.012 QALYs and resulted in an ICER of 205,000 USD. Sensitivity analysis showed that if the MODY prevalence was 6%, the ICER would be ~50,000 USD. If MODY prevalence was >30%, the testing policy was cost saving. Reducing genetic testing costs to 700 USD also resulted in an ICER of ~50,000 USD. CONCLUSIONS Our simulated model suggests that a policy of testing for MODY in selected populations is cost-effective for the U.S. based on contemporary ICER thresholds. Higher prevalence of MODY in the tested population or decreased testing costs would enhance cost-effectiveness. Our results make a compelling argument for routine coverage of genetic testing in patients with high clinical suspicion of MODY.

Rates of complications and mortality in older patients with diabetes mellitus: the diabetes and aging study.

IMPORTANCE: In the coming decades, the population of older adults with type 2 diabetes mellitus is expected to grow substantially. Understanding the clinical course of diabetes in this population is critical for establishing evidence-based clinical practice recommendations, identifying research priorities, allocating resources, and setting health care policies. OBJECTIVE To contrast the rates of diabetes complications and mortality across age and diabetes duration categories. DESIGN, SETTING, AND PARTICIPANTS: This cohort study (2004-2010) included 72,310 older (≥ 60 years) patients with type 2 diabetes enrolled in a large, integrated health care delivery system. Incidence densities (events per 1000 person-years) were calculated for each age category (60-69, 70-79, and ≥ 80 years) and duration of diabetes (shorter [0-9 years] vs longer [≥ 10 years]). MAIN OUTCOMES AND MEASURES: Incident acute hyperglycemic events, acute hypoglycemic events (hypoglycemia), microvascular complications (end-stage renal disease, peripheral vascular disease, lower limb amputation, and diabetic eye disease), cardiovascular complications (coronary artery disease, cerebrovascular disease, and congestive heart failure), and all-cause mortality. RESULTS: Among older adults with diabetes of short duration, cardiovascular complications followed by hypoglycemia were the most common nonfatal complications. For example, among individuals aged 70 to 79 years with a short duration of diabetes, coronary artery disease and hypoglycemia rates were higher (11.47 per 1000 person-years and 5.03 per 1000 person-years, respectively) compared with end-stage renal disease (2.60 per 1000 person-years), lower limb amputation (1.28 per 1000 person-years), and acute hyperglycemic events (0.82 per 1000 person-years). We observed a similar pattern among patients in the same age group with a long duration of diabetes, with some of the highest incidence rates in coronary artery disease and hypoglycemia (18.98 per 1000 person-years and 15.88 per 1000 person-years, respectively) compared with end-stage renal disease (7.64 per 1000 person-years), lower limb amputation (4.26 per 1000 person-years), and acute hyperglycemic events (1.76 per 1000 person-years). For a given age group, the rates of each outcome, particularly hypoglycemia and microvascular complications, increased dramatically with longer duration of the disease. However, for a given duration of diabetes, rates of hypoglycemia, cardiovascular complications, and mortality increased steeply with advancing age, and rates of microvascular complications remained stable or declined. CONCLUSIONS AND RELEVANCE: Duration of diabetes and advancing age independently predict diabetes morbidity and mortality rates. As long-term survivorship with diabetes increases and as the population ages, more research and public health efforts to reduce hypoglycemia will be needed to complement ongoing efforts to reduce cardiovascular and microvascular complications.

Ethnic differences in quality of life in insured older adults with diabetes mellitus in an integrated delivery system.

OBJECTIVES: To explore racial and ethnic (ethnic hereafter) differences in health-related quality of life (HRQL) in older adults with diabetes mellitus in an integrated delivery system. DESIGN: Observational cross-sectional study. SETTING: Kaiser Permanente Northern California. PARTICIPANTS: Ethnic-stratified, random sample of 6,096 adults with diabetes mellitus aged 60 to 75 who completed a HRQL questionnaire. MEASUREMENTS: Physical and mental HRQL were measured based on the Medical Outcomes Study 8-item Short Form Survey (range 0-100, mean 50). Age- and sex-adjusted weighted linear regression models estimated associations between ethnicity and HRQL and evaluated potential mediators (socioeconomic status, acculturation, health behaviors, diabetes mellitus-related conditions). Differences in ethnic-specific, adjusted mean HRQL scores were tested (reference whites). RESULTS: Physical HRQL was better for Filipinos (48.3, 95% confidence interval (CI) = 47.0-49.6, P < .001), Asians (48.1, 95% CI = 46.8-49.3, P < .001), Hispanics (45.1, 95% CI = 44.2-46.0, P < .001), and blacks (44.2, 95% CI = 43.3-45.1, P = .04) than whites (42.9, 95% CI = 42.6-43.2). Adjusting for potential mediators did not change these relationships. Mental HRQL was better only for Asians (52.7, 95% CI = 51.6-53.7, P = .01) than for whites (51.0, 95% CI = 50.7-51.3), but this difference was small and became nonsignificant after adjustment for socioeconomic status, acculturation, health behaviors, and diabetes mellitus-related conditions. CONCLUSION: In older adults with diabetes mellitus in a well-established integrated healthcare delivery system, ethnic minorities had better physical HRQL than whites. Equal access to care in an integrated delivery system may hold promise for reducing health disparities in diabetes mellitus-related patient-reported outcomes.

Association between estimated GFR, health-related quality of life, and depression among older adults with diabetes: the Diabetes and Aging Study.

BACKGROUND: Although chronic kidney disease (CKD) is a highly prevalent condition among older adults with diabetes, the associations between health-related quality of life (HRQoL) and severity of CKD in this population are not well understood. The objective of this study was to assess HRQoL and depressive symptoms across estimated glomerular filtration rate (eGFR) stages. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 5,805 members of Kaiser Permanente Northern California, 60 years or older with diabetes, from the 2005-2006 Diabetes Study of Northern California (DISTANCE) survey. PREDICTOR: eGFR categories were defined as ≥90 (referent category), 75-89, 60-74, 45-59, 30-44, or ≤29 mL/min/1.73 m(2). OUTCOMES: HRQoL was measured using the modified Short Form-8 Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Depressive symptoms were measured using the Patient Health Questionnaire-8. RESULTS: In unadjusted linear regression analyses, physical (PCS) and mental (MCS) HRQoL scores were significantly lower with worsening eGFR level. However, after adjustment for sociodemographics, diabetes duration, obesity, and cardiovascular comorbid conditions and taking into account interactions with proteinuria, none of the eGFR categories was significantly or substantively associated with PCS or MCS score. In both unadjusted and adjusted analyses, higher risk of depressive symptoms was observed in respondents with eGFR ≤29 mL/min/1.73 m(2) (relative risk, 2.02; 95% CI, 1.10-3.71; P < 0.05) compared with the referent group. However, this eGFR-depression relationship was no longer significant after adjusting for hemoglobin level. LIMITATIONS: Participants are part of a single health care delivery system. CONCLUSIONS: Our findings suggest the need for greater attention to and potential interventions for depression in patients with reduced eGFR.

Combating Obesity at Community Health Centers (COACH): a quality improvement collaborative for weight management programs.

Community health centers (CHCs) seek effective strategies to address obesity. MidWest Clinicians' Network partnered with [an academic medical center] to test feasibility of a weight management quality improvement (QI) collaborative. MidWest Clinicians' Network members expressed interest in an obesity QI program. This pilot study aimed to determine whether the QI model can be feasibly implemented with limited resources at CHCs to improve weight management programs. Five health centers with weight management programs enrolled with CHC staff as primary study participants; this study did not attempt to measure patient outcomes. Participants attended learning sessions and monthly conference calls to build QI skills and share best practices. Tailored coaching addressed local needs. Topics rated most valuable were patient recruitment/retention strategies, QI techniques, evidence-based weight management, motivational interviewing. Challenges included garnering provider support, high staff turnover, and difficulty tracking patient-level data. This paper reports practical lessons about implementing a weight management QI collaborative in CHCs.

Public health implications of recommendations to individualize glycemic targets in adults with diabetes.

OBJECTIVE: To estimate how many U.S. adults with diabetes would be eligible for individualized A1C targets based on 1) the 2012 American Diabetes Association (ADA) guideline and 2) a published approach for individualized target ranges. RESEARCH DESIGN AND METHODS: We studied adults with diabetes ≥20 years of age from the National Health and Nutrition Examination Survey 2007-2008 (n = 757). We assigned A1C targets based on duration, age, diabetes-related complications, and comorbid conditions according to 1) the ADA guideline and 2) a strategy by Ismail-Beigi focused on setting target ranges. We estimated the number and proportion of adults with each A1C target and compared individualized targets to measured levels. RESULTS: Using ADA guideline recommendations, 31% (95% CI 27-34%) of the U.S. adult diabetes population would have recommended A1C targets of <7.0%, and 69% (95% CI 66-73%) would have A1C targets less stringent than <7.0%. Using the Ismail-Beigi strategy, 56% (51-61%) would have an A1C target of ≤7.0%, and 44% (39-49%) would have A1C targets less stringent than <7.0%. If a universal A1C <7.0% target were applied, 47% (41-54%) of adults with diabetes would have inadequate glycemic control; this proportion declined to 30% (26-36%) with the ADA guideline and 31% (27-36%) with the Ismail-Beigi strategy. CONCLUSIONS: Using individualized glycemic targets, about half of U.S. adults with diabetes would have recommended A1C targets of ≥7.0% but one-third would still be considered inadequately controlled. Diabetes research and performance measurement goals will need to be revised in order to encourage the individualization of glycemic targets.

Symptom burden of adults with type 2 diabetes across the disease course: diabetes & aging study.

BACKGROUND: Reducing symptom burden is paramount at the end-of-life, but typically considered secondary to risk factor control in chronic disease, such as diabetes. Little is known about the symptom burden experienced by adults with type 2 diabetes and the need for symptom palliation. OBJECTIVE: To examine pain and non-pain symptoms of adults with type 2 diabetes over the disease course - at varying time points before death and by age. DESIGN: Survey follow-up study. PARTICIPANTS: 13,171 adults with type 2 diabetes, aged 30-75 years, from Kaiser Permanente, Northern California, who answered a baseline symptom survey in 2005-2006. MAIN MEASURES: Pain and non-pain symptoms were identified by self-report and medical record data. Survival status from baseline was categorized into ≤ 6, >6-24, or alive >24 months. KEY RESULTS: Mean age was 60 years; 48 % were women, and 43 % were non-white. Acute pain was prevalent (41.8 %) and 39.7 % reported chronic pain, 24.6 % fatigue, 23.7 % neuropathy, 23.5 % depression, 24.2 % insomnia, and 15.6 % physical/emotional disability. Symptom burden was prevalent in all survival status categories, but was more prevalent among those with shorter survival, p< .001. Adults ≥ 60 years who were alive >24 months reported more physical symptoms such as acute pain and dyspnea, whereas participants <60 years reported more psychosocial symptoms, such as depressed mood and insomnia. Adjustment for duration of diabetes and comorbidity reduced the association between age and pain, but did not otherwise change our results. CONCLUSIONS: In a diverse cohort of adults with type 2 diabetes, pain and non-pain symptoms were common among all patients, not only among those near the end of life. However, symptoms were more prevalent among patients with shorter survival. Older adults reported more physical symptoms, whereas younger adults reported more psychosocial symptoms. Diabetes care management should include not only good cardiometabolic control, but also symptom palliation across the disease course.

Classification of older adults who have diabetes by comorbid conditions, United States, 2005-2006.

INTRODUCTION: Older adults who have diabetes vary widely in terms of comorbid conditions; these conditions help determine the risks and benefits of intensive glycemic control. Not all people benefit from intensive glycemic control. The objective of this study was to classify by comorbid conditions older American adults who have diabetes to identify those who are less likely to benefit from intensive glycemic control. METHODS: We used latent class analysis to identify subgroups of a nationally representative sample of community-dwelling older adults (aged 57-85 y) who have diabetes (n = 750). The subgroups were classified according to 14 comorbid conditions prevalent in the older population. Using the Akaike Information Criterion, the Bayesian Information Criterion (BIC), the sample-size adjusted BIC, and the χ(2) goodness-of-fit statistic, we assessed model fit. RESULTS: We found 3 distinct subgroups. Class 1 (63% of the sample) had the lowest probabilities for most conditions. Class 2 (29% of the sample) had the highest probabilities of cancer, incontinence, and kidney disease. Class 3 (9% of the sample) had the highest probabilities (>90%) of congestive heart failure and myocardial infarction. Class 1 had only 0, 1, or 2 comorbid conditions, and both class 2 and class 3 had 6 or more comorbid conditions. The 5-year death rates for class 2 (17%) and class 3 (33%) were higher than the rate for class 1 (9%). CONCLUSION: Older adults who have diabetes, cardiovascular disease, and 6 or more comorbid conditions may represent a subgroup of older adults who are less likely to benefit from intensive glycemic control.

Impact of delaying blood pressure control in patients with Type 2 diabetes: results of a decision analysis.

BACKGROUND: In patients with diabetes, delays in controlling blood pressure are common, but the harms of delays have not been quantified. OBJECTIVE: To estimate the harms of delays in controlling systolic blood pressure in middle-aged adults with newly diagnosed Type 2 diabetes. DESIGN: Decision analysis using diabetes complication equations from the United Kingdom Prospective Diabetes Study (UKPDS). PARTICIPANTS: Hypothetical population of adults aged 50 to 59 years old with newly diagnosed Type 2 diabetes based on characteristics from the National Health and Nutrition Examination Surveys. INTERVENTION: Delays in lowering systolic blood pressure from 150 (uncontrolled) to 130 mmHg (controlled). MAIN MEASURES: Lifetime complication rates (amputation, congestive heart failure, end-stage renal disease, ischemic heart disease, myocardial infarction, and stroke), average life expectancy and quality-adjusted life expectancy (QALE). KEY RESULTS: Compared to a lifetime of controlled blood pressure, a lifetime of uncontrolled blood pressure increased complications by 1855 events per 10,000 patients and decreased QALE by 332 days. A 1-year delay increased complications by 14 events per 10,000 patients and decreased QALE by 2 days. A 10-year delay increased complications by 428 events per 10,000 patients and decreased QALE by 145 days. Among complications, rates of stroke and myocardial infarction increased to the greatest extent due to delays. With a 20-year delay in achieving controlled blood pressure, a baseline blood pressure of 160 mmHg decreased QALE by 477 days, whereas a baseline of 140 mmHg decreased QALE by 142 days. CONCLUSIONS: Among middle-aged adults with diabetes, the harms of a 1-year delay in controlling blood pressure may be small; however, delays of ten years or more are expected to lower QALE to the same extent as smoking in patients with cardiovascular disease.

Correlates of quality of life in older adults with diabetes: the diabetes & aging study.

OBJECTIVE: To evaluate associations between health-related quality of life (HRQL) and geriatric syndromes, diabetes complications, and hypoglycemia in older adults with diabetes. RESEARCH DESIGN AND METHODS: A race-stratified random sample of 6,317 adults with type 2 or type 1 diabetes, aged 60 to 75 years, enrolled in Kaiser Permanente Northern California, who completed a survey that included a HRQL instrument based on the Short Form 8-item health survey. Administrative records were used to ascertain diagnoses of geriatric syndromes, diabetes complications, and hypoglycemia. Associations were estimated between HRQL and exposures in exposure-specific and combined exposure models (any syndrome, any complication, or hypoglycemia). Conservatively, differences of ≥3 points were considered the minimally important difference in HRQL scores. RESULTS: HRQL was lower with nearly all exposures of interest. The lowest physical HRQL was associated with amputation. In combined exposure models, geriatric syndromes (-5.3 [95% CI -5.8 to -4.8], P < 0.001) and diabetes complications (-3.5 [-4.0 to -2.9], P < 0.001) were associated with lower physical HRQL. The lowest mental HRQL was associated with depression, underweight (BMI <18 kg/m(2)), amputation, and hypoglycemia. In combined exposure models, only hypoglycemia was associated with lower mental HRQL (-4.0 [-7.0 to -1.1], P = 0.008). CONCLUSIONS: Geriatric syndromes and hypoglycemia are associated with lower HRQL to a comparable degree as diabetes complications. Addressing geriatric syndromes and avoiding hypoglycemia should be given as high a priority as preventing diabetes complications in older adults with diabetes.

Glycemic control, complications, and death in older diabetic patients: the diabetes and aging study.

OBJECTIVE: To identify the range of glycemic levels associated with the lowest rates of complications and mortality in older diabetic patients. RESEARCH DESIGN AND METHODS: We conducted a retrospective cohort study (2004-2008) of 71,092 patients with type 2 diabetes, aged ≥60 years, enrolled in Kaiser Permanente Northern California. We specified Cox proportional hazards models to evaluate the relationships between baseline glycated hemoglobin (A1C) and subsequent outcomes (nonfatal complications [acute metabolic, microvascular, and cardiovascular events] and mortality). RESULTS: The cohort (aged 71.0 ± 7.4 years [means ± SD]) had a mean A1C of 7.0 ± 1.2%. The risk of any nonfatal complication rose monotonically for levels of A1C >6.0% (e.g., adjusted hazard ratio 1.09 [95% CI 1.02-1.16] for A1C 6.0-6.9% and 1.86 [1.63-2.13] for A1C ≥11.0%). Mortality had a U-shaped relationship with A1C. Compared with the risk with A1C <6.0%, mortality risk was lower for A1C levels between 6.0 and 9.0% (e.g., 0.83 [0.76-0.90] for A1C 7.0-7.9%) and higher at A1C ≥11.0% (1.31 [1.09-1.57]). Risk of any end point (complication or death) became significantly higher at A1C ≥8.0%. Patterns generally were consistent across age-groups (60-69, 70-79, and ≥80 years). CONCLUSIONS: Observed relationships between A1C and combined end points support setting a target of A1C <8.0% for older patients, with the caution that A1Cs <6.0% were associated with increased mortality risk. Additional research is needed to evaluate the low A1C-mortality relationship, as well as protocols for individualizing diabetes care.

The cost-effectiveness of personalized genetic medicine: the case of genetic testing in neonatal diabetes.

OBJECTIVE: Neonatal diabetes mellitus is a rare form of diabetes diagnosed in infancy. Nearly half of patients with permanent neonatal diabetes have mutations in the genes for the ATP-sensitive potassium channel (KCNJ11 and ABCC8) that allow switching from insulin to sulfonylurea therapy. Although treatment conversion has dramatic benefits, the cost-effectiveness of routine genetic testing is unknown. RESEARCH DESIGN AND METHODS: We conducted a societal cost-utility analysis comparing a policy of routine genetic testing to no testing among children with permanent neonatal diabetes. We used a simulation model of type 1 diabetic complications, with the outcome of interest being the incremental cost-effectiveness ratio (ICER, $/quality-adjusted life-year [QALY] gained) over 30 years of follow-up. RESULTS: In the base case, the testing policy dominated the no-testing policy. The testing policy was projected to bring about quality-of-life benefits that enlarged over time (0.32 QALYs at 10 years, 0.70 at 30 years) and produced savings in total costs that were present as early as 10 years ($12,528 at 10 years, $30,437 at 30 years). Sensitivity analyses indicated that the testing policy would remain cost-saving as long as the prevalence of the genetic defects remained >3% and would retain an ICER <$200,000/QALY at prevalences between 0.7 and 3%. CONCLUSIONS: Genetic testing in neonatal diabetes improves quality of life and lowers costs. This paradigmatic case study highlights the potential economic impact of applying the concepts of personalized genetic medicine to other disorders in the future.

Exploring the characteristics of sequence elements in proximal promoters of human genes.

Central to reconstruction of cis-regulatory networks is identification and classification of naturally occurring transcription factor-binding sites according to the genes that they control. We have examined salient characteristics of 9-mers that occur in various orders and combinations in the proximal promoters of human genes. In evaluations of a dataset derived with respect to experimentally defined transcription initiation sites, in some cases we observed a clear correspondence of highly ranked 9-mers with protein-binding sites in genomic DNA. Evaluations of the larger dataset, derived with respect to the 5' end of human ESTs, revealed that a subset of the highly ranked 9-mers corresponded to sites for several known transcription factor families (including CREB, ETS, EGR-1, SP1, KLF, MAZ, HIF-1, and STATs) that play important roles in the regulation of vertebrate genes. We identified several highly ranked CpG-containing 9-mers, defining sites for interactions with the CREB and ETS families of proteins, and identified potential target genes for these proteins. The results of the studies imply that the CpG-containing transcription factor-binding sites regulate the expression of genes with important roles in pathways leading to cell-type-specific gene expression and pathways controlled by the complex networks of signaling systems.