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BackgroundPatient engagement with secure messaging (SM) via digital patient portals has been associated with improved diabetes outcomes, including increased patient satisfaction and better glycemic control. Yet, disparities in SM uptake exist among older patients and racial and ethnic underserved groups. Care partners (family members or friends) may provide a means for mitigating these disparities; however, it remains unclear whether and to what extent care partners might enhance SM use.ObjectiveWe aim to examine whether SM use differs among older patients with diabetes based on the involvement of care partner proxies.MethodsThis is a substudy of the ECLIPPSE (Employing Computational Linguistics to Improve Patient-Provider Secure Emails) project, a cohort study taking place in a large, fully integrated health care delivery system with an established digital patient portal serving over 4 million patients. Participants included patients with type 2 diabetes aged ≥50 years, newly registered on the patient portal, who sent ≥1 English-language message to their clinician between July 1, 2006, and December 31, 2015. Proxy SM was identified by having a registered proxy. To identify nonregistered proxies, a computational linguistics algorithm was applied to detect words and phrases more likely to appear in proxy messages compared to patient-authored messages. The primary outcome was the annual volume of secure messages (sent or received); secondary outcomes were the length of time to the first SM sent by patient or proxy and the number of annual SM exchanges (unique message topics generating ≥1 reply).ResultsThe mean age of the cohort (N=7659) at this study's start was 61 (SD 7.16) years; 75% (n=5573) were married, 15% (n=1089) identified as Black, 10% (n=747) Chinese, 12% (n=905) Filipino, 13% (n=999) Latino, and 30% (n=2225) White. Further, 49% (n=3782) of patients used a proxy to some extent. Compared to nonproxy users, proxy users were older (P

PurposeThis study aimed to evaluate associations between outpatient low-density lipoprotein cholesterol (LDL-C) testing and subsequent statin adherence and intensification in patients after an atherosclerotic cardiovascular (ASCVD) event.MethodsThis was a longitudinal study of adult members of Kaiser Permanente Northern California hospitalized with an ASCVD event (myocardial infarction or stroke) during January 01, 2016, to December 31, 2017, with follow-up through December 31, 2019. Outcomes were statin adherence (estimated using continuous medication gap [CMG]) and intensification (defined by an increased dose or switch to a higher-intensity statin) based on pharmacy dispensing. The exposure of interest was first outpatient LDL-C test after an ASCVD event. Baseline for follow-up was LDL-C test date or a date assigned using incidence density sampling. Multivariate logistic regression models were specified to estimate the odds ratios for statin adherence or intensification among those with vs without an LDL-C test, with adjustment for age, sex, race/ethnicity, smoking, hypertension, diabetes, body mass index, and estimated glomerular filtration rate.ResultsThere were 19,604 adults hospitalized with ASCVD, including 7054 adults not on high-intensity statins. The mean age was 69.5 years and 33.0% were female. Prevalence of good adherence (continuous medication gap ≤20%) was significantly higher (80.2% vs 75.9%; odds ratio 1.38; 95% confidence interval, 1.28-1.49; P

IntroductionThe incidence of both type 1 diabetes (T1D) and type 2 diabetes (T2D) is increasing. Life expectancy is improving in T1D, resulting in a growing population of elderly adults with diabetes. While it is well established that older adults with T2D are at increased risk of cognitive impairment, little is known regarding cognitive aging in T1D and how their cognitive profiles may differ from T2D.Research design and methodsWe compared baseline cognitive function and low cognitive function by diabetes status (n=734 T1D, n=232 T2D, n=247 without diabetes) among individuals from the Study of Longevity in Diabetes (mean age=68). We used factor analysis to group cognition into five domains and a composite measure of total cognition. Using linear and logistic regression models, we examined the associations between diabetes type and cognitive function, adjusting for demographics, comorbidities, depression, and sleep quality.ResultsT1D was associated with lower scores on total cognition, language, executive function/psychomotor processing speed, and verbal episodic memory, and greater odds of low executive function/psychomotor processing speed (OR=2.99, 95% CI 1.66 to 5.37) and verbal episodic memory (OR=1.92, 95% CI 1.07 to 3.46), compared with those without diabetes. T2D was associated with lower scores on visual episodic memory. Compared with T2D, T1D was associated with lower scores on verbal episodic memory and executive function/psychomotor processing speed and greater odds of low executive function/psychomotor processing speed (OR=1.74, 95% CI 1.03 to 2.92).ConclusionsOlder adults with T1D had significantly poorer cognition compared with those with T2D and those without diabetes even after accounting for a range of comorbidities. Future studies should delineate how to reduce risk in this vulnerable population who are newly surviving to old age.

Limited health literacy is a barrier to optimal healthcare delivery and outcomes. Current measures requiring patients to self-report limitations are time-consuming and may be considered intrusive by some. This makes widespread classification of patient health literacy challenging. The objective of this study was to develop and validate "literacy profiles" as automated indicators of patients' health literacy to facilitate a non-intrusive, economic and more comprehensive characterization of health literacy among a health care delivery system's membership. To this end, three literacy profiles were generated based on natural language processing (combining computational linguistics and machine learning) using a sample of 283,216 secure messages sent from 6,941 patients to their primary care physicians. All patients were participants in Kaiser Permanente Northern California's DISTANCE Study. Performance of the three literacy profiles were compared against a gold standard of patient self-reported health literacy. Associations were analyzed between each literacy profile and patient demographics, health outcomes and healthcare utilization. T-tests were used for numeric data such as A1C, Charlson comorbidity index and healthcare utilization rates, and chi-square tests for categorical data such as sex, race, poor adherence and severe hypoglycemia. Literacy profiles varied in their test characteristics, with C-statistics ranging from 0.61-0.74. Relations between literacy profiles and health outcomes revealed patterns consistent with previous health literacy research: patients identified via literacy profiles indicative of limited health literacy: (a) were older and more likely of minority status; (b) had poorer medication adherence and glycemic control; and (c) exhibited higher rates of hypoglycemia, comorbidities and healthcare utilization. This represents the first successful attempt to employ natural language processing to estimate health literacy. Literacy profiles can offer an automated and economical way to identify patients with limited health literacy and greater vulnerability to poor health outcomes.

ObjectiveTo determine whether severe hypoglycemic and hyperglycemic events are associated with longitudinal dementia risk in older adults with type 1 diabetes.MethodsA longitudinal cohort study followed up 2,821 members of an integrated health care delivery system with type 1 diabetes from 1997 to 2015. Hypoglycemic and hyperglycemic events requiring emergency room or hospitalization were abstracted from medical records beginning January 1, 1996, through cohort entry. Participants were followed up for dementia diagnosis through September 30, 2015. Dementia risk was examined with Cox proportional hazard models adjusted for age (as time scale), sex, race/ethnicity, hemoglobin A1c, depression, stroke, and nephropathy.ResultsAmong 2,821 older adults (mean age 56 years) with type 1 diabetes, 398 (14%) had a history of severe hypoglycemia, 335 (12%) had severe hyperglycemia, and 87 (3%) had both. Over a mean 6.9 years of follow-up, 153 individuals (5.4%) developed dementia. In fully adjusted models, individuals with hypoglycemic events had 66% greater risk of dementia than those without a hypoglycemic event (hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.09, 2.53), while those with hyperglycemic events had >2 times the risk (HR 2.11, 95% CI 1.24, 3.59) than those without a hyperglycemic event. There was a 6-fold greater risk of dementia in individuals with both severe hypoglycemia and hyperglycemia vs those with neither (HR 6.20, 95% CI 3.02, 12.70).ConclusionsFor older individuals with type 1 diabetes, severe hypoglycemic and hyperglycemic events are associated with increased future risk of dementia.

ObjectiveIn the National Library of Medicine funded ECLIPPSE Project (Employing Computational Linguistics to Improve Patient-Provider Secure Emails exchange), we attempted to create novel, valid, and scalable measures of both patients' health literacy (HL) and physicians' linguistic complexity by employing natural language processing (NLP) techniques and machine learning (ML). We applied these techniques to > 400,000 patients' and physicians' secure messages (SMs) exchanged via an electronic patient portal, developing and validating an automated patient literacy profile (LP) and physician complexity profile (CP). Herein, we describe the challenges faced and the solutions implemented during this innovative endeavor.Materials and methodsTo describe challenges and solutions, we used two data sources: study documents and interviews with study investigators. Over the five years of the project, the team tracked their research process using a combination of Google Docs tools and an online team organization, tracking, and management tool (Asana). In year 5, the team convened a number of times to discuss, categorize, and code primary challenges and solutions.ResultsWe identified 23 challenges and associated approaches that emerged from three overarching process domains: (1) Data Mining related to the SM corpus; (2) Analyses using NLP indices on the SM corpus; and (3) Interdisciplinary Collaboration. With respect to Data Mining, problems included cleaning SMs to enable analyses, removing hidden caregiver proxies (e.g., other family members) and Spanish language SMs, and culling SMs to ensure that only patients' primary care physicians were included. With respect to Analyses, critical decisions needed to be made as to which computational linguistic indices and ML approaches should be selected; how to enable the NLP-based linguistic indices tools to run smoothly and to extract meaningful data from a large corpus of medical text; and how to best assess content and predictive validities of both the LP and the CP. With respect to the Interdisciplinary Collaboration, because the research required engagement between clinicians, health services researchers, biomedical informaticians, linguists, and cognitive scientists, continual effort was needed to identify and reconcile differences in scientific terminologies and resolve confusion; arrive at common understanding of tasks that needed to be completed and priorities therein; reach compromises regarding what represents "meaningful findings" in health services vs. cognitive science research; and address constraints regarding potential transportability of the final LP and CP to different health care settings.DiscussionOur study represents a process evaluation of an innovative research initiative to harness "big linguistic data" to estimate patient HL and physician linguistic complexity. Any of the challenges we identified, if left unaddressed, would have either rendered impossible the effort to generate LPs and CPs, or invalidated analytic results related to the LPs and CPs. Investigators undertaking similar research in HL or using computational linguistic methods to assess patient-clinician exchange will face similar challenges and may find our solutions helpful when designing and executing their health communications research.

BackgroundMail order pharmacy (MOP) use has been linked to improved medication adherence and health outcomes among patients with diabetes. However, no large-scale intervention studies have assessed the effect of encouraging MOP use on medication adherence.ObjectiveTo assess an intervention to encourage MOP services to increase its use and medication adherence.DesignRandomized encouragement trial.Patients63,012 diabetes patients from three health care systems: Kaiser Permanente Northern California (KPNC), Kaiser Permanente Hawaii (KPHI), and Harvard Pilgrim Health Care (HPHC) who were poorly adherent to at least one class of cardiometabolic medications and had not used MOP in the prior 12 months.InterventionPatients were randomized to receive either usual care (control arm) or outreach encouraging MOP use consisting of a mailed letter, secure email message, and automated telephone call outlining the potential benefits of MOP use (intervention arm). HPHC intervention patients received the letter only.MeasurementsWe compared the percentages of patients that began using MOP and that became adherent to cardiometabolic medication classes during a 12-month follow-up period. We also conducted a race/ethnicity-stratified analysis.ResultsDuring follow-up, 10.6% of intervention patients began using MOP vs. 9.3% of controls (p

IntroductionDiabetic ketoacidosis (DKA) is a serious complication of diabetes. DKA is associated with poorer cognition in children with type 1 diabetes (T1D), but whether this is the case in older adults with T1D is unknown. Given the increasing life expectancy in T1D, understanding the role of DKA on brain health in older adults is crucial.Research design and methodsWe examined the association of DKA with cognitive function in 714 older adults with T1D from the Study of Longevity in Diabetes. Participants self-reported lifetime exposure to DKA resulting in hospitalization; DKA was categorized into 0 hospitalization, 1 hospitalization or ≥2 hospitalizations (recurrent DKA). Global and domain-specific cognition (language, executive function/psychomotor speed, episodic memory and simple attention) were assessed. The association of DKA with cognitive function was evaluated via linear and logistic regression models.ResultsTwenty-eight percent of participants (mean age=67 years; mean age at diagnosis=28 years; average duration of diabetes=39 years) reported a lifetime history of DKA resulting in hospitalization (18.5% single DKA; 9.7% recurrent DKA). In fully adjusted models, those with recurrent DKA had lower global cognitive function (β=-0.13; 95% CI -0.22 to 0.02) and lower scores on the executive function/psychomotor speed domain (β=-0.34; 95% CI -0.51 to 0.17). Individuals with recurrent DKA were also more likely to have the lowest level of cognitive function on the executive function/psychomotor speed domain (defined as 1.5 SD below the population mean; OR=3.26, 95% CI 1.43 to 7.42).ConclusionsAmong 714 older adults with T1D, recurrent DKA was associated with lower global cognitive function, lower scores on the executive function/psychomotor speed domain and 3.3 times greater risk of having the lowest level of cognitive function in our sample on the executive function/psychomotor speed domain. These findings suggest that recurrent DKA may negatively impact the brain health of older patients with T1D and highlight the importance of DKA prevention.

ObjectiveIn children with type 1 diabetes (T1D), severe hypoglycemia (SH) is associated with poorer cognition, but the association of SH with cognitive function in late life is unknown. Given the increasing life expectancy in people with T1D, understanding the role of SH in brain health is crucial.Research design and methodsWe examined the association between SH and cognitive function in 718 older adults with T1D from the Study of Longevity in Diabetes (SOLID). Subjects self-reported recent SH (previous 12 months) and lifetime history of SH resulting in inpatient/emergency department utilization. Global and domain-specific cognition (language, executive function, episodic memory, and simple attention) were assessed. The associations of SH with cognitive function and impaired cognition were evaluated via linear and logistic regression models, respectively.ResultsThirty-two percent of participants (mean age 67.2 years) reported recent SH and 50% reported lifetime SH. Compared with those with no SH, subjects with a recent SH history had significantly lower global cognition scores. Domain-specific analyses revealed significantly lower scores on language, executive function, and episodic memory with recent SH exposure and significantly lower executive function with lifetime SH exposure. Recent SH was associated with impaired global cognition (odds ratio [OR] 3.22, 95% CI 1.30, 7.94) and cognitive impairment on the language domain (OR 3.15, 95% CI 1.19, 8.29).ConclusionsAmong older adults with T1D, recent SH and lifetime SH were associated with worse cognition. Recent SH was associated with impaired global cognition. These findings suggest a deleterious role of SH on the brain health of older patients with T1D and highlight the importance of SH prevention.

Study objectiveThe objective was to examine the association between sleep quality and global and domain-specific cognitive function among older individuals with type 1 diabetes (T1D).MethodsWe evaluated 695 individuals with T1D aged 60 years or above who participated in the baseline assessment of the Study of Longevity in Diabetes (SOLID), which captured subjective sleep quality (Pittsburgh Sleep Quality Index) and global and domain-specific (language, executive function, episodic memory, and simple attention) cognitive function. Multivariable linear regressions estimated the associations between sleep quality quartiles and overall and domain-specific cognitive function adjusting for age, sex, race/ethnicity, education, depressive symptoms, and severe hypoglycemic episodes. Sensitivity analyses examined the associations between aspects of sleep quality and global cognitive function.ResultsThe worst sleep quality quartile was associated with lower global cognition (β=-0.08; 95% confidence interval: -0.17, -0.01) and lower executive function (β=-0.17, 95% confidence interval: -0.30, -0.03) compared with the best quartile of sleep quality adjusting for demographics and comorbidities. Sleep quality was not associated with language, episodic memory, or simple attention. Sleep medications and daytime dysfunction were most strongly associated with global cognition.ConclusionOur results suggest that sleep quality may be a modifiable risk factor for global cognitive function and executive function among elderly individuals with T1D.

BackgroundMedication non-adherence is a major contributor to poor outcomes in diabetes. Previous research has shown an association between use of mail order pharmacy delivery and better medication adherence, but little is known about the barriers and facilitators to mail order pharmacy use in diabetes patients. This qualitative study examined factors related to mail order pharmacy use versus traditional "brick and mortar" pharmacies to refill prescriptions.MethodsWe conducted four 90-min focus groups in 2016 among 28 diabetes patients in the Hawaii and Northern California regions of Kaiser Permanente, a large integrated health care delivery system. We queried participants on their preferred mode for refilling prescriptions and perceived barriers and facilitators of mail order pharmacy use. One researcher independently coded each focus group transcript, with two of these transcripts double-coded by a second researcher to promote reliability. We employed thematic analysis guided by the Capability, Opportunity, Motivation, and Behavior (COM-B) framework using NVivo 11 software.ResultsA total of 28 diabetes patients participated. Participants' average age was 64.1 years; 57% were female; and racial/ethnic backgrounds included Asian/Native Hawaiian/Pacific Islander (36%), Black/African-American (21%) Hispanic/Latino (7%), and non-Hispanic White (36%). Analysis uncovered 26 themes related to the decision to use mail order pharmacy, with each theme representing a barrier or facilitator mapped to the COM-B framework. Most themes (20/26) fell into the COM-B category of 'Opportunity.' Opportunity barriers to mail order pharmacy use included unpredictability of medication delivery date, concerns about mail security, and difficulty coordinating refill orders for multiple prescriptions. In contrast, facilitators included greater access and convenience (e.g., no need to wait in line or arrange transportation) compared to traditional pharmacies. Motivational facilitators to mail order pharmacy use included receiving a pharmacy benefit plan incentive of a free one-month supply of prescriptions.ConclusionsThis study found that while patients with diabetes may benefit from mail order pharmacy use, they perceive numerous barriers to using the service. These findings will inform the design of interventions and quality improvement initiatives to increase mail order pharmacy use, which in turn may improve medication adherence and outcomes in diabetes patients, across health care systems.

BackgroundLittle is known about patients who have caregiver proxies communicate with healthcare providers via portal secure messaging (SM). Since proxy portal use is often informal (e.g., sharing patient accounts), novel methods are needed to estimate the prevalence of proxy-authored SMs.Objective(1) Develop an algorithm to identify proxy-authored SMs, (2) apply this algorithm to estimate predicted proxy SM (PPSM) prevalence among patients with diabetes, and (3) explore patient characteristics associated with having PPSMs.DesignRetrospective cohort study.ParticipantsWe examined 9856 patients from Diabetes Study of Northern California (DISTANCE) who sent ≥ 1 English-language SM to their primary care physician between July 1, 2006, and Dec. 31, 2015.Main measuresUsing computational linguistics, we developed ProxyID, an algorithm that identifies phrases frequently found in registered proxy SMs. ProxyID was validated against blinded expert categorization of proxy status among an SM sample, then applied to identify PPSM prevalence across patients. We examined patients' sociodemographic and clinical characteristics according to PPSM penetrance, "none" (0%), "low" (≥ 0-50%), and "high" (≥ 50-100%).Key resultsOnly 2.3% of patients had ≥ 1 registered proxy-authored SM. ProxyID demonstrated moderate agreement with expert classification (Κ = 0.58); 45.7% of patients had PPSMs (40.2% low and 5.5% high). Patients with high percent PPSMs were older than those with low percent and no PPSMs (66.5 vs 57.4 vs 56.2 years, p

ObjectiveDepression afflicts 14% of individuals with type 1 diabetes (T1D). Depression is a robust risk factor for dementia but it is unknown if this holds true for individuals with T1D, who recently started living to an age conferring dementia risk. We examined if depression is a dementia risk factor among elderly individuals with T1D.Methods3,742 individuals with T1D age ≥50 were followed for dementia from 1/1/96-9/30/2015. Depression, dementia, and comorbidities were abstracted from electronic medical records. Cox proportional hazard models estimated the association between depression and dementia adjusting for demographics, glycosylated hemoglobin, severe dysglycemic epidsodes, stroke, heart disease, nephropathy, and end stage renal disease. The cumulative incidence of dementia by depression was estimated conditional on survival dementia-free to age 55.ResultsFive percent (N = 182) were diagnosed with dementia and 20% had baseline depression. Depression was associated with a 72% increase in dementia (fully adjusted HR = 1.72; 95% CI:1.12-2.65). The 25-year cumulative incidence of dementia was more than double for those with versus without depression (27% vs. 12%).ConclusionsFor people with T1D, depression significantly increases dementia risk. Given the pervasiveness of depression in T1D, this has major implications for successful aging in this population recently living to old age.

BACKGROUND: Racial and ethnic disparities in type 2 diabetes outcomes are a major public health concern. Interventions targeting multiple barriers may help address disparities. PURPOSE: To conduct a systematic review and meta-analysis of diabetes self-management education (DSME) interventions in minority populations. We hypothesized that interventions addressing multiple levels (individual, interpersonal, community, and societal) and/or domains (biological, behavioral, physical/built environment, sociocultural environment, and health care system) would have the greatest effect on hyperglycemia. DATA SOURCES: We performed an electronic search of research databases PubMed, Scopus, CINAHL, and PsycINFO (1985–2019). STUDY SELECTION: We included randomized controlled trials of DSME interventions among U.S. adults with type 2 diabetes from racial and ethnic minority populations. DATA EXTRACTION: We extracted study parameters on DSME interventions and changes in percent hemoglobin A1c (HbA1c). DATA SYNTHESIS: A total of 106 randomized controlled trials were included. Twenty-five percent (n = 27) of interventions were exclusively individual-behavioral, 51% (n = 54) were multilevel, 66% (n = 70) were multidomain, and 42% (n = 45) were both multilevel and multidomain. Individual-behavioral interventions reduced HbA1c by −0.34 percentage points (95% CI −0.46, −0.22; I 2 = 33%) (−3.7 [−5.0, −2.4] mmol/mol). Multilevel interventions reduced HbA1c by −0.40 percentage points (95% CI −0.51, −0.29; I 2 = 68%) (−4.4 [−5.6, −3.2] mmol/mol). Multidomain interventions reduced HbA1c by −0.39 percentage points (95% CI −0.49, −0.29; I 2 = 68%) (−4.3 [−5.4, −3.2] mmol/mol). Interventions that were both multilevel and multidomain reduced HbA1c by −0.43 percentage points (95% CI −0.55, −0.31; I 2 = 69%) (−4.7 [−6.0, −3.4] mmol/mol). LIMITATIONS: The analyses were restricted to RCTs. CONCLUSIONS: Multilevel and multidomain DSME interventions had a modest impact on HbA1c. Few DSME trials have targeted the community and society levels or physical environment domain. Future research is needed to evaluate the effects of these interventions on outcomes beyond HbA1c. [ABSTRACT FROM AUTHOR]

ObjectiveIndividuals with type 1 diabetes have experienced an increase in life expectancy, yet it is unknown what level of glycemic control is ideal for maintaining late-life brain health. We investigated the association of long-term glycemic control with dementia in older individuals with type 1 diabetes.Research design and methodsWe followed 3,433 members of a health care system with type 1 diabetes, aged ≥50 years, from 1996 to 2015. Repeated measurements of hemoglobin A1c (HbA1c), dementia diagnoses, and comorbidities were ascertained from health records. Cox proportional hazards models were fit to evaluate the association of time-varying glycemic exposure with dementia, with adjustment for age, sex, race/ethnicity, baseline health conditions, and frequency of HbA1c measurement.ResultsOver a mean follow-up of 6.3 years, 155 individuals (4.5%) were diagnosed with dementia. Patients with ≥50% of HbA1c measurements at 8-8.9% (64-74 mmol/mol) and ≥9% (≥75 mmol/mol) had 65% and 79% higher risk of dementia, respectively, compared with those with

ObjectiveTo examine the association between traumatic brain injury (TBI) and dementia risk among a cohort of middle-aged and elderly individuals with type 1 diabetes (T1D).MethodsWe evaluated 4,049 members of an integrated health care system with T1D ≥50 years old between January 1, 1996, and September 30, 2015. Dementia and TBI diagnoses throughout the study period were abstracted from medical records. Cox proportional hazards models estimated associations between time-dependent TBI and dementia adjusting for demographics, HbA1c, nephropathy, neuropathy, stroke, peripheral artery disease, depression, and dysglycemic events. Fine and Gray regression models evaluated the association between baseline TBI and dementia risk accounting for competing risk of death.ResultsA total of 178 individuals (4.4%) experienced a TBI and 212 (5.2%) developed dementia. In fully adjusted models, TBI was associated with 3.6 times the dementia risk (hazard ratio [HR] 3.64; 95% confidence interval [CI] 2.34, 5.68). When accounting for the competing risk of death, TBI was associated with almost 3 times the risk of dementia (HR 2.91; 95% CI 1.29, 5.68).ConclusionThis study demonstrates a marked increase in risk of dementia associated with TBI among middle-aged and elderly people with T1D. Given the complexity of self-care for individuals with T1D, and the comorbidities that predispose them to trauma and falls, future work is needed on interventions protecting brain health in this vulnerable population, which is now living to old age.

ContextPrediabetes is prevalent and significantly increases lifetime risk of progression to type 2 diabetes. This review summarizes the evidence surrounding metformin use for type 2 diabetes prevention.Evidence acquisitionArticles published between 1998 and 2017 examining metformin use for the primary indication of diabetes prevention available on MEDLINE.Evidence synthesisForty articles met inclusion criteria and were summarized into four general categories: (1) RCTs of metformin use for diabetes prevention (n=7 and n=2 follow-up analyses); (2) observational analyses examining metformin use in heterogeneous subgroups of patients with prediabetes (n=9 from the Diabetes Prevention Program, n=1 from the biguanides and the prevention of the risk of obesity [BIGPRO] trial); (3) observational analyses examining cost effectiveness of metformin use for diabetes prevention (n=11 from the Diabetes Prevention Program, n=1 from the Indian Diabetes Prevention Program); and (4) real-world assessments of metformin eligibility or use for diabetes prevention (n=9). Metformin was associated with reduced relative risk of incident diabetes, with the strongest evidence for use in those at highest risk (i.e., aged

Though eating with others is often a social behavior, relationships between social contexts of eating and nutrient intake have been underexplored. This study evaluates how social aspects of eating - frequencies of eating meals with others, meals prepared at home, and meals outside the home - are associated with nutrient intake. Because diet improvement can reduce complications of diabetes mellitus, we surveyed a multi-ethnic cohort of persons with type 2 diabetes (n = 770) about social aspects of diet (based on 24-hour recalls). Sex-stratified multiple regression analyses adjusted for confounders assessed the relationship between frequency of eating with others and nutrient intake (total energy, energy from fat, energy from carbohydrates, Healthy Eating Index/HEI, Dietary Approaches to Stop Hypertension/DASH score). Although there was slight variation in men's versus women's propensity to share meals, after adjustment for confounders, there was no consistently significant association between meals with others and the 5 nutrient intake measures for either men or women. The directions of association between categories of eating with others and diet quality (HEI and DASH scores) - albeit not significant - were different for men (positive) and women (mostly negative), which warrants further investigation. The next analyses estimated nutrient intake associated with meals prepared at home, and meals consumed outside the home. Analyses indicated that greater meal frequency at home was associated with significantly better scores on diet quality indices for men (but not women), while meal frequency outside the home was associated with poorer diet quality and energy intake for women (but not men). Better measurement of social dimensions of eating may inform ways to improve nutrition, especially for persons with diabetes for whom diet improvement can result in better disease outcomes.

ObjectiveBoth food insecurity (limited food access owing to cost) and living in areas with low physical access to nutritious foods are public health concerns, but their relative contribution to diabetes management is poorly understood.Research design and methodsThis was a prospective cohort study. A random sample of patients with diabetes in a primary care network completed food insecurity assessment in 2013. Low physical food access at the census tract level was defined as no supermarket within 1 mile in urban areas and 10 miles in rural areas. HbA1c measurements were obtained from electronic health records through November 2016. The relationship among food insecurity, low physical food access, and glycemic control (as defined by HbA1c) was analyzed using hierarchical linear mixed models.ResultsThree hundred and ninety-one participants were followed for a mean of 37 months. Twenty percent of respondents reported food insecurity, and 31% resided in an area of low physical food access. In adjusted models, food insecurity was associated with higher HbA1c (difference of 0.6% [6.6 mmol/mol], 95% CI 0.4-0.8 [4.4-8.7], P < 0.0001), which did not improve over time (P = 0.50). Living in an area with low physical food access was not associated with a difference in HbA1c (difference 0.2% [2.2 mmol/mol], 95% CI -0.2 to 0.5 [-2.2 to 5.6], P = 0.33) or with change over time (P = 0.07).ConclusionsFood insecurity is associated with higher HbA1c, but living in an area with low physical food access is not. Food insecurity screening and interventions may help improve glycemic control for vulnerable patients.

ObjectiveTo estimate the effect of out-of-pocket (OOP) cost on nonadherence to classes of cardiometabolic medications among patients with diabetes.Data sources/settingElectronic health records from a large, health care delivery system for 223,730 patients with diabetes prescribed 842,899 new cardiometabolic medications during 2006-2012.Study designObservational, new prescription cohort study of the effect of OOP cost on medication initiation and adherence.Data collectionAdherence and OOP costs were based on pharmacy dispensing records and benefits.Principal findingsPrimary nonadherence (never dispensed) increased monotonically with OOP cost after adjusting for demographics, neighborhood socioeconomic status, Medicare, medical financial assistance, OOP maximum, deductibles, mail order pharmacy incentive and use, drug type, generic or brand, day's supply, and comorbidity index; 7 percent were never dispensed the new medication when OOP cost ≥$11, 5 percent with OOP cost of $1-$10, and 3 percent when the medication was free of charge (p

ObjectiveSevere hyperglycemia and hypoglycemia ("severe dysglycemia") are serious complications of type 1 diabetes (T1D). Depression has been associated with severe dysglycemia in type 2 diabetes but has not been thoroughly examined specifically in T1D. We evaluated bidirectional associations between depression and severe dysglycemia among older people with T1D.Research design and methodsWe abstracted depression and severe dysglycemia requiring emergency room visit or hospitalization from medical health records in 3,742 patients with T1D during the study period (1996-2015). Cox proportional hazards models estimated the associations between depression and severe dysglycemia in both directions, adjusting for demographics, micro- and macrovascular complications, and HbA1c.ResultsDuring the study period, 41% had depression and 376 (11%) and 641 (20%) had hyperglycemia and hypoglycemia, respectively. Depression was strongly associated with a 2.5-fold increased risk of severe hyperglycemic events (hazard ratio [HR] 2.47 [95% CI 2.00, 3.05]) and 89% increased risk of severe hypoglycemic events (HR 1.89 [95% CI 1.61, 2.22]). The association was strongest within the first 6 months (HRhyperglycemia 7.14 [95% CI 5.29, 9.63]; HRhypoglycemia 5.58 [95% CI 4.46, 6.99]) to 1 year (HRhyperglycemia 5.16 [95% CI 3.88, 6.88]; HRhypoglycemia 4.05 [95% CI 3.26, 5.04]) after depression diagnosis. In models specifying severe dysglycemia as the exposure, hyperglycemic and hypoglycemic events were associated with 143% (HR 2.43 [95% CI 2.03, 2.91]) and 74% (HR 1.75 [95% CI 1.49, 2.05]) increased risk of depression, respectively.ConclusionsDepression and severe dysglycemia are associated bidirectionally among patients with T1D. Depression greatly increases the risk of severe hypoglycemic and hyperglycemic events, particularly in the first 6 months to 1 year after diagnosis, and depression risk increases after severe dysglycemia episodes.

BackgroundData-sharing is encouraged to fulfill the ethical responsibility to transform research data into public health knowledge, but data sharing carries risks of improper disclosure and potential harm from release of individually identifiable data.MethodsThe study objective was to develop and implement a novel method for scientific collaboration and data sharing which distributes the analytic burden while protecting patient privacy. A procedure was developed where in an investigator who is external to an analytic coordinating center (ACC) can conduct original research following a protocol governed by a Publications and Presentations (P&P) Committee. The collaborating investigator submits a study proposal and, if approved, develops the analytic specifications using existing data dictionaries and templates. An original data set is prepared according to the specifications and the external investigator is provided with a complete but de-identified and shuffled data set which retains all key data fields but which obfuscates individually identifiable data and patterns; this" scrambled data set" provides a "sandbox" for the external investigator to develop and test analytic code for analyses. The analytic code is then run against the original data at the ACC to generate output which is used by the external investigator in preparing a manuscript for journal submission.ResultsThe method has been successfully used with collaborators to produce many published papers and conference reports.ConclusionBy distributing the analytic burden, this method can facilitate collaboration and expand analytic capacity, resulting in more science for less money.

We estimated associations between neighborhood supermarket gain or loss and glycemic control (assessed by glycated hemoglobin (HbA1c) values) in patients from the Kaiser Permanente Northern California Diabetes Registry (n = 434,806 person-years; 2007-2010). Annual clinical measures were linked to metrics from a geographic information system for each patient's address of longest residence. We estimated the association between change in supermarket presence (gain, loss, or no change) and change in HbA1c value, adjusting for individual- and area-level attributes and according to baseline glycemic control (near normal,

Associations between neighborhood food environment and adult body mass index (BMI; weight (kg)/height (m)2) derived using cross-sectional or longitudinal random-effects models may be biased due to unmeasured confounding and measurement and methodological limitations. In this study, we assessed the within-individual association between change in food environment from 2006 to 2011 and change in BMI among adults with type 2 diabetes using clinical data from the Kaiser Permanente Diabetes Registry collected from 2007 to 2011. Healthy food environment was measured using the kernel density of healthful food venues. Fixed-effects models with a 1-year-lagged BMI were estimated. Separate models were fitted for persons who moved and those who did not. Sensitivity analysis using different lag times and kernel density bandwidths were tested to establish the consistency of findings. On average, patients lost 1 pound (0.45 kg) for each standard-deviation improvement in their food environment. This relationship held for persons who remained in the same location throughout the 5-year study period but not among persons who moved. Proximity to food venues that promote nutritious foods alone may not translate into clinically meaningful diet-related health changes. Community-level policies for improving the food environment need multifaceted strategies to invoke clinically meaningful change in BMI among adult patients with diabetes.

ImportanceMedication adherence is essential to diabetes care. Patient-physician language barriers may affect medication adherence among Latino individuals.ObjectiveTo determine the association of patient race/ethnicity, preferred language, and physician language concordance with patient adherence to newly prescribed diabetes medications.Design, setting, and participantsThis observational study was conducted from January 1, 2006, to December 31, 2012, at a large integrated health care delivery system with professional interpreter services. Insured patients with type 2 diabetes, including English-speaking white, English-speaking Latino, or limited English proficiency (LEP) Latino patients with newly prescribed diabetes medication.ExposuresPatient race/ethnicity, preferred language, and physician self-reported Spanish-language fluency.Main outcomes and measuresPrimary nonadherence (never dispensed), early-stage nonpersistence (dispensed only once), late-stage nonpersistence (received ≥2 dispensings, but discontinued within 24 months), and inadequate overall medication adherence (>20% time without sufficient medication supply during 24 months after initial prescription).ResultsParticipants included 21 878 white patients, 5755 English-speaking Latino patients, and 3205 LEP Latino patients with a total of 46 131 prescriptions for new diabetes medications. Among LEP Latino patients, 50.2% (n = 1610) had a primary care physician reporting high Spanish fluency. For oral medications, early adherence varied substantially: 1032 LEP Latino patients (32.2%), 1565 English-speaking Latino patients (27.2%), and 4004 white patients (18.3%) were either primary nonadherent or early nonpersistent. Inadequate overall adherence was observed in 1929 LEP Latino patients (60.2%), 2975 English-speaking Latino patients (51.7%), and 8204 white patients (37.5%). For insulin, early-stage nonpersistence was 42.8% among LEP Latino patients (n = 1372), 34.4% among English-speaking Latino patients (n = 1980), and 28.5% among white patients (n = 6235). After adjustment for patient and physician characteristics, LEP Latino patients were more likely to be nonadherent to oral medications and insulin than English-speaking Latino patients (relative risks from 1.11 [95% CI, 1.06-1.15] to 1.17 [95% CI, 1.02-1.34]; P  .28).Conclusions and relevanceNonadherence to newly prescribed diabetes medications is substantially greater among Latino than white patients, even among English-speaking Latino patients. Limited English proficiency Latino patients are more likely to be nonadherent than English-speaking Latino patients independent of the Spanish-language fluency of their physicians. Interventions beyond access to interpreters or patient-physician language concordance will be required to improve medication adherence among Latino patients with diabetes.

The housing foreclosure crisis was harmful to the financial well-being of many households. In the present study, we investigated the health effects of the housing foreclosure crisis on glycemic control within a population of patients with diabetes. We hypothesized that an increase in the neighborhood foreclosure rate could worsen glycemic control by activating stressors such as higher neighborhood crime, lower housing prices, and erosion of neighborhood social cohesion. To test this, we linked public foreclosure records at the census-block level with clinical records from 2006 to 2009 of patients with diabetes. We specified individual fixed-effects models and controlled for individual time-invariant confounders and area-level time-varying confounders, including housing prices and unemployment rate, to estimate the effect of the foreclosure rate per census-block group on glycated hemoglobin. We found no statistically significant relationship between changes in the neighborhood foreclosure rate per block group in the prior year and changes in glycated hemoglobin. There is no evidence that increased foreclosure rates worsened glycemic control in this continuously insured population with diabetes. More research is needed to inform our knowledge of the role of insurance and health-care delivery systems in protecting the health of diabetic patients during times of economic stress.

ObjectivesTo assess changes in medication use after a diagnosis of dementia in individuals with type 2 diabetes mellitus.DesignDifference-in-differences analysis of changes in the number of dispensed chronic medications between individuals with and without newly diagnosed dementia.SettingIntegrated healthcare delivery system, Kaiser Permanente Northern California.ParticipantsIndividuals aged 50 and older without prevalent dementia with type 2 diabetes mellitus enrolled in a baseline survey. During 5 years of follow-up, 193 individuals with a new diagnosis of dementia were identified, and risk-set sampling was used to randomly select five reference subjects per case matched on 5-year age categories and sex (965 matched participants), resulting in an analytical sample of 1,158.MeasurementsThe exposure was new diagnosis of dementia. The primary outcome was change in number of current chronic medications (total, cardiovascular (blood pressure and lipid control), diabetes mellitus) at three times: 1 year before index date (preindex date), date of diagnosis of dementia or matched reference date (index date), and up to 1 year after index date or end of follow-up if censored before 1 year (postindex date).ResultsAfter adjustment, the number of chronic medications and the subset of cardiovascular medications declined after a dementia diagnosis in the overall cohort and in age-, sex-, and time-matched reference individuals, but the decline was significantly greater in the group with dementia (0.71 medications fewer than the reference group, P = .02). The number of diabetes mellitus medications declined in both groups, but the declines were not statistically different (0.18 medications fewer than the reference group, P = .008).ConclusionsUse of cardiometabolic medications fell after a diagnosis of dementia, as recommended in national guidelines.

Health systems are heavily promoting patient portals. However, limited health literacy (HL) can restrict online communication via secure messaging (SM) because patients' literacy skills must be sufficient to convey and comprehend content while clinicians must encourage and elicit communication from patients and match patients' literacy level. This paper describes the Employing Computational Linguistics to Improve Patient-Provider Secure Email (ECLIPPSE) study, an interdisciplinary effort bringing together scientists in communication, computational linguistics, and health services to employ computational linguistic methods to (1) create a novel Linguistic Complexity Profile (LCP) to characterize communications of patients and clinicians and demonstrate its validity and (2) examine whether providers accommodate communication needs of patients with limited HL by tailoring their SM responses. We will study >5 million SMs generated by >150,000 ethnically diverse type 2 diabetes patients and >9000 clinicians from two settings: an integrated delivery system and a public (safety net) system. Finally, we will then create an LCP-based automated aid that delivers real-time feedback to clinicians to reduce the linguistic complexity of their SMs. This research will support health systems' journeys to become health literate healthcare organizations and reduce HL-related disparities in diabetes care.

INTRODUCTION: Although poor glycemic control is associated with dementia, it is unknown if variability in glycemic control, even in those with optimal glycosylated hemoglobin A1c (HbA1c) levels, increases dementia risk. METHODS: Among 171,964 people with type 2 diabetes, we evaluated the hazard of dementia association with long‐term HbA1c variability using five operationalizations, including standard deviation (SD), adjusting for demographics and comorbidities. RESULTS: The mean baseline age was 61 years (48% women). Greater HbA1c SD was associated with greater dementia hazard (adjusted hazard ratio = 1.15 [95% confidence interval: 1.12, 1.17]). In stratified analyses, higher HbA1c SD quintiles were associated with greater dementia hazard among those with a mean HbA1c < 6% (P = 0.0004) or 6% to 8% (P < 0.0001) but not among those with mean HbA1c ≥ 8% (P = 0.42). DISCUSSION: Greater HbA1c variability is associated with greater dementia risk, even among those with HbA1c concentrations at ideal clinical targets. These findings add to the importance and clinical impact of recommendations to minimize glycemic variability. Highlights: We observed a cohort of 171,964 people with type 2 diabetes (mean age 61 years).This cohort was based in Northern California between 1996 and 2018.We examined the association between glycosylated hemoglobin A1c (HbA1c) variability and dementia risk.Greater HbA1c variability was associated with greater dementia hazard.This was most evident among those with normal–low mean HbA1c concentrations. [ABSTRACT FROM AUTHOR]

While stress has been linked to poor health outcomes, little is known about the impact of objective measures of neighborhood crime on stress in patients with chronic disease. Using the Kaiser Permanente Diabetes Study of Northern California (DISTANCE), we examined associations between police-recorded crime (2005-2007) and stress (Perceived Stress Scale-4) in four large Northern California cities (Oakland, Sacramento, San Francisco, and San Jose). We performed stratified analysis by gender and race/ethnicity using generalized linear regression models. In our study sample (n = 3188, mean age 59, range 30-77), 10 % reported high stress. In adjusted analyses, higher neighborhood all crimes rate was associated with modest increase in high stress for African-American (OR = 1.10; 95 % CI 1.02-1.22) and Latina women (OR = 1.36; 95 % CI 1.10-1.67) and property crime showed similar associations with stress for these groups of women. Visible crime was associated with stress only for Latina women (OR = 1.43; 95 % CI 1.14-1.78). We found no association between crime and stress among men or other racial/ethnic groups of women. High crime levels may disproportionately impact health among certain subpopulations. Studies using additional measures of stress are necessary to differentiate the health impact of crime-related stress from other forms of stressors among individuals living with diabetes.

We examined whether residing within 2 miles of a new supermarket opening was longitudinally associated with a change in body mass index (BMI). We identified 12 new supermarkets that opened between 2009 and 2010 in 8 neighborhoods. Using the Kaiser Permanente Northern California Diabetes Registry, we identified members with type 2 diabetes residing continuously in any of these neighborhoods 12 months prior to the first supermarket opening until 10 months following the opening of the last supermarket. Exposure was defined as a reduction (yes/no) in travel distance to the nearest supermarket as a result of a new supermarket opening. First difference regression models were used to estimate the impact of reduced supermarket distance on BMI, adjusting for longitudinal changes in patient and neighborhood characteristics. Among patients in the exposed group, new supermarket openings reduced travel distance to the nearest supermarket by 0.7 miles on average. However, reduced distance to nearest supermarket was not associated with BMI changes. Overall, we found no evidence that reduced supermarket distance was associated with reduced levels of obesity for residents with type 2 diabetes.

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.

Little is known about how neighborhood crime may relate to health in diabetes patients. We examined associations between individuals' perceptions of neighborhood safety or violent crime and stress, physical activity, body mass index (BMI) or hemoglobin A1c (HbA1c) in a sample (n=721) of adults (mean age:63) with diabetes. Self-reported neighborhood safety, violent crime, physical activity, and stress were collected and linked to clinical measures of BMI and HbA1c. Approximately 54% and 15% of patients reported neighborhood safety concerns and violent crimes, respectively. Any neighborhood safety concerns (β=1.14, 95% C.I. 0.04-2.24) and violent crime (β=2.04, 95% C.I. 0.34-3.73) were associated with BMI in adjusted analysis. Any violent crime was associated with class II-III obesity (BMI≥35) (OR=1.34, 95% C.I.: 1.02, 1.75). There were no significant associations between neighborhood safety concerns or violent crime with stress, physical activity, or HbA1c. Neighborhood safety is associated with BMI and obesity. Further studies, including longitudinal designs, are needed to study how people with diabetes may be influenced by a sense of poor personal safety in their neighborhoods.

BackgroundFor more than a decade, the presence of diabetes has been considered a coronary heart disease (CHD) "risk equivalent".ObjectiveThe objective of this study was to revisit the concept of risk equivalence by comparing the risk of subsequent CHD events among individuals with or without history of diabetes or CHD in a large contemporary real-world cohort over a period of 10 years (2002 to 2011).DesignPopulation-based prospective cohort analysis.ParticipantsWe studied a cohort of 1,586,061 adult members (ages 30-90 years) of Kaiser Permanente Northern California, an integrated health care delivery system.Main measurementsWe calculated hazard ratios (HRs) from Cox proportional hazard models for CHD among four fixed cohorts, defined by prevalent (baseline) risk group: no history of diabetes or CHD (None), prior CHD alone (CHD), diabetes alone (DM), and diabetes and prior CHD (DM + CHD).Key resultsWe observed 80,012 new CHD events over the follow-up period (~10,980,800 person-years). After multivariable adjustment, the HRs (reference: None) for new CHD events were as follows: CHD alone, 2.8 (95% CI, 2.7-2.85); DM alone 1.7 (95% CI, 1.66-1.74); DM + CHD, 3.9 (95% CI, 3.8-4.0). Individuals with diabetes alone had significantly lower risk of CHD across all age and sex strata compared to those with CHD alone (12.2 versus 22.5 per 1000 person-years). The risk of future CHD for patients with a history of either DM or CHD was similar only among those with diabetes of long duration (≥10 years).ConclusionsNot all individuals with diabetes should be unconditionally assumed to be a risk equivalent of those with prior CHD.

ObjectiveTo examine self-reported financial strain in relation to pharmacy utilization adherence data.Data sources/study settingSurvey, administrative, and electronic medical data from Kaiser Permanente Northern California.Study designRetrospective cohort design (2006, n = 7,773).Data collection/extraction methodsWe compared survey self-reports of general and medication-specific financial strain to three adherence outcomes from pharmacy records, specifying adjusted generalized linear regression models.Principal findingsEight percent and 9 percent reported general and medication-specific financial strain. In adjusted models, general strain was significantly associated with primary nonadherence (RR = 1.37; 95 percent CI: 1.04-1.81) and refilling late (RR = 1.34; 95 percent CI: 1.07-1.66); and medication-specific strain was associated with primary nonadherence (RR = 1.42, 95 percent CI: 1.09-1.84).ConclusionsSimple, minimally intrusive questions could be used to identify patients at risk of poor adherence due to financial barriers.

ObjectiveOnline patient portals are being widely implemented; however, no studies have examined whether portals influence health behaviors or outcomes similarly across patient racial/ethnic subgroups. We evaluated longitudinal changes in statin adherence to determine whether racial/ethnic minorities initiating use of the online refill function in patient portals had similar changes over time compared with Whites.MethodsWe examined a retrospective cohort of diabetes patients who were existing patient portal users. The primary exposure was initiating online refill use (either exclusively for all statin refills or occasionally for some refills), compared with using the portal for other tasks (eg, exchanging secure messages with providers). The primary outcome was change in statin adherence, measured as the percentage of time a patient was without a supply of statins. Adjusted generalized estimating equation models controlled for race/ethnicity as a primary interaction term.ResultsFifty-eight percent of patient portal users were white, and all racial/ethnic minority groups had poorer baseline statin adherence compared with Whites. In adjusted difference-in-difference models, statin adherence improved significantly over time among patients who exclusively refilled prescriptions online, even after comparing changes over time with other portal users (4% absolute decrease in percentage of time without medication). This improvement was statistically similar across all racial/ethnic groups.DiscussionPatient portals may encourage or improve key health behaviors, such as medication adherence, for engaged patients, but further research will likely be required to reduce underlying racial/ethnic differences in adherence.ConclusionIn a well-controlled examination of diabetes patients' behavior when using a new online feature for their healthcare management, patient portals were linked to better medication adherence across all racial/ethnic groups.