Faculty Bibliography

Importance:Interindividual variability in postprandial glycemic response (PPGR) to the same foods may explain why low glycemic index or load and low-carbohydrate diet interventions have mixed weight loss outcomes. A precision nutrition approach that estimates personalized PPGR to specific foods may be more efficacious for weight loss. Objective:To compare a standardized low-fat vs a personalized diet regarding percentage of weight loss in adults with abnormal glucose metabolism and obesity. Design, Setting, and Participants:The Personal Diet Study was a single-center, population-based, 6-month randomized clinical trial with measurements at baseline (0 months) and 3 and 6 months conducted from February 12, 2018, to October 28, 2021. A total of 269 adults aged 18 to 80 years with a body mass index (calculated as weight in kilograms divided by height in meters squared) ranging from 27 to 50 and a hemoglobin A1c level ranging from 5.7% to 8.0% were recruited. Individuals were excluded if receiving medications other than metformin or with evidence of kidney disease, assessed as an estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 using the Chronic Kidney Disease Epidemiology Collaboration equation, to avoid recruiting patients with advanced type 2 diabetes. Interventions:Participants were randomized to either a low-fat diet (<25% of energy intake; standardized group) or a personalized diet that estimates PPGR to foods using a machine learning algorithm (personalized group). Participants in both groups received a total of 14 behavioral counseling sessions and self-monitored dietary intake. In addition, the participants in the personalized group received color-coded meal scores on estimated PPGR delivered via a mobile app. Main Outcomes and Measures:The primary outcome was the percentage of weight loss from baseline to 6 months. Secondary outcomes included changes in body composition (fat mass, fat-free mass, and percentage of body weight), resting energy expenditure, and adaptive thermogenesis. Data were collected at baseline and 3 and 6 months. Analysis was based on intention to treat using linear mixed modeling. Results:Of a total of 204 adults randomized, 199 (102 in the personalized group vs 97 in the standardized group) contributed data (mean [SD] age, 58 [11] years; 133 women [66.8%]; mean [SD] body mass index, 33.9 [4.8]). Weight change at 6 months was -4.31% (95% CI, -5.37% to -3.24%) for the standardized group and -3.26% (95% CI, -4.25% to -2.26%) for the personalized group, which was not significantly different (difference between groups, 1.05% [95% CI, -0.40% to 2.50%]; P = .16). There were no between-group differences in body composition and adaptive thermogenesis; however, the change in resting energy expenditure was significantly greater in the standardized group from 0 to 6 months (difference between groups, 92.3 [95% CI, 0.9-183.8] kcal/d; P = .05). Conclusions and Relevance:A personalized diet targeting a reduction in PPGR did not result in greater weight loss compared with a low-fat diet at 6 months. Future studies should assess methods of increasing dietary self-monitoring adherence and intervention exposure. Trial Registration:ClinicalTrials.gov Identifier: NCT03336411.

OBJECTIVE:Confirmatory testing is recommended for diabetes diagnosis in clinical practice. However, national estimates of undiagnosed diabetes are based on single elevated test measures, potentially resulting in overestimation. Our objective was to update trends in undiagnosed diabetes using definitions consistent with clinical practice. RESEARCH DESIGN AND METHODS:We included 30,492 adults (aged ≥20 years) from the National Health and Nutrition Examination Survey (1988-2020). Among adults without diagnosed diabetes, confirmed undiagnosed diabetes was defined as having both elevated levels of fasting plasma glucose (FPG) (≥126 mg/dL) and elevated glycated hemoglobin (HbA1c; ≥6.5%), and persistent undiagnosed diabetes was defined as having elevated HbA1c or FPG levels, adjusted for the within-person variability in HbA1c and FPG tests. RESULTS:From the periods 1988-1994 to 2017 to March 2020, there was an increase in the prevalence of diagnosed diabetes (from 4.6% to 11.7%), but no change in prevalence of persistent undiagnosed diabetes (from 2.23% to 2.53%) or confirmed undiagnosed diabetes (from 1.10% to 1.23%). Consequently, the proportion of all undiagnosed diabetes cases declined from 32.8% to 17.8% (persistent undiagnosed diabetes) and from 19.3% to 9.5% (confirmed undiagnosed diabetes). Undiagnosed diabetes was more prevalent in older and obese adults, racial/ethnic minorities, and those without health care access. Among persons with diabetes, Asian Americans and those without health care access had the highest proportion of undiagnosed cases, with rates ranging from 23% to 61%. CONCLUSIONS:From 1988 to March 2020, the proportion of undiagnosed diabetes cases declined substantially, suggesting major improvements in diabetes screening and detection. Undiagnosed diabetes currently affects 1-2% of US adults; up to 90% of all cases are diagnosed.

Importance/UNASSIGNED:Older adults vary widely in age at diagnosis and duration of type 2 diabetes, but treatment often ignores this heterogeneity. Objectives/UNASSIGNED:To investigate the associations of diabetes vs no diabetes, age at diagnosis, and diabetes duration with negative health outcomes in people 50 years and older. Design, Setting, and Participants/UNASSIGNED:This cohort study included participants in the 1995 through 2018 waves of the Health and Retirement Study (HRS), a population-based, biennial longitudinal health interview survey of older adults in the US. The study sample included adults 50 years or older (n = 36 060) without diabetes at entry. Data were analyzed from June 1, 2021, to July 31, 2022. Exposures/UNASSIGNED:The presence of diabetes, specifically the age at diabetes diagnosis, was the main exposure of the study. Age at diagnosis was defined as the age when the respondent first reported diabetes. Adults who developed diabetes were classified into 3 age-at-diagnosis groups: 50 to 59 years, 60 to 69 years, and 70 years and older. Main Outcomes and Measures/UNASSIGNED:For each diabetes age-at-diagnosis group, a propensity score-matched control group of respondents who never developed diabetes was constructed. The association of diabetes with the incidence of key outcomes-including heart disease, stroke, disability, cognitive impairment, and all-cause mortality-was estimated and the association of diabetes vs no diabetes among the age-at-diagnosis case and matched control groups was compared. Results/UNASSIGNED:A total of 7739 HRS respondents developed diabetes and were included in the analysis (4267 women [55.1%]; mean [SD] age at diagnosis, 67.4 [9.9] years). The age-at-diagnosis groups included 1866 respondents at 50 to 59 years, 2834 at 60 to 69 years, and 3039 at 70 years or older; 28 321 HRS respondents never developed diabetes. Age at diagnosis of 50 to 59 years was significantly associated with incident heart disease (hazard ratio [HR], 1.66 [95% CI, 1.40-1.96]), stroke (HR, 1.64 [95% CI, 1.30-2.07]), disability (HR, 2.08 [95% CI, 1.59-2.72]), cognitive impairment (HR, 1.30 [95% CI, 1.05-1.61]), and mortality (HR, 1.49 [95% CI, 1.29-1.71]) compared with matched controls, even when accounting for diabetes duration. These associations significantly decreased with advancing age at diagnosis. Respondents with diabetes diagnosed at 70 years or older only showed a significant association with the outcome of elevated mortality (HR, 1.08 [95% CI, 1.01-1.17]). Conclusions and Relevance/UNASSIGNED:The findings of this cohort study suggest that age at diabetes diagnosis was differentially associated with outcomes and that younger age groups were at elevated risk of heart disease, stroke, disability, cognitive impairment, and all-cause mortality. These findings reinforce the clinical heterogeneity of diabetes and highlight the importance of improving diabetes management in adults with earlier diagnosis.

BACKGROUND:Cannabis outlets may affect health and health disparities. Local governments can regulate outlets, but little is known about the effectiveness of local policies in limiting outlet densities and discouraging disproportionate placement of outlets in vulnerable neighborhoods. METHODS:For 241 localities in California, we measured seven policies pertaining to density or location of recreational cannabis outlets. We geocoded outlets using web-scraped data from the online finder Weedmaps between 2018 and 2020. We applied Bayesian spatiotemporal models to evaluate associations of local cannabis policies with Census block group-level outlet counts, accounting for confounders and spatial autocorrelation. We assessed whether associations differed by block group median income or racial-ethnic composition. RESULTS:Seventy-six percent of localities banned recreational cannabis outlets. Bans were associated with fewer outlets, particularly in block groups with higher median income, fewer Hispanic residents, and more White and Asian residents. Outlets were disproportionately located in block groups with lower median income [posterior RR (95% credible interval): 0.76 (0.70, 0.82) per $10,000], more Hispanic residents [1.05 (1.02, 1.09) per 5%], and fewer Black residents [0.91 (0.83, 0.98) per 5%]. For the six policies in jurisdictions permitting outlets, two policies were associated with fewer outlets and two with more; two policy associations were uninformative. For these policies, we observed no consistent heterogeneity in associations by median income or racial-ethnic composition. CONCLUSIONS:Some local cannabis policies in California are associated with lower cannabis outlet densities, but are unlikely to deter disproportionate placement of outlets in racial-ethnic minority and low-income neighborhoods.

BACKGROUND:Financial distress is a barrier to cessation among low-income smokers. OBJECTIVE:To evaluate an intervention that integrated financial coaching and benefits referrals into a smoking cessation program for low-income smokers. DESIGN/METHODS:Randomized waitlist control trial conducted from 2017 to 2019. PARTICIPANTS/METHODS:Adult New York City residents were eligible if they reported past 30-day cigarette smoking, had income below 200% of the federal poverty level, spoke English or Spanish, and managed their own funds. Pregnant or breastfeeding people were excluded. Participants were recruited from two medical centers and from the community. INTERVENTION/METHODS:The intervention (n = 208) offered smoking cessation coaching, nicotine replacement therapy, money management coaching, and referral to financial benefits and empowerment services. The waitlist control (n=202) was usual care during a 6-month waiting period. MAIN MEASURES/METHODS:Treatment engagement, self-reported 7-day abstinence, and financial stress at 6 months. KEY RESULTS/RESULTS:At 6 months, intervention participants reported higher abstinence (17% vs. 9%, P=0.03), lower stress about finances (β, -0.8 [SE, 0.4], P=0.02), and reduced frequency of being unable to afford activities (β, -0.8 [SE, 0.4], P=0.04). Outcomes were stronger among participants recruited from the medical centers (versus from the community). Among medical center participants, the intervention was associated with higher abstinence (20% vs. 8%, P=0.01), higher satisfaction with present financial situation (β, 1.0 [SE, 0.4], P=0.01), reduced frequency of being unable to afford activities (β, -1.0 [SE, 0.5], P=0.04), reduced frequency in getting by paycheck-to-paycheck (β, -1.0 [SE, 0.4], P=0.03), and lower stress about finances in general (β, -1.0 [SE, 0.4], P = 0.02). There were no group differences in outcomes among people recruited from the community (P>0.05). CONCLUSIONS:Among low-income smokers recruited from medical centers, the intervention produced higher abstinence rates and reductions in some markers of financial distress than usual care. The intervention was not efficacious with people recruited from the community. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov Identifier: NCT03187730.

Maternal-fetal attachment (MFA), a woman's relationship with and affiliative behaviors toward her unborn child, has been linked to near-term infant physical and developmental outcomes. However, further longitudinal research is needed to understand whether the impact of MFA extends past the earliest years of life. The current study explored relationships between MFA and child socioemotional competence and behavior problems at age 3 and whether parenting stress mediated the association between MFA and child outcomes. Data were collected from 221 primarily Black/African-American mothers who completed a scale of MFA during pregnancy. Mothers reported on parenting stress at infant age 7 months and reported on child socioemotional competence and problem behaviors at child age 3 years. In path analyses, MFA was directly associated with child socioemotional competence at age 3 years, but an indirect association between MFA and socioemotional competence via parenting stress was not significant. We also observed a significant indirect association between lower MFA and child internalizing behavior problems via parenting stress that was related to maternal dissatisfaction regarding interactions with her child. Findings suggest that assessing MFA may serve as a means to identify dyads who would benefit from support to promote individual health outcomes.

BACKGROUND:Plant-based diets are increasingly popular and have many well-established benefits for health and environmental sustainability. Our objective was to perform a systematic review of plant-based diets and prostate cancer. METHODS:We performed a systematic database and citation search in February 2022. Studies were included if they reported primary data on plant-based dietary patterns (i.e., vegan, vegetarian, plant-based) and incidence among at-risk men for prostate cancer, or oncologic, general health/nutrition, or quality of life outcomes among patients with prostate cancer or caregivers. RESULTS:A total of 32 publications were eligible for the qualitative synthesis, representing 5 interventional and 11 observational studies. Interventional studies primarily focused on lifestyle modification including plant-based diets for men on active surveillance for localized prostate cancer or with biochemical recurrence after treatment, showing improvements in short-term oncologic outcomes alongside improvements in general health and nutrition. Observational studies primarily focused on prostate cancer risk, showing either protective or null associations for plant-based dietary patterns. Studies of the vegan diet consistently showed favorable associations with risk and/or outcomes. Gaps in the current literature include impact for long-term disease-specific outcomes. CONCLUSIONS:Interventional studies showed generally favorable results of lifestyle modifications incorporating a plant-based diet with prostate cancer outcomes as well as improvements in nutrition and general health. Observational studies demonstrated either a lower risk of prostate cancer or no significant difference. These results are encouraging in light of the many benefits of plant-based diets for overall health, as well as environmental sustainability and animal welfare.

BACKGROUND:STRIVE was a prospective, 4-year, multicenter, observational, open-label, single-arm study of natalizumab treatment in anti-JC virus antibody-negative patients with early relapsing-remitting multiple sclerosis (RRMS). OBJECTIVE:Study objectives examined the effects of natalizumab on cognitive processing speed, confirmed disability improvement (CDI), and patient-reported outcomes (PROs). METHODS:Clinical and PRO secondary endpoints were assessed annually over 4 years in STRIVE. The Symbol Digit Modalities Test (SDMT) was used as a measure of cognitive processing speed. PROs were assessed using the Multiple Sclerosis Impact Score (MSIS-29) and the Work Productivity and Activity Impairment Questionnaire (WPAI). RESULTS:At all four annual assessments, the proportion of patients in the intent-to-treat (ITT) population (N = 222) who exhibited clinically meaningful improvement in their SDMT score from baseline (i.e., change ≥ 4 points) ranged from 41.9 to 54.0%. The cumulative probability of CDI at 4 years in patients in the ITT population with a baseline Expanded Disability Status Scale score ≥ 2 (N = 133) was 43.9%. Statistically significant reductions in the mean change from screening in the MSIS-29 physical and psychological scores, indicating improved quality of life, were observed over all 4 years (P ≤ 0.0012 for all). A statistically significant decrease from screening in the impact of MS on regular activities, signifying an improvement in this WPAI measure, was also observed over all 4 years of the study. CONCLUSION/CONCLUSIONS:These results further extend our knowledge of the effectiveness, specifically regarding improvements in cognitive processing speed, disability and PROs, of long-term natalizumab treatment in early RRMS patients. CLINICALTRIALS/RESULTS:GOV: NCT01485003 (5 December 2011).

RATIONALE & OBJECTIVE/UNASSIGNED:Novel metabolite biomarkers of kidney failure with replacement therapy (KFRT) may help identify people at high risk for adverse kidney outcomes and implicated pathways may aid in developing targeted therapeutics. STUDY DESIGN/UNASSIGNED:Prospective cohort. SETTING & PARTICIPANTS/UNASSIGNED:The cohort included 3,799 Atherosclerosis Risk in Communities study participants with serum samples available for measurement at visit 1 (1987-1989). EXPOSURE/UNASSIGNED:Baseline serum levels of 318 metabolites. OUTCOMES/UNASSIGNED:, or death from kidney disease). ANALYTICAL APPROACH/UNASSIGNED:Because metabolites are often intercorrelated and represent shared pathways, we used a high dimension reduction technique called Netboost to cluster metabolites. Longitudinal associations between clusters of metabolites and KFRT and kidney failure were estimated using a Cox proportional hazards model. RESULTS/UNASSIGNED:Mean age of study participants was 53 years, 61% were African American, and 13% had diabetes. There were 160 KFRT cases and 357 kidney failure cases over a mean of 23 years. The 314 metabolites were grouped in 43 clusters. Four clusters were significantly associated with risk of KFRT and 6 were associated with kidney failure (including 3 shared clusters). The 3 shared clusters suggested potential pathways perturbed early in kidney disease: cluster 5 (15 metabolites involved in alanine, aspartate, and glutamate metabolism as well as 5-oxoproline and several gamma-glutamyl amino acids), cluster 26 (6 metabolites involved in sugar and inositol phosphate metabolism), and cluster 34 (21 metabolites involved in glycerophospholipid metabolism). Several individual metabolites were also significantly associated with both KFRT and kidney failure, including glucose and mannose, which were associated with higher risk of both outcomes, and 5-oxoproline, gamma-glutamyl amino acids, linoleoylglycerophosphocholine, 1,5-anhydroglucitol, which were associated with lower risk of both outcomes. LIMITATIONS/UNASSIGNED:Inability to determine if the metabolites cause or are a consequence of changes in kidney function. CONCLUSIONS/UNASSIGNED:We identified several clusters of metabolites reproducibly associated with development of KFRT. Future experimental studies are needed to validate our findings as well as continue unraveling metabolic pathways involved in kidney function decline.