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Kaycee M Sink,1 Mark A Espeland,2 Julia Rushing,2 Cynthia M Castro,3 Timothy S Church,4 Ronald Cohen,5 Thomas M Gill,6 Leora Henkin,2 Janine M Jennings,7 Diana R Kerwin,8 Todd M Manini,5 Valerie Myers,9 Marco Pahor,5 Kieran F Reid,10 Nancy Woolard,1 Stephen R Rapp,11 Jeff D Williamson1 On behalf of LIFE Investigators 1Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, USA; 2Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA; 3Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, USA; 4Pennington Biomedical, Louisiana State University, Baton Rouge, LA, USA; 5Institute on Aging and Department of Aging and Geriatric Research, University of Florida, Gainesville, FL, USA; 6Yale School of Medicine, Department of Internal Medicine, New Haven, CT, USA; 7Department of Psychology, Wake Forest University, Winston-Salem, NC, USA; 8Texas Alzheimer’s and Memory Disorders, Texas Health Presbyterian Hospital Dallas, TX, USA; 9Klein Buendel, Inc., Golden, CO, USA; 10Nutrition, Exercise Physiology and Sarcopenia Laboratory, Jean Mayer United States Department of Agriculture Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA; 11Department of Psychiatry and Behavioral Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA Abstract: Observational studies have shown beneficial relationships between exercise and cognitive function. Some clinical trials have also demonstrated improvements in cognitive function in response to moderate–high intensity aerobic exercise; however, these have been limited by relatively small sample sizes and short durations. The Lifestyle Interventions and Independence for Elders (LIFE) Study is the largest and longest randomized controlled clinical trial of physical activity with cognitive outcomes, in older sedentary adults at increased risk for incident mobility disability. One LIFE Study objective is to evaluate the effects of a structured physical activity program on changes in cognitive function and incident all-cause mild cognitive impairment or dementia. Here, we present the design and baseline cognitive data. At baseline, participants completed the modified Mini Mental Status Examination, Hopkins Verbal Learning Test, Digit Symbol Coding, Modified Rey–Osterrieth Complex Figure, and a computerized battery, selected to be sensitive to changes in speed of processing and executive functioning. During follow up, participants completed the same battery, along with the Category Fluency for Animals, Boston Naming, and Trail Making tests. The description of the mild cognitive impairment/dementia adjudication process is presented here. Participants with worse baseline Short Physical Performance Battery scores (prespecified at ≤7) had significantly lower median cognitive test scores compared with those having scores of 8 or 9 with modified Mini Mental Status Examination score of 91 versus (vs) 93, Hopkins Verbal Learning Test delayed recall score of 7.4 vs 7.9, and Digit Symbol Coding score of 45 vs 48, respectively (all P

Aims: To determine contemporary incidence rates and risk factors for major adverse events in youth-onset T1D and T2D., Methods: Participant interviews were conducted once during in-person visits from 2018 to 2019 in SEARCH (T1D: N = 564; T2D: N = 149) and semi-annually from 2014 to 2020 in TODAY (T2D: N = 495). Outcomes were adjudicated using harmonized, predetermined, standardized criteria., Results: Incidence rates (events per 10,000 person-years) among T1D participants were: 10.9 ophthalmologic; 0 kidney; 11.1 nerve, 3.1 cardiac; 3.1 peripheral vascular; 1.6 cerebrovascular; and 15.6 gastrointestinal events. Among T2D participants, rates were: 40.0 ophthalmologic; 6.2 kidney; 21.2 nerve; 21.2 cardiac; 10.0 peripheral vascular; 5.0 cerebrovascular and 42.8 gastrointestinal events. Despite similar mean diabetes duration, complications were higher in youth with T2D than T1D: 2.5-fold higher for microvascular, 4.0-fold higher for macrovascular, and 2.7-fold higher for gastrointestinal disease. Univariate logistic regression analyses in T1D associated age at diagnosis, female sex, HbA1c and mean arterial pressure (MAP) with microvascular events. In youth-onset T2D, composite microvascular events associated positively with MAP and negatively with BMI, however composite macrovascular events associated solely with MAP., Conclusions: In youth-onset diabetes, end-organ events were infrequent but did occur before 15 years diabetes duration. Rates were higher and had different risk factors in T2D versus T1D., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To evaluate the relation between household food insecurity (HFI) and fear of hypoglycemia among young adults with type 1 and type 2 diabetes and adolescents with type 1 diabetes and their parents., Research Design and Methods: We analyzed cross-sectional data of 1,676 young adults with youth-onset diabetes (84% type 1, 16% type 2) and 568 adolescents (<18 years old; mean age 15.1 years) with type 1 diabetes from the SEARCH for Diabetes in Youth study. Adult participants and parents of adolescent participants completed the U.S. Household Food Security Survey Module. Adults, adolescents, and parents of adolescents completed the Hypoglycemia Fear Survey, where answers range from 1 to 4. The outcomes were mean score for fear of hypoglycemia and the behavior and worry subscale scores. Linear regression models identified associations between HFI and fear of hypoglycemia scores., Results: Adults with type 1 diabetes experiencing HFI had higher fear of hypoglycemia scores (0.22 units higher for behavior, 0.55 units for worry, 0.40 units for total; all P < 0.0001) than those without HFI. No differences by HFI status were found for adolescents with type 1 diabetes. Parents of adolescents reporting HFI had a 0.18 unit higher worry score than those not reporting HFI (P < 0.05). Adults with type 2 diabetes experiencing HFI had higher fear of hypoglycemia scores (0.19 units higher for behavior, 0.35 units for worry, 0.28 units for total; all P < 0.05) than those in food secure households., Conclusions: Screening for HFI and fear of hypoglycemia among people with diabetes can help providers tailor diabetes education for those who have HFI and therefore fear hypoglycemia., (© 2023 by the American Diabetes Association.)

Objective: We evaluated the association of household food insecurity (FI) with cognition in youth and young adults with type 1 diabetes (T1D) or type 2 diabetes (T2D)., Design: In this cross-sectional study, age-adjusted scores for composite Fluid Cognition, and sub-domain scores for Receptive Language and Inhibitory Control and Attention, were modeled stratified by diabetes-type using linear regression, with FI in the past year as the predictor, controlling for covariates. Tests for processing speed, inhibitory control/attention, working memory, episodic memory, and cognitive flexibility were administered to measure composite Fluid Cognition score. The NIHT-CB Picture Vocabulary Test was used to assess Crystallized Cognition score and rapid identification of congruent versus noncongruent items were used to assess Inhibitory Control and Attention score., Setting: The SEARCH for Diabetes in Youth study, representative of 5 U.S. states., Participants: Included 1574 youth and young adults with T1D or T2D, mean age of 21 years, mean diabetes duration of 11 years, 51% non-Hispanic white, and 47% had higher HbA1c levels (>9% HbA1c)., Results: Approximately 18% of the 1,240 participants with T1D and 31% of the 334 with T2D experienced FI. The food-insecure group with T1D had a lower composite Fluid Cognition score (β= -2.5, 95% confidence interval (CI)= -4.8, -0.1) and a lower Crystallized Cognition score (β= -3.4, CI= -5.6, -1.3) than food-secure peers. Findings were attenuated to non-significance after adjustment for demographics. Among T2D participants, no associations were observed. In participants with T1D effect modification by glycemic levels were found in the association between FI and composite Fluid Cognition score but adjustment for socioeconomic characteristics attenuated the interaction (p=0.0531)., Conclusions: Food-insecure youth and young adults with T1D or T2D did not have different cognition compared to those who were food-secure after adjustment for confounders. Longitudinal research is needed to further understand relations amongst these factors., Competing Interests: Conflicts of interest The authors declare that there is no conflict of interest regarding the publication of this article.

Objective: To examine short-term mortality and cause of death among youth and young adults (YYAs) with youth-onset diabetes., Research Design and Methods: We included 19,717 YYAs newly diagnosed with diabetes before 20 years of age from 1 January 2002 to 31 December 2015 enrolled in the SEARCH for Diabetes in Youth Study. Of these, 14,721 had type 1; 4,141 type 2; and 551 secondary and 304 other/unknown diabetes type. Cases were linked with the National Death Index through 31 December 2017. We calculated standardized mortality ratios (SMRs) and 95% CIs based on age, sex, and race/ethnicity for state and county population areas and examined underlying causes of death., Results: During 170,148 person-years (PY) (median follow-up 8.5 years), 283 individuals died: 133 with type 1 (103.0/100,000 PY), 55 with type 2 (161.5/100,000 PY), 87 with secondary (1,952/100,000 PY), and 8 with other/unknown diabetes type (312.3/100,000 PY). SMRs (95% CI) for the first three groups were 1.5 (1.2-1.8), 2.3 (1.7-3.0), and 28.0 (22.4-34.6), respectively. Diabetes was the underlying cause of death for 42.1%, 9.1%, and 4.6% of deaths, respectively. The SMR was greater for type 2 than for type 1 diabetes ( P < 0.001). SMRs were significantly higher for individuals with type 1 diabetes who were <20 years of age, non-Hispanic White and Hispanic, and female and for individuals with type 2 diabetes who were <25 years of age, from all race/ethnic minority groups, and from both sexes., Conclusions: Excess mortality was observed among YYAs for each type of diabetes with differences in risk associated with diabetes type, age, race/ethnicity, and sex. The root causes of excess mortality among YYAs with diabetes merit further study., (© 2021 by the American Diabetes Association.)

Objective: Poor cognition has been observed in children and adolescents with youth-onset type 1 (T1D) and type 2 diabetes (T2D) compared with control subjects without diabetes. Differences in cognition between youth-onset T1D and T2D, however, are not known. Thus, using data from SEARCH for Diabetes in Youth, a multicenter, observational cohort study, we tested the association between diabetes type and cognitive function in adolescents and young adults with T1D ( n = 1,095) or T2D ( n = 285)., Research Design and Methods: Cognition was assessed via the National Institutes of Health Toolbox Cognition Battery, and age-corrected composite Fluid Cognition scores were used as the primary outcome. Confounder-adjusted linear regression models were run. Model 1 included diabetes type and clinical site. Model 2 additionally included sex, race/ethnicity, waist-to-height ratio, diabetes duration, depressive symptoms, glycemic control, any hypoglycemic episode in the past year, parental education, and household income. Model 3 additionally included the Picture Vocabulary score, a measure of receptive language and crystallized cognition., Results: Having T2D was significantly associated with lower fluid cognitive scores before adjustment for confounders (model 1; P < 0.001). This association was attenuated to nonsignificance with the addition of a priori confounders (model 2; P = 0.06) and Picture Vocabulary scores (model 3; P = 0.49). Receptive language, waist-to-height ratio, and depressive symptoms remained significant in the final model ( P < 0.01 for all, respectively)., Conclusions: These data suggest that while youth with T2D have worse fluid cognition than youth with T1D, these differences are accounted for by differences in crystallized cognition (receptive language), central adiposity, and mental health. These potentially modifiable factors are also independently associated with fluid cognitive health, regardless of diabetes type. Future studies of cognitive health in people with youth-onset diabetes should focus on investigating these significant factors., (© 2021 by the American Diabetes Association.)

Objective: Although severe hypoglycaemia (SH) can lead to adverse health outcomes, little is known about its occurrence and re-occurrence among youth with type 1 or type 2 diabetes., Methods: This study included 2740 participants aged <20 years at diabetes diagnosis and 5-14 years diabetes duration from the SEARCH for Diabetes in Youth Cohort Study. Participants reported SH events in the past 6 months. Differences in SH events by demographic and clinical factors were tested using logistic regression models., Results: Severe hypoglycaemia in the past 6 months was more common among youth with type 1 (7.0%, 168 of 2399) than with type 2 diabetes (2.6%, nine of 341) ( P  < 0.002). The median number of SH events per youth who had at least one SH event in the past 6 months was 1 for both type 1 type 2 diabetes. For youth with type 1 diabetes, those who reported SH events were older, were more likely to have obesity or to be physically active, and had lower HbA1c. After adjustments, one unit increase in HbA1c was associated with 16% lower likelihood (OR 0.84, 95% CI 0.75, 0.94) and being physically active was associated with an 87% higher likelihood (OR 1.87, 95% CI 1.23, 2.86) of reporting a SH event. There were too few SH events among youth with type 2 diabetes to analyse further., Conclusions: In youth with diabetes, SH was common even within a short 6-month window. Better understanding the causes of SH may help prevent them from occurring., Competing Interests: Nothing to declare.

Purpose: To investigate whether active smoking and/or exposure to environmental tobacco smoke (ETS) is associated with insulin sensitivity., Methods: Insulin sensitivity and tobacco use history were measured in 1481 participants in the Insulin Resistance Atherosclerosis Study (IRAS). IRAS is a large mulitcenter epidemiologic study designed to explore the cross-sectional relationships among insulin resistance, cardiovascular disease risk factors and behaviors, and disease in African-American, Hispanic, and non-Hispanic white men and women, aged 40-69 years, selected to represent a broad range of glucose tolerance. Multiple linear regression models and linear contrasts were employed to describe the association between smoking history, as assessed via structured interview, and insulin sensitivity, as assessed by an insulin modified frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model analysis., Results: Active smoking was not associated with insulin sensitivity. Exposure to ETS was associated with lower insulin sensitivity. Specifically, for all participants combined, levels of SI were lower, indicating reduced insulin sensitivity, for those exposed to ETS when compared to those who were not exposed (p = 0.019). This association persisted for female participants (p = 0.013) and exhibited the same trend for males but failed to achieve statistical significance (p = 0.264)., Conclusions: Our study did not reveal an association between active smoking and insulin sensitivity, as has been shown previously. The association between ETS exposure and insulin sensitivity is a puzzling finding which deserves further investigation in the longitudinal data from IRAS as well as in other populations.