Self-reported Type 2 Diabetes Research Articles

Weight-related discrimination, perceived stress and psychological and physical well-being of persons with type 2 diabetes: A mediation analysis.

The aim of the study was to examine perceived stress as a mediator of the association between weight-related discrimination and physical and psychological well-being among persons with type 2 diabetes (T2D). Data were obtained from 5104 persons with self-reported T2D participating in the All of Us research programme in the United States. The Everyday Discrimination Scale, Cohen's Perceived Stress Scale (PSS) and PROMIS Global Health Scale were used to measure weight-related discrimination, perceived stress and health outcomes (physical and psychological), respectively. Mediation effects of PSS were tested by bootstrapping with 5000 random samples. Participants were, on average, 63.62 (SD 11.38) years old. Majority of them were female (55.53%), non-Hispanic White (72.61%), married or living with a partner (56.92%), had a household income of <$35,000 (31.99%) and had some college education (33.54%). We found that approximately 18% of study participants reported having experienced weight-related discrimination. We also found that weight-related discrimination was independently associated with poor physical and psychological well-being. These associations were partially mediated by perceived stress such that weight-related discrimination was associated with greater perceived stress, which was in turn associated with poorer physical and psychological well-being. Given that weight-related discrimination is associated with poor outcomes through elevated stress, interventions that target stress may disrupt this pathway thereby helping to reduce the health impact of weight-related discrimination. This assertion should, however, be tested in future studies.

Abstract P432: Validation and Optimization of the American Diabetes Association Score for Undiagnosed Type 2 Diabetes Risk in Hispanic or Latino Adults

Background: The prevalence of type 2 diabetes (T2D) is increasing in Hispanic or Latino adults. The American Diabetes Association (ADA) score to identify current risk of T2D was developed with limited Hispanic or Latino representation. Therefore, we sought to validate the ADA score in a cohort of Hispanic or Latino adults. Methods: At enrollment in the Sangre Por Salud Biobank, 3,625 Hispanic or Latino adults from Phoenix, Arizona completed a baseline questionnaire. Current risk of undiagnosed T2D was based on non-laboratory risk factors and ADA score ≥5 (Table). Participants also completed T2D screening (ie, fasting glucose, 2-hour oral glucose tolerance test, and/or hemoglobin A1c). Undiagnosed T2D was based on 'no self-reported T2D but meeting T2D diagnostic’ criteria. Multivariable logistic regression analyzed associations of ADA risk factors and undiagnosed T2D, and model performance was based on sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: At enrollment, 7.3% of participants had undiagnosed T2D (n=265/3,625). In multivariable analysis, most risk factors described for the ADA score were significantly associated with T2D, except for sex, which showed no association. ADA score ≥5 had sensitivity 50%, specificity 79%, PPV 18%, and NPV 95%. However, ADA score ≥4 had sensitivity 72%, specificity 61%, PPV 14%, and NPV 96%. ADA score ≥4 vs ≥5 identified 22% (n=59) additional cases of undiagnosed T2D. Furthermore, using the revised definition for elevated blood pressure (&gt;120/80 mmHg) vs ≥140/90 mmHg (current ADA score) further improved the ADA score ≥4 (sensitivity 81%; specificity 52%). Other scores had lower performance using both hypertension definitions. Conclusion: In Hispanic or Latino adults, a lower ADA score than currently recommended identified additional cases of undiagnosed T2D. The ADA score requires validation and recalibration, including for the updated hypertension guidelines.

Abstract P437: Cumulative Effect of Early-Onset Type 2 Diabetes on Left Ventricular Geometry - The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Type 2 diabetes (T2D) is increasingly common in young adults. Increases in left ventricular (LV) mass and wall thickness are early manifestations of myocardial involvement in T2D. The association between the cumulative burden of risk factors (RFs) and LV structural abnormalities in patients with early-onset T2D has not been well characterized. Objective: Investigate how metabolic RFs accumulated in a 25-year period among patients with early-onset T2D relate to LV mass index (LVMI) and relative wall thickness (RWT). Methods: We used data from the Coronary Artery Risk Development in Young Adults study (CARDIA, baseline to year 25). We defined early-onset T2D by self-reported T2D or anti-diabetic medication use, fasting glucose (FG) ≥126 mg/dL, or oral glucose ≥200 mg/dL at or before follow-up year 10 (age&lt;40). LV outcomes were measured by Doppler echocardiography (LVMI by Devereux formula indexed to body surface area; RWT = LV posterior wall thickness at end diastole x 2/LV internal dimension at end-diastole). Hypertrophy was defined by LVMI ≥115 g/m 2 in men or ≥95 g/m 2 in women. We used the area under the growth curve (AUC) that was derived from quadratic random-effects models of ≥4 repeated measures of RFs (BMI, SBP, DBP, LDL-c, HDL-c, triglycerides, fasting glucose, and fasting insulin) to estimate the cumulative burden of T2D through adulthood. We performed linear regressions to examine the associations of the total AUC of each RF with LVMI or RWT, accounting for sex, race, mid-life age, education, smoking, and control for hypertension, lipids, and diabetes. We assessed the associations by sex and race. Results: Among 227 patients with early-onset T2D, 39% had hypertrophy, and 13% had RWT&gt;0.42 at midlife. Each standard deviation (SD) increase in total AUCs of BMI, SBP, DBP, triglycerides, FG, and fasting insulin was significantly associated with increased LVMI (β coefficients =5.9, 11.5, 10, 7, 4.1, and 6.7, respectively), while high total AUC of HDL-c was inversely associated with LVMI (β = -5.1). Increased total AUC of triglycerides was associated with increased RWT (β = 0.2). Significant sex and race differences were shown in the cumulative effect of RFs on outcomes. The positive associations between AUC of RFs and LVMI were significant in both sexes, but the associations were stronger in male patients than in women. The inverse association between AUC of HDL-c and LVMI was only significant in male patients (P-interaction &lt;0.05). Women with early-onset T2D but not men exhibited significantly increased RWT related to the increase in AUCs of SBP, DBP, triglycerides, FG, and insulin (P-interaction &lt;0.05). The positive association between AUC of BMI and LVMI was significant in Whites but not Blacks (P-interaction &lt;0.05). Conclusion: Cumulative RFs alter mid-adulthood LV geometry in patients with early-onset T2D. This cumulative impact of early-onset T2D on LV geometry varies by sex and race.

3 Type 2 Diabetes Moderates the Association between Amyloid PET and Attention/Executive Functioning in Older Veterans

Objective:Type 2 diabetes (T2D) is a risk factor for cognitive impairment/dementia and has been shown to modify the impact of Alzheimer’s disease (AD) biomarkers on cognition and everyday functioning. Studies examining amyloid-ß (Aß), one of the hallmark AD pathologies, have shown mixed results regarding associations of Aß biomarkers with cross-sectional cognition as well as T2D, though Aß is generally associated with future cognitive declines. The purpose of the present study is to examine whether T2D impacts the associations between amyloid positron emission tomography (PET) and cognition in older Veterans.Participants and Methods:The current study included 202 mostly male Vietnam-Era Veterans from the Department of Defense-Alzheimer’s Disease Neuroimaging Initiative (DOD ADNI) study (age M=69.38 years, SD=4.37; 40% with self-reported T2D) who completed neuropsychological testing and florbetapir PET imaging. The Aß PET standardized uptake variable ratio (SUVR) was measured using a previously-validated summary SUVR calculated by dividing the mean uptake across 4 AD-vulnerable cortical regions by whole cerebellar uptake. General linear models examined whether T2D moderated the relationship of Aß PET with memory, attention/executive functioning, and language composite scores. Models adjusted for age, education, apolipoprotein E e4 carrier status, vascular risk burden, depressive symptoms, post-traumatic stress disorder (PTSD) symptom severity, and history of traumatic brain injury (TBI).Results:There was no main effect of diabetes on memory, attention/executive functioning, or language performance, and higher Aß PET SUVR was only associated with worse attention/executive functioning performance (ß=-.146, 95% CI [-.261, -.031], p=.013). The Aß PET x T2D interaction was significant for attention/executive functioning such that higher Aß PET SUVR was associated with lower attention/executive functioning scores, but only in those with T2D (ß=-.116, [-.225, -.006], p=.038). This interaction was not significant for language or memory.Conclusions:The results show that Aß may negatively impact attention/executive functioning, but this effect was only found in Veterans with T2D. Prior work has suggested that T2D may be more associated with tau biomarkers than markers of Aß, so it is possible that the current results are due to a compounding effect of Aß pathology plus microvascular and/or tau pathology. Notably, the sample was relatively young, a relatively large proportion had elevated PTSD symptoms and/or a TBI history (which have both been shown to relate to attention/executive function), and the measures that made up the attention/executive composite (Trail Making Test A and B) have been shown to be particularly sensitive - all of which may have contributed to the domain-specific effects. Future research is needed to investigate the role that tau and vascular pathology may play in cognition among individuals with T2D. Longitudinal studies are also needed to better understand the timing and progression of these relationships.

543-P: A Peer-Led Diabetes Self-Management Education (DSME) and Support (DSMS) Intervention for Black Men with Type 2 Diabetes—Results of a Three-Month Pilot Randomized Clinical Control Trial

Black men are disproportionately impacted by Type 2 diabetes (T2D) and are more likely to die from diabetes complications than non-Hispanic White men. To address the unique challenges this group faces in diabetes self-management, we implemented a 3-month peer-led and empowerment-based DSME/S intervention in metro-Detroit. Twenty-five Black men ≥55 years of age with self-reported T2D were recruited and randomized to either the intervention group (n=12) − 10 hours of DSME and 9 hours of DSMS, or to an enhanced usual care (EUC) group (n=13) − 10 hours of DSME. Peer leaders (n=3), trained by certified diabetes care and education specialists (CDCES) who used training materials related to Black men with diabetes, led the sessions (mean age: 59.7 years; 100% Black, male, and with at least some college education). Changes in A1C levels, diabetes self-care activities, and diabetes distress levels were assessed at baseline and post-intervention. In the intervention group, the mean A1C at baseline was 7.73%, SD 2.16, and at follow-up, 7.06%, SD 1.39. The EUC group experienced a 0.13% decrease in A1C levels (p = 0.68). Within the intervention group, differences in average diet and blood-glucose testing scores, both measured using the Summary of Diabetes Self-Care Activities (SDSCA) measure, from baseline were statistically significant [(p = 0.03, mean change: 1.32, SD 1.71) and (p &amp;lt; 0.05, mean change: 0.50, SD 0.74), respectively]; EUC group general diet scores were: p = 0.08, mean change: 1.77. Diabetes distress scores among those who attended 1-6 sessions, ≤ 50%, (n=4): p = 0.92, mean change: −0.75, SD 14.06. Of those who attended 7-12 sessions, &amp;gt; 50%, (n=7), the decrease in score was statistically significant: p = 0.003, mean change: −5.71, SD 3.20. Implementing a peer-led DSMS program for Black men was feasible, adopted, and led to positive changes in outcomes. Scaling up the program is warranted to measure sustainability. Disclosure A.Ewen: None. K.A.Kloss: None. R.Nwankwo: None. M.M.Funnell: None. G.Piatt: None. J.M.Hawkins: None. Funding National Institute on Aging (2P30AG024824–16); Blue Cross Blue Shield Foundation of Michigan (003063.MG)

0818 Comorbid obstructive sleep apnea and insomnia in type 2 diabetes: Association with diabetes-related distress and glycemic control

Abstract Introduction It is unclear how comorbid insomnia and sleep duration may influence diabetes-related distress and glycemic control in adults with obstructive sleep apnea (OSA) and type 2 diabetes (T2D). This analysis examined whether diabetes-related distress mediates the associations of OSA and insomnia severity with glycemic control in adults with T2D and OSA based on sleep duration. Methods This study was a secondary analysis of merged baseline assessment data from two clinical trials of adults (N=240) with self-reported T2D and OSA. OSA (apnea-hypopnea index ≥ 5) was determined by a home sleep study. Participants completed questionnaires to elicit insomnia severity, diabetes-related distress, sleep duration, daytime sleepiness, and global sleep quality. Sleep duration was classified as normal (&amp;gt;6 h) or short (≤ 6h). Glycemic control was measured by HbA1c (%). Mediation analyses with bootstrapped samples were employed after controlling for sociodemographic covariates in participants with normal and short sleep durations. Results More participants (mean age 57.8 years; 49.6% female; 65% White; 56.3% post high school education, mean HbA1c 7.93%) had short sleep duration (n=128; 53.5%) than normal sleep duration (n=111, 46.5%). Participants with short sleep duration had significantly worse sleep quality, daytime sleepiness, insomnia, and HbA1c levels compared to those with normal sleep duration (all p&amp;lt;.05). In participants with normal sleep duration, insomnia severity was associated with diabetes-related distress (b=0.942, p=0.008); diabetes-related distress did not mediate the association between insomnia severity and HbA1c (indirect effect [IE]=0.013, 95% CI: -0.003, 0.036). In participants with short sleep duration, insomnia severity was significantly associated with diabetes-related distress (b=1.470, p&amp;lt; 0.001), and diabetes-related distress mediated the association between insomnia severity and HbA1c (IE=0.023, 95% CI: 0.001, 0.053). Regardless of sleep duration, OSA severity was not associated with diabetes-related distress or HbA1c. Conclusion Only among participants with short sleep duration, comorbid insomnia significantly contributes to greater diabetes-related distress, which leads to higher HbA1c levels. Short sleep duration in persons with insomnia could be a potential mechanism involved in the association between diabetes-related distress and glycemic control in adults with T2D and OSA. Support (if any) The NIH (R01- DK0960281; K24-NR016685) and the CTSI grants (UL1-RR024153; UL1-TR000005) funded the parent studies

Abstract P324: Female Reproductive Factors and Risk of Type 2 Diabetes and Cardiovascular Disease Among Women With a History of Gestational Diabetes

Introduction: The link between gestational diabetes mellitus (GDM) and long-term risk of type 2 diabetes (T2D) and cardiovascular disease (CVD) is well established; however, risk factors underlying the progression of disease remain uncertain. Hypothesis: Female reproductive factors including ages at menarche, menopause, and first birth, number of live births, and surgically-induced menopause (uni- or bilateral oophorectomy or hysterectomy) are associated with higher risk of progression, while breastfeeding is associated with lower risk of progression from GDM to T2D/CVD. Methods: Participants in the Nurses’ Health Study II reported reproductive history at cohort baseline and over follow-up, including 5346 women with a history of GDM. Self-reported incident T2D or CVD (myocardial infarction, coronary revascularization or stroke) were confirmed via questionnaire or medical records. We estimated the hazard ratios (HR [95%]) across quintiles of each reproductive factor with incident T2D and CVD using Cox models adjusting for age, race/ethnicity, smoking, BMI at 18 years, physical activity, family history of T2D or CVD, alcohol intake, menopausal status, aspirin use, and Alternate Healthy Eating Index. Results: We documented 988 incident T2D and 149 CVD cases over 25 years of follow-up. In adjusted models, higher total lactation duration was associated with lower risk of T2D (5 categories: 0, 1-6, 7-12, 13-24, &gt;24 months, p for trend=0.01; highest vs. lowest category: HR 0.77 [95%CI: 0.60, 0.98]) and CVD (p for trend=0.03, HR 0.39 [95%CI: 0.19, 0.80]). Early age at menarche was linearly associated with higher risk of T2D (5 categories: ≤11, 12, 13, 14, &gt;14 y: p for trend &lt;0.0001), lowest (≤11 y) vs. reference (13 y) category: HR 1.28 [95%CI: 1.06, 1.53], while no trend could be observed for CVD outcomes (p for trend=0.48). Higher age at 1 st birth was associated with lower CVD risk (5 categories: &lt;23, 23-25 [reference], 26-29, 30-34, ≥35 y, p for trend=0.001; highest vs reference category: HR 0.17 [95%CI: 0.05, 0.57]), but not T2D). Compared with natural menopause, surgically induced menopause was associated with higher T2D risk: 1.32 (1.00, 1.73). Number of live births and age at menopause were not associated with T2D or CVD among women with GDM history. Conclusions: Breastfeeding was associated with lower T2D and CVD risks among women with GDM history, suggesting some shared risk factors or etiologies across reproductive lifespan and long-term cardiometabolic health. Ages at menarche and 1 st birth showed differential associations with T2D and CVD.

Abstract P158: Intake of Chocolate by Subtypes and Risk of Type 2 Diabetes: Results From Three Prospective Cohort Studies

Backgrounds: Cocoa and cocoa flavonoids may exert health benefits including improving insulin sensitivity and lowering type 2 diabetes (T2D) risk. Previous studies have reported inverse associations between chocolate consumption and T2D risk, although it is largely unknown regarding whether the associations differ between dark chocolate and milk chocolate. The objective of this study is to prospectively examine the associations between the consumption of dark chocolate, milk chocolate, and total chocolate, and the risk of T2D, in three large cohort studies with repeat dietary measurements over 10 years of follow-up. Methods: Data from three prospective cohorts in the United States were used, including Nurses’ Health Study (2006-2020), Nurses’ Health Study II (2007-2019), and Health Professionals Follow-Up Study (2006-2020). Dark and milk chocolate consumption information was assessed at baseline and updated every 4 years through a validated food frequency questionnaire. Chocolate consumption was categorized into 4 groups: never or &lt;1 serving/month, 1 serving/month to 1 serving/week, 1-4 servings/week, and ≥5 servings/week. Self-reported T2D cases were confirmed using a supplementary questionnaire. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between total, dark, and milk chocolate intake, and the risk of T2D. Results: After adjusting for lifestyle and dietary risk factors for diabetes, compared to participants who never or rarely eat chocolate, those who consumed any chocolate ≥5 servings/week had a 22% (95% CI: 10% to 32%; p for trend = 0.0003) lower rate of T2D. For dark chocolate, those who consumed ≥5 servings/week had a non-significant 16% (95% CI: -2% to 31%; p for trend = 0.005) lower rate of T2D than those who never or rarely eat dark chocolate. The associations between milk chocolate intake and T2D risk are largely null. Spline regression shows an L-shaped non-linear dose-response relationship between total chocolate intake and the risk of T2D (p=0.02 for curvature). The risk reduction plateaus when the total chocolate intake is higher than 5 servings/week. There is a linear dose-response association between dark chocolate intake with the risk of T2D (p=0.006 for linearity). Conclusion: Higher consumption of total chocolate and especially dark chocolate was significantly associated with a lower risk of type 2 diabetes. These findings support the potential cardiometabolic benefits of consuming chocolates that are rich in flavonoids.

Association of alcohol drinking with incident type 2 diabetes and pre-diabetes: The Guangzhou Biobank Cohort Study.

We examined associations of baseline alcohol drinking with incident type 2 diabetes (T2D) or impaired fasting glucose (IFG), and explore whether the associations were modified by genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B). All participants were aged 50+ (mean=60.45; standard deviation=6.88) years. Information of alcohol consumption was collected at baseline from 2003 to 2008. Incident T2D was defined as fasting glucose ≥7.0mmol/L or post-load glucose ≥11.1mmol/L at follow-up examination (2008-2012), self-reported T2D and/or initiation of hypoglycaemia medication or insulin during follow-up. Impaired fasting glucose was defined as fasting glucose ≥5.6mmol/L and <7mmol/L. Of 15,716 participants without diabetes and 11,232 participants without diabetes and IFG at baseline, 1624 (10.33%) developed incident T2D and 1004 (8.94%) developed incident IFG during an average 4years of follow-up. After multivariable adjustments, compared with never drinking, occasional or moderate alcohol drinking was not associated with risk of incident hyperglycaemia (T2D+IFG) (odds ratio (OR)=1.10, 95% confidence interval (CI) 0.95-1.27, and 0.90 (0.69-1.18), respectively), whereas heavy alcohol drinking was associated with a higher risk of incident hyperglycaemia (T2D+IFG) (OR=1.82, 95% CI 1.24-2.68). No interactions of sex, overweight/obesity and genetic polymorphisms of ADH1B/ALDH2 genes with alcohol drinking on incident T2D and/or IFG were found (P for interaction from 0.12 to 0.85). Our results support a detrimental effect of heavy alcohol use on IFG and T2D. No protective effect was found for those carrying lower risk alleles for ADH1B/ALDH2 genes.

Relationship Between Type 2 Diabetes Control and Cognition in Older Adults: Findings From NHANES

Cognitive health has emerged as an important public health concern for America’s aging population. Type 2 Diabetes (T2D) may be associated with an exacerbated decline in cognitive performance. This study aimed to examine the relationship between T2D control and cognitive performance in older adults (≥60 years) using the 2013-2014 National Health and Nutrition Examination Surveys. Participants who completed the following cognitive assessments were included: 1) Consortium to Establish a Registry for Alzheimer’s Disease Word List (CERAD-WL), 2) Animal Fluency (AF), 3) Digit Symbol Substitution Test (DSST) (higher scores associated with better cognition). Participants were stratified by four groups: no T2D (N=557), treated/controlled T2D (controlled; N=41), treated/uncontrolled T2D (uncontrolled; N=120), untreated T2D (N=86), based on self-reported T2D treatment, fasting plasma glucose, and hemoglobin A1c. Logistic regression was used to examine the relationship between T2D control and cognition. We observed that those with uncontrolled and untreated T2D each had ~15% lower DSST than those with no T2D (P<0.01). CERAD-WL and AF were similar across all groups. Unadjusted analyses showed that individuals with 1) lower CERAD-WL were more likely to have controlled and untreated T2D, 2) lower AF were more likely to have controlled and uncontrolled T2D, and 3) lower DSST were more likely to have uncontrolled and untreated T2D (P’s<0.05). After adjusting for significant demographics and cardiovascular risk factors, only having uncontrolled T2D was associated with lower DSST (β=-3.164, P=0.04). These data indicate the need for longitudinal studies to further explore dynamic relationship and causal pathway between T2D control and cognitive impairment.

Dietary Patterns Characterized by Fat Type in Association with Obesity and Type 2 Diabetes: A Longitudinal Study of UK Biobank Participants.

The fat type consumed is considered a risk factor for developing obesity and type 2 diabetes (T2D). However, these associations have not been investigated using a dietary patterns approach, which can capture combinations of foods and fat type consumed. This study aimed to investigate associations between dietary patterns with varying proportions of SFAs, MUFAs, or PUFAs and obesity, abdominal obesity, and self-reported T2D incidence. This study included UK Biobank participants with 2 or more 24-h dietary assessments, free from the outcome of interest at recruitment, and with outcome data at follow-up (n=16,523; mean follow-up: 6.3 y). Reduced rank regression was used to derive dietary patterns with SFAs, MUFAs, and PUFAs (% of energy intake) as response variables. Logistic regression, adjusted for sociodemographic and health characteristics, was used to investigate the associations between dietary patterns and obesity [BMI (kg/m2) ≥30], abdominal obesity (waist circumference; men: ≥102cm; women: ≥88cm) and T2D incidence. Two dietary patterns, DP1 and DP2, were identified: DP1 positively correlated with SFAs (r = 0.48), MUFAs (r = 0.67), and PUFAs (r = 0.56), characterized by higher intake of nuts, seeds, and butter and lower intake of fruit and low-fat yogurt; DP2 positively correlated with SFAs (r = 0.76) and negatively with PUFAs (r = -0.64) and MUFAs (r = -0.01), characterized by higher intake of butter and high-fat cheese and lower intake of nuts and seeds. Only DP2 was associated with higher obesity and abdominal obesity incidence (OR: 1.24; 95% CI: 1.02, 1.45; and OR: 1.19; 95% CI: 1.02, 1.38, respectively). Neither of the dietary patterns was associated with T2D incidence. These findings provide evidence that a dietary pattern characterized by higher SFA and lower PUFA foods is associated with obesity and abdominal obesity incidence, but not T2D.

The gut microbiome and type 2 diabetes status in the Multiethnic Cohort.

BackgroundThe gut microbiome may play a role in inflammation associated with type 2 diabetes (T2D) development. This cross-sectional study examined its relation with glycemic status within a subset of the Multiethnic Cohort (MEC) and estimated the association of circulating bacterial endotoxin (measured as plasma lipopolysaccharide-binding protein (LBP)) with T2D, which may be mediated by C-reactive protein (CRP).MethodsIn 2013–16, cohort members from five ethnic groups completed clinic visits, questionnaires, and stool and blood collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose >125 and 100–125 mg/dL were classified as undiagnosed (UT2D) and pre-diabetes (PT2D) cases, respectively. We characterized the gut microbiome through 16S rRNA gene sequencing and measured plasma LBP and CRP by standard assays. Linear regression was applied to estimate associations of the gut microbiome community structure and LBP with T2D status adjusting for relevant confounders.ResultsAmong 1,702 participants (59.9–77.4 years), 735 (43%) were normoglycemic (NG), 506 (30%) PT2D, 154 (9%) UT2D, and 307 (18%) T2D. The Shannon diversity index decreased (ptrend = 0.05), while endotoxin, measured as LBP, increased (ptrend = 0.0003) from NG to T2D. Of 10 phyla, Actinobacteria (ptrend = 0.007), Firmicutes (ptrend = 0.003), and Synergistetes (ptrend = 0.02) were inversely associated and Lentisphaerae (ptrend = 0.01) was positively associated with T2D status. Clostridium sensu stricto 1, Lachnospira, and Peptostreptococcaceae were less, while Escherichia-Shigella and Lachnospiraceae were more abundant among T2D patients, but the associations with Actinobacteria, Clostridium sensu stricto 1, and Escherichia-Shigella may be due metformin use. PT2D/UT2D values were closer to NG than T2D. No indication was detected that CRP mediated the association of LBP with T2D.ConclusionsT2D but not PT2D/UT2D status was associated with lower abundance of SCFA-producing genera and a higher abundance of gram-negative endotoxin-producing bacteria suggesting that the gut microbiome may contribute to chronic systemic inflammation and T2D through bacterial translocation.

The relationship between dietary exposure to persistent organic pollutants from fish consumption and type 2 diabetes among First Nations in Canada

ObjectiveWe previously examined the associations between dietary dichlorodiphenyldichloroethylene (DDE) and polychlorinated biphenyls (PCBs) intake from fish consumption and type 2 diabetes (T2D) prevalence in Ontario and Manitoba. This study aims to further explore the relationship in a regionally representative sample of First Nations adults living on-reserve across Canada.MethodsDietary, health and lifestyle data collected by the cross-sectional First Nations Food, Nutrition and Environment Study (2008–2018) were analyzed. This participatory study included 6091 First Nations adult participants who answered questions on T2D. The consumption of locally caught fish was estimated with a food frequency questionnaire. A total of 551 samples from 96 fish species were collected and analyzed for the presence of DDE and PCBs. The associations between fish and dietary DDE/PCBs intake with self-reported T2D were investigated using multiple logistic regression models adjusted for confounders.ResultsDietary exposure to DDE (>2.11 ng/kg/bw) and PCBs (>1.47 ng/kg/bw) vs no exposure was positively associated with T2D with ORs of 2.33 (95% CI: 1.24–4.35) for DDE and 1.43 (95% CI: 1.01–3.59) for PCBs. The associations were stronger among females (DDE OR = 3.11 (1.41–6.88); PCBs OR = 1.76 (1.10–3.65)) and older individuals (DDE OR = 2.64 (1.12–6.20); PCBs OR = 1.44 (1.01–3.91)) as compared with males and younger participants. Also, significant dose-response relationships were found for fish consumption in females only.ConclusionThis study confirms our previous findings that dietary DDE/PCBs exposure may increase the risk of T2D. The effect of DDE/PCBs from fish consumption is driven by geographical differences in DDE/PCBs concentrations in fish and by the amount of fish consumed, and is more prominent in females than in males.

A prospective study of type 2 diabetes, metformin use, and risk of breast cancer

Type 2 diabetes (T2D) has been associated with increased breast cancer risk, but commonly prescribed antidiabetic medications such as metformin may reduce risk. Few studies have investigated T2D and medications together in relation to breast cancer. Data came from 44541 Sister Study participants aged 35 to 74 years at enrollment (2003-2009) who satisfied eligibility criteria, followed through 15 September 2017. Information on time-varying, self-reported, physician-diagnosed, prevalent and incident T2D, use of antidiabetic medications, and covariates was obtained from baseline and follow-up questionnaires. Incident breast cancers were confirmed with medical records. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated. During follow-up (median, 8.6 years), 2678 breast cancers were diagnosed at least 1 year after enrollment. There were 3227 women (7.2%) with prevalent and 2389 (5.3%) with incident T2D, among whom 61% (n= 3386) were ever treated with metformin. There was no overall association between T2D and breast cancer risk (HR 0.99; 95% CI, 0.87-1.13). However, T2D was associated with increased risk of triple-negative breast cancer (HR 1.40; 95% CI, 0.90-2.16). Compared with not having T2D, T2D with metformin use was not associated with overall breast cancer risk (HR 0.98; 95% CI, 0.83-1.15), but it was associated with decreased risk of estrogen receptor (ER)-positive breast cancer (HR 0.86; 95% CI 0.70-1.05) and increased risk of ER-negative (HR 1.25; 95% CI, 0.84-1.88) and triple-negative breast cancer (HR 1.74; 95% CI, 1.06-2.83). The inverse association with ER-positive cancer was stronger for longer duration (≥10 year) metformin use (HR 0.62; 95% CI, 0.38-1.01; P for trend= 0.09). Results were supported by sensitivity analyses. Our findings suggest that associations between T2D and breast cancer may differ by hormone receptor status and that associations between T2D and ER-positive breast cancer may be reduced by long-term metformin use.

A Behavioral Lifestyle Intervention to Improve Frailty in Overweight or Obese Older Adults with Type 2 Diabetes: A Feasibility Study.

BackgroundOlder adults with Type 2 diabetes (T2D) are more likely to be frail, which increases the risk for disability and mortality.ObjectivesTo determine the feasibility of a behavioral lifestyle intervention, enhanced with mobile health technology for self-monitoring of diet and activity, to improve frailty in overweight/obese older adults (≥65 years) diagnosed with T2D.Design, Setting, and ParticipantsSingle arm, 6-month study of a behavioral lifestyle intervention in 20 overweight/obese (BMI>25) older adults (≥ 65 years) with self-reported T2D diagnosis who owned a smartphone. A Fitbit tracker was provided to all participants for self-monitoring of diet and physical activity. Our primary outcome of feasibility was measured by session attendance, adherence to Fitbit usage to self-monitor diet and physical activity, and study retention. Secondary outcomes included the preliminary efficacy of the intervention on frailty, physical function, quality of life, and T2D-related outcomes.ResultsEighteen participants completed the study. The mean age was 71.5 (SD ± 5.3) years, 56% were female, and half were Hispanic. At baseline, 13 (72%) were pre-frail, 4 (22%) were frail, and 1 (6%) were non-frail. At follow-up, frailty scores improved significantly from 1.61 ± 1.15 to 0.94 ± 0.94 (p=0.01) and bodyweight improved from 205.66 ± 45.52 lbs. to 198.33 ± 43.6 lbs. (p=<0.001).ConclusionThis study provides evidence for the feasibility of a behavioral lifestyle intervention in overweight/obese older adults with T2D and preliminary results support its potential efficacy in improving frailty score.

Test-Retest Reliability of activPAL in Measuring Sedentary Behavior and Physical Activity in People With Type 2 Diabetes.

To investigate how changes in sedentary behavior relate to health outcomes, it is important to establish the test-retest reliability of activity monitors in measuring habitual sedentary behavior in people with type 2 diabetes (T2D) as a prerequisite for interpreting this information. Thus, the authors' objective was to examine the test-retest reliability of a common activity monitor (activPAL™) in measuring sedentary behavior and physical activity in people with T2D. Sedentary-time, standing-time, stepping-time, step-count, and sit-to-stand transitions were obtained from two 7-day assessment periods separated by at least 1 week. Test-retest reliability was determined with the intraclass correlation coefficient (ICC) to compare sedentary and activity measures between the 2 time points. A total of 30 participants with self-reported T2D completed the study (age 65 [6]y, 63% women, body mass index 33.3 [5] kg/m2). High test-retest reliability was found for sedentary-time (ICC = .79; 95% confidence interval [CI], .61-.89) and standing-time (ICC = .74; 95% CI, .53-.87). Very high test-retest reliability was found for stepping-time (ICC = .90; 95% CI, .81-.95), step-count (ICC = .91; 95% CI, .83-.96), and sit-to-stand transitions (ICC = .90; 95% CI, .79-.95). The activPAL™ device showed high to very high test-retest reliability in measuring all tested activity categories in people with T2D.

Association between Walking Pace and Diabetes: Findings from the Chilean National Health Survey 2016-2017.

Background: Walking pace is a well-known indicator of physical capability, but it is also a strong predictor of type 2 diabetes (T2D). However, there is a lack of evidence on the association between walking pace and T2D, specifically, within developing countries such as Chile. Aim: To investigate the association between self-reported walking pace and T2D in the Chilean adult population. Methods: 5520 Chilean participants (aged 15 to 90 years, 52.1% women) from the Chilean National Health Survey 2016–2017 were included in this cross-sectional study. Both walking pace (slow, average, and brisk) and diabetes data were collected through self-reported methods. Fasting blood glucose (reported in mg/dl) and glycosylated haemoglobin A (HbA1c) scores were determined via blood exams. Results: In the unadjusted model, and compared to people who reported a slow walking pace, those with average and brisk walking pace had lower blood glucose levels (β = −7.74 mg/dL (95% CI: −11.08 to −4.40) and β = −11.05 mg/dL (95% CI: −14.36 to −7.75), respectively) and lower HbA1c (β = −0.34% (95% CI: −0.57 to −0.11) and β= −0.72% (95% CI: −0.94 to −0.49)), respectively. After adjusting for sociodemographic, Body Mass Index and lifestyle factors, the association between glycaemia and HbA1c remained only for brisk walkers. Both the average and brisk walker categories had lower odds of T2D (OR: 0.59 (95% CI: 0.41 to 0.84) and (OR 0.48 (95% CI: 0.30 to 0.79), respectively). Conclusion: Brisk walkers were associated with lower blood glucose and HbA1c levels. Moreover, average to brisk walking pace also showed a lower risk for T2D.

Cooking Oil Consumption Is Positively Associated with Risk of Type 2 Diabetes in a Chinese Nationwide Cohort Study

Evidence suggests that the relations between intakes of individual fatty acids and risk of type 2 diabetes (T2D) vary. However, associations between intakes of different cooking oils as sources of fatty acids and incident T2D remain largely unknown. We aimed to evaluate relations between intakes of individual cooking oils and incident T2D in a nationwide Chinese cohort. Overall 15,022 Chinese adults aged≥20 y from the China Health and Nutrition Survey (CHNS) without self-reported T2D at entry in the 1997, 2000, 2004, 2006, or 2009 rounds were followed up until 2011. Consumption of various cooking oils/fats including lard, peanut oil, soybean oil, canola oil, sesame oil, and refined blended plant oil was assessed using 3-d 24-h records in each survey and the cumulative mean intake was calculated. Multivariable-adjusted Cox proportional hazards regression models were constructed to estimate the HRs of T2D. A total of 1014 cases were recorded after a median follow-up of 14 y. The intakes of animal and plant cooking oils/fats were both associated with higher T2D risk. Compared with nonconsumers, multivariable-adjusted HRs and 95% CIs for the highest tertiles were 1.31 (1.03, 1.67) for lard, 1.36 (1.10, 1.66) for peanut oil, 1.14 (0.91, 1.43) for soybean oil, 1.11 (0.87, 1.43) for canola oil, 1.02 (0.79, 1.32) for sesame oil, and 1.42 (1.12, 1.82) for refined blended plant oil. Substituting 1 tablespoon/d (8 g · 2000 kcal-1 · d-1) of soybean oil for the sum of lard, peanut oil, refined blended plant oil, and other plant oils was associated with a 3% (HR: 0.97; 95% CI: 0.95, 0.99) lower risk of T2D. Intakes of lard, peanut oil, and refined blended plant oil but not soybean oil, canola oil, and sesame oil are associated with higher T2D risk. Reducing the consumption of cooking oils in general may be protective against T2D among the Chinese population.This trial was registered at clinicaltrials.gov as NCT03259321.

1373-P: Adherence to Healthy Lifestyle on Subsequent Risk of Type 2 Diabetes (T2D) among Women with a History of Gestational Diabetes Mellitus (GDM): A Prospective Cohort Study

Background: Women with a history of GDM are at exceptionally high risk of T2D but adopting a healthy lifestyle may mitigate this risk. Methods: We analyzed 4,287 women with a prior clinician diagnosis of GDM from the Nurses’ Health Study II cohort as part of the Diabetes and Women’s Health Study. Healthy lifestyle factors, which were assessed every 2-4 years, included no current smoking, normal body mass index (&amp;lt;25 kg/m2), regular moderate-to-vigorous physical activity (&amp;gt;500 MET-min/week), high-quality diet (above median for the Alternative Healthy Eating Index), and moderate alcohol consumption (&amp;gt;0-15 g/day). Self-reported incident T2D was confirmed via validated supplementary questionnaire (98% concordance with medical records). Multivariate-adjusted Cox models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI), adjusting for demographic, reproductive, and clinical characteristics. Results: We ascertained 835 incident T2D cases during a median 27.9 years of follow-up. Compared to women reporting no healthy lifestyle factors, HR (95% CI) for risk of T2D among those with 1, 2, 3, 4, or 5 factors were 0.91 (0.64, 1.30), 0.62 (0.44, 0.87), 0.45 (0.31, 0.64), 0.33 (0.22, 0.48), and 0.13 (0.06, 0.28), respectively (P&amp;lt;trend&amp;lt;0.001) (Table 1). When number of health lifestyle factors was modeled continuously, each additional factor was associated with a 29% lower risk of T2D, HR (95% CI): 0.71 (0.67, 0.76). In addition, &amp;gt;86% (population attributable risk [PAR]%: 86.3%; 95% CI: 70.6%, 93.7%) of T2D cases were theoretically preventable if participants had adherence to all 5 healthy lifestyle factors. Conclusion: Adherence to healthy lifestyle factors was associated with a substantially lower likelihood of progressing to T2D in women with a history of GDM, and strategies to improve long-term adherence are warranted. Disclosure F. Qian: None. J.E. Chavarro: None. S.H. Ley: None. D. Tobias: None. E. Yeung: None. M. Li: None. A. Liu: None. J. Mills: None. Q. Sun: None. F. Hu: None. C. Zhang: None.

The Gut Microbiome and Diabetes Status in the Multiethnic Cohort

Abstract Objectives As features of the gut microbiome may promote the development of type 2 diabetes (T2D), we examined the hypothesis that gut microbiome composition differs by glycemic/diabetes status within a subset of the Multiethnic Cohort. We also estimated the association of lipopolysaccharide-binding protein (LBP) as a measure of circulating bacterial endotoxin with T2D. This outer membrane component of gram-negative bacteria may affect glucose metabolism. Methods In 2013–16, cohort members from 5 ethnic groups completed clinic visits, questionnaires, and stool collections. Participants with self-reported T2D and/or taking medication were considered T2D cases. Those with fasting glucose &amp;gt;125 and 100–125 mg/dL were classified as undiagnosed (UT2D) and prediabetes (PT2D). We characterized the gut microbiome through 16S rRNA gene sequencing (V1-V3). Plasma LBP was measured by ELISA. Linear regression was applied to estimate associations of gut microbiome community structure and LBP with T2D status adjusting for relevant confounders. Results Among 1756 participants (59.9–77.4 years), 315 (18%) were T2D, 158 (9%) UT2D, 518 (29%) PT2D, and 765 (44%) normoglycemic (NG). The Shannon diversity index was lower (6.30, 6.25, 6.28, 6.18; P = 0.02) and LBP was higher (26.0, 26.6, 28.6, 28.2 µg/mL; P = 0.0009) in T2D than NG participants. Of 10 phyla, Actinobacteria and Firmicutes were inversely associated with T2D status (P = 0.004). Six of 161 genera were significantly related to T2D status after Bonferroni adjustment: the abundance of Clostridium sensu stricto 1, Lachnospira, Lachnospiraceae NC2004, and Peptostreptococcaceae was lower, while Lachnospiraceae uncultured and Escherichia-Shigella were more abundant among T2D than NG participants. In general, those with PT2D and UT2D had values closer to NG than T2D individuals. Conclusions Participants with T2D showed a lower abundance of bacteria capable of fermenting plant polysaccharides and higher levels of gram-negative endotoxin-producing bacteria indicating that a less favorable pattern of gut microbiome community structure may contribute to T2D through endotoxin binding to toll-like receptors via LBP and activation of the NFkB pathway associated with chronic systemic inflammation. Funding Sources NIH grants P01CA169530, U01CA164973, P30CA071789, #UL1TR000130, R01HL140335.