Obesity and the development of type 2 diabetes: the effects of fatty tissue inflammation

Obesity is a worldwide epidemic with multiple obesity-associated health problems including type 2 diabetes, hypertension, and cardiovascular disease. Adipose tissue serves as a fuel storage depot, but also plays a pivotal role in homeostasis of energy expenditure, appetite regulation, glucose regulation, and immunity. Both genetics and environment play important roles in adipose tissue function and dysfunction. Obesity represents an abnormal accumulation of adipose tissue resulting from chronic overnutrition and reduced physical activity. The nature of this increased accumulation of fat tissue, whether hyperplasia or hypertrophy, local or ectopic, is associated with deleterious perturbations including excess fatty acid secretion, increased production of inflammatory cytokines, and abnormal adipocyte hormone signaling resulting in insulin resistance. In the setting of obesity, insulin resistance and chronic inflammation is postulated to play a role in development of type 2 diabetes and other obesity-related comorbidities including obstructive sleep apnea, hepatic steatosis, polycystic ovarian syndrome, hypertension and cardiovascular disease. Although the exact mechanism of these relationships are complex and not completely understood, the ability to store and limit fatty acid deposition to adipose tissue is a common component to remaining insulin sensitive, controlling the inflammatory cascade and reducing the risk of developing obesity-related comorbidities

Is margin all you need? An extensive empirical study of active learning on tabular data

Given a labeled training set and a collection of unlabeled data, the goal of active learning (AL) is to identify the best unlabeled points to label. In this comprehensive study, we analyze the performance of a variety of AL algorithms on deep neural networks trained on 69 real-world tabular classification datasets from the OpenML-CC18 benchmark. We consider different data regimes and the effect of self-supervised model pre-training. Surprisingly, we find that the classical margin sampling technique matches or outperforms all others, including current state-of-art, in a wide range of experimental settings. To researchers, we hope to encourage rigorous benchmarking against margin, and to practitioners facing tabular data labeling constraints that hyper-parameter-free margin may often be all they need

Confident Adaptive Language Modeling

Recent advances in Transformer-based large language models (LLMs) have led to significant performance improvements across many tasks. These gains come with a drastic increase in the models' size, potentially leading to slow and costly use at inference time. In practice, however, the series of generations made by LLMs is composed of varying levels of difficulty. While certain predictions truly benefit from the models' full capacity, other continuations are more trivial and can be solved with reduced compute. In this work, we introduce Confident Adaptive Language Modeling (CALM), a framework for dynamically allocating different amounts of compute per input and generation timestep. Early exit decoding involves several challenges that we address here, such as: (1) what confidence measure to use; (2) connecting sequence-level constraints to local per-token exit decisions; and (3) attending back to missing hidden representations due to early exits in previous tokens. Through theoretical analysis and empirical experiments on three diverse text generation tasks, we demonstrate the efficacy of our framework in reducing compute -- potential speedup of up to $\times 3$ -- while provably maintaining high performance

Cognitive Behavior Modification and Exercise + Group Counseling for Patients After Bariatric Surgery

The growing obesity epidemic is paralleled by an increasing number of bariatric surgeries. Patients lose significant weight within the first 12-18 months post-surgery with corresponding resolution of many co-morbidities. However, weight loss stabilizes after 18-24 months and 50% or more of patients eventually regain weight (Bond, Phelan, Leahey, Hill, & Wing, 2009; Magro, et al., 2008). Weight regain after loss is associated with return of co-morbidities and deteriorations in health-related quality of life and mood (Karlsson, Taft, Ryden, Sjostrom, & Sullivan, 2007). The purpose of this pilot study was to analyze the effects of a post-surgical behavioral plus counseling intervention on bariatric surgery patients who are struggling to maintain their weight loss ≥ 2 years after surgery. Methods: Project REACH (Relearn how to Eat, increase Activity and Create better Habits) was a 12-week intervention designed to change psychosocial mediators of health behaviors and fitness variables. Patients met for 1 hr each week for cognitive behavior modification and exercise instruction and practice followed by 1 hr of a closed counseling session. Psychosocial variables and fitness were measured before and after the intervention. Descriptive statistics, paired-samples t-tests, and Cohen’s d were applied to the data. Results: Eight women aged 39-68 yr (M = 54.37, SD = 9.62), BMI range 24.4-50.5 kg/m2 (M = 38.16, SD = 7.61) self-selected into the program. At the pre-test, BMI was correlated with diet/lifestyle self-efficacy (r = -.913, p = .002), social support for exercise-friends (r = -.800, p = .017), and exercise planning (r = -.730, p = .040). Distance walked in 6 min (6MWT) increased for the 4 women who completed the post-test (p = .040, d = 1.68). Changes in some fitness (e.g., BMI: d = -0.77) and psychosocial variables (e.g., exercise planning: d = 1.02; dietary cognitive restraint: d = 0.73) had medium and large effects. Conclusions: Targeting exercise, nutrition, and psychological issues together in an intervention can have positive effects on fitness and psychosocial factors that may help patients more than 2 yr post-surgery manage their weight

Effect of diabetes on caregiver burden in an observational study of individuals with Alzheimer’s disease

Background The burden on caregivers of patients with Alzheimer’s disease (AD) is associated with the patient’s functional status and may also be influenced by chronic comorbid medical conditions, such as diabetes. This post-hoc exploratory analysis assessed whether comorbid diabetes in patients with AD affects caregiver burden, and whether caregivers with diabetes experience greater burden than caregivers without diabetes. Caregiver and patient healthcare resource use (HCRU) were also assessed. Methods Baseline data from the GERAS observational study of patients with AD and their caregivers (both n = 1495) in France, Germany and the UK were analyzed. Caregiver burden was assessed using the Zarit Burden Interview (ZBI). Caregiver time on activities of daily living (ADL: basic ADL; instrumental ADL, iADL) and supervision (hours/month), and caregiver and patient HCRU (outpatient visits, emergency room visits, nights hospitalized) were assessed using the Resource Utilization in Dementia instrument for the month before the baseline visit. Regression analyses were adjusted for relevant covariates. Time on supervision and basic ADL was analyzed using zero-inflated negative binomial regression. Results Caregivers of patients with diabetes (n = 188) were younger and more likely to be female (both p < 0.05), compared with caregivers of patients without diabetes (n = 1307). Analyses showed caregivers of patients with diabetes spent significantly more time on iADL (+16 %; p = 0.03; increases were also observed for basic ADL and total caregiver time but did not reach statistical significance) and had a trend towards increased ZBI score. Patients with diabetes had a 63 % increase in the odds of requiring supervision versus those without diabetes (p = 0.01). Caregiver and patient HCRU did not differ according to patient diabetes. Caregivers with diabetes (n = 127) did not differ from those without diabetes (n = 1367) regarding burden/time, but caregivers with diabetes had a 91 % increase in the odds of having outpatient visits (p = 0.01). Conclusions This cross-sectional analysis found caregiver time on iADL and supervision was higher for caregivers of patients with AD and diabetes versus without diabetes, while HCRU was unaffected by patient diabetes. Longitudinal analyses assessing change in caregiver burden over time by patient diabetes status may help clarify the cumulative impact of diabetes and AD dementia on caregiver burden

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

METABOLIC SYNDROME IN NONDIABETIC, OBESE, FIRST-DEGREE RELATIVES OF AFRICAN AMERICAN PATIENTS WITH TYPE 2 DIABETES: AFRICAN AMERICAN TRIGLYCERIDES-HDL-C AND INSULIN RESISTANCE PARADOX

Objective: Metabolic syndrome (MetS) defines cardiovascular disease (CVD) risks. Despite higher rates of obesity, type 2 diabetes, and hypertension, African Americans have lower rates of MetS when compared to Caucasians, which is paradoxical, since African Americans are more insulin resistant and have higher rates of cardiovascular morbidity and mortality when compared to White Americans. We hypothesized that genetic inheritance predisposes African Americans to the greater cardiovascular risk and the associated morbidity and mortality. Therefore, we investigated the prevalence of components of MetS in obese, glucose-tolerant, first degree relatives of African American patients with type 2 diabetes. Methods: We examined the clinical and metabolic characteristics of 201 first-degree relatives (159 females and 42 males, mean age 41 6 8 years, and mean body mass index (BMI) of 32 6 8 (kg/m2). The subjects were categorized with MetS according to the Adult Treatment Panel (ATP) III criteria. Insulin sensitivity (Bergman minimal model method) and insulin resistance (homeostasis model assessment [HOMA]) were determined. We compared the clinical and metabolic characteristics in the relatives with and without MetS. Where appropriate, we compared the prevalence of the components of MetS in our African American sample with those of African American data in the National Health and Nutrition Evaluation Survey (NHANES) III. Results: Comparing the MetS group (n565) vs control subjects (n5136), the mean age, BMI, and percent body fat were greater in the MetS group. Mean fasting serum glucose, insulin and C-peptide levels were also greater in the MetS group. Insulin resistance index (HOMA-IR) was higher in the MetS group (HOMA-IR: 3.7 6 2.7 vs 2.2 6 1.7, P5.0002). Mean insulin sensitivity tended to be lower in the MetS group (2.16 6 2.64 vs 2.82 6 2.31, P5.08). In addition, despite the moderately severe insulin resistance, the MetS group had very low serum triglyceride levels and was the parameter least likely to meet the ATP criteria. The metabolic cutoff points for ATP III criteria were much lower in African American first-degree relatives with MetS. Of the five components of the ATP III criteria, waist circumference was the single most common parameter to likely meet the MetS criteria. We found that the prevalence of MetS was 29% in women and 40% in men when compared with 20.9% in African American women and 13.9% for African American men in the NHANES III. Conclusion: We found that: 1) the prevalence of MetS is higher in a subgroup of African Americans who were first-degree relatives of patients with type 2 diabetes than that of African Americans in the NHANES III; and 2) waist circumference rather than metabolic parameters was the single most important parameter and was more likely to meet the MetS criteria in African American relatives