Risk of Foot Ulcer and Lower-Extremity Amputation Among Participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Objective: Intensive glycemic control reduces risk of kidney, retinal, and neurologic complications in type 1 diabetes (T1D), but whether it reduces risk of lower extremity complications is unknown. We examined whether former intensive versus conventional glycemic control among Diabetes Control and Complications Trial (DCCT) participants with T1D reduced the long-term risk of diabetic foot ulcers (DFU) and lower extremity amputations (LEA) in the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) study. <p>Research Design and Methods: DCCT participants [n=1441] completed 6.5 years on average of intensive vs conventional diabetes treatment, after which 1408 were enrolled in EDIC and followed annually over 23 years for DFU and LEA occurrences by physical examination. Multivariable Cox models estimated associations of DCCT treatment assignment and time-updated exposures with DFU or LEA. </p> <p>Results: Intensive versus conventional glycemic control was associated with a significant risk reduction for all DFU (Hazard Ratio [HR] 0.77, 95% CI 0.60 to 0.97), and a similar magnitude but nonsignificant risk reduction for first recorded DFU (HR 0.78, 95% CI 0.59 to 1.03) and first LEA (HR 0.70, 95% CI 0.36 to 1.36). In adjusted Cox models, clinical neuropathy, lower sural nerve conduction velocity and cardiovascular autonomic neuropathy were associated with higher DFU risk; eGFR < 60 mL/min/1.73 m², albuminuria, and macular edema with higher LEA risk; and any retinopathy and greater time-weighted mean DCCT/EDIC HbA1c with higher risk of both outcomes (p<0.05).</p> <p>Conclusions: Early intensive glycemic control decreases long-term DFU risk, the most important antecedent in the causal pathway to LEA.</p>

Risk of Foot Ulcer and Lower-Extremity Amputation Among Participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

Objective: Intensive glycemic control reduces risk of kidney, retinal, and neurologic complications in type 1 diabetes (T1D), but whether it reduces risk of lower extremity complications is unknown. We examined whether former intensive versus conventional glycemic control among Diabetes Control and Complications Trial (DCCT) participants with T1D reduced the long-term risk of diabetic foot ulcers (DFU) and lower extremity amputations (LEA) in the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) study. <p>Research Design and Methods: DCCT participants [n=1441] completed 6.5 years on average of intensive vs conventional diabetes treatment, after which 1408 were enrolled in EDIC and followed annually over 23 years for DFU and LEA occurrences by physical examination. Multivariable Cox models estimated associations of DCCT treatment assignment and time-updated exposures with DFU or LEA. </p> <p>Results: Intensive versus conventional glycemic control was associated with a significant risk reduction for all DFU (Hazard Ratio [HR] 0.77, 95% CI 0.60 to 0.97), and a similar magnitude but nonsignificant risk reduction for first recorded DFU (HR 0.78, 95% CI 0.59 to 1.03) and first LEA (HR 0.70, 95% CI 0.36 to 1.36). In adjusted Cox models, clinical neuropathy, lower sural nerve conduction velocity and cardiovascular autonomic neuropathy were associated with higher DFU risk; eGFR < 60 mL/min/1.73 m², albuminuria, and macular edema with higher LEA risk; and any retinopathy and greater time-weighted mean DCCT/EDIC HbA1c with higher risk of both outcomes (p<0.05).</p> <p>Conclusions: Early intensive glycemic control decreases long-term DFU risk, the most important antecedent in the causal pathway to LEA.</p>

Risk of Foot Ulcer and Lower-Extremity Amputation Among Participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study

OBJECTIVE Intensive glycemic control reduces the risk of kidney, retinal, and neurologic complications in type 1 diabetes (T1D), but whether it reduces the risk of lower-extremity complications is unknown. We examined whether former intensive versus conventional glycemic control among Diabetes Control and Complications Trial (DCCT) participants with T1D reduced the long-term risk of diabetic foot ulcers (DFUs) and lower-extremity amputations (LEAs) in the subsequent Epidemiology of Diabetes Interventions and Complications (EDIC) study. RESEARCH DESIGN AND METHODS DCCT participants (n = 1,441) completed 6.5 years on average of intensive versus conventional diabetes treatment, after which 1,408 were enrolled in EDIC and followed annually over 23 years for DFU and LEA occurrences by physical examination. Multivariable Cox proportional hazard regression models estimated associations of DCCT treatment assignment and time-updated exposures with DFU or LEA. RESULTS Intensive versus conventional glycemic control was associated with a significant risk reduction for all DFUs (hazard ratio 0.77 [95% CI 0.60, 0.97]) and a similar magnitude but nonsignificant risk reduction for first-recorded DFUs (0.78 [0.59, 1.03]) and first LEAs (0.70 [0.36, 1.36]). In adjusted Cox models, clinical neuropathy, lower sural nerve conduction velocity, and cardiovascular autonomic neuropathy were associated with higher DFU risk; estimated glomerular filtration rate &lt;60 mL/min/1.73 m2, albuminuria, and macular edema with higher LEA risk; and any retinopathy and greater time-weighted mean DCCT/EDIC HbA1c with higher risk of both outcomes (P &lt; 0.05). CONCLUSIONS Early intensive glycemic control decreases long-term DFU risk, the most important antecedent in the causal pathway to LEA.

Network Mendelian randomization study: exploring the causal pathway from insomnia to type 2 diabetes

IntroductionInsomnia is a novel pathogen for type 2 diabetes mellitus (T2DM). However, mechanisms linking insomnia and T2DM are poorly understood. In this study, we apply a network Mendelian randomization (MR) framework to determine the causal association between insomnia and T2DM and identify the potential mediators, including overweight (body mass index (BMI), waist-to-hip ratio, and body fat percentage) and glycometabolism (HbA1c, fasting blood glucose, and fasting blood insulin).Research design and methodsWe use the MR framework to detect effect estimates of the insomnia–T2DM, insomnia–mediator, and mediator–T2DM associations. A mediator between insomnia and T2DM is established if MR studies in all 3 steps prove causal associations.ResultsIn the Inverse variance weighted method, the results show that insomnia will increase the T2DM risk (OR 1.142; 95% CI 1.072 to 1.216; p=0.000), without heterogeneity nor horizontal pleiotropy, strongly suggesting that genetically predicted insomnia has a causal association with T2DM. Besides, our MR analysis provides strong evidence that insomnia is causally associated with BMI and body fat percentage. There is also suggestive evidence of an association between insomnia and the waist-to-hip ratio. At the same time, our results indicate that insomnia is not causally associated with glycometabolism. Higher BMI, waist-to-hip ratio, and body fat percentage levels are strongly associated with increased risk of T2DM.ConclusionsGenetically predicted insomnia has a causal association with T2DM. Being overweight (especially BMI and body fat percentage) mediates the causal pathway from insomnia to T2DM.

Gene-Environment Causal Pathway to Impoverished Cognitive Development Contributes to Psychotic-Like Experience in Children

Identifying the social and biological mechanisms of cognitive and psychological development of children is essential for optimizing preventive and educational efforts. However, the causal pathways by which genetic and environmental factors affect cognitive and psychiatric outcomes remain unknown, especially in early childhood. We examined the causal relationships among genes, the environment, intelligence, and psychotic-like experiences in 7,632 multiethnic (5,905 with European ancestry) children aged 9-10 years old from the Adolescent Brain Cognitive Development (ABCD) Study. Using up-to-date computational causal analysis and rigorous path modeling, we found a significant causal influence of residential, family, and school environments and genome-wide polygenic scores of cognitive capacities on preadolescents' psychotic-like experiences mediated by intelligence. Mitigation of good parenting behavior and positive school environments on psychotic-like experiences dominated the pernicious effects of genetic and residential adversities. Our findings support that intelligence may be a biological resilience factor for psychosis. To the best of our knowledge, this is the first study to identify casual trajectories of neurocognitive development in early childhood and the first to provide empirical evidence that positive parenting behavior and school environment can impose a considerable degree of causal impact on children's cognitive and psychiatric outcomes. We suggest the implementation of socioeconomic policies to improve family and school environments and promote local economic development to enhance children's cognitive ability and mental health.

Unintentional Inception: When a Premium Is Offered to Unintentional Creations

Creations can be fundamentally intended or unintended from their outset. Past work has focused on intentional creations, finding that people place a premium on effort. We examine the role of unintentionality in the inception of creations in six studies using a variety of stimuli ( N = 1,965), finding that people offer a premium to unintentional creations versus otherwise identical intentional creations. We demonstrate that the unintentionality involved in the inception of a creation results in greater downward counterfactual thought about how the unintentional creation may have never been created at all, and this in turn heightens perceptions that the creation was a product of fate, causing people to place a premium on such creations. We provide evidence for this causal pathway using a combination of mediation and moderation approaches. Further, we illuminate that this premium is not offered when a negative outcome is ascribed to an unintentional creation.

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&lt;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&lt;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.

Using Theory of Change to inform the design of the HIV+D intervention for integrating the management of depression in routine HIV care in Uganda

There is growing recognition of the burden of depression in people living with HIV/AIDS (PLWHA), associated with negative behavioural and clinical outcomes. Unfortunately, most HIV care providers in sub-Saharan Africa do not routinely provide mental health services to address this problem. This article describes the process of developing a model for integrating the management of depression in HIV care in Uganda. Theory of Change (ToC) methodology was used to guide the process of developing the model. Three successive ToC workshops were held with a multi-disciplinary group of 38 stakeholders within Wakiso district, in the Central region of Uganda. The first 2 workshops were for generating practical ideas for a feasible and acceptable model of integrating the management of depression in HIV care at all levels of care within the district healthcare system; while the third and final workshop was for consensus building. Following meaningful brainstorming and discussions, the stakeholders suggested improved mental wellbeing among PLWHA as the ultimate outcome of the program. This would be preceded by short-term and intermediate outcomes including reduced morbidity among persons with HIV attributable to depression, allocation of more resources towards management of depression, increased help-seeking among depressed PLWHA and more health workers detecting and managing depression. These would be achieved following several interventions undertaken at all levels of care. The participants further identified some indicators of successful implementation such as emphasis of depression management in the district healthcare plans, increased demand for anti-depressants etc; as well as various assumptions underlying the intervention. All these were graphically aligned in a causal pathway, leading to a ToC map, contextualizing and summarizing the intervention model. The ToC was a valuable methodology that brought together stakeholders to identify key strategies for development of a comprehensible contextualized intervention model for managing depression within HIV care in Uganda; allowing greater stakeholder engagement and buy-in.

Methods to Analyze Time-to-Event Data: The Cox Regression Analysis

The Cox model is a regression technique for performing survival analyses in epidemiological and clinical research. This model estimates the hazard ratio (HR) of a given endpoint associated with a specific risk factor, which can be either a continuous variable like age and C-reactive protein level or a categorical variable like gender and diabetes mellitus. When the risk factor is a continuous variable, the Cox model provides the HR of the study endpoint associated with a predefined unit of increase in the independent variable (e.g., for every 1-year increase in age, 2 mg/L increase in C-reactive protein). A fundamental assumption underlying the application of the Cox model is proportional hazards; in other words, the effects of different variables on survival are constant over time and additive over a particular scale. The Cox regression model, when applied to etiological studies, also allows an adjustment for potential confounders; in an exposure-outcome pathway, a confounder is a variable which is associated with the exposure, is not an effect of the exposure, does not lie in the causal pathway between the exposure and the outcome, and represents a risk factor for the outcome.

A Critical Review of Social Resilience Properties and Pathways in Disaster Management

Resilience as a concept is multi-faceted with complex dimensions. In a disaster context, there is lack of consistency in conceptualizing social resilience. This results in ambiguity of its definition, properties, and pathways for assessment. A number of key research gaps exist for critically reviewing social resilience conceptualization, projecting resilience properties in a disaster-development continuum, and delineating a resilience trajectory in a multiple disaster timeline. This review addressed these research gaps by critically reviewing social resilience definitions, properties, and pathways. The review found four variations in social resilience definitions, which recognize the importance of abilities of social systems and processes in disaster phases at different levels. A review of resilience properties and pathways in the disaster resilience literature suggested new resilience properties—“risk-sensitivity” and “regenerative” in the timeline of two consecutive disasters. This review highlights a causal pathway for social resilience to better understand the resilience status in a multi-shock scenario by depicting inherent and adaptive resilience for consecutive disaster scenarios and a historical case study for a resilience trajectory in a multiple disaster timeline. The review findings will assist disaster management policymakers and practitioners to formulate appropriate resilience enhancement strategies within a holistic framework in a multi-disaster timeline.