A randomized controlled trial to test the effectiveness of two technology-enhanced diabetes prevention programs in primary care: The DiaBEAT-it study.

Objective: To evaluate the effectiveness of two technology-enhanced interventions for diabetes prevention among adults at risk for developing diabetes in a primary care setting. Methods: The DiaBEAT-it study employed a hybrid 2-group preference (Choice) and 3-group randomized controlled (RCT) design. This paper presents weight related primary outcomes of the RCT arm. Patients from Southwest Virginia were identified through the Carilion Clinic electronic health records. Eligible participants (18 and older, BMI ≥ 25, no Type 2 Diabetes) were randomized to either Choice (n = 264) or RCT (n = 334). RCT individuals were further randomized to one of three groups: (1) a 2-h small group class to help patients develop a personal action plan to prevent diabetes (SC, n = 117); (2) a 2-h small group class plus automated telephone calls using an interactive voice response system (IVR) to help participants initiate weight loss through a healthful diet and regular physical activity (Class/IVR, n = 110); or (3) a DVD with same content as the class plus the same IVR calls over a period of 12 months (DVD/IVR, n = 107). Results: Of the 334 participants that were randomized, 232 (69%) had study measured weights at 6 months, 221 (66%) at 12 months, and 208 (62%) at 18 months. Class/IVR participants were less likely to complete weight measures than SC or DVD/IVR. Intention to treat analyses, controlling for gender, race, age and baseline BMI, showed that DVD/IVR and Class/IVR led to reductions in BMI at 6 (DVD/IVR -0.94, p < 0.001; Class/IVR -0.70, p < 0.01), 12 (DVD/IVR -0.88, p < 0.001; Class/IVR-0.82, p < 0.001) and 18 (DVD/IVR -0.78, p < 0.001; Class/IVR -0.58, p < 0.01) months. All three groups showed a significant number of participants losing at least 5% of their body weight at 12 months (DVD/IVR 26.87%; Class/IVR 21.62%; SC 16.85%). When comparing groups, DVD/IVR were significantly more likely to decrease BMI at 6 months (p < 0.05) and maintain the reduction at 18 months (p < 0.05) when compared to SC. There were no differences between the other groups. Conclusions: The DiaBEAT-it interventions show promise in responding to the need for scalable, effective methods to manage obesity and prevent diabetes in primary care settings that do not over burden primary care clinics and providers. Registration: https://clinicaltrials.gov/ct2/show/NCT02162901, identifier: NCT02162901.

Effects of 6-month episodic future thinking training on delay discounting, weight loss and HbA1c changes in individuals with prediabetes.

People with prediabetes are at risk for type 2 diabetes. They may discount the future delay discounting (DD), and not engage in preventive health behaviors. Episodic future thinking (EFT) can reduce DD when future scenarios are cued, but research is needed to assess long-term effects of EFT and when EFT is not cued. This study tested EFT training compared to control for people with prediabetes enrolled in a 6-month weight loss program on DD, weight, HbA1c, and physical activity. Results showed a reliable EFT effect on reducing DD in cued (p = 0.0035), and uncued DD tasks (p = 0.048), and significant overall changes in weight (p < 0.001), HbA1c (p, 0.001) and physical activity (p = 0.003), but no significant differences in these outcomes by group (p's > 0.05). Sixty-eight percent of the sample ended below the prediabetes HbA1c range. These results suggest that DD can be modified over extended periods, and the effects of EFT can be observed without EFT cues. However, these data do not suggest that changes in weight, HbA1c or physical activity were due to EFT training. The study was initiated before the COVID-19 pandemic which provided the opportunity to compare differences for people treated in-person or remotely. Analyses showed no differences in DD, weight, HBA1c or physical activity outcomes were observed between in-person and remote treatment, suggesting telehealth is a scalable approach to treating prediabetes.

Delay Discounting, Glycemic Regulation and Health Behaviors in Adults with Prediabetes.

The majority of people with prediabetes transition to type 2 diabetes. Research has suggested that persons with type 2 diabetes are likely to discount the future and focus on immediate rewards. This study was designed to assess whether this process of delay discounting (DD) is associated with glycemic regulation, medication adherence and eating and exercise behaviors in adults with prediabetes. Participants included 81 adults with prediabetes who were also prescribed hypertension or dyslipidemia drugs, which is common for people with prediabetes. Participants completed adjusting amount DD $100 and $1000 tasks, as well assessments of glycemic control (Hemoglobin (Hb) A1c), medication adherence, diet quality, and objectively measured physical activity. Relationships between DD and these variables were assessed. Results showed higher rates of DD were related to higher HbA1c; as well as poorer medication adherence, lower diet quality and lower physical activity. Hierarchical regression showed that the association between minority status, a known risk factor for type 2 diabetes, was moderated by DD, as minorities with higher DD had greater HbA1c values. Delay discounting may represent a novel target to prevent progression from prediabetes to type 2 diabetes.

Bleak present, bright future: II. Combined effects of episodic future thinking and scarcity on delay discounting in adults at risk for type 2 diabetes.

The present study sought to determine if episodic future thinking (EFT) can decrease delay discounting (DD) and demand for fast food under simulations of economic scarcity in adults at risk for diabetes (i.e., overweight/obese and with hemoglobin A1c values in, or approaching, the prediabetic range). Across two sessions, participants completed assessments of DD and food demand at baseline and while prompted to: (1) engage in either EFT or control episodic recent thinking, and (2) while reading a brief narrative describing either economic scarcity or neutral income conditions. Results showed that EFT significantly reduced DD, whereas the economic scarcity narrative significantly increased DD; no significant interaction between EFT and scarcity was observed. No significant effect of either EFT or scarcity was observed on food demand. We conclude that EFT decreases DD even when challenged by simulated economic scarcity in adults at risk for diabetes. The absence of a significant interaction between EFT and scarcity suggests that these variables operate independently to influence DD in opposing directions. Effects of EFT and economic scarcity on food demand require further study. The present study was registered on clinicaltrials.gov (NCT03664726).

Does Episodic Future Thinking Repair Immediacy Bias at Home and in the Laboratory in Patients With Prediabetes?

OBJECTIVE: This study aimed to determine if episodic future thinking (EFT) can decrease delay discounting (DD) among adults with prediabetes both in and out of the laboratory. DD measures how much the value of a reinforcer decreases as a function of the delay to receive it. METHODS: Adults with prediabetes (n = 67) completed a three-session study. At session 1, baseline measures (including DD) were collected. At sessions 2 and 3, participants were prompted to engage in either EFT or control episodic thinking (CET) while completing DD and other measures. In addition, between the completion of sessions 2 and 3, participants engaged in EFT or CET at home and completed DD tasks remotely via smartphones or other Internet-connected devices. RESULTS: Results showed significant -1.2759 (-20.24%) reductions in DD in the EFT group compared with a + 0.0287 (+0.46%) DD increase in the CET group (p = .0149) in the laboratory; and -0.4095 (-8.85%) reduction in DD in the EFT group compared with a + 0.2619 (+5.64%) increase in the CET group (p = .011) at home. Working memory (measured by Backwards Corsi and Digit Span) was found to moderate the effects of EFT on some measures of DD. EFT did not change measures from the food purchase task or a food ad libitum procedure. CONCLUSIONS: Results show that EFT decreases DD in and out of the laboratory and supports the further exploration of EFT as an intervention for prediabetes and related chronic diseases. CLINICAL TRIAL REGISTRATION: NCT03664726.

Using Integrated Research-Practice Partnerships to Move Evidence-Based Principles Into Practice.

The implementation of evidence-based physical activity interventions is improved when integrated research-practice partnerships are used. These partnerships consider both research- and practice-based evidence that moves beyond only assessing program efficacy. Our novel hypothesis is that integrated research-practice partnerships may lead to interventions that are practical and effective, reach more participants, and are more likely to be sustained in practice.

Role of delay discounting in predicting change in HBA1c for individuals with prediabetes.

The majority of people with prediabetes transition to type 2 diabetes. Weight gain is a known predictor of increasing the risk of diabetes, but another reason may be a focus on immediate rewards and discounting of the future. Delay discounting (DD: devaluation of future consequences) is related to obesity and poor glycemic control in persons with type 2 diabetes. This study was designed to assess whether changes in DD are associated with HbA1c change beyond BMI change in individuals with prediabetes. Hierarchical regression showed changes in BMI (p = 0.008) and the $1000 DD task (p = 0.04) were associated with HbA1c change beyond demographic characteristics, with the full model accounting for 25.8% of the variance. Those with greater BMI increases and greater increases in discounting of the future showed the greatest increases in HbA1c. DD represents a novel target to prevent progression from prediabetes to type 2 diabetes.

Mitochondrial Epigenetic Changes Link to Increased Diabetes Risk and Early-Stage Prediabetes Indicator.

Type 2 diabetes (T2D) is characterized by mitochondrial derangement and oxidative stress. With no known cure for T2D, it is critical to identify mitochondrial biomarkers for early diagnosis of prediabetes and disease prevention. Here we examined 87 participants on the diagnosis power of fasting glucose (FG) and hemoglobin A1c levels and investigated their interactions with mitochondrial DNA methylation. FG and A1c led to discordant diagnostic results irrespective of increased body mass index (BMI), underscoring the need of new biomarkers for prediabetes diagnosis. Mitochondrial DNA methylation levels were not correlated with late-stage (impaired FG or A1c) but significantly with early-stage (impaired insulin sensitivity) events. Quartiles of BMI suggested that mitochondrial DNA methylation increased drastically from Q1 (20 < BMI < 24.9, lean) to Q2 (30 < BMI < 34.9, obese), but marginally from Q2 to Q3 (35 < BMI < 39.9, severely obese) and from Q3 to Q4 (BMI > 40, morbidly obese). A significant change was also observed from Q1 to Q2 in HOMA insulin sensitivity but not in A1c or FG. Thus, mitochondrial epigenetic changes link to increased diabetes risk and the indicator of early-stage prediabetes. Further larger-scale studies to examine the potential of mitochondrial epigenetic marker in prediabetes diagnosis will be of critical importance for T2D prevention.

Diagnosis and Management of Osteoporosis.

Osteoporosis-related fractures affect approximately one in two white women and one in five white men in their lifetime. The impact of fractures includes loss of function, significant costs, and increased mortality. The U.S. Preventive Services Task Force recommends using dual energy x-ray absorptiometry to screen all women 65 years and older, and younger women who have an increased fracture risk as determined by the World Health Organization's FRAX Fracture Risk Assessment Tool. Although guidelines are lacking for rescreening women who have normal bone mineral density on initial screening, intervals of at least four years appear safe. The U.S. Preventive Services Task Force found insufficient evidence to recommend screening for osteoporosis in men; other organizations recommend screening all men 70 years and older. In patients with newly diagnosed osteoporosis, suggested laboratory tests to identify secondary causes include serum 25-hydroxyvitamin D, calcium, creatinine, and thyroid-stimulating hormone. First-line treatment to prevent fractures consists of fall prevention, smoking cessation, moderation of alcohol intake, and bisphosphonate therapy. Clinicians should consider discontinuing bisphosphonate therapy after five years in women without a personal history of vertebral fractures. Raloxifene, teriparatide, and denosumab are alternative effective treatments for certain subsets of patients and for those who are unable to take or whose condition does not respond to bisphosphonates. The need for follow-up bone mineral density testing in patients receiving treatment for osteoporosis is uncertain.

Insulin resistance is associated with epigenetic and genetic regulation of mitochondrial DNA in obese humans.

BACKGROUND: Mitochondrial alterations have been observed in subjects with metabolic disorders such as obesity and diabetes. Studies on animal models and cell cultures suggest aberrant glucose and lipid levels, and impaired insulin signaling might lead to mitochondrial changes. However, the molecular mechanism underlying mitochondrial aberrance remains largely unexplored in human subjects. RESULTS: Here we show that the mitochondrial DNA copy number (mtDNAn) was significantly reduced (6.9-fold lower, p < 0.001) in the leukocytes from obese humans (BMI >30). The reduction of mtDNAn was strongly associated with insulin resistance (HOMA-IR: -0.703, p < 0.05; fasting insulin level: -0.015, p < 0.05); by contrast, the correlation between fasting glucose or lipid levels and mtDNAn was not significant. Epigenetic study of the displacement loop (D-loop) region of mitochondrial genome, which controls the replication and transcription of the mitochondrial DNA as well as organization of the mitochondrial nucleoid, revealed a dramatic increase of DNA methylation in obese (5.2-fold higher vs. lean subjects, p < 0.05) and insulin-resistant (4.6-fold higher vs. insulin-sensitive subjects, p < 0.05) individuals. CONCLUSIONS: The reduction of mtDNAn in obese human subjects is associated with insulin resistance and may arise from increased D-loop methylation, suggesting an insulin signaling-epigenetic-genetic axis in mitochondrial regulation.

Design and methods of "diaBEAT-it!": a hybrid preference/randomized control trial design using the RE-AIM framework.

BACKGROUND: Diabetes prevention is a public health priority that is dependent upon the reach, effectiveness, and cost of intervention strategies. However, understanding each of these outcomes within the context of randomized controlled trials is problematic. PURPOSE: To describe the methods and design of a hybrid preference/randomized control trial using the RE-AIM framework. METHODS: The trial, which was developed using the RE-AIM framework, will contrast the effects of 3 interventions: (1) a standard care, small group, diabetes prevention education class (SG), (2) the small group intervention plus 12 months of interactive voice response telephone follow-up (SG-IVR), and (3) a DVD version of the small group intervention with the same IVR follow-up (DVD-IVR). Each intervention includes personal action planning with a focus on key elements of the lifestyle intervention from the Diabetes Prevention Program (DPP). Adult patients at risk for diabetes will be randomly assigned to either choice or RCT. Those assigned to choice (n=240) will have the opportunity to choose between SG-IVR and DVD-IVR. Those assigned to RCT group (n=360) will be randomly assigned to SG, SG-IVR, or DVD-IRV. Assessment of primary (weight loss, reach, & cost) and secondary (physical activity, & dietary intake) outcomes will occur at baseline, 6, 12, and 18 months. CONCLUSION: This will be the first diabetes prevention trial that will allow the research team to determine the relationships between reach, effectiveness, and cost of different interventions.

12-hour protocol safe for cocaine-associated chest pain.

A 12-hour emergency department observation period is safe for patients with cocaine-associated chest pain, provided they have symptoms consistent with low-to-intermediate likelihood of unstable angina according to the Braunwald classification, and normal serial troponin I levels and cardiogram. Patients with traditional cardiac risk factors should undergo cardiac stress testing within 2 weeks following the chest pain event, as atherosclerosis enhances the vasoconstrictive effects of cocaine. All patients should be referred for substance abuse counseling, as recurrent cocaine use was associated with subsequent nonfatal myocardial infarction.