Effect of Cognitive Behavioral Therapy for Insomnia on Insomnia Symptoms for Individuals With Type 2 Diabetes: Protocol for a Pilot Randomized Controlled Trial

A grant from the One-University Open Access Fund at the University of Kansas was used to defray the author's publication fees in this Open Access journal. The Open Access Fund, administered by librarians from the KU, KU Law, and KUMC libraries, is made possible by contributions from the offices of KU Provost, KU Vice Chancellor for Research & Graduate Studies, and KUMC Vice Chancellor for Research. For more information about the Open Access Fund, please see http://library.kumc.edu/authors-fund.xml.Background: Insomnia symptoms are a common form of sleep difficulty among people with type 2 diabetes (T2D) affecting sleep quality and health outcomes. Several interventional approaches have been used to improve sleep outcomes in people with T2D. Nonpharmacological approaches, such as cognitive behavioral therapy for insomnia (CBT-I), show promising results regarding safety and sustainability of improvements, although CBT-I has not been examined in people with T2D. Promoting sleep for people with insomnia and T2D could improve insomnia severity and diabetes outcomes. Objective: The objective of this study is to establish a protocol for a pilot randomized controlled trial (RCT) to examine the effect of 6 sessions of CBT-I on insomnia severity (primary outcome), sleep variability, and other health-related outcomes in individuals with T2D and insomnia symptoms. Methods: This RCT will use random mixed block size randomization with stratification to assign 28 participants with T2D and insomnia symptoms to either a CBT-I group or a health education group. Outcomes including insomnia severity; sleep variability; diabetes self-care behavior (DSCB); glycemic control (A1c); glucose level; sleep quality; daytime sleepiness; and symptoms of depression, anxiety, and pain will be gathered before and after the 6-week intervention. Chi-square and independent t tests will be used to test for between-group differences at baseline. Independent t tests will be used to examine the effect of the CBT-I intervention on change score means for insomnia severity, sleep variability, DSCB, A1c, fatigue, sleep quality, daytime sleepiness, and severity of depression, anxiety, and pain. For all analyses, alpha level will be set at .05. Results: This study recruitment began in February 2019 and was completed in September 2019. Conclusions: The intervention, including 6 sessions of CBT-I, will provide insight about its effect in improving insomnia symptoms, sleep variability, fatigue, and diabetes-related health outcomes in people with T2D and those with insomnia symptoms when compared with control

Kepler-16: A Transiting Circumbinary Planet

We report the detection of a planet whose orbit surrounds a pair of low-mass stars. Data from the Kepler spacecraft reveal transits of the planet across both stars, in addition to the mutual eclipses of the stars, giving precise constraints on the absolute dimensions of all three bodies. The planet is comparable to Saturn in mass and size, and is on a nearly circular 229-day orbit around its two parent stars. The eclipsing stars are 20% and 69% as massive as the sun, and have an eccentric 41-day orbit. The motions of all three bodies are confined to within 0.5 degree of a single plane, suggesting that the planet formed within a circumbinary disk.Comment: Science, in press; for supplemental material see http://www.sciencemag.org/content/suppl/2011/09/14/333.6049.1602.DC1/1210923.Doyle.SOM.pd

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Polyamides Reveal a Role for Repression in Latency within Resting T Cells of HIV-Infected Donors

Background. The persistence of human immunodeficiency virus (HIV) type 1 within resting CD4+ T cells poses a daunting therapeutic challenge. Histone deacetylase (HDAC)-1, a chromatin-remodeling enzyme that can mediate gene silencing, is recruited to the HIV-1 long terminal repeat by the host transcription factor LSF. Pyrroleimidazole polyamides, small molecules that target specific DNA sequences, can access the nucleus of cells and specifically block transcription-factor binding. Methods. We used polyamides to directly test the role of chromatin remodeling in HIV quiescence in primary resting CD4^+ T cells obtained from HIV-infected patients. Results. After exposure to any of 4 different polyamides that specifically block HDAC-1 recruitment by LSF to the HIV promoter, replication-competent HIV was recovered from cultures of resting CD4^+ T cells in 6 of 8 HIV-infected patients whose viremia had been suppressed by therapy. In comparison, HIV was not recovered after exposure to control, mismatched polyamides but was recovered from 7 of 8 of these patients' samples after the activation of T cells. Conclusions. We identify histone deacetylation as a mechanism that can dampen viral expression in infected, activated CD4^+ T cells and establish a persistent, quiescent reservoir of HIV infection

Sleep Efficiency and Total Sleep Time in Individuals with Type 2 Diabetes with and without Insomnia Symptoms

There is increasing awareness of the high prevalence of insomnia symptoms in individuals with type 2 diabetes (T2D). Past studies have established the importance of measuring sleep parameters using measures of central tendency and variability. Additionally, subjective and objective methods involve different constructs due to the discrepancies between the two approaches. Therefore, this study is aimed at comparing the averages of sleep parameters in individuals with T2D with and without insomnia symptoms and comparing the variability of sleep parameters in these individuals. This study assessed the between-group differences in the averages and variability of sleep efficiency (SE) and total sleep time (TST) of 59 participants with T2D with and without insomnia symptoms. Actigraph measurements and sleep diaries were used to assess sleep parameter averages and variabilities calculated by the coefficient of variation across 7 nights. Mann–Whitney U tests were utilized to compare group differences in the outcomes. Validated instruments were used to assess the symptoms of depression, anxiety, and pain as covariates. Objective SE was found to be statistically lower on average (85.98±4.29) and highly variable (5.88±2.57) for patients with T2D and insomnia symptoms than in those with T2D only (90.23±6.44 and 3.82±2.05, respectively). The subjective average and variability of SE were also worse in patients with T2D and insomnia symptoms, with symptoms of depression, anxiety, and pain potentially playing a role in this difference. TST did not significantly differ between the groups on averages or in variability even after controlling for age and symptoms of depression, anxiety, and pain. Future studies are needed to investigate the underlying mechanisms of worse averages and variability of SE in individuals with T2D and insomnia symptoms. Additionally, prompting the associated risk factors of insomnia symptoms in individuals with T2D might be warranted

Multitasking in older adults with type 2 diabetes: A cross-sectional analysis

<div><p>Background and purpose</p><p>Deficits in the ability to multitask contribute to gait abnormalities and falls in many at-risk populations. However, it is unclear whether older adults with type 2 diabetes mellitus (DM) also demonstrate impairments in multitasking. The purpose of this study was to compare multitasking performance in cognitively intact older adults with and without DM and explore its relationship to measures of gait and functional ability.</p><p>Methods</p><p>We performed a cross-sectional analysis of 40 individuals aged 60 and older with type 2 DM and a matched group of 40 cognitively intact older adults without DM. Multitasking was examined via the ambulatory Walking and Remembering Test (WART) and seated Pursuit Rotor Test (PRT). Self-selected normal and fast walking speed and stride length variability were quantitatively measured, and self-reported functional ability was assessed via the Late Life Function and Disability Index (LLFDI).</p><p>Results</p><p>Participants with DM walked slower and took more steps off path when multitasking during the WART. No between-group differences in multitasking performance were observed on the PRT. Multitasking performance demonstrated little correlation with gait and functional ability in either group.</p><p>Discussion and conclusions</p><p>Older adults with DM appear to perform poorly on an ambulatory measure of multitasking. However, we analyzed a relatively small, homogenous sample of older adults with and without type 2 DM and factors such as peripheral neuropathy and the use of multiple comparisons complicate interpretation of the data. Future research should explore the interactions between multitasking and safety, fall risk, and function in this vulnerable population. Clinicians should recognize that an array of factors may contribute to gait and physical dysfunction in older adults with type 2 diabetes, and be prepared to assess and intervene appropriately.</p></div

Relationships between sample characteristics and WART task performance in subjects with diabetes.

<p>Relationships between sample characteristics and WART task performance in subjects with diabetes.</p