Infectious Diseases Society of America.

Diabetes mellitus is a disease of metabolic dysregulation, most notably abnormal glucose metabolism, accompanied by characteristic long-term complications. The complications that are specific to diabetes include retinopathy, nephropathy, and neuropathy. Patients with all forms of diabetes of sufficient duration, including insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM), are vulnerable to these complications, which cause serious morbidity (Table 1 and Table 2). Retinopathy is so characteristic of diabetes that its presence has been incorporated into the nosologic definition of NIDDM. Only hyperglycemia of sufficient magnitude to be associated with retinopathy is classified as NIDDM, while lower levels of hyperglycemia that are . . .

Long-term complications of diabetes mellitus

Heart rate variability (HRV), the change in the time intervals between adjacent heartbeats, is an emergent property of interdependent regulatory systems that operate on different time scales to adapt to challenges and achieve optimal performance. This article briefly reviews neural regulation of the heart, and its basic anatomy, the cardiac cycle, and the sinoatrial and atrioventricular pacemakers. The cardiovascular regulation center in the medulla integrates sensory information and input from higher brain centers, and afferent cardiovascular system inputs to adjust heart rate and blood pressure via sympathetic and parasympathetic efferent pathways. This article reviews sympathetic and parasympathetic influences on the heart, and examines the interpretation of HRV and the association between reduced HRV, risk of disease and mortality, and the loss of regulatory capacity. This article also discusses the intrinsic cardiac nervous system and the heart-brain connection, through which afferent information can influence activity in the subcortical and frontocortical areas, and motor cortex. It also considers new perspectives on the putative underlying physiological mechanisms and properties of the ultra-low-frequency (ULF), very-low-frequency (VLF), low-frequency (LF), and high-frequency (HF) bands. Additionally, it reviews the most common time and frequency domain measurements as well as standardized data collection protocols. In its final section, this article integrates Porges’ polyvagal theory, Thayer and colleagues’ neurovisceral integration model, Lehrer et al.’s resonance frequency model, and the Institute of HeartMath’s coherence model. The authors conclude that a coherent heart is not a metronome because its rhythms are characterized by both complexity and stability over longer time scales. Future research should expand understanding of how the heart and its intrinsic nervous system influence the brain.

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A healthy heart is not a metronome: an integrative review of the heart's anatomy and heart rate variability.

Objective: To perform serial neuropsychological assessments to detect vascular risk factors for cognitive decline in the Atherosclerosis Risk in Communities cohort, a large biracial, multisite, longitudinal investigation of initially middle-aged individuals. Methods: The authors administered cognitive assessments to 10,963 individuals (8,729 white individuals and 2,234 black individuals) on two occasions separated by 6 years. Subjects ranged in age at the first assessment from 47 to 70 years. The cognitive assessments included the delayed word recall (DWR) test, a 10-word delayed free recall task in which the learning phase included sentence generation with the study words, the digit symbol subtest (DSS) of the Wechsler Adult Intelligence Scale–Revised and the first-letter word fluency (WF) test using letters F, A, and S. Results: In multivariate analyses (controlling for demographic factors), the presence of diabetes at baseline was associated with greater decline in scores on both the DSS and WF (p Conclusions: Hypertension and diabetes mellitus were positively associated with cognitive decline over 6 years in this late middle-aged population. Interventions aimed at hypertension or diabetes that begin before age 60 might lessen the burden of cognitive impairment in later life.

https://n.neurology.org/content/neurology/56/1/42.full.pdf

Cardiovascular risk factors and cognitive decline in middle-aged adults

Anxiety and related disorders are among the most common mental disorders, with lifetime prevalence reportedly as high as 31%. Unfortunately, anxiety disorders are under-diagnosed and under-treated. These guidelines were developed by Canadian experts in anxiety and related disorders through a consensus process. Data on the epidemiology, diagnosis, and treatment (psychological and pharmacological) were obtained through MEDLINE, PsycINFO, and manual searches (1980–2012). Treatment strategies were rated on strength of evidence, and a clinical recommendation for each intervention was made, based on global impression of efficacy, effectiveness, and side effects, using a modified version of the periodic health examination guidelines. These guidelines are presented in 10 sections, including an introduction, principles of diagnosis and management, six sections (Sections 3 through 8) on the specific anxiety-related disorders (panic disorder, agoraphobia, specific phobia, social anxiety disorder, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder), and two additional sections on special populations (children/adolescents, pregnant/lactating women, and the elderly) and clinical issues in patients with comorbid conditions. Anxiety and related disorders are very common in clinical practice, and frequently comorbid with other psychiatric and medical conditions. Optimal management requires a good understanding of the efficacy and side effect profiles of pharmacological and psychological treatments.

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Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders

Healthy biological systems exhibit complex patterns of variability that can be described by mathematical chaos. Heart rate variability (HRV) consists of changes in the time intervals between consecutive heartbeats called interbeat intervals (IBIs). A healthy heart is not a metronome. The oscillations of a healthy heart are complex and constantly changing, which allow the cardiovascular system to rapidly adjust to sudden physical and psychological challenges to homeostasis. This article briefly reviews current perspectives on the mechanisms that generate 24 h, short-term (~5 min), and ultra-short-term (<5 min) HRV, the importance of HRV, and its implications for health and performance. The authors provide an overview of widely-used HRV time-domain, frequency-domain, and non-linear metrics. Time-domain indices quantify the amount of HRV observed during monitoring periods that may range from ~2 min to 24 h. Frequency-domain values calculate the absolute or relative amount of signal energy within component bands. Non-linear measurements quantify the unpredictability and complexity of a series of IBIs. The authors survey published normative values for clinical, healthy, and optimal performance populations. They stress the importance of measurement context, including recording period length, subject age, and sex, on baseline HRV values. They caution that 24 h, short-term, and ultra-short-term normative values are not interchangeable. They encourage professionals to supplement published norms with findings from their own specialized populations. Finally, the authors provide an overview of HRV assessment strategies for clinical and optimal performance interventions.

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An Overview of Heart Rate Variability Metrics and Norms.

https://www.amjmed.com/article/0002-9343(84)90186-4/pdf

Decreased cognitive function in aging non-insulin-dependent diabetic patients

While the immunological dysfunction in combat Veterans with post-traumatic stress disorder (PTSD) has been well documented, the precise mechanisms remain unclear. The current study evaluated the role of microRNA (miR) in immunological dysfunction associated with PTSD. The presence of peripheral blood mononuclear cells (PBMC) and various lymphocyte subsets in blood collected from PTSD patients were analyzed. Our studies demonstrated that the numbers of both PBMC and various lymphocyte subsets increased significantly in PTSD patients. When T cells were further analyzed, the percentage of Th1 cells and Th17 cells increased, regulatory T cells(Tregs) decreased, while Th2 cells remained unaltered in PTSD patients. These data correlated with increased plasma levels of IFN-γ and IL-17 while IL-4 showed no significant change. The increase in PBMC counts, Th1 and Th17 cells seen in PTSD patients correlated with the clinical scores. High-throughput analysis of PBMCs for 1163 miRs showed that the expression of a significant number of miRs was altered in PTSD patients. Pathway analysis of dysregulated miRs seen in PTSD patients revealed relationship between selected miRNAs and genes that showed direct/indirect role in immunological signaling pathways consistent with the immunological changes seen in these patients. Of interest was the down-regulation of miR-125a in PTSD, which specifically targeted IFN-γ production. Together, the current study demonstrates for the first time that PTSD was associated with significant alterations in miRNAs, which may promote pro-inflammatory cytokine profile. Such epigenetic events may provide useful tools to identify potential biomarkers for diagnosis, and facilitate therapy of PTSD.

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Dysregulation in microRNA expression is associated with alterations in immune functions in combat veterans with post-traumatic stress disorder.

Background The need for treatment of posttraumatic stress disorder (PTSD) among combat veterans returning from Afghanistan and Iraq is a growing concern. PTSD has been associated with reduced cardiac coherence (an indicator of heart rate variability [HRV]) and deficits in early stage information processing (attention and immediate memory) in different studies. However, the co-occurrence of reduced coherence and cognition in combat veterans with PTSD has not been studied before. Primary study objective A pilot study was undertaken to assess the covariance of coherence and information processing in combat veterans. An additional study goal was assessment of effects of HRV biofeedback (HRVB) on coherence and information processing in these veterans. Methods/design A two-group (combat veterans with and without PTSD), pre-post study of coherence and information processing was employed with baseline psychometric covariates. Setting The study was conducted at a VA Medical Center outpatient mental health clinic. Participants Five combat veterans from Iraq or Afghanistan with PTSD and five active-duty soldiers with comparable combat exposure who were without PTSD. Intervention Participants met with an HRVB professional once weekly for 4 weeks and received visual feedback in HRV patterns while receiving training in resonance frequency breathing and positive emotion induction. Primary outcome measures Cardiac coherence, word list learning, commissions (false alarms) in go-no go reaction time, digits backward. Results Cardiac coherence was achieved in all participants, and the increase in coherence ratio was significant post-HRVB training. Significant improvements in the information processing indicators were achieved. Degree of increase in coherence was the likely mediator of cognitive improvement. Conclusion Cardiac coherence is an index of strength of control of parasympathetic cardiac deceleration in an individual that has cardinal importance for the individual's attention and affect regulation.

/pdf/cardiac-coherence-and-posttraumatic-stress-disorder-in-4mutj5zocq.pdf

Cardiac coherence and posttraumatic stress disorder in combat veterans.

Memory function was studied in combat veterans with posttraumatic stress disorder (PTSD), combat veterans without PTSD, and noncombat veterans. The Vocabulary and Digit Span subtests of the WAIS and Logical Memory (LMS) and Verbal Paired Associates (VPAS) subtests of the Wechsler Memory Scale III were administered. Combat veterans with PTSD showed impaired memory on the LMS and VPAS compared to combat veterans without PTSD or noncombat veterans. Veterans with PTSD also showed lower WAIS Vocabulary subtest scores--but not digit span subtest scores--than combat veterans without PTSD or noncombat veterans. Medication status, co-morbid diagnosis, and age all failed to account for these memory differences, but when self-assessed depression--as measured by the Zung Self-Rating Depression Scale--or anxiety--as measured by the Spielberger State-Trait Anxiety Scale--was statistically removed, group differences on these memory measures were no longer significant. However, using a stepwise regression procedure, in which both anxiety and depression were employed to predict the LMS and VPAS scores, only the Zung scale reliably predicated performance. The present results, showing that PTSD is associated with general learning and memory impairments, is an important finding, but the specific effects of depression as a mediator of these deficits should be further studied.

Jay P. Ginsberg

Papers

An Overview of Heart Rate Variability Metrics and Norms.

Decreased cognitive function in aging non-insulin-dependent diabetic patients

Dysregulation in microRNA expression is associated with alterations in immune functions in combat veterans with post-traumatic stress disorder.

Cardiac coherence and posttraumatic stress disorder in combat veterans.

Learning and memory impairment in PTSD: relationship to depression