A muscarinic receptor antagonist reverses multiple indices of diabetic peripheral neuropathy: preclinical and clinical studies using oxybutynin.

Preclinical studies indicate that diverse muscarinic receptor antagonists, acting via the M sub-type, promote neuritogenesis from sensory neurons in vitro and prevent and/or reverse both structural and functional indices of neuropathy in rodent models of diabetes. We sought to translate this as a potential therapeutic approach against structural and functional indices of diabetic neuropathy using oxybutynin, a muscarinic antagonist approved for clinical use against overactive bladder. Studies were performed using sensory neurons maintained in vitro, rodent models of type 1 or type 2 diabetes and human subjects with type 2 diabetes and confirmed neuropathy.

Utilizing a quality of life tool to examine the presence of fatigue in subjects with diabetes mellitus.

Introduction: The prevalence of fatigue in patients with diabetes mellitus (DM) can be as high as 50 %. Physical, mental, and psychosocial components of fatigue negatively impact quality of life (QOL), morbidity and mortality. Several tools have been developed to address fatigue, but none specifically for measuring fatigue in DM.

Cardiac and Sudomotor Autonomic Function in Subjects with Psoriasis With and Without Metabolic Syndrome.

Studies have shown that subjects with psoriasis (PsO) are associated with an increased risk of developing metabolic syndrome (MetS), diabetes, and cardiovascular disease. In addition, MetS and diabetes are associated with autonomic dysfunction (AD). The aim of this study was to investigate cardiac and sudomotor autonomic function in subjects with PsO and without diabetes.

Development and Validation of the Norfolk Quality of Life Fatigue Tool (QOL-F): A New Measure of Perception of Fatigue.

Objectives: To design a questionnaire to evaluate and distinguish between cognitive and physical aspects of fatigue in different age groups of "nondiseased" people and guide appropriate prevention and interventions for the impact of frailty occurring in normative aging.

Study Design And Participants: The Norfolk QOL-Fatigue (QOL-F) with items of cognitive and physical fatigue, anxiety, and depression from validated questionnaires including items from the Patient-Reported Outcomes Measure Information System (PROMIS) databank was developed. The preliminary QOL-F was administered to 409 healthy multiethnic local participants (30-80 years old) in 5 age groups.

Cardiac Autonomic Neuropathy in Diabetes: A Predictor of Cardiometabolic Events.

Autonomic nervous system (ANS) imbalance manifesting as cardiac autonomic neuropathy in the diabetic population is an important predictor of cardiovascular events. Symptoms and signs of ANS dysfunction, such as resting heart rate elevations, diminished blood pressure responses to standing, and altered time and frequency domain measures of heart rate variability in response to deep breathing, standing, and the Valsalva maneuver, should be elicited from all patients with diabetes and prediabetes. With the recognition of the presence of ANS imbalance or for its prevention, a rigorous regime should be implemented with lifestyle modification, physical activity, and cautious use of medications that lower blood glucose.

Supervised Balance Training and Wii Fit-Based Exercises Lower Falls Risk in Older Adults With Type 2 Diabetes.

Objectives: This study examined the benefits of and differences between 12 weeks of thrice-weekly supervised balance training and an unsupervised at-home balance activity (using the Nintendo Wii Fit) for improving balance and reaction time and lowering falls risk in older individuals with type 2 diabetes mellitus (T2DM).

Design: Before-after trial.

Setting: University research laboratory, home environment.

Bariatric Surgery Restores Cardiac and Sudomotor Autonomic C-Fiber Dysfunction towards Normal in Obese Subjects with Type 2 Diabetes.

Objective: The aim was to evaluate the impact of bariatric surgery on cardiac and sudomotor autonomic C-fiber function in obese subjects with and without Type 2 diabetes mellitus (T2DM), using sudorimetry and heart rate variability (HRV) analysis.

Method: Patients were evaluated at baseline, 4, 12 and 24 weeks after vertical sleeve gastrectomy or Roux-en-Y gastric bypass. All subjects were assessed using SudoscanTM to measure electrochemical skin conductance (ESC) of hands and feet, time and frequency domain analysis of HRV, Neurologic Impairment Scores of lower legs (NIS-LL), quantitative sensory tests (QST) and sural nerve conduction studies.

Walking-Induced Fatigue Leads to Increased Falls Risk in Older Adults.

Background: For older adults, falls are a serious health problem, with more than 30% of people older than 65 suffering a fall at least once a year. One element often overlooked in the assessment of falls is whether a person's balance, walking ability, and overall falls risk is affected by performing activities of daily living such as walking.

Objective: This study assessed the immediate impact of incline walking at a moderate pace on falls risk, leg strength, reaction time, gait, and balance in 75 healthy adults from 30 to 79 years of age.

Exercise improves gait, reaction time and postural stability in older adults with type 2 diabetes and neuropathy.

Aims: For older adults with type 2 diabetes (T2DM), declines in balance and walking ability are risk factors for falls, and peripheral neuropathy magnifies this risk. Exercise training may improve balance, gait and reduce the risk of falling. This study investigated the effects of 12weeks of aerobic exercise training on walking, balance, reaction time and falls risk metrics in older T2DM individuals with/without peripheral neuropathy.

Sudoscan, a noninvasive tool for detecting diabetic small fiber neuropathy and autonomic dysfunction.

Objective: Sudomotor dysfunction may be an early detectable abnormality in diabetic small fiber neuropathy. The aim of this study was to evaluate the efficacy of Sudoscan™ (Impeto Medical, Paris, France) in detecting diabetic neuropathy (DN), in comparison with other standardized tests, in patients with diabetes mellitus (DM).

Subjects And Methods: Sudoscan measures electrochemical skin conductance (ESC) of hands and feet through reverse iontophoresis.

Contact heat-evoked potential stimulation for the evaluation of small nerve fiber function.

Background: Small fiber peripheral neuropathy (SFN) is emerging as a common complication in diabetes. Currently there are few, not easily available methods of determining the integrity of small nerve fibers. This study was designed to determine the utility of a noninvasive technique, contact heat-evoked potential stimulation (CHEPS), on the identification of SFN and compare it with standardized measures of diabetic peripheral neuropathy (DPN).

Role of prostaglandin D2 and the autonomic nervous system in niacin-induced flushing.

Background: Although niacin often has beneficial effects on the lipoprotein profile, flushing is an untoward effect associated with its use. Aspirin can only reduce the flushing response by 30-40%. Thus, the aim of the present study was to investigate the mechanisms of niacin-induced flushing, with and without aspirin, in normal, healthy individuals.

Cardiac autonomic imbalance in newly diagnosed and established diabetes is associated with markers of adipose tissue inflammation.

Introduction: Diabetics die from cardiovascular disease at a much greater rate than nondiabetics. Cardiac autonomic imbalance predicts increased cardiovascular risk and mortality. We studied the relationship between cardiac autonomic imbalance and adipose tissue-derived inflammation in newly diagnosed and established type 2 diabetes.

Loss of RAGE defense: a cause of Charcot neuroarthropathy?

Objective: This study investigated the relationship between circulating soluble receptor for advanced glycation end products (sRAGE) and parameters of bone health in patients with Charcot neuroarthropathy (CNA).

Research Design And Methods: Eighty men (aged 55.3±9.

Balance training reduces falls risk in older individuals with type 2 diabetes.

Objective: This study assessed the effects of balance/strength training on falls risk and posture in older individuals with type 2 diabetes.

Research Design And Methods: Sixteen individuals with type 2 diabetes and 21 age-matched control subjects (aged 50-75 years) participated. Postural stability and falls risk was assessed before and after a 6-week exercise program.

Aerobic training increases skin perfusion by a nitric oxide mechanism in type 2 diabetes.

It is well known that a number of locally released vasodilatory and vasoconstrictive compounds can affect skin perfusion. This study investigated the effects of aerobic training on the contribution of nitric oxide (NO), prostaglandins (PG), and endothelial-derived hyperpolarizing factor (EDHF) in stimulated dorsal foot skin perfusion in individuals with type 2 diabetes (T2DM). Ten previously sedentary, older individuals with T2DM (57.

Pleiotropic effects of rosuvastatin on microvascular function in type 2 diabetes.

Rosuvastatin is known to reduce low-density lipoprotein (LDL)-cholesterol and improve endothelial function. In addition to lipid-lowering, statins may exert pleiotropic (nonlipid lowering) effects on microvascular function. We compared the neurophysiological and vascular responses of dietary control and treatment with 10 mg of rosuvastatin in 16 subjects with neuropathy and established type 2 diabetes.

Exercise status affects skin perfusion via prostaglandin, nitric oxide, and EDHF pathways in diabetes.

Participation in regular exercise training improves dorsal skin perfusion, while type 2 diabetes mellitus (T2 DM) often limits it via reductions in the action or release of vasodilatory compounds. This study was undertaken to investigate the relative contributions of prostaglandins (PG), nitric oxide (NO), and endothelial-derived hyperpolarizing factor (EDHF) in dorsal foot skin perfusion in individuals with and without T2 DM and a sedentary lifestyle. Participants included 24 individuals with T2 DM and 28 nondiabetic controls whose exercise status was determined via questionnaire.

Diabetic neuropathies: clinical manifestations and current treatment options.

Diabetic neuropathies are a heterogeneous group of disorders that include a wide range of abnormalities. They can be focal or diffuse, proximal or distal, affecting both peripheral and autonomic nervous systems, causing morbidity with significant impact on the quality of life of the person with diabetes, and can result in early death. Distal symmetric polyneuropathy, the most common form of diabetic neuropathy, usually involves small and large nerve fibers.

Pioglitazone treatment improves nitrosative stress in type 2 diabetes.

Objective: The purpose of this study was to determine the effect of 24 weeks of treatment with 45 mg/day pioglitazone on peripheral skin blood flow (SkBF) and skin nitric oxide (NO) production in vivo in patients with type 2 diabetes.

Research Design And Methods: This was a randomized, parallel, cross-over, double-blind, within- and between-subject study designed to compare vascular responses before and after treatment. We studied 12 subjects with type 2 diabetes (average age 58.

Effect of an 8-week resistance training program on cutaneous perfusion in type 2 diabetes.

A positive association has previously been demonstrated between chronic aerobic exercise and prior maximal exercise and enhanced dorsal foot skin perfusion in physically active individuals with type 2 diabetes. The current study examined whether an 8-week resistance training program would also positively affect cutaneous perfusion in type 2 diabetic individuals. Ten individuals with type 2 diabetes and nine similar nondiabetic controls participated in 8 weeks of moderate-intensity resistance training.