ABSTRACT
BACKGROUND: Structured education programmes are now established as an essential component to assist effective self-management of diabetes. In the case of Type 1 diabetes, the Dose Adjustment For Normal Eating (DAFNE) programme improves both glycaemic control and quality of life. Traditionally delivered over five consecutive days, this format has been cited as a barrier to participation by some patients, such as those who work full-time. Some centres in the UK have organised structured education programmes to be delivered one day a week over several consecutive weeks. This type of format may add benefit by allowing more time in which to practice skills between sessions, but may suffer as a result of weaker peer support being generated compared to that formed over five consecutive days. METHODS/DESIGN: We aim to compare DAFNE delivered over five consecutive days (1 week course) with DAFNE delivered one day a week over five weeks (5 week course) in a randomised controlled trial. A total of 213 patients were randomised to attend either a 1 week or a 5 week course delivered in seven participating centres. Study outcomes (measured at baseline, 6 and 12 months post-course) include HbA1c, weight, self-reported rates of severe hypoglycaemia, psychosocial measures of quality of life, and cost-effectiveness. Generalisability was optimised by recruiting patients from DAFNE waiting lists at each centre, and by mailing eligible patients from hospital clinic lists. The inclusion and exclusion criteria were identical to those used to recruit to a standard DAFNE course (e.g., HbA1c <12%, with no lower limit). Qualitative interviews were undertaken with a sub-sample of n=30 patients and their course educators (n=11) to help understand and interpret differences and similarities in outcomes between the two arms, and to identify logistical problems and unanticipated issues arising from the adaptation and delivery of a 5 week course. DISCUSSION: This trial has been designed to test the hypothesis that the benefits of delivering a structured education programme over 5 weeks are comparable to those observed after a 1 week course. The results of the trial and the qualitative sub-study will both inform the design and delivery of future DAFNE courses, and the development of structured education programmes in other fields of medicine. TRIAL REGISTRATION: Clinicaltrials.gov NCT01069393.
ABSTRACT
OBJECTIVE: The pathogenesis of diabetic peripheral neuropathy (DPN) is poorly understood. We have recently reported a significant reduction in spinal cord cross-sectional area at the stage of clinically detectable DPN. In this study, we investigated whether spinal cord atrophy occurs in early (subclinical) DPN. RESEARCH DESIGN AND METHODS: Eighty-one male type 1 diabetic subjects, 24 nondiabetic control subjects, and 8 subjects with hereditary sensory motor neuropathy (HSMN) type 1A underwent detailed clinical and neurophysiological assessments. Diabetic subjects were subsequently divided into three groups based on neuropathy severity (19 with no DPN, 23 with subclinical DPN, and 39 with clinically detectable DPN). All subjects underwent magnetic resonance imaging of the cervical spine and cord area measurements at disc level C2/C3. RESULTS: Mean corrected spinal cord area index (SCAI) (corrected for age, height, and weight) was 67.5 mm [95% CI 64.1-70.9] in diabetic subjects without DPN. Those with subclinical (62.4 mm [59.5-65.3]) and clinically detectable DPN (57.2 mm [54.9-59.6]) had lower mean SCAIs compared with subjects with no DPN (P = 0.03 and P < 0.001, respectively). No significant difference was found between diabetic subjects without DPN and nondiabetic control subjects (69.2 mm [66.3-72.0], P = 0.47). Mean SCAIs in subjects with HSMN type 1A (71.07 mm [65.3-76.9]) were not significantly different from those for nondiabetic control subjects and diabetic subjects without DPN. Among diabetic subjects, SCAI was significantly related to sural sensory conduction velocities and the Neuropathy Composite and Symptom Scores. CONCLUSIONS: Spinal cord involvement occurs early in DPN. There is also a significant relation between reduction in SCAI and neurophysiological assessments of DPN.
Subject(s)
Diabetic Neuropathies/physiopathology , Peripheral Nervous System Diseases/physiopathology , Spinal Cord/physiopathology , Adult , Aged , Blood Flow Velocity , Diabetes Mellitus, Type 1/physiopathology , Glycated Hemoglobin/analysis , Heart Rate , Hereditary Sensory and Autonomic Neuropathies/physiopathology , Humans , Male , Middle Aged , Peroneal Nerve/blood supply , Reference ValuesABSTRACT
Pulmonary hypertension, as a result of adverse drug reactions, must be considered as a rare occurrence. With good medicinal chemistry and screening of compounds before entry into man, it should be almost totally avoidable. Life and medicine are a continuing challenge as our exploration of the regions of unknown biology throw up new targets and new mechanisms and may catch us again as the anorectic (anorectic) drug caught our predecessors.
Subject(s)
Hypertension, Pulmonary/chemically induced , Appetite Depressants/adverse effects , Dexfenfluramine/adverse effects , Eosinophilia-Myalgia Syndrome/chemically induced , Fenfluramine/adverse effects , Humans , Hypertension, Pulmonary/physiopathology , Iatrogenic Disease , Selective Serotonin Reuptake Inhibitors/adverse effectsABSTRACT
Sleep apnoea (SA) is common, especially in elderly people. In severe cases, arterial P(O2) may be lowered for a third or more in a night of sleep. To simulate the degree and duration of severe SA we exposed rats in a normobaric environmental chamber to 10% O(2) for 4h daily for 56 days (intermittent hypoxia: IH group) and compared them with rats continuously exposed for 8 weeks (continuous hypoxia: CH group) and control rats breathing room air (normoxic: N group). We found significant cardiopulmonary and cerebral changes. Right ventricular hypertrophy developed in IH and to a greater extent in CH. Small peripheral lung vessels developed thicker walls (assessed by a new method), which reduced their lumen, more in CH than IH. Coronal brain sections were immunostained for the glucose-transporter 1 (GLUT1) and the vascular endothelial growth factor (VEGF). The percentages of immunoreactivity in the frontal and temporal cortex, hippocampus, accumbens and putamen were determined by image-capture analysis. We noted GLUT1 immunoreactivity of the capillaries was similarly increased in all regions after CH but less so after IH. However, there was a significant linear trend in GLUT1 reactivity from N to IH to CH (R(2) = 0.73, P = 0.007) that was also confirmed by analysis of variance. The extent of VEGF-stained neurones and glial cells was significantly increased in all regions after IH but not after CH. This suggests that the signals for angiogenesis were complete or arrested after CH. Our findings have implications for the elderly subjected to hypoxic episodes during sleep apnoea.
Subject(s)
Cerebral Cortex/metabolism , Hypertrophy, Right Ventricular/pathology , Hypoxia/metabolism , Hypoxia/pathology , Lung/pathology , Sleep Apnea Syndromes/metabolism , Sleep Apnea Syndromes/pathology , Adaptation, Physiological , Animals , Blood Pressure/physiology , Cerebral Cortex/blood supply , Disease Models, Animal , Endothelium, Vascular/pathology , Glucose Transporter Type 1 , Hypertrophy/etiology , Hypertrophy, Right Ventricular/etiology , Hypoxia/complications , Immunohistochemistry , Lung/blood supply , Monosaccharide Transport Proteins/metabolism , Rats , Rats, Wistar , Sleep Apnea Syndromes/complications , Vascular Endothelial Growth Factor A/metabolismABSTRACT
AIMS: To examine the contribution of demographic, social, clinical and psychological factors to emotional distress in patients with painful diabetic neuropathy (DN). METHODS: In total, 142 patients with confirmed painful DN underwent detailed clinical and self-assessment measures (Neuropathic Pain Scale, Hospital Anxiety and Depression Scale, Pain Acceptance Questionnaire and Pain Catastrophizing Scale). RESULTS: The prevalence of emotional distress was 51.4% in this cohort. Age, sex, marital status, employment history, pain intensity, duration of diabetes and the presence of diabetic and non-diabetic complications were significantly correlated to anxiety and depressive symptom scores. Multiple regression analysis confirmed that the presence of catastrophic thinking was an independent contributor to greater symptoms of anxiety and depression. Being young, single and unemployed significantly contributed to greater anxiety symptoms. Pain-related restriction of quality of life was associated with greater depression symptom scores. CONCLUSIONS: This study found a high prevalence of emotional distress in patients with painful DN. It highlights that the differing independent contributors to anxiety and depressive symptoms are based on an individual's circumstances and experience. We conclude by highlighting the importance of adopting a holistic approach to pain management, incorporating interventions to increase psychological flexibility alongside conventional pharmacological treatments to improve emotional distress in painful DN.
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BACKGROUND: Continuous glucose monitoring devices measure interstitial glucose and are commonly used to investigate hypoglycemia. The relationship between interstitial glucose and blood glucose is not completely understood, particularly at low blood glucose concentrations. Interstitial glucose during hypoglycemia is generally lower than blood glucose in young subjects without diabetes and those with type 1 diabetes, but the effect of insulin resistance and obesity in type 2 diabetes on this relationship has not been examined previously. We studied the relationship between blood and interstitial glucose during experimental hypoglycemia in subjects with type 2 diabetes treated with insulin or sulfonylureas and matched controls without diabetes. METHODS: Twenty subjects with type 2 diabetes (10 sulfonylurea-treated and 10 insulin-treated) and 10 controls without diabetes of similar age and weight underwent stepped hyperinsulinemic hypoglycemic clamps. We compared blood and interstitial glucose at different levels of hypoglycemia using random effects modeling. RESULTS: Interstitial glucose was significantly higher than blood glucose at all levels of hypoglycemia (P<0.001), and this difference increased as glucose fell. For every 1 mmol/L drop in blood glucose, the difference increased by 0.32 mmol/L (P<0.001). This difference was not affected by presence of type 2 diabetes or by modality of treatment (P=0.10). CONCLUSIONS: In older subjects with or without type 2 diabetes, interstitial glucose is significantly higher than blood glucose, and this difference increases with increasing severity of hypoglycemia. Continuous glucose monitors may underestimate hypoglycemia in this group, and this should be taken into account when interpreting results obtained using this technology.
Subject(s)
Blood Glucose/analysis , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Extracellular Fluid/drug effects , Hypoglycemia/blood , Hypoglycemic Agents/adverse effects , Aged , C-Peptide/blood , Extracellular Fluid/chemistry , Humans , Hypoglycemia/chemically induced , Hypoglycemic Agents/therapeutic use , Insulin/adverse effects , Insulin/therapeutic use , Insulin Resistance , Middle Aged , Severity of Illness Index , Sulfonylurea Compounds/adverse effects , Sulfonylurea Compounds/therapeutic useABSTRACT
OBJECTIVE: To assess the efficacy of Sativex, a cannabis-based medicinal extract, as adjuvant treatment in painful diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS: In this randomized controlled trial, 30 subjects with painful DPN received daily Sativex or placebo. The primary outcome measure was change in mean daily pain scores, and secondary outcome measures included quality-of-life assessments. RESULTS: There was significant improvement in pain scores in both groups, but mean change between groups was not significant. There were no significant differences in secondary outcome measures. Patients with depression had significantly greater baseline pain scores that improved regardless of intervention. CONCLUSIONS: This first-ever trial assessing the efficacy of cannabis has shown it to be no more efficacious than placebo in painful DPN. Depression was a major confounder and may have important implications for future trials on painful DPN.
Subject(s)
Depression/chemically induced , Diabetic Neuropathies/drug therapy , Plant Extracts/adverse effects , Plant Extracts/therapeutic use , Adult , Aged , Cannabidiol , Diabetic Neuropathies/psychology , Double-Blind Method , Dronabinol , Drug Combinations , Female , Humans , Male , Middle Aged , Pain/drug therapy , Pain Measurement , Placebos , Quality of Life , Treatment OutcomeABSTRACT
OBJECTIVE: Although a clear link between diabetic peripheral neuropathy (DPN) and autonomic neuropathy is recognized, the relationship of autonomic neuropathy with subtypes of DPN is less clear. This study aimed to investigate the relationship of autonomic neuropathy with painless and painful DPN. RESEARCH DESIGN AND METHODS: Eighty subjects (20 healthy volunteers, 20 with no DPN, 20 with painful DPN, 20 with painless DPN) underwent detailed neurophysiological investigations (including conventional autonomic function tests [AFTs]) and spectral analysis of short-term heart rate variability (HRV), which assesses sympathovagal modulation of the heart rate. Various frequency-domain (including low frequency [LF], high frequency [HF], and total power [TP]) and time-domain (standard deviation of all normal-to-normal R-R intervals [SDNN] and root mean square of successive differences [RMSSD]) parameters were assessed. RESULTS: HRV analysis revealed significant differences across the groups in LF, HF, TP, SDNN, and RMSSD (ANOVA P < 0.001). Subgroup analysis showed that compared with painless DPN, painful DPN had significantly lower HF (3.59 +/- 1.08 [means +/- SD] vs. 2.67 +/- 1.56), TP (5.73 +/- 1.28 vs. 4.79 +/- 1.51), and SDNN (2.91 +/- 0.65 vs. 1.62 +/- 3.5), P < 0.05. No significant differences were seen between painless DPN and painful DPN using an AFT. CONCLUSIONS: This study shows that painful DPN is associated with significantly greater autonomic dysfunction than painless DPN. These changes are only detected using spectral analysis of HRV (a simple test based on a 5-min electrocardiogram recording), suggesting that it is a more sensitive tool to detect autonomic dysfunction, which is still under-detected in people with diabetes. The greater autonomic dysfunction seen in painful DPN may reflect more predominant small fiber involvement and adds to the growing evidence of its role in the pathophysiology of painful DPN.
Subject(s)
Autonomic Nervous System Diseases/epidemiology , Diabetes Mellitus, Type 1/epidemiology , Diabetic Neuropathies/epidemiology , Neuralgia/epidemiology , Adult , Autonomic Nervous System Diseases/diagnosis , Chronic Disease , Diabetic Neuropathies/diagnosis , Heart Rate , Humans , Middle Aged , Neuralgia/diagnosis , PrevalenceABSTRACT
OBJECTIVE: Diabetic large-nerve fiber dysfunction, as measured by vibration perception threshold (VPT), predicts foot ulceration, amputation, and mortality. Thus, determination of modifiable risk factors is of great clinical importance. RESEARCH DESIGN AND METHODS: We assessed 1,407 patients with type 1 diabetes and a normal VPT participating in the EURODIAB Prospective Complications Study, at baseline mean +/- SD age of 32.7 +/- 10.2 years with diabetes duration of 14.7 +/- 9.3 years and follow-up of 7.3 +/- 0.6 years. VPT was measured using biothesiometry on the right big toe and medial malleolus. An abnormal result was defined as >2 SD from the predicted mean for the patient s age. RESULTS: An abnormal VPT was associated with an increased incidence of gangrene, amputation, foot ulceration, leg bypass or angioplasty, and mortality (P < OR = 0.02). The incidence of abnormal VPT was 24% over the 7.3-year follow-up. Duration of diabetes and A1C significantly influenced the incidence of abnormal VPT (P < 0.0001). After correction for these, established risk factors for cardiovascular disease (CVD), including male sex (P = 0.0004), hypertension (P < 0.0001), total cholesterol (P = 0.002), LDL cholesterol (P = 0.01), smoking (P < 0.0001), weight (P < 0.0001), and diabetes complications (retinopathy [P = 0.0001], nephropathy [P = 0.01], and autonomic neuropathy [P = 0.001]), were all found to be significant risk factors. A previous history of CVD doubled the incidence of abnormal VPT. CONCLUSIONS: This prospective study indicates that cardiovascular risk factors predict development of large-fiber dysfunction, which may account for the high mortality rate in patients with an abnormal VPT, and emphasizes the importance of early determination of VPT to detect subclinical neuropathy and to address cardiovascular risk factors.
Subject(s)
Cardiovascular Diseases/metabolism , Diabetes Mellitus, Type 1/complications , Diabetic Neuropathies/etiology , Perception/physiology , Peripheral Nervous System Diseases/etiology , Adult , Cholesterol/metabolism , Cholesterol, LDL/metabolism , Diabetes Complications , Diabetic Nephropathies/complications , Diabetic Neuropathies/metabolism , Female , Humans , Hypertension/complications , Male , Peripheral Nervous System Diseases/metabolism , Prospective Studies , Risk Factors , Sensory Thresholds/physiology , Sex Factors , Smoking , Young AdultABSTRACT
Autonomic neuropathy (AN) is a common and serious complication of diabetes. Early detection is essential to enable appropriate interventional therapy. It has long been recognized that subjects with diabetic peripheral neuropathy (DPN) are at much greater risk of developing AN, but there is currently no simple screening tool to assess them. The aim of this study was to investigate pupil responsiveness in diabetic subjects with and without DPN using dynamic pupillometry. During the first test, one flash was administered and the pupil response recorded for 3 seconds. In the second test, twenty-five flashes at one-second intervals were administered and the pupil response recorded for 30 seconds. Several time related parameters were computed from the results. A total of 29 diabetic subjects (17 no DPN, 12 DPN) and 25 healthy volunteers took part in the study. In the first test, pupil-iris ratios in darkness, large deviation and plateau were significantly different between groups. Latency time from flash exposure to the start of constriction was significantly longer in diabetic subjects with DPN compared to healthy volunteers. There was no difference in latency times of largest deviation, plateau or duration of constriction between groups. In the second test, the pupil-iris ratios evaluated in the frame preceding the tenth and the twenty-fifth light flash were significantly greater in healthy volunteers than diabetic subjects with DPN. Latency time from the tenth and twenty-fifth flash exposure to the start of constriction was significantly shorter in healthy volunteers than in diabetic subjects with DPN.