RESUMEN
AIM: To validate the Composite Autonomic Symptom Score (COMPASS) 31, in its Italian version, for the diagnosis of diabetic cardiovascular autonomic neuropathy in a clinic-based, single-centre study. METHODS: A total of 73 participants with diabetes (age 55 ± 14 years) completed the COMPASS 31 questionnaire before undergoing cardiovascular autonomic neuropathy and diabetic polyneuropathy assessment according to cardiovascular reflex tests, neuropathic symptoms and signs, and vibration and thermal thresholds. RESULTS: The COMPASS 31 total weighted score differed between participants with and without cardiovascular autonomic neuropathy (29.9 ± 19.5 vs 16.1 ± 14.7; P = 0.003) and with and without diabetic polyneuropathy (28.9 ± 19.1 vs 12.7 ± 11.3; P < 0.0001). It was related to cardiovascular reflex tests score (rho = 0.38, P = 0.0013) as well as diabetic polyneuropathy symptoms (rho=0.61, P < 0.0001) and signs scores (rho = 0.49, P < 0.0001). Receiver-operating curve analysis showed a fair diagnostic accuracy of total score for cardiovascular autonomic neuropathy (area under the curve 0.748 ± 0.068, 95% CI 0.599-0.861) and diabetic polyneuropathy (area under the curve 0.742 ± 0.061, 95% CI 0.611-0.845). The best score thresholds were 16 for early cardiovascular autonomic neuropathy (sensitivity 75.0%, specificity 64.9%, positive predictive value 37.5% and negative predictive value 90.2%), and 17 for both confirmed cardiovascular autonomic neuropathy and diabetic polyneuropathy (sensitivity 70.0% and 65.5%, respectively; specificity 66.7% and 79.5%, respectively; positive predictive value 25.0% and 67.9%, respectively; and negative predictive value 93.0% and 77.8%, respectively). COMPASS 31 had a good internal consistency according to Cronbach's α coefficient of 0.73. CONCLUSIONS: COMPASS 31 can represent a valid, easy-to-use, quantitative assessment tool for autonomic symptoms in diabetic neuropathy, with a fair diagnostic accuracy for both cardiovascular autonomic neuropathy and diabetic polyneuropathy.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Angiopatías Diabéticas/líquido cefalorraquídeo , Neuropatías Diabéticas/diagnóstico , Técnicas de Diagnóstico Endocrino , Técnicas de Diagnóstico Neurológico , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Proyectos de Investigación , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
AIMS/HYPOTHESIS: The aim was to evaluate the efficacy and safety of transcutaneous frequency-modulated electromagnetic neural stimulation (frequency rhythmic electrical modulation system, FREMS) as a treatment for symptomatic peripheral neuropathy in patients with diabetes mellitus. METHODS: This was a double-blind, randomised, multicentre, parallel-group study of three series, each of ten treatment sessions of FREMS or placebo administered within 3 weeks, 3 months apart, with an overall follow-up of about 51 weeks. The primary endpoint was the change in nerve conduction velocity (NCV) of deep peroneal, tibial and sural nerves. Secondary endpoints included the effects of treatment on pain, tactile, thermal and vibration sensations. Patients eligible to participate were aged 18-75 years with diabetes for ≥ 1 year, HbA(1c) <11.0% (97 mmol/mol), with symptomatic diabetic polyneuropathy at the lower extremities (i.e. abnormal amplitude, latency or NCV of either tibial, deep peroneal or sural nerve, but with an evocable potential and measurable NCV of the sural nerve), a Michigan Diabetes Neuropathy Score ≥ 7 and on a stable dose of medications for diabetic neuropathy in the month prior to enrolment. Data were collected in an outpatient setting. Participants were allocated to the FREMS or placebo arm (1:1 ratio) according to a sequence generated by a computer random number generator, without block or stratification factors. Investigators digitised patients' date of birth and site number into an interactive voice recording system to obtain the assigned treatment. Participants, investigators conducting the trial, or people assessing the outcomes were blinded to group assignment. RESULTS: Patients (n = 110) with symptomatic neuropathy were randomised to FREMS (n = 54) or placebo (n = 56). In the intention-to-treat population (50 FREMS, 51 placebo), changes in NCV of the three examined nerves were not different between FREMS and placebo (deep peroneal [means ± SE]: 0.74 ± 0.71 vs 0.06 ± 1.38 m/s; tibial: 2.08 ± 0.84 vs 0.61 ± 0.43 m/s; and sural: 0.80 ± 1.08 vs -0.91 ± 1.13 m/s; FREMS vs placebo, respectively). FREMS induced a significant reduction in day and night pain as measured by a visual analogue scale immediately after each treatment session, although this beneficial effect was no longer measurable 3 months after treatment. Compared with the placebo group, in the FREMS group the cold sensation threshold was significantly improved, while non-significant differences were observed in the vibration and warm sensation thresholds. No relevant side effects were recorded during the study. CONCLUSIONS/INTERPRETATION: FREMS proved to be a safe treatment for symptomatic diabetic neuropathy, with immediate, although transient, reduction in pain, and no effect on NCV. TRIAL REGISTRATION: ClinicalTrials.gov NCT01628627. FUNDING: The clinical trial was sponsored by Lorenz Biotech (Medolla, Italy), lately Lorenz Lifetech (Ozzano dell'Emilia, Italy).
Asunto(s)
Neuropatías Diabéticas/terapia , Campos Electromagnéticos , Magnetoterapia/métodos , Adolescente , Adulto , Anciano , Método Doble Ciego , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
A simple non-invasive indicator test (Neuropad(®)) has been developed for the assessment of sweating and, hence, cholinergic innervation in the diabetic foot. The present review summarizes current knowledge on this diagnostic test. The diagnostic ability of this test is based on a colour change from blue to pink at 10 min, with excellent reproducibility, which lends itself to patient self-examination. It has a high sensitivity (65.1-100%) and negative predictive value (63-100%), with moderate specificity (32-78.5%) and positive predictive value (23.3-93.2%) for the diagnosis of diabetic peripheral neuropathy. It also has moderate to high sensitivity (59.1-89%) and negative predictive value (64.7-91%), but low to moderate specificity (27-78%) and positive predictive value (24-48.6%) for the diagnosis of diabetic cardiac autonomic neuropathy. There are some data to suggest that Neuropad can detect early diabetic neuropathy, but this needs further evaluation. It remains to be established whether this test can predict foot ulceration and amputation, thereby contributing to the identification of high-risk patients.
Asunto(s)
Pie Diabético/diagnóstico , Indicadores y Reactivos/química , Juego de Reactivos para Diagnóstico , Sudor/química , Amputación Quirúrgica , Biomarcadores/análisis , Pie Diabético/metabolismo , Pie Diabético/fisiopatología , Diagnóstico Precoz , Femenino , Humanos , Masculino , Selección de Paciente , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Umbral Sensorial , Sudor/metabolismoRESUMEN
AIMS: DN4 (Douleur Neuropathique en 4 Questions) is a screening tool for neuropathic pain consisting of interview questions (DN4-interview) and physical tests. It has not formally been validated in diabetes. We evaluated the validity and diagnostic accuracy of DN4 and DN4-interview in identifying neuropathic pain of painful diabetic polyneuropathy. METHODS: In 158 patients with diabetes, the presence of diabetic polyneuropathy and neuropathic pain was assessed using scoring system for symptoms and signs, quantitative sensory testing, nerve conduction studies, pain history, numerical rating scale, and Short-Form McGill Pain Questionnaire. Painful diabetic polyneuropathy was defined as the presence of diabetic polyneuropathy plus chronic neuropathic pain in the same area as neuropathic deficits. A blinded investigator performed DN4. RESULTS: The DN4 score was significantly related to all the neurological and electrophysiological measurements and to Short-Form McGill Pain Questionnaire (ρ = 0.58, P < 0.0001). DN4 and DN4-interview scores showed a high diagnostic accuracy for painful diabetic polyneuropathy with areas under the receiver operating characteristic curve of 0.94 and 0.93, respectively. At the cut-off of 4, DN4 displayed sensitivity of 80%, specificity of 92%, positive predictive value (PPV) of 82%, negative predictive value (NPV) of 91%, and likelihood ratio for a positive result (LR(+) ) of 9.6. At the cut-off of 3, DN4-interview showed sensitivity and specificity of 84%, PPV of 71%, NPV of 92%, and LR(+) of 5.3. CONCLUSIONS: This is the first validation study of DN4 for painful diabetic polyneuropathy, which supports its usefulness as both a screening tool for neuropathic pain in diabetes and a reliable component of the diagnostic work up for painful diabetic polyneuropathy.
Asunto(s)
Neuropatías Diabéticas/diagnóstico , Neuralgia/diagnóstico , Dimensión del Dolor/métodos , Estudios Transversales , Neuropatías Diabéticas/epidemiología , Femenino , Humanos , Italia/epidemiología , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Neuralgia/epidemiología , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Encuestas y Cuestionarios , VibraciónRESUMEN
Despite its prevalence, clinical and prognostic impact, diabetic autonomic neuropathy, is widely under-diagnosed. The need for training and expertise to perform the cardiovascular tests (usually the task of diabetologists) is one possible reason. The availability of computer-assisted systems has allowed a wider diffusion of testing, but has also highlighted the need for an adequate knowledge of physiopathological backgrounds for their correct application and interpretation. The recommendations presented here were developed by the Neuropathy Study Group of the Italian Society of Diabetology and then endorsed by the Italian Association for the Study of Neurovegetative System, to promote the widespread adoption of good clinical practice in diabetic cardiovascular autonomic testing by outlining main evidence-based aspects, i.e. which tests, how to perform them, adequate interpretation of the results and their diagnostic use, confounding conditions that can impact on tests reliability. Therefore, these recommendations include the essential aspects of the physiopathological substrate of the tests, the controversial points in their analysis, their diagnostic characteristics, as well as safety. Detailed information is given on the physiological (age, weight, body position, resting heart rate and blood pressure, respiratory pattern, exercise, meals, acute blood glucose changes) and pathophysiological confounding factors, with emphasis on the effects of drugs. Instructions on how to perform the tests and interpret their results are also considered together with indications of candidate patients and periodicity of testing. A patient instruction sheet on why and how to perform the tests is included. Finally, the specific requirements for computerized systems to perform and evaluate cardiovascular tests are provided.
Asunto(s)
Fenómenos Fisiológicos Cardiovasculares , Neuropatías Diabéticas/diagnóstico , Biomarcadores , Cardiomiopatías Diabéticas/diagnóstico , Progresión de la Enfermedad , Guías como Asunto , Humanos , Cooperación del Paciente , Selección de Paciente , Estándares de Referencia , Medición de RiesgoRESUMEN
Despite the high prevalence of diabetic neuropathy, its early start, and its impact on quality of life and mortality, unresolved clinical issues persist in the field regarding its screening implementation, the understanding of its mechanisms, and the search for valid biomarkers, as well as disease-modifying treatment. Genetics may address these needs by providing genetic biomarkers of susceptibility, giving insights into pathogenesis, and shedding light on how to select possible responders to treatment. After a brief summary of recent studies on the genetics of diabetic neuropathy, the current review focused mainly on microRNAs (miRNAs), including the authors' results in this field. It summarized the findings of animal and human studies that associate miRNAs with diabetic neuropathy and explored the possible pathogenetic meanings of these associations, in particular regarding miR-128a, miR-155a, and miR-499a, as well as their application for diabetic neuropathy screening. Moreover, from a genetic perspective, it examined new findings of polymorphisms of miRNA genes in diabetic neuropathy. It considered in more depth the pathogenetic implications for diabetic neuropathy of the polymorphism of MIR499A and the related changes in the downstream action of miR-499a, showing how epigenetic and genetic studies may provide insight into pathogenetic mechanisms like mitochondrial dysfunction. Finally, the concept and the data of genotype-phenotype association for polymorphism of miRNA genes were described. In conclusion, although at a very preliminary stage, the findings linking the genetics and epigenetics of miRNAs might contribute to the identification of exploratory risk biomarkers, a comprehensive definition of susceptibility to specific pathogenetic mechanisms, and the development of mechanism-based treatment of diabetic neuropathy, thus addressing the goals of genetic studies.
Asunto(s)
Neuropatías Diabéticas/genética , Epigénesis Genética , MicroARNs/genética , Polimorfismo Genético , Animales , Neuropatías Diabéticas/metabolismo , Neuropatías Diabéticas/terapia , Predisposición Genética a la Enfermedad , Humanos , MicroARNs/metabolismo , Fenotipo , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de RiesgoRESUMEN
AIMS: The aim of the present study was to determine the diagnostic accuracy of the Neuropad sudomotor test for diabetic cardiovascular autonomic neuropathy (CAN) and diabetic polyneuropathy (DPN), the latter assessed using a multi-level diagnostic approach. METHODS: In 51 diabetic patients, CAN, symptoms and signs of DPN, vibration perception threshold (VPT), cold (CTT) and warm thermal perception thresholds (WTT) were measured. Neuropad response was determined as normal (complete colour change) or abnormal (absent or incomplete colour change). The time until the complete colour change (CCC time) was recorded. RESULTS: CCC time showed significant correlations with all the neurological parameters, the strongest of which were with Valsalva ratio (rho = -0.64, P < 0.0001), symptoms of DPN (rho = 0.66, P < 0.0001), postural hypotension (rho = 0.54, P = 0.0001) and CTT (rho = -0.54, P = 0.0001). CCC time showed moderate diagnostic accuracy for both CAN and DPN: the areas under the receiver operating characteristic (ROC) curves were 0.71 and 0.76, respectively. The diagnostic characteristics of three cut-off values of CCC time, identified by ROC analysis (i.e. 10, 15 and 18 min), were analysed. Compared with 10 min, the 15-min cut-off value provided better specificity (from 27% to 52% and from 31% to 62% for CAN and DPN, respectively) and a better likelihood ratio for negative result (from 0.67 to 0.34 and from 0.58 to 0.33) without lowering sensitivity (from 82% to 82% and from 85% to 80%). CONCLUSIONS: Neuropad is a reliable diagnostic tool for both CAN and DPN, albeit of only moderate accuracy. Extending the observation period to 15 min provides greater diagnostic usefulness.
Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Neuropatías Diabéticas/diagnóstico , Adolescente , Adulto , Anciano , Frío , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polineuropatías/diagnóstico , Estadística como Asunto , Sensación Térmica , Factores de Tiempo , Vibración , Adulto JovenRESUMEN
This study investigated whether nondipping (defined as a day-night change in blood pressure (BP) Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/fisiopatología
, Monitoreo Ambulatorio de la Presión Arterial
, Presión Sanguínea
, Diabetes Mellitus Tipo 1/fisiopatología
, Neuropatías Diabéticas/fisiopatología
, Adulto
, Análisis de Varianza
, Biomarcadores/sangre
, Biomarcadores/orina
, Estudios de Casos y Controles
, Ritmo Circadiano
, Femenino
, Humanos
, Modelos Lineales
, Modelos Logísticos
, Masculino
, Persona de Mediana Edad
, Valor Predictivo de las Pruebas
, Curva ROC
, Ciudad de Roma
RESUMEN
OBJECTIVE: To validate nerve-axon reflex-related vasodilatation as an objective method to evaluate C-nociceptive fibre function by comparing it with the standard diagnostic criteria. METHODS: Neuropathy was evaluated in 41 patients with diabetes (26 men and 15 women) without peripheral vascular disease by assessing the Neuropathy Symptom Score, the Neuropathy Disability Score (NDS), the vibration perception threshold (VPT), the heat detection threshold (HDT), nerve conduction parameters and standard cardiovascular tests. The neurovascular response to 1% acetylcholine (Ach) iontophoresis was measured at the forearm and at both feet by laser flowmetry. An age-matched and sex-matched control group of 10 healthy people was also included. RESULTS: Significant correlations were observed between the neurovascular response at the foot and HDT (r(s) = -0.658; p<0.0001), NDS (r(s) = -0.665; p<0.0001), VPT (r(s) = -0.548; p = 0.0005), tibial nerve conduction velocity (r(s) = 0.631; p = 0.0002), sural nerve amplitude (r(s) = 0.581; p = 0.0002) and autonomic function tests. According to the NDS, in patients with diabetes who had mild, moderate or severe neuropathy, a significantly lower neurovascular response was seen at the foot than in patients without neuropathy and controls. A neurovascular response <50% was found to be highly sensitive (90%), with a good specificity (74%), in identifying patients with diabetic neuropathy. CONCLUSION: Small-fibre dysfunction can be diagnosed reliably with neurovascular response assessment. This response is already reduced in the early stages of peripheral neuropathy, supporting the hypothesis that small-fibre impairment is an early event in the natural history of diabetic neuropathy.
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Axones/patología , Fibras Colinérgicas/patología , Neuropatías Diabéticas/diagnóstico , Reflejo Anormal , Anciano , Electrofisiología , Femenino , Humanos , Iontoforesis , Masculino , Persona de Mediana Edad , Conducción Nerviosa , Examen Neurológico , Curva ROC , Sensibilidad y Especificidad , VasodilataciónRESUMEN
The utility of standard cardiovascular tests for diagnosis of cardiac autonomic neuropathy in diabetes has been well documented. Attention must be paid to standardizing the procedure with regard to time of day, metabolic status, distance from meal and insulin, coffee and smoking avoidance, and patient's collaboration. In the presence of cardiovascular disease or drugs affecting the cardiovascular or autonomic nervous system, some caution is needed in interpreting the results. More recent reflex tests, which evaluate mainly sympathetic or baroreflex activity, despite their ability to detect early autonomic involvement, lack sufficient standardization and still need to be proved as valid alternatives. Of the different methods of measuring heart rate variability, spectral analysis has a greater ability to differentiate vagal and sympathetic modulation of heart rate than do time-domain methods. However, since these latter methods are easier and more widely available, they can be used as a screening approach. Twenty-four-hour evaluation of heart rate variability provides data on the circadian rhythm of sympathovagal activity, which can be affected earlier than and differently from cardiovascular reflex tests. Information obtained could have prognostic implications in terms of cardiovascular morbidity and mortality and offer therapeutic opportunities. However, a wide consensus on many technical aspects of both time-domain and frequency-domain methods is needed. Furthermore, large prospective studies in the diabetic population to assess the prognostic value of 24-h heart rate variability parameters on cardiovascular morbidity and mortality are lacking. Recently, I123 meta-iodobenzylguanidine (MIBG) scintigraphy has documented abnormalities of sympathetic myocardial innervation also in newly diagnosed IDDM. The meaning of this finding, whether it is an expression of functional or structural defects, needs to be clarified. Preliminary data point to a possible pathogenetic meaning of the known association between autonomic neuropathy and other diabetic complications. This area of investigation could provide useful insights into the complex and multifactorial pathogenesis of diabetic complications.
Asunto(s)
Enfermedades Cardiovasculares/diagnóstico , Complicaciones de la Diabetes , Neuropatías Diabéticas/diagnóstico , Factores de Edad , Sistema Nervioso Autónomo/fisiopatología , Barorreflejo , Presión Sanguínea , Ritmo Circadiano , Frecuencia Cardíaca , Humanos , Reflejo , Sistema Nervioso Simpático/fisiopatologíaRESUMEN
In diabetic autonomic neuropathy, abnormal circadian patterns of blood pressure and sympathovagal balance with reduced fall of blood pressure and prevalence of sympathetic activity during the night have been described. To correlate the abnormalities of blood pressure to those of sympathovagal balance, we simultaneously performed 24-h noninvasive monitoring of blood pressure and ECG in 25 diabetic patients (45.6 +/- 13.6 yr of age with a 17.6 +/- 9.1 yr duration of diabetes) with various degrees of cardiovascular reflex impairment. Autoregressive power spectrum analysis of RR interval variability was applied to 24-h ECG recordings to obtain for day and night periods the mean power of low- (0.03-0.15 Hz) and high-frequency (0.18-0.40 Hz) components, which are relative markers of sympathetic and vagal activity, respectively, and their ratio (low frequency/high frequency), assumed as index of sympathovagal balance. Diabetic patients showed a lower percentage of day-night change in systolic blood pressure (9 +/- 5.48 vs. 11.6 +/- 4.78%, P < 0.037), a lower day low frequency (5.9 +/- 0.81 vs. 6.62 +/- 0.73 In-ms2, P < 0.001), a lower night high frequency (6.06 +/- 0.71 vs. 6.52 +/- 0.85 In-ms2, P < 0.05), a lower day low frequency:high frequency ratio (1.82 +/- 1.77 vs. 3.05 +/- 1.82, P < 0.01), and a lower percentage of day-night change in low-frequency:high frequency ratio (-13.4 +/- 109.9 vs. 28.7 +/- 29.7%, P < 0.05), when compared with control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Presión Sanguínea , Ritmo Circadiano , Neuropatías Diabéticas/fisiopatología , Nervio Vago/fisiopatología , Adulto , Monitores de Presión Sanguínea , Diástole , Electrocardiografía Ambulatoria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , SístoleRESUMEN
OBJECTIVE: To evaluate the relationship between autonomic neuropathy, nephropathy, and 24-h blood pressure (BP) pattern in insulin-dependent diabetes mellitus (IDDM). RESEARCH DESIGN AND METHODS: We studied 30 normotensive IDDM patients without overt nephropathy, divided into two groups and matched for age, duration of diabetes, and HbA1, according to the presence of cardiovascular autonomic neuropathy. We simultaneously measured 24-h BP and urinary albumin excretion rate (UAE) on urine collections timed overnight and at 2-h intervals during the day. RESULTS: Mean day and night systolic and diastolic BP values did not significantly differ between the groups. Mean night albuminuria was significantly higher in patients with autonomic neuropathy than in those without (61.4 +/- 104.6 [mean +/- SD] vs. 16 +/- 25.2 micrograms/min, P < 0.04). The percentages day-night changes in systolic BP, diastolic BP, and UAE were significantly lower in neuropathic patients (systolic BP: 2.4 +/- 7.7 vs. 9.6 +/- 4.2%, P < 0.001; diastolic BP: 8.4 +/- 6.9 vs. 15.5 +/- 5.4%, P < 0.002; UAE: -8 +/- 99.4 vs. 49.3 +/- 29.4%, P < 0.02) and were inversely related to autonomic score, index of autonomic neuropathy degree (r = -0.54, P < 0.002; r = -0.58, P < 0.001; and r = -0.53, P < 0.005, respectively). In patients with autonomic neuropathy, 2-h day periods and day and night UAE were more strongly related, respectively, to mean 2-h day periods (r = 0.58, P < 0.0001), day systolic BP (r = 0.67, P < 0.04), and night systolic BP (r = 0.69, P < 0.04) than in patients without autonomic neuropathy (2-h day periods: r = 0.32, P < 0.001; day: r = 0.37, NS; night: r = 0.35, NS). CONCLUSIONS: Autonomic neuropathy in IDDM patients is associated with reduced nocturnal falls in BP and UAE and with a stronger relationship of UAE to systolic BP. We suggest a pathogenetic role of autonomic neuropathy in the development of diabetic nephropathy through changes in nocturnal glomerular function and by enhanced kidney vulnerability to hemodynamic effects of BP.
Asunto(s)
Presión Sanguínea , Diabetes Mellitus Tipo 1/fisiopatología , Nefropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/fisiopatología , Adulto , Sistema Nervioso Autónomo/fisiopatología , Creatinina/sangre , Diabetes Mellitus Tipo 1/sangre , Nefropatías Diabéticas/sangre , Neuropatías Diabéticas/sangre , Retinopatía Diabética/sangre , Retinopatía Diabética/fisiopatología , Diástole , Femenino , Humanos , Masculino , Postura , Valores de Referencia , Análisis de Regresión , Respiración , Sístole , Maniobra de ValsalvaRESUMEN
In patients with insulin-dependent diabetes, antihypertensive treatment has a beneficial effect on the rate of progression toward uremia of overt diabetic nephropathy (albumin excretion rate [AER] greater than 300 mg/24 hour). The influence of hypertension on the progression of "incipient" nephropathy (AER ranging between 30 and 300 mg/24 hours) is not well defined, particularly in patients with noninsulin-dependent diabetes. In this study, 21 patients with noninsulin-dependent diabetes and hypertension (11 with normoalbuminuria and 10 with microalbuminuria), who were comparable for age, duration of diabetes and hypertension, were treated with indapamide, 2.5 mg once daily, and followed up for 24 months. Blood pressure, glomerular filtration rate (GFR), albumin excretion rate and subclass 4 of urinary immunoglobulin G (IgG4) were indicated. In normoalbuminuric patients, blood pressure was significantly reduced, whereas AER, IgG4 and GFR did not show any variation throughout the study. In microalbuminuric patients, blood pressure, AER and IgG4 were significantly reduced, and GFR remained unchanged. In patients with noninsulin-dependent diabetes, antihypertensive treatment, which is begun during incipient diabetic nephropathy, may have a beneficial effect on the progression of the disease, although a long-term follow-up study is needed to confirm this.
Asunto(s)
Albuminuria/fisiopatología , Diabetes Mellitus Tipo 1 , Nefropatías Diabéticas/fisiopatología , Diuréticos/uso terapéutico , Tasa de Filtración Glomerular/efectos de los fármacos , Hipertensión/tratamiento farmacológico , Inmunoglobulina G/orina , Indapamida/uso terapéutico , Adulto , Albuminuria/orina , Glucemia/análisis , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 1/fisiopatología , Nefropatías Diabéticas/orina , Dieta para Diabéticos , Estudios de Seguimiento , Humanos , Hipertensión/sangre , Hipertensión/fisiopatología , Persona de Mediana Edad , Potasio/sangre , Sodio/sangreRESUMEN
The possible relationship between diabetic autonomic neuropathy, circadian blood pressure changes, and echocardiographic parameters was investigated in 27 normotensive diabetic patients (10 with and 17 without autonomic neuropathy) who underwent 24 h noninvasive ambulatory blood pressure monitoring and M-mode echocardiographic recording. The two groups were comparable for age, sex, duration of diabetes, body mass index, and metabolic control. There were no significant differences in 24 h average and diurnal values of systolic, diastolic, or mean blood pressure. The percent changes from day to night of systolic, diastolic, and mean blood pressures were significantly lower in diabetics with neuropathy than in those without (P < .04 or less). Increased left ventricular mass index (LVMI) (135.4 +/- 10.2 v 102.9 +/- 6.3; P < .005), septal wall thickness, and posterior wall width were observed in neuropathic patients. Fractional shortening, peak velocity of early left ventricular filling (E), peak velocity of late ventricular filling (A), and their ratio (E/A) were similar in the two groups. The increased LVMI we observed may represent a possible link between diabetic autonomic neuropathy, nocturnal blood pressure levels, and higher cardiovascular mortality rate.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/complicaciones , Angiopatías Diabéticas/etiología , Neuropatías Diabéticas/complicaciones , Hipertrofia Ventricular Izquierda/etiología , Adulto , Anciano , Envejecimiento/patología , Envejecimiento/fisiología , Enfermedades del Sistema Nervioso Autónomo/patología , Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Presión Sanguínea/fisiología , Índice de Masa Corporal , Angiopatías Diabéticas/patología , Angiopatías Diabéticas/fisiopatología , Neuropatías Diabéticas/patología , Neuropatías Diabéticas/fisiopatología , Ecocardiografía , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Hipertrofia Ventricular Izquierda/patología , Hipertrofia Ventricular Izquierda/fisiopatología , Masculino , Persona de Mediana Edad , Caracteres SexualesRESUMEN
Some controversy still exists about factors involved in the abnormal circadian pattern of blood pressure (BP) in diabetes, while prognostic value of non-dipping condition is being increasingly recognised. This study was aimed at evaluating the relative influence of autonomic neuropathy (AN) and albumin excretion on 24-h BP profile in type 1 and type 2 diabetes. We measured AN cardiovascular tests, 24-h ambulatory BP, and urinary albumin excretion rate (UAE) in 47 type 1 and 34 type 2 normotensive non-proteinuric diabetic patients. In type 1 diabetic patients day-night differences (Delta) in systolic and diastolic BP were lower in those with AN than in those without (3 +/- 9 vs 10 +/- 6%, P < 0.01, and 8 +/- 9 vs 16 +/- 6%, P < 0.001), and in univariate regression analysis they were inversely related to both autonomic score, index of degree of AN (r = -0.61, P < 0.001 and r = -0.65, P < 0.001), and to 24-h UAE (r = -0.39, P < 0.01 and r = -0.46, P < 0.001). In type 1 diabetic patients AN was also associated with lower nocturnal decrease in UAE (patients with AN vs without AN: -37 +/- 214 vs 49 +/- 37%, P < 0.05), and with a stronger relationship between simultaneous 24-h UAE and 24-h BP (for systolic BP patients with AN vs without AN: r = 0.62, P < 0.01 vs r = 0.28, NS). In type 2 diabetic patients Delta systolic BP was reduced in patients with AN compared to those without (4 +/- 7 vs 10 +/- 4%, P < 0.01), and it was related only to autonomic score (r = -0.42, P < 0.01). Using a stepwise regression analysis, in type 1 diabetic patients autonomic score was the variable of primary importance for Delta BP, while in type 2 diabetic patients it was the unique determinant not only of Delta systolic BP but also of 24-h systolic BP. In conclusion, AN is the pivotal factor of blunted nocturnal fall in BP in both type 1 and type 2 diabetic patients. In type 1 diabetic patients AN is associated with attenuated circadian pattern of albuminuria and with a steeper relationship between albuminuria and BP, in type 2 diabetic patients AN is the only factor related to elevated 24-h BP levels. Longitudinal studies are needed to establish the potential role of autonomic dysfunction as a progression promoter for nephropathy and hypertension in type 1 and type 2 diabetes respectively.
Asunto(s)
Presión Sanguínea/fisiología , Ritmo Circadiano/fisiología , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Hipertensión/fisiopatología , Adulto , Albuminuria/complicaciones , Albuminuria/fisiopatología , Monitoreo Ambulatorio de la Presión Arterial , Femenino , Humanos , Hipertensión/etiología , Masculino , Persona de Mediana EdadRESUMEN
In 97 IDDM and 64 NIDDM patients aged under 65 years, we evaluated the relationship between autonomic neuropathy (AN) and retinopathy, nephropathy, glycemic control and cardiovascular risk factors. Diabetes duration and HbA1 were significantly higher and body mass index was significantly lower in IDDM patients with AN compared to those without. In NIDDM only age was significantly higher in neuropathic patients. AN was associated with retinopathy in both IDDM (chi2 = 10, P < 0.03) and NIDDM patients (chi2 = 14, P < 0.007), while only in IDDM albumin excretion was significantly higher in patients with AN. Blood pressure (BP) was significantly higher in both IDDM and NIDDM patients with AN compared to those without. There were no differences in smoking and serum lipids between patients with and those without AN. We performed a multiple regression analysis using autonomic score, index of cardiovascular tests impairment, as the dependent variable and age, diabetes duration, body mass index, HbA1, albumin excretion, cholesterolemia, triglyceridemia, systolic BP, and retinopathy as independent variables. With this model in IDDM autonomic score was only related to body mass index (r = -0.29, P < 0.05), to HbA1 (r = 0.46, P < 0.001), and to systolic BP (r = 0.24, P < 0.05), while in NIDDM it was only related to systolic BP (r = 0.54, P < 0.001). In conclusion, AN was related to age in NIDDM, and to diabetes duration and glycemic control in IDDM. AN was associated with retinopathy, with nephropathy (only in IDDM), and with BP levels, but not with dyslipidemia, smoking, or obesity. Excess mortality rate observed in diabetic AN cannot be referred to an association with cardiovascular risk factors.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/etiología , Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Angiopatías Diabéticas/etiología , Neuropatías Diabéticas/etiología , Adulto , Análisis de Varianza , Enfermedades Cardiovasculares/metabolismo , Estudios Transversales , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
Previous studies have shown an increased incidence of sudden deaths and lower survival in diabetics with autonomic neuropathy. In hypertensive non diabetic patients a direct correlation has been found between nocturnal blood pressure levels and left ventricular hypertrophy. We have shown in diabetics with autonomic neuropathy a flattening in nocturnal blood pressure reduction and increased 24 hours blood pressure values compared to diabetics without autonomic neuropathy and controls. Our results suggest that abnormalities in 24 hours blood pressure profile might play a role in the increased incidence of cardiovascular morbidity and mortality in diabetics with autonomic neuropathy.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/fisiopatología , Monitores de Presión Sanguínea , Presión Sanguínea/fisiología , Ritmo Circadiano/fisiología , Neuropatías Diabéticas/fisiopatología , Frecuencia Cardíaca/fisiología , Adulto , Sistema Nervioso Autónomo/fisiopatología , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The development of sensitive techniques evaluating functions under autonomic control has allowed the early detection of widespread abnormalities in diabetes mellitus. However, despite a high frequency of functional abnormalities, an overt clinical syndrome develops slowly and is quite rare. Characteristic clinical features, more recent methods for evaluating autonomic function, diagnostic procedures, and main instrumental findings in a diabetic population are reported. Emphasis is given to more promising techniques evaluating autonomic control of the cardiovascular system, such as myocardial scintigraphy and assessment of 24-h blood pressure and heart rate variability. The clinical meaning of the number of functional abnormalities observed in diabetic patients is considered. While the role of autonomic neuropathy in the pathogenesis of gastrointestinal motor disorders, hypoglycaemia unawareness or diabetic impotence needs to be revised, the importance of autonomic-related sweating and blood flow abnormalities in the pathogenesis of diabetic foot lesions is now better documented. Moreover, growing evidence of the importance of autonomic control of cardiovascular system, together with cardiovascular dysfunction linked to diabetic autonomic neuropathy, supports the hypothesis of a possible role of autonomic neuropathy in the increased cardiovascular morbidity and mortality observed in diabetic patients.
Asunto(s)
Neuropatías Diabéticas/fisiopatología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Ritmo Circadiano/fisiología , Neuropatías Diabéticas/diagnóstico , Enfermedades de la Vesícula Biliar/fisiopatología , Enfermedades Gastrointestinales/fisiopatología , Corazón/inervación , Humanos , Flujo Sanguíneo Regional , Sistema Nervioso Simpático/fisiologíaRESUMEN
Epidemiologic studies suggest a close association between hypertension, obesity, and diabetes. It has been demonstrated that essential hypertension, per se, is an insulin-resistant state. However, the pathogenesis of the association between insulin resistance and hypertension is poorly understood. Elevated plasma insulin levels may contribute to the development of hypertension through renal sodium reabsorption, the sympathetic nervous system, the transmembranous cation transport, the renin-angiotensin system, the cardiovascular reactivity, and the atrial natriuretic peptide. Diuretics, beta-blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, and alpha 1-antagonists are first-choice drugs in the management of hypertension. Diuretics, except indapamide, impair insulin sensitivity and glucose tolerance. The same negative effects, exerted by beta-blockers, are reduced employing those with selective activity. With few exceptions, calcium antagonists have no adverse influence on carbohydrate metabolism. ACE inhibitors and alpha 1-antagonists do not influence or even improve glucose metabolism.