RESUMEN
Obstructive sleep apnea (OSA) and periodic limb movements during sleep (PLMs) are sleep-related disorders with a high prevalence in type 2 diabetes. Commonly OSA is considered as a consequence of obesity, but several previous studies have shown the presence of OSA in non-obese diabetic patients. A previous study showed higher PLMs prevalence in patients with type 2 diabetes, compared to age-matched controls. We speculated that both OSA and PLMs may reflect the presence of diabetic autonomic neuropathy. To test this hypothesis, we compared a group of 112 non-obese patients with type 2 diabetes with 66 age-, sex-, and body mass index- matched nondiabetic patients. Both groups have been investigated through a set of tests including the Epworth Sleepiness Scale, polysomnography, and the Orthostatic Grading Scale (OGS), a questionnaire to assess the degree of autonomic dysfunction. Diabetic patients with OSA and PLMs scored higher on the OGS than controls. Our results confirm that both OSA and PLMs are related to dysautonomy and may be unrelated to obesity in type 2 diabetes patients.
RESUMEN
The microcirculatory response to thermal stimulation involves both an axon reflex and NO-mediated activation. The analysis of the microcirculatory flow following thermal stimulation may therefore enhance the detection of any impairment of the small unmyelinated fibres that are involved in the axon reflex. The aim of this work is to establish a method of non-invasive measurement of small fibre impairment. The microcirculatory flow in response to local heating is measured by using a laser Doppler instrument, and mathematically modelled to extract a set of quantitative parameters. The results confirm that there is a significant difference in the parameters modelling the axon reflex between diabetic and control subjects, while no significant difference is found in the parameters modelling the NO-mediated activation.
Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Hiperemia/fisiopatología , Modelos Biológicos , Piel/irrigación sanguínea , Adulto , Anciano , Regulación de la Temperatura Corporal/fisiología , Estudios de Casos y Controles , Neuropatías Diabéticas/fisiopatología , Femenino , Humanos , Flujometría por Láser-Doppler , Masculino , Microcirculación/fisiología , Persona de Mediana Edad , Piel/fisiopatología , Fenómenos Fisiológicos de la PielRESUMEN
BACKGROUND/AIMS: Uremic Neuropathy (UN) highly limits the individual self-sufficiency causing near-continuous pain. An estimation of the actual UN prevalence among hemodialysis patients was the aim of the present work. METHODS: We studied 225 prevalent dialysis patients from two Italian Centers. The Michigan Neuropathy Score Instrument (MNSI), already validated in diabetic neuropathy, was used for the diagnosis of UN. It consisted of a questionnaire (MNSI_Q) and a physical-clinical evaluation (MNSI_P). Patients without any disease possibly inducing secondary neuropathy and with MNSI score ≥ 3 have been diagnosed as affected by UN. Electroneurographic (ENG) lower limbs examination was performed in these patients to compare sensory conduction velocities (SCV) and sensory nerve action potentials (SNAP) with the MNSI results. RESULTS: 37 patients (16.4%) were identified as being affected by UN, while 9 (4%) presented a score < 3 in spite of neuropathic symptoms. In the 37 UN patients a significant correlation was found between MNSI_P and SCV (r2 = 0.1959; p < 0.034) as well as SNAP (r2 = 0.3454; p = 0.027) both measured by ENG. CONCLUSIONS: UN is an underestimated disease among the dialysis population even though it represents a huge problem in terms of pain and quality of life. MNSI could represent a valid and simple clinical-instrumental screening test for the early diagnosis of UN in view of an early therapeutic approach.
Asunto(s)
Enfermedades Renales/terapia , Enfermedades del Sistema Nervioso Periférico/epidemiología , Diálisis Renal , Potenciales de Acción , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Italia/epidemiología , Enfermedades Renales/epidemiología , Masculino , Persona de Mediana Edad , Conducción Nerviosa , Examen Neurológico , Nervios Periféricos/fisiopatología , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/fisiopatología , Valor Predictivo de las Pruebas , Prevalencia , Diálisis Renal/efectos adversos , Células Receptoras Sensoriales , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Uremia/epidemiología , Uremia/terapiaRESUMEN
BACKGROUND: It is generally considered that changes in serum phosphate levels do not alter parathyroid hormone (PTH) secretion in the absence of concomitant changes in ionized serum calcium level in humans. An acute rise in PTH was shown after phosphate administration by intraduodenal gavage in rats. We aimed to study gastrin, phosphate, PTH, ionized calcium (iCa), and blood pH responses to oral peptones in morbidly obese patients before and after roux-en-Y gastric bypass (RYGB) surgery. METHODS: These parameters were evaluated in response to an oral peptone load in 24 (18 male and 6 female) obese subjects before and 6 months after RYGB surgery. In 12 gastric bypass patients, we also evaluated PTH and phosphate after peptones plus aluminum hydroxide administration to suppress phosphate absorption. RESULTS: Before RYGB, peptones increased gastrin (P < .001), and decreased iCa (P < .01) without changes in PTH or pH. Both phosphate and PTH markedly increased after RYGB with the peptones oral load (P < .01), without changes in pH, iCa, or gastrin. There was a significant, direct relationship between the increase of phosphate and the increase of PTH in the patients treated with aluminum hydroxide (r(2) = 0.78; P < .0001). CONCLUSION: Rapid delivery of peptones in the jejunum in bypassed obese patients results in a significant rise in phosphate and PTH, in the absence of changes of other PTH regulators, possibly mediated by a signaling from the gastrointestinal tract. RYGB patients provide an opportunity to study the control of PTH secretion, with potential relevant clinical implications.
Asunto(s)
Derivación Gástrica , Obesidad Mórbida , Hormona Paratiroidea/sangre , Peptonas/administración & dosificación , Fosfatos/sangre , Administración Oral , Adulto , Hidróxido de Aluminio/administración & dosificación , Calcio/sangre , Femenino , Gastrinas/sangre , Humanos , Concentración de Iones de Hidrógeno , Absorción Intestinal/efectos de los fármacos , Yeyuno/metabolismo , Masculino , Obesidad Mórbida/tratamiento farmacológico , Obesidad Mórbida/metabolismo , Obesidad Mórbida/cirugía , Hormona Paratiroidea/metabolismo , Fosfatos/farmacocinética , Periodo Posoperatorio , Estudios Prospectivos , Adulto JovenRESUMEN
Absorptive hypercalciuria (AH) is associated with elevated levels of 1,25-dihydroxyvitamin D (1,25(OH)(2)D). While no increase of 1,25(OH)(2)D after oral administration of 25-hydroxyvitamin D (25OHD) at high doses has been claimed in normal subjects, a substrate-product relationship has been reported in normal children, young people after UV irradiation, older persons, postmenopausal women, primary hyperparathyroidism, renal failure, osteomalacia, and sarcoidosis. No data of this relationship in AH is available. To investigate 25OHD-1,25(OH)(2)D substrate-product relationship in AH, 161 AH patients (mean age 60.9+/-11.7 years) and 110 age- and sex-matched controls (mean age 61.5+/-12.4 years) were studied. In 57 controls and 52 AH subjects 25OHD-1,25(OH)(2)D relationship in basal conditions and after 2-week oral 25OHD (25 microg/day) administration were evaluated. In basal conditions 25OHD and 1,25(OH)(2)D were correlated in both, controls and AH; 25OHD treatment was followed by an increase in serum 25OHD and 1,25(OH)(2)D in both groups. However, delta responses of 25OHD and 1,25(OH)(2)D to 25OHD were higher in AH suggesting an enhanced activity of 1 alpha-hydroxylase. In conclusion, the higher response of 1,25(OH)(2)D after oral 25OHD in AH patients suggests a differential capacity between both groups in handling the increases in 1,25(OH)(2)D.
Asunto(s)
Hipercalciuria/metabolismo , Vitamina D/análogos & derivados , Administración Oral , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Hipercalciuria/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Estaciones del Año , Vitamina D/administración & dosificación , Vitamina D/metabolismo , Vitamina D/uso terapéuticoRESUMEN
UNLABELLED: We analyzed gastrin, PTH, and calcitonin responses to oral calcium and peptones in hypocalciuric hypercalcemia, mild primary hyperparathyroidism, and normal controls. We observed diverse hormonal responses that may help in the differential diagnosis of these conditions. INTRODUCTION: Hypocalciuric hypercalcemia (HH) is consequent to calcium-sensing receptor (CaSR) genetic mutations or anti-CaSR antibodies. CaSR is expressed in parathyroid tissue, thyroid C cells, and gastrin-secreting cells, where it has been suggested that on calcium and/or amino acid allosteric activation, promotes gastrin secretion. MATERIALS AND METHODS: We evaluated gastrin, PTH, and calcitonin responses to oral calcium (1 g) and peptones (10 g) in 10 patients with HH (mean age, 58.5 +/- 10.3 years; F/M = 9/1), 15 patients with primary hyperparathyroidism (PH; mean age, 60.4 +/- 8.3 years; F/M = 11/4), and 30 healthy controls (mean age, 60.3 +/- 8.1 years). Statistical analyses for differences during oral loading tests were calculated with ANOVA for repeated measurements and comparisons between two groups were performed with Student's t-test. RESULTS: PTH response to peptones was markedly increased in patients with PH compared with flat responses in controls and HH patients (p < 0.05). Gastrin increase after oral calcium was absent in HH and PH subjects (p < 0.05 versus controls), and gastrin responses to peptones were blunted in HH and PH subjects compared with controls (p < 0.05). PTH drop and calcitonin increase after calcium load observed in controls were absent in HH and PH subjects (p < 0.05). CONCLUSIONS: The marked difference in PTH response elicited by peptones observed in PH compared with subjects with HH may help in the differential diagnosis of these conditions without genetic studies. Peptones may stimulate CaSR-controlled hormones as an allosteric regulatory pathway. CaSR abnormalities may help to explain the different calcium- and peptones-induced hormonal responses observed in PH and HH compared with normal subjects.
Asunto(s)
Calcio/administración & dosificación , Hiperparatiroidismo/diagnóstico , Hipocalcemia/diagnóstico , Hormonas Peptídicas/sangre , Peptonas/administración & dosificación , Anciano , Calcitonina/sangre , Diagnóstico Diferencial , Femenino , Gastrinas/sangre , Humanos , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/sangreRESUMEN
The lipid triad is the association of small, dense (sd) low-density lipoprotein (LDL), low high-density lipoprotein (HDL), and hypertriglyceridemia, all of which play a role in coronary artery disease in patients with type 2 diabetes. Although statins have demonstrated clear positive effects on cardiovascular morbidity/mortality in patients with diabetes and on single components of the lipid triad, it remains controversial whether they affect all components of the triad in these patients. Therefore, we performed a single-center, parallel-group, prospective, randomized, open-label, blinded-endpoint (PROBE)-type comparison of fluvastatin extended-release (XL) 80 mg (n=48) and simvastatin 20 mg (n=46), each given once daily for 2 months to patients with type 2 diabetes with the lipid triad, who were enrolled after a 1-month lifestyle modification and dietary intervention program. After fluvastatin therapy, LDL (-51%; P<.01), apolipoprotein B (ApoB; -33%; P<.01), intermediate-density LDL (idLDL) (-14.3%; P<.05), sdLDL (-45%; P<.01), and triglycerides (-38%; P<.01) were significantly decreased, and HDL (+14.3%; P<.05) and apolipoprotein A-I (ApoA-I; +7%; P<.05) were increased; large buoyant (lb) LDL did not change (P=NS). Simvastatin therapy decreased LDL (-55.1%; P<.01), ApoB (-46%; P<.01), lbLDL (-33.3%; P<.05), idLDL (-22.7%; P<.05), sdLDL (-33.3%; P<.05), and triglycerides (-47.9%; P<.01); HDL was not changed (P=NS) after simvastatin, but ApoA-I was increased (+11.3%; P<.01). HDL increases (P<.01) and sdLDL decreases (P<.01) were significantly greater after fluvastatin compared with simvastatin therapy; LDL, triglycerides, ApoB, and idLDL changes were similar after both therapies (P=NS), and lbLDL decreases were greater with simvastatin therapy (P<.05). With both treatments, classic mean LDL and ApoB target levels were achieved in most patients. We conclude that the lipid triad can be controlled with fluvastatin XL 80 mg in patients with type 2 diabetes.
Asunto(s)
Anticolesterolemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Ácidos Grasos Monoinsaturados/uso terapéutico , Hipertrigliceridemia/tratamiento farmacológico , Indoles/uso terapéutico , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Simvastatina/uso terapéutico , Anciano , Anticolesterolemiantes/administración & dosificación , Anticolesterolemiantes/efectos adversos , Preparaciones de Acción Retardada , Ácidos Grasos Monoinsaturados/administración & dosificación , Ácidos Grasos Monoinsaturados/efectos adversos , Femenino , Fluvastatina , Humanos , Indoles/administración & dosificación , Indoles/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Simvastatina/efectos adversosRESUMEN
The calcium-sensing receptor (CaSR) has been detected in human antral gastrin-secreting cells, where, upon calcium and/or amino acid allosteric activation, it stimulates gastrin secretion. Patients with absorptive hypercalciuria (AH) display an enhanced gastric acid output; therefore, we evaluated the secretion of gastrin in subjects with AH (30 subjects vs. 30 healthy female controls, all postmenopausal) after oral calcium administration (1 g calcium gluconate) and, on a separate occasion, after peptone loading test (protein hydrolyzed, 10 g). Gastrin and monomeric calcitonin responses were higher in AH after both oral calcium administration (P < 0.01) and peptone loading (P < 0.01). Because the activation of CaSR by oral calcium and peptones directly induces gastrin release, the higher gastrin responses to these stimuli suggest an increased sensitivity of gastrin-secreting cells CaSR in patients with AH. A similar alteration in thyroid C cells might explain the enhanced calcitonin responses to both calcium and peptones. If the same alterations should in addition be present in the distal tubule (where CaSR is expressed as well), then a possible explanation for amino acid-induced hypercalciuria in AH would have been identified.
Asunto(s)
Calcitonina/metabolismo , Trastornos del Metabolismo del Calcio/orina , Gastrinas/metabolismo , Receptores Sensibles al Calcio/metabolismo , Administración Oral , Anciano , Gluconato de Calcio/administración & dosificación , Gluconato de Calcio/orina , Trastornos del Metabolismo del Calcio/diagnóstico , Femenino , Células Secretoras de Gastrina/efectos de los fármacos , Células Secretoras de Gastrina/metabolismo , Humanos , Cálculos Renales/diagnóstico , Cálculos Renales/orina , Persona de Mediana Edad , Hormona Paratiroidea/metabolismo , Peptonas/administración & dosificación , Glándula Tiroides/efectos de los fármacos , Glándula Tiroides/metabolismoRESUMEN
BACKGROUND: Diabetic dyslipidemia is characterized by greater triglyceridation of all lipoproteins and low levels of plasma high-density lipoprotein cholesterol (HDL-C). In this condition, the serum level of low-density lipoprotein cholesterol (LDL-C) is only slightly elevated. The central role of decreased serum HDL-C level in diabetic cardiovascular disease has prompted the establishment of a target of ≥50 mg/dL in patients with diabetes mellitus (DM). OBJECTIVE: The aim of the study was to assess the effects of once-daily administration of fluvastatin extended release (XL) 80 mg or atorvastatin 20 mg on serum HDL-C levels in patients with type 2 DM and low levels of serum HDL-C. METHODS: This 4-month, prospective, open-label, randomized, blinded-end point (PROBE) trial was conducted at Endocrinology and Diabetology Service, L. Sacco-Polo University Hospital (Milan, Italy). Patients aged 45 to 71 years with type 2 DM receiving standard oral antidiabetic therapy, with serum HDL-C levels <50 mg/dL, and with moderately high serum levels of LDL-C and triglycerides (TG) were enrolled. After 1 month of lifestyle modification and dietary intervention, patients who were still showing a decreased HDL-C level were randomized, using a 1:1 ratio, to receive fluvastatin XL 80-mg tablets or atorvastatin 20-mg tablets, for 3 months. Lipoprotein metabolism was assessed by measuring serum levels of LDL-C, HDL-C, TG, apolipoprotein (apo) A-I (the lipoprotein that carries HDL), and apo B (the lipoprotein that binds very low-density lipoprotein cholesterol, intermediate-density lipoprotein, and LDL on a molar basis). Patients were assessed every 2 weeks for treatment compliance and subjective adverse events. Serum creatine phosphokinase and liver enzymes were assessed before the run-in period, at the start of the trial, and at 1 and 3 months during the study. RESULTS: One hundred patients were enrolled (50 patients per treatment group; fluvastatin XL group: 33 men, 17 women; mean [SD] age, 58 [12] years; atorvastatin group: 39 men, 11 women; mean [SD] age, 59 [11] years). In the fluvastatin group after 3 months of treatment, mean (SD) LDL-C decreased from 149 (33) to 95 (25) mg/dL (36%; P < 0.01), TG decreased from 437 (287) to 261 (164) mg/dL (40%; P < 0.01), and HDL-C increased from 41 (7) to 46 (10) mg/dL (12%; P < 0.05). In addition, apo A-I increased from 118 (18) to 124 (15) mg/dL (5%; P < 0.05) and apo B decreased from 139 (27) to 97 (19) mg/dL (30%; P < 0.05). In the atorvastatin group, LDL-C decreased from 141 (25) to 84 (23) mg/dL (40%; P < 0.01) and TG decreased from 411 (271) to 221 (87) mg/dL (46%; P < 0.01). Neither HDL-C (41 [7] vs 40 [6] mg/dL; 2%) nor apo A-I (117 [19] vs 114 [19] mg/dL; 3%) changed significantly. However, apo B decreased significantly, from 131 (20) to 92 (17) mg/dL (30%; P < 0.05). Mean changes in HDL-C (+5 [8] vs -1 [2] mg/dL; P < 0.01) and apo A-I (+6 [18] mg/dL vs -3 [21] mg/dL; P < 0.01) were significantly greater in the fluvastatin group than in the atorvastatin group, respectively. However, the decreases in LDL-C (54 [31] vs 57 [32] mg/ dL), TG (177 [219] vs 190 [65] mg/dL), and apo B (42 [26] vs 39 [14] mg/dL) were not significantly different between the fluvastatin and atorvastatin groups, respectively. No severe adverse events were reported. CONCLUSIONS: Fluvastatin XL 80 mg and atorvastatin 20 mg achieved mean serum LDL-C (≤ 100 mg/dL) and apo B target levels (≤ 100 mg/dL) in the majority of this population of patients with type 2 DM, but mean serum HDL-C level was increased significantly only with fluvastatin-16 patients (32%) in the fluvastatin group compared with none in the atorvastatin group achieved HDL-C levels ≥50 mg/dL. The increase in HDL-C in the fluvastatin-treated patients was associated with an increase in apo A-I, suggesting a potential pleiotropic and selective effect in patients with low HDL-C levels.