RESUMEN
AIMS: Despite high-dose s.c. insulin therapy, some Type 2 diabetes mellitus (DM) patients remain in poor metabolic control. We investigated whether a period of euglycaemia using i.v. insulin, followed by continuous subcutaneous insulin infusion (CSII), would ameliorate the deleterious effects of hyperglycaemia on insulin sensitivity and result in sustained, improved metabolic control. METHODS: In a prospective observational study, eight Type 2 DM patients with severe insulin resistance (insulin dose 1.92 +/- 0.66 U/kg per day (mean +/-sd)), in poor metabolic control (HbA(1c) 12.0 +/- 1.7%), were treated with i.v. insulin for 31 +/- 10 days aimed at euglycaemia, followed by CSII therapy for 12 months, using insulin lispro. Before and after 28 +/- 6 days of i.v. insulin treatment, insulin sensitivity was measured by a hyperinsulinaemic euglycaemic clamp. RESULTS: Euglycaemia was reached after 12 +/- 6 days of i.v. insulin treatment. Subsequently, the i.v. insulin dose required to maintain euglycaemia decreased from 1.7 +/- 0.9 to 1.1 +/- 0.6 U/kg per day (P < 0.005). Whole body glucose uptake increased from 12.7 +/- 5.7 to 22.4 +/- 8.8 micromol/kg per min (P < 0.0005). HbA(1c) decreased to 8.9 +/- 1.2% after 28 +/- 6 days, to 7.1 +/- 0.6% after 6 months and to 8.3 +/- 1.4% after 12 months (P < 0.001 vs. pretreatment, for all). Lipid profile improved and plasminogen activator inhibitor type 1 levels decreased significantly. Mean body weight did not change. CONCLUSIONS: In Type 2 diabetic patients, who are poorly controlled despite high-dose s.c. insulin treatment, a period of 2 weeks of euglycaemia achieved by i.v. insulin reverses hyperglycaemia-induced insulin resistance and substantially improves metabolic control. Subsequent CSII treatment, using insulin analogues, appears to maintain improved metabolic control for at least 1 year. This approach is promising but needs further evaluation.
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Glucemia/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hiperglucemia/prevención & control , Insulina/administración & dosificación , Anciano , Diabetes Mellitus Tipo 2/metabolismo , Resistencia a Medicamentos , Femenino , Humanos , Infusiones Intravenosas , Inyecciones Subcutáneas/métodos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
A 41-year-old Somalian female inhabitant of The Netherlands presented with malaise and cervical lymph node swelling. Enlarged mediastinal, hilar and abdominal lymph nodes were found on CT scan. Subsequently the left lacrimal gland became swollen, accompanied by periostitis of the lateral orbit margin. Mycobacterium tuberculosis was cultured from lymph node tissue and the diagnosis of tuberculous dacryoadenitis with periostitis was made on CT images and histology. All lesions responded well to tuberculostatic treatment. Although tuberculous dacryoadenitis is a very rare manifestation of tuberculosis, it is still important to recognise this presentation, especially since the incidence of tuberculosis continues to increase in Western countries.
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Dacriocistitis/etiología , Tuberculosis Ocular/complicaciones , Adulto , Dacriocistitis/diagnóstico por imagen , Femenino , Humanos , Radiografía , Tuberculosis Ocular/diagnóstico , Tuberculosis Ocular/diagnóstico por imagenRESUMEN
Despite considerable scientific efforts, no clinical method is currently available for the continuous monitoring of glucose in subcutaneous tissue fluid. In general, good results were obtained during in-vitro experiments with various implantable glucose sensors. However, after implantation these devices exhibited a progressive loss of sensor function. It is evident that the tissue reaction to the implanted sensor, especially the interactions at the sensor-tissue interface, plays an important role in this loss of function. Adequate strategies to improve in-vivo sensor performance can only be developed if there is a better understanding of the processes involved in sensor inactivation.
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Técnicas Biosensibles/instrumentación , Glucemia/análisis , Diabetes Mellitus/sangre , Técnicas Biosensibles/métodos , Automonitorización de la Glucosa Sanguínea/métodos , Diseño de Equipo , Falla de Equipo , Humanos , Monitoreo Fisiológico , Prótesis e Implantes , Sensibilidad y EspecificidadRESUMEN
AIMS: World Health Organization (WHO) guidelines recommend that the blood pressure (BP) should be routinely measured in sitting or supine followed by standing position, providing that the arm of the patient is placed at the level of the right atrium in each position. The aim of our study was to test the influence of body and arm position on BP measurement in diabetic patients. METHODS: In 142 patients with diabetes mellitus the BP was measured using a semiautomatic oscillometric device (Bosomat-R): (i) after 5 min of rest sitting on a chair with one arm supported at the right atrial level and with the other arm placed on the arm support of the chair, (ii) after 5 min of rest lying on a bed with both arms placed on a bed, and (iii) after 30 s and after 2 min of standing with one arm (the same as in sitting position) supported at the right atrial level and with the other arm vertical, parallel to the body. RESULTS: Both systolic (SBP) and diastolic (DBP) blood pressures were significantly lower in sitting position with the arm at the right atrial level than in supine position (by 7.4 and 6.6 mmHg, respectively, P < 0.01). In sitting and standing positions, SBP and DBP were higher when the arm was placed either on the arm support of the chair or vertical, parallel to the body, than when the arm was supported at the level of the right atrium (by 6-10 mmHg, P < 0.001). Duration of standing did not influence the estimation of orthostatic hypotension. CONCLUSIONS: The data of this study indicate that the WHO recommendation with regard to the equivalence of sitting and supine BP readings is incorrect at least in diabetic patients, as the sitting BP is lower than the supine BP when the arm was positioned at the right atrial level. In addition, incorrect positioning of the arm in standing position results in an underestimation of prevalence of orthostatic hypotension. We conclude that during BP measurement the arm should be placed at the right atrial level regardless of the body position.
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Determinación de la Presión Sanguínea , Diabetes Mellitus/fisiopatología , Postura , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brazo/fisiología , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Glibenclamide inhibits the opening of vascular ATP-sensitive potassium (K(ATP)) channels, which represents a protective mechanism during ischaemia. This effect may imply harmful cardiovascular effects of glibenclamide when used under conditions of ischaemia in patients with Type II diabetes. Acarbose is not associated with effects on the cardiovascular system, because the drug is not absorbed from the bowel. Therefore we hypothesized that treatment of Type II diabetes patients with glibenclamide will impair the vasodilator function of K(ATP) opening, unlike treatment with acarbose. A double-blind randomized cross-over study in 12 patients with Type II diabetes was performed to compare the effects of glibenclamide with those of acarbose on the vasodilator responses to K(ATP) channel opening in the forearm vascular bed. The study consisted of two periods: 8 weeks of treatment with orally administered glibenclamide (10 mg x day(-1)) followed by 8 weeks of treatment with acarbose (300 mg x day(-1)), or vice versa. At the end of each treatment period, forearm blood flow (venous occlusion plethysmography) in response to intra-arterially administered diazoxide, acetylcholine and dipyridamole and to forearm ischaemia was measured. The diazoxide-mediated increase in the forearm blood flow ratio (infused/control arm) was significantly less pronounced after glibenclamide than after acarbose (290 +/- 58% and 561 +/- 101% respectively; P<0.0005). Forearm blood flow responses to acetylcholine, dipyridamole and forearm ischaemia were similar during glibenclamide and acarbose treatment. Thus, in patients with Type II diabetes mellitus, treatment with glibenclamide is associated with an attenuated response to K(ATP) opening as compared with treatment with acarbose. This implies that glibenclamide may affect defensive mechanisms under conditions of K(ATP) channel activation.
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Acarbosa/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Gliburida/uso terapéutico , Bloqueadores de los Canales de Potasio/uso terapéutico , Acetilcolina/farmacología , Estudios Cruzados , Diabetes Mellitus Tipo 2/fisiopatología , Diazóxido/farmacología , Dipiridamol/farmacología , Método Doble Ciego , Femenino , Antebrazo/irrigación sanguínea , Humanos , Hipoglucemiantes/uso terapéutico , Isquemia/fisiopatología , Masculino , Persona de Mediana Edad , Pletismografía , Vasodilatadores/farmacologíaRESUMEN
AIMS: Glibenclamide attenuates the protective responses to opening of vascular ATP-sensitive potassium (K(ATP)) channels during ischaemia. Therefore, glibenclamide treatment of Type 2 diabetes mellitus may have hazardous cardiovascular effects when used under conditions of ischaemia. Glimepiride and metformin seem to lack such characteristics. Based on these data, we hypothesized that, in contrast to glibenclamide, chronic treatment of Type 2 diabetic patients with glimepiride or metformin will not impair the vasodilator function of K(ATP) opening in vivo. METHODS: Two groups of 12 Type 2 diabetes mellitus patients participated in a double-blind randomized cross-over study consisting of two 8-week periods, in which treatment with orally administered glibenclamide (15 mg/day) was compared with either glimepiride or metformin (6 mg and 1500 mg/day, respectively). At the end of each treatment period, the increase in forearm blood flow (FBF, venous occlusion plethysmography) in response to intra-arterial administered diazoxide (K(ATP) opener), acetylcholine (endothelium-dependent vasodilator) and dipyridamole (adenosine-uptake blocker) and to forearm ischaemia was measured. RESULTS: There were no significant differences in vasodilator responses to diazoxide, acetylcholine, dipyridamole and forearm ischaemia after glibenclamide compared with glimepiride and metformin. CONCLUSIONS: Chronic treatment of Type 2 diabetes mellitus with glimepiride or metformin has similar effects on vascular K(ATP) channels compared with chronic glibenclamide treatment.
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Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Gliburida/uso terapéutico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Compuestos de Sulfonilurea/uso terapéutico , Acetilcolina/farmacología , Adulto , Anciano , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Índice de Masa Corporal , Peso Corporal/efectos de los fármacos , Péptido C/sangre , Estudios Cruzados , Diabetes Mellitus Tipo 2/fisiopatología , Diazóxido/farmacología , Dipiridamol/farmacología , Método Doble Ciego , Femenino , Antebrazo/irrigación sanguínea , Humanos , Masculino , Persona de Mediana Edad , Vasodilatación/efectos de los fármacosRESUMEN
BACKGROUND: It has been reported that sodium-lithium countertransport (Na/Li CT) activity is increased in patients with diabetes mellitus and that this increased Na/Li CT activity is associated with the development of diabetic nephropathy. It is unclear however, whether Na/Li CT is related to other pathophysiological factors in diabetic patients. We studied kinetic parameters of Na/Li CT activity together with other putative risk factors for microangiopathy in normoalbuminuric type 1 diabetic patients and matched control subjects. SUBJECTS AND METHODS: We measured maximum velocity (Vmax) and sodium affinity (Km) of Na/Li CT in 53 diabetic patients and 45 healthy controls. Endothelial function was assessed by monitoring forearm vascular response to intrabrachial infusion of acetylcholine. Blood samples were collected for measurement of HbA1c, glucose, insulin and lipids. Blood pressure was measured intra-arterially. Renal haemodynamics were measured by inulin/p-aminohippurate clearance. Urinary albumin was measured by enzyme-linked immunosorbent assay. Transcapillary escape of albumin (TERalb) was calculated by the disappearance curve of 125I-labelled albumin. RESULTS: Vmax was increased in diabetic patients (779 +/- 36 micromol Li+ h-1 L-1 erythrocytes vs. 623 +/- 35 in controls, P < 0.01), whereas Km was decreased (64 +/- 16 mmol L-1 vs. 76 +/- 27 in controls, P = 0.03). The ratio of Vmax : Km was 12.4 +/- 0.6 in diabetic patients and 8.9 +/- 0.9 in controls (P < 0.001). When comparing diabetic patients in the lowest and highest quartile of Vmax or Km there were no differences in blood pressure, renal haemodynamics, urinary albumin excretion, TERalb, endothelial function, HbA1c, glucose, insulin, or lipid profile. CONCLUSION: Na/Li CT is increased in uncomplicated type 1 diabetes and characterized by an increase in Vmax and a decrease in Km. The increase in Na/Li CT is not associated with changes in endothelial function, degree of metabolic control, blood pressure or renal haemodynamics.
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Antiportadores/sangre , Diabetes Mellitus Tipo 1/sangre , Angiopatías Diabéticas/sangre , Angiopatías Diabéticas/etiología , Albuminuria/sangre , Albuminuria/fisiopatología , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/fisiopatología , Angiopatías Diabéticas/fisiopatología , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/etiología , Nefropatías Diabéticas/fisiopatología , Eritrocitos/metabolismo , Hemodinámica , Humanos , Transporte Iónico , Cinética , Circulación Renal , Factores de RiesgoRESUMEN
BACKGROUND: Recent investigations have shown that glibenclamide inhibits the opening of vascular ATP-sensitive potassium channels during ischemia. This observation may implicate cardiovascular effects of sulphonylurea derivatives when used under conditions of ischemia in patients with Type 2 diabetes mellitus. In addition to resistance arteries, the (pre) capillary vessels also contain ATP-dependent potassium channels. Closure of these channels by sulphonylurea derivatives might affect the development of microvascular disease in Type 2 diabetes mellitus. Therefore, we investigated the microcirculatory effects of sulphonylurea derivatives in Type 2 diabetic patients as compared with healthy volunteers. MATERIALS AND METHODS: Arteriovenous blood flow (skin temperature and laser Doppler flux) and capillary blood cell velocity were measured before and during infusion of four doses of glibenclamide (0.1, 0.3, 1.0 and 3.0 microg min-1 dL-1) into the brachial artery of 14 Type 2 diabetic patients and 13 healthy controls. The experiments included appropriate time control studies. RESULTS: Both skin temperature and laser Doppler flux decreased in response to glibenclamide in healthy volunteers (-7 +/- 2%, P < 0.0005 and -31 +/- 11%, P = 0.001, respectively), but did not change in Type 2 diabetic patients (1 +/- 3%, P = 0.29 and 4 +/- 14%, P = 0.97). However, capillary blood cell velocity decreased in Type 2 diabetic patients (-38 +/- 18%, P = 0.04), but did not change in healthy volunteers (-1 +/- 11%, P = 0.28). CONCLUSIONS: The results of the present study indicate that glibenclamide indeed affects microvascular blood flow. Glibenclamide may induce redistribution of the microvascular skin flow from nutritive flow to arteriovenous shunt flow in Type 2 diabetic patients. Therefore, closure of ATP-dependent potassium channels by glibenclamide possibly plays a role in the development of microangiopathy in Type 2 diabetic patients.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Gliburida/administración & dosificación , Hipoglucemiantes/administración & dosificación , Bloqueadores de los Canales de Potasio/administración & dosificación , Canales de Potasio/metabolismo , Adenosina Trifosfato/metabolismo , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Flujometría por Láser-Doppler , Masculino , Microcirculación/efectos de los fármacos , Persona de Mediana Edad , Isquemia Miocárdica/fisiopatología , Piel/irrigación sanguíneaRESUMEN
Charcot's arthropathy is a relative uncommon complication of diabetic neuropathy. The aetiology remains poorly understood. According to the neurotraumatic theory, the foot, which has become insensitive through neuropathy, is subjected to extensive (micro)trauma through continuation of use. Ultimately this leads to destruction. According to the neurovascular theory, autonomic neuropathy results in an increased blood flow in the foot with osteopenia consequently resulting due to increased osteoclastic activity and decreased osteoblastic activity. Acute Charcot's arthropathy presents with a red, warm, swollen foot, which is usually not painful and which eventually becomes ulcerated. An insidious development of the condition is also possible. The X-ray of the foot often is normal at presentation, but will later show local osteoporosis, erosions, subluxations or fractures. Technetium scintigraphy will be abnormal from the beginning, while IgG scans are usually normal. The traditional treatment is cast immobilisation with careful introduction of protected weight-bearing. After stabilisation, orthopaedic footwear is necessary to improve foot function and to prevent ulceration. Regular checkups are important.
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Artropatía Neurógena/etiología , Complicaciones de la Diabetes , Pie Diabético/prevención & control , Neuropatías Diabéticas/complicaciones , Artropatía Neurógena/diagnóstico , Artropatía Neurógena/fisiopatología , Artropatía Neurógena/terapia , Enfermedades Óseas/diagnóstico , Pie Diabético/etiología , Diagnóstico Diferencial , HumanosRESUMEN
Overactivity of the hexosamine biosynthetic pathway may underlie hyperglycemia-associated insulin resistance, but to date human studies are lacking. Hexosamine pathway activation can be mimicked by glucosamine (GlcN). In the present placebo-controlled study we determined whether GlcN infusion affects insulin resistance in vivo. In 18 healthy subjects, we applied the double forearm balance technique (infused arm vs. control arm) combined with the euglycemic hyperinsulinemic clamp (60 mU/m(2).min insulin) for at least 300 min. During the clamp, subjects received infusions in the brachial artery of 4 micromol/dL.min GlcN from 90-240 min (n = 6) or from 0-300 min (n = 6) or saline (placebo; n = 6). We studied the effects of GlcN on forearm glucose uptake (FGU; infused arm vs. control arm, and vs. placebo experiments) and on whole body glucose uptake. GlcN infusion raised the plasma GlcN concentration in the infusion arms to 0.42 +/- 0.14 and 0.81 +/- 0.46 mmol/L; plasma GlcN remained very low (< 0.07 mmol/L) in the control arms and in the placebo group. GlcN infusion did not change forearm blood flow. During insulin, FGU increased more than 10-fold. At all time points, FGU was similar in the GlcN-infused arm compared with the control arm and was not different from FGU in the placebo experiments. Similar results were obtained for forearm arteriovenous glucose differences or extraction and for whole body glucose uptake. Thus, despite relevant GlcN concentrations for 5 h in the infused forearm, GlcN had no effect on insulin-induced glucose uptake. These results do not support involvement of the hexosamine pathway in the regulation of insulin sensitivity in humans, at least not in the short-term setting.
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Glucosamina/farmacología , Insulina/farmacología , Adulto , Glucemia/análisis , Femenino , Antebrazo/irrigación sanguínea , Glucosa/metabolismo , Humanos , Insulina/sangre , Masculino , Músculo Esquelético/metabolismo , Flujo Sanguíneo Regional/efectos de los fármacosRESUMEN
The objective of this investigation was to evaluate the influence of polymorphonuclear granulocytes on the performance of uncoated and cellulose acetate/Nafion coated amperometric glucose sensors in vitro. The response of these sensors was also investigated in serum. Uncoated and coated sensors showed lower sensitivities to glucose, with a significant drift in sensor output upon exposure to serum or leukocytes. Although the use of a coating resulted in higher sensitivity, the progressive loss of output was not completely prevented. Stimulated granulocytes were shown to excrete components, probably catalase and myeloperoxidase, which consumed the hydrogen peroxide formed by the oxidation of glucose. In addition, adsorbed serum proteins formed a diffusional barrier for glucose. Furthermore, serum was found to contain low-molecular weight components that alone inhibited glucose oxidase activity. Based on preliminary electrochemical results, we postulate that rabbit serum contains oxidizing substrates that compete with molecular oxygen for the acceptance of electrons from the oxidized enzyme. Consequently, future efforts should be aimed at elucidating the mechanisms involved in the interference of unknown serum components with electron transfer. In addition, further investigations have to be performed to develop an outer membrane that minimizes protein adsorption as well as the actions of inflammatory cells.
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Técnicas Biosensibles , Glucemia/análisis , Inflamación/patología , Prótesis e Implantes , Animales , Materiales Biocompatibles , Tampones (Química) , Celulosa , Materiales Biocompatibles Revestidos , Enzimas Inmovilizadas , Polímeros de Fluorocarbono , Glucosa Oxidasa/sangre , Glucosa Oxidasa/metabolismo , Granulocitos/metabolismo , Granulocitos/patología , Técnicas In Vitro , Neutrófilos/metabolismo , Neutrófilos/patología , Conejos , Zimosan/químicaRESUMEN
Glucose kinetics were investigated in subcutaneous tissue of rabbits, in which a percutaneous device was implanted. The device was used for collection of tissue fluid and as carrier of an amperometric glucose sensor. Changes in glycaemia were reflected in subcutaneous tissue fluid. However, a limited number of responses of the implanted sensors were observed. Histologic evaluation showed thin fibrous capsules surrounding the implants. Accumulations of inflammatory cells were observed inside the subcutaneous chamber. The experiments again showed that changes in blood glucose concentration can be measured in subcutaneous tissue fluid collected with a percutaneous device. Nevertheless, implanted glucose sensors could not reliably monitor these changes. Supported by our histological observations and sufficient in vitro performance, we suppose that the cellular reaction to the sensor plays an important role in this poor in vivo performance. In combination with adsorption of tissue fluid proteins, this results in a reversible deactivation of implanted sensors. The exact mechanisms involved in this process are currently unknown and need further investigation.
RESUMEN
The objective of this investigation was to study the influence of impaired wound healing on the tissue response to bone-anchored percutaneous devices. For this reason, diabetes mellitus was induced in rabbits with alloxan. Untreated rabbits were used as controls. Skin-penetrating titanium implants were inserted in the tibial bone of diabetic and healthy animals. The enossal part of half of the implants was provided with a thin magnetron-sputtered calcium-phosphate coating. The soft-tissue and bone response was evaluated clinically, histologically, and histomorphometrically. We did not observe more infectious complications in diabetic animals. Furthermore, histological analysis revealed no differences in soft-tissue response between diabetic and healthy animals. A close bone-implant contact was observed for all implants. Nevertheless, the density of cortical bone around the implants was clearly lower in diabetic animals compared with control animals. In control rabbits, but not diabetic animals, coated implants showed more downgrowth of bone into the marrow cavity than uncoated ones. In general, diabetes mellitus was shown to have no adverse effect on the clinical performance of the percutaneous devices. We think that this is due to the good fixation of the implants in diabetic as well as control animals. Therefore, we conclude that the presence of impaired healing in chronic health disorders like diabetes is no contra-indication for the anchorage of percutaneous implants in cortical bone.
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Huesos/fisiología , Diabetes Mellitus Experimental/patología , Prótesis e Implantes , Titanio , Cicatrización de Heridas/fisiología , Animales , Glucemia/metabolismo , Huesos/patología , Fosfatos de Calcio , Cerámica , Diabetes Mellitus Experimental/fisiopatología , Femenino , Conejos , Piel/patología , Propiedades de Superficie , Tibia/patología , Tibia/fisiologíaRESUMEN
The objective of this investigation was to study the influence of impaired wound healing on the soft-tissue response to percutaneous devices using titanium fiber mesh anchorage. For this reason, diabetes mellitus was induced in rabbits with alloxan. Untreated rabbits were used as controls. Two implant types were inserted subcutaneously: two-stage percutaneous devices as well as separate titanium fiber mesh sheets. The soft-tissue response to both implants was assessed by clinical, histologic, and histomorphometric evaluation. Clinically, we observed a higher number of infectious complications around percutaneous implants in diabetic animals. Histologic and histomorphometric analyses revealed that severe diabetes effected matrix maturation and delayed neovascularization (p<0.05). We also observed higher numbers of inflammatory cells in the mesh porosity of percutaneous implants in severely diabetic animals (p = 0.09). Our results indicate that severe, uncontrolled diabetes negatively influences the maturity and neovascularization of connective tissue inside the fiber mesh porosity. The higher number of infectious complications in diabetic animals suggests that the presence of impaired healing conditions facilitates infection around skin penetrating devices.
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Materiales Biocompatibles , Titanio , Cicatrización de Heridas , Animales , Equipos y Suministros , ConejosRESUMEN
The objective was to evaluate the prevalence and severity of osteopenia in patients with uncomplicated insulin-dependent diabetes mellitus (IDDM) and to obtain more information on the pathophysiology of diabetic osteopenia. In 35 patients with uncomplicated IDDM (21 men and 14 women; age 37.6+/-9.9 yr; duration of disease 8.5+/-3.5 years) bone mineral density was measured by dual energy X-ray absorptiometry (DEXA). In addition, markers of bone formation [plasma insulin-like growth factor I (IGF-I), serum alkaline phosphatase (ALP), serum bone alkaline phosphatase (BAP) and serum osteocalcin] and bone resorption [urinary excretion of calcium and of the cross-linked N-telopeptide of type 1 collagen, both corrected for the excretion of creatinine] were measured in the diabetic patients and in 33 healthy controls, matched for sex, age, height, weight and body mass index (BMI). In 67% of the diabetic men and 57% of the diabetic women osteopenia of the femoral neck and/or the lumbar spine (T-value < or = -1 SD) was present. Fourteen percent of the male patients, but none of the female patients, met the criteria for osteoporosis (T-value < or = -2.5 SD). In the whole group of diabetic patients the mean plasma IGF-I level tended to be lower (p<0.10) as compared to that in the controls. In the diabetic patients with femoral neck osteopenia, the mean plasma IGF-I level was significantly lower (p<0.05) than in those without osteopenia at this site. There were no differences in the mean serum ALP, BAP and osteocalcin levels between the diabetic patients and the controls, nor between the diabetic patients with and without femoral neck osteopenia. Considering only the male diabetic patients, significantly lower mean plasma IGF-I (-26%), serum ALP (-24%) and serum osteocalcin (-38%) levels were present in the patients with femoral neck osteopenia than in those without osteopenia at this site, suggesting lowered bone formation. The bone resorption markers were similar in all (sub)groups of diabetic patients and not different between diabetic patients and controls. Bone mineral density (BMD) did not correlate with plasma levels of glycosylated hemoglobin (HbA1c). BMD values were not related to any of the bone resorption or formation markers, except for plasma IGF-I both in the femoral neck (r=+0.38, p=0.026) and the lumbar spine (r=+0.34, p=0.043). Our data demonstrate that at least in male patients with IDDM, osteopenia is the consequence of a lowered bone formation with a predominance of bone resorption over formation.
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Enfermedades Óseas Metabólicas/epidemiología , Enfermedades Óseas Metabólicas/etiología , Diabetes Mellitus Tipo 1/complicaciones , Absorciometría de Fotón , Adolescente , Adulto , Fosfatasa Alcalina/sangre , Biomarcadores/sangre , Biomarcadores/orina , Densidad Ósea , Enfermedades Óseas Metabólicas/metabolismo , Remodelación Ósea , Resorción Ósea , Huesos/enzimología , Huesos/metabolismo , Calcio/sangre , Calcio/orina , Colágeno/orina , Colágeno Tipo I , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/análisis , Masculino , Persona de Mediana Edad , Osteocalcina/sangre , Hormona Paratiroidea/sangre , Péptidos/orina , Fósforo/sangreRESUMEN
The objective of the current investigation is to determine the soft-tissue biocompatibility of sol-gel matrices which can be used to optimize the properties of implantable glucose sensors. The biocompatibility of sol-gel matrices with heparin, dextran sulphate, Nafion, polyethylene glycol, and polystyrene sulphonate was examined in vitro in simulated body fluid and with cell culture experiments using human dermal fibroblasts. Finally, an in vivo study was performed. Therefore, sol-gel coated polystyrene discs were inserted subcutaneously in the back of rabbits. After 4 and 12 weeks, the implants with surrounding tissue were retrieved and processed histologically. In simulated body fluid, the formation of a granular calcium phosphate precipitate was observed. Cell proliferation on polyethylene glycol, Nafion, and heparin coated substrates was comparable to control samples and significantly higher than on dextran sulphate and polystyrene sulphate coated substrates. Light microscopic evaluation of the retrieved in vivo samples showed a fair tissue reaction to all materials. Histomorphometric analysis demonstrated that there were no differences in tissue response to the different sol-gel coatings. In conclusion, sol-gel matrices exhibit a fair biocompatibility both in vitro and in vivo. These results will form the basis for further research into the real merits of sol-gel coatings in optimizing the properties of subcutaneously implantable glucose sensors.
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Técnicas Biosensibles , Materiales Biocompatibles Revestidos , Glucosa/análisis , Implantes Experimentales , Animales , Líquidos Corporales , Células Cultivadas , Femenino , Fibroblastos/ultraestructura , Geles , Humanos , Microscopía Electrónica de Rastreo , Conejos , Piel/ultraestructura , Propiedades de SuperficieRESUMEN
In the current study subcutaneous glucose kinetics were investigated in tissue fluid collected with a percutaneous device (PD). PDs containing a subcutaneous tissue chamber were implanted subcutaneously in New Zealand white rabbits. Sintered titanium fiber mesh sheets were used for subcutaneous anchorage of the PD. The bottom of the subcutaneous tissue chamber was either covered with a titanium fiber mesh sheet, a cellulose acetate membrane, or left uncovered. Subcutaneous glucose kinetics were determined after injection of octreotide and glucagon. The tissue reaction to the implants was evaluated histologically. No dynamic relationship was observed between glycaemia and subcutaneous tissue fluid glucose for all membrane covered devices. Histological evaluation showed that the presence of a seroma cavity in combination with obstruction of the membrane prevented adjustment of the subcutaneous glucose concentration in response to changes in glycaemia. In the uncovered devices, on the other hand, changes in glycaemia were reflected in subcutaneous tissue fluid. Our results prove that it is possible to measure changes in the glucose concentration in subcutaneous tissue fluid collected with a percutaneous device. Therefore, we conclude that a percutaneous device has an application as model to study the in vivo performance of implantable glucose sensors. The use of porous membranes in such devices has to be avoided.
RESUMEN
Capillary hyperperfusion precedes and contributes to the occurrence of diabetic microangiopathy. Vascular tone is regulated by the balance of vasodilating and vasoconstricting factors, of which nitric oxide (NO; an endothelium dependent vasodilator) and norepinephrine (NE; a potent vasoconstrictor), respectively, are of primary importance. To investigate the role of these factors in hyperperfusion, we measured forearm blood flow (FBF) in 50 patients with noncomplicated type 1 diabetes (DP) and 50 healthy control subjects (CS) under baseline conditions and during intrabrachial infusion of N(G)-monomethyl-L-arginine (L-NMMA), an endothelium-dependent vasoconstrictor, and acetylcholine (ACh), an endothelium-dependent vasodilator. Furthermore, we determined arterial plasma NE concentration at baseline and then determined alpha-adrenergic receptor sensitivity by measuring FBF response to intra-arterially infused NE. We found that basal FBF was increased in DP (2.9+/-0.1 versus 2.0+/-0.1 mL. min(-1). dL(-1) in CS; P<0.01). L-NMMA caused a similar vasoconstriction in both groups (28.5+/-1. 7% in DP versus 31.2+/-2.2% in CS; P=NS). Maximum blood flow during infusion of ACh was not different (23.3+/-1.9 mL. min(-1). dL(-1) in DP versus 20.1+/-1.6 in CS). Arterial plasma NE concentrations were significantly decreased in DP (0.57+/-0.03 versus 0.81+/-0.05 nmol/L in CS; P<0.01). The vasoconstrictive effect of NE was increased in DP (slope log dose-response curve, 31.3+/-1.5 versus 24.3+/-1.8 in CS; P<0.01). We conclude that basal FBF is increased in noncomplicated type 1 diabetes. We found no evidence of a disturbance of basal or stimulated NO production. Arterial plasma NE concentrations are decreased in noncomplicated type 1 diabetes. This may explain the vasodilatation at baseline and the increased vascular response to intra-arterially NE.
Asunto(s)
Diabetes Mellitus Tipo 1/fisiopatología , Músculo Esquelético/irrigación sanguínea , Óxido Nítrico/fisiología , Sistema Nervioso Simpático/fisiología , Acetilcolina/farmacología , Adulto , Glucemia/análisis , Ácidos Grasos no Esterificados/sangre , Femenino , Humanos , Masculino , Norepinefrina/sangre , Receptores Adrenérgicos alfa/fisiología , Flujo Sanguíneo Regional/efectos de los fármacos , omega-N-Metilarginina/farmacologíaRESUMEN
It was previously shown that systemic hyperinsulinemia induces vasodilation in human skeletal muscle. The mechanism mediating this vasodilation is not yet completely clarified. Based on data from animal experiments, we hypothesized that stimulation of the adenosine receptor is involved in insulin-induced vasodilation. To test this hypothesis, a 105-min hyperinsulinemic euglycemic clamp was performed in three groups of eight healthy volunteers. In group 1, placebo was infused into the left brachial artery (experimental forearm). In the second and third group, respectively, draflazine (an adenosine-uptake blocker) and theophylline (an adenosine-receptor antagonist) were administered by intrabrachial infusion. Forearm blood flow (FBF) was measured by venous-occlusion plethysmography, both at the experimental and the control forearms. The percentage decrease in flow ratio (FBF experimental arm/control arm) in the draflazine group was significantly less pronounced than that in the placebo group, whereas the percentage decrease in flow ratio was larger in the theophylline group. These results demonstrate that the insulin-induced increase in blood flow in the experimental arm was more pronounced at the site of adenosine-uptake blockade by draflazine, whereas this was reduced during adenosine-receptor antagonism by theophylline. Our observations are compatible with the hypothesis that insulin-induced vasodilation is mediated by the release of adenosine.