Infrapopliteal arterial occlusive disease in elderly men: a population based study.

AIM: The aim of this paper was to determine prevalence, cardiovascular risk factors and association with coronary heart disease (CHD) of isolated infrapopliteal arterial disease in old-adult men. DESIGN: cross-sectional; participants: population-based sample of 699 men aged 55 to 74 years, measurements: cardiovascular history and risk factors, electrocardiogram, segmental pressures and velocity waveforms in lower limbs. RESULTS: Peripheral arterial occlusive disease (PAOD) was observed in 13.4% subjects, of whom 39.4% (37 patients) had isolated infrapopliteal PAOD. Of these, 11 (29.7%) patients were symptomatic. Isolated infrapopliteal PAOD was significantly associated with increased age, smoking, diabetes and hypertriglyceridemia. Subjects with extended PAOD differed from those with isolated infrapopliteal PAOD in increased tobacco exposure, higher levels of LDL and lower levels of HDL cholesterol. Association between PAOD and CHD was almost always significant (odds ratio from 1.8 to 3.4) irrespective of PAOD topographic pattern and symptom characteristics of CHD subjects. CONCLUSION: Isolated infrapopliteal PAOD is a frequent asymptomatic disorder in old-adult men, clearly associated with both symptomatic and asymptomatic CHD. In contrast to an expected risk factor profile biased by clinical practice, these subjects only differed from those with PAOD significantly extended to proximal arteries in their smoking exposition and a more atherogenic lipid profile.

Clinical screening and diagnosis of diabetic polyneuropathy: the North Catalonia Diabetes Study.

BACKGROUND: To evaluate the prevalence of diabetic polyneuropathy (DPN) and develop a simple and accurate method for the evaluation of DPN risk in primary care settings. MATERIALS AND METHODS: Cross-sectional descriptive study in a random sample (N = 307) of type 2 diabetes mellitus participants. DPN was diagnosed by both clinical neurological examination and simplified DPN Selection Method in each patient. Correlation between the two methods was obtained. RESULTS: Prevalence of DPN was 23.13% (confidence interval,18.38-27.87) according to clinical neurological examination. Noteworthy, clinical neurological evaluation scores were related to nerve conduction studies (r = 0.882; P < 0.0005). DPN presence was positively related to age, metabolic control (HbA1c levels), known duration of diabetes, diabetic retinopathy, cardiovascular disease, peripheral ischemia and systolic and diastolic blood pressure, but was negatively related to current high-density lipoprotein cholesterol (HDL-C) levels (P < 0.0001). The sensitivity and specificity of our DPN Selection Method (using four clinical parameters: age, retinopathy, HbA1c and HDL-C plasma levels) for diagnosis of DPN was 74.20% and 74.90%, respectively. CONCLUSIONS: The expected prevalence of DPN was observed. The sensitivity of the DPN Selection Method correlated well with formal clinical neurological exam in detection of the condition. We therefore conclude the DPN Selection Method is a useful tool in primary care settings in the evaluation and diagnosis of DPN.

Relationship of obesity distribution and peripheral arterial occlusive disease in elderly men.

OBJECTIVE: To examine the relationships between total body fatness and abdominal fat distribution with peripheral arterial disease. DESIGN: Cross-sectional. SUBJECTS: Population-based sample of 708 men aged 55-74. MEASUREMENTS: Body mass index (BMI) to estimate total body fatness and waist-to-hip ratio for abdominal fat distribution; peripheral arterial disease defined by ankle/brachial index <0.9; cardiovascular risk factors. RESULTS: Peripheral arterial disease was observed in 13.4% of subjects. BMI did not correlate with peripheral arterial disease, whereas an increased waist-to-hip ratio over 0.966 (median value) doubled the prevalence of arterial disease. After controlling for smoking, diabetes, hypertension, high-density lipoprotein cholesterol and triglycerides, increased waist-to-hip ratio was independently associated with peripheral arterial disease (odds ratio 1.68; 95% confidence interval 1.05-2.70). CONCLUSION: Abdominal fat distribution, but not total body fatness, is associated with peripheral arterial occlusive disease, independently of concurrent cardiovascular risk factors.

Physical training decreases plasma thrombomodulin in type I and type II diabetic patients.

AIMS/HYPOTHESIS: Endothelial damage is an early step in the pathogenesis of atherosclerosis and its improvement through physical training can contribute to the known reduction of cardiovascular risk associated with exercise. An increase in some endothelium-dependent haemostatic parameters, considered as markers of endothelial damage, has been observed in diabetic patients. METHODS: The effect of a three-month physical exercise programme on thrombomodulin, tissue factor pathway inhibitor, plasminogen activator inhibitor, tissue-type plasminogen activator and von-Willebrand factor was evaluated in 14 well-controlled patients with Type I (insulin-dependent) diabetes mellitus and 13 patients with Type II (non-insulin-dependent) diabetes mellitus (HbA1c 6.5 +/- 0.8 and 7.4 +/- 0.8%, respectively). A matched control group was also studied. RESULTS: Thrombomodulin at baseline was higher in both Type I and Type II diabetic patients than in their respective matched control subjects (50.0 +/- 16 vs 31.1 +/- 8.7 microg/l, p < 0.05; 51.0 +/- 10 vs 28.5 +/- 11 microg/l, p <0.05, respectively). After the exercise programme, thrombomodulin plasma concentrations had decreased (p < 0.05) in both groups of patients, with final thrombomodulin values being similar to those observed in their control groups (38.2 +/- 11 microg/l for Type I and 34.6 +/- 12 microg/l for Type II patients). The thrombomodulin decrement correlated with baseline thrombomodulin and VO2max increase in Type I diabetic patients. A decrease in tissue factor pathway inhibitor was also observed in Type II diabetic patients. CONCLUSION/INTERPRETATION: We conclude that the normalisation of plasma thrombomodulin concentrations in Type I and Type II diabetic patients after physical training might reflect the improvement in endothelial function associated with physical exercise.

Prevalence and phenotypic distribution of dyslipidemia in type 1 diabetes mellitus: effect of glycemic control.

BACKGROUND: Data on the prevalence of dyslipidemia in type 1 diabetes mellitus are scarce and are based on total triglyceride and total cholesterol concentrations alone. OBJECTIVE: To assess the effect of glycemic optimization on the prevalence of dyslipidemia and low-density lipoprotein cholesterol (LDL-C) concentrations requiring intervention in patients with type 1 diabetes. PATIENTS: A total of 334 adults with type 1 diabetes and 803 nondiabetic control subjects. METHODS: Levels of glycosylated hemoglobin, total cholesterol, total triglyceride, high-density lipoprotein cholesterol (HDL-C), and LDL-C were assessed at baseline and after 3 to 6 months of intensive therapy with multiple insulin doses. RESULTS: Levels of LDL-C greater than 4.13 mmol/L (>160 mg/dL) and total triglyceride greater than 2.25 mmol/L (>200 mg/dL) and low HDL-C levels (<0.9 mmol/L [<35 mg/dL] in men or <1.1 mmol/L [<45 mg/dL] in women) were found in 16%, 5%, and 20% of patients and 13%, 6%, and 9% of controls, respectively (P<.001 for HDL-C). Diabetic women showed more hypercholesterolemia than nondiabetic women (15.6% vs 8.5%; P =.04). After glycemic optimization (mean +/- SD glycosylated hemoglobin decrease, 2.2 +/- 1.96 percentage points), the prevalence of LDL-C levels greater than 4.13 mmol/L (>160 mg/dL) became lower in diabetic men than in nondiabetic men (9.7% vs 17.5%; P =.04), but women showed frequencies of dyslipidemia similar to their nondiabetic counterparts. The proportion of patients with LDL-C concentrations requiring lifestyle (>2.6 mmol/L [>100 mg/dL]) or drug (>3.4 mmol/L [>130 mg/dL]) intervention decreased from 78% and 42% to 66% and 26%, respectively. CONCLUSIONS: Low HDL-C is the most frequent dyslipidemic disorder in patients with poorly controlled insulin-treated type 1 diabetes, and a high proportion show LDL-C levels requiring intervention. Less favorable lipid profiles could explain the absence of sex protection in diabetic women. The improvement caused by glycemic optimization puts forward intensive therapy as the initial treatment of choice for dyslipidemia in poorly controlled type 1 diabetes.

Modulation of vasoconstrictor and dilator pancreatic metabolites in streptozotocine diabetic rats: effect of bradykinin blockage and NO inhibition.

This study was designed to investigate the effect of HOE 140 (a bradykinin beta2 receptor antagonist) and N(w)-nitro-L-arginine methyl-ester (L-NAME, a nitric oxide synthase inhibitor) on endothelial and beta-cell function in induced streptozotocine (Stz) diabetic rats. The decrease in the insulinogenic index after Stz effect (control 286.03+/-104.12 and Stz 18.22+/-10.77, P<0.001 vs. Control) was partially prevented by L-NAME (46.54+/-10.12, P<0.001) and HOE 140 (105.12+/-23.06, P<0.001). It was observed in diabetic rats: L-NAME increased the pancreatic endothelin-1 (ET-1) production and HOE 140 did not. L-NAME and HOE 140 decreased the nitric oxide (NO) synthesis, increased prostacyclin 1-2 (PGI2), and did not modify thromboxane A-2 (TxA2). These results indicate that L-NAME and HOE 140 had a protective effect on the development of diabetes in the rat. The protective effect of L-NAME and HOE 140 on the insulinogenic index could be related to ET-1, bradykinin, PGI2, and NO.

[Echo-endoscopy: the clinical implications after a period of more than 16 years of its existence]. / Ecoendoscopia: implicaciones clínicas después de un período de más de 16 años de existencia.

Endosonography is an imaging diagnostic technique recently introduced in our country. It allows us to perform an ultrasound from within the digestive tube. Because of the transducer proximity to the gut wall and the high frequency of emission we are able to visualize with great resolution small lesions as well as differentiate the five layers of the gastric wall and examine structures close to the digestive lumen with a 7 to 8 cm penetration. This is a brief introduction to the basic pillars of endosonography and its main indications, well defined after sixteen years of clinical practice.

[The value of endoscopic ultrasonography in the study of submucosal tumors of the digestive tract]. / Valor de la ultrasonografía endoscópica en el estudio de los tumores submucosos del tracto digestivo.

Twenty-one consecutive patients with 24 possible submucosal lesions of the digestive tract were studied. Endoscopic ultrasonography (EUS) differentiated between 17 true positive submucosal tumors and 3 true negative extrinsic compressions. False positives were interpreted in 3 cases and in one patient no lesion was echoendoscopically observed (false negative). The sensitivity was 94%, the specificity 50% and the positive and negative predictive values were 82% and 75%, respectively. In conclusion, EUS may be the method of choice for the study of submucosal tumors since it allows visualization of the five layers of the wall of the digestive tract in which a tumor may originate, determination of its sonographic features, depth and exact size, in addition to the invasion of neighboring organs. Moreover, EUS may aid in collecting material for cytology and microscopy by fine needle aspiration puncture (FNAP) by EUS.

[Prevalence of nephropathy in type I diabetes]. / Prevalencia de nefropatía en la diabetes mellitus tipo I.

BACKGROUND: Diabetic nephropathy is a serious complication of diabetes, of which there are few epidemiological data in Spain. The aim of this study is to determine diabetic nephropathy prevalence in a group of patients with type I diabetes mellitus, representative of the population of Barcelona, Spain, evaluating several risk factors related with its development. PATIENTS AND METHODS: 639 patients (296 males and 343 women), from 6 hospitals, selected according with the diabetes duration (194 between 5 and 9 years [group I], 227 between 10 and 19 years [group II] and 218 with 20 years or more [group III]) were studied. In all patients urinary albumin excretion and plasma levels of creatinine, HbA1c, cholesterol and triglycerides were determined. The presence of retinopathy, neuropathy, vasculopathy and tobacco consumption were also evaluated. RESULTS: The prevalence of diabetic nephropathy increased with longer diabetes duration (8.1% [CI: 4.3-11.9] in group I, 24.7% [CI: 19.1-30.3] in group II and 44.7% [CI: 38.1-51.3] in group III), as well as that of hypertension, diabetes complications, cholesterol and triglycerides plasma levels. Related to people with normal renal function, after logistic regression, microalbuminuria was associated with hypertension and longer diabetes duration. Clinical nephropathy (macroalbuminuria + renal failure) to hypertension, longer duration, hypertriglyceridemia, male sex and tobacco consumption. CONCLUSIONS: The prevalence of diabetic nephropathy in Barcelona area is high and similar to that observed in other european regions. Its existence is associated with other diabetic complications. In addition to the classic risk factors, tobacco consumption must also be considered as a factor for diabetic nephropathy.

Lipoprotein compositional abnormalities in type I diabetes: effect of improved glycaemic control.

Major lipoprotein mass and composition were assessed in 45 subjects with insulin dependent diabetes mellitus (IDDM), before and after 2 months of intensive insulin therapy (IIT) and in 40 healthy control subjects. As compared to the control group, diabetic subjects at baseline had higher low density lipoprotein (LDL) and lower high density lipoprotein (HDL) masses. Expressing each lipoprotein constituent as a percent of total lipoprotein mass, very low density lipoprotein (VLDL) of diabetic patients was enriched in cholesterol and phospholipid and depleted in triglyceride and protein; IDL had higher triglyceride and phospholipid and lower cholesterol and protein proportion; LDL was depleted in protein and enriched in triglyceride; HDL was depleted in protein and enriched in triglyceride, cholesterol and phospholipid. After 2 months of IIT, HbA1c fell from 10.3 +/- 2 to 7.5 +/- 2% (P < 0.0001) and so did VLDL mass, which was lower than in control subjects. In addition, LDL and HDL masses, as well as triglyceride and cholesterol proportion in IDL particles normalized. The other compositional abnormalities improved without complete normalization. Thus, intensive insulin therapy in IDDM subjects brought quantitative lipoprotein alterations to normal even subnormal range, while most of the composition abnormalities improved without reaching complete normalization.

Lipoprotein(a) concentrations and non-insulin-dependent diabetes mellitus: relationship to glycaemic control and diabetic complications.

UNLABELLED: The aim of our study was to determine the lipoprotein(a) (Lp(a)) levels in patients with non-insulin-dependent diabetes mellitus (NIDDM) and to evaluate Lp(a) concentrations in relation to glycaemic control and diabetic complications. We evaluate in a cross-sectional study a total of 103 NIDDM patients (52 males and 51 females; mean age of 62.5 years; mean of diabetes duration: 12 years) referred to our hospital because of poor glycaemic control, and a group of 108 non-diabetic subjects (57 males and 51 females). RESULTS: mean Lp(a) concentration did not significantly differ between NIDDM patients and non-diabetic subjects (11.1 +/- 14 vs. 16.2 +/- 14 mg/dl). The distribution of Lp(a) levels was highly skewed towards the lower levels in both groups, being over 30 mg/dl in only 6% of NIDDM patients and 12% of controls. Patients with Lp(a) levels over 10 mg/dl had lower haemoglobin Alc (HbA1c) than patients with Lp(a) levels over 10 mg/dl (8.5% vs. 10.4%; P < 0.01). Lp(a) concentration was positively correlated with body mass index (BMI) (P < 0.05) and HbA1c (P < 0.05). No association was found between Lp(a) and sex, age, other lipidic parameters, microalbuminuria, type of treatment and presence of cardiovascular disease. These findings may suggest that glycaemic control could have a modulatory role on Lp(a) concentration in NIDDM patients. In this study, diabetic complications did not seem to be associated with higher Lp(a) concentrations.

Interleukin-1 and beta-cell function: more than one second messenger?

Cytokines, in particular IL-1, released mainly by infiltrating macrophages, can be one of the key mediators of immune-induced beta-cell destruction in IDDM. IL-1 is able to induce suppression of insulin release and biosynthesis in cultured rat pancreatic islets. In addition, the cytokine shows clear cytotoxic effects leading to beta-cell death. The proposed mechanisms of action of IL-1 after binding to the beta-cell receptors are varied. Concerning the cytotoxic effects of the cytokine, the role of oxygen free radicals, mainly derived from arachidonate metabolism (see Fig. 1) is clear, and possibly potentiated by a cytosolic Na(+)-mediated alkalinization of the beta-cell exposed to the cytokine. In fact, an increased influx of Na+ may explain some of the cytotoxicity since it results in concomitant water uptake leading to swelling of the endoplasmic reticulum. NO formation also seems to be related to the cytokine-induced cytotoxicity since inhibition of the NO synthase abolishes the effects of the cytokine (see Fig. 1). In relation to the inhibitory effects of the cytokine on the beta-cell, different studies point toward almost all known second messenger systems already described for several hormones, such as cAMP formation, increased phospholipase C activity, changes in cytosolic Ca++, and altered gene transcription (see Fig. 1). Of particular interest is the protease activation associated with IL-1 (a serine protease) that seems to be clearly connected with the effects of the cytokine upon the beta-cell. In conclusion, the different studies devoted to the problem of IL-1 signal transduction on the beta-cell seem to indicate that the action of the cytokine on the pancreatic insulin-secreting cells is not associated with an individual second messenger system but rather seems to be related to a plurifactorial transduction system.

[Rebound hyperglycemia and peroperative normalization of insulinemia. Complete excision of insulinoma?]. / Rebond hyperglycémique et normalisation per-opératoire de l'insulinémie. Exérèse totale de l'insulinome?

Clinical usefulness of the hyperglycemic rebound and the normalization of plasma insulin level as intraoperative markers of complete removal of insulinoma was assessed. Surgical removal was curative (no clinical or biological recurrence) in six patients harboring a single adenoma (mean follow-up = 32.2 months). In these patients plasma glucose increased an average of 32 mg/dl 30 minutes after resection, 68 mg/dl after 60 minutes, and 91 mg/dl after 90 minutes. Sensitivity of hyperglycemic rebound (defined as a plasma glucose increment of at least 30 mg/dl after tumor removal) as a marker of complete resection of the insulinoma was 40% at 30 min and 83% at 60 minutes after resection. Preresectional values of plasma immunoreactive insulin were elevated in 3 out of 4 patients with adenoma. All postresectional values were within normal ranges. Two patients operated on because of malignant insulinoma, underwent partial tumor resection; hyperglycemic rebound was also present, and high preresectional insulin values became normal 30 minutes after partial tumor removal. We conclude that information provided by intraoperative monitoring of both plasma glucose and insulin cannot be used as the only markers of complete resection of all insulinomas. Only long term clinical and biological follow-up can guarantee the complete resection of an insulinoma.

Serum fructosamine is not a useful screening test for gestational diabetes.

Serum fructosamine was measured in 569 samples of pregnant women without gestational diabetes. We defined abnormal fructosamine as mean + 2SD, and analysed its potential value to detect patients with gestational diabetes diagnosed with current screening criteria. We found serum fructosamine to be an insensitive parameter: Measured at the time of a positive 50 g glucose screening, SF would have detected 4/48 gestational diabetes.

Effect of L-asparaginase on insulin secretion from isolated rat islets of Langerhans.

The effects of L-asparaginase were evaluated on glucose-induced insulin release from isolated rat islets of Langerhans. Islets were obtained by enzymatic digestion of pancreas from Sprague-Dawley rats. The study of L-asparaginase effects on insulin secretion was performed in a static incubation of islets. Insulin secretion was measured at 60 min of incubation with different secretagogues with and without L-asparaginase. L-Asparaginase at concentrations from 310 to 5,000 U/ml could inhibit the glucose-induced insulin secretion in a dose-dependent manner. This effect was not recovered after incubation in the absence of the drug for another 2 h. The half-maximal inhibitory effect of the enzyme on insulin secretion was observed at L-asparaginase concentrations of 1,000 U/ml. Tolbutamide (200 microM) and ketoisocaproic acid (20 mM) did not induce insulin secretion in the presence of moderately high L-asparaginase concentrations. L-Asparaginase did not inhibit glucose-induced insulin secretion in the presence of isobutyl-methyl-xanthine (IBMX) (20 microM) or forskolin (20 microM). L-Asparaginase promoted a decrease in total c-AMP in isolated rat islets at concentrations from 500 to 1,500 U/ml when they were stimulated by glucose. If islets were treated with IBMX or forskolin, L-asparaginase did not inhibit the glucose-induced total c-AMP levels in islets.

Superficial esophageal carcinoma: a report of 12 cases.

Twelve cases of superficial carcinoma of the esophagus, representing 4.9% of patients with carcinoma of the esophagus, were evaluated. All the patients were male smokers who drank alcohol excessively. The main clinical features were dysphagia, asthenia, anorexia, and weight loss. Most of the lesions were elevated and all endoscopic biopsies were positive for cancer. Half of the cases showed invasion of the submucosa; the remainder involved mucosa only. Ten patients are alive and free of metastatic disease.