Vascular involvement in diabetic subjects with ischemic foot ulcer: a new morphologic categorization of disease severity.

OBJECTIVES: Arteriographic lesions of diabetic subjects with critical limb ischemia (CLI) and ischemic foot ulcer were reviewed retrospectively, to provide new criteria for stratification of these patients on the basis of their vascular involvement. PATIENTS: In 417 consecutive CLI diabetic subjects with ischemic foot ulcer undergoing lower limb angiography, lesions were defined as stenosis or occlusion, localization, and length (<5 cm, 5-10 cm, >10 cm). In a subgroup of 389 subjects, foot arteries also were evaluated. Patients then were categorized into 7 classes of progressive vascular involvement based on angiographic findings. RESULTS: Of the 2893 found lesions (55% occlusions) 1% were in the iliac arteries, whereas 74% were in below-the-knee (BTK) arteries. Sixty-six % of all BTK lesions were occlusions, and 50% were occlusions >10 cm (p<0.001 vs proximal segments). Occlusions of all BTK were present in 28% of patients, although there was patency of at least one foot artery in 55% of patients. The morphologic Class 4 (two arteries occluded and multiple stenoses of tibial/peroneal and/or femoral/popliteal vessels) was the most common (36%). An inverse correlation between morphologic class and TcPO2 was observed (r=-0.187, p=0.003). CONCLUSIONS: In CLI diabetic subjects with ischemic foot ulcer, the vascular involvement is extremely diffuse and particularly severe in tibial arteries, with high prevalence of long occlusions. A new morphologic categorization of these patients is proposed.

Screening for peripheral arterial disease by means of the ankle-brachial index in newly diagnosed Type 2 diabetic patients.

AIM: To evaluate the prevalence of peripheral arterial disease (PAD) with the ankle-brachial index (ABI) in newly diagnosed Type 2 diabetic subjects. METHODS: Between autumn 2002 and spring 2003, 2559 newly diagnosed Type 2 diabetic subjects (about 15% of the cases/year in Italy) were enrolled in 265 diabetology centres. Family history of diabetes, smoking, height, weight, waistline, fasting glycaemia, glycosylated haemoglobin, total and HDL-cholesterol and triglyceride values were collected. Claudication, cyanosis, cold foot, foot hair anomalies, skin thinning and femoral, popliteal, posterior tibial and dorsalis pedis pulses were assessed. The ABI was measured with a portable Doppler continuous-wave instrument. RESULTS: An ABI < 0.9 was found in 539 (21.1%) patients. Claudication was present in 187 (7.3%). Femoral pulse was absent in 218 (8.5%), popliteal in 316 (12.3%), tibial in 563 (22.0%) and dorsalis pedis in 578 (22.6%). Foot cyanosis was observed in 88 (3.4%), cold foot in 359 (13.9%), skin thinning in 468 (18.3%) and hair anomalies in 857 (33.5%). Multivariate analysis of the variables associated with ABI < 0.9 in the univariate analysis confirmed the independent role of age [relative risk (RR) 1.02, P < 0.001, confidence interval (CI) 1.01, 1.04], claudication (RR 4.53, P < 0.001, CI 2.97, 6.93), absence of tibial pulse (RR 3.45, P < or = 0.001. CI 2.54, 4.68) and pedis pulse (RR 1.96, P < or = 0.001, CI 1.4, 2.68). CONCLUSIONS: PAD, as represented by ABI < 0.9, is common in newly diagnosed Type 2 diabetic patients.

[Hemolytic anemia associated with breast neoplasm]. / Anemia emolitica associata a neoplasia mammaria.

We describe a patient with a microangiopathic hemolytic anemia, associated with thrombocytopenia, in consequence of breast cancer in an advanced phase. Microangiopathic hemolytic anemia is a rare and serious compliance of malignant neoplasms, in particular of breast and gastric carcinomas. Microangiopathic hemolytic anemia has always a serious prognosis: survivance in non-treated patients is of a few weeks. Our patient, treated by chemotherapy, has gained a partial remission of MHA, with a reduction of blood transfusions.

Effect of metabolic control on nitrite and nitrate metabolism in type 2 diabetic patients.

1. The measurement of nitrite and nitrate levels in plasma and urine is an approach to assess the activity of the endogenous nitric oxide (NO) system. The aim of the present study was to evaluate whether metabolic control may affect plasma levels and urinary excretion of nitrates and nitrites in type 2 diabetic patients. 2. Twenty consecutive type 2 diabetic patients were studied twice: first (study 1), under poor metabolic control; and, second, after improved metabolic conditions. Determinations of the main metabolic parameters and of plasma nitrates and nitrites (NOX) were performed in the fasting state. A 24 h urinary specimen was obtained for glycosuria, NOX and creatinine. Diet compliance and home blood glucose monitoring was evaluated on a weekly basis until study 2 was performed after 32 +/- 7 days: then, an identical protocol was repeated (study 2). 3. Fasting plasma glucose was lower in study 2 (8.27 +/- 2.11 vs 10.77 +/- 3.88 mmol/L, respectively; P < 0.05); similarly glycosylated haemoglobin (HbA1c) improved significantly. Plasma NOX levels were similar between the first and second studies (14.3 +/- 7.8 vs 13.5 +/- 8.1 micromol/L, respectively); nor were any differences observed in urinary NOX excretion rates (726 +/- 607 vs 689 +/- 444 micromol/day, respectively). The urinary excretion fraction of NOX was higher during study 1 than during study 2 (3.22 +/- 2.38 vs 1.88 +/- 1.98%, respectively; P = 0.031). A relationship was observed between fasting plasma glucose levels and the urinary excretion fraction of NOX (r2 = 0.12; P = 0.026). 4. In type 2 diabetic patients, plasma and urinary levels of NOX do not change after improvement of metabolic control. A worse metabolic control is associated with an increased urinary fraction excretion of NOX: thus, changes in plasma NOX concentration may reflect the effect of hyperglycaemia in the renal handling of these compounds rather than the effects on the L-arginine-NO pathway.

Effect of acute ketosis on the endothelial function of type 1 diabetic patients: the role of nitric oxide.

In type 1 diabetic patients, acute loss of metabolic control is associated with increased blood flow, which is believed to favor the development of long-term complications. The mechanisms for inappropriate vasodilation are partially understood, but a role of endothelium-derived nitric oxide (NO) production can be postulated. We assessed, in type 1 diabetic patients, the effect of the acute loss of metabolic control and its restoration on forearm endothelial function in 13 type 1 diabetic patients who were studied under conditions of mild ketosis on two different occasions. In study 1, after basal determination, a rapid amelioration of the metabolic picture was obtained by insulin infusion. In study 2, seven type 1 diabetic patients underwent the same experimental procedure, except that fasting plasma glucose was maintained constant throughout. Basal plasma venous concentrations of nitrites/nitrates (NO2- + NO3-) were determined both before and after intravenous insulin infusion. Endothelium-dependent and -independent vasodilation of the brachial artery was assessed by an intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA) and sodium nitroprusside (SNP), respectively. The same parameters were determined in 13 control subjects at baseline conditions and during a hyperinsulinemic-euglycemic glucose clamp. Baseline forearm blood flow (4.89 +/- 0.86 vs. 3.65 +/- 0.59 ml x (100 ml tissue)(-1) x min(-1)) and NO2- + NO3- concentration (30 +/- 8 vs. 24 +/- 3 micromol/l) were higher in type 1 diabetic patients than in control subjects (P < 0.05). Insulin infusion was associated with lower forearm blood flow and plasma (NO2- + NO3-) concentration (P < 0.05), irrespective of the prevailing glucose levels, as compared with patients under ketotic conditions. The responses to L-NMMA were significantly lower in type 1 diabetic patients during euglycemia and hyperglycemic hyperinsulinemia (-11 +/- 5 and -10 +/- 4%, respectively, of the ratio of the infused arm to the control arm) than in control subjects at baseline (-18 +/- 6%, P < 0.05) and during hyperinsulinemia (-32 +/- 11%, P < 0.01). We conclude that the acute loss of metabolic control is associated with a functional disturbance of the endothelial function characterized by hyperemia and increased NO release during ketosis and blunted NO-mediated vasodilatory response during restoration of metabolic control by intravenous insulin. This functional alteration is unlikely to be explained by hyperglycemia itself.

Myocardial dysfunction and adrenergic cardiac innervation in patients with insulin-dependent diabetes mellitus.

BACKGROUND: Insulin-dependent diabetes mellitus (IDDM) is associated with an increased incidence of heart failure due to several factors, and in some cases a specific cardiomyopathy has been suggested. OBJECTIVES: This study sought to assess the mechanisms of exercise-induced left ventricular (LV) dysfunction in asymptomatic patients with IDDM in the absence of hypertensive or coronary artery disease. METHODS: Fourteen consecutive patients with IDDM were enrolled (10 men, 4 women; mean [+/- SD] age 28.5 +/- 6 years); 10 healthy subjects matched for gender (7 men, 3 women) and age (28.5 +/- 3 years) constituted the control group. LV volume, LV ejection fraction (LVEF) and end-systolic wall stress were calculated by two-dimensional echocardiography at rest and during isometric exercise. LV contractile reserve was assessed by post-extrasystolic potentiation (PESP) obtained by transesophageal cardiac electrical stimulation and dobutamine infusion. Myocardial iodine-123 metaiodobenzylguanidine (MIBG) scintigraphy was performed to assess adrenergic cardiac innervation. RESULTS: Diabetic patients were classified into group A (n = 7), with an abnormal LVEF response to handgrip (42 +/- 7%), and group B (n = 7), with a normal response (72 +/- 8%). Baseline LVEF was normal in both group A and B patients (60 +/- 6% vs. 61 +/- 7%, p = NS). In group A patients, the LV circumferential wall stress-LVEF relation showed an impairment in LVEF disproportionate to the level of LV afterload. No significant changes in LVEF occurred during dobutamine (60 +/- 6% vs. 64 +/- 10%, p = NS), whereas PESP significantly increased LVEF (60 +/- 6% vs. 74 +/- 6%, p < 0.001); PESP at peak handgrip normalized the abnormal LVEF (42 +/- 7% vs. 72 +/- 5%, p < 0.001); and MIBG uptake normalized for body weight or for LV mass was lower than that in normal subjects (1.69 +/- 0.30 vs. 2.98 +/- 0.82 cpm/MBq per g, p = 0.01) and group B diabetic patients (vs. 2.79 +/- 0.94 cpm/MBq per g, p = 0.01). Finally, a strong linear correlation between LVEF at peak handgrip and myocardial MIBG uptake normalized for LV mass was demonstrated in the study patients. CONCLUSIONS: Despite normal contractile reserve, a defective blunted recruitment of myocardial contractility plays an important role in determining exercise LV dysfunction in the early phase of diabetic cardiomyopathy. This abnormal response to exercise is strongly related to an impairment of cardiac sympathetic innervation.

[Endosteal hyperostosis with recessive transmission (Van Buchem's disease). A case report]. / Iperostosi endostale a trasmissione recessiva (malattia di Van Buchem). Segnalazione di un caso.

A rare case of Van Buchem's disease is described. This disease is a hereditary sclerosis dysplasia of bone which particularly affects the skull and long bones, the characteristic features being the endosteal deposition of bone, particularly in the diaphyses.

Metabolic effects of physical training in subjects with oral glucose intolerance.

A group of normal weight subjects with oral glucose intolerance was studied for 4 months before, during, and after a physical training program (8 km/day/run). There were no significant differences in weight, basal blood glucose, lactate, and total cholesterol during and after training as compared with before training. Serum triglycerides significantly (P less than 0.05) decreased during the training period, and cholesterol-HDL significantly (P less than 0.01) increased during and after the physical program. Our data show that in previously inactive subjects with oral glucose intolerance physical training improves serum lipid patterns and thereby reduces atherosclerotic risk.