Andrea Manto

Defective Plasma Antioxidant Defenses and Enhanced Susceptibility to Lipid Peroxidation in Uncomplicated IDDM

Oxidative stress is postulated to be increased in patients with IDDM. Accumulating evidence suggests that oxidative cell injury caused by free radicals contributes to the development of IDDM complications. On the other side, a decreased efficiency of antioxidant defenses (both enzymatic and nonenzymatic) seems to correlate with the severity of pathological tissue changes in IDDM. Thus, we determined plasma antioxidant defenses, measuring the total radical-trapping antioxidant capacity (TRAP) and the two markers of oxidative stress, lipid hydroperoxides (ROOHs) and conjugated dienes, in 72 patients with well-controlled IDDM and without evident complications, compared with 45 nondiabetic subjects. Compared with control subjects, IDDM patients showed significantly reduced plasma TRAP (669 ±131 vs. 955 ± 104 μmol/1, P < 0.001) and significantly increased levels of ROOHs (7.13 ± 2.11 vs. 2.10 ± 0.71 μmol/1, P < 0.001) and conjugated dienes (0.0368 ± 0.0027 vs. 0.0328 ± 0.0023 arbitrary units [AU], P < 0.01), especially in the trans-trans conformation (0.0340 ± 0.0028 vs. 0.0259 ± 0.0022 AU, P < 0.001), with a concurrent reduction of conjugated dienes in the cis-trans conformation (0.0028 ± 0.0011 vs. 0.0069 ± 0.0012 AU, P < 0.001). The oxidative parameters studied did not appear to be correlated with metabolic control (HbA1c levels) and lipid profile (cholesterol or triglyceride levels). The reduced TRAP and the increased ROOH and conjugated diene plasma levels, together with the decreased ratio of cis-trans/trans-trans conjugated dienes, which reflects an altered redox status of plasma, indicate that in IDDM patients, oxidative stress is enhanced and antioxidant defenses are defective, regardless of diabetes duration, metabolic control, or presence of complications.

Lower limb arterio-venous shunts, autonomic neuropathy and diabetic foot

We have quantitatively assessed the percentage of lower limb arterio-venous (a-v) shunting using a radioisotopic technique and correlated it with autonomic neuropathy evaluated by cardiovascular tests. We have studied three groups of diabetic patients: Group A, 12 non-neuropathic subjects without foot lesions; Group B, 12 neuropathic subjects without foot lesions; Group C, 12 neuropathic subjects with recurrent foot ulcers. Shunting was higher in Group C (10.4 +/- 2.7%) than in Group B (6.8 +/- 2.3%, P less than 0.01) and Group A (3.8 +/- 1.2%, P less than 0.001). Shunts in Group B were higher than in Group A (P less than 0.05). All the tests exploring autonomic function were more impaired in Groups B and C than in Group A, with no difference between Groups B and C. A direct correlation was found between a-v shunting and the following cardiovascular tests: postural hypotension (PH) (r = 0.41, P less than 0.02), sustained handgrip (SH) (r = 0.56, P less than 0.001), deep breathing (DB) (r = 0.40, P less than 0.005) and lying to standing (LS) (r = 0.44, P less than 0.01). A positive correlation was also found between a-v shunts and duration of the disease (r = 0.62, P less than 0.001). Arterio-venous shunting was found to be directly related to autonomic neuropathy even if the higher shunting found in the patients with foot ulcers was not related to a higher degree of autonomic involvement; in addition, this group of patients was characterized by having a more advanced sensory and motor neuropathy. In conclusion, autonomic neuropathy, through its influence on a-v shunts, may play a role in the pathogenesis of diabetic foot, but peripheral neuropathy probably plays a key role in conditioning the development of the overt clinical manifestations of diabetic foot.

Factors associated with cognitive impairment among older Italian inpatients

OBJECTIVE: To examine the association of cognitive impairment with educational, demographic, and nutritional variables in older hospitalized people.

Effect of α-Lipoic Acid on Platelet Reactivity in Type 1 Diabetic Patients

OBJECTIVE Type 1 diabetes is associated with increased platelet reactivity. We investigated whether α-lipoic acid (ALA) has any effect on platelet reactivity in these patients. RESEARCH DESIGN AND METHODS We randomly assigned 51 type 1 diabetic patients to ALA (600 mg once daily) or placebo for 5 weeks. Platelet reactivity was evaluated by the PFA-100 method and by measuring CD41 and CD62 platelet expression. C-reactive protein (CRP) and 8-iso-prostaglandin F2α serum levels also were measured. RESULTS Baseline variables were similar in the two groups. After treatment, closure time was longer (P = 0.006) and CD62P platelet expression was lower, both before (P = 0.002) and after (P = 0.009) ADP stimulation in the ALA group compared with the placebo group. CRP and 8-iso-prostaglandin F2α levels showed no differences between the two groups. CONCLUSIONS Our data show that ALA reduces measures of platelet reactivity ex vivo in type 1 diabetic patients, independently of antioxidant or anti-inflammatory effects.

Trends of the characteristics and appropriateness of admissions to acute geriatric and medical wards in Italy from 1988 through 1993

Recent modifications in the health care system in Italy reduced the number of inpatient care beds and limited the access to outpatient services while the proportion of older persons increased. To assess the burden of these changes on hospital care the characteristics of admissions to 35 acute geriatric wards and 31 internal medicine wards in Italy were studied between 1988 and 1993. All patients admitted during 4 months in 1988, 1 month in 1991 and 4 months in 1993 were enrolled in the study. The appropriateness of admission was assessed by means of the Appropriateness Evaluation Protocol criteria. The Charlson comorbidity index score was used to quantify comorbidity. Between 1988 and 1993, 18,790 patients were studied. The mean age increased from 67.9 ± 0.2 to 71.7 ± 0.2 years (p < 0.0001), the mean number of drugs taken during hospital stay increased from 5.2 ± 0.0 to 5.5 ± 0.0 drugs (p < 0.0001), the mean Charlson comorbidity index score increased from 1.33 ± 0.02 to 1.50 ± 0.03 (p < 0.0001) and the mean length of stay decreased from 17.6 ± 0.2 to 16.1 ± 0.2 days (p < 0.0001). The rate of appropriate admissions increased from 68.6% to 85.5% (p < 0.0001). Consistent results were found when the data were stratified according to gender and type of ward. It was concluded that in Italy, concurrently to an increased load of hospital care, inappropriate admissions diminished over time. These data show that the need for geriatric care is increasing.

Possible Radio Interference Between Video Capsule Endoscopy and Second-Generation OmniPod Patch Pump

Video capsule endoscopy (VCE) is a noninvasive diagnostic tool used to observe the small intestinal mucosa. We report a case of a 57-year-old woman with T2DM, treated with continuous subcutaneous insulin infusion using second-generation OmniPod patch pump, undergoing VCE (Given M2A; VCE Ltd, Yoqneam, Israel) for melena and anemia. During VCE, an abnormal interruption of communication between video capsule and its receiver occurred. Two hours after capsule ingestion, the patient activated the insulin pump infusion through the Personal Diabetes Manager (PDM) because she drank a sugary beverage for the first time after ingestion. Due to this, we decided to repeat VCE after the removal of the insulin pump and PDM: at this time, the capsule recorded for more than 10u2009h without any interruption. The video capsule and second-generation OmniPod patch pump use the same radio frequency and this may cause interference between these two devices. In patients using second-generation OmniPod patch pump undergoing VCE, we suggest to switch to intravenous insulin infusion or multiple daily injection or to use a different model of VCE, as MiRoCam (Intromedic, Seoul, Korea).

Somatostatin response to a mixed meal in normals and in type I diabetics

Somatostatin has been proposed as a regulatory peptide of nutrient entry and fuel homeostasis because of its ability to inhibit the release of substances involved in food digestion and metabolism. The aim of the study was to evaluate the somatostatin response to a test meal in type I diabetics at the clinical onset of the disease and after two months of intensive insulin therapy. Normal subjects and diabetics in good metabolic control showed a characteristic biphasic somatostatin rise after a test meal; this response was lacking in diabetics at the onset of the disease. The response of somatostatin to a mixed meal in normals confirms its involvement in nutrient digestion and metabolism. The lacking somatostatin response in newly diagnosed type I diabetics might be related to deficient GIP response to the test meal or to other factors such as the insulinopenia or metabolic derangement characteristic of the clinical onset of the disease.

Abnormal Agonist-Stimulated Cardiac Parasympathetic Acetylcholine Release in Streptozocin-Induced Diabetes

We examined the effect of three distinct depolarizing conditions on [3H]ACh release from cardiac postganglionic parasympathetic neurons in age-matched controls and insulin-treated STZ-induced diabetic rats to determine whether alterations in neurotransmitter release were present in the diabetic group. The effect of TTX, which exerts a use- and voltage-dependent block of sodium channels, was examined on the release of ACh stimulated by SRIF14 (preferentially acts at the cell body). We also studied the effect of STZ-induced diabetes on [3H]ACh release by the relatively site-specific depolarizing agent VT (preferentially acts at the axon) and high potassium (non-site-specific). Basal, SRIF14-(10−7 M), VT-(1CT4 M), and K+ (100 mM)-stimulated [3H]ACh release was similar in control and STZ-induced diabetic animals. However, in STZ-induced diabetic but not control rats, SRIF14-induced [3H]ACh release was resistant to TTX (2 × 107 M). In addition, the response to submaximal K+ (25 mM) stimulation was greater in STZ-induced diabetic compared with control animals. Treatment with insulin corrected these abnormalities. These data indicate that in the acute STZ-induced diabetic rat, SRIF14-, VT-, and high K+-evoked release of ACH is not impaired, which suggests that the mechanisms associated with ACh storage and release in postganglionic cardiac parasympathetic neurons are not affected in this model. However, the TTX insensitivity and the increase in ACh release in response to submaximal K+ stimulation inSTZ-induced diabetes are consistent with a positive shift in the resting membrane potential in postganglionic cardiac parasympathetic axons similar to that reported in peripheral somatic nerve axons in experimental diabetes.

Association among sarcoidosis, type 1 diabetes, and Charcot neuro-osteoarthropathy.

Sarcoidosis is a multisystemic inflammatory disease. The association between sarcoidosis and type 1 diabetes is rare. We report two cases of sarcoidosis associated with type 1 diabetes complicated by Charcot neuro-osteoarthropathy (CN).nnA subject with type 1 diabetes complicated by peripheral and autonomic neuropathy presented cough and cervical lymphadenopathy. The chest computed tomography (CT) scan revealed bilateral hilar lymphadenopathy. A mediastinal lymph node biopsy showed noncaseating giant epithelioid cell granulomas. The immunohistological examination of a follicle showed the prevalence of T-cells. The result of a Mantoux test was negative. Bronchoalveolar lavage was sterile. ACE was absent from bronchoalveolar lavage fluid and increased to 40 UI/l (normal <20 UI/l; colorimetric …