Neutrophils and monocytes as potentially important sources of proinflammatory cytokines in diabetes.

Neutrophils and monocytes play a central role in host defence. The invading leucocytes are capable of synthesizing and releasing a variety of proinflammatory mediators including cytokines. Given the importance of cytokines in the progression of chronic and acute inflammatory processes, we aimed to ascertain whether the release of interleukin (IL)-8, IL-1beta, tumour necrosis factor (TNF)-alpha and IL-1ra of neutrophils and monocytes was modified in diabetes. To this end, we measured the release of cytokines in suspensions of cell culture in basal and lipopolysaccharide (LPS)-stimulated conditions. In basal conditions, neutrophils of diabetics release 1.6, 3.2, 1.9 and 1.9-fold higher amounts of IL-8, IL-1beta, TNF-alpha and IL-1ra, respectively, than do healthy controls. Under our experimental conditions, this effect was more evident for neutrophils than for monocytes. Incremental cytokine production was also found to occur when neutrophils were stimulated with LPS. IL-8, IL-1beta and TNF-alpha increased, respectively, by 4.0, 1.7 and 2.8-fold. Although the effect was more marked for neutrophils, monocytes showed a tendency for increased cytokine production. The discovery of this increase in cytokines released by the neutrophils of diabetics contributes towards a clearer understanding of other deficiencies described for neutrophils in diabetes, such as the migration of neutrophils to inflammatory sites, phagocytes, release of lytic proteases, production of reactive oxygen species and apoptosis. The excessive production of cytokines may lead to inappropriate activation and tissue injury and even to increased susceptibility to invasive microorganisms. Thus, the increased responsiveness of neutrophils of diabetics demonstrated in this study may be considered part of the scenario of diabetes physiopathology.

A comparison between different parameters in F-wave studies.

Ulnar nerve F-waves were studied in 23 healthy volunteers and 27 diabetic patients. Latencies and chronodispersion were analyzed in each group. In the diabetic group all the parameters were normal in 14 patients (52%) and in 13 (48%) at least one parameter was altered. In these patients the most frequently altered parameter was the maximum latency (92%), followed by mean latency (85%), minimum latency (54%) and chronodispersion (54%). These findings suggest that maximum and mean latencies are better parameters to be analyzed in ulnar F-wave studies than minimum latency.

F-waves and conduction velocities range.

A controversial aspect in F-wave studies is if these potentials are generated preferentially by large motoneuron or by motoneuron of all sizes. The purpose of this work is to compare the maximum and minimum conduction velocities of the fibers that generate the M-wave with the maximum and minimum conduction velocities of the F-waves elicited by ulnar nerve stimulation. There were no significant differences between maximum velocities. However, minimum F-wave velocity was significantly higher than minimum conduction velocity, suggesting that the F-waves registered were preferentially generated by the fastest conducting axons.

Influence of autonomic neuropathy upon left ventricular dysfunction in insulin-dependent diabetic patients.

BACKGROUND: Diabetic cardiomyopathy is a well-defined complication of diabetes that occurs in the absence of ischemic, vascular, and hypertensive disease. HYPOTHESIS: The study was undertaken to test the relationship among autonomic neuropathy (AN), 24-h blood pressure (BP) profile, and left ventricular function. METHODS: Nineteen type-1 diabetic patients underwent autonomic tests and echocardiographic examination. Patients were divided according to the presence (AN+) or absence (AN-) of AN. RESULTS: In the AN+ group (n = 8), the E/A ratio at echo was lower than in the AN- group (n = 11) (1.1 +/- 0.3 vs. 1.6 +/- 0.3; p < 0.005). Systolic and diastolic BP reductions during sleep were smaller in the AN+ than in the AN- group (6.6 +/- 6.6 vs. 13.0 +/- 4.3%; p < 0.03 for systolic and 12.8 +/- 6.8 vs. 20.0 +/- 4.0% for diastolic BP reduction; p < 0.03, respectively). Considering all patients, the E/A ratio correlated inversely with awake diastolic BP (r - 0.63; p = 0.005); sleep systolic BP (r - 0.48; p = 0.04), and sleep diastolic BP (r - 0.67; p = 0.002). The AN correlated with diastolic interventricular septum thickness (r 0.57; p = 0.01), sleep systolic BP (r 0.45; p = 0.05), sleep diastolic BP (r 0.54; p = 0.02), and correlated inversely with systolic and diastolic sleep BP reduction (r - 0.49; p = 0.03 and r - 0.67; p = 0.002, respectively). Finally, E/A ratio and AN score correlated between themselves (r - 0.6; p = 0.005). CONCLUSION: Our results suggest that left ventricular diastolic dysfunction may be detected very early in type-1 diabetic patients with AN. Parasympathetic lesion and nocturnal elevations in BP could be the link between AN and diastolic ventricular dysfunction.

Sample size and the study of F waves.

Ulnar nerve F waves were studied in 23 healthy volunteers and 27 diabetic patients. Latencies and chronodispersion were analyzed in each group for different sample sizes. Significant differences were not detected with the different sample sizes for mean latencies, with samples above 16 stimuli or 10 waves for minimum and maximum latencies and above 20 stimuli or 16 waves for chronodispersion. These findings suggest that these limits may be adequate for group comparison. However, for the analysis of individual patients, the evidence suggests that larger samples are required for the determination of the minimum and maximum latencies and chronodispersion.

Microangiopathic complications in type 1 diabetes mellitus: differences in severity when isolated or associated with autoimmune polyendocrinopathies.

CONTEXT: The development and evolution of different chronic diabetic complications may present variations among the different types and conditions of this disease. OBJECTIVE: To evaluate the degree of microangiopathy in Type 1 diabetes mellitus (DM1) associated with autoimmune polyendocrinopathies (OSAD) or isolated DM1 (iDM1). PATIENTS: OSAD (n = 17) and iDM1 (n = 13) were over 15 years old at diagnosis of DM and were matched for diabetes duration (13.9 +/- 8.2 and 13.2 +/- 5.9 years respectively) and metabolic control (HbA1c: 6.4 +/- 1.9 and 6.8 +/- 1.4%). MAIN OUTCOME MEASURES: Urinary albumin excretion (UAE; ELISA), the inversion of serum creatinine (1/C) level and indirect ophthalmoscopy. RESULTS: Although the prevalence of hypertension was similar in both groups, the OSAD had inferior levels of UAE (7.4 +/- 2.5 vs. 17.3 +/- 9.2 micrograms/min; p < 0.05). Nephropathy was detected in 12% of the OSAD (none of them macroproteinuric) and in 39% of the iDM1. The UAE in the iDM1 correlated negatively with 1/C values (r = -0.7, p < 0.005), but the same did not occur in the OSAD (r = 0.2, ns). Among patients with retinopathy, the severe form was found in 29% of the OSAD and in 46% of the iDM1. CONCLUSIONS: OSAD was associated with a lower degree of microangiopathy, in spite of age at diagnosis, duration of diabetes and the metabolic control. In contrast with the iDM1, the increase in UAE of OSAD was not associated with reductions in GFR.

Altered blood pressure profile, autonomic neuropathy and nephropathy in insulin-dependent diabetic patients.

To evaluate the relationship between autonomic neuropathy (AN) and nephropathy we measured 24-h blood pressure (BP) and overnight urinary albumin excretion (UAE) in 38 patients with insulin dependent diabetes mellitus (IDDM). Autonomic function was evaluated by the heart rate response to deep breathing. Valsalva maneuver, heart rate at rest and BP variation with posture. Sympathetic cutaneous reflex was also tested in both inferior and superior limbs. Patients with mean day diastolic BP (DDBP) < or = 90 mmHg without AN (N = 15) compared to 12 normal controls had similar BP values, but compared to those with DDBP < or = 90 mmHg and AN (N = 12) they had lower night diastolic BP (NDBP) (66 +/- 4.8 vs 72 +/- 8.8 mmHg: p < 0.05) and UAE (9.8 +/- 2.3 vs 107.2 +/- 3.5 micrograms/min; p < 0.001). No difference in DDBP was observed between these two diabetic groups (80 +/- 3.9 vs 83 +/- 6.1 mmHg). Of the 11 patients with DDBP > 90 mmHg, only three were free of AN and only two of the eight with AN where free of diabetic nephropathy. The percentage day/night changes in systolic BP were lower in patients with AN (13 vs 7.9%; p < 0.05) and were inversely related to autonomic score, used as an index of the degree of autonomic dysfunction (r = -0.48; p < 0.01) and to UAE (r = -0.39; p < 0.05). Furthermore, UAE correlated with autonomic score (r = 0.69; p < 0.0001) and with NDBP (r = 0.44; p < 0.01). Our results show that AN in IDDM patients is associated with a reduced nocturnal fall in BP and suggest a pathogenic role of autonomic dysfunction in the development of diabetic nephropathy, possibly favoring both BP elevation during the night and increases in intraglomerular pressure.