Unsteady walking as a symptom in type 2 diabetes mellitus: independent association with depression and sedentary lifestyle and no association with diabetic neuropathy

The purpose of this study was to look at the determinants of the unsteady walking (UW) symptom in patients with type 2 diabetes mellitus (T2DM) by defining if UW and/or the Diabetic Neuropathy Symptoms Score (DNSS) are associated with positive scores in Beck's Depression Inventory (BDI) and with a positive Michigan Neuropathy Screening Instrument score (MNSI). We evaluated 203 T2DM patients without visible gait disturbances. They were divided into UW (+) and UW (−) or DNSS (+) and DNSS (−) according to symptoms. We found a prevalence of 48.3% for UW (+) and of 63% for DNSS (+) in our sample. In univariate analysis, the presence of UW was significantly associated with waist circumference (P=0.024), number of comorbidities (P=0.012), not practicing physical exercise (P=0.011), positive BDI score (P=0.003), presence of neuropathic symptoms by the MNSI questionnaire (P<0.001), and positive diabetic neuropathy screening by MNSI (P=0.021). In multivariate analysis, UW (used as a dependent variable) was independently associated with a positive BDI score (P<0.001; 95%CI=1.01-1.03), T2DM duration (P=0.023; 95%CI=1.00-1.03), number of co-morbidities (P=0.032; 95%CI=1.01-1.37), and a sedentary lifestyle (P=0.025; 95%CI=1.06-2.5). The UW symptom and a positive DNSS are more closely related to a positive score for depression than to presence of neuropathy in T2DM.

Relationship between cardiovascular dysfunction and hyperglycemia in streptozotocin-induced diabetes in rats

Streptozotocin (STZ)-induced diabetes in rats is characterized by cardiovascular dysfunction beginning 5 days after STZ injection, which may reflect functional or structural autonomic nervous system damage. We investigated cardiovascular and autonomic function, in rats weighing 166 ± 4 g, 5-7, 14, 30, 45, and 90 days after STZ injection (N = 24, 33, 27, 14, and 13, respectively). Arterial pressure (AP), mean AP (MAP) variability (standard deviation of the mean of MAP, SDMMAP), heart rate (HR), HR variability (standard deviation of the normal pulse intervals, SDNN), and root mean square of successive difference of pulse intervals (RMSSD) were measured. STZ induced increased glycemia in diabetic rats vs control rats. Diabetes reduced resting HR from 363 ± 12 to 332 ± 5 bpm (P < 0.05) 5 to 7 days after STZ and reduced MAP from 121 ± 2 to 104 ± 5 mmHg (P = 0.007) 14 days after STZ. HR and MAP variability were lower in diabetic vs control rats 30-45 days after STZ injection (RMSSD decreased from 5.6 ± 0.9 to 3.4 ± 0.4 ms, P = 0.04 and SDMMAP from 6.6 ± 0.6 to 4.2 ± 0.6 mmHg, P = 0.005). Glycemia was negatively correlated with resting AP and HR (r = -0.41 and -0.40, P < 0.001) and with SDNN and SDMMAP indices (r = -0.34 and -0.49, P < 0.01). Even though STZ-diabetic rats presented bradycardia and hypotension early in the course of diabetes, their autonomic function was reduced only 30-45 days after STZ injection and these changes were negatively correlated with plasma glucose, suggesting a metabolic origin.

Time course of changes in heart rate and blood pressure variability in streptozotocin-induced diabetic rats treated with insulin

Autonomic neuropathy is a frequent complication of diabetes associated with higher morbidity and mortality in symptomatic patients, possibly because it affects autonomic regulation of the sinus node, reducing heart rate (HR) variability which predisposes to fatal arrhythmias. We evaluated the time course of arterial pressure and HR and indirectly of autonomic function (by evaluation of mean arterial pressure (MAP) variability) in rats (164.5 + 1.7 g) 7, 14, 30 and 120 days after streptozotocin (STZ) injection, treated with insulin, using measurements of arterial pressure, HR and MAP variability. HR variability was evaluated by the standard deviation of RR intervals (SDNN) and root mean square of successive difference of RR intervals (RMSSD). MAP variability was evaluated by the standard deviation of the mean of MAP and by 4 indices (P1, P2, P3 and MN) derived from the three-dimensional return map constructed by plotting MAPn x [(MAPn+1) - (MAPn)] x density. The indices represent the maximum concentration of points (P1), the longitudinal axis (P2), and the transversal axis (P3) and MN represents P1 x P2 x P3 x 10(-3), STZ induced increased urinary glucose in diabetic (D) rats compared to controls (C). Seven days after STZ, diabetes reduced resting HR from 380.6 + 12.9 to 319,2 + 19.8 bpm, increased HR variability, as demonstrated by increased SDNN, from 11.77 + 1.67 to 19.87 + 2.60 ms, did not change MAP, and reduced P1 from 61.0 + 5.3 to 51.5 + 1.8 arbitrary units (AU), P2 from 41.3 + 0.3 to 29.0 + 1.8 AU, and MN from 171.1. + 30.2 to 77.2 + 9.6 AU of MAP. These indices, as well as HR and MAP, were similar for D and C animals 14, 30 and 120 days after STZ. Seven-day rats showed a negative correlation of urinary glucose with resting HR (r=-0.76, P=0.03) as well as with the MN index (r=-0.83, P=0.01). We conclude that rats with short-term diabetes mellitus induced by STZ presented modified autonomic control of HR and MAP which was reversible. The metabolic control may influence the results, suggesting that insulin treatment and a better metabolic control in this model may modify arterial pressure, HR and MAP variability.

Standardization of a computerized method for calculating autonomic function test responses in healthy subjects and patients with diabetes mellitus

The objectives of the present study were 1) to compare results obtained by the traditional manual method of measuring heart rate (HR) and heart rate response (HRR) to the Valsalva maneuver, standing and deep breathing, with those obtained using a computerized data analysis system attached to a standard electrocardiograph machine; 2) to standardize the responses of healthy subjects to cardiovascular tests, and 3) to evaluate the response to these tests in a group of patients with diabetes mellitus (DM). In all subjects (97 healthy and 143 with DM) we evaluated HRR to deep breathing, HRR to standing, HRR to the Valsalva maneuver, and blood pressure response (BPR) to standing up and to a sustained handgrip. Since there was a strong positive correlation between the results obtained with the computerized method and the traditional method, we conclude that the new method can replace the traditional manual method for evaluating cardiovascular responses with the advantages of speed and objectivity. HRR and BPR of men and women did not differ. A correlation between age and HRR was observed for standing (r =-0.48, P<0.001) and deep breathing (r = -0.41; P<0.002). Abnormal BPR to standing was usually observed only in diabetic patients with definite and severe degrees of autonomic neuropathy.

Relationship between the degree of cardiovascular automic dysfunction and symptoms of neuropathy and other complications of diabetes mellitus

A cross-sectional study was designed to identify a relationship between the presence of symptoms usually related to nervous system involvement as well as other chronic complications of diabetes with three objectively defined degrees of autonomic neuropathy (AN). Symtoms usually related to peripheral sensitive neuropathy and AN were assessed using a questionnaire applied to 132 diabetcs (38 IDDM and 94 NIDDM), 65 without and 67 with AN. AN was classified as follows according to 5 cardiovascular autonomic tests described by Ewing: 1) early involvement - 1 abnormal test (N = 27); 2) definite involvement - 2 or 3 abnormal tests (N = 26); 3) severe involvement - 4 or 5 abnormal tests (N = 14). A statistically significant asssociation was observed between degree of autonomic inovlvement and the presence of the following symptoms: dizziness on standing, dysphagia, vomiting, diarrhea, fecal incontinence, gustatory sweating, urinary retention, numbness and hyperesthesia of the feet or legs. Constipation and cystitis were not significantly related to cardiovascular AN. Only 3 percent of the patients without neuropathy and with early involvement had four or more than four of the symptoms. The prevalence of proliferative retnopathy and nephropathy was increased among patients with more severe degrees of AN. For IDDM patients there was a positive correlation between the degree of cardiovascular AN and the duration of diabetes. We conclude that: 1) severe cardiovascular AN is usually related to 4 or more of the evaluated symptoms and those patients usually have the other complications of diabetes; 2) severe AN could be a risk factor or an indicator of the same underlying process that determines the beginning of proliferative retinopathy and/ or nephropathy