RESUMO
BACKGROUND: Diabetes mellitus is a highly prevalent disease with rapid universal growth. In 2013, there were already 382 million people with diabetes, and it is expected that by 2035, this number will double. Chronic hyperglycemia causes a series of biochemical and structural changes, especially in the eyes, kidneys, heart, arteries, and peripheral nerves, which usually leads to the progression of microvascular disease. Several literature reports showed that the chronic use of phosphodiesterase-5 inhibitors enhances the insulin sensitivity, improves the markers of endothelial function, and helps in the treatment of severe extremity ischemia and pulmonary hypertension. We aim to test the effect of sildenafil citrate (SC) as a glucose and microcirculation regulator in diabetic patients, paying special attention to the consequences of its use in the regulation of blood glucose level. Case Presentation. Two male patients, aged 53 and 73 years, with type II diabetes, using oral hypoglycemic agents and presenting pathology associated with microcirculation alterations and ischemia, were medicated daily with SC. Both patients presented a reduction in the glycemic level, requiring lower doses or no other oral diabetes medications. Patient 1, who presented diabetic foot, was treated in the ambulatory, and patient 2, with chronic obstructive pulmonary disease and consequent mild pulmonary hypertension, was treated in the office. In addition to the clinical improvement of foot wounds and dyspnea due to the increase in microcirculatory perfusion, hypoglycemic episodes were observed in both patients under SC. The patient with pulmonary hypertension experienced one severe hypoglycemia episode and had to be taken to an emergency room. CONCLUSION: Type 2 diabetic patients may benefit from the use of a phosphodiesterase-5 inhibitor in order to improve the microcirculatory perfusion as well as glycemic control. However, adverse side effects may involve hypoglycemia. Since off-label use of SC in patients suffering from microcirculatory alterations has increased recently, our results showed that more studies are needed to verify the prevalence of hypoglycemia episodes as well as it's possible physiologic mechanism.
RESUMO
BACKGROUND: The occurrence of hypoglycemia has been associated with the presence of cardiovascular autonomic neuropathy. Cardiovascular autonomic reflex tests are the gold standard diagnostic method for cardiovascular autonomic neuropathy. Nevertheless, impaired heart rate variability indices on spectral analysis have been reported before cardiovascular autonomic reflex test abnormalities arise. The objective of the present study was to analyse the association between the severity of hypoglycemia and indices of heart rate variability on spectral analysis. METHODS: Consecutive type 1 diabetes patients were prospectively enrolled. Heart rate variability indices were assessed by spectral analysis. One abnormal test result was used to define impaired spectral analysis. The severity of hypoglycemia was evaluated by a hypoglycemia score and patients were classified into absent/minor or moderate/severe hypoglycemia groups. RESULTS: Patients with moderate/severe hypoglycemia were older, had longer duration of diabetes and had higher rates of diabetic complications. After adjusting for baseline clinical characteristics, impaired spectral analysis (OR: 3.85; 95% IC 1.23 - 12.02; p = 0.020), nephropathy (OR: 4.15, 95% IC 1.27 - 13.54; p = 0.018) and macrovascular complications (OR: 12.18, 95% IC 1.14 - 129.84; p = 0.038) remained independent predictors of moderate/severe hypoglycemia. Patients with moderate/severe hypoglycemia had lower heart rate variability in the high frequency band of spectral analysis, reflecting a decreased parasympathetic tonus on the heart. These patients also had higher low frequency/high frequency ratios, ultimately denoting the occurrence of cardiovascular autonomic imbalance. CONCLUSIONS: Impaired heart rate variability on spectral analysis, nephropathy and macrovascular complication were shown to independently predict moderate/severe hypoglycemia. Patients with moderate/severe hypoglycemia showed loss of the cardio protective effect of vagal activity according to spectral analysis. Copyright © 2016 John Wiley & Sons, Ltd.