Clinical Study On Treatment Of Autonomic Neuropathy And Lipoic Acid In Type 2 Diabetic Heart

Part One The clinical study of cardiovascular autonomic neuropathy in type 2 diabetesObjective: To discuss the prevalence and risk factors of cardiovascular autonomic neuropathy (CAN) in type 2 diabetes.Methods: three hundred and Thirty two type 2 diabetic (T2DM) patients hospitalized and accepted conventional hypoglycemic therapy in the endocrinology department of the NO.1 hospital of Yunnan from March 2013 to September 2014 were enrolled.And all conforms to 1999 WHO Diabetes Diagnostic Criteria.Those who take affecting the heart rate of drugs such as nitroglycerin, β receptor blocker, atropine, digitalis in recent two weeks and who have coronary disease, arrhythmia and other cardiovascular diseases and severe liver、kidney and brain diseases, also who have acute complications of diabetes, malignant tumor, mental disorders and who cannot provide for oneself in life and who have Severe hypertension subjecting to cardiac autonomic nerve function were all ruled out. Clinical datas such as gender, age, BMI, duration of diabetes, Smoking history were collected. The level of fasting plasma glucose, HbAlc, profile of blood lipid, The urine trace albumin were also collected. ankle brachial index (ABI), toe brachial index (TBI) were measured. SDNN and RMSSD were collected by SA-3000 p heart rate variability analyzer. and improve cardiovascular reflex test was used to diagnose CAN:(1) resting heart rate; (2) fist clenching test; (3) blood pressure difference between erect and supine positions; (4) heart rate difference per minute between erect and supine positions. Score 1 point for each abnormality in (1), (2) and (4), and score 2 points for abnormality in (3). The patients who get a total score<2 were defined as non-CAN; score= 2 as early CAN; score>3 as CAN. Early CAN and CAN were defined as cardiovascular autonomic nerve damage.Results:(1)There were 188 males and 144 females in the enrolled T2DM patients with an average age of 55.37 years old (55.37 ± 10.86 years old), a mean diabetic duration of 6.53 years(6.53±5.62years), a mean BMI of 24.81 kg·m-2(24.81 ± 3.80 kg·m-2), a mean HbA1c values of 9.56% (9.56 ± 2.92%), a mean Trace albumin of 34.03 mg·L-1(34.03±111.69 mg·L-1), a mean Low density lipoprotein cholesterol of 3.23 mmol·L-1(3.23±7.96 mmol·L-1), a mean triglycerides of 2.98 mmol·L-1 (2.98±0.50mmol·L-1); (2) In the enrolled T2DM patients, the prevalence of early CAN, CAN, cardiovascular autonomic nerve injury and No cardiac autonomic neuropathy was separately 59.94% (199/332),17.17%(57/332),77.11%(256/332)and 22.89%(76/332). (3) Compared with non-CAN group, the age was older (56.63 ±10.06vs51.70±11.95 years old, t=4.94, P=0.001), the diabetic duration was longer (6.64±5.76vs4.79±3.92 years,1=1.85, P=0.013), SDNN was smaller (21.86±12.62 vs30.04±14.62, t=-1.18, P=0.000). but HbAlc, Trace albumin, Low density lipoprotein cholesterol, RMSSD and the right side of TBI were all No statistical differences in early CAN group. (4) Compared with non-CAN group, the age was older (55.88±11.11vs51.70±11.95 years old, t=4.18, p=0.026), the diabetic duration was longer (8.46±6.37vs4.79±3.92 years, t=3.68, p=0.000), Trace albumin was higher (72.05±200.83vs34.24±103.27, t=37.80, p=0.052), SDNN was smaller (16.21 ±10.87vs30.04±14.62, t=-13.83, p=0.000), RMSSD was smaller (11.61±8.48vs20.57 ±10.73, t=-8.96, p=0.000), but HbAlc, LDL and the right side of TBI were all No statistical differences in CAN group. (5) Compared with early CAN group, the diabetic duration was longer (8.46±6.37vs6.64±5.76 years, t=1.83, p=0.028), Trace albumin was higher (72.05±200.83vs23.06±69.75 mmol·L-1, t=48.98, p=0.003), LDL was higher (5.21±19.14vs2.79±0.81mmol·L-1, t=2.42, p=0.043), SDNN was smaller (16.21±10.87vs21.86±12.62, t=-5.65, p=0.004), RMSSD was smaller (11.61±8.48vs 17.46±15.47, t=-5.85, p=0.004), the right side of TBI was smaller (0.79±0.09 vs0.83 ±0.01, t=-0.04, p=0.048). but the age and HbAlc were No statistical differences in CAN group.Conclusion:In the present study, the prevalence of early CAN and CAN was separately 59.94% and 17.17% in T2DM. Poor blood glucose is not the only factor which causes diabetic cardiac autonomic neuropathy, CAN may be correlated with the age, diabetic duration, Trace albumin, LDL and TBI in T2DM.Part Two The clinical study of the treatment of type 2 diabetic cardiac autonomic neuropathy with Alpha lipoic acidObjective: To discuss curative effect of the treatment of type 2 diabetic cardiac autonomic neuropathy with Alpha lipoic acid.Methods: one hundred and Twenty five type 2 diabetic (T2DM) patients hospitalized and accepted conventional hypoglycemic therapy in the endocrinology department of the NO.1 hospital of Yunnan from March 2013 to September 2014 were enrolled. and all conforms to 1999 WHO Diabetes Diagnostic Criteria. Those who were more than 80 year-old, Those who take drugs of Nutrition nerve and antioxidant such as A cobalt amine, in accordance with Mr He, vitamin E and vitamin C in recent two weeks, Those who take affecting the heart rate of drugs such as nitroglycerin, β receptor blocker, atropine, digitalis in recent two weeks and who have coronary disease, arrhythmia and other cardiovascular diseases and severe liver, kidney and brain diseases, also who have acute complications of Diabetes, malignant tumor, mental disorders and who cannot provide for oneself in life and who have Severe hypertension subjecting to cardiac autonomic nerve function were all ruled out. SDNN and RMSSD were collected by SA-3000p heart rate variability analyzer, and improve cardiovascular reflex test was used to diagnose CAN:(1) resting heart rate; (2) fist clenching test; (3) blood pressure difference between erect and supine positions; (4) heart rate difference per minute between erect and supine positions. Score 1 point for each abnormality in (1), (2) and (4), and score 2 points for abnormality in (3). The patients who get a total score<2 were defined as non-CAN; score= 2 as early CAN; score≥3 as CAN. Early CAN and CAN were defined as cardiovascular autonomic nerve damage, cardiovascular reflex tests and heart rate variability were measured after taking intravenous alpha-lipoic acid (600 mg/d) treatment for 1 week for eighty-three DCAN patients, and cardiovascular reflex tests and heart rate variability were also measured after taking oral lipoic acid (600 mg/d) treatment for 4 week for forty-two DCAN patients. And observing the treatment effects of the same dose different method.Results:(1) There were 83 DCAN accepted intravenous alpha-lipoic acid treatment in the enrolled T2DM patients. SDNN (16.19±9.70) and RMSSD (12.45±15.86) were No treatment. At the same time, There were 42 DCAN accepted oral lipoic acid treatment in the enrolled T2DM patients. SDNN (15.95±8.02) and RMSSD (11.17±8.39) were No treatment. (2) Compared with No treatment. SDNN was more higher (22.25±19.58vs16.19±9.70, t=3.59, p=0.001), RMSSD was more higher (19.26±28.19vsl2.45±15.86, t=-3.39, p=0.01) after intravenous alpha-lipoic acid (600 mg/d) treatment for 1 week. (3) Compared with No treatment. SDNN was more higher (23.66±17.63vs15.95±8.02, t=2.97, p=0.005) and RMSSD was more higher (15.67±9.51vs11.17±8.39, t=4.20, p=0.000) after oral lipoic acid treatment for 4 week. (4) Compared with Intravenous therapy group. SDNN and RMSSD were No statistical differences in oral therapy group.Conclusion: Intravenous and oral lipoic acid in the treatment of type 2 diabetic cardiac autonomic neuropathy are effective, the same dose different method curative effect was quite but intravenous treatment effect was more quickly.Part Three The clinical study of the effect of nocturnal hypoglycemia by Alpha lipoic acid treat type 2 diabetic cardiac autonomic neuropathyObjective: To discuss the causal relationship between Nocturnal hypoglycemia and type 2 diabetic cardiac autonomic neuropathy.Methods: forty type 2 diabetic (T2DM) patients of Cardiac autonomic neuropathy with nocturnal hypoglycemia hospitalized and accepted conventional hypoglycemic therapy in the endocrinology department of the NO.1 hospital of Yunnan from March 2013 to September 2014 were enrolled, and all conforms to 1999 WHO Diabetes Diagnostic Criteria. Those who were more than 80 year-old, Those who take drugs of Nutrition nerve and antioxidant such as A cobalt amine, in accordance with Mr He, vitamin E and vitamin C in recent two weeks, Those who take affecting the heart rate of drugs such as nitroglycerin, β receptor blocker, atropine, digitalis in recent two weeks and who have coronary disease, arrhythmia and other cardiovascular diseases and severe liver、kidney and brain diseases, also who have acute complications of diabetes, malignant tumor, mental disorders and who cannot provide for oneself in life and who have Severe hypertension subjecting to cardiac autonomic nerve function were all ruled out. SDNN and RMSSD were collected by SA-3000p heart rate variability analyzer. and improve cardiovascular reflex test was used to diagnose CAN: (1) resting heart rate; (2) fist clenching test; (3) blood pressure difference between erect and supine positions; (4) heart rate difference per minute between erect and supine positions. Score 1 point for each abnormality in (1), (2) and (4), and score 2 points for abnormality in (3). The patients who get a total score<2 were defined as non-CAN; score= 2 as early CAN; score≥3 as CAN. Early CAN and CAN were defined as cardiovascular autonomic nerve damage. Dynamic Glucose Monitoring System (DGMS), which records one glucose value every 3 minutes was used to evaluate nocturnal hypoglycemia. Glucose value<3.9mmol/L founded for three consecutive times during 00:00-08:00 period was defined as nocturnal hypoglycemia. cardiovascular reflex tests, heart rate variability and Dynamic Glucose Monitoring System were also measured after taking oral lipoic acid treatment for 4 week. And taking cardiovascular reflex test score, recording SDNN and RMSSD value and the blood glucose of DGMS monitoring.Results:(1) Compared with No treatment. SDNN was more higher (24.25±19.91vs 17.07±9.14,t=2.708, p=0.010), RMSSD was more higher (17.10±11.99vs11.95±9.14, t=3.618,p=0.001) afcter oral lipoic acid treatment for 4 week. (2) five type 2 diabetic (T2DM) patients of Cardiac autonomic neuropathy with nocturnal hypoglycemia take oral lipoic acid treatment for 4 week, the proportion of nocturnal hypoglycemia is 20%(1/5), and the proportion of no nocturnal hypoglycemia is 80%(4/5). one type 2 diabetic (T2DM) patients of Cardiac autonomic neuropathy with nocturnal hypoglycemia take oral lipoic acid treatment for 6 week, nocturnal hypoglycemia is disappear.Conclusion:Frequency of nocturnal hypoglycemia is obvious less even no as the improvement of Cardiac autonomic neuropathy with taking oral lipoic acid. Therefore, the causal relationship between Nocturnal hypoglycemia and type 2 diabetic cardiac autonomic neuropathy.