***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
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    ***EXAMPLES*** 
    Input: Background It is presently unclear whether glycemic variability ( GV ) is associated with baroreflex sensitivity ( BRS ) , which is an early indicator of cardiovascular autonomic neuropathy . The present study is the first to examine the relationships between BRS and GV measured using continuous glucose monitoring ( CGM ) . Methods This was a multicenter , prospect i ve , open-label clinical trial . A total of 102 patients with type 2 diabetes were consecutively recruited for this study . GV was assessed by measuring the st and ard deviation ( SD ) , glucose coefficient of variation ( CV ) , and the mean amplitude of glycemic excursions ( MAGE ) during CGM . The BRS was analyzed from  electrocardiogram and blood pressure recordings  using the sequence method on the first day of hospitalization . Results A total of 94 patients ( mean diabetes duration 9.7 ± 9.6 years , mean HbA1c 61.0 ± 16.8 mmol/mol [ 7.7 ± 1.5 % ] ) were analyzed . In the univariate analysis , CGM-SD ( r = − 0.375 , p = 0.000 ) , CGM-CV ( r = − 0.386 , p = 0.000 ) , and MAGE ( r = − 0.395 , p = 0.000 ) were inversely related to BRS . In addition to GV , the level of BRS correlated with the coefficient of variation in the R – R intervals ( CVR-R ) ( r = 0.520 , p = 0.000 ) , heart rate ( HR ) ( r = − 0.310 , p = 0.002 ) , cardio-ankle vascular index ( CAVI ) ( r = − 0.326 , p = 0.001 ) , age ( r = − 0.519 , p = 0.000 ) , and estimated glomerular filtration rate ( eGFR ) ( r = 0.276 , p = 0.007 ) . Multiple regression analysis showed that CGM-CV and MAGE were significantly related to a decrease in BRS . These findings remained after adjusting the BRS for age , sex , hypertension , dyslipidemia , HR , eGFR , CAVI , and CGM-mean glucose . Additionally , BRS was divided according to quartiles of the duration of diabetes ( Q1–4 ) . BRS decreased after a 2-year duration of diabetes independently of age and sex . Conclusions GV was inversely related to BRS independently of blood glucose levels in type 2 diabetic patients . Measurement of BRS may have the potential to predict CV events in consideration of GV.Trial registration UMIN Clinical Trials Registry UMIN000025964 , Effects of hypoglycemia on cardiac autonomic regulation may contribute to the occurrence of adverse cardiac events . This study assessed the effects of sustained hyperinsulinemic hypoglycemia on cardiovascular autonomic regulation in type 1 diabetic patients and their nondiabetic counterparts . The study consisted of 16 type 1 diabetic patients and 8 age-matched healthy control subjects who underwent euglycemic and hypoglycemic clamp procedures in a r and om order .  Heart rate variability was measured from continuous electrocardiogram recordings by time and frequency domain methods , along with Poincare plot analysis during both a hyperinsulinemic-euglycemic and hypoglycemic clamp at three different glucose levels ( 4.5 - 5.5 , 3.0 - 3.5 , and 2.0 - 2.5 mmol/l ) . Controlled hypoglycemia result ed in an increase of supine heart rate in both the diabetic patients ( from 72 + /- 9 to 80 + /- 11 bpm , P < 0.01 ) and the control subjects ( from 59 + /- 5 to 65 + /- 5 bpm , P < 0.05 ) and progressive reductions of the high-frequency spectral component and beat-to-beat heart rate variability ( SD1 ; P < 0.05 in the diabetic patients and P < 0.01 in control subjects ) . No significant changes in heart rate variability occurred during the euglycemic clamp . We conclude that hypoglycemia results in a reduction of cardiac vagal outflow in both diabetic and nondiabetic subjects . Altered autonomic regulation may contribute to the occurrence of cardiac events during hypoglycemia Objectives Cardiovascular autonomic neuropathy ( CAN ) and abnormal circadian blood pressure ( BP ) rhythm are independent cardiovascular risk factors in patients with diabetes and associations between CAN , non-dipping of nocturnal BP and coronary artery disease have been demonstrated . We aim ed to test if bedtime dosing ( BD ) versus morning dosing ( MD ) of the ACE inhibitor enalapril would affect the 24-hour BP profile in patients with type 1 diabetes ( T1D ) , CAN and non-dipping . Setting Secondary healthcare unit in Copenhagen , Denmark . Participants 24 normoalbuminuric patients with T1D with CAN and non-dipping were included , consisting of mixed gender and Caucasian origin . Mean±SD age , glycosylated haemoglobin and diabetes duration were 60±7 years , 7.9±0.7 % ( 62±7 mmol/mol ) and 36±11 years . Interventions In this r and omised , placebo-controlled , double-blind cross-over study , the patients were treated for 12 weeks with either MD ( 20 mg enalapril in the morning and placebo at bedtime ) or BD ( placebo in the morning and 20 mg enalapril at bedtime ) , followed by 12 weeks of switched treatment regimen . Primary and secondary outcome measures Primary outcome was altered dipping of nocturnal BP . Secondary outcomes included a measurable effect on other cardiovascular risk factors than BP , including left ventricular function ( LVF ) . Results Systolic BP dipping increased 2.4 % ( 0.03–4.9 % ; p=0.048 ) with BD compared to MD of enalapril . There was no increase in mean arterial pressure dipping ( 2.2 % ( −0.1 % to 4.5 % ; p=0.07 ) ) . No difference was found on measures of LVF ( p≥0.15 ) . No adverse events were registered during the study . Conclusions We demonstrated that patients with T1D with CAN and non-dipping can be treated with an ACE inhibitor at night as BD as opposed to MD increased BP dipping , thereby diminishing the abnormal BP profile . The potentially beneficial effect on long-term cardiovascular risk remains to be determined . Trial registration number EudraCT2012 - 002136 - 90 ; Post- results CONTEXT There is a paucity of data regarding the association between glycosylated hemoglobin ( HbA1c ) variability and risk of microvascular complications in adolescents with type 1 diabetes ( T1D ) . OBJECTIVE To investigate the association between HbA1c variability and risk of microvascular complications in adolescents with T1D . DESIGN Prospect i ve cohort study from 1990 to 2014 ( median follow-up , 8.1 y ) . SETTING Tertiary pediatric hospital . PARTICIPANTS A total of 1706 adolescents ( aged 12 - 20 minimum diabetes duration 5 y ) with median age of 15.9 years ( interquartile range , 14.3 - 17.5 ) and diabetes duration of 8.1 years ( 6.3 - 10.8 ) . MAIN OUTCOME MEASURES Glycemic variability was computed as the SD of all HbA1c measurements ( SD-HbA1c ) after diagnosis . Retinopathy was detected using 7-field fundal photography , renal function assessed using albumin excretion rate , peripheral neuropathy detected using thermal and vibration threshold testing , and cardiac autonomic neuropathy ( CAN ) detected using time- and frequency-domain analyses of electrocardiogram recordings . Generalized estimating equations were used to examine the relationship between complications outcomes and HbA1c variability , after adjusting for known risk factors , including HbA1c , diabetes duration , blood pressure , and lipids . RESULTS In multivariable analysis , SD-HbA1c was associated with early retinopathy ( odds ratio [ OR ] 1.32 ; 95 % confidence interval , 1.00 - 1.73 ) , albuminuria ( OR 1.81 ; 1.04 - 3.14 ) , increased log10 albumin excretion rate ( OR 1.10 ; 1.05 - 1.15 ) and CAN ( OR 2.28 ; 1.23 - 4.21 ) but not peripheral neuropathy . CONCLUSIONS Greater HbA1c variability predicts retinopathy , early nephropathy , and CAN , in addition to established risk factors , in adolescents with T1D . Minimizing long term fluctuations in glycemia may provide additional protection against the development of microvascular complications INTRODUCTION The clinical usefulness of baroreflex sensitivity ( BRS ) in the early detection of autonomic dysfunction in patients with diabetes is not well established . The aim of the study was the evaluation of BRS in subjects with type 1 diabetes with and without cardiovascular autonomic neuropathy ( CAN ) . MATERIAL AND METHODS The group examined consisted of 39 patients with type 1 diabetes ( mean age 30.5 + /- 8.8 years ; diabetes duration 12.1 + /- 6.9 years ; BMI 23.7 + /- 2.8 kg/m2 ; HbA(1c ) 7.6 + /- 1.9 % ) . The control group consisted of 18 sex and age-matched healthy adults .  Blood pressure , heart rate and chest respiratory movements were monitored continuously by non-invasive means ( Portapres ) . In order to recognise CAN st and ard Ewing tests were performed . BRS was assessed in the lying ( L-BRS ) and st and ing ( S-BRS ) positions by the frequency domain technique . RESULTS Ten patients ( 25.6 % ) had CAN ( the CAN(+ ) group ) . In the CAN(+ ) group BRS was significantly lower than in the CAN(- ) group in the lying and st and ing positions ( respectively L-BRS 4.4 + /- 2.1 vs. 10.0 + /- 4.9 ms/mm Hg ; p < 0.05 ; S-BRS 3.3 + /- 1.6 vs. 7.0 + /- 2.2 ms/mm Hg p < 0.001 ) . BRS did not differ significantly between the CAN(- ) and control group ( respectively L-BRS 10.0 + /- 4.9 vs. 13.1 + /- 5.5 ms/mm Hg p = NS ; S-BRS 7.0 + /- 2.2 vs. 7.9 + /- 4.0 ms/mm Hg p = NS ) . CONCLUSIONS BRS differentiated well the subjects with CAN from the group without CAN . However , the study did not enable us to confirm the value of BRS in the early detection of autonomic dysfunction among patients with type 1 diabetes who showed no abnormalities in st and ard cardiovascular tests BACKGROUND Long-term microvascular and neurologic complications cause major morbidity and mortality in patients with insulin-dependent diabetes mellitus ( IDDM ) . We examined whether intensive treatment with the goal of maintaining blood glucose concentrations close to the normal range could decrease the frequency and severity of these complications . METHODS A total of 1441 patients with IDDM--726 with no retinopathy at base line ( the primary -prevention cohort ) and 715 with mild retinopathy ( the secondary -intervention cohort ) were r and omly assigned to intensive therapy administered either with an external insulin pump or by three or more daily insulin injections and guided by frequent blood glucose monitoring or to conventional therapy with one or two daily insulin injections . The patients were followed for a mean of 6.5 years , and the appearance and progression of retinopathy and other complications were assessed regularly . RESULTS In the primary -prevention cohort , intensive therapy reduced the adjusted mean risk for the development of retinopathy by 76 percent ( 95 percent confidence interval , 62 to 85 percent ) , as compared with conventional therapy . In the secondary -intervention cohort , intensive therapy slowed the progression of retinopathy by 54 percent ( 95 percent confidence interval , 39 to 66 percent ) and reduced the development of proliferative or severe nonproliferative retinopathy by 47 percent ( 95 percent confidence interval , 14 to 67 percent ) . In the two cohorts combined , intensive therapy reduced the occurrence of microalbuminuria ( urinary albumin excretion of > or = 40 mg per 24 hours ) by 39 percent ( 95 percent confidence interval , 21 to 52 percent ) , that of albuminuria ( urinary albumin excretion of > or = 300 mg per 24 hours ) by 54 percent ( 95 percent confidence interval 19 to 74 percent ) , and that of clinical neuropathy by 60 percent ( 95 percent confidence interval , 38 to 7 
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In conclusion , this systematic review found some preliminary evidence supporting an association between GV and cardiovascular autonomic dysfunction in T1DM .
Hence , uncertainty remains whether high GV can independently contribute to the onset or progression of CAN .