***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 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE Sleep deprivation  in healthy men has been experimentally found to result in disturbances in glucose metabolism and in sympathovagal imbalance . The aim of the present study was to investigate whether sleep disturbances and elevated resting heart rate are associated with increased risk of developing diabetes . RESEARCH DESIGN AND METHODS A group of 6,599 initially healthy , nondiabetic men aged 44.5 + /- 4.0 years took part in a prospect i ve , population -based study in Malmö , Sweden . The incidence of diabetes during a mean follow-up of 14.8 + /- 2.4 years was examined in relation to self-reported difficulties in falling asleep and resting heart rate at baseline . Diabetes was assessed at follow-up in all subjects by question naire and in a subgroup of 1,551 men by blood glucose measurement . RESULTS A total of 615 ( 9.3 % ) subjects reported either difficulties in falling asleep or regular use of hypnotics ( seen as markers of sleep disturbances ) , and 158 ( 2.4 % ) subjects reported both of these . Altogether , 281 ( 4.3 % ) of the men developed diabetes during the follow-up period . Logistic regression models showed difficulties in falling asleep or regular use of hypnotics ( odds ratio [ OR ] 1.52 [ 95 % CI 1.05 - 2.20 ] ) and resting heart rate ( OR per 10 bpm 1.13 [ 0.99 - 1.30 ] ) to be associated with development of diabetes when full adjustments were made for baseline age , biological risk factors , lifestyle , family history of diabetes , and social class . CONCLUSIONS The results suggest that sleep disturbances and , possibly , elevated resting heart rate , in middle-aged men , are associated with an increased risk of diabetes BACKGROUND Blood pressure reduction achieved with beta-blockers and diuretics is the best recorded intervention to date for prevention of cardiovascular morbidity and death in patients with hypertension . Left ventricular hypertrophy ( LVH ) is a strong independent indicator of risk of cardiovascular morbidity and death . We aim ed to establish whether selective blocking of angiotensin II improves LVH beyond reducing blood pressure and , consequently , reduces cardiovascular morbidity and death . METHODS We did a double-masked , r and omised , parallel-group trial in 9193 participants aged 55 - 80 years with essential hypertension ( sitting blood pressure 160 - 200/95 - 115 mm Hg ) and LVH ascertained by electrocardiography ( ECG ) . We assigned participants once daily losartan-based or atenolol-based antihypertensive treatment for at least 4 years and until 1040 patients had a primary cardiovascular event ( death , myocardial infa rct ion , or stroke ) . We used Cox regression analysis to compare regimens . FINDINGS Blood pressure fell by 30.2/16.6 ( SD 18.5/10.1 ) and 29.1/16.8 mm Hg ( 19.2/10.1 ) in the losartan and atenolol groups , respectively . The primary composite endpoint occurred in 508 losartan ( 23.8 per 1000 patient-years ) and 588 atenolol patients ( 27.9 per 1000 patient-years ; relative risk 0.87 , 95 % CI 0.77 - 0.98 , p=0.021 ) . 204 losartan and 234 atenolol patients died from cardiovascular disease ( 0.89 , 0.73 - 1.07 , p=0.206 ) ; 232 and 309 , respectively , had fatal or non-fatal stroke ( 0.75 , 0.63 - 0.89 , p=0.001 ) ; and myocardial infa rct ion ( non-fatal and fatal ) occurred in 198 and 188 , respectively ( 1.07 , 0.88 - 1.31 , p=0.491 ) . New-onset diabetes was less frequent with losartan . Interpretation Losartan prevents more cardiovascular morbidity and death than atenolol for a similar reduction in blood pressure and is better tolerated . Losartan seems to confer benefits beyond reduction in blood pressure BACKGROUND The Valsartan Antihypertensive Long-term Use Evaluation ( VALUE ) trial was design ed to test the hypothesis that for the same blood-pressure control , valsartan would reduce cardiac morbidity and mortality more than amlodipine in hypertensive patients at high cardiovascular risk . METHODS 15?245 patients , aged 50 years or older with treated or untreated hypertension and high risk of cardiac events participated in a r and omised , double-blind , parallel-group comparison of therapy based on valsartan or amlodipine . Duration of treatment was event-driven and the trial lasted until at least 1450 patients had reached a primary endpoint , defined as a composite of cardiac mortality and morbidity .  Patients from 31 countries were followed up for a mean of 4.2 years . FINDINGS Blood pressure was reduced by both treatments , but the effects of the amlodipine-based regimen were more pronounced , especially in the early period ( blood pressure 4.0/2.1 mm Hg lower in amlodipine than valsartan group after 1 month ; 1.5/1.3 mm Hg after 1 year ; p<0.001 between groups ) . The primary composite endpoint occurred in 810 patients in the valsartan group ( 10.6 % , 25.5 per 1000 patient-years ) and 789 in the amlodipine group ( 10.4 % , 24.7 per 1000 patient-years ; hazard ratio 1.04 , 95 % CI 0.94 - 1.15 , p=0.49 ) . INTERPRETATION The main outcome of cardiac disease did not differ between the treatment groups . Unequal reductions in blood pressure might account for differences between the groups in cause-specific outcomes . The findings emphasise the importance of prompt blood-pressure control in hypertensive patients at high cardiovascular risk OBJECTIVE Sympathetic nerve activation is causally related to insulin resistance as both a cause and a consequence . Resting heart rate ( RHR ) reflects sympathetic nerve activity . We investigated the effect of RHR on the incidence of  type 2 diabetes mellitus ( T2DM ) in patients with clinical ly manifest vascular diseases . DESIGN Data were used from the second manifestations of arterial disease ( SMART ) study : a prospect i ve cohort study of patients with clinical ly manifest vascular diseases ( n=3646 ) . METHODS RHR was obtained using an electrocardiogram .  Patients were followed up for incident type 2 diabetes ( n=289 ) during a median period of 5.5 ( interquartile range 3.2 - 8.4 ) years . The relation between RHR and incident T2DM was estimated by Cox proportional hazard analysis . As age was an effect modifier ( P=0.048 ) , analyses were stratified for age . RESULTS Patients in quartile 4 ( Q4 ) of RHR had a 65 % increased risk of T2DM compared with those in Q1 ( reference ; hazard ratios ( HR ) , 1.65 ; 95 % confidence interval ( 95 % CI ) , 1.15 - 2.36 ) adjusted for age , gender , smoking , estimated glomerular filtration rate , systolic blood pressure , location of vascular disease , and antihypertensive medication . Every 10 beats per minute ( bpm ) increase in RHR increased the risk for T2DM with 10 % ( HR , 1.10 ; 95 % CI , 1.00 - 1.21 ) in the total population . This risk was particularly high in subjects aged 55 - 63 years ( per 10 bpm : HR , 1.22 ; 95 % CI , 1.04 - 1.43 ) and was independent of the location of vascular disease and beta-blocker use . CONCLUSIONS Increased RHR , an indicator of sympathetic nerve activity , is associated with an increased risk for T2DM in patients with manifest vascular diseases , particularly in middle-aged patients Diabetes mellitus often develops in patients with hypertension . We investigated predictors of diabetes mellitus development in hypertensives at risk of developing the disease in the VALUE trial population . Among the 9995 non-diabetic hypertensive patients at baseline , 1298 patients developed diabetes mellitus during the average follow-up of 4.2 years . New-onset diabetes mellitus was defined from adverse event reports , information about  new antidiabetic medication  and /or a fasting glucose ⩾7.0 mmol l−1 at the end of trial . Twenty-five potential baseline predictors of new-onset diabetes mellitus were analysed by univariate logistic regression and 14 of 25 predictors were found to be statistically significant with a P-value < 0.05 . The predictors were in order of decreasing significance ; glucose , body mass index ( BMI ) , age , uric acid , non-Caucasian race , haemoglobin , heart rate , r and omized study treatment , history of coronary heart disease ( CHD ) , gender , total cholesterol , proteinuria , potassium and creatinine . Multivariate stepwise logistic regression analyses were used and potential baseline predictors of new-onset diabetes mellitus were considered significant by four different models ( P-value < 0.001 ) . The final multivariate model selected included all patients , but not treatment group as a potential predictor , and the six significant predictors identified from this model were glucose , BMI , non-Caucasian race , age , heart rate and history of CHD . In conclusion , glucose and BMI were the most important predictors of new-onset diabetes mellitus in hypertensive patients at high cardiovascular risk , and easily accessible clinical characteristics strongly predict patients at risk of developing diabetes mellitus BACKGROUND Emerging evidence indicates an association between sympathetic activation and metabolic syndrome . However , sympathetic activation in metabolic syndrome may be a cause , consequence , or just epiphenomenon . To eluci date this issue , the predictive power of resting heart rate for the development of abnormal glucose and lipid metabolisms after 20 years was evaluated in a general population . METHODS A total of 637 participants ( > 20 years old ) underwent a health examination in 1979 including measurements of blood chemistries . Resting heart rate ( bpm ) was measured by an electrocardiogram .  In 1999 , all of the study participants again underwent a health examination , including electrocardiogram and blood chemistries .  Because four of them had atrial fibrillation , and 19 subjects were taking antihypertensive medication in 1979 , they were excluded from analysis . Therefore , a complete data set of 614 subjects was available . RESULTS As was reported in our previous article , in 1999 we found a linear and significant ( P < 0.05 ) cross-sectional relationship between resting heart rate and a cluster of cardiometabolic risk factors ( blood pressure ( BP ) , free fatty acid ( FFA ) , plasma glucose , and homeostasis model assessment ( HOMA ) index ) . Baseline higher heart rate ( heart rate > or=80 bpm in 1979 ) predicted the development of obesity , diabetes mellitus ( DM ) , and insulin resistance in 1999 after adjustments for age , sex , and other confounders . CONCLUSION This is one of the first prospect i ve reports demonstrating that higher heart rate may predispose to the development of obesity and DM , suggesting that the sympathetic nerve system may play a role in the development of obesity and DM Abstract Objective : To determine the risk factors for non-insulin dependent diabetes in a cohort representative of middle aged British men . Design : Prospect i ve study . Subjects and setting : 7735 men aged 40 - 59 , drawn from one group practice in each of 24 towns in Britain . Known and probable cases of diabetes at screening ( n=158 ) were excluded . Main outcome measures : Non-insulin dependent diabetes ( doctor diagnosed ) over a mean follow up period of 12.8 years . Results : There were 194 new cases of non-insulin dependent diabetes . Body mass index was the dominant risk factor for diabetes , with an age adjusted relative risk ( upper fifth to lower fifth ) of 11.6 ; 95 % confidence interval 5.4 to 16.8 . Men engaged in moderate levels of physical activity had a substantially reduced risk of diabetes , relative to the physically inactive men , after adjustment for age and body mass index ( 0.4 ; 0.2 to 0.7 ) , an association which persisted in full multivariate analysis . A non-linear relation between alcohol intake and diabetes was observed , with the lowest risk among moderate drinkers ( 16 - 42 units/week ) relative to the baseline group of occasional drinkers ( 0.6 ; 0.4 to 1.0 ) . Additional significant predictors of diabetes in multivariate analysis included serum triglyceride concentration , high density lipoprotein cholesterol concentration ( inverse association ) , heart rate , uric acid concentration , and prevalent coronary heart disease . Conclusion : These findings emphasise the interrelations between risk factors for non-insulin dependent diabetes 
    Output:
    
There was evidence of nonlinear associations between resting heart rate ( pnonlinearity < 0.0001 ) and risk of type 2 diabetes .
CONCLUSION The current meta- analysis indicates a strong positive association between high resting heart rate and the risk of type 2 diabetes .
As a non-invasive marker of type 2 diabetes risk , resting heart rate may have potential in the clinical setting , especially for interventions aim ed at lowering the risk of type 2 diabetes .