***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: Nonenzymatic reactions between glucose and proteins yield advanced glycation end products ( AGE ) such as pentosidine . AGE accumulate in diabetic patients , alter the structure and function of tissue proteins , stimulate cellular response , and have thus been implicated in diabetic tissue damage . The present study was undertaken to assess the factors determining plasma total pentosidine level in diabetic patients and the possible relation between plasma pentosidine level and diabetic complications . In diabetic patients , including patients with renal failure , plasma pentosidine levels , assessed by HPLC assay , were correlated with serum creatinine ( P < 0.0001 ) . In patients with normal renal function , pentosidine levels were correlated with blood glucose control ( hemoglobin Alc : P = 0.0028 ; fructoselysine : P = 0.0133 ) , serum creatinine ( P = 0.029 ) , patient age ( P = 0.0416 ) , duration of diabetes ( P = 0.0431 ) , and total cholesterol ( P = 0.0056 ) and LDL-cholesterol ( P = 0.0208 ) . Multiple regression analysis revealed an independent influence of hemoglobin Alc and serum creatinine on pentosidine levels ( r2 = 0.216 , P = 0.0026 ) . Pentosidine levels were higher in patients with than in those without hypertension ( P = 0.043 ) or ischemic heart diseases ( P = 0.0061 ) . No such differences were observed between patients with and without albuminuria or retinopathy . Multiple regression analysis revealed an independent influence of plasma pentosidine on the presence of hypertension ( r2 = 0.129 , P = 0.0382 ) and of plasma pentosidine and HDL-cholesterol on the presence of ischemic heart disease ( r2 = 0.326 , P = 0.0012 ) . The present study demonstrated that plasma pentosidine level was significantly influenced by the quality of glycemic control and renal function . Pentosidine level was also correlated with hypertension and ischemic heart disease , and might be taken as a biomarker of diabetic cardiovascular risk The bioavailability of nitric oxide is decreased in animal models and humans with diabetes mellitus . Hyperglycemia , in particular , attenuates endothelium-dependent vasodilation in healthy subjects . In vitro and in vivo animal studies implicate activation of protein kinase C&bgr ; as an important mechanism whereby hyperglycemia decreases endothelium-derived nitric oxide . Accordingly , this study tested the hypothesis that inhibition of protein kinase C&bgr ; would prevent impairment of endothelium-dependent vasodilation in healthy humans exposed to hyperglycemia . This study was a r and omized , double-blind , placebo-controlled , crossover trial . Healthy subjects were treated with an orally active , selective , protein kinase C&bgr ; inhibitor , LY333531 , or matching placebo once a day for 7 days before vascular function testing . Forearm blood flow was measured using venous-occlusion , strain-gauge plethysmography . Endothelium-dependent vasodilation was measured via incremental brachial artery administration of methacholine chloride ( 0.3 to 10 & mgr;g/min ) during euglycemia and after 6 hours of hyperglycemic clamp . The forearm blood flow dose-response curve to methacholine was significantly attenuated by hyperglycemia after placebo treatment ( P = 0.009 by ANOVA , euglycemia versus hyperglycemia ) but not after treatment with LY333531 . Inhibition of protein kinase C&bgr ; prevents the reduction in endothelium-dependent vasodilation induced by acute hyperglycemia in healthy humans in vivo . These findings suggest that hyperglycemia impairs endothelial function , in part , via protein kinase C&bgr ; activation Abstrac Objective : To evaluate different methods for community based screening for  sight threatening diabetic eye disease .  Design : Prospect i ve study . Setting : Mobile screening unit visiting inner city community clinics ; hospital assessment clinic ( tertiary centre ) . Subjects : 395 diabetic patients registered with four general practice s in an inner city location . Interventions : Community based photography with mydriasis and direct ophthalmoscopy through dilated pupils by an experienced ophthalmologist , both compared with reference st and ard of slit lamp biomicroscopy by a consultant specialist in medical retinal disease . Main outcome measures : Sensitivity and specificity of screening method and prevalence of sight threatening diabetic eye disease  ( moderate preproliferative retinopathy , circinate maculopathy , exu date within 1 disc diameter of fixation , other diabetes related eye disease ) . Results : 358 subjects underwent photography , 326 attended hospital clinic for ophthalmoscopy , and six were ungradable on photographs and biomicroscopy , leaving 320 for analysis . Of these 295 ( 91 % ) attended clinic within four months of photography .  Sensitivity of detection of eye disease by photography was 89 % ( 95 % confidence interval 80 % to 98 % ) , significantly better than for direct ophthalmoscopy ( 65 % ( 51 % to 79 % ) ) . Analysis of patients with false negative results indicated possible improvement of photographic sensitivity to 93 % by addition of stereoscopic macular pair photographs . Specificity of detection of sight threatening eye disease was 86 % ( 82 % to 90 % ) for photography and 97 % ( 95 % to 99 % ) for direct ophthalmoscopy . Conclusions : Since high sensitivity is essential for an effective screening programme , a photographic method should be considered as preferred option in national , community based screening programmes . Even in the h and s of an experienced ophthalmologist , direct ophthalmoscopy is limited by weaknesses inherent to the instrument Aim : To compare two reference st and ards when evaluating a method of screening for referable diabetic retinopathy . Method : Clinics at Oxford and Norwich Hospitals were used in a two centre prospect i ve study of 239 people with diabetes receiving an ophthalmologist ’s examination using slit lamp biomicroscopy , seven field 35 mm stereophotography and two field mydriatic digital photography . Patients were selected from those attending clinics when the ophthalmologist and ophthalmic photographer were able to attend . The main outcome measures were the detection of referable diabetic retinopathy as defined by the Gloucestershire adaptation of the European Working Party guidelines . Results : In comparison with seven field stereophotography , the ophthalmologist ’s examination gave a sensitivity of 87.4 % ( confidence interval 83.5 to 91.5 ) , a specificity of 94.9 % ( 91.5 to 98.3 ) , and a kappa statistic of 0.80 . Two field mydriatic digital photography gave a sensitivity of 80.2 % ( 75.2 to 85.2 ) , specificity of 96.2 % ( 93.2 to 99.2 ) , and a kappa statistic of 0.73 . In comparison with the ophthalmologist ’s examination , two field mydriatic digital photography gave a sensitivity of 82.8 % ( 78.0 to 87.6 ) , specificity of 92.9 % ( 89.6 to 96.2 ) , and a kappa statistic of 0.76 . Seven field stereo gave a sensitivity of 96.4 % ( 94.0 to 98.8 ) , a specificity of 82.9 % ( 77.4 to 88.4 ) , and a kappa statistic of 0.80 . 15.3 % of seven field sets , 1.5 % of the two field digital photographs , and none of the ophthalmologist ’s examinations were un grade able . Conclusion : An ophthalmologist ’s examination compares favourably with seven field stereophotography , and two field digital photography performs well against both reference st and ards OBJECTIVE To examine the cross-sectional association between plasma vitamin C , self-reported diabetes , and HbA1c . RESEARCH DESIGN AND METHODS Data from a population -based study of diet , cancer , and chronic disease were analyzed . A total of 2,898 men and 3,560 women 45 - 74 years of age who were registered with general practice s in Norfolk , U.K. , were recruited to the European Prospect i ve Investigation Into Cancer-Norfolk study between 1995 and 1998 . RESULTS Mean plasma vitamin C levels were significantly higher in individuals with HbA1c levels < 7 % than in those with self-reported diabetes or prevalent undiagnosed hyperglycemia ( HbA1c > or = 7 % ) . An inverse gradient of mean plasma vitamin C was found in both sexes across quintiles of HbA1c distribution < 7 % . The odds ratio ( 95 % CI ) of having prevalent undiagnosed hyperglycemia per 20 micromol/l ( or 1 SD ) increase in plasma vitamin C was 0.70 ( 0.52 - 0.95 ) ( adjusted for sex , age , BMI , waist-to-hip ratio , tertiary education , any use of dietary supplements , vegetarian diet , alcohol consumption , physical activity , dietary vitamin E , dietary fiber , dietary saturated fat , and smoking history ) . The unadjusted change in HbA1c per 20 micromol/l increase in vitamin C estimated by linear regression was -0.12 % ( -0.14 to -0.09 ) in men and -0.09 % ( -0.11 to -0.07 ) in women . After adjusting for the possible confounders , these values were -0.08 % ( -0.11 to -0.04 ) in men and -0.05 % ( -0.07 to -0.03 ) in women . CONCLUSIONS An inverse association was found between plasma vitamin C and HbA1c .  Dietary measures to increase  plasma vitamin C  may be an important public health strategy for reducing the prevalence of diabetes Aims : To assess the effects of ( 1 ) mydriasis and ( 2 ) single versus three field photography on screening for diabetic eye disease using digital photography Method : Slit lamp examination findings were compared to digital fundal photographs for the detection of any retinopathy and for referable retinopathy in 398 patients ( 794 eyes ) . A Topcon TRC-NW6S digital non-mydriatic fundus camera was used . Three photographic strategies were used : undilated single field , dilated single field , and dilated multiple fields . The photographs were presented in r and om order to one of two retinal screeners . For the single field photographs the screeners were masked to the use of mydriatics . In 13 % of fundal photographs , grading was performed by both , rather than just one grade r. Results : Mydriasis reduced the proportion of ungradable photographs from 26 % to 5 % ( p<0.001 ) . Neither mydriasis nor three field photography improved the sensitivity or specificity for the detection of any retinopathy or of referable retinopathy when compared with undilated single field photography . The sensitivity and specificity for detecting referable retinopathy using undilated single field photography was 77 % ( 95 % CI 71 to 84 ) and 95 % ( 95 % CI 93 to 97 ) respectively . Using dilated single field photography the figures were 81 % ( 95 % CI 76 to 87 ) and 92 % ( 95 % CI 90 to 94 ) respectively . Using dilated three field photography the figures were 83 % ( 95 % CI 78 to 88 ) and 93 % ( 95 % CI 91 to 96 ) respectively . Inter grade r reliability for the detection of referable retinopathy in gradable photographs was excellent ( Kappa values 0.86–1.00 ) . Conclusions : Mydriasis reduces the technical failure rate .  Mydriasis and the three field photography as used in this study do not increase the sensitivity or specificity of detecting diabetic retinopathy BACKGROUND Experimental studies in animals and cross-sectional studies in humans have suggested that low serum magnesium levels might lead to type 2 diabetes ; however , this association has not been examined prospect ively . METHODS We assessed the risk for type 2 diabetes associated with low serum magnesium level and low dietary magnesium intake in a cohort of nondiabetic middle-aged adults ( N = 12,128 ) from the Atherosclerosis Risk in Communities Study during 6 years of follow-up .  Fasting serum magnesium level  , categorized into 6 levels , and  dietary magnesium intake  , categorized into quartiles , were measured at the baseline examination . Incident type 2 diabetes was defined by self-report of physician diagnosis , use of diabetic medication , fasting glucose level of at least 7.0 mmol/L ( 126 mg/dL ) , or nonfasting glucose level of at least 11.1 mmol/L ( 200 mg/dL ) . RESULTS Among white participants , a grade d inverse relationship between ser 
    Output:
    
For vitamin C , hospital-based studies reported an inverse association between plasma levels with retinopathy , whereas population -based studies showed no association between dietary intake and retinopathy .
For vitamin E , there was no association with dietary intake or plasma levels and retinopathy .
The evidence suggests that dietary intake or plasma levels of vitamins C and E and magnesium do not seem to be associated with  diabetic retinopathy .