***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: CONTEXT Diabetes is frequently diagnosed late , when the development of complications is almost inevitable , decreasing the quality of life of patients . However , early detection of affected individuals would allow the implementation of timely and effective therapies . OBJECTIVE Here we set to describe the profile of circulating microRNAs ( miRNAs ) in prediabetic patients with the intention of identifying novel diagnostic and therapeutic tools . DESIGN We used real-time RT-PCR to measure the abundance of 176 miRNAs in serum of a cohort of 92 control and prediabetic individuals with either impaired fasting glucose or impaired glucose tolerance , as well as newly diagnosed diabetic patients . We vali date d the results in a second cohort of control and prediabetic subjects undergoing a therapeutic exercise intervention , as well as in a mouse model of glucose intolerance . RESULTS We identified two miRNAs , miR-192 and miR-193b , whose abundance is significantly increased in the prediabetic state but not in diabetic patients . Strikingly , these miRNAs are also increased in plasma of glucose-intolerant mice . Moreover , circulating levels of miR-192 and miR-193b return to baseline in both prediabetic humans and glucose-intolerant mice undergoing a therapeutic intervention consisting in chronic exercise , which succeeded in normalizing metabolic parameters . CONCLUSIONS Our data show that the pattern of circulating miRNAs is modified by defects in glucose metabolism in a similar manner in mice and humans . This circulating miRNA signature for prediabetes could be used as a new diagnostic tool , as well as to monitor response to intervention Saturated fatty acids ( SFA ) and monounsaturated fatty acids ( MUFA ) show different effects on the development of insulin resistance . In this study , we compared the effect of dietary SFA and MUFA on the insulin signaling pathway in the skeletal muscle of a type 2 diabetic animal model . Twenty-nine-week-old male Otsuka Long-Evans Tokushima fatty ( OLETF ) rats were r and omly divided into three groups and fed one of the following diets for 3 weeks ; a normal chow diet , an SFA ( lard oil ) enriched or a MUFA ( olive oil ) enriched high-fat diet . The vastus lateralis muscle was used for analyses . Insulin tolerance test showed improved insulin sensitivity in rats fed the MUFA diet , as compared to those fed the SFA diet ( p < 0.001 ) . The SFA diet reduced IRS-1 expression and phosphorylated PI3 K levels in skeletal muscle , as compared with a chow diet ( p < 0.001 , respectively ) . On the contrary , muscle IRS-2 expression and phosphorylated ERK1/2 was significantly increased in rats fed the SFA diet ( p < 0.001 , respectively ) . Membrane translocation of glucose transporter type 4 decreased in the skeletal muscle of rats fed the SFA diet , as compared to those fed a chow diet ( p < 0.001 ) . These changes in insulin signaling pathway in skeletal muscle were not observed in rats fed the MUFA diet . In conclusion , the beneficial effect of dietary MUFA on insulin sensitivity is associated with a conserved IRS-1/PI3 K insulin signaling pathway which was altered by dietary SFA OBJECTIVE Fat intake , especially monounsaturated fatty acid ( MUFA ) , has been liberalized in diabetic diets to preserve HDL cholesterol and improve glycemic control , yet the exact sources have not been clearly defined . Therefore , we assessed the effect of mixed nut consumption as a source of vegetable fat on serum lipids and HbA1c in type 2 diabetes . RESEARCH DESIGN AND METHODS A total of 117 type 2 diabetic subjects were r and omized to one of three treatments for 3 months . Supplements were provided at 475 kcal per 2,000-kcal diet as mixed nuts ( 75 g/day ) , muffins , or half portions of both . The primary outcome was change in HbA1c . RESULTS The relative increase in MUFAs was 8.7 % energy on the full-nut dose compared with muffins . Using an intention-to-treat analysis ( n = 117 ) , full-nut dose ( mean intake 73 g/day ) reduced HbA1c ( −0.21 % absolute HbA1c units , 95 % CI −0.30 to −0.11 , P < 0.001 ) with no change after half-nut dose or muffin . Full-nut dose was significantly different from half-nut dose ( P = 0.004 ) and muffin ( P = 0.001 ) , but no difference was seen between half-nut dose and muffins . LDL cholesterol also decreased significantly after full-nut dose compared with muffin . The LDL cholesterol reduction after half-nut dose was intermediate and not significantly different from the other treatments . Apolipoprotein ( apo ) B and the apoB : apoA1 ratio behaved similarly . Nut intake related negatively to changes in HbA1c ( r = −0.20 , P = 0.033 ) and LDL cholesterol ( r = −0.24 , P = 0.011 ) . CONCLUSIONS Two ounces of nuts daily as a replacement for carbohydrate foods improved both glycemic control and serum lipids in type 2 diabetes Rationale : MicroRNAs ( miRNAs ) have been implicated in the epigenetic regulation of key metabolic , inflammatory , and antiangiogenic pathways in type 2 diabetes ( DM ) and may contribute to common disease complications . Objective : In this study , we explore plasma miRNA profiles in patients with DM . Methods and Results : Total RNA was extracted from plasma sample s of the prospect i ve population -based Bruneck study . A total of 13 c and i date miRNAs identified by microarray screening and miRNA network inference were quantified by quantitative PCR in all diabetic patients of the Bruneck study and age- and sex-matched controls ( 1995 evaluation , n=80 each ) .  Quantitative PCR assessment revealed lower plasma levels of miR-20b , miR-21 , miR-24 , miR-15a , miR-126 , miR-191 , miR-197 , miR-223 , miR-320 , and miR-486 in prevalent DM , but a modest increase of miR-28 - 3p . Findings emerged as robust in multivariable analysis and were independent of the st and ardization procedure applied . For endothelial miR-126 , results were confirmed in the entire Bruneck cohort ( n=822 ) in univariate ( odds ratio [ 95 % confidence interval ] , 0.38 [ 0.26 to 0.55 ] ; P=2.72 × 10−7 ) and multivariate analyses ( 0.57 [ 0.37 to 0.86 ] ; P=0.0082 ) . Importantly , reduced miR-15a , miR-29b , miR-126 , miR-223 , and elevated miR-28 - 3p levels ante date d the manifestation of disease . Most differences in miRNA levels were replicated in plasma obtained from hyperglycemic Lepob mice . High glucose concentrations reduced the miR-126 content of endothelial apoptotic bodies . Similarly in patients with DM , the reduction of miR-126 was confined to circulating vesicles in plasma . Conclusions : We reveal a plasma miRNA signature for DM that includes loss of endothelial miR-126 . These findings might explain the impaired peripheral angiogenic signaling in patients with DM OBJECTIVE Recent studies have suggested that nuts have favorable effects beyond lipid lowering . We aim ed to investigate effect of the Antep pistachio ( Pistacia vera L. ) on blood glucose , lipid parameters , endothelial function , inflammation , and oxidation in healthy young men living in a controlled environment . METHODS A Mediterranean diet was administered to normolipidemic 32 healthy young men ( mean age 22 y , range 21 - 24 ) for 4 wk . After 4 wk , participants continued to receive the Mediterranean diet but pistachio was added for 4 wk by replacing the monounsaturated fat content constituting approximately 20 % of daily caloric intake . Fasting blood sample s and brachial endothelial function measurements were performed at baseline and after each diet . RESULTS Compared with the Mediterranean diet , the pistachio diet decreased glucose ( P<0.001 , -8.8+/-8.5 % ) , low-density lipoprotein ( P<0.001 , -23.2+/-11.9 % ) , total cholesterol ( P<0.001 , -21.2+/-9.9 % ) , and triacylglycerol ( P=0.008 , -13.8+/-33.8 % ) significantly and high-density lipoprotein ( P=0.069 , -3.1+/-11.7 % ) non-significantly . Total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios decreased significantly ( P<0.001 for both ) . The pistachio diet significantly improved endothelium-dependent vasodilation ( P=0.002 , 30 % relative increase ) , decreased serum interleukin-6 , total oxidant status , lipid hydroperoxide , and malondialdehyde and increased superoxide dismutase ( P<0.001 for all ) , whereas there was no significant change in C-reactive protein and tumor necrosis factor-alpha levels . CONCLUSION In this trial , we demonstrated that a pistachio diet improved blood glucose level , endothelial function , and some indices of inflammation and oxidative status in healthy young men . These findings are in accordance with the idea that nuts , in particular pistachio nuts , have favorable effects beyond lipid lowering that deserve to be evaluated with prospect i ve follow-up studies BACKGROUND AND AIMS Carotenoids may reduce diabetes risk , due to their antioxidant properties . However , the association between dietary carotenoids intake and type 2 diabetes risk is still unclear . Therefore , the objective of this study was to examine whether higher dietary carotenoid intakes associate with reduced type 2 diabetes risk . METHODS AND RESULTS Data from 37,846 participants of the European Prospect i ve Investigation into Cancer and Nutrition- Netherl and s study were analyzed . Dietary intakes of β-carotene , α-carotene , β-cryptoxanthin , lycopene , lutein & zeaxanthin and the sum of these carotenoids were assessed using a vali date d food frequency question naire . Incident type 2 diabetes was mainly self-reported , and verified against general practitioner information . Mean ±SD total carotenoid intake was 10 ± 4 mg/day . During a mean ±SD follow-up of 10 ± 2 years , 915 incident cases of type 2 diabetes were ascertained . After adjustment for age , sex , diabetes risk factors , dietary intake , waist circumference and BMI ,  higher  β-carotene intakes associated inversely with diabetes risk [ Hazard Ratio quartile 4 versus quartile 1 ( HR(Q4 ) ) : 0.78 ( 95%CI:0.64,0.95 ) , P-linear trend 0.01 ] . For α-carotene , a borderline significant reduced risk was observed , with a HR(Q4 ) of 0.85 ( 95%CI:0.70,1.03 ) , and P-linear trend 0.05  . β-cryptoxanthin , lycopene , lutein & zeaxanthin , and the sum of all carotenoids did not associate with diabetes risk . CONCLUSIONS This study shows that diets high in β-carotene and α-carotene are associated with reduced type 2 diabetes in generally healthy men and women BACKGROUND Diabetes is a chronic , potentially debilitating , and often fatal disease . Dietary strategies to reduce postpr and ial glycemia are important in the prevention and treatment of diabetes . Nuts are rich in mono- and polyunsaturated fatty acids , which may reduce hyperglycemia and improve metabolism . OBJECTIVES To evaluate the effectiveness of pistachio nut supplementation on glycemic and inflammatory measures in patients with type 2 diabetes . METHODS In this double-blind , r and omized , placebo-controlled , crossover trial , 48 diabetic patients were equally assigned to groups A and B. Patients in group A received a snack of 25 g pistachio nuts twice a day for 12 weeks and group B received a control meal without nuts . After 12 weeks of intervention , the patients had an 8-week washout . Then the groups were displaced , and group B received the same amount of pistachios for 12 weeks . RESULTS With respect to the total change in variables over both phases , there was a marked decrease in Hb 
    Output:
    
The synergism between PUFA , MUFA , polyphenols and carotenoids present in pistachios can modulate specific miRNA , increasing insulin sensitivity through the PI3K-AKT signaling pathway .