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Fructose induces uric acid production by increasing adenosine triphosphate ATP degradation to adenosine monophosphate AMP , a uric acid precursor. The phosphorylation of fructose to fructosephosphate by fructokinase leads to the degradation of ATP to adenosine diphosphate ADP. As fructosephosphate entraps inorganic phosphate Pi , intracellular Pi levels decrease. Context Fructose-rich beverages such as sugar-sweetened soda and orange juice can increase serum uric acid levels and, thus, the risk of gout, but prospective data on the relationship are limited. Objective To examine the relationship between intake of fructose-rich beverages and fructose and the risk of incident gout among women. Design, Setting, and Participants In the Nurses' Health Study, a US prospective cohort study spanning 22 years , we analyzed data from 78 women with no history of gout at baseline who provided information on intake of beverages and fructose through validated food frequency questionnaires. Results During 22 years of follow-up, we documented confirmed incident cases of gout. Increasing intake of sugar-sweetened soda was independently associated with increasing risk of gout. Compared with consumption of less than 1 serving per month of sugar-sweetened soda, the multivariate relative risk of gout for 1 serving per day was 1. The corresponding relative risks for orange juice were 1. The absolute risk differences corresponding to these relative risks were 36 and 68 cases per person-years for sugar-sweetened soda and 14 and 47 cases per person-years for orange juice, respectively. Compared with the lowest quintile of fructose intake, the multivariate relative risk of gout in the top quintile was 1. Conclusion Among this cohort of women, consumption of fructose-rich beverages is associated with an increased risk of incident gout, although the contribution of these beverages to the risk of gout in the population is likely modest given the low incidence rate among women. Gout is a common and excruciatingly painful inflammatory arthritis. Emerging evidence suggests that gout is strongly associated with metabolic syndrome and may lead to myocardial infarction, 1 , 2 diabetes, and premature death. A recent prospective study of men found that sugar-sweetened sodas, fruit juices, and fructose were associated with a substantially increased risk of gout among men. Furthermore, because animal experiments 14 and 2 National Health and Nutrition Examination Survey NHANES studies have suggested that the magnitude of the urate-increasing effect of sugar-sweetened soft drinks may be weaker among women than among men, 15 extrapolation of data on this potentially important risk factor for gout from men to women should be carried out with caution. To address these issues, we prospectively evaluated the relationship between intake of fructose-rich bever-ages and fructose and incidence of gout in a cohort of 78 women with no history of gout. In , a food frequency questionnaire was added and in , participants were asked about intake of sodas in detail. For our analysis, we excluded women with a previous diagnosis of gout before or participants who did not complete more than 10 items on the dietary questionnaire, leaving 78 eligible women who were followed up from to The Partners HealthCare System institutional review board approved this study; return of a completed questionnaire was accepted by the institutional review board as implied participant informed consent. To assess dietary intake including soft drink intake, we used a validated food frequency questionnaire that inquired about average use of foods and beverages during the previous year. Different types of fruits and fruit juices including orange juice, apple juice, grapefruit juice, tomato juice, and other fruit juices were also assessed. We summed the intakes of single items to create a total of sugar-sweetened soda, diet soda, and fruit juice consumption. Nutrient intakes were computed by multiplying the frequency response by the nutrient content of the specified portion sizes. Half of the disaccharide sucrose is fructose, which is split from sucrose in the small intestine. Food intake assessed by this dietary questionnaire has been validated previously against two 1-week diet records in this cohort. At baseline and every 2 years thereafter, participants provided information on weight, regular use of medications including diuretics , and medical conditions including hypertension. Body mass index was calculated as updated weight in kilograms divided by baseline height in meters squared. We ascertained incident cases of gout using the American College of Rheumatology gout survey criteria, as previously described. Starting in , we mailed a supplementary questionnaire to participants with self-reported incident gout diagnosed in onward to confirm the report and to ascertain whether the cases met the American College of Rheumatology gout survey criteria. We computed person-time of follow-up for each participant from the return date of the questionnaire ie, the first questionnaire with detailed intake information on soft drinks and fruit juices to the date of diagnosis of gout, death due to any cause, or the end of the study period June , whichever came first. Women who died or reported having gout on previous questionnaires were excluded from subsequent follow-up. To represent long-term average intakes of fructose and fructose-rich beverages by individual participants, we used cumulative average intakes based on the dietary information from baseline to the latest point of follow-up as a time-varying variable. Secondary analyses using only information from the baseline questionnaire yielded similar results. For these analyses, soda and juice consumption were categorized into 6 groups: less than 1 serving per month, 1 per month to 1 per week, 2 to 4 per week, 5 to 6 per week, 1 per day, and 2 or more per day. Free fructose and total fructose intake were categorized into quintiles based on percentage of energy nutrient density Multivariate models for soda and juice consumption were adjusted for the following variables in a time-varying manner: age continuous , total energy intake continuous , alcohol none, 0. In multivariate nutrient density models for fructose intake, 27 we simultaneously included energy intake, percentages of energy derived from protein and carbohydrate or nonfructose carbohydrate , intakes of vitamin C and alcohol, and other nondietary variables. The coefficients from these models can be interpreted as the estimated effect of substituting a specific percentage of energy from fructose for the same percentage of energy from nonfructose carbohydrates or fat. Trends in gout risk across categories of soda, juice, or fructose intake were assessed in Cox proportional hazards models by using the median values of intake for each category to minimize the influence of outliers. We tested the significance of the interaction with a likelihood ratio test by comparing a model with the main effects of each intake and the stratifying variable and the interaction terms with a reduced model with only the main effects. The characteristics of the cohort according to consumption levels of sugar-sweetened soda and free fructose at baseline are shown in Table 1. With increasing sugar-sweetened soda consumption, intake of fructose, sucrose, meat, high-fat dairy foods, and coffee tended to increase, but mean age, prevalence of menopause, and intake of low-fat dairy, fruit, and vitamin C tended to decrease Table 1. Alcohol intake was lower in the middle categories of sugar-sweetened soda consumption. With increasing free fructose consumption, body mass index and intake of alcohol, coffee, meat, and high-fat dairy foods tended to decrease but prevalence of menopause and intake of fruit and vitamin C tended to increase Table 1. Compared with consumption of less than 1 serving per month, the multivariate RR of gout was 1. The corresponding absolute risk differences were 36 and 68 cases per person-years. Orange juice intake was associated with risk of gout Table 3. Compared with women who consumed less than a glass 6 oz of orange juice per month, the multivariate RR for gout was 1. The corresponding absolute risk differences were 14 and 47 cases per person-years, respectively. No other individual fructose-rich food item eg, apples or oranges was significantly associated with risk of gout. Increasing fructose intake was associated with increasing risk of gout Table 4. Compared with women in the lowest quintile of free fructose intake, the multivariate RR of gout in the highest quintile was 1. The corresponding RR increased after we adjusted for total carbohydrate intake to reflect the substitution effect of fructose for other types of carbohydrates multivariate RR, 1. The corresponding absolute risk difference was 28 cases per person-years. Similar trends were observed with intake of total fructose ie, free fructose plus half the intake of sucrose , although the magnitudes of associations tended to be smaller Table 4. We also conducted stratified analyses to evaluate whether the association between sweetened soda and fructose consumption and risk of gout varied according to body mass index, alcohol use, and dairy intake. In this large prospective study of women, we found that risk of incident gout increased with increasing intake of sugar-sweetened soda. In contrast, diet soda intake was not associated with risk of incident gout. Similarly, women who consumed 2 servings or more of orange juice showed a 2. Furthermore, risk of gout was significantly increased with increasing intake of fructose, the main ingredient thought to cause the increased risk. These associations were independent of risk factors for gout such as body mass index, age, hypertension, menopause, diuretic use, alcohol, and intake of dairy, meat, seafood, coffee, and vitamin C. These findings confirm the associations observed in the recent prospective study of men 13 and provide the first prospective evidence among women that fructose and fructose-rich beverages are important risk factors to be considered in the primary prevention of gout. Although the RRs of gout associated with fructose-rich beverages among women were substantial, the corresponding absolute risk differences were modest given the low incidence rate of gout among women. Although the RR data suggest a substantial biologic link, the risk difference data suggest that their contribution to the risk of gout in the population is likely modest given the low incidence rate among women. Because the urate-increasing effect of fructose is greatest in patients with gout and hyperuricemia, 8 - 10 , 28 our findings may be even more relevant in those patients. Previous animal experiments 14 , 29 , 30 and NHANES studies 15 , 31 have suggested that the magnitude of the urate-increasing effect of fructose or sugar-sweetened sodas may be weaker among females than among males. For example, an analysis based on NHANES III found that the increase in serum uric acid level associated with sugar-sweetened soda intake was significantly larger among men than women, although the association among women was still statistically significant. Nevertheless, as gout among women occurs predominantly after menopause, when the female hormonal influence substantially declines, the sex difference of the fructose effect on the risk of gout may be less apparent than that on serum uric acid levels observed in the general population that included premenopausal women. Fructose induces uric acid production by increasing adenosine triphosphate ATP degradation to adenosine monophosphate, a uric acid precursor Figure. Furthermore, fructose could indirectly increase serum uric acid level and risk of gout by increasing insulin resistance and circulating insulin levels. Our findings have practical implications for the prevention of gout in women. As conventional dietary recommendations for gout have focused on restriction of purine intake, low-purine diets are often high in carbohydrates, including fructose-rich foods. Several strengths and potential limitations of our study deserve comment. Our study had a large number of cases of confirmed incident gout among women, and dietary data including beverage and fructose intake information were prospectively collected and validated. Although there was a relatively large number of cases in the highest fructose quintile groups, the numbers in the top intake categories of fructose-rich beverage items were small. Nevertheless, it was reassuring that the next highest categories also showed significant positive associations with a dose-response relationship. Potential biased recall of diet was avoided in this study because intake data were collected before the diagnosis of gout. Because dietary consumption was self-reported by questionnaire, some misclassification of exposure is inevitable. However, self-reported dietary consumption has been extensively validated in subsamples of this cohort, 16 , 22 and any remaining misclassification would have likely biased the results toward the null. The use of repeated dietary assessments in the analyses not only accounts for changes in dietary consumption over time but also decreases measurement error. The validity of gout ascertainment in this cohort and our companion male cohort 4 , 18 , 19 has been documented by the high degree of concordance with medical record review. The restriction to registered nurses in our cohort is both a strength and a limitation. The cohort of well-educated women minimizes potential for confounding associated with socioeconomic status, and we were able to obtain high-quality data with minimal loss to follow-up. Although the absolute rates of gout and related measures, as well as distribution of fructose intake, may not be representative of a random sample of US women, the biological effects of fructose intake on gout as reflected in RRs should be similar. Our findings are most directly generalizable to middle-aged and elderly white women with no history of gout. Since the prevalence of risk factors for gout and its incidence tend to be higher in the general population and among African Americans, the magnitude of the absolute risk increase associated with these beverages might be greater than the increase we observed. In conclusion, our findings provide prospective evidence that consumption of sugar-sweetened sodas, orange juice, and fructose is associated with an increased risk of incident gout among women, although their contribution to the risk of gout in the population is likely modest given the low incidence rate among women. In contrast, diet soda intake is not associated with the risk of gout. Physicians should be aware of the potential effect of these beverages on the risk of gout, a common and excruciatingly painful arthritis. Corresponding Author: Hyon K. Author Contributions: Dr Choi had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Critical revision of the manuscript for important intellectual content : Choi, Willett, Curhan. Financial Disclosures: Dr Choi reports receiving research funding for other projects from Takeda Pharmaceuticals and serving on advisory boards for Takeda Pharmaceuticals and Savient Pharmaceuticals. Dr Curhan reports serving as a consultant for Takeda Pharmaceuticals. No other disclosures were reported. Role of the Sponsor: The sponsor had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, or approval of the manuscript. View Large Download. Table 1. Table 2. Table 3. Table 4. Table 5. Table 6. Gout and the risk of acute myocardial infarction. Arthritis Rheum. Choi HK, Curhan G. Independent impact of gout on mortality and risk for coronary heart disease. Incidence and risk factors for gout in white men. Purine-rich foods, dairy and protein intake, and the risk of gout in men. N Engl J Med. Estimates of the prevalence of arthritis and other rheumatic conditions in the United States, part II. Epidemiology of gout: is the incidence rising? J Rheumatol. Apovian CM. Sugar-sweetened soft drinks, obesity, and type 2 diabetes. Fructose-induced hyperuricaemia. Emmerson BT. Effect of oral fructose on urate production. Ann Rheum Dis. Perheentupa J, Raivio K. Stimulation of human purine synthesis de novo by fructose infusion. A controlled study of diet in patients with gout. Soft drinks, fructose consumption, and the risk of gout in men: prospective cohort study. Female rats are protected against fructose-induced changes in metabolism and blood pressure. Sugar-sweetened soft drinks, diet soft drinks, and serum uric acid level: the Third National Health and Nutrition Examination Survey. Reproducibility and validity of an expanded self-administered semiquantitative food frequency questionnaire among male health professionals. Am J Epidemiol. Reproducibility and validity of a semiquantitative food frequency questionnaire. Alcohol intake and risk of incident gout in men: a prospective study. Obesity, weight change, hypertension, diuretic use, and risk of gout in men: the health professionals follow-up study. Arch Intern Med. US Department of Agriculture. Composition of Foods—Raw, Processed, and Prepared. Intakes and food sources of fructose in the United States. Am J Clin Nutr. Reproducibility and validity of food intake measurements from a semiquantitative food frequency questionnaire. J Am Diet Assoc. Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. Preliminary criteria for the classification of the acute arthritis of primary gout. Dietary fat intake and the risk of coronary heart disease in women. Dietary protein and risk of ischemic heart disease in women. Willett W. Nutritional Epidemiology. Studies on the mechanism of fructose-induced hyperuricemia in man. Differential regulation of insulin resistance and hypertension by sex hormones in fructose-fed male rats. Female rats do not develop sucrose-induced insulin resistance. Am J Physiol. Intake of added sugar and sugar-sweetened drink and serum uric acid concentration in US men and women. Prevalence of the metabolic syndrome in patients with gout: the Third National Health and Nutrition Examination Survey. Pathogenesis of gout. Ann Intern Med. Fox IH. Metabolic basis for disorders of purine nucleotide degradation. Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. Nat Clin Pract Nephrol. Fructose, glycemic load, and quantity and quality of carbohydrate in relation to plasma C-peptide concentrations in US women. Fructose-induced in vivo insulin resistance and elevated plasma triglyceride levels in rats. Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects. Fam AG. Gout, diet, and the insulin resistance syndrome. Osler W. In: Principles and Practice of Medicine. New York, NY: Appleton; See More About Rheumatology. Save Preferences. Privacy Policy Terms of Use. This Issue. Citations 0. View Metrics. X Facebook More LinkedIn. Original Contribution. Hyon K. Study Population. Assessment of Nondietary Factors. Ascertainment of Incident Cases of Gout. Statistical Analysis. Baseline Characteristics. Fruit Juice Intake and Incident Gout. Fructose Intake and Incident Gout. Back to top Article Information. Access your subscriptions. Access through your institution. Add or change institution. Free access to newly published articles. Purchase access. Rent article Rent this article from DeepDyve. Sign in to access free PDF. Save your search. Customize your interests. Create a personal account or sign in to:. Privacy Policy. Make a comment.
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Air Jordan was an airline based in Jordan. It was founded in It ceased operating in Alpico Kotsu Co. The company was known as Matsumoto Electric Railway Co. Matsumoto Denki-tetsudo Kabushiki-gaisha until its merger with two affiliate companies on April 1, It was mainly a mineral carrier, with supplementary passenger service. Minerals included limestone, fluorspar, gritstone and later coal. It opened in , being constructed and equipped using mainly surplus materials from WW1, and lasted until by which time it was worn out. Louis, Missouri-based private refrigerator car line established in by the Missouri Pacific and Wabash railroads. It is now a subsidiary of the Union Pacific Corporation. Its services are branded 'one'. The company had previously been known as Northern Spirit before being taken over Arriva. The franchise was taken over by Northern Rail in December Arriva won the Wales and Borders franchise in and promptly renamed the company Arriva Trains Wales. They operate almost all services in Wales, with the execption of long distance express services. The AZCR runs An excursion train also runs on the line through Verde Canyon and is operated by the same owners under the Verde Canyon Railroad. Banedanmark is the infrastructure manager responsible for the national network in Denmark. BDK is responsible for - Maintenance and renewal of the railway network - Safety systems - Railway traffic management across the entire railway network - Construction of timetable and path allocation. They started with passenger trains, but later freight trains followed. In May it was sold in a management buyout. This new track maintenance company originates from the company Bau und Unterhaltung von Gleisanlagen BUG , founded in It is based in Berlin. Banverket actually 'owns' all the Swedish tracks. They keep the tracks in good shape, and SJ and the regional railways have to pay for the use of the tracks to Banverket. Banverket owns some locomotives and shunters for track maintenance trains, and snow plows. Spantax S. It was formed by the privatisation of British Rail in and it operates train mainline services from Marylebone station in London, to Aylesbury and Birmingham Snow Hill. Initially the line was franchised to a company formed by the British Rail managers of the route, but since has been a wholly owned subsidiary of Laing Rail, who owned a much smaller shareholding at privatisation. In a new 20 year franchise began which promises significant investment in the route. It had its origins as a coal carrier from the pits at Drumlemble to the quays at Campbeltown, but during the era of the Clyde steamers, Campbeltown became a very popular destination for day trippers and the railway capitalised on this by extending itself to Macrihanish offering access to the Atlantic Ocean and the local golf links! Its final length was about 6 miles. The line originally opened for coal traffic in , and for passenger traffic through to Macrihanish in It then led a relatively prosperous life until after the first world war, but succumbed to the inevitable road transport, closure of the pits and changing holiday patterns in It was independent throughout its existence. The railway was interesting in that its coaches were enormous for such a small gauge, and that the early coal trains consisted of 2ft 3in gauge transporter wagons carrying 4 small colliery wagons known as 'hutches', transversely. Cotswold Rail is a spot-hire company of shunting and mainline locomotives, based in Moreton-in-Marsh, Gloucestershire. The German Army was formed after the unification of Germany under Prussian leadership in and dissolved in , after the defeat of the German Empire in World War I. Since then it has expanded greatly, and has acquired many more locomotives, most bought second-hand and subsequently refurbished. DRS remains unique in Britain, remaining a publicly-owned rail freight company. DRS now operates all nuclear-flask trains in the country. DTS was formed by the consolidation of various privately owned transit companies and streetcar lines. On 1 April , London Buses was divided into 11 separate business units, one of which was East London. Elipsos Internacional S. It was created to handle the logistics of Trenhotel night railway services between Spain and France, Switzerland and Italy. The Ffestiniog Railway is a 2ft nom. It is probably the most famous and influential narrow gauge railway in the world! The railway was built to carry slate from the quarries in Blaenau Ffestiniog to the quays in Porthmadog. Without the railway it is doubtful that either of these places would have developed anywhere near to the extent they have today. At first a mixture of horse and gravity power was used, but horses were later replaced by steam power. The railway operated continuously from until it closed in It now operates as a preserved tourist line, reopening in stages from until From April 1, , all First Great Eastern services were transferred to 'one', a new company operating all services from Liverpool Street. Most lines previously served by First Great Eastern are electrified 25 kV AC overhead catenary with the exception of the Marks Tey to Sudbury line, which is served by diesel units. First were announced as the operator of the combined franchise in December for a year period. Freightliner is a British freight operating company, founded in It is the second largest railfreight operator, after EWS. The origins of the Freightliner concept go back to the mid's British Rail under Richard Beeching. As part of an overall modernisation and rationalisation programme, British Rail began moving freight using ISO containers on flat wagons between a series of dedicated inland terminals using gantry cranes for transhipment from road to rail. Although initially intended for domestic freight, this was soon overtaken by freight between deep sea ports, such as Southampton Maritime an and inland distribution terminals associated with centres of manufacturing or population such as Birmingham Landor Street. In , Freightliner was privatised as a stand alone company, being bought out by its own management. The company was formed in January following the merging of charter company Merlin Rail with spot-hire company Fragonset Railways. FM Rail lauched its new livery in September First Group has its headquarters in Aberdeen, Scotland. This was the first time the franchise has been renegotiated since the privatisation of British Rail. In the British company Go Ahead won the tender to operate passenger trains in Southwestern Norway from December for 8 years, with a possible extension of another two years. The trainsets - owned by Norske Tog and currently used on the same lines by NSB - got or will get refreshed interiors. It was an expansion of an earlier 3ft gauge line and involved reducing the gauge to 2ft nom. It was expected to lead to the expansion of quarrying and mining at the head of the Pennant Valley, but unlike the Blaenau Ffestiniog region, little useful material was found and the quarries and therefore the railway were all spectacularly unsuccessful. The railway was active from to , and due to the remote country through which it ran most of the trackbed is still intact. They operate high-speed express train services on the East Coast Main Line. It was founded in , kept its identity through the grouping, and became part of British Railways at nationalisation in Known admiringly to some as 'God's Wonderful Railway', jocularly to others as the 'Great Way Round' some of its earliest routes were not the most direct , and by some as the 'Goes When Ready' due to the casual way in which some of its branch lines were run, it gained great fame as the 'Holiday Railway', taking huge numbers of people to resorts in the southwest. The service follows the same route as the faster Heathrow Express service but serves intermediate stations on its route, thus connecting several locations in west London with each other, the airport, and central London. The service is not part of the National Rail system, despite part of its journey sharing track with National Rail trains and terminating at a London mainline station. Hankyu Railway Hankyu- Dentetsu is a Japanese private railway that provides commuter and interurban service to the northern Kansai region. Its main terminal is at Umeda Station in Osaka. The signature color of Hankyu cars is maroon. From June trains are operated between Paddington and the entrance of the tunnel under the airport, every 15 minutes. The Kuroyama station divergence new Katahigashi port private line - the Niigata seaside railroad. This company used to be known as Lausitzbahn, but because they also started operating trains outside the Lausitz region the name was changed to Connex Sachsen. Early in Connex was renamed in Veolia Verkehr. It was formed in prior to the privatisation of British Rail. The first loco to have this livery was which attended the event. It ran through picturesque but rural country, with a very sparse population to sustain it, from Waterhouses at the end of the North Staffordshire Railway's branch from Leek to Hulme End, a distance of just over 8 miles. The LMS continued to operate it at an ever increasing loss due to competition from road transport until finally, in , the dairy that was its main source of traffic closed, and the railway itself soon succumbed. All was not lost, however, because the local council ensured that most of the track-bed was retained as a cycle-way and footpath, and thus can still be enjoyed today. Der Landbus Unterland ist auf Basis eines Gemeindeverbands organisiert, welcher sich aus den Gemeinden des unteren Rheintals, sowie des Leiblachtals zusammensetzt. In April the company was rebranded as 'The Shires', with a new blue and yellow livery and local area operating titles. Cowie Group took over in June , and renamed Arriva in November The Lynton and Barnstaple Railway was a 19 mile long 1ft It also carried a reasonable quantity of local goods traffic.
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