Urine glucose levels are disordered before blood glucose level increase was observed in Zucker diabetic fatty rats
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摘要
Many patients with diabetes are not diagnosed at all or are diagnosed too late to be effectively treated, resulting in nonspecific symptoms and a long period of incubation of the disease. Pre-diabetes is an early warning signal of diabetes, and the change of urine glucose in this period has been ignored even though urine has long been related with diabetes. In this study, Zucker diabetic fatty (ZDF) rats were used to test if there were changes in urine glucose before blood glucose increases. Six 8-week-old male ZDF rats (fa/fa) and Zucker lean (ZL) rats (fa/+) were fed with Purina 5008 high-fat diet and tested for fasting blood glucose and urine glucose. After 12 weeks of feeding, the urine glucose values of the ZL rats were normal (0–10 mmol L~(-1)), but the values of the ZDF model rats increased 10 weeks before their blood glucose levels elevated. The urine glucose values of the ZDF model rats showed a state of disorder that was frequently elevated (>10 mmol L~(-1)) and occasionally normal (0–10 mmol L~(-1)). This finding may provide an easy early screening for diabetes by long-term monitoring of urine glucose levels: pre-diabetes may be revealed by frequently disordered urine glucose levels over a period.
Many patients with diabetes are not diagnosed at all or are diagnosed too late to be effectively treated, resulting in nonspecific symptoms and a long period of incubation of the disease. Pre-diabetes is an early warning signal of diabetes, and the change of urine glucose in this period has been ignored even though urine has long been related with diabetes. In this study, Zucker diabetic fatty (ZDF) rats were used to test if there were changes in urine glucose before blood glucose increases. Six 8-week-old male ZDF rats (fa/fa) and Zucker lean (ZL) rats (fa/+) were fed with Purina 5008 high-fat diet and tested for fasting blood glucose and urine glucose. After 12 weeks of feeding, the urine glucose values of the ZL rats were normal (0–10 mmol L~(-1)), but the values of the ZDF model rats increased 10 weeks before their blood glucose levels elevated. The urine glucose values of the ZDF model rats showed a state of disorder that was frequently elevated (>10 mmol L~(-1)) and occasionally normal (0–10 mmol L~(-1)). This finding may provide an easy early screening for diabetes by long-term monitoring of urine glucose levels: pre-diabetes may be revealed by frequently disordered urine glucose levels over a period.
Many patients with diabetes are not diagnosed at all or are diagnosed too late to be effectively treated, resulting in nonspecific symptoms and a long period of incubation of the disease. Pre-diabetes is an early warning signal of diabetes, and the change of urine glucose in this period has been ignored even though urine has long been related with diabetes. In this study, Zucker diabetic fatty (ZDF) rats were used to test if there were changes in urine glucose before blood glucose increases. Six 8-week-old male ZDF rats (fa/fa) and Zucker lean (ZL) rats (fa/+) were fed with Purina 5008 high-fat diet and tested for fasting blood glucose and urine glucose. After 12 weeks of feeding, the urine glucose values of the ZL rats were normal (0–10 mmol L~(-1)), but the values of the ZDF model rats increased 10 weeks before their blood glucose levels elevated. The urine glucose values of the ZDF model rats showed a state of disorder that was frequently elevated (>10 mmol L~(-1)) and occasionally normal (0–10 mmol L~(-1)). This finding may provide an easy early screening for diabetes by long-term monitoring of urine glucose levels: pre-diabetes may be revealed by frequently disordered urine glucose levels over a period.
引文
Alberti, K.G.M.M., and Zimmet, P.Z. (1998). Definition, diagnosis and classificationof diabetes mellitus and its complications. Part 1: diagnosis andclassification of diabetes mellitus. Provisional report of a WHO consultation.Diabetic Med 15, 7539–7553.
American Diabetes Association. (2016). Standards of medical care in diabetes—2016. Diabetes Care 39, S16.
Bansal, N. (2015). Prediabetes diagnosis and treatment: a review. World JDiabetes 6, 296.
Chua, S.C.Jr., Chung, W.K., Wu-Peng, X.S., Zhang, Y., Liu, S.M., Tartaglia,L., and Leibel, R.L. (1996). Phenotypes of mouse diabetes and rat fattydue to mutations in the OB (Leptin) receptor. Science 271, 994–996.
The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration.(2014). Cardiovascular disease, chronic kidney disease, and diabetesmortality burden of cardiometabolic risk factors from 1980 to 2010:a comparative risk assessment. Lancet Diabetes Endocrinol 2, 634–647.
Durham, H.A., and Truett, G. E. (2006). Development of insulin resistanceand hy-perphagia in Zucker fatty rats. Am J Physiol 290, 652–658.
Hempe, J., Elvert, R., Schmidts, H.L., Kramer, W., and Herling, A.W. (2012).Appropriateness of the Zucker Diabetic Fatty rat as a model for diabeticmicrovascular late complications. Lab Anim 46, 32–39.
Liang, Y., Arakawa, K., Ueta, K., Matsushita, Y., Kuriyama, C., Martin,T., Du, F., Liu, Y., Xu, J., Conway, B., Conway, J., Polidori, D., Ways,K., and Demarest, K. (2012). Effect of canagliflozin on renal thresholdfor glucose, glycemia, and body weight in normal and diabetic animalmodels. PLoS ONE 7, e30555.
Polidori, D., Sha, S., Ghosh, A., Plum-M?rschel, L., Heise, T., and Rothenberg,P. (2013a). Validation of a novel method for determining the renalthreshold for glucose excretion in untreated and canagliflozin-treatedsubjects with type 2 diabetes mellitus. J Clin Endocrinol Metab 98,E867–E871.
Polidori, D., Sha, S., Mudaliar, S., Ciaraldi, T.P., Ghosh, A., Vaccaro, N.,Farrell, K., Rothenberg, P., and Henry, R.R. (2013b). Canagliflozin lowerspostprandial glucose and insulin by delaying intestinal glucose absorptionin addition to increasing urinary glucose excretion: results of arandomized, placebo-controlled study. Diabetes Care 36, 2154–2161.
Poretsky, L. (2010). Principles of diabetes mellitus. Jama J Am Med Assoc,304, 1615–1616.
Seuring, T., Archangelidi, O., and Suhrcke, M. (2015). The economic costsof type 2 diabetes: a global systematic review. Pharmacol Econom 33,811–831.
Tabák, A.G., Herder, C., Rathmann, W., Brunner, E.J., and Kivim?ki, M.(2012). Prediabetes: a high-risk state for diabetes development. Lancet379, 2279–2290.
World Health Organization. (1985). Diabetes Mellitus: Report of a WHOStudy Group. (Geneva: Technical Report Series), pp. 727.
World Health Organization. (2016). Global report on diabetes. Geneva,Available from: http://apps.who.int/iris/handle/10665/204871.
Xu, Y., Wang, L., He, J., Bi, Y., Li, M., Wang, T., Wang, L., Jiang, Y., Dai,M., Lu, J., Xu, M., Li, Y., Hu, N., Li, J., Mi, S., Chen, C.S., Li, G.,Mu, Y., Zhao, J., Kong, L., Chen, J., Lai, S., Wang, W., Zhao, W., Ning,G., and Ning, G. (2013). Prevalence and control of diabetes in Chineseadults. JAMA 310, 948.
Yang, W., Zhao, W., Xiao, J., Li, R., Zhang, P., Kissimova-Skarbek, K.,Schneider, E., Jia, W., Ji, L., Guo, X., Shan, Z., Liu, J., Tian, H., Chen, L.,Zhou, Z., Ji, Q., Ge, J., Chen, G., and Brown, J. (2012). Medical care andpayment for diabetes in China: enormous threat and great opportunity.PLoS ONE 7, e39513.
Zucker, L.M., and Zucker, T.F. (1961). Fatty, a new mutation in the rat. JHered 52, 275–278.
American Diabetes Association. (2016). Standards of medical care in diabetes—2016. Diabetes Care 39, S16.
Bansal, N. (2015). Prediabetes diagnosis and treatment: a review. World JDiabetes 6, 296.
Chua, S.C.Jr., Chung, W.K., Wu-Peng, X.S., Zhang, Y., Liu, S.M., Tartaglia,L., and Leibel, R.L. (1996). Phenotypes of mouse diabetes and rat fattydue to mutations in the OB (Leptin) receptor. Science 271, 994–996.
The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration.(2014). Cardiovascular disease, chronic kidney disease, and diabetesmortality burden of cardiometabolic risk factors from 1980 to 2010:a comparative risk assessment. Lancet Diabetes Endocrinol 2, 634–647.
Durham, H.A., and Truett, G. E. (2006). Development of insulin resistanceand hy-perphagia in Zucker fatty rats. Am J Physiol 290, 652–658.
Hempe, J., Elvert, R., Schmidts, H.L., Kramer, W., and Herling, A.W. (2012).Appropriateness of the Zucker Diabetic Fatty rat as a model for diabeticmicrovascular late complications. Lab Anim 46, 32–39.
Liang, Y., Arakawa, K., Ueta, K., Matsushita, Y., Kuriyama, C., Martin,T., Du, F., Liu, Y., Xu, J., Conway, B., Conway, J., Polidori, D., Ways,K., and Demarest, K. (2012). Effect of canagliflozin on renal thresholdfor glucose, glycemia, and body weight in normal and diabetic animalmodels. PLoS ONE 7, e30555.
Polidori, D., Sha, S., Ghosh, A., Plum-M?rschel, L., Heise, T., and Rothenberg,P. (2013a). Validation of a novel method for determining the renalthreshold for glucose excretion in untreated and canagliflozin-treatedsubjects with type 2 diabetes mellitus. J Clin Endocrinol Metab 98,E867–E871.
Polidori, D., Sha, S., Mudaliar, S., Ciaraldi, T.P., Ghosh, A., Vaccaro, N.,Farrell, K., Rothenberg, P., and Henry, R.R. (2013b). Canagliflozin lowerspostprandial glucose and insulin by delaying intestinal glucose absorptionin addition to increasing urinary glucose excretion: results of arandomized, placebo-controlled study. Diabetes Care 36, 2154–2161.
Poretsky, L. (2010). Principles of diabetes mellitus. Jama J Am Med Assoc,304, 1615–1616.
Seuring, T., Archangelidi, O., and Suhrcke, M. (2015). The economic costsof type 2 diabetes: a global systematic review. Pharmacol Econom 33,811–831.
Tabák, A.G., Herder, C., Rathmann, W., Brunner, E.J., and Kivim?ki, M.(2012). Prediabetes: a high-risk state for diabetes development. Lancet379, 2279–2290.
World Health Organization. (1985). Diabetes Mellitus: Report of a WHOStudy Group. (Geneva: Technical Report Series), pp. 727.
World Health Organization. (2016). Global report on diabetes. Geneva,Available from: http://apps.who.int/iris/handle/10665/204871.
Xu, Y., Wang, L., He, J., Bi, Y., Li, M., Wang, T., Wang, L., Jiang, Y., Dai,M., Lu, J., Xu, M., Li, Y., Hu, N., Li, J., Mi, S., Chen, C.S., Li, G.,Mu, Y., Zhao, J., Kong, L., Chen, J., Lai, S., Wang, W., Zhao, W., Ning,G., and Ning, G. (2013). Prevalence and control of diabetes in Chineseadults. JAMA 310, 948.
Yang, W., Zhao, W., Xiao, J., Li, R., Zhang, P., Kissimova-Skarbek, K.,Schneider, E., Jia, W., Ji, L., Guo, X., Shan, Z., Liu, J., Tian, H., Chen, L.,Zhou, Z., Ji, Q., Ge, J., Chen, G., and Brown, J. (2012). Medical care andpayment for diabetes in China: enormous threat and great opportunity.PLoS ONE 7, e39513.
Zucker, L.M., and Zucker, T.F. (1961). Fatty, a new mutation in the rat. JHered 52, 275–278.