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Serum Uric Acid and Disorders of Glucose Metabolism: the Role of Glycosuria

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Serum Uric Acid and Disorders of Glucose Metabolism: the Role of Glycosuria Brazilian Journal of Medical and Biological Research (2014) 47(10): 917-923, http://dx.doi.org/10.1590/1414-431X20143878 ISSN 1414-431X Serum uric acid and disorders of glucose metabolism: the role of glycosuria J.A.M. Andrade1, H.C. Kang2, S. Greffin1, M.L. Garcia Rosa3 and J.R. Lugon1 1Divisa˜o de Nefrologia, Departamento de Medicina Clı´nica, Faculdade de Medicina, Universidade Federal Fluminense, Nitero´i, RJ, Brasil 2Departamento de Patologia, Faculdade de Medicina, Universidade Federal Fluminense, Nitero´i, RJ, Brasil 3Departamento de Epidemiologia e Bioestatı´stica, Universidade Federal Fluminense, Nitero´i, RJ, Brasil Abstract Hyperuricemia has been associated with hypertension, diabetes mellitus, and metabolic syndrome. We studied the association between hyperuricemia and glycemic status in a nonrandomized sample of primary care patients. This was a cross-sectional study of adults §20 years old who were members of a community-based health care program. Hyperuricemia was defined as a value .7.0 mg/dL for men and .6.0 mg/dL for women. The sample comprised 720 participants including controls (n=257) and patients who were hypertensive and euglycemic (n=118), prediabetic (n=222), or diabetic (n=123). The mean age was 42.4±12.5 years, 45% were male, and 30% were white. The prevalence of hyperuricemia increased from controls (3.9%) to euglycemic hypertension (7.6%) and prediabetic state (14.0%), with values in prediabetic patients being statistically different from controls. Overall, diabetic patients had an 11.4% prevalence of hyperuricemia, which was also statistically different from controls. Of note, diabetic subjects with glycosuria, who represented 24% of the diabetic participants, had a null prevalence of hyperuricemia, and statistically higher values for fractional excretion of uric acid, Na excretion index, and prevalence of microalbuminuria than those without glycosuria. Participants who were prediabetic or diabetic but without glycosuria had a similarly elevated prevalence of hyperuricemia. In contrast, diabetic patients with glycosuria had a null prevalence of hyperuricemia and excreted more uric acid and Na than diabetic subjects without glycosuria. The findings can be explained by enhanced proximal tubule reabsorption early in the course of dysglycemia that decreases with the ensuing glycosuria at the late stage of the disorder. Key words: Hyperuricemia; Glycosuria; Diabetes mellitus; Prediabetes Introduction Elevated serum uric acid is an independent predictor lower serum uric acid than prediabetic or normoglycemic of vascular complications and mortality in type 2 diabetes ones (12,13). Based on this information, we evaluated the mellitus patients (1) and is associated with excess risk for association between uric acid and glycemic status in a development of diabetes (2,3). nonrandomized sample of members of a community-based The association between hyperuricemia and cardiovas- health care program. cular disease has been observed since the nineteenth century (4). This issue gained more attention in the late Material and Methods 1950s and since then several studies have stressed the correlation between uric acid and conditions such as arterial The study sample was derived from the CAMELIA hypertension (5,6), diabetes mellitus (7), metabolic syn- (cardiometabolic renal) study, a cross-sectional observa- drome (8), atherosclerosis (9), and renal disease (10,11). tional study of familial aggregation of metabolic syndrome, However, the relationship between diabetes mellitus conducted between July 2006 and December 2007 as a and hyperuricemia is still subject to controversy. Although partnership between Universidade Federal Fluminense several studies have reported hyperuricemia as a risk and the Nitero´i Healthcare Foundation. The protocol was factor for development of diabetes mellitus, especially in approved by the Ethics Committee of the Faculdade de the context of insulin resistance, others have suggested Medicina, Universidade Federal Fluminense, Nitero´i, RJ, that patients with recently diagnosed diabetes tend to have Brazil, under the number 220/05. Correspondence: J.R. Lugon, Rua Marques de Parana´, 303, 2o andar, Centro de Dia´lise, 24033-900 Centro, Nitero´i, RJ, Brasil. Fax: +55-21-2629-9260. E-mail: [email protected] Received January 30, 2014. Accepted June 13, 2014. First published online August 22, 2014. www.bjournal.com.br Braz J Med Biol Res 47(10) 2014 918 J.A.M. Andrade et al. A total of 1098 subjects who were enrolled in the Family analyzer (NE Vital Scientific, Netherlands). Standard serum Doctor Program of Nitero´i city, Rio de Janeiro, RJ, Brazil, parameters included glucose, creatinine (Cr), LDL choles- were recruited following an initial selection of index cases. terol (LDL-C), HDL cholesterol (HDL-C), triglycerides, and The present study included data from participants who uric acid (UA). Urinary biochemical parameters were were at least 20 years old. To be accepted as an index measured in a first morning urine sample and included case, individuals were required to have a partner who Cr, albumin (Alb), sodium, and uric acid. Glycosuria was agreed to participate in the study and to have at least one assessed semiquantitatively by dipsticks. We calculated the descendant with that partner, aged 12 to 30 years, who sodium excretion index (EINa) in mEq/g Cr, Alb:Cr ratio would also enroll. Four groups of index cases were initially (ACR) in mg/g Cr, and fractional excretion of uric acid selected. These were controls whose partners were also (FEUA) as a percentage. Microalbuminuria was defined as neither hypertensive nor diabetic, nondiabetic hypertensive an ACR between 30 and 300 mg/g Cr. Glomerular filtration patients, diabetic patients without hypertension, and diabetic rate (eGFR) was estimated by CKD-EPI (the Chronic Kidney patients who were hypertensive. Patients with immunode- Disease Epidemiology Collaboration) formula, recom- ficiency, malignancy, chronic renal failure (stage V), heart mended as more appropriate for studies in the general failure, coronary artery disease, stroke, severe peripheral population (15). vascular disease, pregnant women, or users of immuno- Continuous variables are reported as means±SD, suppressive drugs (corticosteroids or cytostatics) were categorical variables as frequencies. For continuous vari- excluded. Likewise, controls found to have a systolic ables, differences between groups were tested using T- test blood pressure .140 mmHg and/or diastolic pressure for comparing two groups or, alternatively, one-way ANOVA .90 mmHg, or whose fasting glucose was §100 mg/dL complemented by the Duncan test; for frequencies, chi- were not included. Written informed consent was obtained square or the Fisher test was employed as appropriate. from all participants. Subjects were interviewed by trained Values of P ,0.05 were considered to be significant. investigators using a standardized questionnaire. Statistical analyses were performed using SPSS (Statistical Blood pressure was measured with an electronic Package for Social Sciences, USA), version 18.0. sphygmomanometer (HEM-711AC Omron Co., Japan). Subjects whose reading was .140 mmHg (systolic) or Results .90 mmHg (diastolic) as well as those who reported using antihypertensive drugs were considered hypertensive. Body A total of 720 patients were evaluated: controls weight was measured by a digital electronic scale (PL80, (n=257) and euglycemic and hypertensive (n=118), Filizola, Brazil) and height by a portable digital stadiometer prediabetic (n=222), and diabetic (n=123) patients. (Kirchnner Wilhelm, Medizintechnik, Germany). The body None of the subjects was using drugs for hyperuricemia. mass index (BMI) was calculated as the ratio of weight in The general characteristics of the study population are kilograms to height in meters squared. Waist circumference shown in Table 1. was assessed on three occasions using an inextensible tape The overall prevalence of hyperuricemia in the study measure, at the midpoint of the distance between the iliac population was 8.9%. The influence of gender and age upon crest and the last costal margin with the patient upright and the frequency of hyperuricemia can be observed in Figure 1. at end expiration. Despite the adoption of different reference values for each Participants whose fasting glucose was §126 mg/dL, gender, young males tended to be more hyperuricemic than and those who reported oral use of hypoglycemic agents young females at every age range but statistical significance and/or insulin were considered diabetic. Prediabetes was was reached only in those 40-49 years of age. Above the defined as fasting glucose between 100 and 125 mg/dL age of 50 years, gender differences were no longer present, (American Diabetes Association) and hyperuricemia as meaning that the increase of frequency of hyperuricemia in plasma uric acid §6.0 mg/dL for women and §7.0 mg/dL females with aging was more substantial. In both genders, for men. The diagnosis of metabolic syndrome was based the highest frequency of hyperuricemia was seen above 60 on harmonized criteria (14). Subjects who met at least 3 of 5 years of age. of the following criteria were considered as having metabolic Data from the four study groups are shown in Table 2. syndrome: 1) increased waist circumference - in Latin The frequency of hyperuricemia was statistically higher in America .90 cm for men and .80 cm for women; 2) hyper- both prediabetic and diabetic patients than in controls. triglyceridemia (triglycerides
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