Clinical and Laboratory Profile of Patients With Type 2 Diabetes With Low Glomerular Filtration Rate and Normoalbuminuria CAROLINE K. KRAMER, MD CRISTIANE B. LEITA ˜ O, MD LANA C. PINTO SANDRA P. SILVEIRO, MD JORGE L. GROSS, MD LU´ IS H. CANANI, MD T he initial evidence of diabetic ne- phropathy in type 2 diabetic patients is the development of microalbumin- uria (1). However, the UK Prospective Dia- betes Study demonstrated that 51% of patients who progress to chronic renal fail- ure had no preceding albuminuria (1). Patients with low estimated glomeru- lar filtration rate (eGFR) (60 ml/min per 1.73 m 2 ) and normoalbuminuria pre- sented an increased rate of cardiovascular disease (2– 4) due to unknown reasons. Aggregation of conventional cardiovascu- lar risk factors might play a role. There- fore, the aim of this study was to analyze the clinical and laboratory features of type 2 diabetic patients with low eGFR and normoalbuminuria. RESEARCH DESIGN AND METHODS — A cross-sectional study was performed in all consecutive nor- moalbuminuric type 2 diabetic patients attending the outpatient clinic at Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil, between 1999 and 2006 with eGFR 15 ml/min per 1.73 m 2 . Nor- moalbuminuria was defined by urinary albumin excretion (UAE) values 20 g/ min, 17 mg/l (random sample), or 30 mg in 24 h (5) on at least two occasions over the preceding 6 months while on their usual antihypertensive medication. eGFR was calculated using the Modifica- tion of Diet in Renal Disease formula: 186  [plasma creatinine (mg/dl) -1.154  age (years) -0.203  (1.212 if black)  (0.742 if female)] (6). All patients an- swered a standard questionnaire and un- derwent physical examination and laboratory tests. Metabolic syndrome was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria (7). UAE was measured by immunoturbi- dimetry. Serum creatinine was measured by the Jaffe ´ method and the lipid profile by a colorimetric method. Insulin resis- tance was estimated by homeostasis model assessment of insulin resistance (HOMA-IR) (8) in a subset of subjects not on insulin and with serum creatinine 1.5 mg/dl. Fundus examination was performed by an expert ophthalmologist after mydri- asis. For the purpose of this study, pa- tients were classified only according to the presence or absence of any degree of diabetic retinopathy. The presence of cor- onary heart disease was evaluated by the World Health Organization question- naire for cardiovascular disease, a 12-lead resting electrocardiogram, or a fixed and nonperfused area at myocardial scintigra- phy, as previously described (9,10). The presence of cerebrovascular disease was established if a history of stroke and/or sequelae were present. Peripheral vascu- lar disease was defined in the presence of intermittent claudication, as assessed by the World Health Organization question- naire for cardiovascular disease and/or the absence of lower limb pulses. Student’s t test or the  2 tests and Pearson’s correlations were performed. Variables with nonnormal distribution (triglycerides, UAE, and HOMA-IR) were log transformed. Multiple linear regres- sion analysis was performed with eGFR as the dependent variable and age, sex, ACE inhibitor use, systolic blood pressure, triglycerides, and total cholesterol as in- dependent variables. P values 0.05 (two tailed) were considered significant. RESULTS — A total of 660 normoalbu- minuric type 2 diabetic patients were evaluated. Eighty-four (12.7%) had low eGFR (15– 60 ml/min per 1.73 m 2 ), and the remaining 576 comprised the refer- ence group (87.2%) (Table 1). The group of patients with low eGFR was older (62.9  10.3 vs. 56.8  9.5 years, P  0.001), had more women (77.4 vs. 60.2%, P = 0.002), and had higher total cholesterol (222.8  52.0 vs. 205.3  43.9 mg/dl, P = 0.014), LDL cholesterol (143.0  46.0 vs. 122.1  40.1 mg/dl, P = 0.028), triglycerides (median 176 [minimum–maximum 46 – 842] vs. 158 [55–549] mg/dl, P = 0.006), and HOMA-IR (11.4 [1.6 – 44.7] vs. 4.84 [0.3– 45], P = 0.014) than the reference group. Moreover, this group also pre- sented a high proportion of patients with metabolic syndrome (81.9 vs. 70.2%, P = 0.027). There was no difference in the prevalence of micro- and macrovascular diabetes complications between low eGFR and reference groups (diabetic ret- inopathy: 28.4 vs. 31.6%, P = 0.575; cor- onary heart disease: 29.2 vs. 31.2%, P = 0.729; peripheral vascular disease: 33.3 vs. 24.3%, P = 0.089; and cerebrovascu- lar disease: 7.7 vs. 4.4%, P = 0.218). The use of antihypertensive drugs (61 vs. 55%, P = 0.120), including ACE inhibi- tors (45.5 vs. 33.5%, P = 0.132), was also similar. In a univariate analysis, eGFR corre- ●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●●● From the Endocrine Division, Hospital de Clı ´nicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. Address correspondence and reprint requests to Luı ´s Henrique Canani, Servic ¸o de Endocrinologia do Hospital de Clı´nicas de Porto Alegre, Rua Ramiro Barcelos 2350, Pre ´dio 12 4 andar, 90035-003, Porto Alegre-RS, Brazil. E-mail: luiscanani@yahoo.com.br. Received for publication 24 February 2007 and accepted in revised form 21 April 2007. Published ahead of print at http://care.diabetesjournals.org on 27 April 2007. DOI: 10.2337/dc07-0387. Abbreviations: eGFR, estimated glomerular filtration rate; GFR, glomerular filtration rate; HOMA-IR, homeostasis model assessment of insulin resistance; UAE, urinary albumin excretion. A table elsewhere in this issue shows conventional and Syste `me International (SI) units and conversion factors for many substances. © 2007 by the American Diabetes Association. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Clinical Care/Education/Nutrition/Psychosocial Research B R I E F R E P O R T 1998 DIABETES CARE, VOLUME 30, NUMBER 8, AUGUST 2007 Downloaded from http://diabetesjournals.org/care/article-pdf/30/8/1998/596346/zdc00807001998.pdf by guest on 28 February 2023