Strong Association Between Insulin Resistance With Urinary Albumin Excretion in Older Adults

To the Editor: Urinary albumin excretion (UAE) is a risk factor for cardiovascular disease1 and a marker of endothelial dysfunction.2, 3 Insulin resistance is reportedly associated with microalbuminemia with or without diabetes mellitus,4, 5 but the effects of aging on the association betwen UAE and insulin resistance remain largely unknown. The current study aimed to investigate the effects of age on the association between insulin resistance and UAE. Data from a portion of the participants in the Japan Morning Surge—Home Blood Pressure (J-HOP) study were analyzed.6 In the current study, participants with fasting blood sugar (FBS) greater than 140 mg/dL were excluded from the evaluation of an insulin resistance score (homeostasis model assessment–insulin resistance; HOMA-R). To investigate the effects of insulin resistance on the early phase of UAE, only normo- and microalbuminemic individuals were involved (UAE<300 mg/g creatinine). Five hundred eight participants (238 men and 270 women, mean age 63.59) were included in the analysis. Blood samples were drawn from the antecubital vein in a fasting state at the second clinic visit. All blood samples were measured in a single laboratory (SRL, Inc., Tokyo, Japan). Serum insulin levels were measured using an enzyme immunoassay (Eiken Chemical Co., Tokyo, Japan). HOMA-R was computed using the following formula: fasting plasma glucose (mg/dL) × fasting serum insulin (μU/L)/405.7 Plasma brain natriuretic peptide (BNP) was measured using chemiluminescent enzyme immunoassay (Shionogi & Co., Osaka, Japan). Urinary albumin concentration was determined from urine samples collected after overnight fasting. UAE was expressed as albumin:creatinine ratio (mg/g creatinine). Self-measured home blood pressure (BP) was measured using a validated upper arm cuff oscillometric device (HEM-5001, Omron Kyoto, Japan).8 The average of morning and evening BP at home was used for the analysis. Participants were divided into two groups: younger (<65) and older (≥65). Differences in the values between the two groups were analyzed using the Student t-test. The difference in the distribution between the groups was analyzed using the chi-square test. The association between UAE and HOMA-R was analyzed using simple regression analysis and multiple regression analysis adjusted for several factors. The younger participant group (<65) included 268 participants (127 male and 141 female, mean age 57.2 ± 6.0) and the older group (≥65) 240 participants (111 male and 129 female, mean age 70.7 ± 5.1). Antihypertensive medication was prescribed for 93.9% of the participants. Renin-angiotensin system inhibitors were used in 47.7% and 47.0% of the participants in the younger and older groups, respectively. Simple regression analysis demonstrated that there was a stronger association between UAE and HOMA-R in the older than the younger group (coefficient of determination (R2)=0.018 for the younger group, R2=0.047 for the older group). The results of multiple linear regression analysis adjusted for several factors are shown in Table 1. The significant association between HOMA-R and UAE was found only in the older group. Systolic BP was significantly associated with UAE in both groups. The association between glycosylated hemoglobin (HbA1c) and UAE was found only in the younger group. The current study found that the association between insulin resistance and UAE was stronger in older than younger individuals. The mechanism of this phenomenon remains to be elucidated. The treatment of insulin resistance may be more effective in older adults in terms of decrease of UAE. HbA1c was significantly associated with UAE only in the younger group. The mechanism of this difference is unknown and should be explored. Approximately 10% of the participants in the current study had diabetes mellitus. The finding regarding HbA1c must be confirmed in people with diabetes mellitus. Hypertension was associated with UAE in both age groups. The favorable effects of antihypertensive agents on microalbuminuria appear to be proportional to BP reduction.9 The current results demonstrated that BP is significantly associated with UAE and may suggest that antihypertensive treatment is important in older and younger adults in terms of renal protection. In conclusion, the current study showed that systolic BP was associated with UAE in younger and older adults, HbA1c was associated with UAE in younger adults, and HOMA-R was associated with UAE only in older adults. Insulin resistance was more closely associated with UAE in older participants. The authors appreciate Hideki Shibayama, RT, and Yukiharu Watanabe, RT, for their technical assistance. Conflict of Interest: The authors have no conflict of interest to declare. This study was supported in part by a grant from the 21st Century Center of Excellence Project by the Japanese Ministry of Education, Culture, Sports, Science and Technology. Author Contributions: All authors contributed to study design. Hajime Haimoto, Satoshi Hoshide, and Kazuomi Kario: acquisition of participants and data. Hiroyuki Umegaki: analysis of data and preparation of manuscript. Sponsor's Role: None.