Atotal of 5,174 Japanese menwere included in a cross-sectional study to examine the relationship between the glycated hemoglobin (HbAlc) level and the ... weight mayreduce the prevalence of proteinuria in Japanese men. ... justing for age and body-mass index. ... Thegroup with both proteinuria and hematuria showed.
ORIGINAL
ARTICLE
Relationship between Glycosylated Hemoglobin and the Prevalence of Proteinuria in Japanese Men
Yoshiaki Hashimoto, Azusa Futamura, Nobuko Watanabe, Masako Togo*, Hiroaki Sato*, Masumi Hara*, Kazuhisa Tsukamoto*, Satoshi Kimura* and Kazuhiko Nakahara A total of 5,174 Japanese men were included in a cross-sectional study to examine the relationship between the glycated hemoglobin (HbAlc) level and the prevalence of proteinuria as determined using a reagent strip. The prevalence of proteinuria rose significantly at HbAlc levels above 5.9% , whereas no relationship was observed at HbAlc levels below 5.9%. Multiple logistic regression analysis showed that blood pressure and a family history of diabetes were independent factors associated with proteinuria in subjects with a HbAlcbelow 5.9% whowere not under medication for diabetes. In contrast, HbAlc, obesity and smoking were associated with proteinuria in subjects whowere under medication for diabetes and/or have a HbAlcabove 5.9%. These findings suggest that maintaining a HbAlc level below 5.9%, non-smoking and a standard body weight may reduce the prevalence of proteinuria in Japanese men. Healthy life-style and standard body weight are especially important for subjects with a family history of diabetes. (Internal Medicine 38: 6-ll, 1999) Key words: glycated hemoglobin (HbAlc), obesity,
Introduction
family history of diabetes,
smoking, life-style
Subjects and Methods
Prospective studies involving patients with type 2 diabetes have indicated that proteinuria is significantly associated with mortality due to cerebro-cardiovascular and renal diseases in Japan (1) and coronary heart disease in Western countries (24). Proteinuria is related to glycemia (5, 6) and blood pressure (7, 8), and improved control of these factors has been shownto retard the development of nephropathy in type 1 and type 2 diabetes. Most studies investigating the factors associated with proteinuria have involved only diabetic subjects. Recent studies have indicated that a high prevalence of microalbuminuria is related not only to type 1 and type 2 diabetes, but also to a family history of diabetes (1 1), and a prediabetic state, such as impaired glucose tolerance (9-1 1). However, there has been no report on the relation between the degree of plasma glucose levels and the prevalence of albuminuria in the general population. The present study was carried out to assess the prevalence of proteinuria
in relation
to the glycated
hemoglobin
(HbAlc)
level and the factors associated with proteinuria in a cohort of Japanese male workers including diabetics and nondiabetics. surveyed We 5,174 Japanese men aged 22-65 who worked
at during1995-1996. medical hol records. ered diagnosed alarge as history, consumption positive company current was history Family at if diabetic had and Information m obtained of one least hypertensiveby or edication, undergone regarding questionnaire by diabetes parentor familyhistory, smoking hypertensionwas or one ap hysical hysician. checkup astatus sibling nd/ormedical past alcoand considbeen had Body chromatography ing, or liquid HbAlcwas HbAlc>5.9%and/ortreatment weight4.3-5.8%. not but longer. wbAlc measured shoes.Blood H levels as A while was were (BML, h igh for wearing drawnafter measured T level HbAlc diabetes. okyo). lightweight fasting high-performance by reference The defined was for range b Hypertension y was clothhours 12 of
definedwere blood tensive (in smokers as pressure drugs.The kilograms) defined diastolic >140 adivided those defined s blood and/ortreatment mmHg body-mass b awho those sy who pressure index (in height smoked mmHgsmoking >90 with calculated was meters) time the at quit had and/orsystolic anti-hyperas squared. the of weight Smokers study.Exbefore
examination. Proteinuria
and hematuria were defined as a U
From the Department of Clinical Laboratory Medicine and *the First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Tokyo Received for publication May 13, 1998; Accepted for publication October 20, 1998 Reprint requests should be addressed to Dr. Yoshiaki Hashimoto, the Department of Clinical Laboratory Medicine, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku,
Tokyo 1 13-8655
6
7-3-1
Internal
Medicine Vol. 38, No. 1 (January 1999)
HbAlc and Proteinuria riflet (7E) (Kyoto Dai-ichi Kagaku, Kyoto) reading of at least 1+ (0.3-0.6 g/1) and at least 1+ (hemoglobin concentration of 0.6-1 mg/1) or greater, respectively, for a fasting morning spot urine sample. Plasma triglyceride (Dai-ichi Kagaku, Tokyo), cholesterol (Wako Pure Chemical, Osaka), HDL-C (Dai-ichi Kagaku) and uric acid (Dai-ichi Kagaku) were measured by enzymatic methodsusing commercialkits. This study was approved by the Ethics Committee of the workers' company. Statistical
analysis
Data analysis
was performed using Statistical
System (SAS Institute,
Analysis
Cary, NC). The results for continuous
the body-mass index were further taken into account, triglyceride did not differ significantly between the two groups (Table 2). In addition, the group with proteinuria alone had a higher rate of treatment for diabetes, hypertension and hyperuricemia, and a family history of diabetes (Table 1). On the otherhand, the group with hematuria alone did not differ from the normal urine group except on meanage, alcohol consumption and smoking status. The group with both proteinuria and hematuria showed similar clinical characteristics to those of the group with proteinuria alone except that the meanHbAlclevel was not higher than the group with normal urine. The prevalence ofproteinuria without hematuria was approximately four times higher in subjects with high HbAlc than in those with normal HbAlc (Table 3). The prevalence of hematuria without proteinuria and that of both proteinuria and hematuria did not differ significantly between the two groups with respect to the HbAlc level.
variables represent the meanor mean± SD. Analysis of variance (ANOVA)and the two-tailed Fisher' s exact test were used to compare group means and group proportions, respectively. The SASgeneralized linear regression model was used to assess significant differences between group means, after ad- Table 4 shows the relationship between the prevalence of justing for age and body-mass index. The SAS multiple logistic proteinuria alone and the HbAlc level or blood pressure. There regression modelwasused to examinethe variables associated was a significantly higher prevalence of proteinuria in subjects with a HbAlc level above 5.9%, compared to subjects with a with proteinuria. HbAlc level below 4.5%. A similar relationship was obtained Results when the prevalence was adjusted for blood pressure. The prevalence of proteinuria increased in a blood pressure-depenThe subjects were divided into four groups according to the dent fashion at levels above 90 mmHgfor diastolic pressure appearance of proteinuria and hematuria. The group with pro- and above 140 mmHgfor systolic pressure. Next, we assessed the variables associated with proteinuria teinuria alone had a higherandbody-mass index, compared blood pressure, HbAlc, total cholesterol triglyceride, to the by multiple logistic regression analysis (Table 5). For the group with neither proteinuria nor hematuria (Table 1). These subjects with a normal HbAlc level, a family history of diabetes differences were observed even when age was adjusted be- was the most important factor with an odds ratio of 3.16. tween the two groups (Table 2). However, when differences in Hypertensionwas also significantly correlated with an odds Table 1. Characteristics Protei nuri a H em a t ur i a n A g e (y e a rs) Body-mass index (kg/m ) S y s t o li c b l o od p r e s s u re ( m m H g ) D i as t o l i c b lo o d p r e ss u r e ( mm H g ) H b A lc (% ) T o ta l c h o le ste ro l (m g /d l) HDL -C (mg/ dl) T rig ly c e rid e (m g /d l) U ri c a ci d ( mg / dl ) A lc o h o l (m l/w e e k ) E x- a n d c u r r e nt s m ok e r s (% ) F am il y h i st o ry o f d i ab et e s ( %) Fa m i ly hi s t or y of hy p e rt e ns i o n ( %) M ed i ca t i on fo r di a b et e s ( % ) M ed i c a ti o n f o r hy p e r te n s i on ( % ) M e di c a t i on f o r h y p e r ur i c e m i a ( % ) M e di c a ti o n fo r h y pe r l ip i d e mi a ( % )
of Subjects with Respect to Proteinuria and Hematuria No No 4 87 3 42.5 +8.4 23 .0 +2. 8 12 2 . 8 ｱ 1 3 . 0 78/7+ 10.6 5 .1 0+0 .5 4 19 9. 7 + 33 . 2 5 4 .6 ｱ 1 3. 5 131 .2+ 96 .2 5 .9 2+1 .1 7 17 8 + 164 59 . 6 8 .8 22 . 4 0. 7 4. 3 1. 9 1. 7
Y es N o 99 43 .9+ 7. 2 24 . 0 + 3. 2 ** 1 2 9. 1 ｱ 1 5 .6 * * 8 4 . 9 ｱ 1 2 .2 * * 5.45ｱ 1. 08** 2 14.2+ 38.6 ** 54.0+ 13.5 152.5ｱ 10 2.9* 6 .1 3 ｱ 1 .3 6 17 8 + 1 5 9 6 3 .6 2 0. 2 * 2 0. 2 3. 0 * 5. 2 * * 5.1* 3.0
N o Y es 180 46 . 2 +6 .6 * * 2 2 .7 + 2 .9 1 2 2. 4 + 13 . 1 79 .6+ ll .1 5 .1 5 +0 .5 6 198.0 + 29.3 55 .5ｱ 14 .0 127.3 + 76.2 5. 9 2+ 1. 22 2 22 + 177 * * 7 0. 0 ** 7.8 22.8 0. 6 5.0 2. 2 2. 2
Y es Y es 22 4 3 .6 +7 .6 2 3 . 0 +2 . 5 13 1 . 5+ 1 8. 7 * * 87. 5+ 14 .4* * 5 .0 7+ 0. 5 9 210.2 + 44.9 5 3.2 ｱ ll. 8 148.6 + 99.0 5 . 91 ｱ 1. 18 186 + 185 5 4. 5 13.6 31.8 13.6 4. 6
p+
8.0
3 0 1 3 .3 * * 30.3 **
37 10 . 8* 2 5 . 4 **
15 0- 15 9
> 160
+ ad ju st ed f or sy st ol ic a nd di as to li c bl oo d pr ess ur e.
S ys t ol ic bl o od p re s s u re (m m H g )
< 110
1 10 - 1 19
120 - 129
130 - 139
14 0- 14 9
P re v a le n c e (% )
741 1 .3
1, 2 8 8 1 .2
1, 5 0 8 1 .5
1, 16 6 2 .4
330 3 .6 *
Di a st o li c b lo o d pr e s su r e ( m m H g)
1
44 9 .0 *
0 0 17 1 6 .4 * *
*p 22 7 > 2 2 7 /< 2 2 7 S m o k in g Ex a nd cu r r en t / no F am i ly hi s to r y o f D ia b e te s (Y e s/N o ) H y p erte n sio n (Y e s /N o )
O d d s r atio 0 .9 2 (0 .7 0 - 1 .2 1 )
S ub j ec t s w i th a h i g h H b A lc l e ve l
Su b je c ts w it h a n o r ma l H b A l c l e v e l O d d s ra tio 0 .5 5 1 0 . 48 6
0 .9 3 (0 .6 9 - 1 .2 4 )
O d d s ra tio 0 .6 0 6 0.784
1 0 .8 1 (0 .3 9 - 1 .7 0 ) 0 .5 8 4 0 .7 8 (0 .3 7 - 1 .6 3 ) 0 .4 8 0 0.77 (0.37- 1.61) 0.480 1. 2 3 (0 .6 2 - 2 .4 6 ) 0 .5 5 8 1. 5 2 (0 .9 6 - 2 .4 0 ) 0 .0 7 5 2. 74( 1.7 4-4 .30)
