- Email: [email protected]
Risk factors for development of diabetes mellitus, hypertension and dyslipidemia
diabetes research and clinical practice 94 (2011) e15–e18
Contents lists available at ScienceDirect
Diabetes Research and Clinical Practice journ al h ome pa ge : www .elsevier.co m/lo cate/diabres
Brief report
Risk factors for development of diabetes mellitus, hypertension and dyslipidemia Michiaki Fukui a,*, Muhei Tanaka a, Hitoshi Toda b, Takafumi Senmaru a, Kazumi Sakabe a, Emi Ushigome a, Mai Asano a, Masahiro Yamazaki a, Goji Hasegawa a, Saeko Imai c, Naoto Nakamura a a Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan b Department of Internal Medicine, Sakazaki Clinic, Japan c Department of Clinical Nutrition, Faculty of Comprehensive Rehabilitation, Osaka Prefecture University, Japan
article info
abstract
Article history:
We investigated the risk factors for the development of diabetes mellitus, hypertension
Received 25 November 2010
and dyslipidemia simultaneously in a community-based observational cohort study
Received in revised form
(n = 4304). When hypertension or dyslipidemia was present at baseline, hazard ratio
29 June 2011
(95% CI) of developing diabetes mellitus at year 5 is 3.014 (2.131–4.264) or 2.112 (1.520–
Accepted 4 July 2011
2.936), respectively. # 2011 Elsevier Ireland Ltd. All rights reserved.
Published on line 30 July 2011 Keywords: Type 2 diabetes Hypertension Dyslipidemia Risk factor
1.
Introduction
Diabetes mellitus, hypertension and dyslipidemia are associated with an increased risk of cardiovascular disease (CVD) [1– 4]. Thus, identification of risk factors of diabetes mellitus, hypertension and dyslipidemia is important for the development of therapeutic approaches. To our knowledge, there are no reports investigating the risk factors for the development of diabetes mellitus, hypertension and dyslipidemia in the same cohort. Therefore, we investigated the risk factors for the development of diabetes mellitus, hypertension and dyslipidemia simultaneously in a Japanese population.
2.
Materials and methods
2.1.
Subjects
This community-based, observational cohort study was based on annual health examinations at Sakazaki Clinic in Kyoto. The annual examination consists of a detailed medical history; physical examination; blood examination, including blood cell count and biochemical markers. This report includes 4304 subjects (2530 men and 1774 women) who had at least 1 fasting blood examinations between 1998 and 2003 as the baseline examination of this study, and subse-
* Corresponding author. Tel.: +81 75 251 5505; fax: +81 75 252 3721. E-mail address: [email protected] (M. Fukui). 0168-8227/$ – see front matter # 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2011.07.006
e16
diabetes research and clinical practice 94 (2011) e15–e18
quently received at least 1 annual examination through 2009. The follow-up visits took place in the morning after overnight fasting. Demographic data, including sex, age, habits of smoking, drinking and exercise, and family history of diabetes and hypertension were recorded according to a self-administered questionnaire.
2.2. Definition of diabetes mellitus, hypertension and dyslipidemia >Diabetes mellitus was defined as fasting plasma glucose (FPG) (126 mg/dl, i.e. 7.0 mmol/l) or medication for diabetes mellitus. Hypertension was defined as raised blood pressure (systolic, 140 mm Hg or diastolic, 90 mm Hg) or medication for hypertension. Dyslipidemia was defined as raised total cholesterol concentration (220 mg/dl, i.e. 5.7 mmol/l), raised triglyceride concentration (150 mg/dl, i.e. 1.7 mmol/l) or reduced HDL cholesterol concentration (<40 mg/dl, i.e. 1.03 mmol/l) or medication for these lipid abnormalities. Approval for the study was obtained from the local Research Ethics Committee, and informed consent was obtained from all participants.
2.3.
relationship for the development of lifestyle-related disease between subjects with and without other lifestyle-related diseases at baseline. A P value <0.05 was considered statistically significant.
3.
Results
Baseline characteristics of the 4304 subjects (2530 men and 1774 women) in this study are shown in Table 1. Diabetes mellitus, hypertension and dyslipidemia were present in 151 (3.5%), 549 (12.8%) and 2042 (47.4%) subjects at baseline, respectively. Diabetes mellitus, hypertension and dyslipidemia developed in 262 (during 33,852 person-years of followup), 1095 (during 27,196 person-years of follow-up) and 1240 (during 12,899 person-years of follow-up) subjects, giving onsets of diabetes mellitus, hypertension and dyslipidemia rate of 77.4, 402.6, and 961.3 per 10,000 person-years, respectively. The results of multivariate Cox proportional
Statistical analysis
Means and frequencies of potential confounding variables were calculated. Multivariate Cox proportional hazards regression analyses were used to estimate the hazard ratios (HRs) and 95% confidence interval (CI) for the development of diabetes mellitus, hypertension and dyslipidemia using Stat View software (version 5.0; SAS Institute, Cary, NC). Covariates included age, sex, body mass index (BMI), systolic blood pressure, diastolic blood pressure, FPG, total cholesterol, triglyceride, HDL-cholesterol, r-GTP, uric acid, creatinine, white blood cell count, hemoglobin, habits of smoking, alcohol and exercise, family history of diabetes mellitus and hypertension. Kaplan–Meier curves were used to show the risk
Table 1 – Baseline characteristics of subjects. n Sex (male/female) Age (years) BMI (kg/m2) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Fasting plasma glucose (mmol/l) Total cholesterol (mmol/l) Triglyceride (mmol/l) HDL-cholesterol (mmol/l) r-GTP (IU/l) Uric acid (mg/dl) Creatinine (mg/dl) White blood cell (106/l) Hemoglobin (g/dl) Smoking (none/past/current) Alcohol (no/occasional/daily) Exercise (no/yes) Family history of DM (no/yes) Family history of HT (no/yes)
4304 2530/1774 48.2 10.1 22.6 3.0 118 17 71 11 5.16 1.00 5.43 0.88 1.03 (0.71–1.55) 1.60 0.41 39 42 5.3 1.4 0.8 0.2 5400 (4600–6400) 14.2 1.5 3077/557/670 1569/1238/1497 1813/2491 3201/1103 3066/1238
Data are mean SD, median (interquartile range) or number of patients. BMI, body mass index; GTP, glutamyltransferase; DM, diabetes mellitus; HT, hypertension.
Fig. 1 – Survival curves for the development of diabetes mellitus by the presence of hypertension (HT) and/or dyslipidemia (DL) at baseline (A), for the development of hypertension by the presence of diabetes mellitus (DM) and/or dyslipidemia (DL) at baseline (B), and for the development of dyslipidemia by the presence of diabetes mellitus (DM) and/or hypertension (HT) at baseline (C).
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diabetes research and clinical practice 94 (2011) e15–e18
Table 2 – Multivariate Cox proportional hazard regression model for the development of diabetes mellitus, hypertension and dyslipidemia. DM
Age Sex BMI Systolic BP Diastolic BP FPG Total cholesterol Triglyceride HDL-cholesterol r-GTP Uric acid Creatinine White blood cell Hemoglobin Smoking Alcohol Exercise FH of DM FH of HT
Hypertension
Dyslipidemia
HR (95% CI)
P
HR (95% CI)
P
HR (95% CI)
P
1.047 1.719 1.096 1.008 0.995 1.028 1.005 0.999 0.986 1.003 1.145 0.453 1.011 1.052 1.018 0.966 1.218 2.856 0.947
<0.0001 0.0253 <0.0001 0.3723 0.7079 <0.0001 0.0173 0.2218 0.0079 0.0060 0.0070 0.0761 0.0015 0.3966 0.8350 0.6476 0.1269 <0.0001 0.6901
1.034 1.130 1.039 1.046 1.044 1.003 0.999 1.000 0.996 1.000 1.056 1.039 1.003 0.964 1.004 1.115 0.961 0.935 1.501
<0.0001 0.2437 0.0001 <0.0001 <0.0001 0.0484 0.2955 0.8068 0.0932 0.9595 0.0301 0.8675 0.0704 0.1652 0.9271 0.0031 0.4896 0.3456 <0.0001
1.013 0.991 1.015 0.998 1.003 0.998 1.018 1.001 0.996 1.002 1.050 0.960 1.002 0.971 1.021 1.007 1.042 1.085 1.020
<0.0001 0.8993 0.0554 0.4466 0.4827 0.2076 <0.0001 0.0006 0.0048 0.0001 0.0100 0.8035 0.1819 0.1121 0.4697 0.7731 0.2993 0.0877 0.6565
(1.034–1.061) (1.069–2.763) (1.053–1.141) (0.991–1.024) (0.970–1.021) (1.025–1.031) (1.001–1.008) (0.998–1.001) (0.975–0.996) (1.001–1.005) (1.038–1.264) (.0189–1.087) (1.004–1.018) (0.935–1.184) (0.863–1.200) (0.831–1.122) (0.946–1.568) (2.247–3.630) (0.725–1.237)
(1.028–1.040) (0.920–1.388) (1.019–1.059) (1.037–1.054) (1.031–1.057) (1.000–1.005) (0.997–1.001) (0.999–1.001) (0.992–1.001) (0.999–1.001) (1.005–1.110) (0.662–1.630) (1.000–1.007) (0.914–1.015) (0.926–1.088) (1.037–1.199) (0.857–1.077) (0.812–1.076) (1.339–1.683)
(1.009–1.017) (0.863–1.138) (1.000–1.030) (0.992–1.004)) (0.994–1.012) (0.996–1.001) (1.017–1.019) (1.000–1.001) (0.992–0.999) (1.001–1.003) (1.012–1.089) (0.693–1.328) (0.999–1.004) (0.936–1.007) (0.965–1.081) (0.959–1.058) (0.964–1.127) (0.988–1.191) (0.936–1.111)
BMI, body mass index; BP, blood pressure; FPG, fasting plasma glucose; GTP, glutamyltransferase; FH, family history; DM, diabetes mellitus; HT, hypertension. Smoking status was defined as nonsmoker (=0), past smoker (=1), or current smoker (=2), drinking alcohol was defined as no alcohol consumption (=0), occasional alcohol consumption (=1), or daily alcohol consumption (=2), and habits of exercise was defined as no (=0) or yes (=1).
hazards regression analyses for the development of diabetes mellitus, hypertension and dyslipidemia are shown in Table 2. The results of Kaplan–Meier survival analyses are shown in Fig. 1. When hypertension or dyslipidemia was present at baseline, HR (95% CI) of developing diabetes at year 5 is 3.014 (2.131–4.264; P < 0.0001) or 2.112 (1.520–2.936; P < 0.0001), respectively. When diabetes or hypertension was present at baseline, HR (95% CI) of developing dyslipidemia at year 5 is 1.186 (0.762–1.847; P = 0.4502) or 1.202 (0.971–1.487; P = 0.0904), respectively. When diabetes or dyslipidemia was present at baseline, HR (95% CI) of developing hypertension at year 5 is 2.359 (1.700–3.724; P < 0.0001) or 1.525 (1.308–1.777; P < 0.0001), respectively.
4.
Discussion
To our knowledge, this is the first study to investigate the risk factors for the development of diabetes mellitus, hypertension and dyslipidemia simultaneously in a community-based observational cohort study. Although the pathogenesis of the lifestyle-related diseases is not well understood, it is likely that the condition represents a complex interplay between metabolic, genetic, and even environmental factors. Inflammation and oxidative stress have been proposed as common etiologic factors linking these processes and have likewise been implicated in the pathogenesis of lifestyle-related diseases. Uric acid and r-GTP are related to oxidative stress [5–10], and cytokines, including interleukin-6, are produced by activated WBC, it is also possible that an activation of immune system could increase WBC and therefore cytokine production [11,12], which may increase insulin resistance [11].
Kaplan–Meier survival analyses demonstrated that presence of hypertension and/or dyslipidemia at baseline was associated with the development of diabetes mellitus, presence of diabetes mellitus and/or dyslipidemia at baseline was associated with the development of hypertension, and presence of diabetes mellitus and/or hypertension at baseline was associated with the development of dyslipidemia. Presence of hypertension or dyslipidemia at baseline increased the risk of developing diabetes at year 5, and presence of diabetes or dyslipidemia at baseline increased the risk of developing hypertension at year 5. Diabetes mellitus, hypertension and dyslipidemia are cluster of interrelated risk factors robustly associated with the development of atherosclerotic CVD [13]. Our study has several limitations. We could not get the information about individual drug regimens concerning hypertension (e.g., angiotensin II receptor blocker or angiotensin converting enzyme inhibitor) and dyslipidemia (e.g., statin), which might affect the development of diabetes mellitus [14,15]. We could not get the information concerning diet, socioeconomic status, and family history of dyslipidemia, which might also affect the development of diabetes mellitus, hypertension and dyslipidemia. Clustering of diabetes mellitus, hypertension and dyslipidemia is much more associated with CVD. Therefore, we should pay much attention to reduce the risk factors of diabetes mellitus, hypertension and dyslipidemia.
Conflict of interest There are no conflicts of interest.
e18
diabetes research and clinical practice 94 (2011) e15–e18
Acknowledgement
[8]
We thank Ms. Mayumi Kitano, Sakazaki Clinic, for her assistance of data collection. [9]
references [10] [1] Ellis JL, Campos-Outcalt D. Cardiovascular disease risk factors in native Americans: a literature review. Am J Prev Med 1994;10:295–307. [2] Howard BV, Maqee MF. Diabetes and cardiovascular disease. Curr Atheroscler Rep 2000;2:476–81. [3] Mancia G. Blood pressure reduction and cardiovascular outcomes: past, present, and future. Am J Cardiol 2007;100:3J–9J. [4] Harris-Hooker S, Sanford GL. Lipids, lipoproteins and coronary heart disease in minority populations. Atherosclerosis 1994;108:S83–104. [5] Vasquez-Vivar J, Santos AM, Junqueria VB, Augusto O. Peroxynitrite-mediated formation of free radicals in human plasma: EPR detection of ascorbyl, albumin-thiyl and uric acid-derived free radicals. Biochem J 1996;314:869–76. [6] Anker SD, Leyva F, Poole-Wilson PA, Kox WJ, Stevenson JC, Coats AJ. Relation between serum uric acid and lower limb blood flow in patients with chronic heart failure. Heart 1997;78:39–43. [7] Leyva F, Anker S, Swan JW, Godsland IF, Wingrove CS, Chua TP. Serum uric acid as an index of impaired oxidative
[11]
[12]
[13]
[14]
[15]
metabolism in chronic heart failure. Eur Heart J 1997;18:858–65. Drozdz R, Parmentier C, Hachad H, Leroy P, Siest G, Wellman M. r-Glutamyltransferase dependent generation of reactive oxygen species from a glutathione/transferrin system. Free Radic Biol Med 1998;25:786–92. Lee DH, Gross M, Jacobs DR. The association of serum carotenoids and tocopherols with r-glutamyltransferase: the CARDIA study. Clin Chem 2004;50:582–8. Lee DH, Blomhoff R, Jacobs DR. Is serum rglutamyltransferase a marker of oxidative stress? Free Radic Res 2004;38:535–9. Pickup JC, Crook MA. Is type II diabetes mellitus a disease of the innate immune system? Diabetologia 1998;41: 1241–8. Pickup JC, Mattock MB, Chusney GD, Burt D. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 1997;40:1286–92. Hozawa A, Folsom AR, Sharrett AR, Chambless LE. Absolute and attributable risks of cardiovascular disease incidence in relation to optimal and borderline risk factors: comparison of African American with white subjects— Atherosclerosis Risk in Communities Study. Arch Intern Med 2007;167:573–9. Liou YS, Ma T, Tien L, Chien C, Chou P, Jong GP. Long-term effects of antihypertensive drugs on the risk of new-onset diabetes in elderly Taiwanese hypertensives. Int Heart J 2008;49:205–11. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials. Lancet 2010;375:735–42.
Contents lists available at ScienceDirect
Diabetes Research and Clinical Practice journ al h ome pa ge : www .elsevier.co m/lo cate/diabres
Brief report
Risk factors for development of diabetes mellitus, hypertension and dyslipidemia Michiaki Fukui a,*, Muhei Tanaka a, Hitoshi Toda b, Takafumi Senmaru a, Kazumi Sakabe a, Emi Ushigome a, Mai Asano a, Masahiro Yamazaki a, Goji Hasegawa a, Saeko Imai c, Naoto Nakamura a a Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan b Department of Internal Medicine, Sakazaki Clinic, Japan c Department of Clinical Nutrition, Faculty of Comprehensive Rehabilitation, Osaka Prefecture University, Japan
article info
abstract
Article history:
We investigated the risk factors for the development of diabetes mellitus, hypertension
Received 25 November 2010
and dyslipidemia simultaneously in a community-based observational cohort study
Received in revised form
(n = 4304). When hypertension or dyslipidemia was present at baseline, hazard ratio
29 June 2011
(95% CI) of developing diabetes mellitus at year 5 is 3.014 (2.131–4.264) or 2.112 (1.520–
Accepted 4 July 2011
2.936), respectively. # 2011 Elsevier Ireland Ltd. All rights reserved.
Published on line 30 July 2011 Keywords: Type 2 diabetes Hypertension Dyslipidemia Risk factor
1.
Introduction
Diabetes mellitus, hypertension and dyslipidemia are associated with an increased risk of cardiovascular disease (CVD) [1– 4]. Thus, identification of risk factors of diabetes mellitus, hypertension and dyslipidemia is important for the development of therapeutic approaches. To our knowledge, there are no reports investigating the risk factors for the development of diabetes mellitus, hypertension and dyslipidemia in the same cohort. Therefore, we investigated the risk factors for the development of diabetes mellitus, hypertension and dyslipidemia simultaneously in a Japanese population.
2.
Materials and methods
2.1.
Subjects
This community-based, observational cohort study was based on annual health examinations at Sakazaki Clinic in Kyoto. The annual examination consists of a detailed medical history; physical examination; blood examination, including blood cell count and biochemical markers. This report includes 4304 subjects (2530 men and 1774 women) who had at least 1 fasting blood examinations between 1998 and 2003 as the baseline examination of this study, and subse-
* Corresponding author. Tel.: +81 75 251 5505; fax: +81 75 252 3721. E-mail address: [email protected] (M. Fukui). 0168-8227/$ – see front matter # 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2011.07.006
e16
diabetes research and clinical practice 94 (2011) e15–e18
quently received at least 1 annual examination through 2009. The follow-up visits took place in the morning after overnight fasting. Demographic data, including sex, age, habits of smoking, drinking and exercise, and family history of diabetes and hypertension were recorded according to a self-administered questionnaire.
2.2. Definition of diabetes mellitus, hypertension and dyslipidemia >Diabetes mellitus was defined as fasting plasma glucose (FPG) (126 mg/dl, i.e. 7.0 mmol/l) or medication for diabetes mellitus. Hypertension was defined as raised blood pressure (systolic, 140 mm Hg or diastolic, 90 mm Hg) or medication for hypertension. Dyslipidemia was defined as raised total cholesterol concentration (220 mg/dl, i.e. 5.7 mmol/l), raised triglyceride concentration (150 mg/dl, i.e. 1.7 mmol/l) or reduced HDL cholesterol concentration (<40 mg/dl, i.e. 1.03 mmol/l) or medication for these lipid abnormalities. Approval for the study was obtained from the local Research Ethics Committee, and informed consent was obtained from all participants.
2.3.
relationship for the development of lifestyle-related disease between subjects with and without other lifestyle-related diseases at baseline. A P value <0.05 was considered statistically significant.
3.
Results
Baseline characteristics of the 4304 subjects (2530 men and 1774 women) in this study are shown in Table 1. Diabetes mellitus, hypertension and dyslipidemia were present in 151 (3.5%), 549 (12.8%) and 2042 (47.4%) subjects at baseline, respectively. Diabetes mellitus, hypertension and dyslipidemia developed in 262 (during 33,852 person-years of followup), 1095 (during 27,196 person-years of follow-up) and 1240 (during 12,899 person-years of follow-up) subjects, giving onsets of diabetes mellitus, hypertension and dyslipidemia rate of 77.4, 402.6, and 961.3 per 10,000 person-years, respectively. The results of multivariate Cox proportional
Statistical analysis
Means and frequencies of potential confounding variables were calculated. Multivariate Cox proportional hazards regression analyses were used to estimate the hazard ratios (HRs) and 95% confidence interval (CI) for the development of diabetes mellitus, hypertension and dyslipidemia using Stat View software (version 5.0; SAS Institute, Cary, NC). Covariates included age, sex, body mass index (BMI), systolic blood pressure, diastolic blood pressure, FPG, total cholesterol, triglyceride, HDL-cholesterol, r-GTP, uric acid, creatinine, white blood cell count, hemoglobin, habits of smoking, alcohol and exercise, family history of diabetes mellitus and hypertension. Kaplan–Meier curves were used to show the risk
Table 1 – Baseline characteristics of subjects. n Sex (male/female) Age (years) BMI (kg/m2) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg) Fasting plasma glucose (mmol/l) Total cholesterol (mmol/l) Triglyceride (mmol/l) HDL-cholesterol (mmol/l) r-GTP (IU/l) Uric acid (mg/dl) Creatinine (mg/dl) White blood cell (106/l) Hemoglobin (g/dl) Smoking (none/past/current) Alcohol (no/occasional/daily) Exercise (no/yes) Family history of DM (no/yes) Family history of HT (no/yes)
4304 2530/1774 48.2 10.1 22.6 3.0 118 17 71 11 5.16 1.00 5.43 0.88 1.03 (0.71–1.55) 1.60 0.41 39 42 5.3 1.4 0.8 0.2 5400 (4600–6400) 14.2 1.5 3077/557/670 1569/1238/1497 1813/2491 3201/1103 3066/1238
Data are mean SD, median (interquartile range) or number of patients. BMI, body mass index; GTP, glutamyltransferase; DM, diabetes mellitus; HT, hypertension.
Fig. 1 – Survival curves for the development of diabetes mellitus by the presence of hypertension (HT) and/or dyslipidemia (DL) at baseline (A), for the development of hypertension by the presence of diabetes mellitus (DM) and/or dyslipidemia (DL) at baseline (B), and for the development of dyslipidemia by the presence of diabetes mellitus (DM) and/or hypertension (HT) at baseline (C).
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diabetes research and clinical practice 94 (2011) e15–e18
Table 2 – Multivariate Cox proportional hazard regression model for the development of diabetes mellitus, hypertension and dyslipidemia. DM
Age Sex BMI Systolic BP Diastolic BP FPG Total cholesterol Triglyceride HDL-cholesterol r-GTP Uric acid Creatinine White blood cell Hemoglobin Smoking Alcohol Exercise FH of DM FH of HT
Hypertension
Dyslipidemia
HR (95% CI)
P
HR (95% CI)
P
HR (95% CI)
P
1.047 1.719 1.096 1.008 0.995 1.028 1.005 0.999 0.986 1.003 1.145 0.453 1.011 1.052 1.018 0.966 1.218 2.856 0.947
<0.0001 0.0253 <0.0001 0.3723 0.7079 <0.0001 0.0173 0.2218 0.0079 0.0060 0.0070 0.0761 0.0015 0.3966 0.8350 0.6476 0.1269 <0.0001 0.6901
1.034 1.130 1.039 1.046 1.044 1.003 0.999 1.000 0.996 1.000 1.056 1.039 1.003 0.964 1.004 1.115 0.961 0.935 1.501
<0.0001 0.2437 0.0001 <0.0001 <0.0001 0.0484 0.2955 0.8068 0.0932 0.9595 0.0301 0.8675 0.0704 0.1652 0.9271 0.0031 0.4896 0.3456 <0.0001
1.013 0.991 1.015 0.998 1.003 0.998 1.018 1.001 0.996 1.002 1.050 0.960 1.002 0.971 1.021 1.007 1.042 1.085 1.020
<0.0001 0.8993 0.0554 0.4466 0.4827 0.2076 <0.0001 0.0006 0.0048 0.0001 0.0100 0.8035 0.1819 0.1121 0.4697 0.7731 0.2993 0.0877 0.6565
(1.034–1.061) (1.069–2.763) (1.053–1.141) (0.991–1.024) (0.970–1.021) (1.025–1.031) (1.001–1.008) (0.998–1.001) (0.975–0.996) (1.001–1.005) (1.038–1.264) (.0189–1.087) (1.004–1.018) (0.935–1.184) (0.863–1.200) (0.831–1.122) (0.946–1.568) (2.247–3.630) (0.725–1.237)
(1.028–1.040) (0.920–1.388) (1.019–1.059) (1.037–1.054) (1.031–1.057) (1.000–1.005) (0.997–1.001) (0.999–1.001) (0.992–1.001) (0.999–1.001) (1.005–1.110) (0.662–1.630) (1.000–1.007) (0.914–1.015) (0.926–1.088) (1.037–1.199) (0.857–1.077) (0.812–1.076) (1.339–1.683)
(1.009–1.017) (0.863–1.138) (1.000–1.030) (0.992–1.004)) (0.994–1.012) (0.996–1.001) (1.017–1.019) (1.000–1.001) (0.992–0.999) (1.001–1.003) (1.012–1.089) (0.693–1.328) (0.999–1.004) (0.936–1.007) (0.965–1.081) (0.959–1.058) (0.964–1.127) (0.988–1.191) (0.936–1.111)
BMI, body mass index; BP, blood pressure; FPG, fasting plasma glucose; GTP, glutamyltransferase; FH, family history; DM, diabetes mellitus; HT, hypertension. Smoking status was defined as nonsmoker (=0), past smoker (=1), or current smoker (=2), drinking alcohol was defined as no alcohol consumption (=0), occasional alcohol consumption (=1), or daily alcohol consumption (=2), and habits of exercise was defined as no (=0) or yes (=1).
hazards regression analyses for the development of diabetes mellitus, hypertension and dyslipidemia are shown in Table 2. The results of Kaplan–Meier survival analyses are shown in Fig. 1. When hypertension or dyslipidemia was present at baseline, HR (95% CI) of developing diabetes at year 5 is 3.014 (2.131–4.264; P < 0.0001) or 2.112 (1.520–2.936; P < 0.0001), respectively. When diabetes or hypertension was present at baseline, HR (95% CI) of developing dyslipidemia at year 5 is 1.186 (0.762–1.847; P = 0.4502) or 1.202 (0.971–1.487; P = 0.0904), respectively. When diabetes or dyslipidemia was present at baseline, HR (95% CI) of developing hypertension at year 5 is 2.359 (1.700–3.724; P < 0.0001) or 1.525 (1.308–1.777; P < 0.0001), respectively.
4.
Discussion
To our knowledge, this is the first study to investigate the risk factors for the development of diabetes mellitus, hypertension and dyslipidemia simultaneously in a community-based observational cohort study. Although the pathogenesis of the lifestyle-related diseases is not well understood, it is likely that the condition represents a complex interplay between metabolic, genetic, and even environmental factors. Inflammation and oxidative stress have been proposed as common etiologic factors linking these processes and have likewise been implicated in the pathogenesis of lifestyle-related diseases. Uric acid and r-GTP are related to oxidative stress [5–10], and cytokines, including interleukin-6, are produced by activated WBC, it is also possible that an activation of immune system could increase WBC and therefore cytokine production [11,12], which may increase insulin resistance [11].
Kaplan–Meier survival analyses demonstrated that presence of hypertension and/or dyslipidemia at baseline was associated with the development of diabetes mellitus, presence of diabetes mellitus and/or dyslipidemia at baseline was associated with the development of hypertension, and presence of diabetes mellitus and/or hypertension at baseline was associated with the development of dyslipidemia. Presence of hypertension or dyslipidemia at baseline increased the risk of developing diabetes at year 5, and presence of diabetes or dyslipidemia at baseline increased the risk of developing hypertension at year 5. Diabetes mellitus, hypertension and dyslipidemia are cluster of interrelated risk factors robustly associated with the development of atherosclerotic CVD [13]. Our study has several limitations. We could not get the information about individual drug regimens concerning hypertension (e.g., angiotensin II receptor blocker or angiotensin converting enzyme inhibitor) and dyslipidemia (e.g., statin), which might affect the development of diabetes mellitus [14,15]. We could not get the information concerning diet, socioeconomic status, and family history of dyslipidemia, which might also affect the development of diabetes mellitus, hypertension and dyslipidemia. Clustering of diabetes mellitus, hypertension and dyslipidemia is much more associated with CVD. Therefore, we should pay much attention to reduce the risk factors of diabetes mellitus, hypertension and dyslipidemia.
Conflict of interest There are no conflicts of interest.
e18
diabetes research and clinical practice 94 (2011) e15–e18
Acknowledgement
[8]
We thank Ms. Mayumi Kitano, Sakazaki Clinic, for her assistance of data collection. [9]
references [10] [1] Ellis JL, Campos-Outcalt D. Cardiovascular disease risk factors in native Americans: a literature review. Am J Prev Med 1994;10:295–307. [2] Howard BV, Maqee MF. Diabetes and cardiovascular disease. Curr Atheroscler Rep 2000;2:476–81. [3] Mancia G. Blood pressure reduction and cardiovascular outcomes: past, present, and future. Am J Cardiol 2007;100:3J–9J. [4] Harris-Hooker S, Sanford GL. Lipids, lipoproteins and coronary heart disease in minority populations. Atherosclerosis 1994;108:S83–104. [5] Vasquez-Vivar J, Santos AM, Junqueria VB, Augusto O. Peroxynitrite-mediated formation of free radicals in human plasma: EPR detection of ascorbyl, albumin-thiyl and uric acid-derived free radicals. Biochem J 1996;314:869–76. [6] Anker SD, Leyva F, Poole-Wilson PA, Kox WJ, Stevenson JC, Coats AJ. Relation between serum uric acid and lower limb blood flow in patients with chronic heart failure. Heart 1997;78:39–43. [7] Leyva F, Anker S, Swan JW, Godsland IF, Wingrove CS, Chua TP. Serum uric acid as an index of impaired oxidative
[11]
[12]
[13]
[14]
[15]
metabolism in chronic heart failure. Eur Heart J 1997;18:858–65. Drozdz R, Parmentier C, Hachad H, Leroy P, Siest G, Wellman M. r-Glutamyltransferase dependent generation of reactive oxygen species from a glutathione/transferrin system. Free Radic Biol Med 1998;25:786–92. Lee DH, Gross M, Jacobs DR. The association of serum carotenoids and tocopherols with r-glutamyltransferase: the CARDIA study. Clin Chem 2004;50:582–8. Lee DH, Blomhoff R, Jacobs DR. Is serum rglutamyltransferase a marker of oxidative stress? Free Radic Res 2004;38:535–9. Pickup JC, Crook MA. Is type II diabetes mellitus a disease of the innate immune system? Diabetologia 1998;41: 1241–8. Pickup JC, Mattock MB, Chusney GD, Burt D. NIDDM as a disease of the innate immune system: association of acute-phase reactants and interleukin-6 with metabolic syndrome X. Diabetologia 1997;40:1286–92. Hozawa A, Folsom AR, Sharrett AR, Chambless LE. Absolute and attributable risks of cardiovascular disease incidence in relation to optimal and borderline risk factors: comparison of African American with white subjects— Atherosclerosis Risk in Communities Study. Arch Intern Med 2007;167:573–9. Liou YS, Ma T, Tien L, Chien C, Chou P, Jong GP. Long-term effects of antihypertensive drugs on the risk of new-onset diabetes in elderly Taiwanese hypertensives. Int Heart J 2008;49:205–11. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials. Lancet 2010;375:735–42.