- Email: [email protected]
Epidemiologic study of type 2 diabetes in Taiwan
Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59 www.elsevier.com/locate/diabres
Epidemiologic study of type 2 diabetes in Taiwan Chih-Jen Chang a, Feng-Hwa Lu a, Yi-Ching Yang a, Jin-Shang Wu a, Ta-Jen Wu b, Muh-Shy Chen c, Lee-Ming Chuang d, Tong-Yuan Tai d,* a b
Department of Family Medicine, College of Medicine, National Cheng Kung Uni6ersity, Taipei, Taiwan, ROC Department of Internal Medicine, College of Medicine, National Cheng Kung Uni6ersity, Taipei, Taiwan, ROC c Department of Ophthalmology, College of Medicine, National Taiwan Uni6ersity, Taipei, Taiwan, ROC d Department of Internal Medicine, College of Medicine, National Taiwan Uni6ersity, Taipei, Taiwan, ROC
Abstract Diabetes mellitus (DM) in adults is a global health problem, although its prevalence varies widely between different populations and the rate has generally increased worldwide. In Taiwan, the mortality rate from DM has almost doubled over the past 10 years. The prevalence of DM in Taiwan was established between 1985 and 1996 and the rates were between 4.9 and 9.2%. The prevalence of impaired glucose tolerance (IGT) was 15.5% (men 15% and women 15.9%). The prevalence of DM and IGT increased significantly with age for both genders. The significant factors associated with newly diagnosed DM were age, BMI, family history of DM, systolic blood pressure (hypertension), physical activity and serum triglyceride levels. The prevalence of large vessel disease (LVD) in DM and non-diabetic subjects were 20.0 and 12.9%, respectively. Among diabetics, 15.8% had ischemic heart disease (IHD), 1.7% leg vessel disease (leg VD), and 2.5% stroke. In non-diabetics, the prevalence of the aforementioned macroangiopathies were 11.5, 0.2 and 1.2%, respectively. The diabetics had a significantly higher prevalence of macrovascular disease than non-diabetic subjects. The most significantly associated with the LVD was serum cholesterol levels. Serum cholesterol and HbA1c were significantly associated with the development of IHD. Cigarette smoking and female gender were significantly associated with the leg VD. The prevalence of diabetic retinopathy (DR) was 35.0%. (background DR 30%, preproliferative DR 2.8% and proliferative DR 2.2%, respectively.) The prevalence of DR for previously and newly diagnosed diabetics were 45.2 and 28.3% (men 42.8 vs. 33.3% and women 47.5 vs. 24.8%), respectively. From multiple logistic regression analysis, duration of DM was the most important risk factor related to DR. Diabetic subjects treated with insulin had a higher risk of developing retinopathy than those treated with dietary control. The prevalence of nephropathy and neuropathy were 12.9 and 23.5%, respectively. For those patients with and those without nephropathy and neuropathy, the duration of DM, percentage of insulin treatment, percentage of hypertension, and fasting plasma glucose were significantly different. Diabetic duration, hypertension, insulin treatment and glycemic control consistently correlated with nephropathy and neuropathy. In conclusion, the prevalence of DM in Taiwan was between 4.9 and 9.2%, and the prevalence of IGT was 15.5%. The possible risk factors of newly diagnosed diabetes were age, family history of DM, BMI, SBP (hypertension), physical activity and triglyceride levels. Diabetes in Chinese subjects share many characteristics
* Corresponding author. Tel.: + 886-2-23222169; fax: + 886-2-23222169. E-mail address: [email protected] (T.-Y. Tai). 0168-8227/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 8 - 8 2 2 7 ( 0 0 ) 0 0 1 7 9 - 0
S50
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
similar to other Asian populations. The burden imposed by the chronic complications of diabetes is massive. In Taiwan, the mortality rates from DM have increased greatly over the past 10 years. Reduction of the modificable risk factors such as BMI, hypertenion and dyslipidemia, and increase of physical activity and good glycemic control through public health efforts may help to reduce the risk of DM and its chronic complications. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Epidemiology; Prevalence; Risk factor; Chinese, Type 2 (non-insulin-dependent) diabetes
1. Introduction Diabetes mellitus (DM) in adults is a global health problem. Although its prevalence varies widely between different populations from low ( B 3%), moderate (3 – 10%), high (11 – 20%) to extremely high (\20%), the rate has generally increased worldwide [1]. The remarkable economic achievement in the last 30 years has resulted in a great improvement in living standards and prolongation of life expectancy in Taiwan. In Taiwan, the mortality rate from diabetes mellitus has almost doubled over the past 10 years and its ranking in the leading causes of death has increased: one twelfth in 1982, one eighth in 1983, one seventh in 1984 and one fifth since 1987 [2]. It has become one of the major health problems of the country.
2. Material and methods
2.1. Study subjects 2.1.1. Northern Taiwan 2.1.1.1. Taipei Study (1985). This survey was conducted from November 1985 to June 1986. Eight of the 78 subdistricts of the Ta-An precinct were randomly selected. Five villages evenly distributed over the island were also randomly selected. The total number of subjects aged 40 years or older who underwent the survey in Taipei City was 4272 and that of the five villages was 7206, with a response rate of 65.3 and 72.0%, respectively. Among the 715 subjects, 608 subjects, including 225 newly diagnosed and 383 previously diagnosed, participated in a further study.
2.1.1.2. Kin-Hu, Kinmen. The study subjects were those \ 30 years of age in Kin-Hu township. According to household registration, 4097 eligible residents were invited to the community center to attend the screening test from January to February 1991. 2.1.1.3. Ann-Lo, Keelung. This survey was performed between July 1988 and June 1990 in the Ann-Lo district of Keelung in northern. The response rate for a total of 9087 eligible subjects was 67.4%. 2.1.1.4. Taipei Study (1978). A total 217 diabetic patients (110 men and 107 women) who were discovered during 1978 survey for adult diabetics in the Cheng-Chung district of Taipei City. They were examined for diabetic retinopathy, neuropathy and nephropathy. 2.1.2. Southern Taiwan The study was performed in Tainan City of southern Taiwan. The sampling scheme was a three-stage process that generated a stratified systemic cluster sample of households throughout the city. Of the 2416 eligible people, 1638 (67.8%) participated in the study. 2.2. Methods With the help of specially trained assistants, all subjects were interviewed according to a structured questionnaire, while included demographic information, past medical history of diabetes and hypertension, current smoking habit, medication history, physical activity, and family history of DM and hypertension. Obesity was defined as a BMI\ 27 for men and \ 25 for women [3] or
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
BMI \ 30 for both genders [4]. Overnight fasting serum and plasma samples were kept frozen at −20°C until analysis. Serum total cholesterol and triglyceride were measured enzymatically using automated methods. Diabetes mellitus was diagnosed according to the World Health Organization (WHO) criteria [5]. Hypertension was deemed present when the systolic pressure \ 160 mmHg, or when the diastolic pressure \ 95 mmHg or a history of hypertension and currently receiving treatment [6]. Physical activity and the exercise status as were prescribed previously [4]. Total physical activity assessment was calculated in MET-hours per week over all activities for the past year [7]. Subjects who smoked less than 100 cigarettes in their lifetime were classified as nonsmokers, more than 100 cigarettes but had stopped before the examination were classified as ex-smokers, and smoked at the time of the interview were classified as current smokers. According to the protocol of the WHO Multinational Study on Vascular Disease in Diabetes [8], LVD, including stroke, IHD, and leg VD, were investigated. The ophthalmic examinations were performed with direct and indirect ophthalmoscopy after dilating the pupils with tropicamide 1% and phenylepinephrine 10%. The retinopathy status was divided into normal; background, preproliferative and proliferative DR. Ophthalmoscopy was performed in 527 of the diabetic subjects. Urinalysis for screening of clinical proteinuria was conducted at least three times in a 1-month period. Diabetic nephropathy was defined as a positive result on a dipstick test, approximately equivalent to 300 – 500 mg/l of urine. Neuropathy was confirmed if the motor nerves showed abnormal conduction velocity [9]. The statistical significance was assessed by using the Student’s t-test and the chi-square test. Correlation coefficients were estimated by Spearman’s method and multiple logistic regression analysis was also performed to evaluate multivariate-adjusted associations between related factors and diabetic macrovascular and microvascular diseases.
S51
3. Results The prevalence of DM in Taiwan was established between 1985 and 1996 and the rates were between 4.9 and 9.2%. The prevalence of IGT was 15.5% (men 15% and women 15.9%) (see Table 1). The prevalence of DM and IGT increased significantly with age for both genders [4,10–12]. The significant factors associated with newly diagnosed DM were age, BMI (WHR), family history of DM, systolic blood pressure (hypertension), physical activity and serum triglyceride levels [4,10–12]. The prevalence of LVD in DM and non-diabetic subjects were 20.0 and 12.9%, respectively. The diabetics had a significantly higher prevalence of LVD than non-diabetic subjects. Among diabetics, 15.8% had IHD, 1.7% leg VD and 2.5% stroke. In non-diabetics, the prevalence of the aforementioned macroangiopathies were 11.5, 0.2 and 1.2%, respectively. The diabetics had significantly higher prevalences of IHD, leg VD and stroke than non-diabetics (see Table 2). The most significant risk factor associated with the LVD was serum cholesterol. No risk factor was significantly associated with the development of stroke. Cholesterol and HbA1c were significantly associated with development of IHD. Cigarette smoking and female gender were significantly associated with leg VD [13]. The prevalence of DR was 35.0% (background DR 30%, preproliferative DR 2.8% and proliferative DR 2.2%, respectively) (see Table 3). The prevalence of DM for previously and newly diagnosed diabetics were 45.2 and 28.3% (men 42.8 vs. 33.3% and women 47.5 vs. 24.8%), respectively. Previously diagnosed diabetics had higher prevalence of DR than newly diagnosed diabetics, and these finding were particular prominent in women (Fig. 1). From multiple logistic regression analysis, duration of DM was the most important risk factors related to DR. Diabetic subjects treated with insulin had a higher risk of developing DR than those treated with diet control [14]. The prevalence of nephropathy and neuropathy were 12.9 and 23.5%, respectively (see Tables 4 and 5). For those patients with and those without nephropathy and neuropathy, the duration of
S52
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
Table 1 Prevalence of diabetes and IGT in Chinese and Asian populations Country/ population
Age range (years)
Sample size
Study year
DM
IGT
Crude rate Chinese (in Taiwan) Tainana ]20 ]40 Taipeib Ann-Lo, ]40 Keelungc Kin-Hu, ]30 Kinmend Chinese (outside of Taiwan) Da Qing, 25–74 China Singapore ]18 Hong Kong 18–64 Mauritius 25–74 Asian Vietnam South Korea Japan Fiji, indian (urban)
]15 ]30 ]45 ]20
Adjusted rate
Crude rate
Adjusted rate
1638 11478 2448
1996 1985 1988
9.0 6.2 8.0
9.2 5.8 8.0
14.0 – –
15.5 – –
236
1991
6.5
4.9
–
–
110660
1986
0.77
1.6
0.6
0.9
1417 1513 412
1985 1991 1987
4.0 4.5 11.7
M4.6, F4.9 7.7 11.5
0.6 7.3 16.5
M0.8, F0.3 M11.2, F8.8 M16.5, F21.7
4912 2497 916 846
1990 1991 1990 1980
1.2 9.1 11.9 13.1
1.4 7.2 10.4 M12.9, F11.0
1.6 11.8 16.6 10.3
1.7 8.9 15.3 M8.3, F11.8
a
Standard OGTT for each subject. Capillary blood glucose either after overnight fasting or 2-h postprandial by use of glucometer. c Two-hour postprandial blood glucose (Glucocheck SC B-2) or urinary glucose and adjusted with the population in Taiwan. d OGTT for subject with fasting plasma glucose levels between 5.6 and 7.8 mmol/l. b
DM, percentage of insulin treatment, percentage of hypertension, and the fasting plasma glucose were significantly different. Diabetic duration, hypertension, insulin treatment and glycemic control consistently correlated with nephropathy and neuropathy [15].
city of Taiwan, showed age-adjusted prevalence rates of 9.2% for diabetes (men 10.4%, women 8.1%) and IGT of 15.5% (men 15%, women 15.9) [12]. The prevalence of diabetes in southern Taiwan is the highest rate that has been reported here. In comparison with the prevalence rate
4. Discussion
Table 2 Prevalences of LVD, IHD, leg VD and stroke among diabetics and non-diabetics in Taiwana
The prevalence of diabetes in northern Taiwan was established between 1985 and 1991 and the rates were between 4.9 and 8.0% [4,10,11]. Studies from northern Taiwan indicate prevalence rates which are also higher than in China [16] and which are broadly similar to those of Hong Kong [17] and Singapore [18] but lower than Mauritius [19] (see Table 1). A recent study from Taiwan, conducted on an urban population in a southern
Normal LVD IHD Leg VD Stroke a
Non-diabetics (n = 513)
Diabetics (n = 608)
447 66 59 1 6
488 (80.0%) 120* (20.0%) 95* (15.8%) 10* (1.7%) 15* (2.5%)
(87.1%) (12.9%) (11.5%) (0.2%) (1.2%)
LVD, large vessel disease; IHD, ischemic heart disease; leg VD, leg vessel disease. * PB0.05.
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
S53
Table 3 Prevalence and severity of diabetic retinopathy among newly and previously diagnosed diabetica Retinopathy
Absent Background Pre-proliferative Proliferative a
Newly diagnosed diabetics
Previously diagnosed diabetics
Total
No.
No.
No.
145 45 1 0
% 75.9 23.6 0.5 0
196 120 14 6
% 58.4 35.7 4.2 1.8
344 165 15 6
% 65.0 30.0 2.8 2.2
Fisher’s exact test, PB0.005.
among Asian populations (see Table 1), the rate was higher than that in a Vietnamese study [20], the Korean study [21], close to that of the Japanese study [22], but lower than that in the Fiji Asian Indian study [23]. In a comparison with IGT prevalence studies in adult Chinese outside of Taiwan, the rate was higher than that in the Da Qing, China study, [16] the Singapore study, [18] and the Hong Kong study, [17] but close to that of the Mauritius study [19]. Comparing the prevalence rate among Asian populations showed that the Taiwan rate was higher than that in the Vietnamese study, [20] the Korean study, [21] and the Fiji Asian Indians study, [23] but close to that of the Japanese study [22]. Studies in different Chinese populations who have similar genetic characteristics have shown substantial variation in the prevalence of diabetes and IGT. This result indicates that environmental factors may play an important role, since the levels of westernization were very different among the Chinese in these areas. From the results of multiple logistic regression in Taiwan study, the significant risk factors associated with newly diagnosed diabetes were age, family history of DM, BMI, SBP, physical activity and TG [4,10 – 12]. Predictive factors for NIDDM in Chinese population are now quite well described and appear similar to those described for other populations. These factors have been described in studies reported from Taiwan [4,10 –12], China [16] and Mauritius [19], as well as from Hong Kong [17]. Increasing age, obesity, central obesity and a positive family history of diabetes are all major factors. Age as an independent predictor of diabetes has been reported in
many studies [24,25]. Family history of DM as a significant predictor for diabetes has also been demonstrated in several studies [26,27]. Physical inactivity has been less thoroughly examined but has been shown to be important in Mauritius [19] and Taiwan [12]. Many prospective studies have also shown that higher physical activity can reduce the risk of diabetes [28,29]. The mechanism may be related to increasing insulin sensitivity in skeletal muscle caused by physical activity [30]. In addition, BMI [26,27,31], SBP [11,12,31,32] and TG [31,33] have also been associated with the prevalence of diabetes from many studies. It could be explained by insulin resistance and hyperinsulinemia suggested by Reaven in his Banting lecture in 1988 [34] and from many other studies [35,36]. The proposed mechanism is that obese subjects are resistant to insulin-stimulated glucose uptake, which in turn leads to an increase in insulin concentration, enhanced hepatic very-lowdensity lipoprotein triglyceride secretion and hypertriglyceridemia and lead to a reduction of
Fig. 1. Comparison of the prevalence of retinopathy between newly and previously diagnosed diabetics by gender.
S54
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
Table 4 Prevalence of diabetic nephropathy in Chinese and Asian populations Country/population
Age range (years)
Sample size
Study year
Prevalence (%)
Chinese Taiwana Hong Kongb Singaporec
All ages All ages All ages
217 374 300
1978 1991 –
12.9 20.1 19.5
Asian Thailanda Japanc South Koreac Indiad
24–88 All ages 30–75 All ages
2060 2115 631 4941
– 1990 1993 –
18.7 20.1 13.8 1.9
a
Persistent proteinuria in absence of urinary tract infection. Albumin: creatinine \30 mg mmol. c AER\200 mg/min (300 mg/24 h) d AER\500 mg 24 h−1. b
Table 5 Prevalence of diabetic neuropathy in Chinese and Asian populations Country/population
Age range (years)
Sample size
Study year
Prevalence (%)
Chinese Singaporea Taiwanb
All ages All ages
150 217
– 1978
17.2 23.5
Asian Indiaa,c Japandd,c
– All ages
545 2115
– 1990
23.9 36.3
a
Impaired vibration perception and/or other sensation (pinprick, light touch, position). Abnormal nerve conduction velocity. c Absence of knee/ankle reflexes (at least one). d Pain and paraesthesia. b
sodium excretion, enhanced sympathetic nervous system activity, and hypertension [37]. The prevalence of IHD, leg VD and stroke in DM were 15.8, 1.7 and 2.5%, respectively. In a comparison of IHD prevalence studies in adult Chinese outside of Taiwan, the Taiwan rate was higher than that in the Hong Kong study and the Singapore study (see Table 6) [38]. Comparison of the prevalence rate among Asian populations showed that he rate was higher than that in the Sri Lanka study, the India study, the Thailand study and the Korean study but lower than that in the Japanese study [38]. CAD occurs earlier and more frequently in diabetics than non-diabetics, resulting in a higher prevalence for a given age [39]. On ECG, abnormalities are generally twice
as common in diabetics [40]. Correspondingly, the relative risk of cardiovascular death is around two to four times higher in diabetics than in non-diabetics. Hyperlipidemia, cigarette smoking, high BP, obesity, diabetes, physical inactivity, adverse psychosocial events, and thrombogenic factors have been identified as major risk factors of CAD [41–43]. Studies have shown that reduction of total cholesterol can decrease the morbidity and mortality of CAD [42–45]. In this study, the patients with a higher cholesterol level had a significantly increased relative risk of LVD and IHD. The second important risk factor of IHD in this study was HbA1c. Several studies have shown that good blood glucose control could improve the micro-vascular complications of diabetes
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
[46,47]. Our results also implied that good blood glucose control is extremely important in decreasing IHD in diabetic patients. In a comparison of leg VD (PVD) prevalence studies among the Asian population, the Taiwan rate was lower than that in the India study, the Sri Lanka study and the Korean study (see Table 7) [38]. PVD is strongly related to cigarette smoking [48,49]. We found that smoking patients had a significantly increased relative risk of leg VD compared with nonsmoking patients. Women diabetic subjects also had an increased risk of developing leg VD compared with men in this study. The reason why needs further exploration. Epidemiologic studies of DR have been conducted among different populations in many areas
S55
of the world. According to the WHO study [8], the prevalence of retinopathy varies greatly from one country to another, even when corrected for age and duration of diabetes. A study from northern Taiwan showed a prevalence of 35% for DR in NIDDM subjects and was not remarkably different compared with Asian and Western studies (see Table 8) [38]. Despite different study procedures and populations, several factors, including duration of diabetes, age at onset of diabetes, age at examination, type of diabetes treatment, control of diabetes hypertension, proteinuria, serum creatinine level, serum cholesterol level, and BMI have been found to correlate with the prevalence of DR. The duration of diabetes and the prevalence and severity of DR were
Table 6 CHD in diabetes in Chinese and Asian populations Country/population
Age range (years)
Sample size
Chinese Hong Konga,b Singaporea,b North Taiwana,b Southern Taiwana,b
35–54 ] 18 ] 40 ] 20
422 117 479 1638
Asian Indiaa,c Sri Lankab Thailanda,c Japanb South Koreab
All ages All age 24–88 All ages 30–75
4941 500 2060 976 631
Study year
1975 1984 1986 1996 – – – 1960 1993
Prevalence (%)
24.2 2.8 21.8 20.3 18.5 12.0 10.5 31.6 12.6
a
Past history of angina, myocardial infarction, stroke or bypass surgery. ECG coronary probable and/or coronary possible (Minnesota Code). c Ischaemic ECG change (further indefined). b
Table 7 PVD in diabetes in Chinese and Asian populations Country/population
Age range (years)
Chinese Northern Taiwana,b
]40
Asian Indiab,c Sri lankaa,b South Koreab
All ages All ages 30–75
a
Intermittent claudication. Absent arterial pulses on feet and/or amputation. c Ankle: brachial pressure index B0.9. b
Sample size
479 4941 500 631
Study year
Prevalence (%)
1986
1.7
– – 1993
3.9 5.6 5.9
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
S56
Table 8 Prevalence of diabetic retinopathy in Chinese and Asian populations Country/population
Age range (years)
Chinese Chinaa Hong Konga Singaporea Taiwana
All ages 35–54 All ages ]40
114 422 300 527
1995 1975 – 1985
33.0 32.5 38.0 34.9
Asian Indiaa Pakistana,b Sri Lankaa Thailandb Japana South Koreaa
All ages All ages All ages 24–88 All ages 30–75
6792 3000 1003 2060 976 631
– – – – 1960 1993
34.1 26.0 31.3 32.1 33.0 35.2
a b
Sample size
Study year
All retinopatyh (%)
Direct and/or indirect ophthalmoscopy with mydriasis. Fundus photography.
closely associated in the northern Taiwan study. The longer the duration of diabetes, the higher the prevalence of total DR. The prevalence of total DR were 29.1% for those subjects who had diabetes for less than 5 years, and 23.0% for subjects in whom diabetes was newly diagnosed. Similar results have also been demonstrated in other studies [50,51]. Some studies found that the duration of diabetes is the most crucial factor for total DR. [52,53]. The prevalence of nephropathy and neuropathy in the northern Taiwan study were 12.9 and 23.5%, respectively. For those patients with and those without nephropathy and neuropathy, the duration of DM, percentage of insulin treatment, percentage of hypertension, and fasting plasma glucose levels were significantly different. Diabetic duration, hypertension, insulin treatment and glycemic control consistently correlated with nephropathy and neuropathy. In a comparison of the nephropathy prevalence studies in the Chinese outside of Taiwan, the Taiwan rate was lower than that in the Singapore study and the Hong Kong study (see Table 4). Comparing of the prevalence rate among Asian populations (see Table 4) showed that the rate was higher than the India study and close to that of the Korean study but lower than the Thailand and Japanese studies [38]. Proteinuria was 15 times more prevalent in
diabetics than in non-diabetics [54]. Disease duration was a major determinant of nephropathy [8,54,55] and other factors included cholesterol levels [8], blood pressure [8,56], glycemic control [56] and persistent microalbuminuria [57,58]. The prevalence of hypertension was higher among NIDDM patients with proteinuria in the northern Taiwan study. It was well-established that the presence of hypertension can aggravate diabetic nephropathy and retinopathy [59,60]. However, its role in neuropathy is still ambiguous. A previous review summarized several older clinic-based studies with prevalence of various neuropathies ranging from 20 to 100% [61]. A consensus conference, convened in 1988 in San Antonio, Texas [62] made recommendations for the standardization of neuropathy endpoints. Several population-based studies with the prevalence of neuropathy ranged from 10.5 to 32.1% [63–66]. The prevalence of neuropathy was 17.2% in the northern Taiwan study. In comparing the neuropathy prevalence studies in Chinese outside of Taiwan and Asian populations, the Taiwan rate was higher than that in the Singapore study and close to that of the India study but lower than that of the Japanese study (see Table 5). The prevalence of diabetic neuropathy was examined in a recent multicenter study in the UK involving 3949 hospital-treated patients with NIDDM.
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
Neuropathy was present in 32.1% in NIDDM patients and was positively correlated with age and duration of diabetes [67]. There is very little information using the current batteries of tests that can be used to estimate the risk of neuropathy in unselected populations of diabetic patients, whether neuropathy risk increases like that of retinopathy, or plateaus like nephropathy, is an important but unanswered question.
References [1] WHO Ad Hoc Diabetes Reporting Group, H. King, M. Rewers, Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults, Diabetes. Care. 16 (1993) 157 –177. [2] Department of Health, Health and Vital Statistics. I. General Health Statistics, Taipei, Republic of China, Department of Health, Executive Yuan, 1996. [3] National Diabetes Data Group, Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance, Diabetes 28 (1979) 1039–1057. [4] T.Y. Tai, C.L. Yang, C.J. Chang, et al., Epidemiology of diabetes mellitus among adults in Taiwan, ROC, J. Med. Assoc. Thailand 70 (Suppl. 2) (1987) 42–48. [5] WHO Study Group on Diabetes Mellitus, Diabetes mellitus, WHO Technical Report Series 727, Geneva, 1985, pp. 9– 12. [6] World Health Organization, Hypertension and coronary heart disease: classification and criteria for epidemiological study, WHO Technical Report Series 168, Geneva, 1959. [7] R.S. Paffenbarger, S.N. Blair, I.M. Lee, R.T. Hyde, Measurement of physical activity to assess health effects in free-living populations, Med. Sci. Sport Exerc. 25 (1993) 60 – 70. [8] World Health Organization, Multinational study of vascular disease in diabetes: prevalence of small vessel and large vessel disease in diabetic patients from 14 centers, Diabetologia 28 (1985) 615–640. [9] R.C. Chen, S.M. Sung, C.F. Chen, C.J. Tzeng, I.N. Lien, T.P. Hung, Normal motor nerve conduction velocity amongst Chinese in Taiwan, J. Formos. Med. Assoc. 77 (1978) 394 – 401. [10] J.D. Lin, W.B. Shieh, M.J. Hung, H.S. Hung, Diabetes mellitus and hypertension based on the family history and 2-h postprandial blood sugar in the Ann-Lo district (Northern Taiwan), Diabetes Res. Clin. Pract. 20 (1993) 75 – 85. [11] P. Chou, M.J. Liao, H.S. Kuo, K.H. Hsiao, S.T. Tsai, A population survey on the prevalence of diabetes in KinHu, Kinmen, Diabetes Care 17 (1994) 1055–1058. [12] F.H. Lu, Y.C. Yang, J.S. Wu, C.H. Wu, C.J. Chang, A population-based study of the prevalence and associated
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
S57
factors of diabetes in southern Taiwan, Diabet. Med. 15 (1998) 564 – 572. C.C. Fu, C.J. Chang, C.H. Tseng, et al., Development of macrovascular diseases in NIDDM patients in northern Taiwan, Diabetes Care 16 (1993) 137 – 143. M.S. Chen, C.J. Kao, C.J. Chang, T.J. Wu, C.C. Fu, C.J. Chen, T.Y. Tai, Prevalence and risk factors of diabetic retinopathy among non-insulin-dependent diabetic subjects, Am. J. Ophthalmol. 114 (1992) 723 – 731. T.Y. Tai, C.H. Tsneg, S.M. Sung, R.F. Huang, C.J. Chen, S.H. Tsai, Retinopathy, neuropathy and nephropathy in non-insulin-dependent diabetic patients, J. Formos. Med. Assoc. 90 (1991) 936 – 940. S.R. Pan, Y.H. Hu, G.W. Li, P.A. Liu, P.H. Bennett, B.V. Howard, Impaired glucose tolerance and its relationship to ECG-indicated coronary heart disease and risk factors among Chinese-Da Qing IGT and diabetes study, Diabetes Care 16 (1993) 150 – 156. C.S. Cockram, J. Woo, E. Lau, et al., The prevalence of diabetes mellitus and impaired glucose tolerance among Hong Kong Chinese adults of working age, Diabetes Res. Clin. Pract. 21 (1993) 67 – 73. A.C. Thai, P.P.B. Yeo, K.C. Ln, K. Hung, W.Y. Ng, K.F. Lui, J.S. Cheas, Diabetes mellits and its chronic complications in Singapore: an increasing healthcare problem, Ann. Acad. Med. Singapore 19 (1990) 517 – 523. G.K. Dowse, P.Z. Zimmet, H. Gareeboo, et al., Abdominal obesity and physical inactivity as risk factors for NIDDM and impaired glucose tolerance in Indian, Greole and Chinese Mauritians, Diabetes Care 14 (1991) 271 – 282. P.S. Quoc, M.A. Charles, N.H. Cuong, et al., Blood glucose distribution and prevalence of diabetes in Hanoi, Am. J. Epidemiol. 139 (1994) 713 – 722. Y. Park, H. Lee, C.S. Koh, H. Min, K. Yoo, Y. Kim, Y. Shin, Prevalence of diabetes and IGT in Yonchon County, South Korea, Diabetes Care 48 (1995) 545 – 548. A. Sekikawa, M. Tominaga, K. Takahashi, et al., Prevalence of diabetes and impaired glucose tolerance in Funagata area, Japan, Diabetes Care 16 (1993) 570 – 574. P. Zimmet, R. Taylor, P. Ram, H. King, G. Sloman, L.R. Raper, D. Hunt, Prevalence of diabetes and impaired glucose tolerance in the biracial (Melanesian and Indian) population of Fiji: a rural – urban comparison, Am. J. Epidemiol. 118 (1983) 673 – 688. R.B. Lipton, Y. Liao, R.S. Cooper, D. McGee, Determinants of incident non-insulin-dependent diabetes mellitus among blacks and whites in a national sample: the NHANES I epidemiologic follow-up study, Am. J. Epidemiol. 138 (1993) 826 – 839. P.W. Wilson, K.M. Anderson, W.B. Kannel, Epidemiology of diabetes mellitus in the elderly: The Framinghan Study, Am. J. Med. 80 (Suppl. 5A) (1986) 3 – 9. W.J. Butler, L.D. Ostrander, W.J. Carman, D.E. Lamphier, Diabetes mellitus in Techmseh, Michigan: prevalence, incidence, and associated conditions, Am. J. Epidemiol. 116 (1982) 971 – 980.
S58
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
[27] W.C. Knowler, P.H. Bennett, R.F. Hamman, M. Miller, Diabetes incidence and prevalence in Pima Indians: a 19-fold greater incidence than in Rochester, Minnesota, Am. J. Epideniol. 108 (1978) 497–505. [28] S.P. Helmrich, D.R. Ragland, R.W. Leng, R.S. Paffenbarger, Physical activity and reduced occurrence of noninsulin-dependent diabetes mellitus, N. Engl. J. Med. 325 (1991) 147 – 152. [29] J.E. Manson, E.B. Rimm, M.J. Stampfer, et al., Physical activity and incidence of non-insulin-dependent diabetes mellitus in women, Lancet 338 (1991) 774–778. [30] J.T. Devlin, Effects of exercise on insulin sensitivity in humans, Diabetes Care 15 (1992) 1690–1693. [31] J.H. Medalie, C.M. Papier, M.A. Gloodbourt, J.B. Herman, Major factors in the development of diabetes mellitus in 10 000 men, Arch. Intern. Med. 135 (1975) 811 – 817. [32] P.A. Morales, B.D. Mitchell, R.A. Valdez, H.P. Hazuda, M.P. Stern, S.M. Haffner, Incidence of NIDDM and impaired glucose tolerance in hypertensive subjects: The San Antonio Heart Study, Diabetes 42 (1993) 154–161. [33] E. Barrett-Connor, S.M. Grndy, M.J. Holdbrook, Plasma lipids and diabetes mellitus in an adults community, Am. J. Epidemiol. 115 (1982) 657–663. [34] G.M. Reaven, Banting lecture : role of insulin resistance in human disease, Diabetes 37 (1988) 1595–1607. [35] R.A. DeFronzo, E. Ferrannini, Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease, Diabetes Care 14 (1991) 173–194. [36] G.M. Reaven, H. Lithell, L. Landsberg, Hypertension and associated metabolic abnormalities: the role of insulin resistance and the sympathoadrenal system, N. Engl. J. Med. 334 (1996) 374–381. [37] J.M. Flback, J.R. Sowers, Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia, Am. J. Med. 91 (Suppl. 1A) (1991) 115–215. [38] A.F. Amos, D.J. McCarty, P. Zimmet, The rising global burden of diabetes and its complications: estimate and projection to the year 2010, Diabet. Med. 14 (1997) S7 – S85. [39] W.B. Kannel, D.L. MecGee, Diabetes and glucose tolerance as risk factors for cardiovascular disease, the Framingham Study, Diabetes Care 2 (1979) 920–926. [40] E. Barrett-Connor, T. Orchard, Diabetes and heart disease, in: M.I. Harris, R.F. Hmmah (Eds.), Diabetes in America. NIH Publication XVI, 1985, pp. 1–41. [41] The Lipid Research Clinics Coronary Primary Prevention Trial Results 1. Reduction in incidence of coronary heart disease, J. Am. Med. Assoc. 251 (1984) 351–364. [42] M.H. Frick, O. Elo, K. Haapa, et al., Helsinki Heart Study — primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia, N. Engl. J. Med. 317 (1987) 1237 – 1245. [43] D.H. Blankenhom, S.A. Nessim, R.L. Johnson, M.E. Sanmacro, S.P. Azen, L. Cashin-Hemphill, Beneficial effects of combined colestipol-niacin therapy on coronary
[44]
[45]
[46]
[47]
[48]
[49]
[50]
[51]
[52]
[53]
[54]
[55]
[56]
[57]
atherosclerosis and coronary venous bypass grafts, J. Am. Med. Assoc. 257 (1987) 3233 – 3240. Multiple Risk Factor Intervention Trial Research Group, Multiple risk factor intervention trial. Risk factor changes and mortality results, J. Am. Med. Assoc. 248 (1982) 1465 – 1477. W.D. Stamler, J.D. Neaton, Prevalence and prognostic significance of hypercholesterolemia in men with hypertension: prospective data on the primary screenees of the multiple risk factor intervention trial, Am. J. Med. 80 (Suppl. 2A) (1986) 33 – 36. R. Engerman, J.J. Bloodworth, S. Nelson, Relationship of microvascular disease in diabetes to metabolic control, Diabetes 26 (1977) 760 – 769. P. Raskin, J. Rosenstock, Blood glucose control and diabetic complications, Ann. Intern. Med. 105 (1986) 254 – 263. R.B. Paisey, G. Arredondo, A. Villalobos, O. Lozaano, L. Guevara, S. Kelly, Association of differing dietary, metabolic, and clinical risk factors with macrovascular complications of diabetes: a prevalence study of 503 Mexican type II diabetic subjects I, Diabetes Care 7 (1984) 421 – 427. UK Prospective Diabetes Study: 6, Complications in newly diagnosed type 2 diabetic patients and their association with different clinical and biochemical risk factors, Diabetes Res. 13 (1990) 1 – 11. The Wisconsin Epidemiologic Study of Diabetic Retinopathy, III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years, Arch, Ophthalmol, 102 (1984) 527 – 532. L.M. Aiello, L.I. Rand, J.C. Briones, M.Z. Wafai, J.G. Sebestyen, Diabetic retinopathy in Joslin clinic patients with adult-onset diabetes, Ophthalmology 88 (1981) 619 – 623. I.J. Constable, M.W. Knuiman, T.A. Welborn, R.L. Cooper, K.M. Stantion, V.J. McCann, G.C. Grose, Assessing the risk of diabetic retinopathy, Am. J. Ophthalmol. 97 (1984) 53 – 61. B. Jerneld, P. Algvere, Relationship of duration and onset of diabetes to prevalence of diabetic retinopathy, Am. J. Ophthalmol. 102 (1986) 431 – 437. S.A. Kamenetsky, P.H. Bannett, S. Dippe, M. Miller, P.M. Le Compte, A clinical and histologic study of diabetic nephropathy in the Pimas Indians, Diabetes 23 (1974) 61 – 64. W.H. Hemman, S.M. Teutsch, Kidney diseases associated with diabetes, in: M.I. Harrris, R.F. Hammah (Eds.), Diabetes in America. NIH Publlication XIV, 1985, pp. 1 – 31. C.E. Mogensen, C.K. Christensen, Predicting diabetic nephropathy in insulin-dependent diabetes, N. Engl. J. Med. 321 (1982) 1430 – 1432. R.J. Jarrett, G.C. Viberti, A. Argyropoulos, et al., Microalbuminuria predicts mortality in non-insulin-dependent diabetics, Diabet. Med. 1 (1984) 17 – 19.
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59 [58] C.E. Mogensen, R.W. Bilous, D. Mackintosch, J.J. Bending, H. Keen, Long term correction of hyperglycemia and progression of renal failure in insulin-dependent diabetes, Br. Med. J. 286 (1983) 598–621. [59] J.M. Sprafke, A.P.M. Bender, H.G. Jagger, Prevalence of hypertension and associated risk factors among diabetic individuals: the three-city study, Diabetes Care 11 (1982) 685 – 688. [60] C.E. Mogensen, Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy, Br. Med. J. 285 (1982) 685 – 688. [61] D.A. Greene, A.A.F. Sima, M.A. Pfeifer, Neuropathy, in: C.E. Mogensen, E. Standl (Eds.), Prevention and Treatment of Diabetic Late Complications, Wlater de Gruyter, Berlin, 1989, pp. 93 –150. [62] Consensus Statement, Report and recommendations of the San Antonio conference on diabetic neuropathy, Diabetes 37 (1988) 1000–1004. [63] D.P. Walters, W. Gatling, M.A. Muullee, R.D. Hill, The prevalence of diabetic distal sensory neuropathy
.
[64]
[65]
[66]
[67]
S59
in an English community, Diabet. Med. 9 (1992) 349 – 353. J.M. Lethtinen, M. Uusitupa, O. Sitonen, K. Pyorala, Prevalence of neuropathy in newly diagnosed NIDDM and non-diabetic control subjects, Diabetes 38 (1989) 1307 – 1313. M.W. Knuiman, T.A. Welborn, V.J. McCann, K.G. Stanton, I.J. Constable, Prevalence of diabetic complications in relation to risk factors, Diabetes 35 (1986) 1332 – 1339. P.J. Palumbo, L.R. Elveback, J.P. Whisnant, Neurologic complications of diabetes mellitus: transient ischemic attack, stroke, and peripheral neuropathy, Adv. Neurol. 19 (1978) 593 – 601. M.J. Young, A.J.M. Boulton, A.F. Macleod, D.R.R. Williams, P.H. Sonsken, A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population, Diabetologia 36 (1993) 150 – 154.
Epidemiologic study of type 2 diabetes in Taiwan Chih-Jen Chang a, Feng-Hwa Lu a, Yi-Ching Yang a, Jin-Shang Wu a, Ta-Jen Wu b, Muh-Shy Chen c, Lee-Ming Chuang d, Tong-Yuan Tai d,* a b
Department of Family Medicine, College of Medicine, National Cheng Kung Uni6ersity, Taipei, Taiwan, ROC Department of Internal Medicine, College of Medicine, National Cheng Kung Uni6ersity, Taipei, Taiwan, ROC c Department of Ophthalmology, College of Medicine, National Taiwan Uni6ersity, Taipei, Taiwan, ROC d Department of Internal Medicine, College of Medicine, National Taiwan Uni6ersity, Taipei, Taiwan, ROC
Abstract Diabetes mellitus (DM) in adults is a global health problem, although its prevalence varies widely between different populations and the rate has generally increased worldwide. In Taiwan, the mortality rate from DM has almost doubled over the past 10 years. The prevalence of DM in Taiwan was established between 1985 and 1996 and the rates were between 4.9 and 9.2%. The prevalence of impaired glucose tolerance (IGT) was 15.5% (men 15% and women 15.9%). The prevalence of DM and IGT increased significantly with age for both genders. The significant factors associated with newly diagnosed DM were age, BMI, family history of DM, systolic blood pressure (hypertension), physical activity and serum triglyceride levels. The prevalence of large vessel disease (LVD) in DM and non-diabetic subjects were 20.0 and 12.9%, respectively. Among diabetics, 15.8% had ischemic heart disease (IHD), 1.7% leg vessel disease (leg VD), and 2.5% stroke. In non-diabetics, the prevalence of the aforementioned macroangiopathies were 11.5, 0.2 and 1.2%, respectively. The diabetics had a significantly higher prevalence of macrovascular disease than non-diabetic subjects. The most significantly associated with the LVD was serum cholesterol levels. Serum cholesterol and HbA1c were significantly associated with the development of IHD. Cigarette smoking and female gender were significantly associated with the leg VD. The prevalence of diabetic retinopathy (DR) was 35.0%. (background DR 30%, preproliferative DR 2.8% and proliferative DR 2.2%, respectively.) The prevalence of DR for previously and newly diagnosed diabetics were 45.2 and 28.3% (men 42.8 vs. 33.3% and women 47.5 vs. 24.8%), respectively. From multiple logistic regression analysis, duration of DM was the most important risk factor related to DR. Diabetic subjects treated with insulin had a higher risk of developing retinopathy than those treated with dietary control. The prevalence of nephropathy and neuropathy were 12.9 and 23.5%, respectively. For those patients with and those without nephropathy and neuropathy, the duration of DM, percentage of insulin treatment, percentage of hypertension, and fasting plasma glucose were significantly different. Diabetic duration, hypertension, insulin treatment and glycemic control consistently correlated with nephropathy and neuropathy. In conclusion, the prevalence of DM in Taiwan was between 4.9 and 9.2%, and the prevalence of IGT was 15.5%. The possible risk factors of newly diagnosed diabetes were age, family history of DM, BMI, SBP (hypertension), physical activity and triglyceride levels. Diabetes in Chinese subjects share many characteristics
* Corresponding author. Tel.: + 886-2-23222169; fax: + 886-2-23222169. E-mail address: [email protected] (T.-Y. Tai). 0168-8227/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII: S 0 1 6 8 - 8 2 2 7 ( 0 0 ) 0 0 1 7 9 - 0
S50
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
similar to other Asian populations. The burden imposed by the chronic complications of diabetes is massive. In Taiwan, the mortality rates from DM have increased greatly over the past 10 years. Reduction of the modificable risk factors such as BMI, hypertenion and dyslipidemia, and increase of physical activity and good glycemic control through public health efforts may help to reduce the risk of DM and its chronic complications. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Epidemiology; Prevalence; Risk factor; Chinese, Type 2 (non-insulin-dependent) diabetes
1. Introduction Diabetes mellitus (DM) in adults is a global health problem. Although its prevalence varies widely between different populations from low ( B 3%), moderate (3 – 10%), high (11 – 20%) to extremely high (\20%), the rate has generally increased worldwide [1]. The remarkable economic achievement in the last 30 years has resulted in a great improvement in living standards and prolongation of life expectancy in Taiwan. In Taiwan, the mortality rate from diabetes mellitus has almost doubled over the past 10 years and its ranking in the leading causes of death has increased: one twelfth in 1982, one eighth in 1983, one seventh in 1984 and one fifth since 1987 [2]. It has become one of the major health problems of the country.
2. Material and methods
2.1. Study subjects 2.1.1. Northern Taiwan 2.1.1.1. Taipei Study (1985). This survey was conducted from November 1985 to June 1986. Eight of the 78 subdistricts of the Ta-An precinct were randomly selected. Five villages evenly distributed over the island were also randomly selected. The total number of subjects aged 40 years or older who underwent the survey in Taipei City was 4272 and that of the five villages was 7206, with a response rate of 65.3 and 72.0%, respectively. Among the 715 subjects, 608 subjects, including 225 newly diagnosed and 383 previously diagnosed, participated in a further study.
2.1.1.2. Kin-Hu, Kinmen. The study subjects were those \ 30 years of age in Kin-Hu township. According to household registration, 4097 eligible residents were invited to the community center to attend the screening test from January to February 1991. 2.1.1.3. Ann-Lo, Keelung. This survey was performed between July 1988 and June 1990 in the Ann-Lo district of Keelung in northern. The response rate for a total of 9087 eligible subjects was 67.4%. 2.1.1.4. Taipei Study (1978). A total 217 diabetic patients (110 men and 107 women) who were discovered during 1978 survey for adult diabetics in the Cheng-Chung district of Taipei City. They were examined for diabetic retinopathy, neuropathy and nephropathy. 2.1.2. Southern Taiwan The study was performed in Tainan City of southern Taiwan. The sampling scheme was a three-stage process that generated a stratified systemic cluster sample of households throughout the city. Of the 2416 eligible people, 1638 (67.8%) participated in the study. 2.2. Methods With the help of specially trained assistants, all subjects were interviewed according to a structured questionnaire, while included demographic information, past medical history of diabetes and hypertension, current smoking habit, medication history, physical activity, and family history of DM and hypertension. Obesity was defined as a BMI\ 27 for men and \ 25 for women [3] or
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
BMI \ 30 for both genders [4]. Overnight fasting serum and plasma samples were kept frozen at −20°C until analysis. Serum total cholesterol and triglyceride were measured enzymatically using automated methods. Diabetes mellitus was diagnosed according to the World Health Organization (WHO) criteria [5]. Hypertension was deemed present when the systolic pressure \ 160 mmHg, or when the diastolic pressure \ 95 mmHg or a history of hypertension and currently receiving treatment [6]. Physical activity and the exercise status as were prescribed previously [4]. Total physical activity assessment was calculated in MET-hours per week over all activities for the past year [7]. Subjects who smoked less than 100 cigarettes in their lifetime were classified as nonsmokers, more than 100 cigarettes but had stopped before the examination were classified as ex-smokers, and smoked at the time of the interview were classified as current smokers. According to the protocol of the WHO Multinational Study on Vascular Disease in Diabetes [8], LVD, including stroke, IHD, and leg VD, were investigated. The ophthalmic examinations were performed with direct and indirect ophthalmoscopy after dilating the pupils with tropicamide 1% and phenylepinephrine 10%. The retinopathy status was divided into normal; background, preproliferative and proliferative DR. Ophthalmoscopy was performed in 527 of the diabetic subjects. Urinalysis for screening of clinical proteinuria was conducted at least three times in a 1-month period. Diabetic nephropathy was defined as a positive result on a dipstick test, approximately equivalent to 300 – 500 mg/l of urine. Neuropathy was confirmed if the motor nerves showed abnormal conduction velocity [9]. The statistical significance was assessed by using the Student’s t-test and the chi-square test. Correlation coefficients were estimated by Spearman’s method and multiple logistic regression analysis was also performed to evaluate multivariate-adjusted associations between related factors and diabetic macrovascular and microvascular diseases.
S51
3. Results The prevalence of DM in Taiwan was established between 1985 and 1996 and the rates were between 4.9 and 9.2%. The prevalence of IGT was 15.5% (men 15% and women 15.9%) (see Table 1). The prevalence of DM and IGT increased significantly with age for both genders [4,10–12]. The significant factors associated with newly diagnosed DM were age, BMI (WHR), family history of DM, systolic blood pressure (hypertension), physical activity and serum triglyceride levels [4,10–12]. The prevalence of LVD in DM and non-diabetic subjects were 20.0 and 12.9%, respectively. The diabetics had a significantly higher prevalence of LVD than non-diabetic subjects. Among diabetics, 15.8% had IHD, 1.7% leg VD and 2.5% stroke. In non-diabetics, the prevalence of the aforementioned macroangiopathies were 11.5, 0.2 and 1.2%, respectively. The diabetics had significantly higher prevalences of IHD, leg VD and stroke than non-diabetics (see Table 2). The most significant risk factor associated with the LVD was serum cholesterol. No risk factor was significantly associated with the development of stroke. Cholesterol and HbA1c were significantly associated with development of IHD. Cigarette smoking and female gender were significantly associated with leg VD [13]. The prevalence of DR was 35.0% (background DR 30%, preproliferative DR 2.8% and proliferative DR 2.2%, respectively) (see Table 3). The prevalence of DM for previously and newly diagnosed diabetics were 45.2 and 28.3% (men 42.8 vs. 33.3% and women 47.5 vs. 24.8%), respectively. Previously diagnosed diabetics had higher prevalence of DR than newly diagnosed diabetics, and these finding were particular prominent in women (Fig. 1). From multiple logistic regression analysis, duration of DM was the most important risk factors related to DR. Diabetic subjects treated with insulin had a higher risk of developing DR than those treated with diet control [14]. The prevalence of nephropathy and neuropathy were 12.9 and 23.5%, respectively (see Tables 4 and 5). For those patients with and those without nephropathy and neuropathy, the duration of
S52
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
Table 1 Prevalence of diabetes and IGT in Chinese and Asian populations Country/ population
Age range (years)
Sample size
Study year
DM
IGT
Crude rate Chinese (in Taiwan) Tainana ]20 ]40 Taipeib Ann-Lo, ]40 Keelungc Kin-Hu, ]30 Kinmend Chinese (outside of Taiwan) Da Qing, 25–74 China Singapore ]18 Hong Kong 18–64 Mauritius 25–74 Asian Vietnam South Korea Japan Fiji, indian (urban)
]15 ]30 ]45 ]20
Adjusted rate
Crude rate
Adjusted rate
1638 11478 2448
1996 1985 1988
9.0 6.2 8.0
9.2 5.8 8.0
14.0 – –
15.5 – –
236
1991
6.5
4.9
–
–
110660
1986
0.77
1.6
0.6
0.9
1417 1513 412
1985 1991 1987
4.0 4.5 11.7
M4.6, F4.9 7.7 11.5
0.6 7.3 16.5
M0.8, F0.3 M11.2, F8.8 M16.5, F21.7
4912 2497 916 846
1990 1991 1990 1980
1.2 9.1 11.9 13.1
1.4 7.2 10.4 M12.9, F11.0
1.6 11.8 16.6 10.3
1.7 8.9 15.3 M8.3, F11.8
a
Standard OGTT for each subject. Capillary blood glucose either after overnight fasting or 2-h postprandial by use of glucometer. c Two-hour postprandial blood glucose (Glucocheck SC B-2) or urinary glucose and adjusted with the population in Taiwan. d OGTT for subject with fasting plasma glucose levels between 5.6 and 7.8 mmol/l. b
DM, percentage of insulin treatment, percentage of hypertension, and the fasting plasma glucose were significantly different. Diabetic duration, hypertension, insulin treatment and glycemic control consistently correlated with nephropathy and neuropathy [15].
city of Taiwan, showed age-adjusted prevalence rates of 9.2% for diabetes (men 10.4%, women 8.1%) and IGT of 15.5% (men 15%, women 15.9) [12]. The prevalence of diabetes in southern Taiwan is the highest rate that has been reported here. In comparison with the prevalence rate
4. Discussion
Table 2 Prevalences of LVD, IHD, leg VD and stroke among diabetics and non-diabetics in Taiwana
The prevalence of diabetes in northern Taiwan was established between 1985 and 1991 and the rates were between 4.9 and 8.0% [4,10,11]. Studies from northern Taiwan indicate prevalence rates which are also higher than in China [16] and which are broadly similar to those of Hong Kong [17] and Singapore [18] but lower than Mauritius [19] (see Table 1). A recent study from Taiwan, conducted on an urban population in a southern
Normal LVD IHD Leg VD Stroke a
Non-diabetics (n = 513)
Diabetics (n = 608)
447 66 59 1 6
488 (80.0%) 120* (20.0%) 95* (15.8%) 10* (1.7%) 15* (2.5%)
(87.1%) (12.9%) (11.5%) (0.2%) (1.2%)
LVD, large vessel disease; IHD, ischemic heart disease; leg VD, leg vessel disease. * PB0.05.
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
S53
Table 3 Prevalence and severity of diabetic retinopathy among newly and previously diagnosed diabetica Retinopathy
Absent Background Pre-proliferative Proliferative a
Newly diagnosed diabetics
Previously diagnosed diabetics
Total
No.
No.
No.
145 45 1 0
% 75.9 23.6 0.5 0
196 120 14 6
% 58.4 35.7 4.2 1.8
344 165 15 6
% 65.0 30.0 2.8 2.2
Fisher’s exact test, PB0.005.
among Asian populations (see Table 1), the rate was higher than that in a Vietnamese study [20], the Korean study [21], close to that of the Japanese study [22], but lower than that in the Fiji Asian Indian study [23]. In a comparison with IGT prevalence studies in adult Chinese outside of Taiwan, the rate was higher than that in the Da Qing, China study, [16] the Singapore study, [18] and the Hong Kong study, [17] but close to that of the Mauritius study [19]. Comparing the prevalence rate among Asian populations showed that the Taiwan rate was higher than that in the Vietnamese study, [20] the Korean study, [21] and the Fiji Asian Indians study, [23] but close to that of the Japanese study [22]. Studies in different Chinese populations who have similar genetic characteristics have shown substantial variation in the prevalence of diabetes and IGT. This result indicates that environmental factors may play an important role, since the levels of westernization were very different among the Chinese in these areas. From the results of multiple logistic regression in Taiwan study, the significant risk factors associated with newly diagnosed diabetes were age, family history of DM, BMI, SBP, physical activity and TG [4,10 – 12]. Predictive factors for NIDDM in Chinese population are now quite well described and appear similar to those described for other populations. These factors have been described in studies reported from Taiwan [4,10 –12], China [16] and Mauritius [19], as well as from Hong Kong [17]. Increasing age, obesity, central obesity and a positive family history of diabetes are all major factors. Age as an independent predictor of diabetes has been reported in
many studies [24,25]. Family history of DM as a significant predictor for diabetes has also been demonstrated in several studies [26,27]. Physical inactivity has been less thoroughly examined but has been shown to be important in Mauritius [19] and Taiwan [12]. Many prospective studies have also shown that higher physical activity can reduce the risk of diabetes [28,29]. The mechanism may be related to increasing insulin sensitivity in skeletal muscle caused by physical activity [30]. In addition, BMI [26,27,31], SBP [11,12,31,32] and TG [31,33] have also been associated with the prevalence of diabetes from many studies. It could be explained by insulin resistance and hyperinsulinemia suggested by Reaven in his Banting lecture in 1988 [34] and from many other studies [35,36]. The proposed mechanism is that obese subjects are resistant to insulin-stimulated glucose uptake, which in turn leads to an increase in insulin concentration, enhanced hepatic very-lowdensity lipoprotein triglyceride secretion and hypertriglyceridemia and lead to a reduction of
Fig. 1. Comparison of the prevalence of retinopathy between newly and previously diagnosed diabetics by gender.
S54
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
Table 4 Prevalence of diabetic nephropathy in Chinese and Asian populations Country/population
Age range (years)
Sample size
Study year
Prevalence (%)
Chinese Taiwana Hong Kongb Singaporec
All ages All ages All ages
217 374 300
1978 1991 –
12.9 20.1 19.5
Asian Thailanda Japanc South Koreac Indiad
24–88 All ages 30–75 All ages
2060 2115 631 4941
– 1990 1993 –
18.7 20.1 13.8 1.9
a
Persistent proteinuria in absence of urinary tract infection. Albumin: creatinine \30 mg mmol. c AER\200 mg/min (300 mg/24 h) d AER\500 mg 24 h−1. b
Table 5 Prevalence of diabetic neuropathy in Chinese and Asian populations Country/population
Age range (years)
Sample size
Study year
Prevalence (%)
Chinese Singaporea Taiwanb
All ages All ages
150 217
– 1978
17.2 23.5
Asian Indiaa,c Japandd,c
– All ages
545 2115
– 1990
23.9 36.3
a
Impaired vibration perception and/or other sensation (pinprick, light touch, position). Abnormal nerve conduction velocity. c Absence of knee/ankle reflexes (at least one). d Pain and paraesthesia. b
sodium excretion, enhanced sympathetic nervous system activity, and hypertension [37]. The prevalence of IHD, leg VD and stroke in DM were 15.8, 1.7 and 2.5%, respectively. In a comparison of IHD prevalence studies in adult Chinese outside of Taiwan, the Taiwan rate was higher than that in the Hong Kong study and the Singapore study (see Table 6) [38]. Comparison of the prevalence rate among Asian populations showed that he rate was higher than that in the Sri Lanka study, the India study, the Thailand study and the Korean study but lower than that in the Japanese study [38]. CAD occurs earlier and more frequently in diabetics than non-diabetics, resulting in a higher prevalence for a given age [39]. On ECG, abnormalities are generally twice
as common in diabetics [40]. Correspondingly, the relative risk of cardiovascular death is around two to four times higher in diabetics than in non-diabetics. Hyperlipidemia, cigarette smoking, high BP, obesity, diabetes, physical inactivity, adverse psychosocial events, and thrombogenic factors have been identified as major risk factors of CAD [41–43]. Studies have shown that reduction of total cholesterol can decrease the morbidity and mortality of CAD [42–45]. In this study, the patients with a higher cholesterol level had a significantly increased relative risk of LVD and IHD. The second important risk factor of IHD in this study was HbA1c. Several studies have shown that good blood glucose control could improve the micro-vascular complications of diabetes
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
[46,47]. Our results also implied that good blood glucose control is extremely important in decreasing IHD in diabetic patients. In a comparison of leg VD (PVD) prevalence studies among the Asian population, the Taiwan rate was lower than that in the India study, the Sri Lanka study and the Korean study (see Table 7) [38]. PVD is strongly related to cigarette smoking [48,49]. We found that smoking patients had a significantly increased relative risk of leg VD compared with nonsmoking patients. Women diabetic subjects also had an increased risk of developing leg VD compared with men in this study. The reason why needs further exploration. Epidemiologic studies of DR have been conducted among different populations in many areas
S55
of the world. According to the WHO study [8], the prevalence of retinopathy varies greatly from one country to another, even when corrected for age and duration of diabetes. A study from northern Taiwan showed a prevalence of 35% for DR in NIDDM subjects and was not remarkably different compared with Asian and Western studies (see Table 8) [38]. Despite different study procedures and populations, several factors, including duration of diabetes, age at onset of diabetes, age at examination, type of diabetes treatment, control of diabetes hypertension, proteinuria, serum creatinine level, serum cholesterol level, and BMI have been found to correlate with the prevalence of DR. The duration of diabetes and the prevalence and severity of DR were
Table 6 CHD in diabetes in Chinese and Asian populations Country/population
Age range (years)
Sample size
Chinese Hong Konga,b Singaporea,b North Taiwana,b Southern Taiwana,b
35–54 ] 18 ] 40 ] 20
422 117 479 1638
Asian Indiaa,c Sri Lankab Thailanda,c Japanb South Koreab
All ages All age 24–88 All ages 30–75
4941 500 2060 976 631
Study year
1975 1984 1986 1996 – – – 1960 1993
Prevalence (%)
24.2 2.8 21.8 20.3 18.5 12.0 10.5 31.6 12.6
a
Past history of angina, myocardial infarction, stroke or bypass surgery. ECG coronary probable and/or coronary possible (Minnesota Code). c Ischaemic ECG change (further indefined). b
Table 7 PVD in diabetes in Chinese and Asian populations Country/population
Age range (years)
Chinese Northern Taiwana,b
]40
Asian Indiab,c Sri lankaa,b South Koreab
All ages All ages 30–75
a
Intermittent claudication. Absent arterial pulses on feet and/or amputation. c Ankle: brachial pressure index B0.9. b
Sample size
479 4941 500 631
Study year
Prevalence (%)
1986
1.7
– – 1993
3.9 5.6 5.9
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
S56
Table 8 Prevalence of diabetic retinopathy in Chinese and Asian populations Country/population
Age range (years)
Chinese Chinaa Hong Konga Singaporea Taiwana
All ages 35–54 All ages ]40
114 422 300 527
1995 1975 – 1985
33.0 32.5 38.0 34.9
Asian Indiaa Pakistana,b Sri Lankaa Thailandb Japana South Koreaa
All ages All ages All ages 24–88 All ages 30–75
6792 3000 1003 2060 976 631
– – – – 1960 1993
34.1 26.0 31.3 32.1 33.0 35.2
a b
Sample size
Study year
All retinopatyh (%)
Direct and/or indirect ophthalmoscopy with mydriasis. Fundus photography.
closely associated in the northern Taiwan study. The longer the duration of diabetes, the higher the prevalence of total DR. The prevalence of total DR were 29.1% for those subjects who had diabetes for less than 5 years, and 23.0% for subjects in whom diabetes was newly diagnosed. Similar results have also been demonstrated in other studies [50,51]. Some studies found that the duration of diabetes is the most crucial factor for total DR. [52,53]. The prevalence of nephropathy and neuropathy in the northern Taiwan study were 12.9 and 23.5%, respectively. For those patients with and those without nephropathy and neuropathy, the duration of DM, percentage of insulin treatment, percentage of hypertension, and fasting plasma glucose levels were significantly different. Diabetic duration, hypertension, insulin treatment and glycemic control consistently correlated with nephropathy and neuropathy. In a comparison of the nephropathy prevalence studies in the Chinese outside of Taiwan, the Taiwan rate was lower than that in the Singapore study and the Hong Kong study (see Table 4). Comparing of the prevalence rate among Asian populations (see Table 4) showed that the rate was higher than the India study and close to that of the Korean study but lower than the Thailand and Japanese studies [38]. Proteinuria was 15 times more prevalent in
diabetics than in non-diabetics [54]. Disease duration was a major determinant of nephropathy [8,54,55] and other factors included cholesterol levels [8], blood pressure [8,56], glycemic control [56] and persistent microalbuminuria [57,58]. The prevalence of hypertension was higher among NIDDM patients with proteinuria in the northern Taiwan study. It was well-established that the presence of hypertension can aggravate diabetic nephropathy and retinopathy [59,60]. However, its role in neuropathy is still ambiguous. A previous review summarized several older clinic-based studies with prevalence of various neuropathies ranging from 20 to 100% [61]. A consensus conference, convened in 1988 in San Antonio, Texas [62] made recommendations for the standardization of neuropathy endpoints. Several population-based studies with the prevalence of neuropathy ranged from 10.5 to 32.1% [63–66]. The prevalence of neuropathy was 17.2% in the northern Taiwan study. In comparing the neuropathy prevalence studies in Chinese outside of Taiwan and Asian populations, the Taiwan rate was higher than that in the Singapore study and close to that of the India study but lower than that of the Japanese study (see Table 5). The prevalence of diabetic neuropathy was examined in a recent multicenter study in the UK involving 3949 hospital-treated patients with NIDDM.
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
Neuropathy was present in 32.1% in NIDDM patients and was positively correlated with age and duration of diabetes [67]. There is very little information using the current batteries of tests that can be used to estimate the risk of neuropathy in unselected populations of diabetic patients, whether neuropathy risk increases like that of retinopathy, or plateaus like nephropathy, is an important but unanswered question.
References [1] WHO Ad Hoc Diabetes Reporting Group, H. King, M. Rewers, Global estimates for prevalence of diabetes mellitus and impaired glucose tolerance in adults, Diabetes. Care. 16 (1993) 157 –177. [2] Department of Health, Health and Vital Statistics. I. General Health Statistics, Taipei, Republic of China, Department of Health, Executive Yuan, 1996. [3] National Diabetes Data Group, Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance, Diabetes 28 (1979) 1039–1057. [4] T.Y. Tai, C.L. Yang, C.J. Chang, et al., Epidemiology of diabetes mellitus among adults in Taiwan, ROC, J. Med. Assoc. Thailand 70 (Suppl. 2) (1987) 42–48. [5] WHO Study Group on Diabetes Mellitus, Diabetes mellitus, WHO Technical Report Series 727, Geneva, 1985, pp. 9– 12. [6] World Health Organization, Hypertension and coronary heart disease: classification and criteria for epidemiological study, WHO Technical Report Series 168, Geneva, 1959. [7] R.S. Paffenbarger, S.N. Blair, I.M. Lee, R.T. Hyde, Measurement of physical activity to assess health effects in free-living populations, Med. Sci. Sport Exerc. 25 (1993) 60 – 70. [8] World Health Organization, Multinational study of vascular disease in diabetes: prevalence of small vessel and large vessel disease in diabetic patients from 14 centers, Diabetologia 28 (1985) 615–640. [9] R.C. Chen, S.M. Sung, C.F. Chen, C.J. Tzeng, I.N. Lien, T.P. Hung, Normal motor nerve conduction velocity amongst Chinese in Taiwan, J. Formos. Med. Assoc. 77 (1978) 394 – 401. [10] J.D. Lin, W.B. Shieh, M.J. Hung, H.S. Hung, Diabetes mellitus and hypertension based on the family history and 2-h postprandial blood sugar in the Ann-Lo district (Northern Taiwan), Diabetes Res. Clin. Pract. 20 (1993) 75 – 85. [11] P. Chou, M.J. Liao, H.S. Kuo, K.H. Hsiao, S.T. Tsai, A population survey on the prevalence of diabetes in KinHu, Kinmen, Diabetes Care 17 (1994) 1055–1058. [12] F.H. Lu, Y.C. Yang, J.S. Wu, C.H. Wu, C.J. Chang, A population-based study of the prevalence and associated
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
S57
factors of diabetes in southern Taiwan, Diabet. Med. 15 (1998) 564 – 572. C.C. Fu, C.J. Chang, C.H. Tseng, et al., Development of macrovascular diseases in NIDDM patients in northern Taiwan, Diabetes Care 16 (1993) 137 – 143. M.S. Chen, C.J. Kao, C.J. Chang, T.J. Wu, C.C. Fu, C.J. Chen, T.Y. Tai, Prevalence and risk factors of diabetic retinopathy among non-insulin-dependent diabetic subjects, Am. J. Ophthalmol. 114 (1992) 723 – 731. T.Y. Tai, C.H. Tsneg, S.M. Sung, R.F. Huang, C.J. Chen, S.H. Tsai, Retinopathy, neuropathy and nephropathy in non-insulin-dependent diabetic patients, J. Formos. Med. Assoc. 90 (1991) 936 – 940. S.R. Pan, Y.H. Hu, G.W. Li, P.A. Liu, P.H. Bennett, B.V. Howard, Impaired glucose tolerance and its relationship to ECG-indicated coronary heart disease and risk factors among Chinese-Da Qing IGT and diabetes study, Diabetes Care 16 (1993) 150 – 156. C.S. Cockram, J. Woo, E. Lau, et al., The prevalence of diabetes mellitus and impaired glucose tolerance among Hong Kong Chinese adults of working age, Diabetes Res. Clin. Pract. 21 (1993) 67 – 73. A.C. Thai, P.P.B. Yeo, K.C. Ln, K. Hung, W.Y. Ng, K.F. Lui, J.S. Cheas, Diabetes mellits and its chronic complications in Singapore: an increasing healthcare problem, Ann. Acad. Med. Singapore 19 (1990) 517 – 523. G.K. Dowse, P.Z. Zimmet, H. Gareeboo, et al., Abdominal obesity and physical inactivity as risk factors for NIDDM and impaired glucose tolerance in Indian, Greole and Chinese Mauritians, Diabetes Care 14 (1991) 271 – 282. P.S. Quoc, M.A. Charles, N.H. Cuong, et al., Blood glucose distribution and prevalence of diabetes in Hanoi, Am. J. Epidemiol. 139 (1994) 713 – 722. Y. Park, H. Lee, C.S. Koh, H. Min, K. Yoo, Y. Kim, Y. Shin, Prevalence of diabetes and IGT in Yonchon County, South Korea, Diabetes Care 48 (1995) 545 – 548. A. Sekikawa, M. Tominaga, K. Takahashi, et al., Prevalence of diabetes and impaired glucose tolerance in Funagata area, Japan, Diabetes Care 16 (1993) 570 – 574. P. Zimmet, R. Taylor, P. Ram, H. King, G. Sloman, L.R. Raper, D. Hunt, Prevalence of diabetes and impaired glucose tolerance in the biracial (Melanesian and Indian) population of Fiji: a rural – urban comparison, Am. J. Epidemiol. 118 (1983) 673 – 688. R.B. Lipton, Y. Liao, R.S. Cooper, D. McGee, Determinants of incident non-insulin-dependent diabetes mellitus among blacks and whites in a national sample: the NHANES I epidemiologic follow-up study, Am. J. Epidemiol. 138 (1993) 826 – 839. P.W. Wilson, K.M. Anderson, W.B. Kannel, Epidemiology of diabetes mellitus in the elderly: The Framinghan Study, Am. J. Med. 80 (Suppl. 5A) (1986) 3 – 9. W.J. Butler, L.D. Ostrander, W.J. Carman, D.E. Lamphier, Diabetes mellitus in Techmseh, Michigan: prevalence, incidence, and associated conditions, Am. J. Epidemiol. 116 (1982) 971 – 980.
S58
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59
[27] W.C. Knowler, P.H. Bennett, R.F. Hamman, M. Miller, Diabetes incidence and prevalence in Pima Indians: a 19-fold greater incidence than in Rochester, Minnesota, Am. J. Epideniol. 108 (1978) 497–505. [28] S.P. Helmrich, D.R. Ragland, R.W. Leng, R.S. Paffenbarger, Physical activity and reduced occurrence of noninsulin-dependent diabetes mellitus, N. Engl. J. Med. 325 (1991) 147 – 152. [29] J.E. Manson, E.B. Rimm, M.J. Stampfer, et al., Physical activity and incidence of non-insulin-dependent diabetes mellitus in women, Lancet 338 (1991) 774–778. [30] J.T. Devlin, Effects of exercise on insulin sensitivity in humans, Diabetes Care 15 (1992) 1690–1693. [31] J.H. Medalie, C.M. Papier, M.A. Gloodbourt, J.B. Herman, Major factors in the development of diabetes mellitus in 10 000 men, Arch. Intern. Med. 135 (1975) 811 – 817. [32] P.A. Morales, B.D. Mitchell, R.A. Valdez, H.P. Hazuda, M.P. Stern, S.M. Haffner, Incidence of NIDDM and impaired glucose tolerance in hypertensive subjects: The San Antonio Heart Study, Diabetes 42 (1993) 154–161. [33] E. Barrett-Connor, S.M. Grndy, M.J. Holdbrook, Plasma lipids and diabetes mellitus in an adults community, Am. J. Epidemiol. 115 (1982) 657–663. [34] G.M. Reaven, Banting lecture : role of insulin resistance in human disease, Diabetes 37 (1988) 1595–1607. [35] R.A. DeFronzo, E. Ferrannini, Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease, Diabetes Care 14 (1991) 173–194. [36] G.M. Reaven, H. Lithell, L. Landsberg, Hypertension and associated metabolic abnormalities: the role of insulin resistance and the sympathoadrenal system, N. Engl. J. Med. 334 (1996) 374–381. [37] J.M. Flback, J.R. Sowers, Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia, Am. J. Med. 91 (Suppl. 1A) (1991) 115–215. [38] A.F. Amos, D.J. McCarty, P. Zimmet, The rising global burden of diabetes and its complications: estimate and projection to the year 2010, Diabet. Med. 14 (1997) S7 – S85. [39] W.B. Kannel, D.L. MecGee, Diabetes and glucose tolerance as risk factors for cardiovascular disease, the Framingham Study, Diabetes Care 2 (1979) 920–926. [40] E. Barrett-Connor, T. Orchard, Diabetes and heart disease, in: M.I. Harris, R.F. Hmmah (Eds.), Diabetes in America. NIH Publication XVI, 1985, pp. 1–41. [41] The Lipid Research Clinics Coronary Primary Prevention Trial Results 1. Reduction in incidence of coronary heart disease, J. Am. Med. Assoc. 251 (1984) 351–364. [42] M.H. Frick, O. Elo, K. Haapa, et al., Helsinki Heart Study — primary prevention trial with gemfibrozil in middle-aged men with dyslipidemia, N. Engl. J. Med. 317 (1987) 1237 – 1245. [43] D.H. Blankenhom, S.A. Nessim, R.L. Johnson, M.E. Sanmacro, S.P. Azen, L. Cashin-Hemphill, Beneficial effects of combined colestipol-niacin therapy on coronary
[44]
[45]
[46]
[47]
[48]
[49]
[50]
[51]
[52]
[53]
[54]
[55]
[56]
[57]
atherosclerosis and coronary venous bypass grafts, J. Am. Med. Assoc. 257 (1987) 3233 – 3240. Multiple Risk Factor Intervention Trial Research Group, Multiple risk factor intervention trial. Risk factor changes and mortality results, J. Am. Med. Assoc. 248 (1982) 1465 – 1477. W.D. Stamler, J.D. Neaton, Prevalence and prognostic significance of hypercholesterolemia in men with hypertension: prospective data on the primary screenees of the multiple risk factor intervention trial, Am. J. Med. 80 (Suppl. 2A) (1986) 33 – 36. R. Engerman, J.J. Bloodworth, S. Nelson, Relationship of microvascular disease in diabetes to metabolic control, Diabetes 26 (1977) 760 – 769. P. Raskin, J. Rosenstock, Blood glucose control and diabetic complications, Ann. Intern. Med. 105 (1986) 254 – 263. R.B. Paisey, G. Arredondo, A. Villalobos, O. Lozaano, L. Guevara, S. Kelly, Association of differing dietary, metabolic, and clinical risk factors with macrovascular complications of diabetes: a prevalence study of 503 Mexican type II diabetic subjects I, Diabetes Care 7 (1984) 421 – 427. UK Prospective Diabetes Study: 6, Complications in newly diagnosed type 2 diabetic patients and their association with different clinical and biochemical risk factors, Diabetes Res. 13 (1990) 1 – 11. The Wisconsin Epidemiologic Study of Diabetic Retinopathy, III. Prevalence and risk of diabetic retinopathy when age at diagnosis is 30 or more years, Arch, Ophthalmol, 102 (1984) 527 – 532. L.M. Aiello, L.I. Rand, J.C. Briones, M.Z. Wafai, J.G. Sebestyen, Diabetic retinopathy in Joslin clinic patients with adult-onset diabetes, Ophthalmology 88 (1981) 619 – 623. I.J. Constable, M.W. Knuiman, T.A. Welborn, R.L. Cooper, K.M. Stantion, V.J. McCann, G.C. Grose, Assessing the risk of diabetic retinopathy, Am. J. Ophthalmol. 97 (1984) 53 – 61. B. Jerneld, P. Algvere, Relationship of duration and onset of diabetes to prevalence of diabetic retinopathy, Am. J. Ophthalmol. 102 (1986) 431 – 437. S.A. Kamenetsky, P.H. Bannett, S. Dippe, M. Miller, P.M. Le Compte, A clinical and histologic study of diabetic nephropathy in the Pimas Indians, Diabetes 23 (1974) 61 – 64. W.H. Hemman, S.M. Teutsch, Kidney diseases associated with diabetes, in: M.I. Harrris, R.F. Hammah (Eds.), Diabetes in America. NIH Publlication XIV, 1985, pp. 1 – 31. C.E. Mogensen, C.K. Christensen, Predicting diabetic nephropathy in insulin-dependent diabetes, N. Engl. J. Med. 321 (1982) 1430 – 1432. R.J. Jarrett, G.C. Viberti, A. Argyropoulos, et al., Microalbuminuria predicts mortality in non-insulin-dependent diabetics, Diabet. Med. 1 (1984) 17 – 19.
C.-J. Chang et al. / Diabetes Research and Clinical Practice 50 Suppl. 2 (2000) S49 – S59 [58] C.E. Mogensen, R.W. Bilous, D. Mackintosch, J.J. Bending, H. Keen, Long term correction of hyperglycemia and progression of renal failure in insulin-dependent diabetes, Br. Med. J. 286 (1983) 598–621. [59] J.M. Sprafke, A.P.M. Bender, H.G. Jagger, Prevalence of hypertension and associated risk factors among diabetic individuals: the three-city study, Diabetes Care 11 (1982) 685 – 688. [60] C.E. Mogensen, Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy, Br. Med. J. 285 (1982) 685 – 688. [61] D.A. Greene, A.A.F. Sima, M.A. Pfeifer, Neuropathy, in: C.E. Mogensen, E. Standl (Eds.), Prevention and Treatment of Diabetic Late Complications, Wlater de Gruyter, Berlin, 1989, pp. 93 –150. [62] Consensus Statement, Report and recommendations of the San Antonio conference on diabetic neuropathy, Diabetes 37 (1988) 1000–1004. [63] D.P. Walters, W. Gatling, M.A. Muullee, R.D. Hill, The prevalence of diabetic distal sensory neuropathy
.
[64]
[65]
[66]
[67]
S59
in an English community, Diabet. Med. 9 (1992) 349 – 353. J.M. Lethtinen, M. Uusitupa, O. Sitonen, K. Pyorala, Prevalence of neuropathy in newly diagnosed NIDDM and non-diabetic control subjects, Diabetes 38 (1989) 1307 – 1313. M.W. Knuiman, T.A. Welborn, V.J. McCann, K.G. Stanton, I.J. Constable, Prevalence of diabetic complications in relation to risk factors, Diabetes 35 (1986) 1332 – 1339. P.J. Palumbo, L.R. Elveback, J.P. Whisnant, Neurologic complications of diabetes mellitus: transient ischemic attack, stroke, and peripheral neuropathy, Adv. Neurol. 19 (1978) 593 – 601. M.J. Young, A.J.M. Boulton, A.F. Macleod, D.R.R. Williams, P.H. Sonsken, A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population, Diabetologia 36 (1993) 150 – 154.