June 2008, Vol 30, No. 2
Original Articles

Proportions and risk factors for chronic diabetic complications among Type 2 diabetic patients in a primary care clinic

Dominic M W Lau 劉敏維

HK Pract 2008;30:72-85

Summary

Objective: To estimate the proportions of chronic diabetic complications and examine the associations between complications and associated risk factors among Type 2 diabetic patients in a primary care clinic.   

Design: Cross-sectional study.

Subjects: All Type 2 diabetic patients who regularly attended the Hong Kong Families Clinic for follow up of diabetes mellitus in 2005.

Main outcome measures: Three aspects of information were collected: 1) basic demographic data of diabetes mellitus patients recruited for this study, 2) risk factors (the duration of diabetes mellitus, HbA1c level, smoking status, hypertension, hyperlipidaemia, obesity) for chronic diabetic complications and 3) proportions of microvascular (retinopathy, nephropathy and peripheral neuropathy) and macrovascular complications (coronary heart, cerebrovascular, and peripheral vascular diseases). Relevant information obtained was mainly from the clinic's diabetic registry and review of the medical records.

Results: 523 patients were recruited and from these 512 medical records were available for analysis. The mean age was 57.9 years with the mean duration of diabetes mellitus being 5.8 years. 17% suffered from one or more microvascular complications in which retinopathy (9.7%) and nephropathy (7.2%) accounted for the vast majority. 5.3% had one or more macrovascular complications and coronary heart disease (2.5%) was the major condition. 1.6% and 1.4% patients were documented to have cerebrovascular disease and peripheral vascular disease respectively. Logistic regression revealed that the longer the duration of diabetes mellitus was then the more likely the association with retinopathy, nephropathy and presence of any microvascular complication. Duration of diabetes mellitus was also positively and independently associated with cerebrovascular disease, coronary heart disease and the presence of any macrovascular complication. Hypertension was the most significant risk factor for nephropathy, and the presence of any microvascular or macrovascular complication. The presence of microvascular complication was found to be an independent risk factor for cerebrovascular disease.

Conclusion: Chronic microvascular diseases were common among Type 2 diabetic patients in primary care. The major risk factors for diabetic complications were the length of time of having diabetes mellitus and the presence of hypertension. Vigorous complication screening was recommended in these high risk patients.

Keywords: Chronic diabetic complications; risk factors; Type 2 diabetes mellitus; primary care

摘要

目的：評估基層診所第二型糖尿病人罹患糖尿病併發症的比率，檢測這些併發症與相關危險因數的關係。

設計：橫切面調查。

對象：2005年於指定診所定期覆診的所有第二型糖尿病人。

主要測量內容：收集三方面的資料。1)糖尿病人的基本人口統計資料，2)慢性糖尿病併發症的危險因素(糖尿病罹患時間、糖化血紅蛋白水準、吸煙習慣、高血壓、高血脂、肥胖)，3)微血管併發症(視網膜病變、腎臟病變和周邊神經病變)及大血管併發症(心臟血管疾病、腦部血管疾病和周邊血管疾病)的比率。相關資料來自診所內糖尿病註冊記錄和醫療記錄回顧。

結果：523位病人符合條件，其中512份醫療記錄可供分析，平均年齡為57.9歲，平均糖尿病罹患時間是5.8年。17%的病人患上一種或多種微血管併發症，絕大多數屬於視網膜病變(9.7%)和腎臟病變(7.2%)。5.3%的病人患上一種或多種大血管併發症，主要是心臟血管疾病(2.5%)，此外分別有1.6%及1.4%的病人證實出現腦部血管疾病和周邊血管疾病。邏輯迴歸分析顯示罹患糖尿病較長時間與視網膜病變、腎臟病變和任何微血管併發症有密切關係，並顯示與腦部血管疾病、心臟血管疾病和其他大血管併發症有獨立、正向的關係。高血壓是腎臟病變、任何微血管和大血管併發症最顯著的危險因素。微血管併發症是腦部血管疾病的獨立危險因素。

結論：基層醫療中，第二型糖尿病人發生慢性微血管病變十分普遍。糖尿病併發症的主要危險因素是罹患糖尿病的時間和高血壓。為高危病人提供全面的併發症普查值得推廣。主要詞彙：慢性糖尿病併發症、危險因素、第二型糖尿病、基層醫療。

Introduction

The prevalence of diabetes mellitus among the working population of Hong Kong has doubled over the past 10 years. The age adjusted prevalence was estimated to be 8.5%.1 It is the eighth commonest cause of death.2 It results in rising public expenditure because of absence from work and health care expenses.3

Many diabetic patients are treated by primary care physicians. Diabetes mellitus was the third commonest chronic illness encountered, constituting 8.6% and 5.5% in the elderly and adult age group respectively.4

Chronic diabetic complications commonly occur among Type 2 diabetic patients. The prevalence of chronic diabetic complications and associated risk factors have been reported in various local5-7 and overseas studies.8,9 However, most of these studies were conducted in secondary or tertiary institutions. Two local primary care studies focusing on microalbuminuria and diabetic retinopathy have been performed.10,11 Nevertheless, both studies did not include hyperlipidaemia and obesity for analysis. In fact, these two conditions are known major cardiovascular risk factors.9 In addition, problems related to macrovascular complications were not addressed in either study and comparable local data were missing from community based centres. In order to find out the proportions of chronic diabetic complications and the associations between complications and associated risk factors among Type 2 diabetic patients, we performed a study specifically targeting primary care. This information would enable physicians to determine the treatment focus more effectively and develop cost-effective interventions in diabetic management.

Methods

Subjects

This was a cross-sectional study involving all Type 2 diabetic patients who regularly attended the Hong Kong Families Clinic for follow up of diabetes mellitus in 2005. The clinic, with five qualified family physicians, is a Family Medicine Training Centre accredited by the Hong Kong College of Family Physicians. It serves mainly civil servants, their dependents and pensioners.

The majority of patients were diagnosed as having Type 2 diabetes mellitus in the clinic according to the criteria proposed by the American Diabetes Association.12 Others had been referred to the clinic either from public hospitals or from other primary care clinics because of geographical reasons or patients' preferences. The identities of all diabetic patients were recorded in a computerized diabetic registry. A designated nurse was responsible for data entry and updating information. There were in total 523 Type 2 diabetic patients recorded in 2005. Patients with Type 1 diabetes mellitus and those who had regular follow up for diabetes mellitus in other medical institutions were excluded from the study.

Main outcome measures

Three aspects of information were collected in this study 

a) Basic demographic data of recruited subjects
  1. Age
  2. Gender.
     
b) Risk factors for chronic diabetic complications
  1. Duration of diabetes mellitus
  2. Glycaemic control
    This was defined as a percentage of blood glycated haemoglobin (HbA1c) within one year.13 The last reading was used in cases where more than one blood sample were performed within the study period.
  3. Smoking status
    The status was categorized as never or ever smoked.
  4. Hypertension
    Hypertension was defined as having two or more consecutive office blood pressure measurements of " 140/90 mm Hg14 or a documented history of hypertension.
  5. Hyperlipidaemia
    This was defined as having a fasting serum total cholesterol level " 5.2mmol/L or a fasting serum triglyceride level " 2.3mmol/L.13
  6. Obesity
    Obesity was defined as body mass index ( BMI ) " 25 kg/m2 for Chinese15 and " 30 kg/m2 for Caucasian.16
     
c) Proportions of chronic diabetic complications
  1. Microvascular complications
     
   

Retinopathy

This was assessed by taking non-mydriatic fundus photographs (Canon CR-45UAF camera with 45" single field) of both eyes. Numerous studies have supported the use of retinal photography as the preferred method of screening for diabetic retinopathy.17,18 The retinal images were interpreted by a group of trained family physicians who had undergone training in the interpretation of retinal photographs. The grading of retinopathy was defined according to the modified Airlie House classification.19 For doubtful cases, arbitration would be obtained from an ophthalmologist.

Nephropathy

Nephropathy was defined as having a urinary albumin excretion at or above 30 mg/day and screened by checking spot urine samples for microalbuminuria.20 The instrument used was Clinitek 50 (Bayer Diagnostic Manufacturing Ltd, Bridgend, United Kingdom) which is a semiquantitative screening tool that measures the albumin-to-creatinine ratio (ACR) from a spot urine specimen. The test result is positive if ACR is " 30 mg/g. The reported sensitivity of detecting microalbuminuria is 97% with a specificity of 83%.20 Patient would be tested for urinary albumin excretion over 24 hours for at least two times for confirmation in case of positive screening result.

Peripheral neuropathy

This was assessed by examining four pressure points in each foot with the Semmes Weinstein 10g monofilament. The test is regarded as positive if the patient cannot feel the monofilament on two out of three pricking attempts at any of the designated sites.21
     
  2. Macrovascular complications
     
   

Coronary heart disease

This was diagnosed when there was a documented history of myocardial infarction or angina had been reported and recorded in the medical record.

Cerebrovascular disease

This was defined as the presence of a documented history of cerebrovascular accident/stroke or transient cerebral ischaemia in the medical record.

Peripheral vascular disease

This was screened by checking for the presence of the dorsalis pedis and posterior tibial pulses of both legs. The disease is present if one or more pulses on either side are not palpable.

Annual assessments of all diabetic patients who had had regular follow up for diabetes mellitus were performed under the same protocol.22 Registered nurses were responsible for recording basic demographic data, checking of body mass index and blood pressure, assessing for nephropathy and neuropathy of these patients. Data such as the duration of diabetes mellitus, smoking status, checking for retinopathy and macrovascular complications were completed by the case doctor.

Statistical methods

All the data was entered and analyzed using the Statistical Package for the Social Sciences version 10.0 (SPSS Inc, Chicago [IL], United States). For univariate analysis between risk factors and chronic diabetic complications, odds ratio with 95% confidence interval and Mann-Whitney test with p value <0.05 as statistically significant were used for categorical variables and continuous variables respectively. In order to find out the independent risk factors for various diabetic complications, two stage binary logistic regression was performed and the results were interpreted by odds ratio with 95% confidence interval. Analysis with adjustment for all variables was done. Forward stepwise likelihood ratio with entry probability of 0.05 and removal probability of 0.10 was then employed to obtain the most significant logistic regression model. Hosmer and Lemeshow test was used to check the appropriateness of using the logistic regression model with a cut-off point of p value < 0.05 as statistically significant.

Ethical consideration

All the data collected was entered into a computer in the clinic. Password was necessary for data access. On the other hand, as the present project was a cross-sectional descriptive study, measures that secure the safety of subjects were not applicable. The study was approved by the Survey and Behavioral Research Ethics Committee of the Chinese University of Hong Kong

Results

Profile of patients

Out of a total 6859 patients attending the clinic in 2005, there were 523 Type 2 diabetic patients (7.6%). However, 11 medical records (8 male, 3 female) had missing data and as a result, 512 cases (97.9%) were available for analysis. About two-thirds of diabetic patients were male. The mean age was 57.9 years with mean duration of diabetes mellitus of 5.8 years. Table 1 summarizes the patients' characteristics.

Proportions of chronic diabetic complications (Table 1)

There were 86 patients (17%) having one or more microvascular complications. 49 (9.7%) suffered from retinopathy and 37 (7.2%) suffered from nephropathy. 3 patients (0.6%) were diagnosed as having peripheral neuropathy. 27 patients (5.3%) suffered from one or more macrovascular complications. 13 patients (2.5%) and 8 patients (1.6%) were documented to have a history of coronary heart disease and cerebrovascular disease respectively. The remaining 7 patients (1.4%) suffered from peripheral vascular disease. There was no obvious difference in the disease pattern between male and female diabetic patients.

Association of risk factors with chronic diabetic complications

Univariate analysis of association between individual risk factor and chronic diabetic complications are shown in Table 2 and Table 3. For multivariate analysis, Hosmer and Lemeshow test showed that forward stepwise logistic regression model's estimates fitted the data of various chronic diabetic complications at an acceptable level (Table 4). Adjusted odds ratio of statistically significant variables and results of forward stepwise logistic regression are summarized in Table 5 and 6 respectively

1. Microvascular complications

Retinopathy

Patients with diabetic retinopathy were found to have a longer history of diabetes mellitus. Otherwise, there was no significant association between retinopathy and the other risk factors (Table 2). Longer duration of diabetes mellitus was found to be borderline statistically significant (OR=1.047, 95%CI: 1.000-1.097) in the forward stepwise logistic regression model (Table 6). However, the effect was not present after adjustment for other variables (Table 5).

Nephropathy

Patients with diabetic nephropathy were older, and more likely to suffer from hypertension and hyperlipidaemia. They also had a longer history of diabetes mellitus, a higher fasting serum total cholesterol and LDL-cholesterol (Table 2). After adjusting for other variables, the association with hyperlipidaemia was not statistically significant (adjusted OR=2.195, 95%CI: 0.997-4.832) (Table 5). On the other hand, the presence of hypertension (OR=2.709, 95%CI: 1.209-6.070) and a long diabetes mellitus history (OR=1.057, 95CI: 1.005-1.112) were found to be the most significant risk factors for nephropathy (Table 6).

Peripheral neuropathy

None of the risk factors except blood level of HbA1c was associated with diabetic neuropathy in the univariate analysis. Interestingly, patients with neuropathy had a lower level of HbA1c than those without neuropathy (Table 2). Nevertheless, the association between HbA1c level and neuropathy was not statistically significant after adjustment for the other variables and older age was the only independent risk factor for neuropathy (Table 5 and Table 6).

Presence of any microvascular complication

Patients with one or more microvascular complications had a longer history of diabetes mellitus and were more likely to suffer from hypertension. In addition, they had higher LDL-cholesterol levels (Table 2). The association of both the longer duration of diabetes and presence of hypertension with any microvascular complication were also found in the logistic regression model with odds ratios of 1.055 (95%CI: 1.015-1.096) and 1.793 (95%CI: 1.085-2.965) respectively (Table 6) and the relationship were independent of the other variables (Table 5).

2. Macrovascular complications

Cerebrovascular disease

The longer duration of diabetes mellitus and the presence of any microvascular complication were positively associated with cerebrovascular disease (Table 3). On the other hand, a lower fasting serum level of total cholesterol, LDL-cholesterol and triglyceride were seen among patients with cerebrovascular disease (Table 3). The findings were also consistent after adjustment for other risk factors in which the adjusted odds ratios were 1.111 (95%CI: 1.007-1.226) and 4.793 (95%CI: 1.098-20.921) for duration of diabetes and presence of microvascular complication respectively (Table 5). These two variables were also included in the final logistic regression model (Table 6).

Coronary heart disease

Similar to cerebrovascular disease, patients with coronary heart disease had a lower serum total cholesterol than those without the disease (Table 3). None of the risk factors was associated with coronary heart disease statistically. From the regression analysis, the longer duration of diabetes mellitus and hypertension were independent predictors after adjustment (Table 5) and the length of diabetes mellitus was found to be the most significant risk factor for the disease (OR=1.074, 95%CI: 0.999-1.156) (Table 6).

Peripheral vascular disease

A higher body mass index was found to be a risk factor for peripheral vascular disease in the univariate analysis (Table 3). However, the association was not seen in the logistic regression model (Table 5 and Table 6).

Any macrovascular complication

A long history of diabetes mellitus and the presence of hypertension were positively associated with the presence of any macrovascular complications (Table 3). The findings were supported by the results of logistic regression in which both variables were found to be the most significant and independent risk factors even after adjusting for the other variables (Table 5 and Table 6). On the other hand, patients suffering from one or more of these complication(s) had a lower fasting serum total cholesterol and LDL-cholesterol (Table 3).

Discussion

Microvascular complications

A significant proportion of our patients had established diabetic complications. About one-fifth of them suffered from one or more microvascular complications in which retinopathy and nephropathy accounted for the vast majority of cases. The proportions were lower than that reported by the local tertiary institutions (22% for retinopathy,5 15% - 18% for nephropathy6,7) and community based centres (28.4% for retinopathy,11 13.4% for microalbuminuria10 ). This was accountable because of differences in the characteristics of the diabetic patients and the diagnostic criteria of diabetic complications between various studies. Surprisingly, only very few patients were diagnosed to have neuropathy and the figure was much lower than the predicted prevalence of 13%.5 However, comparable local data in primary care are lacking and large scale epidemiological studies are necessary to address this issue.

There is strong evidence suggesting that lowering blood pressure23,24 and improving blood glucose level25,26 can reduce the frequency of microvascular complications. These were consistent with our findings that hypertension was one of the best predictors for nephropathy and any microvascular complication. Nevertheless, the effect of hypertension on nephropathy was not seen after adjusting for the other variables and this may be related to the multi-factorial nature of hypertension on the development of nephropathy. On the other hand, the effect of glycaemic control on microvascular complication was not demonstrated in the analysis of logistic regression. This was probably due to the drawback of this study being a cross sectional study.

A longer duration of diabetes mellitus was found to be one of the risk factors for retinopathy, nephropathy and any microvascular complication from our study. These associations were also noticed in a large multinational cohort study.27,28 However, the effect on retinopathy and nephropathy were not significant after adjustment for other variables. This implies that other factors like age may play some role in the association. On the other hand, in light of the relatively small number of neuropathy events, none of the major modifiable risk factors was found to have statistically significant associations in our analysis.

The role of hyperlipidaemia in diabetic nephropathy has drawn a lot of attention recently. A local prospective trial showed that effective normalization of hypercholesterolaemia might retard the progression of nephropathy in patients with Type 2 diabetes mellitus.29 This was consistent with the finding that hyperlipidaemia was one of the risk factors for nephropathy from both univariate analysis and logistic regression with adjustment in our study.

Macrovascular complications

The proportions of macrovascular complications in our target population were much lower than that reported in western countries. A large scale primary care study conducted in Spain showed that the prevalence was 33%.30 Nevertheless, there is a great variation in the prevalence between eastern and western countries. Compared with Caucasians, Chinese diabetic patients have an extraordinary lower rate of vascular complications.32-34 The reason behind this is not clear but it can be partially explained by the relative lower rate of hypertension, hyperlipidaemia, obesity and smoking among Chinese diabetic patients.33 In our study, coronary heart disease accounted for the vast majority of macrovascular complications and the result was similar to that seen with overseas studies.

Diabetes mellitus is an independent risk factor for the development of cardiovascular disease.34 However, whether or not the traditional cardiovascular risk factors increase the risk of cardiovascular disease in diabetes in the general population has remained controversial.35 Unlike microvascular complication, the causal link between hyperglycaemia and macrovascular disease cannot be established as reflected by the results of the DCCT36 and UKPDS.25 Multiple predictors including classic risk factors like hypertension, smoking and dyslipidaemia as well as diabetes related variables such as glycaemic control, proteinuria and retinopathy could be associated with the development of macrovascular complications.37 In our study, the significant positive relationship between microvascular complication and cerebrovascular disease was demonstrated. Furthermore, hypertension was found to be the most important risk factor for the occurrence of any macrovascular complication even after adjusting for other variables. On the contrary, we failed to demonstrate the effects of other classic risk factors like smoking and dyslipidaemia. This may be due to the relatively low proportion of smokers, hyperlipidaemia and macrovascular complications among our target samples. In addition, the control of hyperlipidaemia in patients with macrovascular complication(s) was significantly better than those without complication in our study. This was probably due to the more vigorous management of dyslipidaemia in these high risk patients. This may further dilute the effect of dyslipidaemia on the development of subsequent macrovascular diseases.

The relationship between the duration of Type 2 diabetes mellitus and macrovascular diseases is controversial. Some prospective studies37,38 did show a statistically significant association while others39,40 did not. In our study, the duration of diabetes mellitus was positively and independently associated with cerebrovascular disease, coronary heart disease and any macrovascular complication. Further large scale prospective studies are necessary before a definitive conclusion can be drawn on this issue.

There are several limitations with our study. The clinic of the author only serves civil servants and their dependents and the results of the study might not represent the true picture of the whole primary care population. In addition, errors in information-gathering such as duration of diabetes mellitus and smoking status might have occurred, especially if the information was only obtained from the patient's history. Furthermore, as the diagnosis of diabetic complications mainly depended on the corresponding screening tests and documentation in the medical records, the findings might not be very accurate. The relatively few cases of macrovascular complications in our study may affect the reliability of the results from the statistical analysis. The interpretation of the effects of some variables like glycaemic control and serum lipid level on diabetic complications would also be limited by the cross sectional design of the study.

Conclusions and recommendations

Chronic microvascular complications are common among Type 2 diabetic patients in primary care. Compared with Caucasians, relatively lower rates of macrovascular diseases were noticed. Longer duration of diabetes mellitus and the presence of hypertension were the major risk factors for both microvascular and macrovascular complications. Vigorous complication screening is recommended in these high risk patients based on the study findings

Acknowledgements

I would like to thank Professor Ignatius TS Yu, Dr Luke CY Tsang and Dr David VK Chao for their valuable comments on this study. This paper arises out of the project work carried out by the author during the Master of Public Health Programme at the Chinese University of Hong Kong.

Key messages

  1. Chronic microvascular complications were common among Type 2 diabetic patients.
  2. Compared with Caucasians, lower rates of macrovascular diseases were noticed.
  3. Longer duration of diabetes mellitus and presence of hypertension were the major risk factors for both microvascular and macrovascular complications

Dominic M W Lau, MPH (CUHK), FRACGP, FHKCFP, FHKAM (Family Medicine)
Medical and Health Officer,
Professional Development and Quality Assurance, Department of Health.

Correspondence to: Dr Dominic M W Lau, Hong Kong Families Clinic, 4/F, Tang Chi Ngong Specialist Clinic, 284 Queen's Road East, Wan Chai, Hong Kong SAR

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