Diabetes Research Centre and M. V. Hospital for Diabetes, Madras, India
Correspondence and offprint requests to: Dr Vijay Viswanathan, Diabetes Research Centre, No. 4, Main Road, Royapuram, Madras, 600 013, India.
Introduction
It has been predicted that world wide the prevalence of diabetes in adults would increase to 5.4% by the year 2025 from the prevalence rate of 4.0% in 1995. Consequently the number of adults with diabetes in the world would rise from 135 million in 1995 to 300 million in the year 2025 [1]. It is expected that much of this increase in prevalence rate will occur in developing countries. While a 42% increase is expected in developed countries, a 170% increase is expected in the developing countries. In the latter, most of the diabetic patients are in the age range of 4564 years, while in developed countries most of them are 65 years. Therefore diabetic patients in developing countries are even more vulnerable to develop the micro- vascular complications of diabetes including diabetic nephropathy.
Type 2 diabetes in Asian-Indians: differences from the West
Studies from the UK have found that type 2 diabetes is three to four times more common in South Asians than in Europeans [2]. Asian-Indians have been identified as one of the ethnic groups with a high prevalence of type 2 diabetes [3] and a high familial aggregation of type 2 diabetes [4]. The prevalence of type 2 diabetes was as high as 50% among the offspring of conjugal type 2 diabetic parents in India, which is the highest prevalence rate reported until now [5]. In a population-based survey in an urban population in South India, it was found that there was a 40% increase in the agestandardized prevalence of diabetes over a period of 6 years, from 8.2% in 19881989 to 11.6% in 19941995 [6].
High prevalence of maturity-onset diabetes of the young (MODY)
MODY refers to a type of non-insulin dependent diabetes in which the patients develop diabetes at <25 years of age and have clinical characteristics similar to type 2 diabetes. The prevalence of MODY in a cohort of 4560 patients was found to be 4.8% in South India [7].
Although the prevalence of obesity is less among Asian-Indians than Caucasians, the former have an increased upper body adiposity as measured by the waist to hip ratio (WHR) which is an independent risk factor for type 2 diabetes [8].
Diabetic nephropathy among migrant Asian-Indians
A recent, large cross-sectional study confirmed the high burden of renal disease in South Asian subjects with type 2 diabetes compared with Europeans [2]. In this study the prevalence of microalbuminuria in South Asian men and woman was higher by 1.2- and 1.7-fold respectively.
Diabetic nephropathy among native Asian-Indians
Diabetic nephropathy is one of the leading causes of chronic renal failure in India. It has been reported that among 4837 patients with chronic renal failure seen over a period of 10 years, the prevalence of diabetic nephropathy was 30.3% followed by chronic interstitial nephritis (23.0%) and chronic glomerulonephritis (17.7%) [10].
Familial aggregation of diabetic nephropathy
A comparison of sibling pairs showed strong familial clustering of diabetic nephropathy in patients with type 2 diabetes in South India [11]. Two groups of diabetic siblings of type 2 diabetic patients matched for age, body mass index and duration of diabetes mellitus were studied. In one group, siblings of probands with diabetic nephropathy were included. The other group comprised siblings of probands with normoalbuminuria. It was found that proteinuria was present in 50% and microalbuminuria in 26.7% of the siblings of probands with diabetic nephropathy. In contrast, the prevalence of proteinuria and microalbuminuria among siblings of probands with normoalbuminuria was 0% and 3.3% respectively (P=0.057 for microalbuminuria).
Progression of renal disease: a 6-year follow-up study
It is impractical to estimate microalbuminuria in all the centres of developing countries, since its estimation is expensive and requires sophisticated instruments. The expected protein excretion, assessed as the protein to creatinine ratio in a random urine sample, was measured in 410 type 2 diabetic patients (M:F 264:146; mean age 55.6±9.5 years) who had regular follow-up for 6 years. During the follow-up, nephropathy (defined as persistent proteinuria of >500 mg/day with diabetic retinopathy) developed in 6.7% of those who had normal protein excretion at baseline (<100 mg/day) and in 43.4% of the mildly proteinuric subjects (100500 mg/day) (2=41.6; P<0.001) (Vijay Viswanathan, unpublished data). Hence the urinary protein to creatinine ratio in a random urine sample was found to be a useful test to predict the risk of overt proteinuria.
In this study the serum creatinine concentration was measured at yearly intervals in all the patients. During the 6-year follow-up, 70 out of 410 patients developed overt diabetic nephropathy. Among them 17 patients developed renal failure, defined as a serum creatinine concentration of 1.2 mg/dl. The incidence of renal failure among the 410 patients was 0.69% per annum (CI 0.281.0%).
Risk factors for proteinuria in type 2 diabetes
In a retrospective analysis, the factors predisposing to proteinuria and its progression were compared in two groups of type 2 diabetic patients matched for age, gender and duration of diabetes, one group without proteinuria (<100 mg/day, n=25) and the other with persistent proteinuria (500 mg/day, n=25) [12]. The factors contributed to the development of proteinuria during the 2-year follow-up period were the initial HbA1 and initial systolic blood pressure. The deterioration of creatinine clearance was related to the presence of proteinuria and initial diastolic pressure.
High risk of cardiovascular morbidity in proteinuric South Indian type 2 diabetic patients
The presence of cardiovascular disease (CVD), viz. myocardial infarction, ischaemic heart disease and hypertension, was compared between 297 patients with diabetic nephropathy and 296 patients with normoalbuminuria (albumin to creatinine ratio <30 µg/mg creatinine) [13]. The risk of CVD was 3-fold higher in the nephropathy group than in the non-proteinuric group (39 vs 13.2%, P<0.001). The prevalence of hypertension was also higher among the proteinuric patients (56.5 vs 24.7%, P>0.001). This study therefore emphasizes the need for early screening of nephropathic patients for cardiovascular risk factors.
Conclusion
Developing countries such as India with its large burden of diabetes and vulnerability to the chronic complications including diabetic nephropathy, obviously must evolve strategies for primary prevention of diabetes and also for prevention of its secondary complications. Early screening and appropriate therapeutic intervention are the first steps towards achieving this goal.
References