Shashank R Joshi*, AK Das**, VJ Vijay*** , V Mohan***

*Department of Endocrinology, Lilavati Hospital and Bhatia Hospital, Seth G. S. Medical College and KEM Hospital, Mumbai. **Additional Director General of Health Service, Govt. of India & Director, Professor of Medicine and M.S. JIPMER Pondicherry. ***Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialities Centre, WHO Collaborating Centre for Noncommunicable Diseases Prevention and Control, Chennai, India.

Abstract

With an estimated 40 million people suffering from the condition, the largest in any country in the world, diabetes has become a major health care problem in India. Recent epidemiological studies from India point to the great burden due to diabetes and its micro and macrovascular complications. This is primarily because the status of diabetes control in India is far from ideal. Based on the available data, the mean glycated hemoglobin levels are around 9% which is at least 2% higher than the goal currently suggested by international bodies. The IMPROVE study has helped identify the barriers to good control of diabetes both among patients as well as physicians in today’s practice. However the recent ACCORD study points to the dangers of overaggressive treatment, especially in high risk in elderly patients. A balanced approach to improve awareness about diabetes and its control both among patients and the medical fraternity is urgent need of the hour in India. The associated risks of tight control in high risk groups should also be kept in mind. ©

Diabetes Burden in India : Medical, Social and Economic

Diabetes has emerged as a major health care problem in India. According to the Diabetes Atlas published by the International Diabetes Federation (IDF), there are an estimated 40 million persons with diabetes in India in 2007 and this number is predicted to rise to almost 70 million people by 2025 by which time every fifth diabetic subject in the world would be an Indian.1 Genetic predisposition combined with life style changes, associated with urbanization and globalization, contribute to this rapid rise of diabetes in India.2 Moreover, type 2 diabetes in the Indian population appears to occur at least a decade earlier compared to Europeans.3 This means that, in the next 10 – 20 years, productivity of the youth of our country could be seriously affected.1,4 Due to these sheer numbers, the economic burden due to diabetes in India is among the highest in the world.5 The real burden of the disease is however due to its micro and macrovascular complications which lead to increased morbidity and mortality.6,7 It is also known that almost 50% of people with diabetes remain undetected and hence some may even present with microvascular and macrovascular complications at the time of diagnosis.8,9

Although sporadic studies on prevalence of diabetes have been available for several decades, reliable epidemiological data became available in India since the 1970’s. Published studies vary in methodologies adopted and sampling frames and hence comparison of prevalence rates is, strictly speaking, not meaningful. However as Table 1 shows, despite all methodological issues, there is little doubt that the prevalence rates are rising in India.10-39 The Indian Council of Medical Research (ICMR) study done in the 1970’s reported a prevalence of 2.3% in urban areas11,12 which has risen to 12-19 % in 2000’s. Correspondingly, in rural areas, prevalence rates have increased from around 1%11,12 to 4-10%, and even 13.2% in one study.36 Thus it is clear that both in urban and rural India, prevalence rates of diabetes are rising rapidly with a rough urban-rural divide of 2:1 or 3:1 being maintained through the last 2-3 decades with the exception of Kerala where rural prevalence rates have caught up with or even overtaken urban prevalence rates.38 The probable explanation for this phenomenon is that in Kerala, there is indeed no clear urban/rural demarcation and the whole of Kerala can now be considered to be urbanized.

Data on various complications of diabetes have also been published by several authors (Table 2).40-58 However, till recently, most such data were hospital or clinic based and therefore subject to referral bias.

Moreover they had often not used standardized technologies (e.g. retinal photography to document diabetic retinopathy).

The Chennai Urban Rural Epidemiology Study (CURES) and the Chennai Urban Population Study (CUPS) provide the first population based data from India on virtually all complications of diabetes.

CURES was a population-based study involving 26,001 participants aged 20 years or above based on a representative population of Chennai. The overall prevalence of diabetic retinopathy based on four-field stereo colour retinal photography was 17.6%.44 The prevalence of overt nephropathy was 2.2% while that of microalbuminuria was 26.9%.51 Peripheral neuropathy
based on biothesiometry was seen in 26.1%.57.

In the CUPS study, coronary artery disease was seen in 21.4% of diabetic subjects, 14.9% of subjects with impaired glucose tolerance and in 9.1% of people with normal glucose tolerance.54 In the same study, peripheral vascular disease was present in 6.3% of diabetic subjects compared to 2.7% among nondiabetic subjects.55 Diabetic subjects also had increased subclinical atherosclerosis as measured by intimal medial thickness at every age point, compared to their non-diabetic counterparts.58 Assuming that 40 million people in India have diabetes, this translates to at least 7 million with retinopathy, 0.8 million with nephropathy, 10.4 million with neuropathy, 8.5 million with CAD and 2.5 million with PVD. Thus, the burden due to diabetic complications is very high in India due to the sheer number of people with diabetes. These figures are in fact very conservative and it is possible that in rural areas, the prevalence of complications is much higher because of poorer control of diabetes and lack of access to health care.

Awareness of Diabetes in India

Not only is there a huge number of people with diabetes in India but awareness levels are also low. CURES reported that nearly 25% of the population was unaware of a condition called diabetes.59 Only around 40% of the participants felt that the prevalence of diabetes was increasing and only 22.2% of the population and 41% of known diabetic subjects felt that diabetes could be prevented.59 Though the awareness levels increased with education, only 42.6% of postgraduates and professionals, which group included doctors and lawyers, knew that diabetes was

preventable. The knowledge of risk factors of diabetes was even lower with only 11.9% of the study subjects reporting obesity and physical inactivity as risk factors for diabetes. More alarming was the fact that even among known diabetic subjects, only 40.6% were aware that diabetes could lead to some organ damage.59 There is another population based study which was done to find out the levels of awareness on diabetes in urban adult Indian population aged ≥ 20 years details regarding awareness about diabetes.60 Knowledge regarding causes of diabetes, its prevention and the methods to improve health was significantly low among the general population. In the total study group, 41% were unaware of health being affected by diabetes and only less than 30% knew about complications related to kidneys, eyes and nerves. Many persons with diabetes (46%) felt it was a temporary phenomenon. Among the diabetic subjects 92.3% had sought the help of a general practitioner to take treatment. Only a small proportion went to a specialist.

Current Status of Diabetes Control in India

The next challenge in India is that the quality of diabetes care varies considerably depending upon the awareness levels, expertise available, attitudes and perceptions amongst diabetes care providers. An estimate based on sales of anti-diabetic pharmaceutical agents shows that on an average only 10-12% of people with diabetes receive modern pharmacological treatment in India.61 In 1998, the Diabcare–Asia study was carried out to investigate the relationship between diabetes control, management and late complications in a subset of urban Indian diabetes population treated at 26 tertiary diabetes care centres.62 A total of 2,269 patients participated in this study and it was observed that approximately half the patients had poor control (HbA1c > 2% points above upper limit of normal) and mean HbA1c was significantly higher (8.9 ± 2.1%) than
the levels recommended by the American Diabetes Association63 and the ICMR guidelines in India.64 Over 54% patients had diabetes related complications. The mean HbA1c levels and frequency of complications were higher in patients with longer diabetes duration. This study also showed that 4% of patients were on diet therapy, 53.9% were receiving oral anti-diabetic agents (OHA’s), 22% were receiving insulin and 19.8% a combination of insulin and OHA’s. This study concluded that with increasing duration of diabetes, glycemic control deteriorates leading to late complications. It also confirmed that diabetes care in India leaves much to be desired and suggested the need for efforts to increase awareness amongst health professionals to improve diabetes care in India.65

The IMPROVETM CONTROL INDIA (ICI) Study

The IMPROVE Control India (ICI) study involved 451 clinicians and was carried out in the 8 metropolitan cities of India. Face to face interviewing using a mix of both qualitative and quantitative techniques was used in the study. The main objectives of the study were to shed light on the doctors and patients’ knowledge, expectations and attitudes with regards to glucose control, and to understand the barriers to achieving good glucose control among patients and health professionals.

This study showed that though insulin therapy is accepted as one of the most effective and dependable treatment option in management of diabetes, there are several barriers to its usage among type 2 diabetic cases particularly the acceptance of insulin therapy. There were many other barriers identified in terms of regular monitoring of diabetes status and lack of standardization in laboratory techniques. Surprisingly, the majority of these barriers involved the treating doctors as well.

From the doctor’s perspective, the ICI study observed no consensus on targets and guidelines amongst the

Moreover, even among patients whose HbA1c values were measured, most (53%) were not given glycemic targets as the study also reported relaxation of targets as duration of diabetes increased. Difficulty in long-term maintenance of HbA1c targets were
recognized by majority of doctors. This might be one of the contributing factors towards lack of motivation to achieve good glycemic control by the patients.

“Clinical Inertia” in Diabetes – Failure to achieve tight control

Failure of initiation of or intensification of therapy, when indicated, is termed “clinical inertia”. Though we have well-defined management goals, effective therapies and practice guidelines, there is often a failure to take appropriate action despite recognition of the problem. This is a common problem in management of patients with asymptomatic chronic illnesses. Use of “soft” reasons to avoid intensification of therapy and lack of education, training and practice organization aimed at achieving therapeutic goals are the common reasons for clinical inertia. Data from the United States suggest that of the 65% of the patients diagnosed with diabetes, only 73% are prescribed pharmacologic therapy and only 33% of those thus treated achieve a hemoglobin A1C value of less then 7% by the ADA goal.66 Clinical inertia in achieving glycemic targets in Indian diabetic subjects could be expected to be even more due to the low rates of awareness of diabetes and its complications in India resulting in poor glycemic control seen in Indians with diabetes. Moreover other factors like poverty, lack of accessibility to health services and inadequate follow-up are additional factors in developing countries like India.

Consequently insulin is delayed until it is absolutely necessary. Most patients are initiated on insulin after a course of multiple oral anti-diabetic drugs. Insulin therapy is initiated only when the HbA1c levels had deteriorated further to around 9%. Doctors often delay insulin therapy worrying that the daily injections, modification of lifestyle due to insulin and dependence on insulin for life and that patients may feel that insulin therapy indicates the last stage of diabetes. However, patients who had moved on to insulin seemed to have a more positive approach towards his/her treatment due to improve in quality of life and better control despite the issues outlined above.

The ICI study also tried to evaluate the patient’s attitudes towards glucose control. Most patients were under the impression that they were in control of their diabetes despite lack of knowledge of their blood sugar levels. The average patient’s perception of being in good control of diabetes was the fact that he/she complied with medication, diet, exercise plan and that they did not feel any untoward symptoms. Too few of them stated or knew target blood glucose or HbA1c values as a measure of control of their diabetes.

The ACORD Trial – The other side of tight control of diabetes

One of the primary objectives of the randomized multicentric trial Action to Control Cardiovascular Risk in Diabetes (ACCORD), was to determine whether intensive lowering of blood sugar levels would reduce the risk of fatal and non-fatal cardiovascular events, specifically in type 2 diabetic subjects, who are at a high risk of developing a cardiovascular event. It was conducted in the USA and in Canada and included adults in the 40-82 years age group who had, in addition to diabetes, two or more other risk factors for heart disease or had been diagnosed with heart disease prior to the study. The participants had been having diabetes for 10 years on an average, at the time of enrollment. Of the 10,251 participants in the study, 5,128 were randomized to the intensive glycemic control group (target HbA1c < 6.0%) and 5123 to the standard glycemic control group (target HbA1c between 7.0 and 7.9%).67 Unfortunately, this study showed that out of the total deaths reported from among the study participants after having been followed up for nearly 4 years, 257 were in the intensively treated group and 203 in the standard treatment group.68 Following this, the intensive treatment given to participants randomized to that group was stopped 18 months ahead of the protocol time and the patients randomized to the intensive glycemic control group also started receiving the same treatment as the standard glycemic control group.67 However, the deaths were due to different causes like surgical
complications, sepsis and strokes, many were heart attacks and no specific cause for the increase in deaths in the intensive treatment group was identifiable and no medication was deemed responsible. A hypothesis proposed was that though atherosclerosis was more in diabetic subjects than in others, the extra sugar in the plaques stabilized them. Hence, when diabetes was over aggressively controlled (target HbA1c < 7.0%), the plaques are believed to lose their stability with increased likelihood of their rupture. The little or no relationship established between HbA1c and cardiovascular problems in type 2 diabetes in studies including the 20-year United Kingdom Prospective Diabetes Study (UKPDS), was quoted as support for this hypothesis. Another hypothesis was that hypoglycemic episodes associated with insulin treatment could cause tachycardia and have untoward effects on the cardiovascular system.68

The ACCORD trial is a warning to clinicians of the consequences of overaggressive treatment of type 2 diabetes especially in high risk groups such as the elderly. It highlights that the treatment goals should be individualized according to the patient’s health profile and not all diabetic subjects should be aggressively treated. Further, it establishes the need of achieving a balance between the benefits of intensive glycemic control and the disadvantages of standard glycemic control.

Conclusions

Considering the enormous burden due to diabetes in India, it is important to realize the cost-effective measures of diabetes care like early screening, tight metabolic control, monitoring of risk factors and assessing of organ damage. The study done for economic analysis in diabetes care in India has also shown that the cost of providing routine care is only a fraction of the overall cost and is perhaps still manageable. However, when this is not available or its quality is poor, the overall direct and indirect costs escalate with disastrous health and economic consequences to the individual, his family and society particularly due to the onset of the micro and macrovascular complications of diabetes.69 Published data from several epidemiological, experimental human and animal studies as well as the data from several mega trials like DCCT, Kumomoto study and UKPDS have convincingly proved the importance of tight metabolic control in arresting and preventing the progression of target organ damage. In the last two decades there is better understanding of pathophysiology of type 2 diabetes and availability of newer oral drugs for diabetes, newer insulin and improved delivery systems should translate to improve diabetes control. However the survey described above indicates the gaps between the guidelines and real life practice.36,70-72 In view of this, appreciation and understanding of both patient and physician barriers regarding proper monitoring and judicious use of therapeutic options including insulin therapy for optimizing diabetes management should be encouraged in order to improve control of diabetes in
India. Result oriented organized programmes involving patient education, updating medical fraternity on various developments in the management of diabetes and providing them the opportunity to use and analyze these newer treatment options in the form of observational studies is required to combat the diabetes epidemic currently threatening to affect the lives of millions of people in India.

Acknowledgements

We thank Mrs. M. Muthu Valli Nayaki for her secretarial help and in compiling references for this article. We thank M/s. Novo Nordisk & AC Nielsen ORG-MARG Pvt. Ltd for providing the IMPROVETM CONTROL INDIA (ICI) study data used in this article.

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