DIABETES TECHNOLOGY & THERAPEUTICS Volume 17, Number 6, 2015 ª Mary Ann Liebert, Inc. DOI: 10.1089/dia.2014.0213
PERSPECTIVE
Need for Ethnic-Specific Guidelines for Prevention, Diagnosis, and Management of Type 2 Diabetes in South Asians Usha Shrivastava, PhD,1–3 and Anoop Misra, MD1–4
Abstract
Noncommunicable diseases, including type 2 diabetes mellitus and cardiovascular diseases (CVDs), cause 7.9 million deaths every year in South Asia. India has nearly 65.1 million cases of diabetes, and Pakistan and Bangladesh are at the 12th and 13th positions in the global list of high prevalence countries, respectively. The prevalence in India is continuously increasing and is recently reported to be nearly 14% and 8% in urban areas and rural areas, respectively. Diabetes in South Asians is, in some manner, different from that in other races; it occurs nearly a decade earlier, at lower body mass index and waist circumference levels, and with more postprandial hyperglycemia, dyslipidemia, nephropathy, and CVD than in whites. Decision regarding prevention and management of diabetes should be taken in the background of heterogeneity of diet, attitudes, and cultural milieu in South Asia. A need for a low-cost, integrated, yet individualized approach specific for South Asian countries has been increasingly felt since escalating research has uncovered characteristic phenotype, dietary and socioeconomic patterns. Although most such guidelines formulated in developed countries such as the United States or the United Kingdom could be generally applied to developing South Asian countries, there are fundamental differences in applicability of lifestyle and diets (heterogeneous, different from western diets), availability and cost of drugs and insulins, monitoring methods and devices, and insulin pump. Moreover, the monitoring, education, care, and rehabilitation will differ according to different socioeconomic strata and levels of health care (primary, secondary, or tertiary). Some of the potential ethnic-specific modifications have been suggested in this review. years, during the most productive period of life. It is significant to note that diabetes, CVDs, and cancers together account for 40% of the NCD-related disability-adjusted lifeyears.1 Some of these diseases appear a decade earlier and, in some aspects, are more severe than seen in other races in South Asians.2 The prevalence rates of NCDs in the South Asian region differ, but the risk factors are similar. They include rapidly changing and imbalanced nutrition, increasing physical inactivity, and increased stress due to urbanized lifestyle. The phenotype of South Asians contributes significantly to insulin resistance, T2DM, and CVDs. This phenotype includes excess body fat at any given level of body mass index, high prevalence of abdominal obesity, excess intraabdominal and truncal subcutaneous adiposity, and fat deposition at ectopic
Introduction
T
he South Asian region (India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan, and Maldives) constitutes one-fifth of the world’s population and accounts for 52% mortality due to noncommunicable diseases (NCDs). (Throughout this article, the term ‘‘Asian Indians’’ signifies Indians with Asian origin, whereas ‘‘South Asians’’ refers to the residents of India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan, and Maldives.) It is important that NCDs, including type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs), among others, cause 7.9 million deaths every year in this region, and the numbers are expected to rise rapidly in the next decade. In 2008, NCDs killed 36 million people, and a large proportion of these deaths occurred before the age of 60
1
Centre for Public Health, National Diabetes, Obesity and Cholesterol Foundation, New Delhi, India. National Diabetes, Obesity and Cholesterol Foundation, New Delhi, India. Diabetes Foundation (India), New Delhi, India. 4 Fortis-C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India. 2 3
1
2
SHRIVASTAVA AND MISRA
sites like liver and skeletal muscles. Furthermore, a combination of hypertriglyceridemia and low high-density lipoprotein cholesterol (‘‘atherogenic dyslipidemia’’), increased levels of pro-coagulant markers, and subclinical inflammation are also seen in them.3 Let us discuss T2DM as a case study in the background of this scenario. India occupies the second position in the global list of high prevalence countries, with nearly 65.1 million cases of diabetes, and Pakistan and Bangladesh are in 12th and 13th positions, respectively.4 The prevalence in India is continuously increasing and has recently been reported to be nearly 14% and 8% in urban and rural areas, respectively.5 The ICMR-INDIAB study conducted in four centers in India showed the prevalence of T2DM to be as high as 13.6% in Chandigarh and 10.4% in Tamilnadu.6 Diabetes in South Asians is, in some aspects manner, different from that in whites; it occurs nearly a decade earlier, at lower body mass index and waist circumference levels, and manifests with higher postprandial hyperglycemia, dyslipidemia, nephropathy, and CVD. Such high burden and poor management of diabetes result in an enormous load of early and severe complications and premature mortality. Other specific problems in South Asians include unawareness of diabetes, delay in treatment, intake of ineffective and often harmful alternative medicines, and frequent noncompliance with lifestyle and drugs.2,7 Low levels of literacy, long travel distance for medical assistance, and inadequately trained human resources further add to suboptimal management.6,8 Treatment of T2DM is often complex, involves expensive polydrug therapy, and needs to be individualized according to ethnic lifestyle, social, and economic considerations. The approach should be flexible and should take into consideration health-seeking behavior of the population. Decision(s) regarding prevention and management should be modulated according to socioeconomic strata, literacy, dietary preferences, and health-seeking behavior of people residing in different regions of India and those of migrant South Asians. Therefore, there is an undeniable need for a lowcost, integrated, yet individualized approach specific for South Asian countries. Guidelines are available regarding prevention, diagnosis, and management of diabetes by several organizations and national associations, including the International Diabetes Federation, World Health Organization, American Diabetes Association, Canadian Diabetes Association, and Australian Diabetes Association. In particular, American Diabetes Association guidelines are popular and are revised every year based on research and inputs from a team of experts. These guidelines are published in January each year in the journal Diabetes Care and can be easily accessed by all medical practitioners.9 Should there be such guidelines for diabetes in South Asians? A need for such guidelines has been increasingly felt in South Asian countries since escalating research has uncovered characteristic phenotype, dietary, and social patterns as stated previously. There are several specific questions that should be addressed while formulating South Asia–specific prevention and management guidelines:
Should we intervene with lifestyle measures at a lower range of body mass index and waist circumference
Table 1. Cutoffs of Obesity and Abdominal Obesity for Asian Indians Versus International Criteria
Variable
Consensus guidelines for Asian Indiansa
Prevalent international criteria
Generalized obesity (BMI cutoffs [kg/m2]) Normal 18.0–22.9 18.5–24.9b Overweight 23.0–24.9 25.0–29.9b Obesity ‡ 25 ‡ 30b Abdominal obesity (waist circumference cutoffs [cm]) Men ‡ 90c ‡ 102d Women ‡ 80c ‡ 88d Data are from Misra and Shrivastava.3 a From consensus guidelines for Asian Indians.11 b According to World Health Organization guidelines.12 c According to both consensus guidelines for Asian Indians11 and the International Diabetes Federation.13 d According to the Modified National Cholesterol Education Program, Adult Treatment Panel III guidelines.14 BMI, body mass index.
as has been cited in guidelines for Asian Indians3,10,11 (Table 1)? Should nutrient-based prevention and management be attempted based on some recently generated evidence15? Is any conventional antihyperglycemic drug more effective in South Asians than in other races16? Are recently introduced antihyperglycemic drugs (dipeptidyl peptidase-IV inhibitors and glucagon-like protein-1 analogs)16,17 more effective in South Asians? Although ethnic-specific responses to drug treatment are not conclusive, an important example of an ethnic-specific drug is hydralazine, which shows better response for treatment of hypertension in blacks than in other ethnic groups.18 Furthermore, a good response to acarbose/voglibose in Japanese patients with T2DM who consume high carbohydrate diets has been clearly recorded,19 making it a drug of choice after metformin in this ethnic group. This situation may be applicable in Asian Indians who, similar to Japanese, consume high carbohydrate meals. In addition, specifically, in a comparative study between South Asians and whites in the United States, response to pioglitazone was shown to be more in the former: significant improvement in insulin sensitivity (glucose disposal was improved by 32%) and a > 50% decrease in levels of high-sensitivity C-reactive protein and plasminogen activator inhibitor-1.16 Some of these important points are listed in Table 2. Unfortunately, only some of these questions can be answered because of a paucity of research data. Despite overall inadequate research and debate on these important questions, some progress has been made. For example, consensus guidelines for diagnosis of obesity, healthy diets, and physical activity have been formulated for Asian Indians. Consensus obesity guidelines for Asian Indians have included lower cutoffs for overweight (23.0–24.9 kg/m2), obesity ( ‡ 25 kg/m2), and waist circumference ( ‡ 90 cm for men and ‡ 80 cm for women) compared with international guidelines (Table 1).11 Consensus dietary guidelines for India include reduction in the intake of carbohydrates, preferential
ETHNIC-SPECIFIC GUIDELINES FOR T2DM
3
Table 2. Formulation of Ethnic-Specific Guidelines for Type 2 Diabetes Mellitus in South Asians: Key Points for Consideration Guideline for
Factors
A. Diagnosis and cutoffs
B. Management and prognostication
C. Complications
Generalized obesity: lower BMI cutoffs than internationally accepted (see Table 1)10,11 Abdominal obesity: lower waist circumference cutoffs than internationally accepted (see Table 1)10,11 Glycosylated hemoglobin for diagnosis and monitoring: problems due to anemia and hemoglobinopathies (fructosamine may be used)20 Lipids: Lower cutoffs than internationally accepted21 More emphasis on non-HDL cholesterol21 High-sensitivity C-reactive protein: problem in interpretation due to high prevalence of infections and inflammation22 Lipoprotein (a): use for risk stratification21 Dietary modifications: Modify according to suggested changes as per published statement for Asian Indians23 Guidelines for management during prolonged fasting24 Physical activity: more intensive; suggested changes as per published statement for Asian Indians25 Statin therapy: more aggressive21 Include guidelines for immunization because of high prevalence of infections26 Use of less costly Glucometers and testing strips27 Drugs (e.g., sulfonylureas, metformin, and pioglitazone)16,17 Tests (e.g., lesser use of expensive tests like computerized tomography estimated coronary artery calcium) Cardiovascular disease prevention: more aggressive use of statins and aspirin21 Renoprotection: more aggressive in view of faster progression of renal dysfunction28 Foot care is essential (e.g., instruction to stop walking barefoot [common in villages]). More aggressive management of infections29
Most of these suggestions have been taken from reviews, consensus guidelines, and research articles. Robust research regarding many suggestions is needed. BMI, body mass index; HDL, high-density lipoprotein.
200
∗P
PERSPECTIVE
Need for Ethnic-Specific Guidelines for Prevention, Diagnosis, and Management of Type 2 Diabetes in South Asians Usha Shrivastava, PhD,1–3 and Anoop Misra, MD1–4
Abstract
Noncommunicable diseases, including type 2 diabetes mellitus and cardiovascular diseases (CVDs), cause 7.9 million deaths every year in South Asia. India has nearly 65.1 million cases of diabetes, and Pakistan and Bangladesh are at the 12th and 13th positions in the global list of high prevalence countries, respectively. The prevalence in India is continuously increasing and is recently reported to be nearly 14% and 8% in urban areas and rural areas, respectively. Diabetes in South Asians is, in some manner, different from that in other races; it occurs nearly a decade earlier, at lower body mass index and waist circumference levels, and with more postprandial hyperglycemia, dyslipidemia, nephropathy, and CVD than in whites. Decision regarding prevention and management of diabetes should be taken in the background of heterogeneity of diet, attitudes, and cultural milieu in South Asia. A need for a low-cost, integrated, yet individualized approach specific for South Asian countries has been increasingly felt since escalating research has uncovered characteristic phenotype, dietary and socioeconomic patterns. Although most such guidelines formulated in developed countries such as the United States or the United Kingdom could be generally applied to developing South Asian countries, there are fundamental differences in applicability of lifestyle and diets (heterogeneous, different from western diets), availability and cost of drugs and insulins, monitoring methods and devices, and insulin pump. Moreover, the monitoring, education, care, and rehabilitation will differ according to different socioeconomic strata and levels of health care (primary, secondary, or tertiary). Some of the potential ethnic-specific modifications have been suggested in this review. years, during the most productive period of life. It is significant to note that diabetes, CVDs, and cancers together account for 40% of the NCD-related disability-adjusted lifeyears.1 Some of these diseases appear a decade earlier and, in some aspects, are more severe than seen in other races in South Asians.2 The prevalence rates of NCDs in the South Asian region differ, but the risk factors are similar. They include rapidly changing and imbalanced nutrition, increasing physical inactivity, and increased stress due to urbanized lifestyle. The phenotype of South Asians contributes significantly to insulin resistance, T2DM, and CVDs. This phenotype includes excess body fat at any given level of body mass index, high prevalence of abdominal obesity, excess intraabdominal and truncal subcutaneous adiposity, and fat deposition at ectopic
Introduction
T
he South Asian region (India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan, and Maldives) constitutes one-fifth of the world’s population and accounts for 52% mortality due to noncommunicable diseases (NCDs). (Throughout this article, the term ‘‘Asian Indians’’ signifies Indians with Asian origin, whereas ‘‘South Asians’’ refers to the residents of India, Pakistan, Bangladesh, Sri Lanka, Nepal, Bhutan, and Maldives.) It is important that NCDs, including type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVDs), among others, cause 7.9 million deaths every year in this region, and the numbers are expected to rise rapidly in the next decade. In 2008, NCDs killed 36 million people, and a large proportion of these deaths occurred before the age of 60
1
Centre for Public Health, National Diabetes, Obesity and Cholesterol Foundation, New Delhi, India. National Diabetes, Obesity and Cholesterol Foundation, New Delhi, India. Diabetes Foundation (India), New Delhi, India. 4 Fortis-C-DOC Centre of Excellence for Diabetes, Metabolic Diseases and Endocrinology, New Delhi, India. 2 3
1
2
SHRIVASTAVA AND MISRA
sites like liver and skeletal muscles. Furthermore, a combination of hypertriglyceridemia and low high-density lipoprotein cholesterol (‘‘atherogenic dyslipidemia’’), increased levels of pro-coagulant markers, and subclinical inflammation are also seen in them.3 Let us discuss T2DM as a case study in the background of this scenario. India occupies the second position in the global list of high prevalence countries, with nearly 65.1 million cases of diabetes, and Pakistan and Bangladesh are in 12th and 13th positions, respectively.4 The prevalence in India is continuously increasing and has recently been reported to be nearly 14% and 8% in urban and rural areas, respectively.5 The ICMR-INDIAB study conducted in four centers in India showed the prevalence of T2DM to be as high as 13.6% in Chandigarh and 10.4% in Tamilnadu.6 Diabetes in South Asians is, in some aspects manner, different from that in whites; it occurs nearly a decade earlier, at lower body mass index and waist circumference levels, and manifests with higher postprandial hyperglycemia, dyslipidemia, nephropathy, and CVD. Such high burden and poor management of diabetes result in an enormous load of early and severe complications and premature mortality. Other specific problems in South Asians include unawareness of diabetes, delay in treatment, intake of ineffective and often harmful alternative medicines, and frequent noncompliance with lifestyle and drugs.2,7 Low levels of literacy, long travel distance for medical assistance, and inadequately trained human resources further add to suboptimal management.6,8 Treatment of T2DM is often complex, involves expensive polydrug therapy, and needs to be individualized according to ethnic lifestyle, social, and economic considerations. The approach should be flexible and should take into consideration health-seeking behavior of the population. Decision(s) regarding prevention and management should be modulated according to socioeconomic strata, literacy, dietary preferences, and health-seeking behavior of people residing in different regions of India and those of migrant South Asians. Therefore, there is an undeniable need for a lowcost, integrated, yet individualized approach specific for South Asian countries. Guidelines are available regarding prevention, diagnosis, and management of diabetes by several organizations and national associations, including the International Diabetes Federation, World Health Organization, American Diabetes Association, Canadian Diabetes Association, and Australian Diabetes Association. In particular, American Diabetes Association guidelines are popular and are revised every year based on research and inputs from a team of experts. These guidelines are published in January each year in the journal Diabetes Care and can be easily accessed by all medical practitioners.9 Should there be such guidelines for diabetes in South Asians? A need for such guidelines has been increasingly felt in South Asian countries since escalating research has uncovered characteristic phenotype, dietary, and social patterns as stated previously. There are several specific questions that should be addressed while formulating South Asia–specific prevention and management guidelines:
Should we intervene with lifestyle measures at a lower range of body mass index and waist circumference
Table 1. Cutoffs of Obesity and Abdominal Obesity for Asian Indians Versus International Criteria
Variable
Consensus guidelines for Asian Indiansa
Prevalent international criteria
Generalized obesity (BMI cutoffs [kg/m2]) Normal 18.0–22.9 18.5–24.9b Overweight 23.0–24.9 25.0–29.9b Obesity ‡ 25 ‡ 30b Abdominal obesity (waist circumference cutoffs [cm]) Men ‡ 90c ‡ 102d Women ‡ 80c ‡ 88d Data are from Misra and Shrivastava.3 a From consensus guidelines for Asian Indians.11 b According to World Health Organization guidelines.12 c According to both consensus guidelines for Asian Indians11 and the International Diabetes Federation.13 d According to the Modified National Cholesterol Education Program, Adult Treatment Panel III guidelines.14 BMI, body mass index.
as has been cited in guidelines for Asian Indians3,10,11 (Table 1)? Should nutrient-based prevention and management be attempted based on some recently generated evidence15? Is any conventional antihyperglycemic drug more effective in South Asians than in other races16? Are recently introduced antihyperglycemic drugs (dipeptidyl peptidase-IV inhibitors and glucagon-like protein-1 analogs)16,17 more effective in South Asians? Although ethnic-specific responses to drug treatment are not conclusive, an important example of an ethnic-specific drug is hydralazine, which shows better response for treatment of hypertension in blacks than in other ethnic groups.18 Furthermore, a good response to acarbose/voglibose in Japanese patients with T2DM who consume high carbohydrate diets has been clearly recorded,19 making it a drug of choice after metformin in this ethnic group. This situation may be applicable in Asian Indians who, similar to Japanese, consume high carbohydrate meals. In addition, specifically, in a comparative study between South Asians and whites in the United States, response to pioglitazone was shown to be more in the former: significant improvement in insulin sensitivity (glucose disposal was improved by 32%) and a > 50% decrease in levels of high-sensitivity C-reactive protein and plasminogen activator inhibitor-1.16 Some of these important points are listed in Table 2. Unfortunately, only some of these questions can be answered because of a paucity of research data. Despite overall inadequate research and debate on these important questions, some progress has been made. For example, consensus guidelines for diagnosis of obesity, healthy diets, and physical activity have been formulated for Asian Indians. Consensus obesity guidelines for Asian Indians have included lower cutoffs for overweight (23.0–24.9 kg/m2), obesity ( ‡ 25 kg/m2), and waist circumference ( ‡ 90 cm for men and ‡ 80 cm for women) compared with international guidelines (Table 1).11 Consensus dietary guidelines for India include reduction in the intake of carbohydrates, preferential
ETHNIC-SPECIFIC GUIDELINES FOR T2DM
3
Table 2. Formulation of Ethnic-Specific Guidelines for Type 2 Diabetes Mellitus in South Asians: Key Points for Consideration Guideline for
Factors
A. Diagnosis and cutoffs
B. Management and prognostication
C. Complications
Generalized obesity: lower BMI cutoffs than internationally accepted (see Table 1)10,11 Abdominal obesity: lower waist circumference cutoffs than internationally accepted (see Table 1)10,11 Glycosylated hemoglobin for diagnosis and monitoring: problems due to anemia and hemoglobinopathies (fructosamine may be used)20 Lipids: Lower cutoffs than internationally accepted21 More emphasis on non-HDL cholesterol21 High-sensitivity C-reactive protein: problem in interpretation due to high prevalence of infections and inflammation22 Lipoprotein (a): use for risk stratification21 Dietary modifications: Modify according to suggested changes as per published statement for Asian Indians23 Guidelines for management during prolonged fasting24 Physical activity: more intensive; suggested changes as per published statement for Asian Indians25 Statin therapy: more aggressive21 Include guidelines for immunization because of high prevalence of infections26 Use of less costly Glucometers and testing strips27 Drugs (e.g., sulfonylureas, metformin, and pioglitazone)16,17 Tests (e.g., lesser use of expensive tests like computerized tomography estimated coronary artery calcium) Cardiovascular disease prevention: more aggressive use of statins and aspirin21 Renoprotection: more aggressive in view of faster progression of renal dysfunction28 Foot care is essential (e.g., instruction to stop walking barefoot [common in villages]). More aggressive management of infections29
Most of these suggestions have been taken from reviews, consensus guidelines, and research articles. Robust research regarding many suggestions is needed. BMI, body mass index; HDL, high-density lipoprotein.
200
∗P
