Stemming the tide of type 2 diabetes and its consequences in south Asian individuals
Authors: Therese Tillin, Nish Chaturvedi
Journal: The Lancet Diabetes & Endocrinology (2013)

Globally, individuals of south Asian descent have increased susceptibility to type 2 diabetes.1Whiting DR Guariguata L Weil C Shaw J IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030.Diabetes Res Clin Pract. 2011; 94: 311-321Summary Full Text Full Text PDF PubMed Scopus (2955) Google Scholar By age 80 years, 50% of south Asian migrants to the UK have diabetes,2Tillin T Hughes AD Godsland IF et al.Insulin resistance and truncal obesity as important determinants of the greater incidence of diabetes in Indian Asians and African Caribbeans compared with Europeans: the Southall And Brent REvisited (SABRE) cohort.Diabetes Care. 2013; 36: 383-393Crossref PubMed Scopus (98) Google Scholar with a younger age of onset and greater effect on cardiovascular outcomes than European comparators.3Tillin T Hughes AD Mayet J et al.The relationship between metabolic risk factors and incident cardiovascular disease in Europeans, south Asians, and African Caribbeans: SABRE (Southall and Brent revisited)—a prospective population-based study.J Am Coll Cardiol. 2013; 61: 1777-1786Summary Full Text Full Text PDF PubMed Scopus (170) Google ScholarWhat can be done to stem this tide? The Indian Diabetes Prevention Programme,4Ramachandran A Snehalatha C Mary S Mukesh B Bhaskar AD Vijay V The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1).Diabetologia. 2006; 49: 289-297Crossref PubMed Scopus (1305) Google Scholar which studied more than 500 people with impaired glucose tolerance, showed a reduction of more than 25% in diabetes incidence over 2·5 years in those randomised to a lifestyle intervention or metformin, alone or in combination, compared with control. In the lifestyle intervention group, no weight loss was noted and increased physical activity seemed to account for the beneficial effects.4Ramachandran A Snehalatha C Mary S Mukesh B Bhaskar AD Vijay V The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1).Diabetologia. 2006; 49: 289-297Crossref PubMed Scopus (1305) Google ScholarIn The Lancet Diabetes & Endocrinology, Raj Bhopal and colleagues5Bhopal RS Douglas A Wallia S et al.Effect of a lifestyle intervention on weight change in south Asian individuals in the UK at high risk of type 2 diabetes: a family-cluster randomised controlled trial.Lancet Diabetes Endocrinol. 2013; (published online Dec 23.)http://dx.doi.org/10.1016/S2213-8587(13)70204-3Google Scholar report outcomes of a family-based intervention (PODOSA) in south Asian individuals with impaired glucose tolerance or impaired fasting glucose, living in the UK. This family-cluster randomised controlled trial was initially designed with incidence of diabetes at 3 years as its primary endpoint. Participants were randomised to an intensive lifestyle intervention (15 dietitian visits focussed on diet and physical activity) or control group (four dietitian visits with standardised advice on diet and physical activity). The intervention was culturally adapted and its acceptability to participants is borne out by impressive retention over 3 years. However, in view of unforeseen difficulties in recruitment of the planned 540 participants (because the frequency of impaired glucose tolerance and impaired fasting glucose was lower than expected), after 2 years of recruitment the primary endpoint was changed to weight loss, and only 171 participants were enrolled. At 3 years, there was a small reduction in weight in the intervention group compared with the control group (adjusted mean difference −1·64 kg [95% CI −2·83 to −0·44]). Although more participants in the intervention group lost weight, about 20% of participants in both groups gained more than 2·5 kg in weight. The number of participants achieving the recommended level of physical activity (≥30 min per day) did not differ significantly between groups (odds ratio [OR] 1·14 [95% CI 0·53–2·47]). While underpowered for this outcome, there was a suggestion of reduced incidence of diabetes in the intervention group compared with the control group (OR 0·68 [95% CI 0·27–1·67]).Having engaged a south Asian population in PODOSA, it would have been informative to include an objective assessment of physical activity using monitors. Additionally, further useful information could have been gained with the inclusion of outcomes such as insulin concentration and bioimpedance measures of body fat and lean mass, which are simple and cost little to implement.PODOSA showed that in a high-risk group of south Asian individuals, a lifestyle intervention resulted in weight loss. Could the modest weight loss achieved in PODOSA result in reduced progression to diabetes? Both the Finnish6Tuomilehto J Lindstrom J Eriksson JG et al.Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.N Engl J Med. 2001; 344: 1343-1350Crossref PubMed Scopus (8270) Google Scholar and US7Diabetes Prevention Program Research GroupReduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002; 346: 393-403Crossref PubMed Scopus (14340) Google Scholar diabetes prevention trials (the former wholly, the latter largely consisting of participants of European origin), reported substantial reductions in progression to diabetes in response to lifestyle intervention. In both these trials, participants in the intervention groups achieved significant weight loss compared with those in the control groups (3·5 kg and 5·5 kg respectively), and major increases in physical activity. By contrast, in the Indian Diabetes Prevention Programme,6Tuomilehto J Lindstrom J Eriksson JG et al.Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.N Engl J Med. 2001; 344: 1343-1350Crossref PubMed Scopus (8270) Google Scholar although participants in the lifestyle intervention group had substantially reduced progression to diabetes, they had no difference in weight change compared with participants in the control group. However, adherence to an exercise regimen requiring 30 min or more of daily brisk walking increased from 42% to 59%. It is surprising that PODOSA, with little change in physical activity, also hints at reduced progression to diabetes in response to lifestyle intervention (OR 0·68). But confidence limits around this estimate are wide (95% CI 0·27–1·67), and consistent with both a beneficial and harmful effect of the intervention, reflecting the too small sample size for this outcome, so that no definitive conclusions can be drawn. Alternatively, if the hint towards a reduction in diabetes is real, people from south Asia might be more responsive, in terms of diabetes progression, to weight loss than people of European origin. This intriguing hypothesis requires testing, and the planned longer term follow up of PODOSA could begin to address this question.What are the next steps for diabetes prevention research? In view of the fact that half of south Asian migrants will develop diabetes, many in early adulthood, an approach that targets high-risk individuals in late adulthood might be unrewarding. Additionally, there is evidence for transgenerational transmission of diabetes risk.8Dabelea D Crume T Maternal environment and the transgenerational cycle of obesity and diabetes.Diabetes. 2011; 60: 1849-1855Crossref PubMed Scopus (240) Google Scholar Future trials could adopt the family-based approach tested successfully in PODOSA, but recruit from the entire south Asian population and provide lifestyle advice to all, coupled with a more intense intervention, including medication, for those at highest risk (eg, overweight, family history).Substantial lifestyle changes are difficult to maintain long term. Crucial periods of development have been identified that strongly contribute to adult disease, including pregnancy, infancy, and adolescence.9Kuh D Ben-Shlomo Y A life course approach to chronic disease epidemiology: tracing the origins of ill-health from early to adult life. 2nd edn. Oxford University Press, Oxford2004Crossref Scopus (1093) Google Scholar Animal and limited human data suggest that short-term interventions, including drugs, during these periods might greatly reduce or even eliminate the risk of disease.10Lawlor DA Chaturvedi N Treatment and prevention of obesity—are there critical periods for intervention?.Int J Epidemiol. 2006; 35: 3-9Crossref PubMed Scopus (131) Google Scholar, 11Srinivasan S Ambler GR Baur LA et al.Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin.J Clin Endocrinol Metab. 2006; 91: 2074-2080Crossref PubMed Scopus (188) Google Scholar Exploration of the effect of brief interventions during key periods of development offers a methodologically challenging, but potentially rewarding, alternative strategy to reduce the effect of diabetes in south Asian individuals.Ultimately, the goal of any diabetes prevention strategy is to reduce the burden of complications and especially cardiovascular disease, which causes the most morbidity and mortality, and to which south Asian individuals are particularly susceptible. Endpoints should include cardiovascular risk factors and subclinical cardiovascular disease. Consideration of multiple risk factors should be as embedded in prevention trials as it now is in clinical practice.We declare that we have no conflicts of interest. Globally, individuals of south Asian descent have increased susceptibility to type 2 diabetes.1Whiting DR Guariguata L Weil C Shaw J IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030.Diabetes Res Clin Pract. 2011; 94: 311-321Summary Full Text Full Text PDF PubMed Scopus (2955) Google Scholar By age 80 years, 50% of south Asian migrants to the UK have diabetes,2Tillin T Hughes AD Godsland IF et al.Insulin resistance and truncal obesity as important determinants of the greater incidence of diabetes in Indian Asians and African Caribbeans compared with Europeans: the Southall And Brent REvisited (SABRE) cohort.Diabetes Care. 2013; 36: 383-393Crossref PubMed Scopus (98) Google Scholar with a younger age of onset and greater effect on cardiovascular outcomes than European comparators.3Tillin T Hughes AD Mayet J et al.The relationship between metabolic risk factors and incident cardiovascular disease in Europeans, south Asians, and African Caribbeans: SABRE (Southall and Brent revisited)—a prospective population-based study.J Am Coll Cardiol. 2013; 61: 1777-1786Summary Full Text Full Text PDF PubMed Scopus (170) Google Scholar What can be done to stem this tide? The Indian Diabetes Prevention Programme,4Ramachandran A Snehalatha C Mary S Mukesh B Bhaskar AD Vijay V The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1).Diabetologia. 2006; 49: 289-297Crossref PubMed Scopus (1305) Google Scholar which studied more than 500 people with impaired glucose tolerance, showed a reduction of more than 25% in diabetes incidence over 2·5 years in those randomised to a lifestyle intervention or metformin, alone or in combination, compared with control. In the lifestyle intervention group, no weight loss was noted and increased physical activity seemed to account for the beneficial effects.4Ramachandran A Snehalatha C Mary S Mukesh B Bhaskar AD Vijay V The Indian Diabetes Prevention Programme shows that lifestyle modification and metformin prevent type 2 diabetes in Asian Indian subjects with impaired glucose tolerance (IDPP-1).Diabetologia. 2006; 49: 289-297Crossref PubMed Scopus (1305) Google Scholar In The Lancet Diabetes & Endocrinology, Raj Bhopal and colleagues5Bhopal RS Douglas A Wallia S et al.Effect of a lifestyle intervention on weight change in south Asian individuals in the UK at high risk of type 2 diabetes: a family-cluster randomised controlled trial.Lancet Diabetes Endocrinol. 2013; (published online Dec 23.)http://dx.doi.org/10.1016/S2213-8587(13)70204-3Google Scholar report outcomes of a family-based intervention (PODOSA) in south Asian individuals with impaired glucose tolerance or impaired fasting glucose, living in the UK. This family-cluster randomised controlled trial was initially designed with incidence of diabetes at 3 years as its primary endpoint. Participants were randomised to an intensive lifestyle intervention (15 dietitian visits focussed on diet and physical activity) or control group (four dietitian visits with standardised advice on diet and physical activity). The intervention was culturally adapted and its acceptability to participants is borne out by impressive retention over 3 years. However, in view of unforeseen difficulties in recruitment of the planned 540 participants (because the frequency of impaired glucose tolerance and impaired fasting glucose was lower than expected), after 2 years of recruitment the primary endpoint was changed to weight loss, and only 171 participants were enrolled. At 3 years, there was a small reduction in weight in the intervention group compared with the control group (adjusted mean difference −1·64 kg [95% CI −2·83 to −0·44]). Although more participants in the intervention group lost weight, about 20% of participants in both groups gained more than 2·5 kg in weight. The number of participants achieving the recommended level of physical activity (≥30 min per day) did not differ significantly between groups (odds ratio [OR] 1·14 [95% CI 0·53–2·47]). While underpowered for this outcome, there was a suggestion of reduced incidence of diabetes in the intervention group compared with the control group (OR 0·68 [95% CI 0·27–1·67]). Having engaged a south Asian population in PODOSA, it would have been informative to include an objective assessment of physical activity using monitors. Additionally, further useful information could have been gained with the inclusion of outcomes such as insulin concentration and bioimpedance measures of body fat and lean mass, which are simple and cost little to implement. PODOSA showed that in a high-risk group of south Asian individuals, a lifestyle intervention resulted in weight loss. Could the modest weight loss achieved in PODOSA result in reduced progression to diabetes? Both the Finnish6Tuomilehto J Lindstrom J Eriksson JG et al.Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.N Engl J Med. 2001; 344: 1343-1350Crossref PubMed Scopus (8270) Google Scholar and US7Diabetes Prevention Program Research GroupReduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002; 346: 393-403Crossref PubMed Scopus (14340) Google Scholar diabetes prevention trials (the former wholly, the latter largely consisting of participants of European origin), reported substantial reductions in progression to diabetes in response to lifestyle intervention. In both these trials, participants in the intervention groups achieved significant weight loss compared with those in the control groups (3·5 kg and 5·5 kg respectively), and major increases in physical activity. By contrast, in the Indian Diabetes Prevention Programme,6Tuomilehto J Lindstrom J Eriksson JG et al.Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.N Engl J Med. 2001; 344: 1343-1350Crossref PubMed Scopus (8270) Google Scholar although participants in the lifestyle intervention group had substantially reduced progression to diabetes, they had no difference in weight change compared with participants in the control group. However, adherence to an exercise regimen requiring 30 min or more of daily brisk walking increased from 42% to 59%. It is surprising that PODOSA, with little change in physical activity, also hints at reduced progression to diabetes in response to lifestyle intervention (OR 0·68). But confidence limits around this estimate are wide (95% CI 0·27–1·67), and consistent with both a beneficial and harmful effect of the intervention, reflecting the too small sample size for this outcome, so that no definitive conclusions can be drawn. Alternatively, if the hint towards a reduction in diabetes is real, people from south Asia might be more responsive, in terms of diabetes progression, to weight loss than people of European origin. This intriguing hypothesis requires testing, and the planned longer term follow up of PODOSA could begin to address this question. What are the next steps for diabetes prevention research? In view of the fact that half of south Asian migrants will develop diabetes, many in early adulthood, an approach that targets high-risk individuals in late adulthood might be unrewarding. Additionally, there is evidence for transgenerational transmission of diabetes risk.8Dabelea D Crume T Maternal environment and the transgenerational cycle of obesity and diabetes.Diabetes. 2011; 60: 1849-1855Crossref PubMed Scopus (240) Google Scholar Future trials could adopt the family-based approach tested successfully in PODOSA, but recruit from the entire south Asian population and provide lifestyle advice to all, coupled with a more intense intervention, including medication, for those at highest risk (eg, overweight, family history). Substantial lifestyle changes are difficult to maintain long term. Crucial periods of development have been identified that strongly contribute to adult disease, including pregnancy, infancy, and adolescence.9Kuh D Ben-Shlomo Y A life course approach to chronic disease epidemiology: tracing the origins of ill-health from early to adult life. 2nd edn. Oxford University Press, Oxford2004Crossref Scopus (1093) Google Scholar Animal and limited human data suggest that short-term interventions, including drugs, during these periods might greatly reduce or even eliminate the risk of disease.10Lawlor DA Chaturvedi N Treatment and prevention of obesity—are there critical periods for intervention?.Int J Epidemiol. 2006; 35: 3-9Crossref PubMed Scopus (131) Google Scholar, 11Srinivasan S Ambler GR Baur LA et al.Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin.J Clin Endocrinol Metab. 2006; 91: 2074-2080Crossref PubMed Scopus (188) Google Scholar Exploration of the effect of brief interventions during key periods of development offers a methodologically challenging, but potentially rewarding, alternative strategy to reduce the effect of diabetes in south Asian individuals. Ultimately, the goal of any diabetes prevention strategy is to reduce the burden of complications and especially cardiovascular disease, which causes the most morbidity and mortality, and to which south Asian individuals are particularly susceptible. Endpoints should include cardiovascular risk factors and subclinical cardiovascular disease. Consideration of multiple risk factors should be as embedded in prevention trials as it now is in clinical practice. We declare that we have no conflicts of interest. Effect of a lifestyle intervention on weight change in south Asian individuals in the UK at high risk of type 2 diabetes: a family-cluster randomised controlled trialModest, medium-term changes in weight are achievable as a component of lifestyle-change strategies, which might control or prevent adiposity-related diseases. Full-Text PDF Open Access