In this individual participant data meta-analysis we found that the overall incidence of diabetes was reduced by 35% in the group receiving the lifestyle modification intervention compared with the control group, with an absolute risk reduction of 7.4% and an NNT of ~14 over a mean of 2 years. Results for diabetes were consistent for men and women and for other key subgroups. The studies included participants with normal and impaired glucose regulation and a range of age and BMI values at baseline, indicating high external validity. We also found evidence of a modest effect on 2 h glucose and simple measures of adiposity (weight and waist circumference). Of note, however, at the last follow-up we observed for both fasting and 2 h glucose a stronger shift on the right side of the distribution curve in the control groups, with significantly more diabetes cases compared with the intervention groups.
The main strength of this study is that it is the first to report summary effects of lifestyle interventions on diabetes incidence in the high-risk South Asian population. Starting with a systematic review of the literature, we used individual participant data meta-analysis from all the six eligible RCTs among South Asians published prior to the inclusion date to produce precise summary effects overall and across subgroups . The data were also analysed for the secondary outcomes: fasting and 2 h glucose and adiposity measures. Compared with meta-analyses based on aggregate data on a study level from published papers, individual participant data meta-analysis facilitates standardisation of analyses and increases the precision of estimates and the quality of subgroup analyses . Further, assessing the quality of evidence according to GRADE, we systematically and transparently assessed all factors that could impact on our certainty in the effects estimates, including risk of bias in each study, heterogeneity, indirectness, imprecision and publication bias .
However, our review is limited by a relatively small number of trials, some with high loss to follow-up, and relatively little variation in settings. The included studies counted approximately 300 incident cases of diabetes, the majority (83%) in the Indian studies. Thus, the power to detect subgroup differences and to further explore between-study heterogeneity for the adiposity measures was limited. Although we consider the evidence to be generally applicable to the target population, we cannot fully rule out potential indirectness due to differences between populations (country of origin or migrant status), interventions (type, content, intensity, mode of delivery, compliance) and settings (family- and community-based vs workplace).
Our meta-analysis included efficacy [12, 16] and more pragmatic trials [15, 17, 18, 26]. The 35% RR reduction in diabetes incidence resembles the RR reduction (39%) reported in a standard meta-analysis of 19 efficacy and pragmatic diabetes prevention trials in individuals with impaired glucose tolerance or impaired fasting glucose after a mean of 2.6 years of active lifestyle intervention . Although ten studies in the latter meta-analysis were conducted in Asia, the results for South Asians were not reported. Of note, the absolute benefit on diabetes prevention was higher in our study than in this meta-analysis (7.4% vs 4.0%, respectively) and so the NNT was lower (14 vs 25) . Our findings compare well with the first efficacy studies, reporting 6.2–12% absolute risk reductions (NNT 16–8, respectively) [8, 9], but are somewhat stronger than those of a meta-analysis of translational studies to prevent diabetes in high-risk populations other than South Asians (RR reduction, 29%; absolute risk reduction, 3%) .
Meta-analysis of diabetes prevention trials indicated that combined dietary and physical activity interventions were more effective than either strategy type alone, but the number of studies was limited for single strategy studies . More studies to date seem to indicate that the dietary interventions are more effective than physical activity interventions to reduce diabetes incidence in high-risk individuals. There is, however, evidence that interventions focused on increasing physical activity in individuals with impaired glucose tolerance are effective at inducing sustained reductions in 2 h glucose concentrations . Although one of the studies with a physical activity intervention that was included in our study found effects on weight and waist , more studies comparing dietary and activity interventions for diabetes prevention are needed in other ethnic groups than of European origin.
Although we could not assess this, the intensity of the interventions in the long-term studies in our review was lower [12, 26] or comparable  with those of the first efficacy studies, which had stronger effects [8, 9]. Even a low-cost community-based peer-support lifestyle intervention programme published too late to be included in our study found a 12% relative reduction in diabetes incidence in individuals with a high Indian diabetes risk score . The smaller effect might be partly attributed to the selection of participants, with the majority having normal blood glucose levels or isolated impaired fasting glucose at baseline, as there are no interventions so far proven to reduce diabetes incidence in such individuals .
In contrast to our finding of an overall 35% reduction on diabetes incidence with a relative small mean 0.75 kg reduction in weight, studies in other populations found weight reduction to be the main driver of the effect [8, 9, 13], i.e. 16% reduction in diabetes incidence for each kg of weight loss . Of note, despite small changes in mean weight and waist circumference values, both for fasting glucose (primarily reflecting hepatic insulin resistance) and 2 h glucose (reflecting muscle insulin resistance), the intervention had a more profound effect on the right side of the distribution curve, indicating reduced insulin resistance . Further, achievements of dietary and physical activity goals, even without weight loss, may improve 2 h glucose and reduce diabetes incidence , as found in the Indian studies in our review [12, 26], where a reduction in portion size, consumption of carbohydrates and oil intake was related to a lower diabetes incidence even without weight loss . Although trials among South Asians are few, there are indications that improvements in the quality of the diet (more complex carbohydrates and monounsaturated and polyunsaturated fatty acids) might improve blood glucose, serum insulin, lipids, inflammatory markers and hepatic fat .
Although only 33% of participants were women in our meta-analysis, as previous studies were underpowered to study potential sex differences, an important new finding was that their diabetes incidence was significantly reduced, despite a slightly smaller non-significant effect estimate for 2 h glucose, weight and waist circumference than in men. Furthermore, the larger effect on weight, with a concomitant non-significant effect estimate for waist circumference, in the European compared with the Indian studies in our meta-analysis is noteworthy. This may reflect different phenotypes, as it would be easier to achieve a larger reduction in weight measures among South Asians residing in Europe, who had higher BMIs, but differences in the diet and/or physical activity level at baseline or induced by the intervention may also be involved. Furthermore, perceptions of weight and health are changing across generations and differ by region . South Asians living in Europe, particularly women, may be more sensitised to the importance of weight loss than those living in their country of origin . Others report that sex did not influence the effects of lifestyle interventions . Lifestyle trials aimed at weight loss which explored sex differences in anthropometric outcomes mostly report stronger effects in men, but actual sex differences were small . Thus, there is little evidence yet to indicate that men and women should generally adopt different weight loss strategies.
The results of our meta-analysis, that lifestyle interventions had comparable and clinically important effects on diabetes incidence across different regions, is important for policymakers and clinicians. The studies outside India in our meta-analysis, conducted mostly among first-generation South Asian migrants in Europe, had suggested only a modest effect. The consistency of effects across subgroups of the South Asian population at risk of diabetes has made us rethink, contrary to our a priori beliefs based on the outcomes of single studies, that benefits may actually be achieved by lifestyle modification interventions, not only under ideal conditions, but also in real-life settings [15, 17, 18, 26]. Cultural adaptations to mode of delivery may be necessary across contexts as cultural adaptations likely promote the effectiveness of interventions among specific ethnic populations [50, 51], although evidence of the effects of cultural targeting on diabetes prevention outside India is still scarce . Interestingly, one study using a culturally targeted physical activity intervention (floorball/field hockey) for men provided strong results for all secondary outcomes, although it was limited by its small size and short duration .
There are, however, several unanswered questions that should be addressed. First, lifestyle intervention studies have used generic recommendations (i.e. based on those for the local majority population) , while different targets for dietary and physical activity recommendations may be necessary [27, 53]. Further work is required on the mechanisms by which these interventions are having their effect, including the role and type of physical activity, diet quality, specific dietary components, cooking practices and timing of meals . Further, we predict that larger effects on diabetes risk in South Asians might be achieved in studies aiming at larger weight reductions [55, 56] and with more intense dietary and physical activity changes . Reach, retention and long-term sustainability may be enhanced through improvements in targeting and delivery, and benefits in the longer term (beyond 2–3 years) should be further investigated. It is hoped that ongoing studies will be complemented with new high-quality trials addressing the issues outlined above. Future systematic reviews should be extended to explore effects by mode of delivery, intensity and contextual factors. In addition to high-risk strategies, there are strong recommendations for population-based strategies as part of national public health policies .
In conclusion, pending deeper understanding of the causation of diabetes in South Asians and the development of new kinds of intervention, this individual participant data meta-analysis of lifestyle modification interventions in South Asian populations at high risk of diabetes provides evidence of a clinically important 35% relative reduction in diabetes incidence, with an NNT of 14 to prevent one case of diabetes over a mean of 2 years. Given the substantial and growing burden of diabetes, particularly in South Asian origin populations, this meta-analysis provides support for ongoing strategies underpinned by weight loss, dietary change and increased physical activity to prevent diabetes. Future work should aim to understand the mechanisms by which these effects occur, evaluate cost effectiveness and develop more effective interventions.