Ancient origins of low lean mass among South Asians and implications for modern type 2 diabetes susceptibility

Abstract: Living South Asians have low lean tissue mass relative to height, which contributes to their elevated type 2 diabetes susceptibility, particularly when accompanied by obesity. While ongoing lifestyle transitions account for rising obesity, the origins of low lean mass remain unclear. We analysed proxies for lean mass and stature among South Asian skeletons spanning the last 11,000 years (n = 197) to investigate the origins of South Asian low lean mass. Compared with a worldwide sample (n = 2,003), South Asian skeletons indicate low lean mass. Stature-adjusted lean mass increased significantly over time in South Asia, but to a very minor extent (0.04 z-score units per 1,000 years, adjusted R2 = 0.01). In contrast stature decreased sharply when agriculture was adopted. Our results indicate that low lean mass has characterised South Asians since at least the early Holocene and may represent long-term climatic adaptation or neutral variation. This phenotype is therefore unlikely to change extensively in the short term, so other strategies to address increasing non-communicable disease rates must be pursued

Evidence for Patterns of Selective Urban Migration in the Greater Indus Valley (2600-1900 BC): A Lead and Strontium Isotope Mortuary Analysis

Just as modern nation-states struggle to manage the cultural and economic impacts of migration, ancient civilizations dealt with similar external pressures and set policies to regulate people’s movements. In one of the earliest urban societies, the Indus Civilization, mechanisms linking city populations to hinterland groups remain enigmatic in the absence of written documents. However, isotopic data from human tooth enamel associated with Harappa Phase (2600-1900 BC) cemetery burials at Harappa (Pakistan) and Farmana (India) provide individual biogeochemical life histories of migration. Strontium and lead isotope ratios allow us to reinterpret the Indus tradition of cemetery inhumation as part of a specific and highly regulated institution of migration. Intra-individual isotopic shifts are consistent with immigration from resource-rich hinterlands during childhood. Furthermore, mortuary populations formed over hundreds of years and composed almost entirely of first-generation immigrants suggest that inhumation was the final step in a process linking certain urban Indus communities to diverse hinterland groups. Additional multi disciplinary analyses are warranted to confirm inferred patterns of Indus mobility, but the available isotopic data suggest that efforts to classify and regulate human movement in the ancient Indus region likely helped structure socioeconomic integration across an ethnically diverse landscape

Estimating body mass and composition from proximal femur dimensions using dual energy x-ray absorptiometry.

Body mass prediction from the skeleton most commonly employs femoral head diameter (FHD). However, theoretical predictions and empirical data suggest the relationship between mass and FHD is strongest in young adults, that bone dimensions reflect lean mass better than body or fat mass and that other femoral measurements may be superior. Here, we generate prediction equations for body mass and its components using femoral head, neck and proximal shaft diameters and body composition data derived from dual-energy x-ray absorptiometry (DXA) scans of young adults (n = 155, 77 females and 78 males, mean age 22.7 ± 1.3 years) from the Andhra Pradesh Children and Parents Study, Hyderabad, India. Sex-specific regression of log-transformed data on femoral measurements predicted lean mass with smaller standard errors of estimate (SEEs) than body mass (12-14% and 16-17% respectively), while none of the femoral measurements were significant predictors of fat mass. Subtrochanteric mediolateral shaft diameter gave lower SEEs for lean mass in both sexes and for body mass in males than FHD, while FHD was a better predictor of body mass in women. Our results provide further evidence that lean mass is more closely related to proximal femur dimensions than body or fat mass and that proximal shaft diameter is a better predictor than FHD of lean but not always body mass. The mechanisms underlying these relationships have implications for selecting the most appropriate measurement and reference sample for estimating body or lean mass, which also depend on the question under investigation.This work was funded by a British Academy International Partnership and Mobility Scheme Grant to EP and VM, and a Leverhulme Trust/Isaac Newton Trust Early Career Fellowship to EP. The third survey wave of APCAPS data collection was supported by a Wellcome Trust Strategic Award (grant no. 084774) and subsidised access to DXA scan facilities given by the National Institute of Nutrition (Directors), Indian Council for Medical Research. TJC was funded by MRC grant MR/M012069/1

Long-term trends in human body size track regional variation in subsistence transitions and growth acceleration linked to dairying

Evidence for a reduction in stature between Mesolithic foragers and Neolithic farmers has been interpreted as reflective of declines in health, however, our current understanding of this trend fails to account for the complexity of cultural and dietary transitions or the possible causes of phenotypic change. The agricultural transition was extended in primary centers of domestication and abrupt in regions characterized by demic diffusion. In regions such as Northern Europe where foreign domesticates were difficult to establish, there is strong evidence for natural selection for lactase persistence in relation to dairying. We employ broad-scale analyses of diachronic variation in stature and body mass in the Levant, Europe, the Nile Valley, South Asia, and China, to test three hypotheses about the timing of subsistence shifts and human body size, that: 1) the adoption of agriculture led to a decrease in stature, 2) there were different trajectories in regions of in situ domestication or cultural diffusion of agriculture; and 3) increases in stature and body mass are observed in regions with evidence for selection for lactase persistence. Our results demonstrate that 1) decreases in stature preceded the origins of agriculture in some regions; 2) the Levant and China, regions of in situ domestication of species and an extended period of mixed foraging and agricultural subsistence, had stable stature and body mass over time; and 3) stature and body mass increases in Central and Northern Europe coincide with the timing of selective sweeps for lactase persistence, providing support for the "Lactase Growth Hypothesis.

"Like sugar in milk": reconstructing the genetic history of the Parsi population.

BACKGROUND: The Parsis are one of the smallest religious communities in the world. To understand the population structure and demographic history of this group in detail, we analyzed Indian and Pakistani Parsi populations using high-resolution genetic variation data on autosomal and uniparental loci (Y-chromosomal and mitochondrial DNA). Additionally, we also assayed mitochondrial DNA polymorphisms among ancient Parsi DNA samples excavated from Sanjan, in present day Gujarat, the place of their original settlement in India. RESULTS: Among present-day populations, the Parsis are genetically closest to Iranian and the Caucasus populations rather than their South Asian neighbors. They also share the highest number of haplotypes with present-day Iranians and we estimate that the admixture of the Parsis with Indian populations occurred ~1,200 years ago. Enriched homozygosity in the Parsi reflects their recent isolation and inbreeding. We also observed 48% South-Asian-specific mitochondrial lineages among the ancient samples, which might have resulted from the assimilation of local females during the initial settlement. Finally, we show that Parsis are genetically closer to Neolithic Iranians than to modern Iranians, who have witnessed a more recent wave of admixture from the Near East. CONCLUSIONS: Our results are consistent with the historically-recorded migration of the Parsi populations to South Asia in the 7th century and in agreement with their assimilation into the Indian sub-continent's population and cultural milieu "like sugar in milk". Moreover, in a wider context our results support a major demographic transition in West Asia due to the Islamic conquest

Ancient origins of low lean mass among South Asians and implications for modern type 2 diabetes susceptibility

Abstract: Living South Asians have low lean tissue mass relative to height, which contributes to their elevated type 2 diabetes susceptibility, particularly when accompanied by obesity. While ongoing lifestyle transitions account for rising obesity, the origins of low lean mass remain unclear. We analysed proxies for lean mass and stature among South Asian skeletons spanning the last 11,000 years (n = 197) to investigate the origins of South Asian low lean mass. Compared with a worldwide sample (n = 2,003), South Asian skeletons indicate low lean mass. Stature-adjusted lean mass increased significantly over time in South Asia, but to a very minor extent (0.04 z-score units per 1,000 years, adjusted R2 = 0.01). In contrast stature decreased sharply when agriculture was adopted. Our results indicate that low lean mass has characterised South Asians since at least the early Holocene and may represent long-term climatic adaptation or neutral variation. This phenotype is therefore unlikely to change extensively in the short term, so other strategies to address increasing non-communicable disease rates must be pursued

Stature estimation equations for South Asian skeletons based on DXA scans of contemporary adults.

OBJECTIVES: Stature estimation from the skeleton is a classic anthropological problem, and recent years have seen the proliferation of population-specific regression equations. Many rely on the anatomical reconstruction of stature from archaeological skeletons to derive regression equations based on long bone lengths, but this requires a collection with very good preservation. In some regions, for example, South Asia, typical environmental conditions preclude the sufficient preservation of skeletal remains. Large-scale epidemiological studies that include medical imaging of the skeleton by techniques such as dual-energy X-ray absorptiometry (DXA) offer new potential datasets for developing such equations. MATERIALS AND METHODS: We derived estimation equations based on known height and bone lengths measured from DXA scans from the Andhra Pradesh Children and Parents Study (Hyderabad, India). Given debates on the most appropriate regression model to use, multiple methods were compared, and the performance of the equations was tested on a published skeletal dataset of individuals with known stature. RESULTS: The equations have standard errors of estimates and prediction errors similar to those derived using anatomical reconstruction or from cadaveric datasets. As measured by the number of significant differences between true and estimated stature, and the prediction errors, the new equations perform as well as, and generally better than, published equations commonly used on South Asian skeletons or based on Indian cadaveric datasets. CONCLUSIONS: This study demonstrates the utility of DXA scans as a data source for developing stature estimation equations and offer a new set of equations for use with South Asian datasets

Estimating body mass and composition from proximal femur dimensions using dual energy x-ray absorptiometry.

Body mass prediction from the skeleton most commonly employs femoral head diameter (FHD). However, theoretical predictions and empirical data suggest the relationship between mass and FHD is strongest in young adults, that bone dimensions reflect lean mass better than body or fat mass and that other femoral measurements may be superior. Here, we generate prediction equations for body mass and its components using femoral head, neck and proximal shaft diameters and body composition data derived from dual-energy x-ray absorptiometry (DXA) scans of young adults (n = 155, 77 females and 78 males, mean age 22.7 ± 1.3 years) from the Andhra Pradesh Children and Parents Study, Hyderabad, India. Sex-specific regression of log-transformed data on femoral measurements predicted lean mass with smaller standard errors of estimate (SEEs) than body mass (12-14% and 16-17% respectively), while none of the femoral measurements were significant predictors of fat mass. Subtrochanteric mediolateral shaft diameter gave lower SEEs for lean mass in both sexes and for body mass in males than FHD, while FHD was a better predictor of body mass in women. Our results provide further evidence that lean mass is more closely related to proximal femur dimensions than body or fat mass and that proximal shaft diameter is a better predictor than FHD of lean but not always body mass. The mechanisms underlying these relationships have implications for selecting the most appropriate measurement and reference sample for estimating body or lean mass, which also depend on the question under investigation.This work was funded by a British Academy International Partnership and Mobility Scheme Grant to EP and VM, and a Leverhulme Trust/Isaac Newton Trust Early Career Fellowship to EP. The third survey wave of APCAPS data collection was supported by a Wellcome Trust Strategic Award (grant no. 084774) and subsidised access to DXA scan facilities given by the National Institute of Nutrition (Directors), Indian Council for Medical Research. TJC was funded by MRC grant MR/M012069/1

Map of the Indus Civilization culture area with locations mentioned in the text.

<p>Dashed line indicates approximate boundary between geochemical catchments. Catchment A, including the Potwar Plateau and adjacent drainages of the Hindu Kush and Karakoram, is relatively less radiogenic than Catchment B, including the Punjab tributaries that drain the Greater and Lesser Himalayas.</p

Local dietary catchment at Rakhigarhi inferred through cluster analysis of faunal isotope ratios.

<p>The structures of the optimal clustering solutions are depicted in Pb-Sr space (²⁰⁶Pb/²⁰⁴Pb vs. ⁸⁷Sr/⁸⁶Sr) with each cluster assigned a different color. Solid circles identify the local faunal cluster determined by the four-cluster solutions, dashed circles identity the local faunal cluster determined by the three-cluster solutions. Arrows indicate optimal clustering solutions. The (A) optimal DBSCAN clustering solution in Pb-Sr space is inferred from (B) a likelihood estimation of all non-trivial clustering solutions. The (C) optimal K-means clustering solution is inferred from (D) the “elbow” in the K-means SSE plot.</p