DIABETES CARE, VOLUME 22, NUMBER 3, MARCH 1999 413 T he development of obesity depends on both genetic and environmental factors (1). Since the positional cloning of the o b gene (2), much interest has focused on the extent to which leptin is involved in the pathophysiology of human obesity. Although little is known about the effects of the environment on leptin, there is some evidence to suggest that diet and physical activity may be involved in the short-term regulation of leptin. After weight loss, leptin decreases out of proportion to the loss of fat mass (3–6), and dietary manipulation, specifically a diet high in car- bohydrate, results in increases in plasma leptin concentration (7). Similarly, changes in leptin concentration have been shown after exercise (8–10). Whether these factors can exert an effect on leptin concentration on a population basis independently of obe- sity is unknown. The U.S. Pima Indians represent one of the best examples of a population who has recently undergone lifestyle changes, and as a result, now have high prevalences of obe- sity (11) and type 2 diabetes (12). In the present study, we investigated the impact of the environment on leptin concentration by comparing Mexican Pima Indians still living a traditional lifestyle in the Sierra Madre Mountains of northwest Mexico with U.S. Pima Indians living a North American lifestyle. Because of the restrictive environ- ment in which they live, Mexican Pima Indians are still very lean compared with their American counterparts (13). We hypothesized that the absolute value of lep- tin would be lower in Mexican Pima Indi- ans because of their lower percent body fat, but could be further influenced by their lifestyle independent of body composition. Our results suggest a role for environmen- tal factors, such as increased dietary carbo- hydrate and physical activity, in association with increased plasma leptin concentration. RESEARCH DESIGN AND METHODS — The village of Maycoba is located high in the mountains of northwest Mexico, in the eastern region of the state of Sonora, 340 km southeast of Hermosillo (13). A group of people live there who call them- selves Pimas. Anthropologic evidence indi- cates ancestry shared with their U.S. counterparts, mostly based on archeological and linguistic data (13). According to a 1990 census, 601 Pima Indians reside in this area. In 1995, a population survey to determine the prevalence of obesity and type 2 diabetes was initiated in this Mexican community. Survey in Mexico All people aged 20 in Maycoba and its surrounding area were invited to partici- From the Phoenix Epidemiology and Clinical Research Branch (C.F., P.H.B., E.R.), Phoenix, Arizona; the Cen- tro De Investigaction En Alimentacion Y Desarrollo (J.E., M.E.V.), Hermosillo, Mexico; AMGEN (M.N.), Thou- sand Oaks, California; Eli Lilly (E.R.), Indianapolis, Indiana; and the Department of Health Sciences, University of Wisconsin-Milwaukee (L.O.S.), Milwaukee, Wisconsin. Address correspondence and reprint requests to Dr. Eric Ravussin, Eli Lilly, Lilly Corporate Center, Drop Code 0545, Indianapolis, IN 46285. E-mail: eric_ravussin@lilly.com. Received for publication 5 May 1998 and accepted in revised form 5 November 1998. M.N. holds stock in AMGEN. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. Plasma Leptin Concentrations in Pima Indians Living in Drastically Different Environments O R I G I N A L A R T I C L E OBJECTIVE — Plasma leptin, an important signal for the regulation of energy stores, is known to be influenced by many hormonal factors, but may also be affected by behavioral and environmental factors. The purpose of this study was to investigate the impact of lifestyle (diet composition, level of physical activity) on plasma leptin concentrations among Pima Indians living in drastically different environments. RESEARCH DESIGN AND METHODS — We studied 224 Mexican Pima Indians (115 women, 109 men) living a traditional lifestyle in a remote, mountainous area of northwest Mex- ico and 418 U.S. Pima Indians (281 women, 137 men) living a North American lifestyle on the Gila River Indian Reservation in Arizona. We hypothesized that the absolute value of leptin would be lower in Mexican Pima Indians because of their lower percent body fat, but could be further influenced by their lifestyle, independent of body composition. RESULTS — Leptin concentration (enzyme-linked immunosorbent assay [ELISA]) was strongly correlated with percent fat (bioimpedance) in Mexican Pima Indians (r = 0.83, P  0.0001) and U.S. Pima Indians (r = 0.86, P  0.0001). Among U.S. Pima Indians, independent of percent fat, subjects with type 2 diabetes had lower leptin than nondiabetic subjects (dif- ference = 6.9 ± 1.0 ng/ml, P  0.002). Among nondiabetic subjects, Mexican Pima Indians had lower absolute leptin concentrations than U.S. Pima Indians, but higher after adjustment for percent body fat, waist circumference, age, and sex. In a subset of 70 pairs of subjects matched for sex and percent body fat, leptin concentration was 4.4 ± 1.0 ng/ml (P  0.0001) higher in Mexican Pima Indians versus U.S. Pima Indians. CONCLUSIONS — These results suggest that independent of body composition, leptin concentration may be increased by environmental factors, such as a high-carbohydrate diet and a high level of physical activity. Diabetes Care 22:413–417, 1999 CAROLINE FOX, MD JULIAN ESPARZA, PHD MARGERY NICOLSON, PHD PETER H. BENNETT , MD LESLIE O. SCHULZ, PHD MAURO E. V ALENCIA, PHD ERIC RAVUSSIN, PHD Epidemiology/Health Services/Psychosocial Researc h Downloaded from http://diabetesjournals.org/care/article-pdf/22/3/413/449321/10097920.pdf by guest on 08 February 2023