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  • 1
    Online Resource
    Online Resource
    Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity
    American Diabetes Association ; 2020
    In:  Diabetes Vol. 69, No. 12 ( 2020-12-01), p. 2806-2818
    Details
    In: Diabetes, American Diabetes Association, Vol. 69, No. 12 ( 2020-12-01), p. 2806-2818
    Abstract: Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 × 10−16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db20-0070
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2020
    detail.hit.zdb_id: 1501252-9
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  • 2
    Online Resource
    Online Resource
    Temporal Relationship Between Insulin Sensitivity and the Pubertal Decline in Physical Activity in Peripubertal Hispanic and African American Females
    American Diabetes Association ; 2013
    In:  Diabetes Care Vol. 36, No. 11 ( 2013-11-01), p. 3739-3745
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 36, No. 11 ( 2013-11-01), p. 3739-3745
    Abstract: Little attention has been paid to possible intrinsic biological mechanisms for the decline in physical activity that occurs during puberty. This longitudinal observational study examined the association between baseline insulin sensitivity (SI) and declines in physical activity and increases in sedentary behavior in peripubertal minority females over a year. RESEARCH DESIGN AND METHODS Participants were Hispanic and African American girls (n = 55; 76% Hispanic; mean age 9.4 years; 36% obese). SI and other insulin indices were measured at baseline using the frequently sampled intravenous glucose tolerance test. Physical activity was measured on a quarterly basis by accelerometry and self-report. RESULTS Physical activity declined by 25% and time spent in sedentary behaviors increased by ∼13% over 1 year. Lower baseline SI predicted the decline in physical activity measured by accelerometry, whereas higher baseline acute insulin response to glucose predicted the decline in physical activity measured by self-report. Time spent in sedentary behavior increased by ~13% over 1 year, and this was predicted by lower baseline SI. All models controlled for adiposity, age, pubertal stage, and ethnicity. CONCLUSIONS When evaluated using a longitudinal design with strong outcome measures, this study suggests that lower baseline SI predicts a greater decline in physical activity in peripubertal minority females.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc13-0083
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2013
    detail.hit.zdb_id: 1490520-6
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  • 3
    Online Resource
    Online Resource
    Insulin Sensitivity as an Independent Predictor of Fat Mass Gain in Hispanic Adolescents
    American Diabetes Association ; 2009
    In:  Diabetes Care Vol. 32, No. 11 ( 2009-11-01), p. 2114-2115
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 32, No. 11 ( 2009-11-01), p. 2114-2115
    Abstract: The purpose of this study was to examine the relationship between changes in insulin sensitivity and subsequent changes in fat mass in obese Hispanic children over 3 consecutive years. RESEARCH DESIGN AND METHODS In a longitudinal research design, insulin sensitivity (Si) of 96 research participants was determined at baseline and 1 year later. Body adiposity was assessed at four assessments. RESULTS The change in Si during the first year of the study was a significant predictor of further fat mass development (P & lt; 0.05). Considering different directions of Si change, Si was a strong predictor for further fat mass development only in the group that decreased their Si (P & lt; 0.05). CONCLUSIONS The results show that the direction of change in insulin sensitivity at an early age is an important independent predictor for further fat mass development and emphasize the importance of insulin sensitivity as a primary target for long-term obesity prevention, as well as the significance of early age intervention.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc09-0833
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2009
    detail.hit.zdb_id: 1490520-6
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  • 4
    Online Resource
    Online Resource
    Effects of PNPLA3 on Liver Fat and Metabolic Profile in Hispanic Children and Adolescents
    American Diabetes Association ; 2010
    In:  Diabetes Vol. 59, No. 12 ( 2010-12-01), p. 3127-3130
    Details
    In: Diabetes, American Diabetes Association, Vol. 59, No. 12 ( 2010-12-01), p. 3127-3130
    Abstract: A genome-wide study of adults identified a variant of PNPLA3 (rs738409) associated with ∼twofold higher liver fat. The purpose of this study was to examine the influence of PNPLA3 genotype on liver fat and other related metabolic outcomes in obese Hispanic children and adolescents. RESEARCH DESIGN AND METHODS Three hundred and twenty-seven Hispanics aged 8–18 years were genotyped for rs738409. One hundred and eighty-eight subjects had measures of visceral (VAT) and subcutaneous (SAT) adipose tissue volume and hepatic (HFF) and pancreatic (PFF) fat fraction by magnetic resonance imaging. One hundred and thirty-nine subjects did not have HFF measures but had extensive measures of insulin sensitivity and fasting lipids. RESULTS Liver fat in GG subjects was 1.7 and 2.4 times higher than GC and CC (11.1 ± 0.8% in GG vs. 6.6 ± 0.7% in GC and 4.7 ± 0.9% in CC; P & lt; 0.0001), and this effect was observed even in the youngest children (8–10 years of age). The variant was not associated with VAT, SAT, PFF, or insulin sensitivity or other glucose/insulin indexes. However, Hispanic children carrying the GG genotype had significantly lower HDL cholesterol (40.9 ± 10.9 in CC vs. 37.0 ± 8.3 in CG vs. 35.7 ± 7.4 in GG; P = 0.03) and a tendency toward lower free fatty acid levels (P = 0.06). CONCLUSIONS These results provide new evidence that the effect of the PNPLA3 variant is apparent in Hispanic children and adolescents, is unique to fat deposition in liver as compared with other ectopic depots examined, and is associated with lower HDL cholesterol.
    Type of Medium: Online Resource
    ISSN: 0012-1797 , 1939-327X
    URL: Article
    DOI: 10.2337/db10-0554
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2010
    detail.hit.zdb_id: 1501252-9
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  • 5
    Online Resource
    Online Resource
    Fasting Indicators of Insulin Sensitivity: Effects of Ethnicity and Pubertal Status
    American Diabetes Association ; 2011
    In:  Diabetes Care Vol. 34, No. 4 ( 2011-04-01), p. 994-999
    Details
    In: Diabetes Care, American Diabetes Association, Vol. 34, No. 4 ( 2011-04-01), p. 994-999
    Abstract: To examine the relationship of fasting indicators of insulin sensitivity with a more invasive measure of insulin sensitivity (frequently sampled intravenous glucose tolerance test [FSIVGTT]) and the effect of Tanner stage and ethnicity on that relationship. RESEARCH DESIGN AND METHODS Data were analyzed from 149 overweight girls (97 Hispanic and 52 African American) who were either in the early stages of maturation defined by Tanner stages 1 or 2 (52 Hispanic and 18 African American) or in the later stages of maturation defined by Tanner stages 4 and 5 (45 Hispanic and 34 African American). Fasting indicators of insulin sensitivity (IS) included fasting insulin and glucose and the homeostasis model assessment of insulin resistance (HOMA-IR). IS was derived from an FSIVGTT with minimal modeling. RESULTS In Tanner stages 1 and 2, all fasting indicators were significantly associated with IS: (fasting insulin: r = −0.67, P & lt; 0.01; HOMA: r = −0.66, P & lt; 0.01) with no significant influence of ethnicity on these relationships. In Tanner stages 4 and 5, however, all fasting indicators were associated with IS in African American girls (fasting insulin: r = −0.55, P & lt; 0.01; HOMA: r = −0.47, P & lt; 0.01), but none of the indicators were significantly associated with IS in Hispanic girls. CONCLUSIONS Fasting indicators were reflective of IS for girls in Tanner stages 1 and 2, regardless of ethnicity and may provide a clinical measure of future risk for type 2 diabetes. In the latter stages of maturation, however, more invasive measures are warranted to adequately determine IS in clinical practice.
    Type of Medium: Online Resource
    ISSN: 0149-5992 , 1935-5548
    URL: Article
    DOI: 10.2337/dc10-1593
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2011
    detail.hit.zdb_id: 1490520-6
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