Ranjana Sinha

Yale University, New Haven, Connecticut, United States

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Publications (2)62.89 Total impact

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    ABSTRACT: The metabolism and composition of skeletal muscle tissue is of special interest because it is a primary site of insulin action and plays a key role in the pathogenesis of insulin resistance. Intramyocellular (IMCL) triglyceride stores are an accessible form of energy that may decrease skeletal muscle glucose utilization, thereby contributing to impaired glucose metabolism. Because of the invasive nature of muscle biopsies, there is limited, if any, information about intramuscular lipid stores in children. The development of (1)H nuclear magnetic resonance (NMR) spectroscopy provides a unique noninvasive alternative method that differentiates intracellular fat from intercellular fat in muscle tissue. The present study was performed to determine whether IMCL and extramyocellular (EMCL) lipid contents are increased early in the development of juvenile obesity and to explore the relationships between IMCL and EMCL to in vivo insulin sensitivity, independently of total body fat and central adiposity in obese and nonobese adolescents. Eight nonobese (BMI 21 kg/m(2), age 11-16 years) and 14 obese (BMI 35 +/- 1.5 kg/m(2), age 11-15 years) adolescents underwent 1) (1)H-NMR spectroscopy to noninvasively quantify IMCL and EMCL triglyceride content of the soleus muscle, 2) a 2-h euglycemic-hyperinsulinemic clamp (40 mU.m(-2).min(-1)) to assess insulin sensitivity, 3) a dual-energy X-ray absorptiometry scan to measure total percent body fat, and 4) magnetic resonance imaging to measure abdominal fat distribution. Both the IMCL and EMCL content of the soleus muscle were significantly greater in the obese adolescents than in the lean control subjects. A strong inverse correlation was found between IMCL and insulin sensitivity, which persisted and became even stronger after controlling for percent total body fat and abdominal subcutaneous fat mass (partial correlation r = -0.73, P < 0.01) but not when adjusting for visceral fat (r = - 0.54, P < 0.08). In obese adolescents, increase in total body fat and central adiposity were accompanied by higher IMCL and EMCL lipid stores. The striking relationships between both IMCL and EMCL with insulin sensitivity in childhood suggest that these findings are not a consequence of aging but occur early in the natural course of obesity.
    Diabetes 05/2002; 51(4):1022-7. DOI:10.2337/diabetes.51.4.1022 · 8.47 Impact Factor
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    ABSTRACT: Childhood obesity, epidemic in the United States, has been accompanied by an increase in the prevalence of type 2 diabetes among children and adolescents. We determined the prevalence of impaired glucose tolerance in a multiethnic cohort of 167 obese children and adolescents. All subjects underwent a two-hour oral glucose-tolerance test (1.75 g [DOSAGE ERROR CORRECTED] of glucose per kilogram of body weight), and glucose, insulin, and C-peptide levels were measured. Fasting levels of proinsulin were obtained, and the ratio of proinsulin to insulin was calculated. Insulin resistance was estimated by homeostatic model assessment, and beta-cell function was estimated by calculating the ratio between the changes in the insulin level and the glucose level during the first 30 minutes after the ingestion of glucose. Impaired glucose tolerance was detected in 25 percent of the 55 obese children (4 to 10 years of age) and 21 percent of the 112 obese adolescents (11 to 18 years of age); silent type 2 diabetes was identified in 4 percent of the obese adolescents. Insulin and C-peptide levels were markedly elevated after the glucose-tolerance test in subjects with impaired glucose tolerance but not in adolescents with diabetes, who had a reduced ratio of the 30-minute change in the insulin level to the 30-minute change in the glucose level. After the body-mass index had been controlled for, insulin resistance was greater in the affected cohort and was the best predictor of impaired glucose tolerance. Impaired glucose tolerance is highly prevalent among children and adolescents with severe obesity, irrespective of ethnic group. Impaired oral glucose tolerance was associated with insulin resistance while beta-cell function was still relatively preserved. Overt type 2 diabetes was linked to beta-cell failure.
    New England Journal of Medicine 04/2002; 346(11):802-10. DOI:10.1056/NEJMoa012578 · 54.42 Impact Factor