RESUMEN
The objective of the study was to provide a comprehensive evaluation of chromium (Cr) supplementation on metabolic parameters in a cohort of type 2 diabetes mellitus subjects representing a wide phenotype range and to evaluate changes in "responders" and "nonresponders." After preintervention testing to assess glycemia, insulin sensitivity (assessed by euglycemic clamps), Cr status, and body composition, subjects were randomized in a double-blind fashion to placebo or 1000 microg Cr. A substudy was performed to evaluate 24-hour energy balance/substrate oxidation and myocellular/intrahepatic lipid content. There was not a consistent effect of Cr supplementation to improve insulin action across all phenotypes. Insulin sensitivity was negatively correlated to soleus and tibialis muscle intramyocellular lipids and intrahepatic lipid content. Myocellular lipids were significantly lower in subjects randomized to Cr. At preintervention, responders, defined as insulin sensitivity change from baseline of at least 10% or greater, had significantly lower insulin sensitivity and higher fasting glucose and A(1c) when compared with placebo and nonresponders, that is, insulin sensitivity change from baseline of less than 10%. Clinical response was significantly correlated (P < .001) to the baseline insulin sensitivity, fasting glucose, and A(1c). There was no difference in Cr status between responder and nonresponders. Clinical response to Cr is more likely in insulin-resistant subjects who have more elevated fasting glucose and A(1c) levels. Chromium may reduce myocellular lipids and enhance insulin sensitivity in subjects with type 2 diabetes mellitus who do respond clinically independent of effects on weight or hepatic glucose production. Thus, modulation of lipid metabolism by Cr in peripheral tissues may represent a novel mechanism of action.
Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Resistencia a la Insulina/fisiología , Ácidos Picolínicos/administración & dosificación , Adulto , Anciano , Glucemia/metabolismo , Composición Corporal/efectos de los fármacos , Composición Corporal/fisiología , Peso Corporal/efectos de los fármacos , Peso Corporal/fisiología , Estudios de Cohortes , Diabetes Mellitus Tipo 2/sangre , Suplementos Dietéticos , Método Doble Ciego , Técnica de Clampeo de la Glucosa , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/análisis , Humanos , Insulina/sangre , Análisis de los Mínimos Cuadrados , Hígado/metabolismo , Masculino , Persona de Mediana Edad , Músculo Esquelético/metabolismo , Adulto JovenRESUMEN
Considerable controversy exists regarding the use of chromium (Cr) supplementation to modulate carbohydrate metabolism in subjects with diabetes. Recently, we reported that Cr supplementation, provided as 1000 microg/d as Cr picolinate, enhanced insulin sensitivity in subjects with type 2 diabetes mellitus. Our data agreed with some, but not all, studies that evaluated a similar dose and formulation in type 2 diabetes mellitus and suggested that subject selection and characteristics may be important considerations when assessing the clinical response. Thus, the goal of this study was to assess which metabolic or clinical characteristics, when obtained at baseline, best determine a clinical response to Cr when assessing changes in insulin sensitivity. Seventy-three subjects with type 2 diabetes mellitus were assessed in a double-blinded, randomized, placebo-controlled study. Subjects were assessed at baseline for glycemic control with glycated hemoglobin measures, oral glucose tolerance tests, and body weight and body fat measures (dual-energy x-ray absorptiometry). After baseline, insulin sensitivity in vivo was assessed with the use of hyperinsulinemic-euglycemic clamps. After the baseline clamp, subjects were randomized to receive Cr supplementation (1000 microg Cr/d provided as Cr picolinate) or placebo daily for 6 months. All study parameters were repeated after 6 months. The relationship of the baseline characteristics of the study subjects to the change in insulin sensitivity was determined. Sixty-three percent of the subjects with type 2 diabetes mellitus responded to the Cr treatment as compared with 30% with placebo. The only subject variable significantly associated with the clinical response to Cr was the baseline insulin sensitivity, as assessed with the hyperinsulinemic-euglycemic clamp (partial R(2) = .4038) (P = .0004). Subject phenotype appears to be very important when assessing the clinical response to Cr because baseline insulin sensitivity was found to account for nearly 40% of the variance in the clinical response to Cr.