Skeletal Muscle Lipid and Insulin Resistance: Effects of Physical Activity and Weight Loss (SHELL)
102 late- life adults at risk for developing type 2 diabetes mellitus, will be randomized to one of three interventions designed to improve insulin sensitivity thereby potentially preventing future progression of type 2 diabetes. The investigators predict that insulin sensitivity will improve equally following either weight loss or exercise, while there will be additive effects from combined intervention.
The investigators hypothesize that weight loss will decrease intermuscular adipose tissue, intramyocellular lipid, and visceral abdominal adipose tissue.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
The primary objective of this project will be to examine the role of skeletal muscle lipid and capacity for fat oxidation in insulin resistance in older adults who either are at high risk for the development of type 2 diabetes mellitus (T2DM) or who are untreated newly diagnosed T2DM. A randomized intervention trial will be conducted to examine the effects of physical activity and weight loss, alone or in combination, on intramyocellular lipid (IMCL), intermuscular adipose tissue (IMAT) and abdominal AT (adipose tissue), oxidative capacity and insulin resistance.
The first aim is to examine the effects of weight loss without exercise on AT distribution, intramyocellular lipid (IMCL) and oxidative capacity of skeletal muscle in conjunction with improvements in insulin sensitivity. We will test the hypotheses that weight loss without exercise will: 1) Improve insulin sensitivity, decrease the lipid interspersed within muscle (intermuscular AT), intramyocellular lipid (IMCL), as well as visceral abdominal AT (VAT); and 2) Will have no effects on either skeletal muscle oxidative capacity determined in vitro or in vivo.
A second aim is to examine the effects of exercise without weight loss on AT, IMCL, oxidative capacity and insulin resistance. We will test the hypotheses that exercise without weight loss will: 1) Increase the oxidative enzyme capacity of muscle; 2) Increase IMCL despite having little effect on AT distribution within muscle (intermuscular AT) or visceral AT; 3) Improve insulin sensitivity to a similar degree as weight loss without exercise.
A third aim will be to examine the combined effects of exercise and weight loss on insulin resistance. Our third hypotheses are that combining weight loss and exercise will 1) Decrease IMAT, VAT and have little overall effect on IMCL 2) Improve the oxidative capacity of skeletal muscle; 3) Confer synergistic improvements in insulin sensitivity through the combined actions on AT and skeletal muscle capacity for oxidation.
A fourth aim will be to examine the combined effects of exercise and weight loss on subjects with newly diagnosed but untreated T2DM. Our final hypotheses are that exercise and weight loss will have similar effects in subjects with newly diagnosed T2DM compared to those at risk for developing T2DM with regards to improved insulin sensitivity, body composition and oxidative capacity of skeletal muscle.
Tipo de estudio
Inscripción (Actual)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
Pennsylvania
-
Pittsburgh, Pennsylvania, Estados Unidos, 15213
- University of Pittsburgh
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- 60-75 years of age
- Stable weight (No Gain/Loss of > 10 lbs in 6 months)
- Impaired Glucose Tolerance or Newly, untreated, undiagnosed type 2 diabetes
- Sedentary
- Non-smoker
- BMI 25.0-38.0 KG/M2
- Resting Blood Pressure ≤ 150mmHg systolic and ≤ 95 mmHg diastolic
- IGT: Fasting Glucose > 100, < 126 2-Hour OGTT > 140 but < 200
- T2D: Fasting Glucose > 126 < 2000 2-Hour OGTT > 200
- Note from PCP/Cardiologist for exercise clearance if positive stress test symptoms were observed from GXT
Exclusion Criteria:
- Clinically significant CVD including h/o MI
- Peripheral Vascular Disease
- Hepatic, renal, muscular/neuromuscular, or active hematologic/oncologic disease
- Clinically diminished pulse
- Presence of bruits in lower extremities
- Previous history of pulmonary emboli
- Peripheral Neuropathy
- Currently not engaged in a regular program and have a VO2 max pre-training value > 55 ml/kg-fat free mass-min., indicative of moderate fitness.
- Anemia (Hematocrit < 34%)
- Any contraindications to moderate exercise (Please specify)
- Inability and/ or unwillingness to comply with the protocol as written
- Active alcohol or substance abuse (Past 5 Years)
- Total cholesterol > 300 mg/dL
- Triglyceride > 350 mg/dL
- ALT > 80, AST > 80, Alk Phos > 240
- Proteinuria (defined as >1 + on routine dipstick), hypothyroidism (sTSH>8)
- Therapeutic Doses of Nicotinic Acid
- Oral glucocorticoids
- Females currently on hormone replacement therapy (HRT) less than 6 months
- Claustrophobia
- Previous difficulty with lidocaine or other local anesthetic
Stress test symptoms:
- Positive ECG (> 2mm ST segment depression) without PCP cardiologist permission to participate
- Signs or symptoms of cardiovascular decomposition (hypotensive response to exercise)
- Onset of angina or angina like symptoms, shortness of breath, change in heart rhythm, signs of poor perfusion (light-headedness), tightness,
- Hypotension
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: 1
Weight Loss
|
The reduction of kcal/day through implementation of low fat diet
|
|
Experimental: 2
Exercise
|
16 week intervention; 6 exercise sessions weekly w 3 supervised exercise sessions weekly utilizing cycling or walking/jogging.
Participants maintain exercise diaries: wks 1-4; 30 minutes at 60-70% MHR, wks 5-8; 40 minutes at 60-70% MHR, weeks 9-16; 40 minutes at 75% MHR
|
|
Experimental: 3
Exercise and Weight Loss
|
Exercise: 16 week intervention; 6 exercise sessions weekly w 3 supervised exercise sessions weekly utilizing cycling or walking/jogging. Participants maintain exercise diaries: wks 1-4; 30 minutes at 60-70% MHR, wks 5-8; 40 minutes at 60-70% MHR, weeks 9-16; 40 minutes at 75% MHR. Weight Loss: Reduction of kcal/day through implementation of a low fat diet. |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
|
Effects of physical activity and weight loss, alone or in combination, on intramyocellular lipid, intermuscular adipose tissue and abdominal AT, oxidative capacity and insulin resistance.
Periodo de tiempo: 16 weeks
|
16 weeks
|
Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
|---|---|
|
Assess the mechanisms by which these interventions may prevent the development of diabetes
Periodo de tiempo: 16 weeks
|
16 weeks
|
Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Bret H Goodpaster, PhD, University of Pittsburgh
Publicaciones y enlaces útiles
Publicaciones Generales
- Amati F, Dube JJ, Coen PM, Stefanovic-Racic M, Toledo FG, Goodpaster BH. Physical inactivity and obesity underlie the insulin resistance of aging. Diabetes Care. 2009 Aug;32(8):1547-9. doi: 10.2337/dc09-0267. Epub 2009 Apr 28.
- Amati F, Dube JJ, Shay C, Goodpaster BH. Separate and combined effects of exercise training and weight loss on exercise efficiency and substrate oxidation. J Appl Physiol (1985). 2008 Sep;105(3):825-31. doi: 10.1152/japplphysiol.90384.2008. Epub 2008 Jul 10.
- Amati F, Dube JJ, Stefanovic-Racic M, Toledo FG, Goodpaster BH. Improvements in insulin sensitivity are blunted by subclinical hypothyroidism. Med Sci Sports Exerc. 2009 Feb;41(2):265-9. doi: 10.1249/MSS.0b013e318187c010.
- Amati F, Pennant M, Azuma K, Dube JJ, Toledo FG, Rossi AP, Kelley DE, Goodpaster BH. Lower thigh subcutaneous and higher visceral abdominal adipose tissue content both contribute to insulin resistance. Obesity (Silver Spring). 2012 May;20(5):1115-7. doi: 10.1038/oby.2011.401. Epub 2012 Jan 19.
- Menshikova EV, Ritov VB, Fairfull L, Ferrell RE, Kelley DE, Goodpaster BH. Effects of exercise on mitochondrial content and function in aging human skeletal muscle. J Gerontol A Biol Sci Med Sci. 2006 Jun;61(6):534-40. doi: 10.1093/gerona/61.6.534.
- Dube JJ, Amati F, Toledo FG, Stefanovic-Racic M, Rossi A, Coen P, Goodpaster BH. Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide. Diabetologia. 2011 May;54(5):1147-56. doi: 10.1007/s00125-011-2065-0. Epub 2011 Feb 17.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- 0406003
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .
Ensayos clínicos sobre Diabetes mellitus tipo 2
-
HighTide Biopharma Pty LtdReclutamientoDM2 (Diabetes Mellitus Tipo 2)Porcelana
-
AstraZenecaAún no reclutando
-
Daewoong Pharmaceutical Co. LTD.Aún no reclutandoDM2 (Diabetes Mellitus Tipo 2)
-
University of ZambiaUniversity Teaching Hospital, Lusaka, ZambiaAún no reclutandoDiabetes Mellitus Tipo 2 Sin Complicaciones
-
Zhongda HospitalReclutamientoDiabetes mellitus tipo 2 (DM2)Porcelana
-
Newsoara Biopharma Co., Ltd.ReclutamientoDM2 (Diabetes Mellitus Tipo 2)Porcelana
-
Shanghai Golden Leaf MedTec Co. LtdActivo, no reclutandoDiabetes mellitus tipo 2 (DM2)Porcelana
-
Haisco Pharmaceutical Group Co., Ltd.TerminadoDM2 (Diabetes Mellitus Tipo 2)Porcelana
-
PegBio Co., Ltd.TerminadoDiabetes mellitus tipo 2 (DM2)Porcelana
Ensayos clínicos sobre Weight Loss
-
University of RochesterTerminadoObesidad | Exceso de pesoEstados Unidos
-
The Miriam HospitalNational Institute on Minority Health and Health Disparities (NIMHD)Aún no reclutando
-
University of North Carolina, Chapel HillWeight Watchers InternationalTerminadoSobrepeso y ObesidadEstados Unidos
-
University Hospital, GhentTerminado
-
University of PennsylvaniaWeight Watchers InternationalTerminado
-
University of RochesterActivo, no reclutandoObesidad | Exceso de peso | Estilo de vida saludable | Riesgos cardiovasculares | Investigación de implementaciónEstados Unidos
-
The Miriam HospitalUniversity of Tennessee; Weight Watchers InternationalTerminado
-
University of North Carolina, Chapel HillWeight Watchers InternationalTerminadoObesidad | Pérdida de peso | Modificación de la dieta | Cambio de Peso, CuerpoEstados Unidos, Canadá, Reino Unido
-
Medical University of South CarolinaWeight Watchers InternationalTerminadoObesidad | Exceso de peso | Diabetes tipo 2Estados Unidos
-
The Miriam HospitalUniversity of Tennessee; Weight Watchers InternationalTerminadoObesidad | Exceso de peso | Peso corporalEstados Unidos