Skeletal Muscle Lipid and Insulin Resistance: Effects of Physical Activity and Weight Loss
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Resistance; Weight Loss
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Exercise; Weight Loss; Exercise and weight loss
Intervention type(s): Behavioral; Behavioral; Behavioral
Intervention description(s): 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; The reduction of kcal/day through implementation of low fat diet; 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.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Exercise; Weight Loss; Physical Activity; Type 2 Diabetes Mellitus