Journal Title (Medline/Pubmed accepted abbreviation): Metab Clin Exp
Page numbers: 1633-1641
doi (if applicable): N/A
Summary of Background and Research Design
Background: There are well established pathologic associations between excess adiposity and insulin resistance. However, insulin resistance has also been shown to be a short-term, rapidly adaptive, physiologic response in lean, physically fit humans. Although the mechanisms for insulin resistance in these individuals are unknown, it has been speculated that restriction of dietary carbohydrates mediates intramyocellular lipid (IMCL) accumulation and subsequent insulin resistance. Unfortunately, previous research has not adequately minimized exogenous carbohydrate intake without also reducing circulating carbohydrate concentrations, thus limiting the ability to determine whether insulin resistance in lean, healthy individuals results from endogenous or exogenous carbohydrate restriction.
Hypothesis/purpose of study:To compare the effects of a moderate-carbohydrate diet versus 2 forms of carbohydrate restriction, high-protein/very low-carbohydrate (HPLC) diet and starvation, on insulin sensitivity and IMCL
Subjects:Six healthy, physically fit men (age 38.8 ± 12.7 yr, body mass 72.9 ± 8.8 kg) volunteered for this study. All participants reported regularly undertaking exercise for ≥ 1.5 hours daily at least 5 days per week.
Experimental design:Randomized, crossover
Treatments and protocol:Submaximal and maximal oxygen uptake were measured1 week before testing and the external power output and maximal oxygen consumption (VO2) attained during the final minute of each submaximal workload and the maximal ramp were used to formulate workloads for the control exercise bout. All participants underwent 3 supervised dietary interventions in random order, each separated by at least 7 days. Each diet period was 67 hours and began when participants ingested 1 of the following: a carbohydrate snack (mixed control diet), a protein snack (HPLC diet), or nothing (water-only starvation diet). Dietary intake and physical activity before initiation of each diet were strictly controlled. All participants not in the starvation group ingested an evening meal 2 hours later. The following morning and the remainder of the dietary treatment (48 hours), participants received diets in both the mixed and HPLC treatment groups that provided energy to match a daily expenditure of 1.5× resting metabolic rate to maintain energy balance. The mixed diet was designed to deliver 50% of energy from carbohydrate, 35% of energy from fat, and 15% of energy from protein. The HPLC diet was designed to deliver negligible carbohydrate, 35% of energy from fat, and 65% of energy from protein. After 65 hours of each diet, vastus lateralis proton magnetic resonances (1H magnetic resonance spectroscopy) were obtained to measure IMCL, and glucose tolerance was assessed by frequently sampled intravenous glucose tolerance tests (IVGTT).
Summary of research findings:
- Carbohydrate intake was significantly lower in the HPLC diet vs the mixed diet (P < .001), the diets provided 15 ± 4 g/day and 389 ± 22 g/day, respectively.
- Dietary protein intake was significantly higher in the HPLC vs the mixed diet (P < .001), yet daily fat and energy intakes were not different between the HPLC and mixed diets.
- Dietary carbohydrate consumption in the HPLC diet was significantly greater than during starvation (P < .001).
- The ratio of vastus lateralis IMCL to water was significantly higher in the starvation condition (25.6 ± 5.9 × 10−3) than in the mixed (13.6 ± 6.1 × 10−3, P < .01) or HPLC (13.6 ± 3.3 × 10−3, P < .01) conditions.
- The ratio of IMCL to water was not different between the mixed and HPLC conditions (P > .99).
- Fasting plasma glucose was significantly reduced ([starvation] 3.5 ± 0.3 mmol/L, vs [HPLC] 4.2 ± 0.4 mmol/L, and [mixed] 4.5 ± 0.3 mmol/L; P < .01).
- The IMCL-to-water ratio (25.6 ± 5.9 ×10−3 [starvation], vs 13.6 ± 6.1×10−3 [HPCL], and 13.6 ± 3.3 × 10−3 [mixed]; P < .01) and fasting free fatty acids (1,179 ± 294 μmol/L [starvation], vs 387 ± 232 μmol/L [HPLC], and 378 ± 120 μmol/L [mixed]; P < .05) were significantly elevated after starvation but were unchanged for HPLC vs mixed diet.
- Minimal model insulin sensitivity was reduced after starvation (5.7 ± 1.5 L/min/mU, vs 14.5 ± 4.8 L/min/mU [HPLC], and 16.5 ± 6.8 L/min/mU [mixed]; P < .05).
Interpretation of findings/Key practice applications:
The primary finding of this study is that carbohydrate restriction in lean, healthy men, did not result in alterations to circulating FFA concentrations, whole-body insulin sensitivity, or vastus lateralis intramuscular lipid concentration. In this report, plasma glucose, plasma FFAs, IMCLs, and insulin sensitivity were maintained on the HPLC diet compared with the mixed diet, despite previous data demonstrating that carbohydrate restriction resulted in marked changes in these measures. It would have been interesting to see how a higher fat, lower protein version of a low-carbohydrate diet might have affected these measures, given that many low-carbohydrate diets are much higher in fat than the 34% kcal level in this study. The authors conclude that dietary carbohydrate restriction does not per se elevate circulating FFA concentrations. However, it remains probable that circulating carbohydrate status has an important influence on circulating FFA concentrations, as well as subsequent insulin sensitivity and healthy IMCL accumulation.