Regulation of net hepatic glycogenolysis and gluconeogenesis during exercise: impact of type 1 diabetes.
Level 3 - non-randomized controlled study
Matched non-randomized comparative physiological study
PubMed 15356077 · doi:10.1210/jc.2004-0408
What was done
Evaluated glucose production using [6,6-(2)H(2)]glucose tracer and net hepatic glycogenolysis using noninvasive 13C nuclear magnetic resonance spectroscopy in 6 healthy controls and 5 subjects with type 1 diabetes matched for age, weight, and maximum aerobic capacity. Measurements were conducted at rest and during moderate and high intensity running.
What was found
In control subjects, glucose production increased with exercise intensity (rest: 14.3 +/- 0.5, moderate: 18.1 +/- 0.9, high: 28.8 +/- 1.3 micromol/[kg-min]; P = 0.001), driven by an increased contribution of net hepatic glycogenolysis (rest: 32 +/- 1%, moderate: 49 +/- 5%, high: 57 +/- 5%; P = 0.006). In diabetic subjects, resting glucose production was 60% higher than in controls (P < 0.0001) and increased with workload, but the relative contribution of net hepatic glycogenolysis was lower (rest: 20 +/- 6%, moderate: 32 +/- 13%, high: 32 +/- 3%; P = 0.006 vs. control), with exaggerated glucose production entirely accounted for by increased gluconeogenesis.
Why it matters
This study shows that the excessive hepatic glucose output during exercise in individuals with type 1 diabetes is driven by elevated gluconeogenesis rather than glycogen breakdown.
Limits
Small sample size (n = 11 total: 6 controls and 5 diabetic subjects). Non-randomized observational design. The study only examined moderately controlled type 1 diabetes during running, limiting generalizability to other glycemic states or exercise modalities.
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