High-fructose diet linked to impaired energy homeostasis in patients with diabetes

Abdelmalek MF. Hepatology. 2012;doi:10.1002/hep.25741.

  • August 16, 2012

Increased fructose consumption may reduce concentrations of hepatic ATP in obese patients with diabetes, according to recent results.

Researchers established the dietary fructose consumption of 244 obese patients with type 2 diabetes via a 130-item food frequency questionnaire. Hepatic ATP and uric acid (UA) levels were measured in 105 participants, and a subset of 25 patients also underwent an IV fructose challenge. Changes to levels of UA and hepatic ATP post-challenge were evaluated according to low (less than 15 g/day) and high (15 g/day or more) fructose intake levels.

Manal F. Abdelmalek, MD, MPH

Manal F. Abdelmalek

This study followed two prior studies evaluating the association between dietary fructose and NAFLD, as well as risk for liver injury, researcher Manal F. Abdelmalek, MD, MPH, Associate Professor of Medicine in the Gastroenterology/Hepatology Division at Duke University, told Healio.com. “We previously reported that increased consumption of fructose-containing beverages was not only associated with increased risk of NAFLD compared with matched controls, but also with hepatic fibrosis in a dose-dependent manner in patients with NAFLD. Given the unique metabolism of fructose (one that required hepatic ATP), we hypothesized that the mechanism for fructose-related liver injury could be attributable to alterations in hepatic ATP.  This exploratory study probes the question further.”

Mean fructose consumption was 22.3±1.95 g/day in the high-fructose group compared with 11.13±1.33 g/day in the low-fructose group (P<.001). UA levels were 6.39±0.25 mg/dL in the high group and 4.35±0.18 mg/dL in the low group (P<.001).

Among the 25 patients who completed the fructose challenge, patients with higher fructose intake had lower hepatic ATP levels at baseline, and also underwent larger absolute changes in the ratios of both hepatic alpha and gamma ATP with inorganic phosphate ratio than patients with low fructose intake 50 minutes after the IV challenge (P=.05 and .06, respectively, for difference).

Alpha-ATP declined significantly (P=.002) and beta-ATP trended toward a decline (P=.06) among high-fructose patients after 50 minutes post-challenge, but neither did so among low-fructose patients (P=.56 and 0.1, respectively). Patients with higher UA levels (5.5 mg/dL or more) had a larger post-challenge decrease in ATP/Pi ratio than those with lower UA levels (P=.04 for difference). Patients with higher baseline UA levels also trended toward post-challenge declines in alpha-ATP (P=.06).

“Dietary intake of fructose in patients who already have metabolic syndrome may influence energy homeostasis, and alterations in energy homeostasis may have implications for the worsening of metabolic syndrome or potentially increased risk for cellular injury,” Abdelmalek said. “[This] provides some supporting evidence for clinicians who advise patients to avoid excess refined sugars, particularly in the form of fructose, as we treat complications of insulin resistance, including NAFLD.”

Disclosure: See the study for a full list of relevant financial disclosures.

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