A hypothesis linking hypoglycemia, hyperuricemia, lactic acidemia, and reduced gluconeogenesis in alcoholics to inactivation of glucose-6-phosphatase activity by acetaldehyde

Brecher, Arthur S.; Lehti, Melissa D.

doi:10.1016/s0741-8329(96)00067-5

Cited by 19 publications

(13 citation statements)

References 24 publications

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“…infusions were performed under euglycemia, acetate metabolism in heavy drinkers showed a profile that was similar to what has been seen in patients with type 1 diabetes who have experienced antecedent recurrent hypoglycemia (28). Heavy drinking promotes a wide range of health problems related to hypoglycemia, such as impairment of gluconeogenesis, malnutrition, and confounding conditions like diabetes (44). Binge drinking itself decreases levels of NADH, thereby decreasing pyruvate levels and reducing gluconeogenesis (45).…”

Section: Figurementioning

confidence: 52%

Increased brain uptake and oxidation of acetate in heavy drinkers

Jiang

Gulanski²,

Feyter³

et al. 2013

J. Clin. Invest.

119

114

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When a person consumes ethanol, the body quickly begins to convert it to acetic acid, which circulates in the blood and can serve as a source of energy for the brain and other organs. This study used 13 C magnetic resonance spectroscopy to test whether chronic heavy drinking is associated with greater brain uptake and oxidation of acetic acid, providing a potential metabolic reward or adenosinergic effect as a consequence of drinking. Seven heavy drinkers, who regularly consumed at least 8 drinks per week and at least 4 drinks per day at least once per week, and 7 light drinkers, who consumed fewer than 2 drinks per week were recruited. The subjects were administered [2-13 C]acetate for 2 hours and scanned throughout that time with magnetic resonance spectroscopy of the brain to observe natural 13 C abundance of N-acetylaspartate (NAA) and the appearance of 13 C-labeled glutamate, glutamine, and acetate. Heavy drinkers had approximately 2-fold more brain acetate relative to blood and twice as much labeled glutamate and glutamine. The results show that acetate transport and oxidation are faster in heavy drinkers compared with that in light drinkers. Our finding suggests that a new therapeutic approach to supply acetate during alcohol detoxification may be beneficial.

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Section: Figurementioning

confidence: 52%

Increased brain uptake and oxidation of acetate in heavy drinkers

Jiang

Gulanski²,

Feyter³

et al. 2013

J. Clin. Invest.

119

114

View full text Add to dashboard Cite

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“…Uric acid is subsequently filtered by the glomeruli, reabsorbed in the proximal tubule only to be later secreted by a distal segment of the proximal tubule [23]. Serum concentrations of uric acid are affected by diet [24], metabolism [25], cell turnover [26], and kidney function [27]. There is substantial evidence suggesting that uric acid confers antioxidant capability to humans [28].…”

Section: Discussionmentioning

confidence: 99%

Serum uric acid and the risk of mortality during 23 years follow-up in the Scottish Heart Health Extended Cohort Study

Juraschek¹,

Tunstall‐Pedoe²,

Woodward³

2014

Atherosclerosis

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Background Elevated uric acid is a prevalent condition with controversial health consequences. Observational studies disagree with regard to the relationship of uric acid with mortality, and with factors modifying this relationship. Objective We examined the association of serum uric acid with mortality in 15,083 participants in the Scottish Heart Health Extended Cohort (SHHEC) Study. Methods Serum uric acid measured at study enrollment. Death was ascertained using both the Scottish death register and record linkage. Results During a median follow-up of 23 years, there were 3,980 deaths. In Cox proportional hazards models with sexes combined, those in the highest fifth of uric acid had significantly greater mortality (HR 1.18, 95% CI: 1.06, 1.31) compared with the second fifth, after adjustment for traditional cardiovascular risk factors. This relationship was modified by sex (P-interaction = 0.002) with adjusted HRs of 1.69 (95% CI: 1.40, 2.04) and 0.99 (95% CI: 0.86, 1.14) in women and men, respectively. Compared with the second fifth, the highest fifth of uric acid was most associated with kidney-related death (HR: 2.08, 95% CI: 1.31, 3.32). Conclusion Elevated uric acid is associated with earlier mortality, especially in women. Future studies should evaluate mechanisms for these interactions and explore the strong association with renal-related mortality.

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“…In contrast, plasma lactate in the rested, fasted state represents a balance between gluconeogenesis [26] and the rate of extrahepatic glycolysis [25]. A rise in resting lactate can be observed when gluconeogenesis is disrupted by alcohol use [27] or genetic disorders [28], [29]. Higher resting lactate concentrations may also be seen with increased extrahepatic glucose disposal or glycolysis [25] or with an increase in the concentration of lactate due to hypoxia [30], or oxidative insufficiency [31].…”

Section: Discussionmentioning

confidence: 99%

Lactate and Risk of Incident Diabetes in a Case-Cohort of the Atherosclerosis Risk in Communities (ARIC) Study

et al. 2013

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BackgroundOxidative capacity is decreased in type 2 diabetes. Whether decreased oxidative capacity is a cause or consequence of diabetes is unknown. Our purpose is to evaluate whether lactate, a marker of oxidative capacity, is associated with incident diabetes.Methods and FindingsWe conducted a case-cohort study in the Atherosclerosis Risk in Communities (ARIC) study at year 9 of follow-up. We evaluated lactate’s association with diabetes risk factors at baseline and estimated the hazard ratio for incident diabetes by quartiles of plasma lactate in 544 incident diabetic cases and 533 non-cases. Plasma lactate showed a graded positive relationship with fasting glucose and insulin (P<0.001). The relative hazard for incident diabetes increased across lactate quartiles (P-trend ≤0.001). Following adjustment for demographic factors, medical history, physical activity, adiposity, and serum lipids, the hazard ratio in the highest quartile was 2.05 times the hazard in the lowest quartile (95% CI: 1.28, 3.28). After including fasting glucose and insulin the association became non-significant.ConclusionsLactate, an indicator of oxidative capacity, predicts incident diabetes independent of many other risk factors and is strongly related to markers of insulin resistance. Future studies should evaluate the temporal relationship between elevated lactate and impaired fasting glucose and insulin resistance.

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A hypothesis linking hypoglycemia, hyperuricemia, lactic acidemia, and reduced gluconeogenesis in alcoholics to inactivation of glucose-6-phosphatase activity by acetaldehyde

Cited by 19 publications

References 24 publications

Increased brain uptake and oxidation of acetate in heavy drinkers

Increased brain uptake and oxidation of acetate in heavy drinkers

Serum uric acid and the risk of mortality during 23 years follow-up in the Scottish Heart Health Extended Cohort Study

Lactate and Risk of Incident Diabetes in a Case-Cohort of the Atherosclerosis Risk in Communities (ARIC) Study

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