Also see:
Aldosterone, Sodium Deficiency, and Insulin Resistance
Diabetes: Conversion of Alpha-cells into Beta-cells
Women, Estrogen, and Circulating DHA
Insulin Inhibits Lipolysis
The Randle Cycle
Comparison: Carbon Dioxide v. Lactic Acid
Carbon Dioxide Basics
Carbon Dioxide as an Antioxidant
Comparison: Oxidative Metabolism v. Glycolytic Metabolic
Promoters of Efficient v. Inefficient Metabolism
Trauma & Resuscitation: Toxicity of Lactated Ringer’s Solution
Enzyme to Know: Pyruvate Dehydrogenase
Glycolysis Inhibited by Palmitate
Insulin Inhibits Lipolysis
PUFA Breakdown Products Depress Mitochondrial Respiration
PUFA Decrease Cellular Energy Production
Free Fatty Acids Suppress Cellular Respiration
“Diabetics typically have elevated lactate, which shows that glucose doesn’t have a problem getting into their cells, just getting oxidized.” -Ray Peat, PhD
“Diabetics are relatively unable to oxidize glucose, they produce lactate in the presence of O2, and may synthesize fat inappropriately. Diabetes is relevant to cancer exactly because of their shared inability to oxidize sugar and lactic acid.” -Ray Peat, PhD
“The presence of lactic acid in our tissues is very meaningful, but it is normally treated as only an indicator, rather than as a cause, of biological problems. Its presence in rosacea, arthritis, heart disease, diabetes, neurological diseases and cancer has been recognized, and recently it is being recognized that suppressing it can be curative, after fifty years of denial.
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Lactate contributes to diabetes, inhibiting the ability to oxidize glucose.
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A focus on correcting the respiratory defect would be relevant for all of the diseases and conditions (including heart disease, diabetes, dementia) involving inflammation and inappropriate excitation, not just for cancer.” -Ray Peat, PhD
Glucose is said to not be able to enter the cell in diabetes, but the presence of lactic acid suggest glucose is entering the cell but is being wasted, producing lactate via inefficient and stress promoting glycolytic metabolism.
Clin Endocrinol (Oxf). 2011 Feb;74(2):191-6. doi: 10.1111/j.1365-2265.2010.03891.x.
Diabetes, metformin and lactic acidosis.
Scale T, Harvey JN.
OBJECTIVE:
Metformin has long been thought to cause lactic acidosis (LA) but evidence from various sources has led researchers to question a direct causative relationship. We assessed the relationship of metformin prescription and other factors to the incidence of LA.
METHODS:
All cases of LA at a single hospital were identified from laboratory lactate measurements. We compared patients classified as Cohen and Woods class A and B, patients with and without diabetes, and those taking metformin or not.
RESULTS:
LA was more common than in published analyses based on hospital coding of diagnoses. The incidence of LA was greater in diabetes than in the nondiabetic population but with no further increase in patients taking metformin. Lactate levels were no greater in patients on metformin than in patients with type 2 diabetes not on metformin even if patients with acute cardiorespiratory disturbance (Cohen and Woods class A) were excluded. Acidosis was greater in diabetes (hydrogen ion 94·9 ± 4·6 vs 83·2 ± 2·3 10(-9) m, P = 0·027) but factors besides lactate contributed. Acute cardiorespiratory illness, acute renal impairment and sepsis were the most common of the recognized precipitating factors. Age (P = 0·01), acute renal failure (P = 0·015) and sepsis (P = 0·005) were associated with mortality.
CONCLUSIONS:
Diabetes rather than metformin therapy is the major risk factor for the development of LA. Lactic acidosis occurs in association with acute illness particularly in diabetes. Current guidance for the prevention of lactic acidosis may overemphasize the role of metformin.
Int J Epidemiol. 2010 Dec;39(6):1647-55. Epub 2010 Aug 25.
Association of blood lactate with type 2 diabetes: the Atherosclerosis Risk in Communities Carotid MRI Study.
Crawford SO, Hoogeveen RC, Brancati FL, Astor BC, Ballantyne CM, Schmidt MI, Young JH.
BACKGROUND:
Accumulating evidence implicates insufficient oxidative capacity in the development of type 2 diabetes. This notion has not been well tested in large, population-based studies.
METHODS:
To test this hypothesis, we assessed the cross-sectional association of plasma lactate, an indicator of the gap between oxidative capacity and energy expenditure, with type 2 diabetes in 1709 older adults not taking metformin, who were participants in the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study.
RESULTS:
The prevalence of type 2 diabetes rose across lactate quartiles (11, 14, 20 and 30%; P for trend <0.0001). Following adjustment for demographic factors, physical activity, body mass index and waist circumference, the relative odds of type 2 diabetes across lactate quartiles were 0.98 [95% confidence interval (CI) 0.59-1.64], 1.64 (95% CI 1.03-2.64) and 2.23 (95% CI 1.38-3.59), respectively. Furthermore, lactate was associated with higher fasting glucose among non-diabetic adults.
CONCLUSIONS:
Plasma lactate was strongly associated with type 2 diabetes in older adults. Plasma lactate deserves greater attention in studies of oxidative capacity and diabetes risk.
Diabetes. 1988 Aug;37(8):1020-4.
Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM.
Reaven GM, Hollenbeck C, Jeng CY, Wu MS, Chen YD.
Fasting and postprandial plasma glucose, free fatty acid (FFA), lactate, and insulin concentrations were measured at hourly intervals for 24 h in 27 nonobese individuals—9 with normal glucose tolerance, 9 with mild non-insulin-dependent diabetes mellitus (NIDDM, fasting plasma glucose < 175 mg/dl), and 9 with severe NIDDM (fasting plasma glucose > 250 mg/dl). In addition, hepatic glucose production (HGP) was measured from midnight to 0800 in normal individuals and patients with severe NIDDM. Plasma glucose concentration was highest in patients with severe NIDDM, lowest in those with normal glucose tolerance, and intermediate in those with mild NIDDM (two-way ANOVA, P < .001). Variations in plasma FFA and lactate levels of the three groups were qualitatively similar, with lowest concentrations seen in normal individuals, intermediate levels in the group with mild NIDDM, and the highest concentration in those with severe NIDDM (two-way ANOVA, P < .001). Of particular interest was the observation that plasma FFA concentrations were dramatically elevated from midnight to 0800 in patients with severe NIDDM. The 24-h insulin response was significantly increased in patients with mild NIDDM, with comparable values seen in the other two groups. Values for HGP fell progressively throughout the night in normal individuals and patients with severe NIDDM, despite a concomitant decline in plasma glucose and insulin levels. Although the magnitude of the fall in HGP was greater in NIDDM, the absolute value was significantly (P < .001) greater than normal throughout the period of observation. These results demonstrate that there are differences in substrate level between individuals with normal glucose tolerance and patients with NIDDM and differing degrees of glucose intolerance, unrelated to ambient insulin level, and these changes persist over 24 h.
