Decreased Erythrocyte Membrane Fluidity in Poorly Controlled IDDM: Influence of ketone bodies

Abstract

The factors that most influence membrane fluidity in IDDM patients appear to be hyperglycemia and ketone bodies.

Hyperketonemia Increases Tumor Necrosis Factor-α Secretion in Cultured U937 Monocytes and Type 1 Diabetic Patients and Is Apparently Mediated by Oxidative Stress and cAMP Deficiency

“…These include increased polyol pathway and associated changes in the intracellular redox state, increased diacylglycerol synthesis with consequent activation of specific protein kinase C (PKC) isoforms, increased nonenzymatic glycation of both intra-and extracellular proteins, and increased oxidative stress (33)(34)(35)(36)(37)(38)(39). Oxidative stress may arise from a variety of mechanisms, such as excessive oxygen radical production as a result of the auto-oxidation of glucose (39), the activation of P-450 -like activity by the glucose metabolite NADPH (36), glycated proteins (40 -42) and the ketone body AA (22)(23)(24)(25)(26), and the depletion of NADH by the activation of aldose reductase (35) and glycation of antioxidative enzymes, which limits their capacity to detoxify oxygen radicals (38). Type 1 diabetic patients may experience oxidative stress from both hyperglycemia and ketosis.…”

“…Nevertheless, ketonemia levels of 1-2 mmol/l (1-2 mol/ml) are frequently seen in diabetic patients, even at the time of routine check-up visits to the clinic (22). It is known that diabetic patients with frequent episodes of ketosis experience an increased incidence of vascular disease, morbidity, and mortality (21)(22)(23). However, the underlying mechanisms by which ketosis promotes vascular disease in type 1 diabetic patients are unclear.…”

“…Current standards of clinical practice do not allow even a milder degree of ketosis in diabetic patients (21,23). Nevertheless, ketonemia levels of 1-2 mmol/l (1-2 mol/ml) are frequently seen in diabetic patients, even at the time of routine check-up visits to the clinic (22). It is known that diabetic patients with frequent episodes of ketosis experience an increased incidence of vascular disease, morbidity, and mortality (21)(22)(23).…”

“…In addition to hyperglycemia, type 1 diabetic patients frequently experience hyperketonemia (ketosis) from excessive fat breakdown because body fuel is derived mainly from fat when the body is in a state of insulin deficiency (21). The blood concentration of ketone bodies (acetoacetate [AA] and ␤-hydroxybutyrate [BHB]) may reach 10 mmol/l in patients with severe ketosis compared with Ͻ0.5 mmol/l in normal individuals (21,22). The immediate concern in ketotic patients is acidosis and dehydration.…”

Vitamin D Up-regulates Glucose Transporter 4 (GLUT4) Translocation and Glucose Utilization Mediated by Cystathionine-γ-lyase (CSE) Activation and H2S Formation in 3T3L1 Adipocytes

“…In the HG study, cells were exposed to a medium having a HG concentration of 25 mM. Many previous studies have reported that glucose concentrations as high as 50 mM have been found in the blood of patients with uncontrolled diabetes (12). It is true that blood glucose levels in patients are not likely to stay as high as 25 mM for 24 h. However, tissue damage in diabetic patients occurs over many years of countless hyperglycemic episodes.…”