(2) Prothrombotic:
While we are trying to use anti-coagulating medications such as aspirin, heparin, plavix, coumadin, and et cetera for preventing blood clotting and keeping the blood flowing inside the body, we must know hyperglycemia promotes formation of thrombus (blood clot.) Aneta Undas and her colleagues, in their study reported in 2008, affirmed that acute hyperglycemia on admission is positively linked to the prognosis of acute coronary syndrome. The study used 20 participants from each group of diabetic, non-diabetic with blood glucose levels at/or higher than 7 mmol/L (126 mg%), and non-diabetic with blood glucose levels lower than 7 mmol/L (126 mg%.) The groups of DM and non-diabetic with hyperglycemia yielded higher titers of IL-6, soluble platelet activation markers, thrombin-antithrombin complex, and prothrombin 1.2 activation peptide during the conversion from prothrombin to thrombin, and reduced fibrinolysis. [9] In other words, people with acute high blood glucose level have a greater risk of acute inflammation and blood clotting, which would lead to acute coronary event and stroke.
Mike J. Sampson and his coworkers, published a study in 2002, gave 75 grams of oral glucose to the study participants including diabetics and non-diabetics, and took their blood samples at 0, 120, and 240 minutes respectively for biomarkers. Both the diabetic and non-diabetic groups had a significant increase in Mac-1 (macrophage-1 antigen), which lasted a long period, even after the blood glucose levels returned to the fasting. Mac-1 is the factor to attract monocytes and neutrophils to the endothelium for developing blood coagulation and plaque formation. in a separate study, the treatment with an eight week-worth of alpha-tocopherol, which is an antioxidant, to those participants helped nullify the capability of hyperglycemia for increasing Mac-1. The antioxidant effects were best observed with the diabetic group. [10]
Here is a caution. While antioxidants could reduce the risk of blood clotting, the limitation on their daily dosages would make the medications an underdog in the race against blood clotting, as described in the attached figure, “An Unfair Race”, with this article, if the level of blood glucose is much higher after consuming a larger amount of carbohydrates.
(3) Vasoconstrictive and pro-hypertensive:
In 1997, an article published in Circulation by Dario Giugliano et al., reported a study on the vascular effects of 10 healthy men and 10 healthy women in response to acute hyperglycemia. In their first study, with an artificial pancreas, they used hyperglycemic glucose clamp for reaching an acute hyperglycemia at 15 mmol/L, or 270 mg/dL. Data collected at 30, 60, and 90 minutes after infusion of glucose. They found: (A) Statistically significant: Systolic and diastolic blood pressures, heart rate, and plasma catecholamines increased at 30 minutes and thereafter; the leg blood flow markedly decreased at 60 and 90 minutes. Platelet aggregation and blood viscosity significantly increased. (B) Infusion of L-arginine (1 g/min) but not D-arginine or L-lysine during the last 30 minutes of the hyperglycemic clamp totally reversed all hemodynamic and blood flow changes caused by hyperglycemia. In their second study, they used NG-monomethyl-L-arginine (L-NMMA; 2 mg/min) to inhibit endogenous nitric oxide synthesis produced vascular effects qualitatively similar to those of hyperglycemia but much stronger; however, heart rate and plasma catecholamine levels decreased, a possible consequence of baroreflex activation. Infusion of L-NMMA with and without hyperglycemia yielded similar changes. Thus, acute hyperglycemia in normal subjects causes significant hemodynamic and rheological (or flowmatter) changes by reducing the availability of nitric oxide that is reversed by L-arginine. [11] For your information: Baroreflex activation is the baroreceptors, which are located in the carotid sinuses and the sensors to blood pressure, signal to slow down the heart rate and relax the artery for reducing the blood pressure in response to high blood pressure.
This explains why the diabetics and those, with postprandial hyperglycemia but not a diagnosis with diabetes mellitus, have higher risk of impotence. Treating with Viagra and Cialis for impotence is only for a temporary and symptomatic relief. Those who suffer from impotence should raise their awareness of the underlying problems beyond impotence and take a very serious measure for preventing them from having cardiovascular complications as a result of high blood glucose level.
(4) Arteriosclerotic and atherosclerotic:
In 2006, Yungseng Ma and colleagues published an article, “Association between carbohydrate intake and serum lipids”, in the Journal of American College of Nutrition. The study collected the data of 547 healthy adults in the central Massachusetts area during the period between 1994 and 1998, for five consecutive quarters. Total carbohydrate intake, the percentage of calories from carbohydrate, glycemic index (GI) and/or glycemic load (GL) were inversely related to high-density lipoprotein cholesterol (HDL-cholesterol.) Interestingly, in the cross-sectional analysis, this study found total carbohydrate intake and glycemic load were inversely related to total lipoprotein cholesterol and low-density lipoprotein-cholesterol (LDL-cholesterol.) But, in the one-year longitudinal analysis, glycemic load was positively linked to total lipoprotein cholesterol and low-density lipoprotein-cholesterol. Also, again, the percentage of calories from carbohydrate was inversely related to the HDL-cholesterol level. [12] This study along with others have pointed out that high consumption of carbohydrates is linked to high risks of dyslipidemia, thus, atherosclerosis.
Because of the concern about the relationship between fats and atherosclerosis, a study by Lisa Cooper Hudgins and her colleagues found that “[H]uman Fatty Acid Synthesis Is Stimulated by a Eucaloric Low Fat, High Carbohydrate Diet.” This study used 13C to trace the carbon of dietary carbohydrates in metabolism to determine the relationship between the dietary composition and the fatty acid synthesis, in 10 healthy participants. Two diets were used: low fat liquid formula diet (10% fat and 75% glucose polymers of total calories), and high fat liquid formula diet (40% fat and 45% glucose polymers of total calories) for 25 days. The study found that new fatty acids were still synthesized in the participants with the eucaloric low fat, high carbohydrate diet, but not in those with the eucaloric high fat, low carbohydrate diet. By day 10, VLDL-triglyceride rich in palmitate and low in linoleate was markedly increased in all participants with low fat diet; and 44±10% of its increase was newly synthesized. [13] This study underscores the fact that high consumption of carbohydrates alone can increase the synthesis of fats, independent of the amount of fats and increase of calorie intake.
So, how does hyperglycemia promote arteriosclerosis and atherosclerosis? Peter Libby and his group published a review article in 2002, “Clinical Cardiology: New Frontiers: Inflammation and Atherosclerosis” in Circulation. This review article redirects the etiology of atherosclerosis from “a lipid storage disease” to “an ongoing inflammatory process.” It cites that basic science supports “a fundamental role for inflammation” involved in the making of atherosclerosis throughout all stages. The inflamed endothelium expresses adhesion molecules, which recruit white blood cells and promote them to adhere to the inflamed endothelium. As the inflammation continues in the endothelium, it becomes firmer and creates atheroma. (arteriosclerosis), in which pro-inflammatory cytokines express a chemotactic (cells direct their movement according to certain chemicals in their surroundings) stimulus to the adherent leukocytes and helps them move into the endothelium. Inflammatory mediators such as M-CSF (macrophage-colony stimulating factor) of the endothelial surface help macrophage to take in modified (oxidized) lipoprotein particles and form lipid-laden macrophages or plaques. These inflammatory mediators continue to repeat the process inside the intima too. T-lymphocytes, macrophages and the local vascular wall cells express cytokines and growth factors to help migration and proliferation of the arterial smooth muscle cells (SMCs.) The SMCs’ specialized enzymes degrade the elastin and collagen, thus the arterial extracellular matrix. The latter further allows the invasion of SMCs in the growing plaque. The inflammatory mediators can stop the collagen synthesis and increase collageneses by foam cells, and thin and weaken the cap of the plaque for rupture. T-lymphocytes and macrophages promote the coagulant tissue factors, which help produce thrombus when the plaque is ruptured.
Increase of inflammatory factors predicts the outcome of ACS, independently of myocardial damage. Chronic low-grade inflammation such as an increase of CRP (C-reactive protein) predicts the risk of atherosclerosis complications. Decrease of Inflammation by treatment such as some Statin drugs is not related to the LDL levels. [14] This observation underscores that the concentration of LDLs (or VLDLs) is not the primary determinant for the risk of atherosclerosis. Rather, the level of inflammation is!
Robert Su, Pharm. B., M.D.
Wish to invite Dr. Su to speak at your meeting, contact us at jevpublishing@verizon.net
References:
9. Undus A., et al. “Hyperglycemia Is Associated With Enhanced Thrombin Formation, Platelet Activation, and Fibrin Clot Resistance to Lysis in Patients With Acute Coronary Syndrome.” Diabetes Care 31:1590–1595, 2008
10. Sampson MJ, et al. “Monocyte and Neutrophil Adhesion Molecule Expression During Acute Hyperglycemia and After Antioxidant Treatment in Type 2 Diabetes and Control Patients.” Arteriosclerosis, Thrombosis, and Vascular Biology. Volume 22, Pages 1187-1193. July 2002.
11. Giugliano D, et al. “Vascular Effects of Acute Hyperglycemia in Humans Are Reversed by L-Arginine: Evidence for Reduced Availability of Nitric Oxide During Hyperglycemia.” Circulation. 1997;95:1783-1790
12. Ma Y, et al. “Association between Carbohydrate Intake and Serum Lipids.” Journal of the American College of Nutrition,.Volume 25, Number 2, Pages 155-163. 2006.
13. Hudgins LC. “Effect of High-Carbohydrate Feeding on Triglyceride and Saturated Fatty Acid Synthesis.” Proceedings of the Society for Experimental Biology and Medicine. Volume 225, Pages 178-183. 2000.
14. Libby, P, et al. “Inflammation and Atherosclerosis.” Circulation. 2002;105:1135-1143
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