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Recent Developments Regarding Risk Factors For Heart Disease – Part 1

Sep 16, 2015

Diabetes Solution
Richard K. Bernstein, MD, FACE, FACN, FACCWS
Part 1

In the past twenty years, research studies have generated considerable new information about heart disease and vascular (blood vessel) disease in general, and their relationship to diabetes in particular. Some of this recent information is summarized here.

A number of substances have been found in the blood which relate to risk of heart attacks and vascular disease. These include HDL (high density lipoprotein), LDL (low-density lipoprotein), triglyceride, fibrinogen, homocysteine, C-reactive protein, ferritin (iron), and lipoprotein(a). High serum levels of dense, compact LDL particles, triglyceride, fibrinogen, homocysteine, C-reactive protein, ferritin, and lipoprotein(a) tend to be associated with increased cardiovascular risk, while high levels of HDL tend to protect from cardiovascular disease.  Cholesterol is a component of both LDL and HDL particles. The fraction of total cholesterol found in LDL particles is an index of risk, while the fraction of cholesterol found in HDL particles is an index of protection.  Nowadays, when we want to estimate the effects of lipids (fatty substances) upon the risk of coronary artery disease, we look at the ratio of total cholesterol to HDL and also at fasting triglyceride levels.  Someone with high serum HDL can thus have a high total cholesterol and yet be at low statistical risk for a heart attack. Conversely, a person with low total cholesterol and very low HDL may be at high risk.

A large multicenter study (the Lipid Research Clinics Trial) investigated the effects of a low-fat, high-carbohydrate diet versus a high-fat, low-carbohydrate diet on nondiabetic middle-aged men with elevated cholesterol levels. The study followed 1,900 people for seven years.  Throughout this period, total cholesterol had dropped only 5 percent from baseline in the low-fat group, but serum triglyceride went up about 10 percent! (Serum triglyceride rises very rapidly after a high carbohydrate meal in nondiabetics, and moves up and down with blood sugar levels in most diabetics.) As with prior studies, no significant correlation was found between serum cholesterol levels and mortality rates. Furthermore, a study reported in the Journal of the American Medical Association in 1997 showed that a 20 percent increase in either saturated or monounsaturated dietary fat lowered the risk of stroke to one-eighth of what it was in individuals on lower-fat diets. Unsaturated fats showed no such benefit.

On average, diabetics with chronically high blood sugars have ele vated levels of LDL (the “bad” cholesterol) and depressed levels of HDL (the “good” cholesterol), even though the ADA low-fat diet has now been in use for many years. Of great importance is the recent discovery that the forms of LDL that harm arteries are small, dense LDL, oxidized LDL, and glycated LDL. All of these increase as blood sugar increases. In addition, independently of blood sugars, high serum insulin levels dictated by high-carbohydrate diets bring about increased production of the potentially hazardous small, dense LDL particles
and enlargement of the cells lining the arteries. We now can measure the size distribution of these LDL subparticles as a routine laboratory test. Most labs report the benevolent large, buoyant LDL subparticles as “type A.”

Under normal conditions, receptors in the liver remove LDL from the bloodstream and signal the liver to reduce its manufacture of LDL when serum levels rise even slightly. Glucose may bind to the surface of the LDL particle and also to liver LDL receptors, so that LDL cannot be recognized by its receptors. In people with high blood sugars, many LDL particles become glycosylated, and are therefore not cleared by the liver. This glycosylation is reversible if blood sugar drops. After about 24 hours, however, a rearrangement of electron bonds occurs in glycosylated proteins, so that the glucose can’t be released even if
blood sugar drops. This irreversible glycosylation is called glycation, and the affected protein molecules are said to be “glycated.” They are also referred to as AGEs, or advanced glycosylation end products.  These AGEs accumulate in the blood, where they can become incorporated into the walls of arteries, forming fatty deposits called atherotic plaques. Since liver LDL production cannot be turned off by the glycosylated/glycated LDL (and also the presence of glycosylated/glycated LDL receptors), the liver continues to manufacture more LDL, even though serum levels may be elevated.

The proteins in the walls of arteries can also become glycosylated/glycated, rendering them sticky.Other proteins in the blood then stick to the arterial walls, causing further buildup of plaque.

Serum proteins glycosylate in the presence of glucose. White blood cells called macrophages ingest glycosylated/glycated proteins and glycosylated/glycated LDL. The loaded macrophages swell up, becoming very large. These transformed macrophages, loaded with fatty material, are called foam cells. The foam cells penetrate the now sticky arterial walls, causing disruption of the orderly architecture of the artery, and narrow the channel through which blood can flow.

The middle layer of the walls of large arteries contains smooth muscle cells that can invade the fatty coating (plaque) that these cells create. They then prevent the plaque from breaking loose. When the nerves that control this smooth muscle die, as in diabetic autonomic neuropathy (caused by high blood sugars), the muscle layer dies and calcifies. It then cannot prevent plaque rupture. When a piece of ruptured plaque enters the blood it can block narrow vessels upstream and cause a heart attack or stroke.

In recent years, the tendency of blood to clot has come into focus as a major cause of heart attacks. People whose blood clots too readily are at very high risk. You may recall that one of the medical names for a heart attack is coronary thrombosis. A thrombus is a clot, and coronary thrombosis refers to the formation of a large clot in one of the arteries that feed the heart. People who have elevated levels of certain clotting precursors or depressed levels of clotting inhibitors in their blood are at high risk of dying from heart attacks. This risk probably far exceeds that caused by high LDL or low HDL. Some of the blood factors that enhance clotting include fibrinogen and factor VII. Another factor, lipoprotein(a), inhibits the destruction of small thrombi before they become large enough to cause a heart attack. All of these factors have been found to increase in people with chronically high blood sugars. Platelets, or thrombocytes, are particles in the blood that play major roles in the blocking of arteries and the formation of clots. These have been shown to clump together and stick to arterial walls much more aggressively in people with high blood sugars. What is exciting is that all of these factors, including sticky platelets, tend to normalize as long-term blood sugars improve.

We would like to thank the publisher Little Brown and Company and Dr. Richard K. Bernstein, for allowing us to provide excerpts from The Diabetes Diet.

Copyright © 2005 by Richard K. Bernstein, M.D. All rights reserved. No part of this book may be reproduced in any form or by any electronic or mechanical means, including information storage and retrieval systems, without permission in writing from the publisher, except by a reviewer who may quote brief passages in a review.

Author’s Note:
This book is not intended as a substitute for professional medical care. The reader should regularly consult a physician for all health-related problems and routine care.

For more information on Dr. Bernstein’s and to purchase his books, CD’s or get access to his free monthly webinars, visit his website at DiabetesBook.com.