Monday, April 2, 2012

Diabetes---Part I

     This blog will discuss adult-onset, non insulin-dependent diabetes, otherwise known as Adult Onset Diabetes (AODM), or Diabetes II. The "M", of course, stands for "Mellitus", which is Latin for "sweet", since diabetic urine usually tastes sweet because of its sugar content (there should be no sugar in your urine). This discussion is not meant to be exhaustive, but will cover what I feel to be the essential topics of the disease.

     Every cell in your body needs sugar (usually glucose) to function at peak efficiency. All cells can ingest a little glucose by passive absorption, but the absorption is greatly facilitated by the presence of insulin in the bloodstream along with the glucose. Two groups of metabolically active cells can absorb enough glucose without insulin to continue their normal processes: red blood cells and brain cells. If this were not the case, then all diabetics would die very rapidly. I should mention here that cancer cells have a higher metabolic rate than non-cancerous cells, and therefore have an accelerated uptake of glucose. This is the basis for the PET scan, which replaces one O-16 oxygen atom in glucose with O-17, a radioactive oxygen atom that emits a positron (hence Positron Emitting Test) and is thereby converted to N-17, an isotope of nitrogen.

     Most diabetic patients have one or both of two defects: either their pancreas does not secrete enough insulin,  or their tissues are resistant to the action of insulin. In either case, their blood  sugar is higher than is normal for their given metabolic state, and some sugar may spill over into the urine. The urine test for sugar can have several false positives, so by itself the urine test canNOT be used to diagnose diabetes, but only to suggest its presence. I should  mention here that the metabolism of the liver is also affected by the presence of insulin, because the liver requires insulin both to suppress its generation of glucose and to enhance its absorption of triglycerides, so that most diabetics have elevated fasting triglyceride levels.

     What is a "normal" level of glucose in your blood? There are at least two definitions: the numerical  definition which defines a "normal" range, or the clinical definition which states the level at which clinical intervention, i.e. treatment, either extends the patient's life or prevents damage to any organ. I will not consider here the subset of diabetics with congestive heart failure, except to note that blood is a non-Newtonian viscous fluid, and that the shear resistance to blood being circulated by the heart rises abruptly at sugar levels above 250, so that a patient with a glucose of 300 may be in heart failure while the same patient can be brought out of heart failure by lowering the blood glucose to 200.

     It is universally accepted that a glucose level greater than 200 measured two hours after a full dinner denotes diabetes; this may be quantified by repeating the measurement two hours after the patient ingests 75 grams of glucose on an empty stomach. It is also generally agreed that a fasting (i.e. 8 AM blood test with no food for the previous 8 to 12 hours) blood glucose of less than 100 means that there is no fasting diabetes. Inbetween these two numbers there is some leeway and much argument. It used to be that a fasting glucose of over 140 was called "impaired glucose tolerance" or "pre-diabetes" and some interventions (e.g. with metformin) reduced the risk of progression to full diabetes. Then the "pre" level was lowered to 125, then 110, and then to 100, with the major result that many more patients were labeled "pre-diabetic) and had to pay higher premiums for life insurance and/or long-term care insurance.

     When the blood glucose level is above 200 in most patients, two irreversible events occur. The first, which causes lasting damage, is the deposition of sorbitol, a non water-soluble molecule, into the membranes of the capillaries of some but not all the organs of the body. This renders a capillary bed incapable of transporting oxygen and soluble nutrients across its boundary from the blood  to the affected organ. The second, which is of diagnostic import, is an increased creation of glycosolated hemoglobin, or glycohemoglobin (HbA1c) in your bloodstream. When glucose diffuses across the red blood cell membrane, a small percentage of it forms a stable complex with the hemoblogin molecule that all red blood cells possess to carry their oxygen. Since red blood cells have an average lifetime of 120 days in your blood stream, the concentration of glycohemoglobin is an indirect  measure of your average blood glucose for the past three months. HbA1c concentrations in excess of 7.0 are considered to be indicative of, or even diagnostic of, diabetes mellitus. (Even this test is not 100% accurate because heavy daily users of aspirin will have an elevated level of HbA1c, since acetylated glycohemoglobin is eluted more rapidly.)

     In all individuals, fat cells require insulin to process the conversion of triglycerides to fat molecules. When you become fatter, the number of fat cells does not increase, but rather each fat cell swells. Therefore, the heavier you are, the greater is the total area of fat cell membranes that is exposed to the circulating blood, and the more insulin they will extract from your circulation. This is why as you gain weight you become more and more "pre-diabetic", and why the first advice given to all overweight diabetics is to lose weight. Unfortunately, as I have indicated in earlier blogs, the only method of weight loss that is guaranteed to work  is operative reduction of your stomach volume and food capacity, either by stomach banding or by gastric bypass surgery. I should also mention that daily exercise (about 30 minutes non-stop) is also beneficial, because exercise promotes the cellular uptake of glucose from the bloodstream, and this effect lasts for longer than the 30 minutes you spent exercising. When you exercise, it is sufficient to exercise at such a rate that at the end of the 30 minutes you feel that you  have had a workout; your pulse rate is immaterial.

     P.S. Although elevated blood sugar is pathognomic of diabetes, it is NOT true that eating sugar or carbohydrates will make you diabetic, unless it also makes you gain weight.


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