Knowing All About Sugar: ­Blood Vessel and Tissue Injuries Develop When Blood Glucose Concentrations Circulate Above Normal Even For A Short Time: Part 2 of the Diabetic Story

Glucose is the essential energy molecule that our body's tissues utilize. Glucose exists in fruits and vegetables and grains, either as a simple sugar or as a structural component of plant starches and complex fiber carbohydrates. All carbohydrates must be broken down to glucose and fructose in our intestines prior to their absorption into our blood, as our intestines can absorb only glucose and fructose. 

Glucose absorbed from our food has a programmed journey. First, glucose enters our bloodstream across our intestinal cells where glucose circulates to all tissues and cells. All glucose molecules will quickly exit our blood, crossing cell membranes, and entering the cell interior. Insulin is an essential hormone that facilitates this entry of glucose into our cells and tissues. Once in the cell interior, glucose enters the glycolysis pathway (lysis or breakdown of glucose), yielding carbon dioxide and water and essential energy molecules, which in turn, provide reaction energy for essential cellular life processes.

Type 1 Diabetes: Insulin Lack. However, glucose will linger in the bloodstream if cell uptake of circulating glucose is sluggish. Sluggish cellular uptake of glucose happens when insulin secretion - and insulin presence at cell membranes - is inadequate. This is termed "insulin lack". Though "insulin lack" is valid as an explanation, it is more appropriate to state that there is relative "insulin insufficiency" for the load of circulating glucose, for insulin is never at a "0" concentration; rather in the Type 1 Diabetes Mellitus Disease State, insulin concentrations are lower than normal values and the glucose-provoked-stimulation of insulin secretion is abnormally low, too. This defines "Type 1 Diabetes Mellitus: Elevated Circulating Blood Glucose concentrations because of Insufficient Secretion of Insulin.” Or to say it another way, “Type 1 Diabetes Mellitus" is the accurate diagnosis when glucose circulates in the bloodstream at higher than normal blood concentrations because pancreatic insulin secretion is below normal. In this context, glucose will circulate longer and at higher than normal concentrations, and in essence, cells "starve" in the "midst of plenty." Glucose is available but is not moving into cell interiors where it is needed because of inadequate insulin presence.

Type 2 Diabetes Mellitus: Insulin Insensitivity. Glucose entry into cells can be slow and glucose concentrations in the blood can remain higher than normal if tissue cells are "insulin resistant." In this context, insulin is secreted by the pancreas and circulates, but the cell is not responsive or is not fully responsive to the insulin. The pancreas will even secrete surplus or “supernormal concentrations of insulin” but tissue cells remain “relatively resistant” to the insulin actions. Then, again, glucose is available outside the tissue cells but is not moving into the cell interiors, and again, the cell is "starving" in the "midst of plenty" of energy food. 

This defines "Type 2 Diabetes Mellitus: Elevated circulating Blood Glucose concentrations because of Cellular Receptor Insensitivity to the Action of Circulating Insulin.” Or, to say it another way, “Type 2 Diabetes Mellitus" is the accurate diagnosis when glucose circulates in the bloodstream at higher than normal blood concentrations because tissue cell membranes are “Resistant to the Membrane Actions of Circulating Insulin.” Pancreatic insulin secretion is actually higher than normal but its actions on target tissue cells are faulty. In this context, again, glucose will circulate longer and at higher than normal concentrations, and in essence, cells "starve" in the "midst of plenty." Glucose is available but is not moving into cell interiors where it is needed because of faulty insulin receptor actions. So, hyperglycemia persists.

Glycation Reactions. In both Type 1 Diabetes and Type 2 Diabetes, the presence of elevated glucose concentrations for prolonged periods of time leads to random spontaneous "glycation reactions" whereby a circulating glucose molecule attaches without enzyme facilitation or mediation to a protein or lipoprotein molecule. Glycation reactions are not governed. Normally, a circulating glucose molecule enters a tissue cell within 90-120  minutes. Insulin drives this tissue uptake of glucose. Any glucose molecule that circulates in plasma longer than 120 minutes will experience structural change and “react” with another molecule, adhering to it and changing this molecule to a “glycated molecule:” i.e. “adhered by glucose.” Glycation is not healthy. Glycation changes the nature of the affected protein or lipoprotein in a non-healthy way. Glycation is not desirable and is harmful. Glycation events that accumulate are irreversible and are the dreaded consequences of "insulin lack" and "insulin resistance" and the ensuant hyperglycemia. Glycation is the dreaded result of hyperglycemia. 

Prediabetes. Prediabetes is now recognized as a true metabolic disorder where glucose circulates transiently at higher than normal concentrations following a meal, and random glycation events begin to accumulate. Prediabetes is diagnosed by higher than normal fasting glucose concentrations OR by the discovery of abnormal concentrations of "glycated hemoglobin" in the red blood cells that circulate. Glycated hemoglobin at barely higher-than-normal concentrations is the principal indicator of a prediabetic state. It is important to realize that the discovery of slightly elevated glycated hemoglobin concentrations in the bloodstream not only reveals abnormal glucose management by our bodies - but this is revealing dreaded glycation events. And, glycation events are the harmful consequences of elevated blood glucose concentrations - and the means of organ and vascular injury from diabetes. Thus, prediabetes not just heralds disease. Prediabetes, as indicated by slightly elevated glycated hemoglobin levels, is a signaling metabolic disorder that requires action. This same glycation event that is occurring on hemoglobin is occurring on proteins of vascular cell walls of every tissue in the prediabetic state. It is mild and minimal in the prediabetic state, but real and additive and progressive. Tissues are harmed and more harm will ensue unless the prediabetic state is remedied. Action is required.

Glucose Intolerance. “Glucose Intolerance” exists in an individual when one’s blood glucose concentration following food or a beverage rises above 140 mg/dL OR remains above 100 mg/dL for more than 120 minutes after ingestion. The phrase “Glucose Intolerance” denotes that our body’s tissues did not “uptake” or “tolerate” the glucose load in the normal and expected time frame, and the ingested glucose is not fully utilized by cells and tissues for energy. The phrase “Glucose Intolerance” may be spoken or explained as a relatively benign or harmless condition, and explained as not true “Diabetes.” This may be explained with relief and assurance, and this is a true statement.

Diabetes mellitus is indeed much more than glucose intolerance.

However, glucose intolerance occurs because of insufficient insulin secretion or because of resistance to the action of insulin. Both of these abnormalities are present in overt diabetes mellitus but to a much greater degree. Ingested carbohydrate leads to blood glucose levels higher than 140 mg/dL in overt diabetes mellitus, and blood glucose concentrations will not decline into the normal zone with overt diabetes unless treated with medications, weight loss, and diet changes.

Thus, it can be comforting to learn that while glucose intolerance is present in one's body, overt diabetes mellitus may not be present. It can be comforting and a relief because overt diabetes mellitus is harmful, hazardous, damaging to tissues, and ultimately disabling for many people.

On the other hand, glucose intolerance is now known to progress to overt diabetes mellitus in 25 to 50 percent of people. Glucose intolerance has therefore been defined and re-explained as "prediabetes." And prediabetes has even been linked to organ impairments, progressive cardiovascular disease, eye disease, and shortened life span.

How can this be? The circulating glucose molecules not utilized by cells and tissues for energy eventually react as toxic molecules by binding to cell membranes and blood vessel walls, causing changes in the nature of these membranes, even promoting internal microscopic scar formations.

Glucose Intolerance may be relatively “mild,” but Glucose Intolerance is not natural, is not always benign, and is known not only to lead eventually to overt diabetes but is known to cause cell and tissue harm before overt diabetes is diagnosed.

Glucose Intolerance is a true Prediabetic condition. Be wary then if you learn that you are showing evidence of Glucose Intolerance on blood testing. My next article will dive into Steps of Care and Remedy for the Prediabetic Glucose Intolerance Condition.

Rex L Mahnensmith, MD