Normoglycemia

You wonder what is the latest definition of normoglycemia, and turn to the  medical oracle, known as  Evidenced Based Medicine (EBM). EBM derives information from clinical trials and comes up with the following definition: Normal fasting glucose level  3.3 - 6.7 mmol/l (60-100 mg /100ml). Some experts are somewhat cautious, and regard the glucose level range 5.6 - 6.7  mmol/l as impaired with  a greater risk of developing diabetes mellitus.

In order to estimate the normal glucose level, EBM epidemiologists measure fasting glucose in a  group of healthy individuals, and get a distribution of values which fluctuate around a mean. Any value  in the range of  two standard deviations (SD) from the mean, is regarded as normal. Values below are hypoglycemic, and above, hyperglycemic. (This estimate requires a log-normal transformation).

How do these experts know that their patients were healthy? They examined them thoroughly and then asked them the crucial question:"Do you feel healthy?" And yet in this healthy population some had already impaired blood glucose values.

Tachycardia

Next day you wonder what would be the normal resting heart rate of a male. EBM experts come with the right answer: 60 - 80 /min. Any value below two SD of the mean is bradycardia, and above, tachycardia.  You look at your patient with a heart rate of  110/ min and ask the EBM expert:"Is his heart rate abnormal?", "Of course not!" he answers benevolently, "Don't you realize that he is  worried?"  Yet this wise guy does not realize that his argument is flawed. He broadened the context in which the significance of heart rate was considered. When EBM estimated the normal heart distribution it disregarded whether  healthy subjects were worried or not. And since some may have been, their estimates may be flawed. According to EBM this heart rate is abnormal. This example illustrates the contradiction between a definition of a normal value based in population studies, and clinical observation.

Context fallacy

A context fallacy occurs when a  theory or a statement valid in a narrow context is applied (extrapolated)  to a different or wider context. Here the narrow context in which the normal heart rate is defined  is a frequency distribution of values. How each patient feels, was not examined, and  belongs to a wider context . Similar flaws accompany many  EBM directives. Clinicians avoid such traps with common sense, however in chronic diseases context fallacies are more subtle.

Hyperglycemia

How many healthy and worried patients contributed to the so called impaired glucose levels?  Yet  experts regard these healthy glucose values indicate a greater risk of developing diabetes!  You might  never meet these 'high risk' patients since they feel healthy. Should they be screened preventively? After all experts suggest  to check their blood glucose more often.  Which illustrates another outcome of the context fallacy. Since EBM  definition of normal is inadequate, borderline cases are suspicious. Some are even proclaimed to be sick, which has some harrowing consequences. Such a 'high risk' individual applies for a job and is told that she is diabetic and will therefore pay a higher life insurance premium.

Biological variation

What went wrong?  Since each individual is different  he has also a slightly different blood sugar value. Epidemiology calls it biological variation, which is conveniently summarized by two parameters, mean and  SD. The fallacy occurs when EBM equates this mean with  normality, like in normoglycemia. Biological variation means that all  different blood sugar levels  are equally  normal and healthy. The distribution  is a spectrum of normal glucose levels, and its mean is not more normal than the other values.

Machine statistics

Yet EBM fails to see it that way. Like physics it attributes variation to chance and regards it as an  error. Like physics it applies the normal distribution function (and its transforms) to describe medical phenomena, and regards the mean as the only correct or normal value, anything else is an error. By equating  mean with  normality, EBM perpetuates a fallacy with a damaging consequences on therapy.

Further reading:
Meta analysis  and Chaos
The normal and he pathological

A simple model

We are concerned here with type-2 diabetes mellitus, and shall illustrate the following arguments on a simple model. Blood glucose level is driven by a demand  for it by  organism, and is controlled by WOB.  A glucose molecule is born upon entering  blood circulation, and dies when leaving  it. Glucose birth rate is also its production, and death rate is glucose utilization.  The terms birth and death in relationship with glucose are preferred over production and utilization, since glucose turnover is regarded here as a process, and these terms are suitable for  describing processes.

Environment drives  demand for glucose  in a variety of ways. During daytime, for instance, demand rises, and at  night it  declines. When demand is high, glucose birth rate rises, death rate declines, and  blood glucose level  rises. When demand declines glucose birth rate declines, death rate rises, and glucose level declines. Demand for glucose  is the only drive  for glucose birth or production.

When mind is worried, like in the patient described above, it instructs WOB to raise glucose birth rate (production).

Solution

WOB controls all processes and adjusts them to meet the requirements of the organism. It is constrained by environment and mind. When it gets cold WOB turns the heat  on , and vice versa.  WOB responds  also to the mind, which receives signals and directives from society (culture). The adjustment of  processes at any instant is called WOB solution.  It is always the most optimal solution in the  circumstances. This is the modern interpretation of Galen’s principle: Nothing is done by Nature in vain.

Rising normoglycemia

Moderate hyperglycemia is WOB solution to patient's worries. Since worrying, he needs more glucose, otherwise WOB would produce less. This optimality principle underlies also the evolution of diabetes mellitus. At any instance WOB adjusts glucose production to the requirement  by the organism.  Diabetes mellitus results from a rising demand for sugar by the brain.  An ongoing sugar craving by the brain. What  appears to the observer as a rising hyperglycemia, is an evolution of optimal solutions. Diabetes mellitus is  a rising normoglycemia.

Diabetes mellitus proceeds through two phases:

1. Full compensation when glucose birth and death rates are high and equal and patient feels healthy.
2. Decompensation, when glucose birth and death rates are high and death rate is lower than birth rate. Patient feels sick, and suffers from secondary manifestations like polyuria,  acidosis, infections, and other complications.

Rising demand for glucose by the brain drives the disease. Although  its cause is still unknown, one might consider a latent infection, or an impeded blood flow due to arteriosclerosis. Either brain cells require more glucose for their activity, or they do not get enough glucose, (a receptor deficiency), and require an ever increasing glucose throughput.

Full compensation

The disease starts with rising glucose birth and death rates. Initially they are equal and blood glucose level does not change. Next, brain  starts demanding a higher throughput and glucose level rises. Then comes polyuria, and disease enters its second phase. Clinical manifestations are interpreted here from WOB perspective. When  WOB fails to supply enough glucose to the brain, it signals the mind a sense of hunger as if saying: "Get more glucose!" Concomitantly WOB catabolizes tissues, and patient loses weight.  Now organs require less sugar, and more is left for the brain. In order to divert even more sugar to the brain WOB signals weakness and fatigue as if saying:" Lie down!"  Organs utilize  less glucose (energy)  and the surplus is  diverted to the brain.

From WOB perspective it's main task is to prevent hypoglycemia, and when it fails, patient will faint, and brain will require less glucose.

Decompensation

As glucose level rises, patient suffers from polyuria. WOB sends to mind a  thirst signal, as if saying: "I lose control of water resources, get me water!" In order to increase blood flow through  the brain WOB raises blood pressure.  Prevalence rates of hypertension  among diabetics are between 40% and 75%.  Rising blood glucose  impairs tissue function, known as glucose toxicity.  Rising  hypertension and glucose toxicity will determine the intensity of other complications, e.g., neurpathy, nephropathy, and cardiovascular events.

All along disease progression, WOB solution remains the most optimal under circumstances. In order to keep the patient alive it has to give up peripheral processes, otherwise patient will die. WOB task is to maintain life at all cost.  Even a stroke may be regarded as WOB effort to divert more glucose to the brain.

Secondary polycythemia

This way to explain the nature of diabetes mellitus is somewhat unusual. Yet similar considerations apply to many chronic diseases.   The following thought experiment  illustrates a  relationship between demand and outcome in secondary polycythemia.   The sixty years old astronomer named Carlos, is asked to work in an observatory high in the Andes. He enters a lift which will bring him there. The voyage lasts about three weeks during which he cannot leave the lift, neither stop it. (A similar lift was applied by Einstein to explain his theory of relativity).

As the lift starts ascending, air becomes thinner, and oxygen scarcer.  Since oxygen is carried by red blood cells (RBC)  we shall follow their fate as Carlos approaches the summit.

His condition proceeds through two phases:
1. Full compensation when RBC birth and death rates are high and equal and patient feels healthy (normocythemia).
2. Decompensation, RBC birth and death rates are high and death rate is lower than birth rate (polycythemia). Patient feels sick, and suffers from secondary manifestations, like tachypnea,  acidosis, infections (bronchitis), and other complications.

Oxygen demand by the brain drives his condition.

Full compensation

RBC  birth and death rates rise. Initially they are equal and RBC  level does not change (normocythemia).  As oxygen becomes scarce,  brain requirements for it remain the same, and RBC level rises (polycythemia). Then comes tachypnea, and disease enters its second phase. Clinical manifestations are interpreted from WOB perspective. When  WOB fails to supply   brain with sufficient oxygen,  it signals the mind a sense of choking as if saying: "Get more air!" Concomitantly WOB catabolizes tissues, and patient loses weight.  Now organs require less oxygen, and more is left for the brain. In order to divert even more oxygen to the brain WOB signals mind  weakness, fatigue, and prostration,  as if saying: "Lie down!"  Organs use less oxygen (energy)  and the rest is  diverted to the brain.

From WOB perspective it's main task is to prevent brain anoxia, and when it fails, patient will faint, and brain will require less oxygen.

Decompensation

In order to increase blood flow through the brain WOB raises blood pressure.   Rising  hypertension, blood viscosity , and patient's arteriosclerosis, will determine the intensity of other complications, e.g., cardiovascular events,  nephropathy, and bronchitis.

All along his ascent toward the observatory WOB solution remains the most optimal under  circumstances. In order to keep the patient alive it has to give up peripheral processes, otherwise patient will die. WOB task is to maintain life at all cost.  Even a stroke may be regarded as WOB effort to divert more oxygen to the brain.

More on Carlos' condition  read: On Cause and Etiology of Disease

Such an  explanatory narrative is applicable also to essential hypertension, Parkinson's disease and some other chronic diseases.

Therapy

WOB solutions do not meet the patient's (mind) expectations, who  wants a better life. The physician has two main responsibilities: To help where WOB failed, and to improve patient's quality of life, without interfering too much with WOB solutions. He has to work out a compromise between  WOB and mind demands. Since patient cannot be cured,  the main objective is to slow down disease progression.  The two major threats to the patient are hypertension and glucose toxicity. Any attempt to lower hypertension and glucose endangers the patient.  Physician ought therefore attempt to lower glucose demand by periphery.

Meditation

During sleep  demand for glucose is the lowest. Patient should therefore be encouraged to sleep at least eight hours. He may have learn how to sleep that long. A meditating  patient may attain a sleep like condition while maintaining his full consciousness.  Her muscles relax, heart beats slower, and  so is breathing . Demand for glucose declines. Meditation has yet another advantage. Patient learns how to manage his worries and ignore the negative impact  on himself by society and culture. Meditation reduces the demand for glucose.  It introduces the patient to a new life. From now on his  mission is to learn how to live with diabetes mellitus.

Sport

Is risky, however  has many advantages. Body building  is not advised  since it increases demand for glucose. Aerobic exercises may be helpful, since  organism learns how to conserve oxygen and utilize less glucose. Aerobics improve blood circulation particularly in the brain, and may lower the demand for blood throughput which will lower also blood pressure and blood glucose level.

Cerebral blood flow

Diminished cerebral blood flow may be the main driving force of diabetes mellitus. Mild muscular activity increases cerebral blood flow. When a muscle is activated, brain neurons controlling it get more blood. This  activity   ought to be gradual so as not to endanger the patient.  It seems that ancient Chinese martial arts might be appropriate for such a task.

Diet

In slim individuals glucose  should not be restricted, since WOB obviously demands it. Even in mild  diabetes mellitus WOB signals  an unusual hunger.  Many diabetics are obese or become so  with time. Obesity utilizes energy and deprives the brain from sugar. Although weight reduction is mandatory it ought to be done gently  since a diet causing abrupt weight loss reduces also blood sugar and may harm the brain.  Alternative healers apply many kinds of diet which seem  promising and ought therefore be tested for their capacity to reduce glucose demand by the periphery.

Insulin

While juvenile diabetes (Type-1) is caused by insulin deficiency, type-2 diabetics don't lack insulin, since islet cells are intact. Only WOB resists its application. Insulin is a last resort measure, since by lowering  blood glucose it deprives the brain of it. It is indicated in acute conditions, like infection and sepsis. With time it becomes less and less effective. The Achilles' heel of insulin therapy remains a combination of weight gain and hypoglycemia. In order to protect itself from insulin induced hypoglycemia, WOB makes it less and less effective, known as insulin resistance. It resists also oral hypoglycemic agents, to which patients  become resistant at a rate of 10% to 20% a year.

Insulin-yogi

The yogi suffix  signifies people capable of living with their disease in harmony, and slow down disease progression. (v. Cancer-Yogi .  Suppose one could diminish  glucose demand by the brain, it might diminish its dependency on glucose blood level, and slow down disease progression. Meditation has such a merit. It introduces the patient into a new way of life.  From now on his mission is to become an insulin-yogi.