Dr Ramakrishnan MD


Hypoglycemia – Beyond 50 mg

Hypoglycemia is a major factor preventing patients from achieving near-normal glucose targets. The risk is due both to inadequacy of current therapy which produces inappropriately high insulin concentration between meals and at night plus a failure in the physiological protective mechanism.

However, none of us who care for patient’s welfare either ignore this fact on pays & can’t respect to this can never don the mantle of health-care-providers. It is time to realize that hypoglycemia is the other side of a coin – Diabetes mellitus. Evidence based medicine brings out the following little known facts about a well-known fact – Hypoglycemia

It can be terrifying for those who live with and love some one with diabetes. For the patient, it can be disruptive, demoralising a condition in which he loses control of his own actions and behaviour in our matched only by epilepsy and some psychiatry.


Why it matters

Incidence of diabetes mellitus is increasing and tight metabolic control is now the watch-word. There are now multiple drug regimes and the expanding use and rarely initiation of insulin in type II Diabetics promote frequent hypoglycemia episodes of varying severity.

How Common

It is very difficult to estimate, patients records are unreliable. A spouse may be the best source of information. There may be retrograde amnesia and emotional denial by the patient.

Normal defense

When the blood glucose falls below 50 mg counter regulatory hormones – glucogen and epivepkrinal followed by cortisol and growth hormone level to normal via glucose analysis and neoglucogenesis. It is suggested that glucose sensing responsible for physiological response is initiated at ventromedial hypothalamus.



Strictly speaking, Hypoglycemia is a biochemical term and exists at a plasma glucose concentration below 50 mg. In infant’s less than 35 mg is considered low during the first 24 hours of life and 40 mg there after is abnormal. Diagnosis cannot be made solely on symptoms and signs since they are non-specific, very among individuals, even from time to time. It cannot also be made solely on the basis of plasma level. It is not possible to define a level below which neoro-glycopenia occurs and above which neuroglycopenia never occurs. The diagnose is mot convincingly established when it is based on “Whipple Triad” – symptoms consistent with hypoglycemia, relief with glucose and a plasma level below 50 mg.



Sympathoadrenal      Neuroglycopenic

Weakness      Headache

Sweating (Cholinergic)         Hypothermia

Tachycardia   Visual Disturbances

Palpitations    Mental dullness

Tremor            Confusion

Nervousness  Amnesia

Irritability         Seizures, Hemiplegia

Tingling           Coma



  1. caused by increased activity of the sympathoadrenergic system; may be triggered by a b.very rapid fall in blood glucose levels

  2. caused by action on the central nervous system; requires a level of blood glucose well in the hypoglycemic range


All patients need NOT manifest all the classical signs and symptoms of hypoglycemia. Thus, diagnosis may have to based on clinical suspicion; if available, capillary blood glucose measurement using finger prick test should aid diagnosis; in its absence, clinical improvement with glucose administration aids diagnosis.




Some patients may manifest sympathoadrenal signs and symptoms, even if the blood glucose is not actually in the “hypoglycemic” range.

Usually seen with a very rapid drop in the blood glucose level. This is termed relative hypoglycemia.

Absence of Sympathoadrenal signs and symptoms

Patients may manifest neuroglycopenic signs and symptoms in the absence of sympathoadrenal reactions under certain conditions:

If the blood glucose level fall very slowly;

Diabetics with significant neuropathic involvement;

Certain drugs such as beta blockers may mask the sympathoadrenal manifestations;

Some elderly diabetics.

Autonomic Neuropathy, Hypoglycemia unawareness.

Non-Classical signs and symptoms

Many diabetics exhibit signs and symptoms which are truly hypoglycemia reactions although they may not fall into the “classical” manifestations.

Patient who become excessively quiet, or conversely, very boisterous, show a lack of interest in normal activities, throw uncalled for temper tantrums, become morose, ambitionless, complain of feeling faint, complain of perioral paraesthesias, etc. may all be manifesting hypoglycemia.

In simple terms,

Any Diabetic undergoing treatment who shows a behaviour pattern which is not in keeping with his normal behaviour, should have the presence of hypoglycemia rules out.


High risk patients

  1. Those who have difficulty in perceiving hypoglycemic symptoms;

  2. Those who do not spontaneously recover from hypoglycemia;

  3. The elderly, as well as, infants and young children;

  4. Patients with angina pectoris, TIA’s renal and hepatic dysfunction, etc;

  5. Patients with erratic eating habits and timings;

  6. Patients whose work may call for sporadic, sudden and vigorous activity.

Nocturnal Hypoglycemia

It is very important to rule out hypoglycemic reactions occurring during sleep. 50% goes unrecognized and is an important cause of pre breakfast Hyperglycemia

These may not be severe enough to cause convulsions or coma. The patient may complain that the experiences night sweats, has recurring vivid dreams or nightmares, has early morning headaches which disappear after he takes his breakfast. This can be prevented by reducing the dose of and moving the timing of intermediate acting insulin to bedtime and by having a bedtime snack.

Such complaints must be investigated to rule out nocturnal hypoglycemia and a 3 AM blood sugar estimation is useful.


Individual Characteristics

Most patients show their own characteristic pattern of hypoglycemic manifestations, and this pattern often remains constant for the patient for a fairly long time.

Thus, it if very important for the patient, family and the doctor to be familiar with this pattern so that hypoglycemia can be correctly and rapidly diagnosed.

Common precipitating factors for hypoglycemia

  1. delayed or missed meals;

  2. unexpected calorie intake reduction;

  3. sudden, undue, vigorous activity;

  4. errors in dosage and/or timing;

  5. renal and hepatic dysfunctions;

  6. defective counter-regulation;

  7. interaction with other drugs;

  8. change in insulin species, i.e. beef to human insulins;

  9. change of injection site,

  10. inadvertent intramuscular injection;

  11. subtle hypothyroidism and/or adrenal insufficiency.


Hypoglycemia unawareness

Some patients, especially the elderly, may show hypoglycemic “unawareness”. In this condition, patients who manifested sympathoadrenal signs and symptoms during earlier hypoglycemic episodes either do no show these manifestations, or they appear at a relatively much lower blood glucose value. Neuroglycopenic manifestations may be the initial presentation.

It is necessary to be aware of this, in order to avoid severe hypoglycemic sequelae.

It is functional, not structural and can be reversed by strict avoidance of hypoglycemic episodes. Future therapics include caffine, cortisol antagonists, Bata blocking agents etc.

Effect on microvasculature

Through chronic hyperglycemia is the principal pathogenic factor, it is postulated that is established micro vascular disease is vulnerable to recurrent episodes of hypoglycemia  there is profuse recreation of vasoactive hormones – adrenaline, vasopressin and angiotensim II and they may damage capillaries leading to worsening of retinopathy and nephropathy. Anecdotal reports have associated acute vitreous hemorrhage with nocturnal hypoglycemic episodes.


Effect on Brain


Neurogycopemia causes cognitive impairment, manifested initially difficulty in concentrating, reduced speed of intellectual functioning; and lapsing into coma. Mood changes are common – amnesia, depression, tense-tiredness. Denial of hypoglycemia is common and some time, irrational and aggressive responses and occasionally a stale of automatism develops most intellectual functions may recover within 40-60 minutes; amnesia and mood changes and in walise may persist. Transient hemiplegia and convulsions may occur. It is better to postpone E.E.G. for a week.

Repeated episodes may elicit long term effects akin to alcohol abuse, boxing injury and sleep amnesia.


Brief, but intensive response that occurs second to the profound sympathoadrenal activation provoked by hyperglycemia may provoke a vascular event on a dysrhymia in people with a pre-existing coronary artery disease, or may compromise myocardial contractively in people with specific heart diseases of Diabetes. The true incidence of these events may be underestimated in clinical practice because precipitating factor is either overlooked, may have already been treated or counter regulation may have raised blood glucose by the time patient received medical attention.


Effect on peripheral blood

Acute hypoglycemia has also significant, albeit transient, effects on peripheral blood which encourage harmostasis and increase blood viscosity. While they do not appear to compromise vascular perfusion in the normal healthy vasculature, they may have potentially adverse effects in diabetics, in whom endothelial dysfunctions is prevalent.



Driving is an everyday activity and hypoglycemia may cause problems - poor road positioning, driving too fast and past destinations, inappropriate breaking, judgment and insight becomes impaired; in addition asymptomatic hypoglycemia impairs visual information processing and contrast sensitivity, particularly in poor visibility.



At the onset of symptoms, patient should take

a)     2-4 dextrose tablet on

b)     2 tsp (10 g) sugar on a small glass of carbonated sugar containing soft drink. If the response is not good, repeat the same. Over-treatment should be avoided if possible. We should remember that cognitive dysfunction may lead to a negative or even hostile response from the patient. Alternatives then include

If cerebral edema is suspected adjunctive treatment – I.V. dexamethasone/manitol/ is usually administered. C.T. scan may be needed. Evidence for efficacy is scarce.



Hypoglycemia is a common side effect with long term consequence. Recurrent episodes promote “Hypoglycemia Awareness”. Repeated episodes can aggravate Macro/microvascular disease that is already existing. It can affect the quality of life, even that of spouses and relatives. It is a preventable tragedy and should not be dismissed by physicians as an unavoidable nuisance, Hypoglycemia may be a number (50 mg) for us but it is a life sentence for the patient.