Pathology of hypoglycaemia

2021-01-27 12:00 AM

The glucose regulation system is compromised in long-term ill diabetic patients. The majority of patients with type 1 diabetes have poor glucagon response to hypoglycaemia.


Hypoglycaemia is also known as hypoglycaemia, to describe the clinical and subclinical manifestations that occur in the human body when the venous plasma glucose concentration (50 mg/dl (2.7 mmol / l) ).

Hypoglycaemia is one of the most common clinical emergencies, one of the causes of death in diabetic patients using hypoglycaemic insulin or sulfamide in which the mortality rate is 3-7%. in patients with type 1 diabetes. However, the clinical reality of the aforementioned blood sugar concentration limitation may vary due to the acute or chronic clinical situation depending on the age as well as the underlying medical condition, especially the diabetic patient who has a long history of chronic disease. long.

Whole disease

Fasting hypoglycaemia with high insulin levels

Insulin reaction:

Diet inadequate in terms of quantity and quality or due to missed meals in treated diabetic patients.

Excessive physical activity: In people, without diabetes, the glucose uptake of rhabdomyolysis (increased 20-30 times above baseline) is compensated for hepatic sugar neoplasm. This is due to a decrease in circulating insulin due to an increase in beta-cell inhibition of the catecholamine. This regulation is decreased in patients on insulin therapy. When subcutaneous drug deposition sites continue to release insulin during action and increase insulin absorption in muscle areas near the base.

The glucose regulation system is compromised in long-term ill diabetic patients. The majority of patients with type 1 diabetes have poor glucagon response to hypoglycaemia.

Insulin overdose. Due to lack of clarity or due to changes in insulin concentration in the vial (40 UI / ml replace 100 UI / ml).

Sulfamide hypoglycaemic overdose, long-acting drugs (Chlorpropamide has a half-life of more than 35 hours ...) Especially patients with liver and kidney damage, the elderly are at risk of hypoglycaemia.

Other resources:

Stress: When under stress (illness, infection, surgery ...) often increase insulin dose to balance blood sugar. When the stress stops, the dose should be reduced.

Failure of the adrenal cortex (Addison's disease) causes hypoglycaemia, so insulin dose should be reduced.

Diabetic gastroenterology: Nervous diseases of the organs make the stomach less tonic to slow the passage of food from the stomach into the intestines, the risk of postprandial hypoglycaemia in patients using insulin.

Pregnancy. The demand for sugar increases during pregnancy so insulin dose should be reduced in the first 3 months.

Renal Failure: Insulin breakdown and hypoglycaemic agents are prolonged.

Combination drugs: Diabetic patients with a combination of therapeutic drugs such as: Allopurinol, beta inhibitor, clofibrate, cimetidine, anticoagulants, hydralazine, indomethacin, Maleate de perhexiline, miconazole, phenobarbital phenylbutazone, probenecid, salycile, sulfamide anti-infection, IMAO.quinine, quinidine, ACE inhibitors, disopyramide, tricycliques, propoxyphene, octreotide, tetracycline, mebendazole, cibenzoline, stanozolol, fluoxetine, ethanol, sertraline, tromethamine, ganciclovir, lithium, temafloxacilline.

False hypoglycaemia (sneaky use of insulin and hypoglycaemic agents): related to patients with combined psychiatric diseases.

Autoimmune hypoglycaemia. There are antibodies to insulin resistance. Hypoglycaemia occurs 3 - 4 hours after eating and is attributed to the dissociation between the antibody immune complex and insulin free insulin ... Free hypoglycaemia by accumulating large amounts of antibodies. ability to react to endogenous insulin, has been reported in patients on methimazole treatment in Basedow disease in Japan, as well as in some patients with lymphoma, multiple myeloma, lupus syndrome, in which paraproteins and antibodies react cross with insulin.

Hypoglycaemia due to antibodies to insulin receptors is relatively rare, this patient has periods of insulin resistance and acanthosis nigricans.

Hypoglycaemia has also been recorded responding to glucocorticoid therapy without being seen in plasma filtration and immunosuppression.

Hypoglycaemia caused by using Pentamidine: A drug used to treat Pneumocystis carinii infections in AIDS patients, drugs that increase insulin levels due to its effect on beta cells (10-20% of patients).

Pancreatic beta-cell tumours.

Fasting hypoglycaemia does not increase insulin

Disorders associated with decreased hepatic glucose flow:

Due to the loss of a number of liver cells such as acute yellow liver atrophy, acute liver toxicity.

Due to disorders of the supply of amino acids to the liver (anorexia nervosa, long-term fasting, high blood urea syndrome, adrenal cortex failure).

Due to abnormal glucose metabolism in infants (lack of glycogen degradation enzyme, glucose neoplasm).

Alcohol-induced hypoglycaemia:

Alcohol (ethanol) is metabolized in the liver by NAD and catalyzed by ethanol dehydrogenase. Therefore, long-term use of alcohol reduces the amount of NAD in the liver. This is essential in the sugar neoplasm reaction. Alcohol-induced hypoglycaemia due to decreased sugar neoplasm associated with decreased hepatic glycogen stores. In addition, blood insulin decreases favourably for increased blood and urine cetone.

Patients with alcohol-induced hypoglycaemia often accompany an acute deficiency of vitamin B1 (Beriberi), so in addition to using glucose should coordinate with vitamin B1. Also due to the two factors mentioned above, the use of Glucagon in hypoglycaemia due to alcohol has no effect.

Symptoms usually occur 8-12 hours after eating. Patients who previously drank a lot of alcohol in quantity as well as time reduced glycogen stores partly due to inadequate eating.

Extra-pancreatic tumour:

Fibrosarcoma retroperitoneal, liver cancer, adrenal cancer, kidney cancer, gastrointestinal cancer, lymphoma and acute leukaemia. Insulin count is about 8 (U / ml during fasting hypoglycaemia. Perhaps misplaced insulin secretion.

Approximately 50% of tumours secrete a low-molecular-weight peptide with an insulin-like effect called a peptide that acts like unrestrained insulin (NSILA peptide = nonsupressible Insulins like activity) including human Insulin like growth factor and several substances. by somatomedin.

Reactive hypoglycaemia (hypoglycaemia does not occur during fasting)

Hypoglycaemia reaction ground after eating 2-3 hours or later 3-5 hours.

Hypoglycaemia caused by food after gastric bypass:

This is a consequence of insulin intensification after gastric bypass. Food drops quickly after eating, rapid glucose absorption increases blood sugar, stimulates insulin secretion, making patients dizzy, invasive, sweating. (A rapid empty stomach after eating, stimulates vagus nerve and gastrointestinal hormone production that stimulates beta cells (beta cytotropic gastrointestinal hormone). Anticholinergics such as propantheline can be used (15 mg / day 4 times). Eat small meals, limit the rapidly absorbed sugar, you can use alpha glucosidase inhibitors.

Functional hypoglycaemia due to food:

Common in patients with chronic fatigue, anxiety, anxiety, weakness, poor concentration, decreased sex drive, headache, hunger after eating ...

Late hypoglycaemia:

Hypoglycaemia after eating 4-5 hours after taking sugar suggests aura of type 2 diabetes.

Mechanism of pathogenesis

When blood glucose levels begin to drop below physiological levels, it stimulates the hypothalamus to stimulate the pituitary to secrete ACTH (increased Cortisol) and STH (increased glucose).

When hypoglycaemia a lot also arouses cravings for sugar and stimulates the reticulum - medullary system causes adrenaline-secreting adrenal marrow, parasympathetic system (nucleus X), pancreas (alpha cell) secreting glucagon, stomach thickened intestine secretes gastrin, secretine, stimulates ADH secretion.

Adrenaline with glucagon increases glycogen degradation and increases the regeneration of glucose in the liver, adrenaline (sympathetic and neurotrophic enhancement: sweating, anxiety, tachycardia)

Gastrin and secretin increase the absorption of glucose in the gastrointestinal tract. Stimulation of the sympathetic system (hunger, nausea and vomiting).

The above symptoms usually appear early but mainly and severe of hypoglycaemia, which primarily affects brain cells (because there is no reserve of glycogen), occurs within minutes. Lack of blood glucose leads to decreased oxygen consumption. Brain cell glucose requirement is about 60 mg / min and coma occur when 30 mg / min remains. Brain cell damage is not reversible if the lack of energy is severe and prolonged. Due to the lack of energy sensitivity of brain regions are different, so the order in which the symptoms of the clinical anatomical stages appear respectively are as follows.

Cortical stage: Lethargy, drowsiness, psychomotor stimulation, diplopia.

Subcortex and intermediate cerebral stage: automatic activity, strenuousness, convulsions.

Middle brain stage: muscle spasms, flexion, quadrature and non-response to light, eyeball twitching.

Pre-cerebrospinal stage: brain loss mark.

Cerebrospinal stage: deep coma, loss of muscle tone, loss of corneal reflex.

The owner of brain tissue is oedema, especially in patients with diabetes, necrosis, haemorrhage, causing allergies. In addition, coronary, digestive and respiratory systems occur later and infrequently.


Clinical symptoms

It should be noted that clinical symptoms are often less correlated with blood glucose levels. Symptoms of hypoglycaemia often occur when hungry or away from meals, corresponding to the duration of the maximum effect of the drug (insulin or sulfamide hypoglycaemia) on patients with diabetes. The above symptom improves rapidly when providing glucose immediately.

Mild hypoglycaemia:

Body signs: Patient has a feeling of physical fatigue, drowsiness, dizziness.

Sweating (a very important sign in this stage).

Gastrointestinal signs: hunger and epigastric spasm, possible vomiting or diarrheal.

Cardiovascular signs: Thrill, tachycardia, or extrasystole. Increased blood pressure. Pre-cardiac pain with arrhythmia or angina form.

Neurological signs: Cramps, headaches and paraesthesia, frequent or paroxysmal headache. Disorders of regulation, diplopia, chills (easy to mistake due to infection.

Psychiatric signs: Personality and mood disturbances: irritable, cheerful, lethargic, or sometimes moody or short-tempered.

Respiratory signs: Asthma-type dyspnoea.

If this phase is detected promptly and treated simply with sugary drinks, the clinical signs will improve rapidly.

Severe hypoglycaemia:

It may be sudden or occur on the background of the above clinical manifestations. In this period, the clinical manifestation is mainly the psychoactive mark.

- Neurological: Shock, drowsiness, depression with suicidal tendencies, agitation or assault, paranoia, hallucinations, passing consciousness.

Jaw stiff (easy to mistake tetanus) and severe hypoglycaemia.

General or focal epilepsy of Bravais Jackson type, hemiplegia, localized, cerebellar - vestibular disorder: dizziness, movement disorder (to mistake stroke).

This stage uses direct intravenous hypertonic glucose rather than oral administration, the patient recovers rapidly.

Hypoglycaemic coma:

The onset is usually not sudden, with muscle spasms, convulsions, tendon reflexes, pupil contractions, jaw stiffness, excessive sweating, with a flush of facial expression and recovery from early glucose transfer before passing irreversible with deep coma irreversible brain damage and death if severe and prolonged hypoglycaemia.


Plasma Glucose: (50 mg / dl (2.7 mmol / l).

Clinical and subclinical symptoms often do not correspond.

Intravenous blood sugar is accurate but the time to return results is often slow, so in the context of an extreme capillary blood glucose is also a reliable indicator and the results are immediate. Should not flag waiting for the results of venous blood glucose but should be done in parallel.


Implementing the quadrants

Whipple's Triad:

Clinical symptoms of hypoglycaemia.

Blood glucose concentration below 2.7 mmol / l (50 mg%).

Symptom improvement when consuming sugar-containing substances.

Diagnose the cause

Patients with diabetes:

Treatment with insulin drugs or hypoglycaemic sulfamide has been recorded several times through patient testimony if conscious, through family members if the patient is comatose.

Determine the onset of the condition as well as the favourable factors (missed meal, insulin overdose, excessive physical activity but forgetting to compensate for energy, or using additional drugs that increase the potential of hypoglycemic agents ( see the causes section) Draw from the above consequences, it is necessary to guide patients and family members in addition to educating hypoglycaemia need.

Reduce the dose of insulin or hypoglycaemic pills.

Review the quantity and quality of diet, especially the glucide content of meals especially during illness.

Adjust meal times to be reasonable.

Increase mid-time meals (snacks) in addition to meals. Attention should be paid:

Diabetic patients with well-regulated blood glucose cannot avoid the risk of hypoglycaemia.

Hypoglycaemia in a young diabetic is not a bad sign, but in the elderly or with cardiovascular disease (coronary failure, hypertension) is a serious factor with the risk of initiating a cardiovascular event. (heart attack, stroke).

Hypoglycaemia usually occurs at night near morning need to check blood sugar at 4am if the patient has suspicious symptoms.

Somogyi (reactive hyperglycaemia) phenomenon is a manifestation of previous hypoglycaemia.

Patients without diabetes:

Tests to do:

Diagnosis is often difficult requires multiple means such as blood insulin levels, C Peptides and other hormones or substances and tests are as follows.

The fasting test. Mandatory hospital stay with complete fasting or limited glucide diet (50 g glucide, 50 g Protide and 70 g lipide)

Fasting time: Fasting until symptoms appear hypoglycaemia or 3 days with labour.

The test should be done simultaneously:

Capillary and venous blood sugar (send to laboratory) every 4 hours until hypoglycaemia develops.

Dosing of insulin.

Quantification of plasma C peptide.

Based on the ratio of insulin / glucose (I / G) according to the following 2 formulas: Insulin (pmol / l) / glucose (mmol / l) (20 (normal).

Or (100 X insulin (U / ml) / (blood sugar - 30 mg%) (50 (normal) Note: 1 (U / ml = 7.17 pmol / l.

Test for hypoglycaemia with insulin

The patient should be closely monitored.

Technique: blood draw to measure sugar and peptide C at times of Gn. Insulin dose 0.1 UI / kg (fast-acting insulin).

Result evaluation:

Hypoglycaemia when blood sugar is below 50 mg / dl.

Endogenous insulin secretion is determined if the plasma C peptide falls below 65% of normal value.

Do not brake or weaken: adenoma secretes insulin, hypoglycaemia due to use of sulfamide. Without inhibiting peptide C, evidence of automatic endogenous insulin secretion requires investigating the cause by imaging diagnosis. Such as Locating insulin secretion by CT scanner. Selective angiography of the upper mesenteric artery. Analysis of insulin-secreting adenoma alone in multihormonal disease I, predominantly in children, with possible diffuse, unseen hyperplasia (nesidioblastose)

Diagnose the physical cause

Lower physical and functional hypoglycaemia.

Lower physical blood sugar

Usually occurs on an empty stomach, in the morning, eating late or skipping meals, after excessive exercise. Clinical manifestations are usually severe. Pay attention to the conditions, what happens, as well as the coordination factor. Simultaneous measurement of blood glucose, insulin and peptide C. Situation can be reconstructed with fasting therapy. There are 3 situations that happen as follows:

Blood insulin, peptide C and insulin / glucose ratio all increased:

Insulin secreting tumours, Stimulating endogenous insulin secretion by drugs or not., Sulfamide hypoglycaemia, Quinine

Both insulin and the insulin / glucose ratio increased but the C peptide was low:

Exogenous insulin use, fake disease., Illegal testing (manoeuvre criminelle). Find antibodies to insulin if using bovine insulin, but no pig if using human insulin.

Low insulin, normal or low insulin / glucose ratio:

May be related to disease, toxicity or drug, hypoglycaemia due to extra-pancreatic tumour (mesenteric tumour locating peritoneum, retroperitoneal, thoracic tumour), liver tumour, adrenocortical tumour, epithelium Often recurrent, severe hypoglycaemia. Easy diagnosis due to large tumours, CT scanner, quantitative increase in IGF2 (insulin like growth factor 2).

Functional hypoglycaemia

Usually occurs 2 to 4 hours after eating, Usually no sensory nerve signs. Very rarely coma. Expression of intense hunger and sweating. Patients often have a history of gastric bypass, colostomy, selective X-ray nerve resection. That is hypoglycaemia due to hyperinsulin (because food drops too quickly in the small intestine) need to distinguish Dumping syndrome. It is necessary to measure blood sugar when the above problem occurs. Need to perform the test again. Patients without gastrointestinal intervention (usually women) with hypoglycaemia due to hyperglycaemia or excessive sensitivity to insulin. Nervous vegetative responses without hypoglycaemia in anxiety and depression women.

Some special situations

Acute alcohol poisoning: Hypoglycaemia is always sought in alcohol-induced coma, malnutrition.

Hepatotoxicity: Glycol, tetrachlorure de carbone, phalloide annannite.

Use Hypoglycine (a green fruit in the Jamaique region).

Severe illnesses: kidney failure, liver failure, pituitary failure, acute adrenal insufficiency, malnutrition, heart failure, infectious shock.

Using some drugs such as (acetaminophen, beta blocker, chlorpromazine + orphenadrine, ethionamide, disopyramide, haloperidol, maleate de perhexiline, quinine, pentamidine, propoxyphene, salicylic) ...


Post-hypoglycaemic cerebral oedema: Persistent coma, although blood sugar returns to normal with popular oedema. Acute pulmonary oedema: Due to pulmonary capillary contraction.

Neurological consequences: Peripheral neuropathy: progressive week muscle atrophy, distal part of extremities occurs several weeks after having one or more severe hypoglycaemic episodes, often combined with paraesthesia. Anterior spinal horn damage may be present.

Prolonged neurological disorders: Crazy, epilepsy after hypoglycaemia, Parkinson’s syndrome, dancing.

Fracture or collapse of the vertebrae: Occurs during a severe menstrual episode.

Note: Patients with the age (over 60 years old), especially with cardiovascular disease, are at risk of cardiovascular events (electrocardiogram examination is required if silent ischemia is suspected).

In patients with diabetes, hypoglycaemia that can occur at night are often unnoticed. So check for capillary blood sugar at 4am.

Frequent sequelae: It is a sequel of acute, repeated and unaware attacks. Paralysis, loss of speech, dancing, Parkinson's syndrome. Gradual dementia, dementia, distal quadriplegic muscular atrophy syndrome, and loss of tendon reflex.


Symptomatic treatment

The patient is conscious:

Drink sugary drinks until symptoms improve.

Do not drink chemical sugars (sacharinate de sodium, saccharineate d'ammonium) for people with diabetes.

Patients in a coma:

Glucose solution 30% or 50%:

The amount of Glucose = [Weight (kg) X 0.2] X [Gbt - Gh]

In which Gbt is the plasma glucose concentration to achieve eg G = 1 g / l, Gh is the concentration of blood glucose at the time of hypoglycaemia eg Gh = 0.2 g / l. Thus a patient weighing 50 kg, the amount of glucose to be pumped initially is: 50 x 0.2 x (1 X 0.2) g = 8 g glucose.

Do not drip infusion but must pump directly intravenously to achieve fast and high blood glucose concentration.

Glucagon (tube 1 mg):

Intravenous, intramuscular or subcutaneous injection at a dose of 1-2 mg, can be repeated after 10-20 minutes (short half-life). Do not use glucagon in subjects with heavy alcohol use due to poor hepatic glycogen storage, or in fasting patients who have no longer had glycogen stores in the liver. Patients with long-term type 1 diabetes also have little response to glucagon.

Hydrocortisone: 100 mg intravenous injection

Maintenance treatment

If the patient is awake able to eat, continue eating as usual.

If there is no food (vomiting, intolerance ...) Intravenous administration of 10% Glucose at a dose of 1500-200 ml / 24 hours (150-200 grams of Glucose) until plasma glucose concentrations return to normal after much hours. Do not give high doses because the body can only tolerate up to 1.5g of glucose/hour

Need to monitor blood sugar is usually based on the half-life of hypoglycaemic drugs (Insulin, Sulfamide, hypoglycaemia ...), treatment must exceed the duration of action of drugs causing hypoglycaemia.

Check electrocardiogram especially in elderly patients, coronary artery disease, hypertension.

Treat the cause

In relation to diabetic patients:

Identify the conditions of occurrence: forgetting to eat, low-sugar food, an overdose of Insulin, excessive physical activity but forgetting to make up for energy. Combination of a drug has the potential to increase the effect of hypoglycaemic sulamide

Need to change treatment directives:

Change or decrease the dose of Insuline, the dose of sulfamide to lower blood sugar.

Adjust the Glucide energy content of each meal to be reasonable.

Adjust meal times, so add snacks between meals.

Sulfamide-lowering blood sugar drugs should not be indicated for patients over 70 years old, especially drugs with a too long half-life (Chlorpropamide).

Renal and hepatic failure (hypersensitivity to hypoglycaemic drugs).

A combination of drugs increases the effect of hypoglycaemic drugs or by reducing the daily dose.

The ideal glycaemic balance criterion does not apply to patients

Diabetes over 60 years old.

It should be noted that Somogyi causes secondary morning hyperglycaemia due to hypoglycaemia during the night

Treatment of diseases causing hypoglycaemia:

Insulin-secreting pancreatic tumours: Surgery, Diazoxide (oral or static) dose 300-1200 mg / day + diuretics. Octreotide is injected subcutaneously at a dose of 100-600 (g / day. Chemotherapy with Streptozotocine-5 fluoro uracile).

Extra-pancreatic tumour secreting insulin: Surgery, Anti-hypoglycaemia (difficult) by passing Glucose, Glucagon continuous subcutaneous transfer by pumping in intermittent rhythm.

Patients with gastric bypass surgery: Educating patients and relatives on the signs and management of hypoglycaemia. Glucose and Glucose Hypertonic Glucose are available at home. Reduce rapidly absorbed sugars. Food with Protide and glucide combination.


It is necessary to educate hypoglycaemia as well as how to manage hypoglycaemia for diabetic patients and their relatives.

Management of hypoglycaemia should be acute, in place with all possible measures before referral to hospital, and should not wait for blood glucose results.

Note the hypoglycaemic effect of some drugs in combination.

Avoid the concept of "Sugar is the enemy" for diabetics.