hyperglycemia



OVERVIEW

Definition

Hyperglycemia is a condition in which the concentration of glucose in the blood is chronically higher than normal, as measured by a fasting blood glucose level above 6.1 mmol/L (millimoles per liter) and a 2-hour postprandial blood glucose level above 7.8 mmol/L. The blood glucose level in the blood is higher than the renal threshold when it exceeds the renal threshold.

Urinary glucose occurs when blood glucose exceeds its renal threshold of 10 mmol/L.

Hyperglycemia is most commonly associated with diabetes mellitus, a chronic metabolic disease characterized by disorders of glucose, lipid, and protein metabolism.

Types

Physiologic

It is a normal phenomenon, which can be caused by emotional excitement, diet, etc. Temporary hyperglycemia and urinary glucose appear, and fasting blood glucose are normal, which will not cause obvious damage to the organism.

Pathologic

Pathological hyperglycemia is commonly seen in impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and diabetes mellitus (DM).

Both IFG and IGT represent an intermediate metabolic state between normal glucose homeostasis and diabetic hyperglycemia, with a predisposition to diabetes mellitus and a risk factor for cardiovascular pathology.

Morbidity

Hyperglycemia is most commonly associated with diabetes.

Diabetes mellitus is a common and frequent disease, and its prevalence and incidence are currently increasing dramatically.

According to the 2017 statistics of the International Diabetes Federation (IDF): there are about 425 million adult patients with diabetes worldwide, and it is expected that it may reach 629 million by 2045.

In recent years, the prevalence of adult diabetes in China has risen significantly, with about 114 million diabetes patients, ranking first in the world, and the incidence of diabetes is becoming younger, and the prevalence of rural populations is growing rapidly.

Causes

Hyperglycemia is mainly caused by the body’s absolute or relative insulin insufficiency or low utilization. It is commonly caused by absolute insulin insufficiency, relative insulin insufficiency, and dysregulation of insulin antagonist hormone secretion.

Causes

Genetic factors

Genetic susceptibility plays an important role in the development of insulin secretion disorders, and certain related genetic mutations can promote or exacerbate the process of autoimmune damage to pancreatic islet B cells.

Viral infections

Infections such as coxsackie B4 virus, cytomegalovirus, mumps virus, hepatitis virus, and rubella virus have been associated with islet B cell damage.

Chemical damage

Such as tetracycline, streptomycin, pentamidine, etc., have direct toxic effects on islet cells, which can lead to a decrease in the number of islet B cells.

Endocrine factors

Abnormal secretion of glucagon, adrenaline, glucocorticoid and growth hormone leads to elevated blood glucose.

The most important of these is glucagon, which is a key regulatory hormone for maintaining blood glucose homeostasis.

Other factors

Liver disease: such as cirrhosis, acute and chronic hepatitis, fatty liver, etc., can cause impaired glucose tolerance and elevated blood glucose.

Kidney disease: uremia, glomerulosclerosis and other severe renal dysfunction can cause hyperglycemia.

Stressful situation: it can be seen in major surgical operation, serious infection, extensive trauma, burns, hemorrhage, shock and so on.

Endocrine diseases: acromegaly, pheochromocytoma, hyperthyroidism, Cushing’s syndrome and so on.

Pregnancy (pregnancy): the placenta can produce estrogen, progesterone, prolactin and placental growth hormone and many other hormones that antagonize insulin during pregnancy, and it can also secrete insulinase, which accelerates the decomposition of insulin and causes the rise of blood glucose.

Drugs: Recombinant human growth hormone, antipsychotic drugs, tacrolimus, etc. may cause hyperglycemia.

Physiological factors: Eating high-calorie food, strenuous exercise, etc. can also cause transient hyperglycemia.

Excessive glucose input: It is the most common cause of hyperglycemia in newborns.

Symptoms

Impaired fasting glucose and impaired glucose tolerance lead to hyperglycemia, and symptoms are often not obvious. Diabetes mellitus may present with “three more and one less”.

Early symptoms

Early symptoms are often asymptomatic, and most patients are found to have elevated blood glucose on physical examination.

Main Symptoms

“Three more and one less”

are polyuria, polydipsia, polyphagia and weight loss; commonly seen in patients with type 1 diabetes mellitus.

Due to the elevated blood glucose causes osmotic diuresis, resulting in increased urine output.

Polyuria leads to water loss and the patient is thirsty and drinks more.

The inability of the body to utilize glucose and the increased consumption of protein and fat cause lethargy, fatigue, and weight loss.

In order to replenish sugar and maintain body activity, the patient is often prone to hunger and overeating.

Itchy skin

Due to hyperglycemia and peripheral neuropathy leading to skin dryness and sensory abnormalities, there may be skin itching.

Female patients may have vulvar itching due to localized skin irritation by urinary glucose.

Other symptoms

Soreness and numbness of limbs, lumbago, loss of libido, impotence and sterility, menstrual disorders, constipation, blurred vision, etc.

Complications

Infectious diseases

For example, pyelonephritis: symptoms such as back pain, urinary urgency and frequency may occur.

Skin suppurative infections (boils, carbuncles): localized redness and swelling of the skin, pain, increased skin temperature, etc. may occur.

Diabetic ketoacidosis

The symptoms of “three more and one less” in the first stage are aggravated.

Followed by fatigue, nausea, vomiting, deep and fast breathing, expiratory odor of rotten apples; severe water loss in the later stage.

In severe cases, there may be unresponsiveness and coma.

Hypertonic hyperglycemic syndrome

Beginning with polyuria, polydipsia, loss of appetite; gradually severe dehydration and neuropsychiatric symptoms, with unresponsiveness, irritability or indifference, drowsiness, and gradually falling into coma; in the late stage, there is little or no urine.

Chronic complications

The most important consequence of long-term hyperglycemia is the emergence of systemic microarterial vasculopathy, which can lead to the damage of the corresponding organs.

The common ones include diabetic nephropathy, diabetic retinopathy, diabetic neuropathy and diabetic foot.

Symptoms such as foamy urine, loss of vision, chest tightness, chest pain, palpitations, itching, loss of skin sensation, and susceptibility to foot infections may occur.

Consultation

Department of Medicine

Endocrinology

If you have any of the following symptoms, it is recommended that you consult a doctor promptly.

Fasting blood glucose ≥ 6.1 mmol/L and 2-hour postprandial blood glucose ≥ 7.8 mmol/L on physical examination.

Symptoms such as excessive drinking, excessive urination, excessive eating, and weight loss.

Emergency Department

In case of emergency such as nausea, vomiting, deep and fast breathing, expiration with rotten apple odor, unresponsiveness, drowsiness, coma, etc., immediate consultation is recommended.

Preparation for medical treatment

Preparation for medical consultation: registration, preparation of documents, common problems

Tips for the doctor

It is recommended to record the time of blood glucose measurement and blood glucose value for the doctor’s reference.

Preparation Checklist

When did you first notice the blood glucose abnormality? What is the blood glucose value?

Do you have symptoms of polydipsia, polyphagia, polyuria, and how long have they lasted?

Has there been any change in weight in the last six months?

Do any blood relatives have a history of diabetes?

Are there any allergies to drugs, food or other substances?

Are there any diseases such as hypertension, coronary heart disease, hyperlipidemia, etc.?

Laboratory tests: blood glucose, glycosylated hemoglobin, glycosylated plasma albumin, glucose tolerance test, insulin autoantibodies, insulin, C-peptide measurement, urine routine, urine protein measurement, liver and kidney function, arterial blood gas analysis.

Imaging tests: ultrasound of both lower limbs, ultrasound of liver, gallbladder, pancreas, spleen and kidneys, abdominal CT, abdominal magnetic resonance examination.

Other tests: electrocardiogram, funduscopic examination, electromyography

Metformin: Metformin, Phenformin

Sulfonylureas: glibenclamide, glimepiride, gliclazide, glipizide, gliquidone

Glargine: Repaglinide, Naglinide, Miglinide

Thiazolidinediones: rosiglitazone, pioglitazone

α-glucosidase inhibitors: acarbose, voglibose, miglitol

Dipeptidyl peptidase IV inhibitors: selegiline, saxagliptin, vigliptin

Sodium-glucose cotransporter protein 2 inhibitors: dagliflozin, empagliflozin, cagliflozin

Insulin: Glucagon, Deguelin, Mentholatum 30/50 Injection, Mentholatum Injection, Arginin Biosynthetic Human Insulin Injection 30R/50R

Glucagon-like peptide-1 receptor agonist: liraglutide

Others: glucose, hydrocortisone, prednisone acetate, methylprednisolone, dexamethasone

Diagnosis

Diagnosis based on

Medical History

Providing a detailed medical history will help the physician diagnose hyperglycemia and develop a rational treatment plan, which may include:

Family history: whether first-degree relatives (father, mother, etc.) have hyperglycemia.

Past history: any comorbidities such as hypertension, cardiovascular and cerebrovascular diseases, dyslipidemia, etc.; previous hyperglycemia treatment plan and blood glucose control.

Lifestyle: including smoking, drinking, exercise and diet.

Clinical manifestations

Symptoms of “three more and one less”, or other chronic complications, such as fatigue, blurred vision, atherosclerosis, sensory abnormalities of the extremities.

In most cases, after microarterial vascular disease leads to damage to the corresponding organs, corresponding signs such as retinopathy, diabetic neuropathy, diabetic foot, etc. can be detected.

Laboratory Tests

Urine Glucose Measurement

To check whether and to what extent the urine sugar is elevated.

Positive urine sugar is an important clue to the diagnosis of hyperglycemia.

Precautions:

A hospital-provided urine cup and tube should be used for the test.

Mid-stage urine should be retained, i.e., urine should be partially expelled during urination, then the urine cup should be used to catch the urine afterward, and collection should be stopped before the urine is completely expelled.

Glycated hemoglobin and glycated plasma albumin measurement

Glycated hemoglobin (GHbA1), of which HbA1c is the most predominant, reflects the average blood glucose level over the past 8 to 12 weeks. Glycated plasma albumin reflects the average blood glucose level over a 2-3 week period.

It may be elevated in the presence of abnormal glucose tolerance or diabetes, or when treatment is not effective.

Blood glucose measurement and oral glucose tolerance test

Measurement of blood glucose, and changes in blood glucose over a period of time after taking oral glucose foods.

Elevated blood glucose is the main basis for the diagnosis of hyperglycemia, and the main indicator of the condition and control of hyperglycemia.

Precautions:

Fasting blood will be drawn on the day of the test, fasting for 8 to 10 hours before the test, and fasting after 12:00 p.m. on the night before the test.

Smoking, alcohol, coffee and tea are prohibited during the test, and no strenuous exercise is done.

On an empty stomach, take 75 grams of glucose orally, dissolve it in 250-300 ml of warm boiled water, and drink it within 5 minutes after it melts.

Start timing from the first sip, measure blood glucose after 2 hours or take blood at half an hour, 1 hour, 2 hours and 3 hours respectively.

Pancreatic B-cell function test

To find out the capacity of basal and glucose-mediated insulin secretion by islet B cells.

Complication test

Including ketone body, electrolyte, acid-base balance examination in acute severe metabolic disorders, heart, liver, kidney, brain, eye, oral cavity and various auxiliary examinations of the nervous system.

Diagnostic Criteria

Glucose metabolism classification

Impaired fasting blood glucose 6.1～＜7.0＜7.8

Impaired fasting glucose

6.1～＜7.0

Impaired fasting glucose 6.1～＜7.0＜7.8

Decreased glucose tolerance ＜7.07.8～＜11.1

Diabetes mellitus

≥7.0

≥11.1

Diagnostic criteria for diabetes mellitus

The diagnostic criteria for diabetes mellitus have the following considerations:

Fasting blood glucose: blood glucose measured after at least 8 hours of fasting.

Random blood glucose: blood glucose measured at any time of the day, regardless of the time of the last meal.

In the absence of the typical symptoms of “three more and one less”, the diagnosis can only be confirmed by another measurement.

Diagnostic criteria venous plasma glucose (mmol/L)

Typical diabetic symptoms (excessive drinking, urination, food intake, weight loss) plus random blood glucose monitoring ≥11.1

Typical diabetic symptoms (excessive drinking, urination, eating, weight loss) plus random glucose monitoring

≥11.1

Fasting blood glucose ≥7.0

Fasting blood glucose

≥7.0

Glucose load test 2-hour blood glucose ≥11.1

Glucose load test 2 hours blood glucose

≥11.1

Differential Diagnosis

Hyperglycemia is usually diagnosed on the basis of a blood glucose test, and the differential diagnosis focuses on differentiating it from hyperglycemia caused by other diseases.

Cushing’s syndrome

Similarities: Hyperglycemia.

Differences: typical symptoms of Cushing’s syndrome may include centripetal obesity, full moon face, purple lines on the skin, hypertension, etc. Laboratory tests show that cortisol secretion is increased, losing the diurnal secretion rhythm, and cannot be suppressed by small doses of dexamethasone.

Primary aldosteronism

Similarities: Hyperglycemia.

Differences: Primary aldosteronism may be characterized by hypertension and higher than normal blood aldosterone levels on laboratory tests.

Acromegaly

Similarity: Hyperglycemia.

Difference: Acromegaly is characterized by an enlarged skull, enlarged hands and feet, thickened skin, etc. Hormone tests show that growth hormone levels are higher than normal.

Treatment

Self-management education

Provide education on hyperglycemia to fully understand the dangers of hyperglycemia.

Master the self-management methods, including the dangers of hyperglycemia, how to prevent and control acute and chronic complications, as well as diet, exercise, blood glucose monitoring, medication and so on.

Stop smoking and drinking.

Dietary treatment

Reasonable diet is conducive to controlling hyperglycemia, reducing body weight and improving metabolic disorders; at the same time, it can reduce the burden of pancreatic islet B cells, so that the structure and function of pancreatic islet tissues can be appropriately restored; and it can reduce the dose of hypoglycemic drugs.

Dietitians are needed to control the intake of carbohydrates, proteins, and fats according to the patient’s condition, accounting for 50% to 60%, 10% to 15%, and 20% to 25%, respectively.

Consume foods with low glycemic index (GI), such as cherries, barley, soybeans, etc., and limit the intake of mono- or disaccharide-rich foods such as honey and maltose.

In principle, the daily calorie intake per kilogram of ideal body weight is 25-30 kcal, ideal body weight = height (cm) – 105, obese patients can reduce the total energy appropriately.

Meals can be reasonably distributed according to the pattern of allocating three meals per day as 1/5, 2/5, 2/5 or 1/3 of each meal.

Exercise therapy

Exercise can increase insulin sensitivity, help control blood glucose and weight, and reduce cardiovascular risk factors.

Sedentary individuals should engage in brief physical activity every 30 minutes, and at least 150 minutes of moderate-intensity aerobic exercise (brisk walking, tai chi, cycling, table tennis, badminton, etc.) should be performed each week.

Blood glucose should be monitored before and after exercise.

Those with blood glucose >16mmol/L, recent frequent episodes of hypoglycemia or large fluctuations in blood glucose, acute complications of diabetes and severe chronic complications of the heart, brain, eyes and kidneys should not exercise for the time being.

Medication

When diet and exercise fail to control blood glucose to the standard, glucose-lowering drugs should be applied in time, including oral drugs and injectable preparations.

Oral hypoglycemic drugs

Oral hypoglycemic drugs include insulin secretagogues, biguanides, thiazolidinediones and α-glucosidase inhibitors.

Insulin secretagogues: sulfonylureas (glibenclamide, glipizide), glinides (repaglinide, nateglinide).

Metformin: Metformin is widely used at present.

Thiazolidinediones: mainly rosiglitazone, pioglitazone and so on.

Alpha-glucosidase inhibitors: including acarbose, voglibose, miglitol.

Injectable preparations

Injectable preparations include insulin and insulin analogs, glucagon-like polypeptide-1 receptor agonists.

They can quickly and effectively lower blood glucose concentration and control hyperglycemia; or serve as lifelong replacement therapy for absolute insulin deficiency in the body, potentially delaying autoimmune damage to B cells.

Precautions: When using hypoglycemic drugs, especially insulin, it is necessary to closely monitor the patient’s blood glucose level to prevent hypoglycemic reactions due to excessive dosage.

Other treatments

Hyperglycemia caused by other diseases requires active treatment of the original disease.

Other treatments can be pancreas transplantation, islet cell transplantation, stem cell therapy, etc. to replace the damaged islet B cells to secrete insulin. However, stem cell therapy is still in the preclinical research stage.

Prognosis

Cure

Untreated

Physiologic hyperglycemia generally does not require treatment and can recover on its own.

Impaired fasting glucose and impaired glucose tolerance are actively controlled and may recover.

Post-treatment

Diabetes mellitus is a chronic disease that can be controlled, but not cured, and may not affect life expectancy if blood glucose is well controlled.

Hazards

Untreated hyperglycemia can cause multi-system damage, leading to chronic progressive lesions, functional decline and failure of tissues and organs such as eyes, kidneys, nerves, heart and blood vessels.

Eye: It can damage the blood vessels of the retina and can lead to blindness. It also increases eye diseases such as cataracts and glaucoma.

Kidneys: can damage the blood vessels of the kidneys and severe damage can lead to kidney failure or irreversible end-stage renal disease.

Cardiovascular damage: It is a predisposing factor for atherosclerosis, which can cause coronary heart disease, ischemic or hemorrhagic cerebrovascular disease.

Nerve damage: excessive sugar can harm nerves, especially peripheral nerves in the extremities, which may lead to tingling, numbness, and burning pain; men may experience erectile dysfunction.

Acute severe metabolic disorders, such as diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome, can occur when the condition is severe or stressful, and can be life-threatening if not treated in time.

High blood sugar can make infections difficult to cure and wounds difficult to heal.

Daily

Life Management

Dietary management

Eat regularly, eat small meals, avoid overeating, and control total calorie intake.

Eat more fiber-rich foods, such as celery, bok choy, oats, etc. Avoid liquid or semi-liquid high-carbohydrate foods such as thin rice and porridge.

The daily salt intake of diabetic patients should not exceed 6 grams, and those with hypertension should have less than 3 grams.

Alcohol should be avoided by diabetic patients. Drinking alcohol can interfere with blood glucose control and the implementation of dietary treatment plan, large amount of alcohol can induce ketoacidosis, and long-term alcohol consumption can cause alcoholic cirrhosis and pancreatitis.

Exercise management

Mode of exercise

Aerobic exercise is the main exercise, such as brisk walking, cycling, doing radio exercises, practicing tai chi, playing table tennis, etc..

The best time for exercise is 1 hour after meals (timed with the start of eating).

If there is no contraindication, it is best to perform resistance exercise 2 times a week.

If there is cardiovascular or cerebrovascular disease or serious microvascular lesions, exercise should be chosen according to specific conditions.

Selection of Exercise Intensity

The appropriate intensity of exercise is the patient’s heart rate at the time of activity at 60% of the individual’s maximum oxygen consumption (heart rate = 200 – age).

The activity time is at least 150 minutes per week, 30-40 minutes each time, including pre-exercise preparatory activities and end-of-exercise finishing exercise time, which can be gradually extended according to the specific conditions of patients.

Obese patients can appropriately increase the number of activities.

Those who use insulin or oral hypoglycemic drugs are better to have regular activities every day.

Precautions

Pay attention to replenish water during exercise.

If chest tightness, chest pain, blurred vision, etc. occur during exercise, exercise should be stopped immediately and treated promptly.

Exercise diary should be kept after exercise in order to observe the efficacy and adverse reactions.

Blood glucose monitoring should be strengthened before and after exercise. When fasting blood glucose > 16.7 mmol/L, activities should be reduced as appropriate.

Exercise should not be performed during fasting to prevent hypoglycemia from occurring.

Blood glucose monitoring