Endocrine Disorders Affecting the Children
Subtopic:
Diabetes Mellitus
Diabetes Mellitus (DM), frequently called diabetes, encompasses a collection of metabolic conditions characterized by persistently elevated blood glucose levels over an extended duration.
Insulin, a crucial hormone, is produced by the beta-cells (β-cells) located within the pancreas. Its primary function is to facilitate the uptake of glucose from the bloodstream into cells, where it can be utilized for energy production through metabolic processes.
When there is an insulin deficiency, meaning the body does not produce enough insulin or the insulin produced is not effective, glucose accumulates in the bloodstream. This results in an elevated blood glucose level, a condition known as hyperglycemia. When blood glucose levels become excessively high, the kidneys’ capacity to reabsorb glucose is overwhelmed, leading to the excretion of glucose in the urine. This condition is termed glycosuria.
The presence of excess glucose in the urine draws more water along with it, leading to increased urine production. This excessive urination is known as polyuria. Therefore, hyperglycemia, glycosuria, and polyuria are considered the three primary or fundamental clinical signs and symptoms that indicate the presence of diabetes mellitus.
Diabetes mellitus stands as the most frequently encountered endocrine disorder globally. It has a significant impact on public health, affecting approximately two percent of the world’s population.
The origin of diabetes can be categorized into several types. It can be primary, meaning it arises independently and not as a result of another underlying condition. Diabetes can also be secondary, indicating that it develops as a consequence of another medical issue, such as certain medications or pancreatic diseases. In some instances, the cause of diabetes cannot be determined, and these cases are classified as idiopathic.
Pathophysiology of Diabetes(Simplified)
Diabetes arises primarily due to two key problems: either the pancreas does not synthesize a sufficient amount of insulin, or the body’s cells fail to respond effectively to the insulin that is produced.
1. Insufficient Insulin: A primary cause is the inability of the pancreas to generate an adequate quantity of insulin. This can be due to damage or dysfunction of the beta-cells (β-cells) which are responsible for insulin production. Consequently, the critical role of insulin in regulating blood sugar levels is compromised, resulting in hyperglycemia, which signifies elevated levels of glucose in the bloodstream.
2. Consequences of Hyperglycemia: When there’s too much glucose in the blood, the kidneys attempt to eliminate the excess glucose through urine. This process is known as glycosuria. The high concentration of glucose in the kidney’s filtration system (glomerular filtrate) draws water along with it, leading to an increase in urine volume. This excessive urination is termed polyuria. The loss of significant amounts of water through urine triggers a powerful sensation of thirst, referred to as polydipsia.
3. Cellular Deprivation and Compensatory Responses: Despite the elevated levels of glucose in the blood, the body’s cells are unable to access it effectively without sufficient or properly functioning insulin. This leads to a state of cellular energy deprivation. In response to this perceived lack of energy, the body signals an increase in appetite, often leading to excessive eating, known as polyphagia. Paradoxically, this increased food intake further contributes to the elevated blood glucose levels, potentially worsening the diabetic condition.
4. Gluconeogenesis: Faced with the inability of cells to utilize glucose for energy, the body initiates a metabolic process called gluconeogenesis. This process involves the creation of glucose from non-carbohydrate sources, primarily proteins and fats, in an attempt to provide energy for the cells.
5. Ketone Body Accumulation: When the body relies heavily on fat breakdown for energy due to the lack of glucose availability, it produces byproducts called ketone bodies. An excessive production of these ketone bodies leads to their accumulation in the bloodstream, a condition known as ketonemia.
6. Acidosis and Respiratory Response: The buildup of ketone bodies is acidic in nature and can lower the pH of the blood, leading to a state of acidosis. To compensate for this increased acidity, the body attempts to expel carbon dioxide, an acidic waste product, through the lungs. This results in a characteristic pattern of rapid and deep breathing known as Kussmaul respirations.
7. Potential Life-Threatening Complication: If the acidic state persists and becomes severe, it can develop into ketoacidosis. This is a serious and potentially life-threatening medical condition requiring immediate medical intervention, often considered a pediatric emergency due to its prevalence in children with type 1 diabetes.
Type 1 Diabetes Mellitus
Type 1 Diabetes Mellitus (T1DM) is distinguished by the pancreas’s inability to produce an adequate amount of insulin, a critical hormone for the proper regulation of blood glucose levels. Previously referred to as “insulin-dependent diabetes mellitus” (IDDM) or “juvenile diabetes,” the precise underlying cause of T1DM remains unknown.
Insulin Deficiency and Beta Cell Loss: A defining feature of T1DM is the progressive destruction and loss of insulin-producing beta cells (β-cells) located within the pancreatic islets. This cellular damage leads to a significant insulin deficiency, severely impairing the body’s fundamental ability to maintain balanced blood sugar levels.
Immune-Mediated or Idiopathic Classification: T1DM is broadly categorized into immune-mediated or idiopathic forms. The vast majority of T1DM cases are immune-mediated, involving an autoimmune process where the body’s own T cells mistakenly attack and destroy the beta cells. While historically known as “juvenile diabetes” due to its frequent diagnosis in children, T1DM can indeed develop in both children and adults.
Associated Complications: Individuals with T1DM may experience various complications, including impaired awareness of hypoglycemia (reduced ability to sense low blood sugar), increased susceptibility to infections, gastroparesis (a condition causing delayed stomach emptying, which can lead to erratic carbohydrate absorption), and other endocrinopathies such as Addison’s disease.
Genetic and Environmental Factors: There is a clear genetic predisposition to T1DM, with certain HLA genotypes significantly increasing an individual’s susceptibility. Furthermore, environmental triggers are believed to play a crucial role in initiating the disease process, particularly in genetically susceptible individuals. These triggers can include viral infections or specific dietary factors, such as gliadin found in gluten.
Autoimmune Attack and Viral Influence: A central feature of T1DM development is an autoimmune attack directed at the pancreatic islets. This autoimmune assault is often triggered by viral infections, which may initiate the destructive process against the insulin-producing cells. T1DM is more likely to manifest during childhood or early adulthood, often presenting with a relatively sudden onset of symptoms.
Management and Risks: Lifelong insulin therapy and a carefully managed diet are essential for the effective management of T1DM. Individuals with T1DM face an elevated risk of coma if concurrent infections, such as pyelonephritis (kidney infection) or gastroenteritis (stomach flu), are not promptly and appropriately treated.
Type 2 Diabetes Mellitus
The underlying disease process of type 2 diabetes mellitus is marked by peripheral insulin resistance, a disruption in the control of glucose production by the liver (impaired regulation of hepatic glucose production), and a progressive decline in the function of the beta-cells (β-cells), ultimately resulting in their failure (declining β-cell function, eventually leading to β-cell failure).
The combined effect of reduced insulin release and diminished responsiveness to insulin leads to an elevated concentration of glucose in the bloodstream (Reduced insulin secretion and absorption leads to high glucose content in the blood).
Insulin Resistance and Reduced Secretion: A hallmark of T2DM is insulin resistance, where the body’s tissues exhibit a decreased sensitivity to the action of insulin. This resistance is frequently accompanied by a concurrent, though sometimes relative, decrease in the amount of insulin being secreted (relative reduction in insulin secretion).
Insulin Receptor Dysfunction: The impaired ability of bodily tissues to respond appropriately to insulin is linked to the insulin receptor; however, the precise molecular defects involved remain to be fully elucidated. Cases of diabetes where the specific genetic or molecular defects are known are classified under separate categories.
Prevalence and Early Stage Abnormality: T2DM represents the vast majority of diabetes cases, accounting for as much as 90% of all diabetes mellitus cases. In the initial stages of the disease, the primary irregularity is a decrease in sensitivity to insulin (reduced insulin sensitivity), a condition that can potentially be reversed through interventions and medications that improve insulin sensitivity or reduce the liver’s output of glucose.
Contributing Factors: A complex interplay of factors contributes to the development of T2DM. These include lifestyle factors, genetics, obesity (particularly with a BMI > 30), insufficient physical activity, an unhealthy diet, stress, and the influences of urbanization. Insulin resistance, excessive food consumption (overeating), a sedentary lifestyle (inactivity), and obesity all play significant roles in the origins and progression of the condition.
Dietary Management and Weight Loss: The management of T2DM frequently involves adhering to a low-energy diet as a key strategy to facilitate weight loss. Broader lifestyle modifications, encompassing changes to dietary habits, regular exercise, and techniques for stress reduction, are integral to effectively managing and controlling T2DM.
Gestational Diabetes
Gestational diabetes mellitus (GDM) shares characteristics with type 2 DM, involving a combination of relatively insufficient insulin secretion and responsiveness. It occurs in approximately 2–10% of all pregnancies and may improve or resolve after childbirth.
Occurrence and Post-Delivery Transition: GDM, similar to type 2 DM, involves inadequate insulin secretion and responsiveness. It affects roughly 2–10% of pregnancies and may improve or disappear after delivery.
Post-Pregnancy Diabetes Risk: Following pregnancy, about 5–10% of women with a history of gestational diabetes develop diabetes mellitus, frequently type 2. Specifically, after pregnancy, approximately 5–10% of women with gestational diabetes are found to have diabetes mellitus, with type 2 being the most common form.
Temporary Nature and Health Impacts: Although temporary during pregnancy, untreated GDM presents risks to both the mother and the developing fetus. Elevated blood glucose levels during pregnancy can lead to babies being born with increased birth weight, skeletal muscle malformations, and a higher risk of mortality. Risks for newborns associated with untreated GDM include macrosomia (high birth weight), congenital heart and central nervous system abnormalities, and skeletal muscle malformations. Elevated insulin levels in the fetal blood can interfere with surfactant production, potentially causing respiratory distress syndrome.
Complications and Perinatal Risks: Complications can arise, such as high blood bilirubin levels due to the breakdown of red blood cells. Severe cases can result in perinatal death, often linked to inadequate placental blood flow due to vascular problems, leading to macrosomia and shoulder dystocia.
Management and Treatment: Gestational diabetes is manageable, but necessitates close medical supervision throughout the pregnancy. Management strategies may include dietary adjustments, regular blood glucose monitoring, and in some instances, the use of insulin may be necessary.
Unspecified Diabetes Mellitus:
Maturity Onset Diabetes of the Young (MODY):
Maturity onset diabetes of the young (MODY) is an inherited form of diabetes passed down through an autosomal dominant pattern. It results from mutations in single genes that cause defects in insulin production. It is considerably less common than the three main types of diabetes.
The name of this condition reflects earlier understandings of its nature.
Being caused by a defective gene, the age at which it appears and its severity can vary depending on the specific gene affected; consequently, there are at least 13 different subtypes of MODY.
Individuals with MODY can often manage their condition without the need for insulin injections.
Others:
Prediabetes: Prediabetes describes a condition where a person’s blood glucose levels are higher than what is considered normal but not yet high enough to be diagnosed as type 2 DM. Many individuals who eventually develop type 2 DM spend a significant period in a prediabetic state.
“Type 3 Diabetes”: The term “Type 3 diabetes” has been proposed as another name for Alzheimer’s disease, suggesting that the underlying processes might involve insulin resistance in the brain.
Aetiological Classification of Diabetes Mellitus:
Primary Diabetes Mellitus (Idiopathic):
Type 1 Diabetes (IDDM): Characterized by beta-cell (β-cell) destruction, typically leading to insulin deficiency.
Type 2 Diabetes (NIDDM): Can range from insulin resistance with a relative insulin deficiency to a primary defect in insulin secretion alongside insulin resistance.
Secondary Diabetes Mellitus: Due to Other Underlying Diseases/Conditions:
Diseases of the pancreas, such as pancreatitis, pancreatic cancer, cystic fibrosis, or hemochromatosis, can cause damage to the gland, resulting in reduced insulin production.
Endocrine disorders (which counteract insulin) like Cushing’s syndrome, acromegaly, and hyperthyroidism.
Drug-induced (lactogenic) diabetes, for example, from therapies involving corticosteroids, phenytoin, or thiazide diuretics.
Genetic/chromosomal defects, such as in Down’s syndrome.
Liver diseases like hepatitis and cirrhosis are associated with glucose intolerance.
Gestational Diabetes Mellitus (Pregnancy-induced Diabetes Mellitus): Occurs during pregnancy and typically resolves after delivery.
Predisposing Causes of Primary Diabetes Mellitus:
1. Age: A significant majority, approximately 80%, of diabetes cases develop after the age of 50. Diabetes Mellitus (DM) is frequently observed in middle-aged and elderly individuals.
2. Sex: Among younger individuals, males are more commonly affected by diabetes than females. However, in middle age, this trend reverses, and females are more frequently affected.
3. Heredity: Diabetes Mellitus demonstrates a clear tendency to run in families. Around 5% of diabetes patients have a documented family history of the condition.
4. Autoimmunity: In certain types of diabetes, the body’s immune system mistakenly produces autoantibodies and autoreactive cells that target and attack the insulin-producing cells in the pancreas.
5. Infections: Certain viral infections, as well as bacteria like staphylococci, have been linked to the development of Insulin-Dependent Diabetes Mellitus (IDDM), also known as Type 1 Diabetes.
6. Obesity: The vast majority of individuals diagnosed with Non-Insulin-Dependent Diabetes Mellitus (NIDDM), also known as Type 2 Diabetes, are obese.
7. Lifestyle Factors: A lifestyle characterized by excessive food intake coupled with insufficient physical activity significantly increases the risk of developing diabetes.
Other Predisposing Factors:
Sedentary lifestyle: A lack of regular physical exercise contributes to the risk.
Poor dietary habits: Consuming an unhealthy diet increases susceptibility.
Metabolic syndrome: A cluster of conditions that increase the risk of diabetes, heart disease, and stroke.
Hypertension: High blood pressure is associated with an increased risk.
Ethnicity: Certain ethnic groups have a higher predisposition to developing diabetes.
Gestational diabetes: Having gestational diabetes during pregnancy increases the risk of developing diabetes later in life.
Certain medications: Some medications, such as glucocorticoids, can increase the risk of developing diabetes.
Previous gestational diabetes: A history of gestational diabetes elevates future risk.
Clinical Features of Diabetes Mellitus
In mild cases of diabetes, individuals may not exhibit any noticeable symptoms, and the condition might be discovered incidentally during routine medical examinations. However, in more severe cases, especially among young children and young adults, prominent symptoms can include:
1. Polyuria: Increased urination occurs because the elevated glucose levels in the kidneys interfere with water reabsorption in the renal tubules due to its osmotic activity.
2. Polydipsia (increased thirst): Excessive thirst develops as a consequence of polyuria, leading to dehydration due to the continuous loss of fluids and essential electrolytes from the body.
3. Polyphagia with Weight Loss: Despite an increased appetite (polyphagia), individuals may experience unintentional weight loss. This occurs because the body starts breaking down fat and protein stores for energy due to the lack of glucose availability within the cells.
4. Weakness or Fatigue/Lassitude: A general feeling of weakness, tiredness, or lack of energy arises because the body’s cells are not receiving an adequate supply of glucose, their primary fuel source.
5. Nocturnal Enuresis: Bed-wetting (involuntary urination at night) can occur, particularly in children, because the amount of glucose in the kidneys exceeds the reabsorption threshold, leading to increased urine production.
6. Glycosuria: The presence of abnormally high levels of glucose in the urine.
7. Peripheral Neuropathy/Paresthesia: Chronically elevated blood sugar levels can cause damage to the peripheral nerves. This nerve damage can lead to a loss of sensation and numbness, particularly in the legs and feet. In more severe cases, symptoms can extend to digestive problems, bladder dysfunction, and difficulties in controlling heart rate. Paresthesia, which includes sensations like tingling, prickling, or burning, is a common symptom associated with neuropathy.
8. Vulvovaginitis: Inflammation and irritation of the vulva and vagina can occur due to the local deposition of glucose, creating an environment conducive to yeast infections. This can be quite uncomfortable and may disrupt sleep.
9. Ketoacidosis: A serious and potentially life-threatening complication characterized by an excessive buildup of acids called ketones in the blood. Symptoms may include blurry vision, headache, persistent fatigue, slow wound healing, and itchy skin.
10. Diabetic dermadromes: Various skin rashes and lesions can develop in individuals with long-standing diabetes. These cutaneous eruptions are associated with the disease.
11. Vision Changes: Sustained high blood glucose levels can cause the lens of the eye to absorb glucose. This absorption can alter the shape of the lens, leading to blurred vision or other visual disturbances.
Comparison of type 1 and 2 diabetes
| Feature | Type 1 | Type 2 |
| Onset | Sudden | Gradual |
| Typical Age of Onset | Mostly children | Mostly adults |
| Body Build | Thin or normal | Often obese |
| Ketoacidosis | Common | Rare |
| Autoantibodies | Usually present | Absent |
| Insulin Levels | Low or totally absent | Normal, decreased, or increased |
| Identical Twins Concordance | Approximately 50% | Approximately 90% |
| Prevalence | Approximately 10% | Approximately 90% |
Diagnosis of Diabetes Mellitus:
Diabetes mellitus, characterized by recurring or persistent high blood sugar levels, is diagnosed by meeting any one of the following criteria:
1. Fasting Plasma Glucose Level: ≥ 7.0 mmol/l (126 mg/dl). According to current standards, two separate fasting glucose measurements at or above 126 mg/dl (7.0 mmol/l) are considered conclusive for a diagnosis of diabetes mellitus.
2. Plasma Glucose Two Hours After Oral Glucose Load: ≥ 11.1 mmol/l (200 mg/dl) measured two hours after the ingestion of a 75-gram oral glucose load, as performed during a standard glucose tolerance test. Individuals with plasma glucose levels at or above 7.8 mmol/l (140 mg/dl) but not exceeding 11.1 mmol/l (200 mg/dl) two hours following the glucose load are classified as having impaired glucose tolerance.
3. Symptoms of High Blood Sugar and Casual Plasma Glucose: ≥ 11.1 mmol/l (200 mg/dl). The presence of classic symptoms of hyperglycemia, combined with a casual plasma glucose measurement of 11.1 mmol/l (200 mg/dl) or higher, is indicative of diabetes. A casual plasma glucose test is taken at any time of day without regard to meal timing.
Note: The World Health Organization defines impaired fasting glucose as having fasting glucose levels between 6.1 to 6.9 mmol/l (110 to 125 mg/dl). Glycated hemoglobin (HbA1c) is considered a valuable tool, potentially more so than fasting glucose, for assessing the risk of cardiovascular disease and overall mortality.
Important Information: Confirmation of diabetes requires two fasting glucose measurements exceeding 126 mg/dl (7.0 mmol/l). Impaired glucose tolerance, particularly with plasma glucose levels falling between 7.8 mmol/l (140 mg/dl) and 11.1 mmol/l (200 mg/dl) after an oral glucose challenge, signifies a significant risk factor for the future development of diabetes and cardiovascular disease.
4. Other Diagnostic Investigations for Diabetes Mellitus:
Glucosuria:
Method: Detect the presence of glucose in urine using a diagnostic test strip (uristicks).
Purpose: To determine if glucose is present in the urine, which can be a sign of diabetes.
Ketonuria:
Method: Detect the presence of ketone bodies in a urine sample.
Purpose: To identify ketones in the urine, which can be an indicator of diabetic ketoacidosis, a serious complication.
Fasting Blood Sugar (FBS):
Method: Measure the concentration of glucose in a blood sample taken after a period of fasting, typically at least 8 hours after the last meal.
Purpose: To assess the baseline blood glucose level after an overnight fast.
Random Blood Sugar (RBS):
Method: Measure the glucose concentration in a blood sample taken at any time of day, regardless of when the last meal was consumed.
Purpose: To provide a snapshot of the current blood glucose level at a given moment.
Oral Glucose Tolerance Test (OGTT):
Method: The patient fasts overnight. The next morning, they ingest a solution containing 75 grams (5 tablespoons) of glucose dissolved in 300 ml of water. Blood samples are then collected at specific intervals, typically 1, 2, and 3 hours after the glucose drink is consumed.
Purpose: This test provides a more detailed assessment of how the body processes glucose over time. It is particularly useful when fasting glucose levels are borderline and helps in identifying abnormalities in glucose metabolism.
Additional Information: Normally, blood glucose levels should return to fasting levels (around 4.5 mmol/l or 80 mg/100 ml) within approximately 2.5 hours after a meal. In individuals with diabetes, fasting blood glucose levels often remain elevated, exceeding 200 mg/100 ml, indicating impaired glucose metabolism.
Treatment and Nursing Management of Diabetes Mellitus
Diabetes mellitus is a long-term condition for which, in most cases, there is no cure. Current treatment strategies focus on maintaining blood sugar levels as close to the normal range as possible without causing hypoglycemia (low blood sugar). The specific management approach depends on the type of diabetes and aims to achieve the following:
Control diabetes and prevent complications.
Lower elevated blood sugar levels.
Support patient adherence to the prescribed treatment plan.
Management (non-pharmacological):
Control traditional Cardiovascular risk factors: This includes smoking cessation, abstaining from excessive alcohol consumption, managing dyslipidemia (abnormal lipid levels), maintaining intensive blood pressure control, and considering antiplatelet therapy when appropriate.
Complication monitoring: Regular monitoring for diabetes-related complications is crucial, including annual eye examinations, annual screening for microalbuminuria (small amounts of albumin in the urine), regular foot examinations, blood pressure monitoring, and lipid profile assessments.
Patient education: Comprehensive patient education is vital. This includes teaching patients how to self-monitor blood glucose levels using a glucometer or urine test strips (uristicks), advising them to carry a diabetes identification card, keeping readily available sugary foods for hypoglycemia, educating them on the proper method of insulin administration (if applicable), and emphasizing the consequences of neglecting treatment. Patients should also be educated on injury prevention strategies.
Diet:
For Type 1 diabetes, the goal is to coordinate insulin administration with a balanced diet.
In most cases, a diet high in complex carbohydrates, low in fat, and low in cholesterol is recommended.
Diet and insulin regimens (for those on insulin) must be consistent to avoid significant fluctuations in blood glucose levels. Vitamin and mineral supplementation may be necessary.
Consuming small, frequent meals throughout the day helps prevent large spikes in blood glucose. Meals should not be skipped or delayed. Healthy snacks should be incorporated between main meals (mid-morning, early afternoon, and before bedtime).
Foods should be palatable and include high-fiber options like legumes, barley, and oats. A low-salt diet (around 6g per day) is advisable.
Fried foods, sweetened beverages, bakery products, honey, and refined sugars should be avoided.
Type 2 DM patients often require caloric restriction to facilitate weight loss. Dietary modifications must be combined with lifestyle changes.
Artificial sweeteners: Artificial sweeteners like aspartame, saccharin, sucralose, and acesulfame are considered safe for consumption by individuals with diabetes.
Nutritive sweeteners: While nutritive sweeteners such as fructose and sorbitol are increasingly used, they can cause acute diarrhea in some individuals.
Activity: Regular exercise improves insulin sensitivity and helps achieve better glycemic control.
Exercise programs should start gradually, especially for individuals with limited prior activity.
Patients with pre-existing cardiovascular diseases should undergo a thorough evaluation before starting any exercise regimen.
Avoid exercising on an empty stomach or when blood sugar levels are either too low or too high.
Strenuous activities like heavy weightlifting can be dangerous as they may trigger hypoglycemia.
Pharmacological therapy of diabetes mellitus: (Detailed information will be provided later)
Insulin (for Type 1 and some Type 2 DM)
Sulfonylureas, e.g., glibenclamide (for Type 2 DM)
Biguanides, e.g., metformin (for Type 2 DM)
Meglitinides (for Type 2 DM)
Thiazolidinediones (Glitazones), e.g., combination products like Competact (pioglitazone + metformin) (for Type 2 DM)
Alpha-Glucosidase inhibitors, e.g., acarbose (Precose) (for Type 2 DM)
Methods of treatment of diabetes:
Diet alone
Diet combined with oral hypoglycemic agents
Diet combined with insulin therapy
INSULIN THERAPY
Insulin is essential for the management of most patients with Type 1 Diabetes Mellitus (IDDM) and also for those with Type 2 Diabetes Mellitus (IIDM) who do not achieve adequate blood glucose control with oral hypoglycemic drugs. Insulin dosages are individualized to meet each patient’s specific needs and glycemic targets.
Administration
Subcutaneous injections: The most common method of insulin delivery.
Continuous subcutaneous insulin infusion pump: Provides a steady and adjustable basal rate of insulin, with bolus options for meals.
IV infusion: Reserved for emergency situations requiring rapid blood glucose control, using regular insulin only.
Aim of insulin therapy
To maintain blood glucose levels within the normal physiological range.
To alleviate symptoms associated with high blood sugar (hyperglycemia).
To correct metabolic and biochemical imbalances caused by insulin deficiency.
To prevent or delay the onset and progression of long-term diabetes-related complications.
Types of Insulin
Unmodified/soluble/rapid acting insulin: Typically administered subcutaneously in multiple daily injections, often three times a day before meals, with adult doses ranging from 40 to 100 IU daily and pediatric doses from 40 to 80 IU. This type of insulin is a clear solution that starts working within 30 minutes and peaks within 2 to 6 hours, necessitating repeated injections. It’s crucial for controlling postprandial hyperglycemia (high blood sugar after meals) and managing diabetic ketoacidosis in emergencies.
1. Ultra short acting-Lispro: A monomeric form of insulin that is absorbed very quickly into the bloodstream, with an active duration of 2-3 hours.
2. Aspart: Another rapid-acting insulin, available in both monomeric and dimeric forms, designed for rapid absorption.
3. Short acting-Regular: This hexameric form of insulin is absorbed more quickly than intermediate or long-acting insulins but slower than lispro and aspart. Examples include Novolin R and Humulin R.
Modified (depot) preparations: These are cloudy preparations or turbid suspensions created by adding either zinc (for lente preparations) or protamine (a protein) for isophane preparations. They are primarily used for the ongoing maintenance treatment of type 1 diabetes.
1. Semi lente/prompt zinc: This is a short-acting insulin containing zinc microcrystals in an acetate buffer. It is not suitable for intravenous administration due to the acetate buffer.
2. Lente insulin: An intermediate-acting insulin with an effective duration of approximately 12 hours. Examples include Humulin L. Typical adult doses are 10-20 IU injected subcutaneously twice daily, and for children, it’s 5-10 IU twice daily.
3. Ultralente: A long-acting insulin with an extended duration of action, typically lasting 24-36 hours. An example is Ultratard.
4. Insulin analogues: These are pre-mixed combinations of modified and unmodified insulin designed to provide both rapid and intermediate-acting effects, generally lasting around 12 hours. Examples include:
* 70% Neutral Protamine Hagedorn (NPH), 30% regular insulin
* 50% NPH, 50% regular insulin
* 75% NPH, 25% lispro insulin
* 70% insulin aspart protamine suspension, 30% insulin aspart.
Insulin mixtures are particularly helpful in managing high blood glucose levels after meals.
Adverse effects of insulin administration
Hypoglycemia: It is crucial for patients to recognize the symptoms of low blood sugar. Treatment involves oral administration of 10-15 grams of glucose. In cases of unconsciousness, intravenous dextrose is needed, or if IV access is unavailable, 1 mg of glucagon can be administered intramuscularly.
Skin rash at injection site: This can sometimes be mitigated by using more purified insulin preparations.
Lipodystrophies: These involve changes in fat tissue at the injection site, either lipoatrophy (loss of fat) or lipohypertrophy (gain of fat). Rotating injection sites helps prevent this.
Insulin resistance: A condition where the body’s cells become less responsive to insulin.
Allergy: Allergic reactions to insulin are rare but can occur.
Weight gain: Insulin can sometimes contribute to weight gain.
Avoid using propranolol or other beta-blockers in diabetic patients as these medications can mask the warning signs of hypoglycemia.
Medications that can increase blood glucose concentration should be used with caution or avoided in diabetic patients. Examples include Diazoxide, thiazide diuretics, streptozotocin, phenytoin, corticosteroids, and oral contraceptives.
How to measure the insulin needed.
A reasonable starting dose for insulin therapy is 0.6 Units per kilogram of body weight per day (U/kg/day). This total daily dose is typically divided as follows:
45% for basal insulin, which provides background insulin coverage throughout the day and night.
55% for prandial insulin, which is taken before meals to cover carbohydrate intake.
The prandial dose is further divided among the three main meals:
25% of the total daily dose administered before breakfast.
15% of the total daily dose administered before lunch.
15% of the total daily dose administered before supper (dinner).
Example: For a patient weighing 50 kg:
The total daily insulin dose = 0.6 U/kg x 50 kg = 30 U/day.
Basal insulin = 45% of 30 U = 13.5 U. This may be administered as a single dose or split into two doses.
Prandial insulin = 55% of 30 U = 16.5 U.
The 16.5 U for prandial insulin is divided as follows:
Pre-breakfast dose = 25% of 30 U = 7.5 U.
Pre-lunch dose = 15% of 30 U = 4.5 U.
Pre-supper dose = 15% of 30 U = 4.5 U.
It’s important to note that the initial insulin regimen often requires adjustments based on individual patient responses and blood glucose monitoring. Most Type 1 diabetes patients eventually need between 0.5 and 1.0 IU/kg/day.
Medications for Type 2 Diabetes:
Anti-diabetic medications (hypoglycemics) play a vital role in managing Type 2 diabetes by lowering blood sugar levels. These medications are available in various classes, with some administered orally (like metformin) and others via injection (like GLP-1 agonists). It’s crucial to remember that insulin is the primary treatment for Type 1 diabetes.
Sulphonylureas: These drugs stimulate the beta cells in the pancreas to secrete and release more insulin. Examples include glibenclamide and chlorpropamide.
Biguanides: Biguanides work by increasing glucose uptake by body cells and decreasing glucose production in the liver. Metformin (Glucophage) is frequently the first-line medication recommended for Type 2 diabetes and has been shown to decrease mortality.
Alpha-Glucosidase Inhibitors: These medications inhibit the enzyme alpha-glucosidase, which slows down the breakdown of carbohydrates in the intestine, thus hindering glucose uptake by cells. Examples include acarbose and miglitol.
Thiazolidinediones: This class of drugs works by decreasing insulin resistance, making the body’s cells more responsive to insulin. An example is pioglitazone.
Insulin Injections: Insulin injections are available in short-acting (e.g., Actrapid), intermediate-acting (e.g., Mixtard), and long-acting (e.g., Insulatard) formulations. They are the mainstay of treatment for Type 1 diabetes and are also used in Type 2 diabetes when oral medications are not sufficient to control blood sugar levels.
Blood Pressure Management:
Given the significantly increased cardiovascular risks associated with diabetes, effective blood pressure management is essential.
Target blood pressure levels are generally recommended to be below 130/80 mmHg, although some evidence supports a range between 140/90 mmHg to 160/100 mmHg.
Angiotensin-converting enzyme inhibitors (ACEIs) are effective in managing blood pressure in individuals with diabetes. Angiotensin receptor blockers (ARBs) may not offer the same level of benefit in this population.
Aspirin is often recommended for diabetic patients with existing cardiovascular problems. However, routine aspirin use has not been proven to be beneficial in individuals with uncomplicated diabetes.
Surgery:
Weight loss surgery (bariatric surgery) has proven to be an effective intervention for managing obesity and Type 2 diabetes. Many individuals undergoing this type of surgery are able to maintain normal blood sugar levels with minimal or no need for medications after the procedure, which can contribute to reduced long-term mortality.
The short-term mortality risk associated with weight loss surgery is typically less than 1%. The specific body mass index cutoffs for eligibility are still being defined.
Pancreas transplant is a rare consideration, typically reserved for individuals with severe complications of Type 1 diabetes, particularly those with end-stage kidney disease.
Support:
In most healthcare systems, the ongoing management of diabetes primarily occurs outside of hospital settings unless complications arise.
Home telehealth support has emerged as an effective strategy for managing diabetes, especially in cases involving complications, difficulties in achieving blood sugar control, or as part of research initiatives.
Sites for Insulin Administration
Prevention of Diabetes:
Type 1 Diabetes: Currently, there are no known preventive strategies for Type 1 diabetes. It is understood to be primarily an autoimmune condition where the body’s immune system mistakenly targets and destroys the insulin-producing beta cells within the pancreas.
Type 2 Diabetes: Preventing Type 2 diabetes largely relies on adopting healthy lifestyle changes and habits.
Maintaining a Healthy Diet:
Prioritize a well-rounded and nutritious dietary pattern that emphasizes fruits, vegetables, whole grains, and lean protein sources.
Reduce the consumption of processed foods, sugar-sweetened beverages, and foods that are high in saturated and trans fats.
Practice portion control to prevent overeating and maintain a healthy caloric intake.
Regular Physical Exercise:
Incorporate regular physical activity into your routine, such as brisk walking, jogging, swimming, or cycling.
Aim for a minimum of 150 minutes of moderate-intensity aerobic exercise each week.
Include strength training exercises to enhance muscle strength and overall physical fitness.
Maintaining a Normal Body Weight:
Achieve and sustain a healthy body weight through a combination of a balanced diet and consistent exercise. Weight loss has significant benefits for individuals at risk or diagnosed with prediabetes.
Avoiding Tobacco Use:
Abstaining from or quitting the use of tobacco products is crucial, as smoking is a significant risk factor for developing Type 2 diabetes.
Smoking cessation offers numerous positive impacts on health and contributes to overall well-being.
Control of Blood Pressure:
Regularly monitor and effectively manage blood pressure levels.
Adopt a heart-healthy lifestyle, which includes a diet low in sodium, regular physical activity, and stress management techniques.
Proper Foot Care:
Individuals with diabetes need to be particularly diligent about foot care.
Regularly examine your feet for any cuts, sores, blisters, or signs of infection.
Choose comfortable, well-fitting footwear and avoid walking barefoot to prevent injuries.
Avoiding Smoking:
Beyond its link to Type 2 diabetes, smoking is a recognized risk factor for various cardiovascular and respiratory illnesses. Quitting smoking provides substantial benefits for overall health and lowers diabetes risk.
Additional Measures:
Schedule regular health check-ups and undergo screenings for diabetes risk factors as recommended by your healthcare provider.
Monitor and manage stress levels through relaxation practices and mindfulness techniques.
Ensure adequate sleep, as it is essential for overall health and may play a role in diabetes prevention.
Limit alcohol consumption, as excessive alcohol intake can contribute to weight gain and negatively impact blood sugar levels.
Complications of diabetes mellitus
Cardiomyopathy: The primary long-term complications of diabetes are related to damage to the blood vessels. Diabetes significantly increases the risk of cardiovascular disease, doubling the risk, and approximately 75% of deaths in individuals with diabetes are attributed to coronary artery disease. Other significant macrovascular complications include stroke and peripheral artery disease.
Retinopathy: The main complications stemming from damage to small blood vessels include issues affecting the eyes, kidneys, and nerves. Damage to the eyes, known as diabetic retinopathy, results from damage to the blood vessels within the retina, potentially leading to gradual vision loss and even blindness. Diabetes also elevates the risk of developing glaucoma, cataracts, and other eye-related problems. Annual visits to an eye doctor are recommended for individuals with diabetes.
Nephropathy: Kidney damage, referred to as diabetic nephropathy, can cause scarring of kidney tissue, loss of protein in the urine, and ultimately, chronic kidney disease, which may necessitate dialysis or a kidney transplant.
Neuropathy: Nerve damage, or diabetic neuropathy, is the most prevalent complication of diabetes. Symptoms can encompass numbness, tingling sensations, pain, and altered pain perception, which can increase the risk of skin damage.
Diabetic foot: Diabetes can lead to various foot problems, including diabetic foot ulcers, which can be challenging to treat and may sometimes require amputation. Additionally, proximal diabetic neuropathy can cause painful muscle wasting and weakness.
Falls: There is a noted association between cognitive impairment and diabetes. Individuals with diabetes have a 1.2 to 1.5 times greater rate of decline in cognitive function compared to those without the disease. Being diabetic, particularly when on insulin therapy, elevates the risk of falls in older adults.
Other Complications:
Eye: Retinopathy leading to impaired vision, premature cataracts, and recurrent styes.
Urinary system: Renal failure, nephrotic syndrome, and pyelonephritis resulting from diabetic nephropathy.
Genital tract: Erectile dysfunction and decreased libido in men, and menstrual irregularities, recurrent miscarriages, purulent vaginitis, and infertility in women.
Nervous system: Neuropathy causing tingling and numbness in the feet, as well as an increased risk of stroke.
Cardiovascular system (CVS): Myocardial infarction (heart attack), peripheral gangrene, and hypertension.
Skin: Staphylococcal skin infections such as boils and carbuncles, slow-healing or non-healing ulcers, and mucocutaneous candidiasis (yeast infections).
Respiratory system: Increased susceptibility to pneumonia, lung abscess, and tuberculosis.
Diabetic Emergencies
Hypoglycemia:
Low blood sugar (hypoglycemia) is a common occurrence in individuals with both Type 1 and Type 2 Diabetes Mellitus (DM). While the majority of episodes are mild and not considered medical emergencies, the severity of effects can range from mild to severe.
Symptoms of Hypoglycemia
| Category | Mild Symptoms | Moderate Symptoms | Physical Signs (Common) |
| Common Signs | – Feelings of unease | – Confusion | – Sweating |
| – Changes in behavior (e.g., irritability, anxiety) | – Behavioral changes (e.g., aggression, irrationality) | – Rapid breathing | |
| – Trembling | – Difficulty concentrating | – Tremors | |
| – Increased appetite | – Weakness or dizziness | ||
| Severe Symptoms | – Seizures | – Sweating | |
| – Loss of consciousness (rare) | – Cold and pale skin |
Management of Hypoglycemia
Mild to Moderate Cases: Self-treatment is usually effective. This involves consuming readily available sugary foods or drinks (e.g., glucose tablets, fruit juice, regular soda).
Severe Cases: Require immediate medical attention. Treatment typically involves the administration of intravenous glucose to rapidly raise blood sugar levels. Glucagon injections can also be used, particularly if intravenous access is not readily available.
Hyperosmolar Hyperglycemic State
Hyperosmolar hyperglycemic state (HHS) is a serious complication more commonly observed in individuals with Type 2 Diabetes Mellitus. The primary underlying cause of HHS is severe dehydration. This condition is characterized by extremely high blood glucose levels.
Treatment of Hyperosmolar Hyperglycemic State
Hospitalization: HHS typically necessitates hospitalization for close medical management.
Fluid Replacement: Rapid and aggressive intravenous fluid replacement is crucial to correct the severe dehydration.
Insulin Administration: Insulin therapy is administered intravenously to gradually lower the significantly elevated blood glucose levels.
Electrolyte Correction: Electrolyte imbalances, which often occur with HHS, are carefully monitored and corrected.
Monitoring: Close and continuous monitoring of vital signs, blood glucose levels, and electrolyte levels is essential throughout the treatment process.
Diabetic Ketoacidosis (DKA):
Diabetic Ketoacidosis (DKA) is a severe and acute complication of Diabetes Mellitus characterized by the excessive production of blood acids (ketones). This condition presents a significant risk of death and morbidity, particularly if treatment is delayed. While historical mortality rates ranged from 5-10%, advancements in therapy have successfully reduced mortality to over 2%, although the prognosis remains poorer in very young and very old patients.
Pathophysiology:
DKA develops due to insulin deficiency combined with the effects of counter-regulatory hormones, leading to high blood sugar (hyperglycemia) and the presence of glucose in the urine (glycosuria). The lack of sufficient insulin forces the body to break down fats for energy instead of glucose, resulting in the production of ketones (ketosis) and a state of metabolic imbalance (metabolic acidosis). Vomiting, loss of water through respiration and perspiration (insensible water losses), and disturbances in electrolyte levels (electrolyte abnormalities) further worsen the condition. Severe dehydration can potentially lead to acute renal failure.
Precipitating Factors:
Several factors can trigger DKA, including:
New onset of type 1 DM: Approximately 25% of DKA cases are the first presentation of the disease.
Infections: Infections are the most common precipitating factor, accounting for about 40% of cases.
Drugs: Certain medications can contribute to DKA, such as steroids, thiazide diuretics, and adrenergic agonists like dobutamine and terbutaline.
Omission of Insulin: Skipping or missing scheduled insulin doses accounts for around 20% of DKA cases.
Diagnosis:
DKA should be suspected in any diabetic patient exhibiting the following signs and symptoms:
Dehydration
Acidotic (Kussmaul’s) breathing which is deep and rapid, often accompanied by a fruity odor on the breath due to acetone.
Abdominal pain and/or distension
Vomiting
Altered mental status ranging from confusion and disorientation to coma.
Diagnostic Criteria:
Specific laboratory findings confirm the diagnosis of DKA:
Hyperglycemia: Blood glucose levels > 300 mg/dl along with glucose in the urine (glucosuria).
Ketonemia and ketonuria: The presence of ketones in both the blood and urine.
Metabolic acidosis: Characterized by a blood pH < 7.25, serum bicarbonate levels < 15 mmol/l, and an anion gap > 10.
Management:
Effective management of DKA requires a systematic approach:
Assessment: A thorough evaluation is necessary to determine the underlying causes and consequences of DKA through detailed history taking and physical examination.
Quick Diagnosis at the ER: Prompt confirmation of hyperglycemia, ketonuria, and acidosis in the emergency room is crucial.
Baseline Investigations: Essential initial laboratory tests include:
Measurements of plasma and urine glucose and ketone levels.
Arterial blood gas (ABG) analysis to assess acid-base balance and oxygenation.
Urea and electrolytes (U&E) to evaluate levels of sodium (Na), potassium (K), calcium (Ca), magnesium (Mg), chloride (Cl), phosphate (PO4), and bicarbonate (HCO3), along with arterial pH.
Complete Blood Count (CBC) with differential to assess overall blood cell counts and identify signs of infection.
Treatment Principles: The core principles of DKA treatment are:
Careful and controlled fluid replacement.
Correction of acidosis and hyperglycemia through the administration of insulin.
Correction of electrolyte imbalances.
Identification and treatment of any underlying causes.
Close monitoring for potential complications.
Fluid Replacement:
Hypovolemic shock: In cases of shock due to severe fluid loss, immediate administration of 0.9% saline, Ringer’s lactate, or plasma expanders is critical.
Dehydration without shock: For dehydration without shock, 0.9% Saline is administered, with adjustments made to the infusion rate to avoid rapid shifts in serum osmolality.
Insulin Therapy:
Begin intravenous infusion of regular insulin at a rate of 0.1 U/kg/hour.
Adjust the composition of intravenous fluids as blood glucose levels decrease.
Continue the insulin infusion until the acidosis is resolved.
Correction of Electrolyte Balance:
Administer potassium supplementation added to the intravenous fluids.
Adjust the amount of potassium supplementation based on regular monitoring of serum potassium levels.
Monitoring:
Utilize a flow chart to meticulously track fluid balance and laboratory measurements.
Regularly measure serum glucose and electrolyte levels.
Conduct frequent neurological and mental status examinations to detect any changes.
Complications:
Potential complications of DKA include:
Cerebral Edema: Swelling of the brain.
Intracranial thrombosis or infarction: Blood clots or blockages in the blood vessels of the brain.
Acute tubular necrosis: Damage to the kidney tubules.
Peripheral edema: Swelling in the extremities.