Overview of Diabetes Mellitus
Diabetes mellitus is a complex, chronic metabolic disorder characterized by persistent hyperglycemia resulting from defects in insulin secretion, insulin action, or both. The condition encompasses two major types: Type 1 diabetes, an autoimmune disorder where insulin-producing beta cells in the pancreas are destroyed, and Type 2 diabetes, often associated with insulin resistance and inadequate insulin production. A distinctive feature of diabetes is its multifactorial etiology, influenced by genetic, environmental, and lifestyle factors, with emerging research implicating the gut microbiome as a potential contributor to insulin sensitivity. Complications of diabetes extend beyond traditional cardiovascular, renal, and neurological impacts; recent studies have revealed its association with conditions like Alzheimer’s disease, now termed “Type 3 diabetes” in some contexts, due to shared insulin signaling impairments. Management includes tailored approaches involving medication, lifestyle modifications, and continuous monitoring, with advancements such as artificial pancreas systems and personalized medicine offering promising improvements in quality of life.
Diabetes Mellitus
Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose (sugar) levels, either due to insufficient insulin production (Type 1 diabetes) or the body’s inability to effectively use insulin (Type 2 diabetes). Insulin, a hormone produced by the pancreas, helps regulate blood sugar levels.
Types of Diabetes Mellitus
1. Type 1 Diabetes Mellitus (T1DM):
• An autoimmune condition where the immune system attacks and destroys insulin-producing beta cells in the pancreas. This leads to an absolute deficiency of insulin.
• Commonly diagnosed in childhood or adolescence but can occur at any age.
2. Type 2 Diabetes Mellitus (T2DM):
• Results from insulin resistance (the body’s cells don’t respond properly to insulin) and relative insulin deficiency. The pancreas may initially produce enough insulin, but the body cannot use it effectively.
• Most commonly associated with lifestyle factors, including obesity and physical inactivity.
3. Gestational Diabetes:
• A form of diabetes that occurs during pregnancy and typically resolves after childbirth. However, women with gestational diabetes are at a higher risk of developing T2DM later in life.
4. Maturity-Onset Diabetes of the Young (MODY):
• A rare, genetic form of diabetes that usually presents in adolescence or early adulthood.
5. Secondary Diabetes:
• Occurs due to other medical conditions or medications that affect insulin production or action, such as pancreatitis or prolonged use of corticosteroids.
Causes of Diabetes
1. Type 1 Diabetes:
• Autoimmune destruction: The immune system mistakenly attacks and destroys beta cells in the pancreas, leading to an insulin deficiency.
• Genetic factors: Family history and certain genetic markers (HLA-DR3, HLA-DR4) increase susceptibility.
• Environmental triggers: Viral infections or other environmental factors may trigger the immune system response in genetically predisposed individuals.
2. Type 2 Diabetes:
• Insulin resistance: The body’s cells become resistant to insulin, requiring higher amounts of insulin to regulate blood glucose levels.
• Genetic factors: A strong family history of T2DM increases the risk.
• Obesity: Excess fat, particularly around the abdomen, contributes to insulin resistance.
• Physical inactivity: Lack of exercise reduces the body’s ability to regulate blood glucose levels.
• Dietary factors: High-calorie, high-sugar diets can contribute to obesity and insulin resistance.
Risk Factors
• Type 1 Diabetes:
• Family history of T1DM or other autoimmune diseases.
• Viral infections, such as Coxsackievirus, rubella, or mumps.
• Genetics (certain HLA gene variations).
• Type 2 Diabetes:
• Obesity and physical inactivity.
• Family history of diabetes.
• Age (more common in people over 45, but increasingly seen in younger populations due to rising obesity rates).
• High blood pressure and abnormal cholesterol levels.
• Gestational diabetes or giving birth to a baby over 9 pounds.
• Polycystic ovary syndrome (PCOS).
Pathology
• Type 1 Diabetes:
• Autoimmune destruction of beta cells in the pancreas leads to a complete deficiency of insulin.
• As a result, glucose cannot enter the cells, leading to elevated blood glucose levels (hyperglycemia).
• Type 2 Diabetes:
• Insulin resistance: Cells fail to respond to insulin effectively, leading to impaired glucose uptake.
• Compensatory hyperinsulinemia: In the early stages, the pancreas produces extra insulin to overcome resistance.
• Beta-cell dysfunction: Over time, the pancreas becomes unable to maintain the high levels of insulin needed to control blood glucose levels, leading to hyperglycemia.
Signs and Symptoms
• Frequent urination (polyuria): Excess glucose in the blood spills into the urine, drawing water with it.
• Increased thirst (polydipsia): Due to dehydration from excessive urination.
• Increased hunger (polyphagia): Cells are deprived of glucose and send hunger signals to the brain.
• Unexplained weight loss: More common in T1DM, as the body starts to break down fat and muscle for energy.
• Fatigue: Lack of glucose in cells leads to low energy.
• Blurred vision: High blood sugar causes swelling in the eye’s lens.
• Slow healing of wounds: Impaired blood circulation and high blood sugar delay wound healing.
• Frequent infections: High blood sugar can impair the immune system.
Laboratory Investigations and Findings
1. Fasting Plasma Glucose (FPG):
• A fasting blood glucose level of ≥126 mg/dL (7.0 mmol/L) on two separate occasions is diagnostic for diabetes.
2. Oral Glucose Tolerance Test (OGTT):
• After fasting, the patient consumes a glucose-rich drink, and blood sugar is measured two hours later. A level of ≥200 mg/dL (11.1 mmol/L) confirms diabetes.
3. Glycated Hemoglobin (HbA1c):
• Reflects average blood glucose levels over the past 2-3 months. An HbA1c level of ≥6.5% is diagnostic for diabetes.
4. Random Plasma Glucose Test:
• A random blood glucose level of ≥200 mg/dL (11.1 mmol/L), along with classic symptoms of hyperglycemia, indicates diabetes.
5. C-peptide Test:
• Helps differentiate between Type 1 and Type 2 diabetes by measuring insulin production. Low C-peptide levels indicate T1DM.
6. Urinalysis:
• Can show glucose in the urine (glucosuria) and the presence of ketones, especially in uncontrolled diabetes or diabetic ketoacidosis (DKA).
Treatment
Treatment depends on the type of diabetes but generally involves lifestyle modifications, medications, and regular monitoring of blood sugar levels.
1. Type 1 Diabetes:
• Insulin therapy: Patients require lifelong insulin injections or an insulin pump. Various forms of insulin are used, including rapid-acting, short-acting, intermediate-acting, and long-acting insulin.
• Blood sugar monitoring: Frequent self-monitoring of blood glucose (SMBG) or use of continuous glucose monitors (CGM).
• Diet and exercise: Healthy eating and regular physical activity help control blood sugar levels and maintain overall health.
2. Type 2 Diabetes:
• Lifestyle changes:
• Diet: Focus on a balanced diet low in sugar, refined carbs, and saturated fats, and rich in fiber.
• Exercise: Regular physical activity to improve insulin sensitivity.
• Weight loss: Can improve insulin resistance and reduce the need for medication.
• Oral medications:
• Metformin: Reduces liver glucose production and improves insulin sensitivity.
• Sulfonylureas: Stimulate the pancreas to produce more insulin (e.g., glimepiride, glyburide).
• DPP-4 inhibitors: Enhance the activity of hormones that regulate insulin release (e.g., sitagliptin).
• SGLT2 inhibitors: Increase glucose excretion in urine (e.g., empagliflozin).
• GLP-1 receptor agonists: Increase insulin secretion and decrease appetite (e.g., liraglutide).
• Insulin: May be necessary in later stages if blood glucose cannot be controlled with oral medications alone.
• Blood sugar monitoring: Regular SMBG or CGM to track blood glucose levels.
3. Gestational Diabetes:
• Diet and exercise: Mainstay of treatment to control blood sugar during pregnancy.
• Insulin: May be required if blood sugar levels remain elevated despite lifestyle changes.
Complications (if untreated or poorly managed)
• Cardiovascular disease: Increased risk of heart attacks and strokes.
• Diabetic neuropathy: Nerve damage, particularly in the feet and hands, leading to numbness or pain.
• Diabetic retinopathy: Damage to blood vessels in the retina, potentially leading to blindness.
• Diabetic nephropathy: Kidney damage, which can lead to kidney failure. • Foot ulcers: Due to poor circulation and nerve damage, increasing the risk of infection and amputation.
