22 Jan, 2025
Diabetes Mellitus: A Chronic Disease and its Treatment
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Dr. Mamta
Assistant Professor

Diabetes Mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycemia (high blood glucose levels) resulting from defects in insulin secretion, insulin action, or both. It is a major public health concern with significant morbidity and mortality globally.

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  1. Classification of Diabetes Mellitus

Diabetes is broadly classified into four main types:

  1. Type 1 Diabetes Mellitus (T1DM)
  • Cause: Autoimmune destruction of pancreatic beta cells leading to absolute insulin deficiency.
  • Onset: Often occurs in childhood or adolescence, but can develop at any age.
  • Symptoms: Rapid onset of polyuria, polydipsia, polyphagia, weight loss, and fatigue.
  • Pathogenesis:
    • Autoimmune mechanisms, involving T-cells and autoantibodies (e.g., GAD antibodies).
    • Genetic predisposition (e.g., HLA-DR3/DR4).
  1. Type 2 Diabetes Mellitus (T2DM)
  • Cause: Insulin resistance combined with progressive beta-cell dysfunction.
  • Onset: Typically in adults over 40 but increasingly common in younger individuals due to obesity.
  • Risk Factors: Obesity, sedentary lifestyle, family history, ethnicity, and age.
  • Pathogenesis:
    • Peripheral insulin resistance in muscle, liver, and adipose tissue.
    • Defective insulin secretion from pancreatic beta cells.
  1. Gestational Diabetes Mellitus (GDM)
  • Definition: Hyperglycemia first recognized during pregnancy.
  • Risk Factors: Family history, obesity, advanced maternal age, or previous macrosomic baby.
  • Complications: Increased risk of preeclampsia, cesarean delivery, and neonatal complications (e.g., macrosomia, neonatal hypoglycemia).
  1. Other Specific Types
  • Monogenic Diabetes: Genetic mutations (e.g., MODY – Maturity Onset Diabetes of the Young).
  • Secondary Diabetes: Caused by medications (e.g., corticosteroids), infections, or diseases (e.g., pancreatitis).
  1. Symptoms of Diabetes Mellitus

Common symptoms include:

  • Hyperglycemia: Elevated blood sugar levels.
  • Polyuria: Frequent urination due to glucose-induced osmotic diuresis.
  • Polydipsia: Excessive thirst caused by dehydration.
  • Polyphagia: Increased hunger due to energy loss.
  • Weight Loss: Despite increased appetite (more common in T1DM).
  • Fatigue: Due to the inability of cells to utilize glucose effectively.
  • Blurred Vision: Due to changes in the lens caused by hyperglycemia.
  • Slow Healing: Wounds heal slowly due to poor circulation and immune function.

 

  1. Pathophysiology
  2. Normal Glucose Metabolism
  • Glucose is the primary energy source.
  • Insulin, produced by pancreatic beta cells, facilitates glucose uptake into cells.
  • After meals:
    • Insulin promotes glucose storage as glycogen in the liver and muscles.
    • Suppresses gluconeogenesis (glucose production) in the liver.
  1. Type 1 Diabetes
  • Autoimmune destruction of beta cells leads to:
    • Absolute insulin deficiency.
    • Unopposed gluconeogenesis and lipolysis, resulting in hyperglycemia and ketoacidosis.
  1. Type 2 Diabetes
  • Insulin Resistance:
    • Cells in muscles, liver, and fat do not respond to insulin effectively.
  • Beta-Cell Dysfunction:
    • Over time, beta cells fail to compensate for increased insulin demand.

 

  1. Diagnosis of Diabetes Mellitus

The diagnosis of diabetes mellitus involves several tests to measure blood glucose (sugar) levels and assess how well the body is managing glucose. Diabetes is typically diagnosed when a person has high blood sugar levels, either consistently over time or as a result of a single test. The diagnosis is confirmed using one or more of the following tests:

  1. Fasting Blood Glucose (FBG) Test
  • What it measures: The blood sugar level after fasting for at least 8 hours (usually done in the morning before eating or drinking anything).
  • Normal Range:
    • Normal: 70–99 mg/dL (3.9–5.5 mmol/L)
    • Pre-diabetes (impaired fasting glucose): 100–125 mg/dL (5.6–6.9 mmol/L)
    • Diabetes: 126 mg/dL (7.0 mmol/L) or higher on two separate occasions
  • Purpose: This test helps to evaluate how well the body manages blood sugar after fasting and is often one of the first steps in diagnosing diabetes.
  1. Oral Glucose Tolerance Test (OGTT)
  • What it measures: The test involves drinking a glucose solution, and blood sugar levels are measured at multiple intervals (typically after 2 hours).
  • Normal Range:
    • Normal: Less than 140 mg/dL (7.8 mmol/L) after 2 hours
    • Pre-diabetes (impaired glucose tolerance): 140–199 mg/dL (7.8–11.0 mmol/L) after 2 hours
    • Diabetes: 200 mg/dL (11.1 mmol/L) or higher after 2 hours
  • Purpose: The OGTT measures how the body responds to a large dose of sugar and is particularly useful for diagnosing gestational diabetes and confirming diabetes in cases of suspected pre-diabetes.
  1. Hemoglobin A1c (HbA1c) Test
  • What it measures: The HbA1c test measures the average blood glucose levels over the past 2 to 3 months. It reflects how much glucose is attached to hemoglobin in red blood cells, which provides an indication of long-term blood sugar control.
  • Normal Range:
    • Normal: Below 5.7%
    • Pre-diabetes (impaired glucose tolerance): 5.7% to 6.4%
    • Diabetes: 6.5% or higher on two separate occasions
  • Purpose: The HbA1c test is used for diagnosing diabetes and is also used for monitoring long-term blood glucose control in people who have already been diagnosed with diabetes.
  1. Random Blood Glucose Test
  • What it measures: A blood sugar test taken at any time of day, regardless of when the person last ate. The test is typically used when diabetes is suspected due to symptoms.
  • Normal Range:
    • Normal: Generally below 140 mg/dL (7.8 mmol/L), though this can vary depending on the laboratory.
    • Diabetes: 200 mg/dL (11.1 mmol/L) or higher, with symptoms of diabetes (e.g., increased thirst, frequent urination, and fatigue)
  • Purpose: This test can help diagnose diabetes, especially in people with classic symptoms. If the result is 200 mg/dL or higher, diabetes is likely, but confirmation with another test is needed.
  1. Urine Test (Less commonly used for diagnosis)
  • What it measures: A urine test checks for the presence of glucose or ketones. Normally, glucose is not present in urine because the kidneys filter it out and reabsorb it back into the bloodstream. In uncontrolled diabetes, excess glucose can spill over into the urine.
  • Purpose: Urine tests are not routinely used for diagnosing diabetes but may indicate the need for further blood testing if glucose or ketones are present.

Diagnosis Criteria Summary:

  • Fasting Blood Glucose (FBG):
    • Normal: < 100 mg/dL
    • Pre-diabetes: 100–125 mg/dL
    • Diabetes: ≥ 126 mg/dL (confirmed with a second test)
  • Oral Glucose Tolerance Test (OGTT):
    • Normal: < 140 mg/dL after 2 hours
    • Pre-diabetes: 140–199 mg/dL after 2 hours
    • Diabetes: ≥ 200 mg/dL after 2 hours
  • Hemoglobin A1c:
    • Normal: < 5.7%
    • Pre-diabetes: 5.7%–6.4%
    • Diabetes: ≥ 6.5%
  • Random Blood Glucose Test:
    • Diabetes: ≥ 200 mg/dL with symptoms of diabetes.
 

Additional Testing:

  • C-Peptide Test: In some cases, a C-peptide test may be performed to assess how much insulin the pancreas is producing. This is particularly useful in distinguishing between Type 1 and Type 2 diabetes.
  • Autoantibody Tests: For suspected Type 1 diabetes, tests for autoimmune markers (such as GAD antibodies) may be done to check for an autoimmune response that destroys the insulin-producing cells in the pancreas.
 

Importance of Early Diagnosis:

  • Early diagnosis and treatment of diabetes can help prevent or delay complications such as cardiovascular disease, nerve damage, kidney disease, and eye problems.
  • Regular screening is recommended for individuals at high risk, including those with a family history of diabetes, obesity, or a history of gestational diabetes.

By diagnosing diabetes early, individuals can manage their condition through lifestyle changes, medications, and monitoring, thereby improving their quality of life and reducing the risk of complications.

  1. Complications of Diabetes
  2. Acute Complications
  1. Hypoglycemia: Low blood glucose (< 70 mg/dL) due to excess insulin or skipped meals.

Cause: Excessive insulin, skipping meals, or intense physical activity.

Symptoms: Sweating, trembling, confusion, dizziness, and in severe cases, seizures or coma.

  1. Diabetic Ketoacidosis (DKA): Severe hyperglycemia with ketosis, more common in T1DM.

Cause: Insulin deficiency leading to the breakdown of fats and production of ketones.

Symptoms: Nausea, vomiting, abdominal pain, rapid breathing, fruity-smelling breath, and confusion.

Common in: Type 1 diabetes.

  1. Hyperosmolar Hyperglycemic State (HHS): Severe hyperglycemia without ketosis, common in T2DM.

Cause: Severe hyperglycemia without ketosis, leading to dehydration and altered consciousness.

Common in: Type 2 diabetes.

  1. Chronic Complications
  1. Microvascular:
  • Retinopathy (eye damage)- Diabetic retinopathy is one of the most common microvascular complications of diabetes mellitus. It affects the eyes and can lead to vision impairment and blindness if not managed effectively. It occurs due to damage to the blood vessels in the retina, the light-sensitive tissue at the back of the eye.
    • Nephropathy (kidney damage)- Diabetic nephropathy is a type of kidney damage that occurs due to long-term uncontrolled diabetes. It is one of the most common complications of diabetes, especially if blood sugar levels are not well managed over time.
    • Neuropathy (nerve damage)- Diabetic nephropathy is a type of kidney damage that occurs due to long-term uncontrolled diabetes. Chronic high blood sugar levels damage the blood vessels in the kidneys, impairing their ability to filter waste from the blood.
  2. Macrovascular:
    • Cardiovascular disease (heart attacks, stroke)- Cardiovascular disease (CVD), including heart attacks and strokes, is a major complication of diabetes. People with diabetes, especially those with poorly controlled blood sugar, are at higher risk for developing various types of cardiovascular problems due to the long-term effects of elevated blood glucose on blood vessels and the heart. Diabetes can also lead to other conditions such as high blood pressure and high cholesterol, which further increase the risk of cardiovascular issues.
    • Peripheral arterial disease (limb ischemia)- Peripheral Artery Disease (PAD), also known as limb ischemia, is a condition where the blood vessels outside the heart and brain become narrowed or blocked, reducing blood flow to the limbs (typically the legs). This is common in people with diabetes due to the damaging effects of long-term high blood sugar on blood vessels.

(b) Macrovascular Complications:

  1. Cardiovascular Disease (CVD):
    • Increased risk of heart attacks, strokes, and coronary artery disease.
  2. Peripheral Arterial Disease (PAD):
    • Reduced blood flow to the limbs, leading to pain, ulcers, and gangrene.
  3. Cerebrovascular Disease: Cerebrovascular Disease (CVD) refers to a group of conditions that affect the blood vessels in the brain, and it includes diseases such as stroke and transient ischemic attack (TIA). People with diabetes are at a significantly higher risk of developing cerebrovascular disease due to the long-term effects of high blood sugar (hyperglycemia) on the blood vessels, heart, and other organs. Diabetes can contribute to the development of cerebrovascular disease through mechanisms such as atherosclerosis, high blood pressure, and other cardiovascular risk factors.
  1. Other Complications

(a) Infections:

  • Poor immune response in diabetics increases susceptibility to infections like urinary tract infections, skin infections, and fungal infections.

(b) Diabetic Foot:

  • Caused by a combination of neuropathy, PAD, and infections.
  • Can lead to ulcers, infections, and in severe cases, amputations.

(c) Gastrointestinal Issues:

  • Gastroparesis (delayed stomach emptying) causing nausea, vomiting, and bloating.

(d) Skin Disorders:

  • Diabetic dermopathy, necrobiosis lipoidica, and fungal infections.

(e) Dental Problems:

  • Increased risk of gum disease and infections.

(f) Cognitive Decline:

  • Higher risk of Alzheimer’s disease or vascular dementia.

 

Management and Prevention of Diabetes Mellitus

Effective management and prevention of diabetes mellitus (DM) involve a combination of lifestyle modifications, medical interventions, and patient education. Below is a detailed overview of strategies for managing and preventing both Type 1 and Type 2 diabetes.

 

Management of Diabetes Mellitus

  1. Lifestyle Modifications
  1. Healthy Diet:
    • Focus on a balanced diet rich in whole grains, lean proteins, healthy fats, vegetables, and fruits.
    • Minimize intake of sugar, refined carbohydrates, and saturated fats.
    • Opt for low glycemic index (GI) foods to prevent blood sugar spikes.
    • Use portion control to avoid overeating.
  2. Regular Exercise:
    • Engage in aerobic exercises like walking, cycling, or swimming for at least 150 minutes per week.
    • Incorporate strength training 2-3 times per week to improve insulin sensitivity.
    • Monitor blood sugar levels before and after exercise.
  3. Weight Management:
    • For overweight or obese individuals, a 5-10% weight loss can significantly improve blood sugar control.
    • Maintain a healthy body mass index (BMI) of 18.5-24.9.
  4. Smoking Cessation:
    • Quit smoking to reduce the risk of cardiovascular complications.
  5. Stress Management:
    • Use stress-reduction techniques such as yoga, meditation, or deep breathing exercises.

 

  1. Medical Management
  1. Blood Glucose Monitoring:
    • Regularly check fasting blood glucose (FBG) and HbA1c levels to assess long-term control.
    • Continuous glucose monitors (CGMs) can provide real-time insights.
  2. Medications:
    • Type 1 Diabetes: Requires insulin therapy (short-acting, long-acting, or both).
    • Type 2 Diabetes: Managed with:
      • Oral hypoglycemic agents like metformin, sulfonylureas, and SGLT2 inhibitors.
      • Non-insulin injectables, such as GLP-1 receptor agonists.
      • Insulin therapy in advanced cases.
  3. Management of Comorbidities:
    • Hypertension: Use antihypertensive drugs (e.g., ACE inhibitors or ARBs).
    • Dyslipidemia: Manage with lifestyle changes and statins to control cholesterol.
    • Antiplatelet Therapy: For those with high cardiovascular risk.
  4. Preventing and Treating Complications:
    • Annual screenings for diabetic retinopathy, nephropathy, and neuropathy.
    • Regular foot exams to prevent ulcers and infections.
    • Early intervention for cardiovascular issues.

Prevention of Diabetes Mellitus

  1. Primary Prevention
  1. Healthy Lifestyle:
    • Maintain an active lifestyle with regular physical activity.
    • Avoid excessive weight gain through a healthy diet and exercise.
    • Limit intake of sugary beverages and processed foods.
  2. Risk Factor Management:
    • Screen for prediabetes in high-risk groups (e.g., those with family history or obesity).
    • Address modifiable risk factors like smoking, hypertension, and dyslipidemia.
  3. Public Health Initiatives:
    • Community awareness programs to educate people about healthy habits.
    • Policies promoting healthier food options and physical activity.

 

  1. Secondary Prevention
  1. Early Screening:
    • Routine screening for blood glucose levels in high-risk individuals.
    • Screen for gestational diabetes during pregnancy.
  2. Prediabetes Intervention:
    • Intensive lifestyle intervention programs (e.g., Diabetes Prevention Program [DPP]).
    • Use of metformin for individuals at high risk of developing Type 2 diabetes.

 

 

  1. Tertiary Prevention
  1. Managing Complications:
    • Intensive glucose control to slow the progression of complications.
    • Regular follow-ups with healthcare providers for early detection and management.
  2. Rehabilitation:
    • Support for individuals with complications such as foot ulcers, vision loss, or cardiovascular disease.
    • Physical therapy or occupational therapy as needed.

Conclusion

Diabetes mellitus is a chronic condition that can lead to serious complications if left undiagnosed or untreated. Early detection is critical to prevent long-term health issues such as cardiovascular disease, nerve damage, kidney problems, and impaired vision. It is essential for individuals with risk factors (e.g., family history, obesity, age, sedentary lifestyle) to undergo regular screening for diabetes to facilitate early intervention. Timely diagnosis allows for effective management through lifestyle changes, medications, and regular monitoring, helping to reduce the risk of complications and improve overall quality of life.

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