Type 1 Diabetes Mellitus

Symptoms Of Type 1 Diabetes

New-onset type 1 diabetes refers to the early stage of type 1 diabetes when symptoms first appear. They include:

• Increased thirst (polydipsia)

• Frequent urination (polyuria)

• Extreme hunger (polyphagia)

• Unintentional weight loss, despite eating well

• Fatigue and weakness

Diabetic Ketoacidosis (DKA) is a life-threatening condition where the body produces high levels of blood acids called ketones due to insulin deficiency, often occurring in type 1 diabetes if not managed promptly. Symptoms of Diabetic Ketoacidosis (DKA)

• High blood sugar with ketones in urine

• Electrolyte imbalance leads to metabolic acidosis

• Fruity-smelling breath

• Severe lethargy or weakness

• In extreme cases, coma.

Causes Of Type 1 Diabetes

Type 1 diabetes is caused by the immune system mistakenly attacking and destroying insulin-producing beta cells in the pancreas, known as autoimmune destruction. This leads to little or no insulin production, which is essential for regulating blood sugar levels. Type 1 diabetes (T1D) develops in three stages:

Stage 1 (Preclinical)

• The autoimmune destruction of insulin-producing β-cells begins, but individuals show no symptoms. 

• Blood sugar levels remain normal, though at least two pancreatic autoantibodies are detected.

Stage 2 (Dysglycemia)

• Significant β-cell damage leads to abnormal blood sugar levels. 

• Diagnosed by pancreatic autoantibodies along with impaired fasting glucose, glucose tolerance, or elevated HbA1c (5.7%-6.4%). Individuals are still asymptomatic.

Stage 3 (Clinical Onset) 

• Symptoms like high blood sugar (hyperglycemia) appear, signaling the onset of diabetes.

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Risk Factors For Type 1 Diabetes

The risk factors for developing Type 1 diabetes (T1D) include:

1. Genetics

• Certain HLA genes, particularly HLA-DR3 and HLA-DR4, are associated with genetic predisposition

• This is linked to increased susceptibility to autoimmune beta-cell destruction. 

2. Family History

• Individuals with a sibling or parent with T1D have a higher likelihood of developing the condition.

• Although most cases occur without a family history.

Interesting Tibit!

Type 1 diabetes is a genetic condition with a 30–70% chance in identical twins, a 6–7% risk in siblings, and a 1–9% risk for children of diabetic parents.

3. Age

• T1D often develops in childhood or adolescence, but it can occur at any age.

4. Environmental Triggers

• Viral infections (e.g., enteroviruses, Coxsackievirus, or SARS-CoV-2)

• Dietary factors (such as early exposure to cow’s milk or gluten)

• Prenatal conditions (like maternal viral infections during pregnancy (e.g., rubella), cesarean delivery, etc.)

5. Autoimmune Conditions

• Thyroid disease

• Celiac disease

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Diagnosis Of Type 1 Diabetes

The right diagnosis of Type 1 diabetes is crucial to prevent life-threatening complications and ensure timely management for better health outcomes. It consists of the following:

1. Medical History

• Given the increased risk of autoimmune disorders, clinicians should screen for conditions such as thyroid disease and celiac disease. 

• Psychosocial factors, eating disorders, and cognitive decline should also be assessed.

2. Physical Examination

• A full physical examination, including a diabetes foot exam and inspection of insulin injection sites for lipodystrophy, is critical.

3. Laboratory Tests

• Fasting blood sugar (FBS): It is a blood sugar test performed after at least 8 hours of fasting to measure glucose levels. Readings ≥126 mg/dL on more than one occasion are suggestive of diabetes.

• Random blood sugar (RBS): It is a blood sugar test done at any time of the day without fasting. Values ≥200 mg/dL with classic hyperglycemia symptoms are indications for diabetes.

• Glucose challenge test (GCT): It measures blood sugar levels before and after drinking a glucose solution to evaluate the body’s ability to process sugar. Blood glucose ≥200 mg/dL, 2 hours after a 75-g glucose load can indicate diabetes.

• HbA1C: Also known as glycated hemoglobin, it is a blood test that measures the average level of blood sugar over the past 2 to 3 months. Readings ≥6.5% suggest diabetes.

• Islet cell antibodies: Test for autoimmune reactions that target the insulin-producing cells in the pancreas, helping diagnose Type 1 diabetes.

• GAD total Antibody (Glutamic Acid Decarboxylase Autoantibodies): It is an autoantibody test used to help diagnose type 1 diabetes, particularly in new-onset cases.

Note: Diagnosis confirmation requires two abnormal results of hyperglycemia (increased blood sugar) symptoms are not evident.

4. Distinguishing T1D from Other Diabetes

• Pancreatic autoantibodies: Tests check for specific antibodies in the blood that help diagnose type 1 diabetes by identifying immune system markers that attack the pancreas. 

• C-Peptide levels: It measures how much insulin-producing function is still active in the pancreas, indicating how much insulin the body can still produce.

5. Screening for Autoimmune Conditions

• Conditions such as thyroid disorders, celiac disease, adrenal insufficiency, and rheumatoid arthritis are more common in people with Type 1 Diabetes (T1D). 

• Screening for these conditions is important when symptoms or clinical signs appear, as they can help in diagnosing T1D and managing associated risks.

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Prevention Of Type 1 Diabetes

Prevention of type 1 diabetes focuses on strategies that aim at identifying key antigens and modifying immunity to delay or prevent onset. They include:

Primary Prevention

• Genetic testing: Identifying individuals at risk based on HLA genotyping and other genetic markers to target prevention efforts effectively.

• Avoiding environmental triggers: Minimizing exposure to factors like early cow’s milk intake, gluten, and viruses that may trigger autoimmune responses in genetically susceptible individuals.

• Immune modulation: Using therapies like vitamin D, nicotinamide, and docosahexaenoic acid, although their effectiveness has been limited in clinical trials.
  
  

• Bystander suppression: Using therapies that expose individuals to specific antigens (like insulin) to induce immune tolerance and prevent autoimmune attacks on pancreatic cells.

Secondary Prevention

• Immunomodulation: Therapies to suppress or alter the immune response targeting beta cells. Examples include:

  • Teplizumab (anti-CD3 monoclonal antibody): FDA-approved for delaying the progression of T1D.

  • Other agents: Targeting immune pathways like CD3, CD20, and CTLA4 (e.g., otelixizumab, abatacept).
    
    

• Antigen-Specific Therapy: Use of insulin (oral, nasal, or injectable) or GAD65 to induce immune tolerance. Outcomes in trials have been mixed, with some success in specific subgroups.

Tertiary Prevention

• Cyclosporine and anti-thymocyte globulin: Induce temporary remission but have serious side effects, limiting their use.

• BCG vaccine: Suggests potential benefit in delaying/preventing T1D onset when administered in childhood.

• Teplizumab: Initially showed promise for tertiary prevention in small studies. 

• Islet cell transplantation: Aims to improve therapy ease and quality of life.

• Beta cell development: Recent breakthroughs in creating glucose-sensing beta cells show promise but are not yet commercially viable.

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Specialist To Visit

Managing Type 1 diabetes requires a comprehensive, team-based approach, involving specialists who can address various symptoms and complications effectively. They include:

• General physician
• Pediatrician 
• Endocrinologist
• Diabetologist
• Dietitian or Nutritionist
• Ophthalmologist
• Podiatrist
• Psychologist 
  

A general physician helps manage Type 1 diabetes by diagnosing the condition, providing initial treatment plans, and coordinating care with specialists for comprehensive management.

A pediatrician manages Type 1 diabetes in children by monitoring growth, development, and ensuring proper glycemic control tailored to their unique needs.

An endocrinologist specializes in managing hormonal imbalances and provides comprehensive care for Type 1 diabetes, including advanced treatment strategies.

A diabetologist focuses on diabetes care, offering expertise in insulin therapy, glucose monitoring, and lifestyle adjustments.

A dietitian creates personalized meal plans to optimize blood sugar control and overall nutrition.

An ophthalmologist monitors and treats diabetes-related eye conditions like retinopathy to prevent vision loss.

A podiatrist addresses foot health to prevent and manage complications like ulcers or neuropathy in diabetes.

A psychologist provides mental health support to manage the emotional and psychological impact of living with Type 1 diabetes.

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When to see a doctor?

See a doctor if you notice the following:

• Dizziness or lightheadedness
• Sweating
• Hunger or nausea
• Skin appears extremely pale
• Shakiness
• Irregular or fast heartbeat
• Difficulty concentrating
• Fatigue
• Irritability or anxiety
• Constant headache
• Numbness in lips, tongue, or cheek

Treatment Of Type 1 Diabetes

The treatment of Type 1 Diabetes focuses on lifelong insulin therapy, blood glucose monitoring, and lifestyle adjustments to achieve optimal glycemic control and prevent complications. It consists of:

1. Insulin Replacement

• T1D management involves replacing insulin physiologically through injections or pumps.

• Types of insulin commonly used include:

  • Short-acting insulin: Regular insulin starts working in ~30 minutes, peaks at 90–120 minutes, and lasts 4–6 hours. Example: Insulin Humulin R

  • Rapid-acting insulin: Works within 15 minutes, peaks at 60 minutes, and lasts about 4 hours; often used before meals. Example: Insulin Aspart (Novolog)

  • Intermediate-acting insulin: NPH insulin begins action in 1–3 hours, peaks at 6–8 hours, and lasts 12–24 hours. Example: Insulin Humulin N (NPH insulin)

  • Long- and ultra-long-acting insulin: Provides coverage for 14–40 hours, ensuring extended glycemic control. Example: Insulin Glargine (Lantus)

2. Multiple Daily Injections (MDI)

• MDI combines long-acting basal insulin and rapid-acting mealtime insulin.

• Doses are tailored to achieve glucose targets while avoiding hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar).

3. Continuous Subcutaneous Insulin Infusion (CSII)

• Insulin pumps deliver continuous basal insulin and mealtime boluses (dose of insulin taken before eating).

• Advanced pumps integrate CGMs (Continuous glucose monitor that tracks blood sugar levels continuously in real-time) for automated glucose control and precision.

4. Combination Drugs

• Pramlintide and metformin reduce blood sugar and aid weight control.

• GLP-1 receptor agonists (e.g., liraglutide) enhance insulin efficiency and support weight loss.

• SGLT2 inhibitors help lower glucose levels by increasing glucose excretion in urine, improving glycemic control.

5. Glucagon Therapy

• Glucagon is a hormone produced by the pancreas that raises blood sugar levels by acting as the opposite of insulin.

• New nasal and stable liquid glucagon forms enhance emergency and exercise-related management options.

• Dual-hormone systems (insulin + glucagon) show promise for improved glucose control.\

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6. Other Medications

• Blood pressure medications: ACE inhibitors like lisinopril or ARBs such as losartan, to help protect kidney health in patients with high blood pressure.

• Aspirin: Low-dose aspirin may be recommended daily to lower the risk of heart attacks in individuals with increased cardiovascular risk.

• Cholesterol-lowering drugs: Statins like atorvastatin are often prescribed to manage high cholesterol and reduce heart disease risk in diabetes.

7. Emerging Technologies

• Machine learning (AI): Predictive models suggest optimized insulin regimens.

• Closed-loop Systems: Fully automated insulin delivery adapts to individual needs (e.g., exercise, diet, illness).

• Virtual platforms: Simulate glucose responses to fine-tune decision-making algorithms.

8. Recent Advancements 

• Digital health management for T1D: Tools like continuous glucose monitoring (CGM) and insulin pumps help manage Type 1 Diabetes (T1D), but challenges like cost and insurance coverage limit their use.

• Smart insulin: Smart insulin self-regulates based on blood glucose levels, providing more personalized and efficient glucose control.

• Artificial pancreas: The artificial pancreas is a system that combines a glucose monitor and insulin pump to regulate insulin delivery automatically based on real-time glucose levels.

Home-care For Type 1 Diabetes

Home tips that can help manage T1D include:

1. Healthy Eating

• Follow a balanced diet tailored for diabetes, focusing on carbohydrate counting and glycemic control.

• Coordinate meals and insulin timing to prevent blood sugar fluctuations.

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What to eat 

• Fruits and vegetables like spinach, broccoli, berries, etc.

• Whole grains such as brown rice, quinoa, or whole-grain bread

• Lean proteins chicken, fish, tofu, or eggs.

• Healthy fats such as avocados, nuts, seeds, and olive oil.

• Low-glycemic carbs like lentils, chickpeas, sweet potatoes, etc.

• Low-fat or unsweetened options like almond milk for dairy alternatives.

What to avoid

• Sugary drinks: Soda, energy drinks, and sweetened juices.

• White bread, pastries, and sugary cereals.

• Fried foods, processed meats, and full-fat dairy.

• Packaged snacks, instant noodles, and canned soups.

• Excessive alcohol.

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2. Stay Active

• Engage in regular physical activity to help manage blood sugar levels.

• Monitor glucose levels before, during, and after exercise to avoid hypoglycemia or hyperglycemia.

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3. Take Care Of Your Mental Health

• Manage stress through mindfulness, yoga, or therapy, as stress can impact glucose levels.

• Seek support groups or counseling to cope with the emotional challenges of T1D.

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4. Focus On Foot Care

• Inspect feet daily for cuts, blisters, or sores, and maintain good hygiene.

• Wear comfortable, well-fitting shoes to prevent injuries.

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5. Be Alert For Complications

• Work with your healthcare provider to create a plan for managing blood sugar during illness.

• Stay hydrated and monitor glucose levels frequently.

Complications Of Type 1 Diabetes

If T1D is not managed properly it can lead to an array of complications. These can include:

Acute Complications

Hypoglycemia: Low blood sugar levels, causing symptoms like shakiness, confusion, and dizziness.

Diabetic Ketoacidosis (DKA): A life-threatening condition where the body produces high levels of blood acids (ketones) due to a lack of insulin, causing dehydration, nausea, and altered mental status.

Chronic Complications

Nephropathy: Kidney damage from high blood sugar, potentially leading to kidney failure.

Peripheral neuropathy: Nerve damage in the limbs, leading to pain, tingling, or loss of sensation, particularly in the feet and hands.

Autonomic neuropathy: Nerve damage affecting involuntary functions such as digestion, heart rate, and bladder control.

Retinopathy: Damage to the blood vessels in the eyes, potentially leading to vision loss.

Heart disease: Includes coronary artery disease, heart failure, and cardiomyopathy (weakness of heart muscles), all of which are more common in people with diabetes due to prolonged high blood sugar levels.

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Peripheral arterial disease: Narrowing of the arteries in the limbs, leading to poor circulation, pain, and increased risk of amputation.

Cerebrovascular disease: Includes stroke and transient ischemic attacks (TIAs are a temporary blockage of blood flow to the brain) caused by impaired blood flow to the brain.

Diabetic foot infections: Infections, often linked with poor circulation and neuropathy, can lead to severe complications like amputations if untreated.

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Alternative Therapies For Type 1 Diabetes

Alternative therapies for Type 1 Diabetes (T1D) are showing promising results in pre-clinical trials, with the potential to reverse or delay disease progression and reduce insulin dependency. They include:

1. Gene Therapy 

• It aims to treat T1D by modifying or introducing genes to reverse or prevent the disease. 

• It can involve adding new genes, replacing defective ones, or deactivating harmful genes.

• Methods include:

  • Direct gene delivery (using viral vectors).

  • Cell-based therapy (using stem cells modified with therapeutic genes).

2. Stem Cell Therapies 

• Stem cell research holds great potential for reversing Type 1 Diabetes (T1D) by regenerating insulin-producing beta cells.

• They include:

  • Embryonic stem cells (ESCs): ESCs have shown promise in generating insulin-producing cells and reversing diabetes in animal models, with advancements in creating safe, scalable protocols for clinical use.

  • Hematopoietic stem cells (HSCs): Stem cells from the patient's own blood are used to halt autoimmune destruction and restore immune tolerance in T1D treatment.

  • Mesenchymal stem cells (MSCs): Multi-potent cells that can repair tissues and may aid in improving insulin production in diabetic patients.

  • Umbilical cord blood (UCB)-derived MSCs: Stem cells from cord blood that can reduce autoimmunity and potentially preserve pancreatic function.

  • Wharton’s jelly-derived MSCs (WJ-MSCs): Stem cells from umbilical cord tissue with regenerative and immune-suppressive potential for T1D treatment.

3. Medical Nutrition Therapy (MNT)

• MNT is a personalized approach to managing Type 1 Diabetes through diet and nutrition. 

• It focuses on optimizing blood sugar levels and managing insulin doses.

• The goal is to balance carbohydrate intake with insulin administration to help maintain blood glucose levels within the target range.

4. Immunotherapy

• It aims to regulate the immune system to prevent β-cell destruction in the pancreas by using immune modulators or biologics.

5. Cell-Based Therapy

• This therapy involves transplanting pancreatic islet cells or β-cells to improve glucose control and reduce complications. 

• It consists of:

  • Islet transplantation: Transplanting healthy donor islet cells into T1D patients can improve glucose control and reduce hypoglycemia risk.

  • Combinational cell therapies: Approaches combining gene therapy and cell encapsulation are being explored to improve diabetes treatment by addressing the challenges of islet transplantation.

Living With Type 1 Diabetes

Living with diabetes can feel overwhelming at times, as it requires constant attention to blood sugar levels, diet, and lifestyle. Here are some practical tips to make daily management a little easier and improve your quality of life:

1. Keep A Check On Blood Glucose 

Regular blood glucose checks are vital in T1D management.  This can be done with:

•  Glucose meter: Use a blood glucose meter at least four times daily, including before meals and at bedtime.

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• Continuous glucose monitors (CGMs): CGMs provide real-time glucose readings and alarms for glucose fluctuations. These devices help predict trends and allow timely adjustments to avoid highs or lows.

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2. Learn More For Self-Management

• Effective T1D management requires continuous education on insulin, diet, physical activity, and glucose monitoring. 

• Individuals and caregivers must understand how these factors impact blood sugar levels.

3. Update Your Nutrition Education

• Learning carbohydrate counting is key to managing mealtime insulin doses. 

• Consulting a dietitian ensures accurate dosing while maintaining consistent carb intake improves glucose control.

4. Always Be Prepared

• Always carry fast-acting glucose like juice or tablets to treat low blood sugar. 

• Teach family and friends to identify and respond to hypoglycemia episodes.

5. Beware Of Hypoglycemia

• Repeated low blood sugar episodes can lead to unawareness of symptoms. 

• CGMs and proper education are crucial for prevention and timely treatment.

6. Give Importance To Follow-up Care

• The diabetes care team provides ongoing T1D education, assesses blood glucose control, and adjusts insulin regimens.

• Regular visits with key specialists like endocrinologists, educators, dietitians, and mental health professionals are also essential for comprehensive management.

7. Get Tested For Overall Health

Guidelines for routine follow-up tests:

• HbA1C testing: Every 3 months to monitor glucose control.

• Creatinine with eGFR: Measures kidney function by estimating how well the kidneys filter waste from the blood.

• Lipid profile: Once blood sugar stabilizes; repeat as needed based on treatment.

• TSH: Initially and as clinically indicated; varies with symptoms or treatment.

• Antithyroid antibodies panel: Test if symptoms appear; repeat as needed.

• Celiac antibody panel: Screen if symptoms are present or for periodic checks.

• Protein-to-creatinine ratio: Begin 5 years post-diagnosis; monitor as needed.