Type 1 Diabetes Mellitus

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) include:

• High blood sugar with ketones in urine
• Electrolyte imbalance leading to metabolic acidosis
• Fruity-smelling breath
• Severe lethargy or weakness
• In extreme cases, coma

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

• Genetics: Certain HLA genes, particularly HLA-DR3 and HLA-DR4, are associated with genetic predisposition linked to increased susceptibility to autoimmune beta-cell destruction.
• 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 Tidbit: 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.
• Age: T1D often develops in childhood or adolescence, but it can occur at any age.
• 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.)
• Autoimmune Conditions:
  • Thyroid disease
  • Celiac disease

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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): 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): 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): 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: Tests for autoimmune reactions that target the insulin-producing cells in the pancreas, helping diagnose Type 1 diabetes.
   • GAD total Antibody (Glutamic Acid Decarboxylase Autoantibodies): An autoantibody test used to help diagnose Type 1 diabetes, particularly in new-onset cases.

   Note: Diagnosis confirmation requires two abnormal results of hyperglycemia when 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: 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 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.

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 approximately 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.

6. Other Medications

   Blood pressure medications: ACE inhibitors like lisinopril or ARBs such as losartan 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 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.
   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.
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.
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.
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.
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.

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.
• 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), which are temporary blockages of blood flow to the brain caused by impaired blood flow.
• Diabetic foot infections: Infections often linked with poor circulation and neuropathy, which can lead to severe complications like amputations if untreated.

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 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.
   • 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.
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.