A Clinical Overview of Diabetes Types: Pathophysiology and Long-Term Impact

Diabetes mellitus is not a monolithic disease, but as a spectrum of various metabolic disorders. Each type has unique causes of elevated blood glucose levels. Whether it is an autoimmune response that attacks the pancreas, or a resistance to the insulin that is present, the diminishment of metabolic health is profound.

Achieving a deeper understanding of the unique pathophysiology of each type of diabetes is key to effective treatment. This clinical overview addresses the core three types of diabetes, the other rare and atypical types and the modern diabetes treatment and the life-altering complications it aims to delay.

1. The Pathophysiology of the Big Three

The core of each diabetes diagnosis is the hormone insulin. Insulin is produced by the beta cells of the pancreas. Insulin is the key hormone that facilitates the entry of glucose into cells and it’s utilization for energy. When this process is defective, glucose accumulates in the blood, resulting in the complications we associate with the disease.

Type 1 Diabetes: The Immune System Error

An autoimmune response occurs in type 1 diabetes when the body’s immune system attacks beta cells conceeding these cells to be foreign invaders. The body will no longer be able to produce insulin in the absence of beta cells. This type of diabetes often runs in families so a strong genetic link along with a suspected environmental trigger is common. Though observed primarily in the Pediatrics population, it can occur at any point in the age spectrum.

Type 2 Diabetes: The Insulin Deficiency

This form of diabetes accounts for 90%-95% of cases in the country. The primary problem in type 2 diabetes is a condition called insulin resistance. This is when body cells fail to respond to insulin. In a futile effort to make the cells respond, the pancreas produces insulin. When the pancreas can no longer produce insulin, the result is an increased blood sugar level. Significant family history, obesity, and a sedentary lifestyle can all be risk factors.

Gestational Diabetes: The Hormonal Shift

Gestational diabetes only occurs when someone is pregnant. The hormones released from the placenta affect the way the pregnant person uses insulin which causes issues with how they are able to regulate sugar glucose. Although this condition usually goes away after giving birth, it poses risks for the mom and the baby because they are both at a greater risk for developing Type 2 diabetes later in life.

2. Rare and Atypical Forms of Diabetes

In order to establish clinical authority, one must step outside common diagnoses and include the more “niche” types of diabetes that may require more specialized care.

• LADA (Latent Autoimmune Diabetes in Adults): Sometimes referred to as “Type 1.5” LADA is a slow-progressing autoimmune response. It is common to receive a diagnosis of Type 2 for LADA because it happens in adults. However, this is not the case. LADA patients will, at some point, require insulin because their beta cells are being destroyed, which is not the case in Type 2.
• Cystic Fibrosis Related Diabetes (CFRD): This is a specific form of diabetes that is only found in people with cystic fibrosis. The thick mucus that is characteristic of the disease may cause scarring of the pancreas and prevent it from making enough insulin.
• Brittle Diabetes: This is a type of Type 1 diabetes that has been diagnosed with severe and unpredictable fluctuations of blood glucose. It is extremely difficult to manage brittle diabetes, and this often includes the use of advanced continuous glucose monitoring devices.
• Neonatal Diabetes: This happens in the first six months of being born and is typically caused by a mutation in a single gene. It is not autoimmune like Type 1 Diabetes, and can sometimes be treated with oral meds instead of insulin.

3. Clinical Diagnosis and Monitoring

When it comes to the diagnostics for Diabetes, the American Diabetes Association (ADA), has put forth, the “Standards of Care,” which the clinicians then test against to be certain. It includes:

• Hemoglobin A1c: measures the average blood sugar over the course of 3 months.
• Fasting Plasma Glucose: After skipping 1 meal (which is 8 hours), blood is drawn and sugar levels are measured.
• Oral Glucose Tolerance Test (OGTT): after consumption of a sugary drink, the body’s response is measured. This is often used to tell if an expecting mother is likely to have gestational diabetes.

Revolutionary Advancements in Diabetes Technology

Recent developments allow modern technology in diabetes care to shift from passive, static diabetes technologies toward active, real-time data analytics and diabetes management as illustrated in the following examples.

• Continuous Glucose Monitors (CGM): Diabetes technology that provides real-time, streaming data on blood glucose levels and rates of change.
• Insulin Pumps: Devices that provide continuous subcutaneous insulin infusion (CSII) to allow for greater control over insulin delivery than that provided by standard insulin injections.

4. Complications of Diabetes Mellitus

Understanding the complications that arise from poor management of blood glucose levels and the resulting damage to the vascular system explains the need for tighter control on blood glucose levels, as elevated blood glucose levels are "toxic" to the vascular system. These diabetes complications are grouped into two categories — the microvascular and the macrovascular.

Microvascular Damage (Small Vessels)

• Retinopathy: Damage to the eye, which can result in blindness.
• Nephropathy: Damage to the kidney, which can progress to kidney disease and ultimately kidney failure.
• Neuropathy: Damage to the nerves, which may result in a tingling or numb feeling in the feet.

Macrovascular Damage (Large Vessels)

Chronic inflammation of the large blood vessels increases the likelihood of developing cardiovascular disease, stroke, and peripheral artery disease. This explains why control of blood pressure and cholesterol are equally important as control of blood glucose levels.

5. Strategies for Treatment and Prevention

A diabetes management plan that achieves the desired goals must be anchored in two fundamental approaches: lifestyle and pharmacotherapy.

Lifestyle: The Non-Negotiable Foundation

Long term positive effect on insulin sensitivity can be achieved through a healthy diet consisting of low glycemic (low carb) foods and physical exercise. Even for those at high risk, changing lifestyle habits can prevent the onset of type 2 diabetes for good.

Pharmacological Treatments

• Metformin: The first step of any type 2 diabetes management, it decreases the liver’s sugar output.
• SGLT2 Inhibitors: Work by aiding the kidneys in sugar secretion through urine.
• GLP-1 Agonists: Newer drugs that speed digestion and instruct pancreatic insulin secretion after eating.
• Insulin therapy: paramount in type 1 and LADA and in many cases, a must for the long management of type 2 diabetes.

Summary: Clinical Comparison Table

Appendix: Clinical Lab Guide & Technology Comparison

Two resources have been brought together for the sake of navigating diabetes care and for the sake of those who have not become patients, but remain empowered.

Part 1: Clinical Lab Results Guide

Clinical Note: Even though the American Diabetes Association sets these guidelines, your specific goal may vary depending on your age, if you are pregnant, or other health issues. Please be sure to go over your individual goals with your provider.

Part 2: Tech Comparison - CGM vs. Insulin Pumps

1. Continuous Glucose Monitors (CGM)

• What do they do? A small sensor is placed underneath the skin to monitor glucose levels in real time, with updates every few minutes.
• The Benefit: CGMs show “Trend Arrows”. A finger prick reading of 110 is less valuable than knowing your glucose is 110 and falling quickly.
• Popular Options: Dexcom G7, Abbott FreeStyle Libre 3.

2. Insulin Pumps

• What do they do? Insulin pumps provide a constant “basal” rate of insulin and allow for you to give “bolus” doses at mealtimes.
• The Benefit: They come closer to mimicking the body’s natural patterns of beta cells than multiple injections do. This reduces the risk of experiencing severe hyperglycemia and hypoglycemia at night.
• Popular Options: Omnipod 5 (tubeless), Tandem t:slim X2.

3. The “Closed Loop” System

The best way of treating diabetes currently is through an Automated Insulin Delivery (AID) system. This means your CGM is “talking” to your Insulin Pump. The CGM sees your sugar go up, and instructs the pump to increase insulin. This is one way to help reduce the risks of heart and kidney disease.

Next Steps for You

Taking charge of your metabolic health is an ongoing process. Now that you have some insight into the types and the technology:

• Request a Lab Review: If you have not done an A1c test in the last 6 months, it’s time to do one.
• Audit Your Tech: If you are still using finger pricks, ask your doctor if you can get a CGM and if it will be covered by your insurance.
• Refine Your Diet: Make sure to include a healthy diet and physical activity in order to help your medication do its job.

Conclusion: Taking a Proactive Stance

Diabetes mellitus is a life-altering diagnosis, but it is not a sentence to poor health. By understanding the specific form of diabetes you are dealing with—whether it's the autoimmune challenges of Type 1 or the metabolic hurdles of Type 2—you can build a targeted defense.

A doctor's insight: "When I explain my patient's BMI to them, I tell them that it is like the check engine light in a car. It signals the owner to see what the problem is, but does not indicate what the problem is. To better understand what I mean, we have to look at your sleep, stress, diet and exercise and blood work before we can decide what path to take."

Prioritizing a healthy diet, utilizing continuous glucose monitors, and staying informed on American Diabetes Association standards will ensure that you can manage your blood glucose levels and lead a full, active life. Knowledge is the ultimate tool for diabetes prevention and long-term wellness.

For more information, visit these clinical resources:

• NIDDK: What is Diabetes?
• WHO: Diabetes Fact Sheet
• Mayo Clinic: Symptoms and Causes