What Is the Pathophysiology of Type I Diabetes Mellitus?

Common risk factors for type I diabetes mellitus include

• Age: Type I diabetes mellitus is common in children and adolescents, although the disease can occur at any age. It is now understood to develop slowly over months or even years. The immune system gradually destroys more and more insulin-producing (beta) cells in the pancreas, eventually leading to the diagnosis of type I diabetes.
• Self-allergy (autoimmunity): Type I diabetes is more likely to develop if you have an autoimmune disorder. Doctors can screen for diabetes antibodies, particularly GAD65. Early detection of this antibody can help your doctor determine if you have type I or II diabetes.
• Genes: People with type I diabetes are more likely to have inherited genes that put them at risk. Over 50% of people diagnosed with type I diabetes have a close family with the condition. 
• Environmental factors: Certain viral infections have been linked to an increased risk of type I diabetes.

It is not fully understood why some people get type I diabetes. Doctors and scientists believe that there is a genetic factor, but possessing diabetes genes is unlikely to be enough to cause the disease to develop. Scientists are investigating whether additional factors such as viral infections, birth weight, or nutrition may make someone who already has the genes for type I diabetes more likely to develop it.

Type I diabetes can develop gradually or unexpectedly. Sometimes, symptoms may not be present and the disease is only diagnosed when blood or urine tests are performed for other reasons. Other times, the person lands in an intensive care unit due to a sudden loss of consciousness or diabetic coma.

Early signs of type I diabetes mellitus include:

• Weight loss or poor weight gain, even when eating a large amount of food
• Increased thirst
• Frequent urination
• Enuresis (bed wetting)
• Constant fatigue
• Fungal infections over the body

Later signs of type I diabetes mellitus include:

• Dry skin and mouth
• Difficulty breathing
• High blood sugar (above 126 mg/dL)
• Loss of appetite
• Fruity-smelling breath odor
• Stomach pain

According to the American Diabetes Association, 1.6 million Americans have type I diabetes, including 187,000 children and adolescents. Type I diabetes mellitus is less common than type II diabetes mellitus, accounting for 5%-10% of all diabetes cases in the United States.

The objective of type I diabetes treatment is to keep your blood sugar levels as close to normal as possible to delay or prevent consequences. The goal is to keep your daytime blood sugar levels before meals between 80 and 130 mg/dL (4.44 to 7.2 mmol/L). Post-meal numbers should be no higher than 180 mg/dL (10mmol/L) two hours after eating.

Anyone with type I diabetes needs insulin therapy for the rest of their lives. Types of insulin available for treating diabetes include:

• Short-acting (regular) insulin
• Rapid-acting insulin
• Intermediate-acting insulin
• Long-acting insulin

Insulin cannot be administered orally to reduce blood sugar because stomach enzymes will break it down, preventing it from working. You will have to get it through injections or an insulin pump.

• Injections: To inject insulin under your skin, you can use a small needle or an insulin pen. Insulin pens resemble ink pens and are available in disposable or refillable forms. If you opt for injections, you'll most likely require a variety of insulin types to use during the day and night. Multiple daily injections of long-acting insulin mixed with rapid-acting insulin more closely replicate the body's natural utilization of insulin than prior insulin regimens requiring only one or two doses each day. A daily insulin injection schedule of three or more doses has been demonstrated to enhance blood sugar levels.
• Insulin pump: This can be worn on the exterior of your body. A tube links an insulin reservoir to a catheter implanted beneath the skin of your belly. Wireless pumps are also available. You wear a pod on your body that stores the insulin reservoir and has a small catheter implanted beneath your skin. The insulin pod can be worn on your stomach, lower back, leg or arm. Pumps are set to automatically deliver particular doses of rapid-acting insulin. This continuous dose of insulin is referred to as your basal rate, and it substitutes any long-acting insulin you were previously receiving. When you eat, you configure the pump with the number of carbs you're eating and your current blood sugar level, and it will provide a bolus dosage of insulin to cover your meal and correct your blood sugar if it's elevated. According to certain studies, an insulin pump may be more efficient than injections in regulating blood sugar levels in some people. However, many people attain normal blood sugar levels using injections. 
• Artificial pancreas: The FDA has authorized the first artificial pancreas for people aged 14 years and older with type I diabetes. It is also known as closed-loop insulin delivery. The implanted gadget connects an insulin pump to a continuous glucose monitor, which examines blood sugar levels every five minutes. When the monitor shows that insulin is required, the device automatically provides the appropriate dose. There are currently more artificial pancreas (closed loop) devices in clinical testing.

Possible complications of type I diabetes mellitus, if left untreated, include:

• Nausea
• Diarrhea
• Vomiting
• Diabetic ketoacidosis

Untreated type I diabetes can cause organ failure, coma, and even death. Because the body can no longer convert glucose into fuel, it begins to burn fat, which creates ketones in the blood and urine. Too many ketones can alter the pH of the blood, resulting in a potentially fatal disease called diabetic ketoacidosis.

Type I diabetes is not preventable. However, some researchers believe it may be stopped at the latent autoimmune stage before the beta cells are destroyed:

• Immunosuppressive drugs:
  • Cyclosporine A is an immunosuppressive drug that appears to slow beta cell death (based on lower insulin consumption), but its renal toxicity and other adverse effects render it unsuitable for long-term use.
  • In people with newly diagnosed type I diabetes, anti-CD3 has shown indications of insulin production preservation (as evidenced by maintained C-peptide production). However, how long it is effective is unclear.
• Diet:
  • Some research suggests that breastfeeding reduces the risk of islet cell autoantibodies later in life.
  • Early introduction of gluten-containing cereals to the diet increases the risk of islet cell autoantibodies.
  • Giving infants 2,000 IU of vitamin D per day for the first year of their lives is linked to a lower incidence of type I diabetes.
  • Children who may be susceptible to type I diabetes mellitus may be given niacinamide (vitamin B3), because niacinamide (vitamin B3) may help delay the progression of type I diabetes mellitus.
  • When followed properly, a gluten-free diet reduces diabetes symptoms and appears to prevent the development of long-term problems.
  • Other dietary risk variables are being investigated, but no conclusive evidence has been discovered.