Introduction to Diabetes Mellitus

What is Diabetes? 

Diabetes is a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. Insulin is a hormone that regulates blood glucose. Hyperglycaemia, also called raised blood glucose or raised blood sugar, is a common effect of uncontrolled diabetes and over time leads to serious damage to many of the body's systems, especially the nerves and blood vessels.

Glucose (sugar) mainly comes from carbohydrates in your food and drinks. It’s your body’s go-to source of energy. Your blood carries glucose to all your body’s cells to use for energy.

When glucose is in your bloodstream, it needs help — a “key” — to reach its final destination. This key is insulin (a hormone). If your pancreas isn’t making enough insulin or your body isn’t using it properly, glucose builds up in your bloodstream, causing high blood sugar or “hyperglycaemia”.

Diabetes affects people of all ages. Most forms of diabetes are chronic (lifelong), and all forms are manageable with medications and/or lifestyle changes.

What are the types of diabetes?

There are several types of diabetes. The most common forms include:

• Prediabetes: This type is the stage before Type 2 diabetes. Your blood glucose levels are higher than normal but not high enough to be officially diagnosed with Type 2 diabetes.
• Type 1 Diabetes: This type is an autoimmune disease in which your immune system attacks and destroys insulin-producing cells in your pancreas for unknown reasons. Up to 10% of people who have diabetes have Type 1. It’s usually diagnosed in children and young adults, but it can develop at any age.
• Gestational diabetes: This type develops in some people during pregnancy. Gestational diabetes usually goes away after pregnancy. However, if you have gestational diabetes, you’re at a higher risk of developing Type 2 diabetes later in life.

Type 2 Diabetes: With this type, your body doesn’t make enough insulin and/or your body’s cells don’t respond normally to the insulin (insulin resistance). This is the most common type of diabetes. It mainly affects adults, but children can have it as well.

Other types of Diabetes include:

• Type 3c Diabetes: This form of diabetes happens when your pancreas experiences damage (other than autoimmune damage), which affects its ability to produce insulin. Pancreatitis, pancreatic cancer, cystic fibrosis and hemochromatosis can all lead to pancreas damage that causes diabetes. Having your pancreas removed (pancreatectomy) also results in Type 3c.
• Latent autoimmune diabetes in adults (LADA): Like Type 1 diabetes, LADA also results from an autoimmune reaction, but it develops much more slowly than Type 1. People diagnosed with LADA are usually over the age of 30.
• Maturity-onset diabetes of the young (MODY): MODY, also called monogenic diabetes, happens due to an inherited genetic mutation that affects how your body makes and uses insulin. There are currently over 10 different types of MODY. It affects up to 5% of people with diabetes and commonly runs in families.
• Neonatal diabetes: This is a rare form of diabetes that occurs within the first six months of life. It’s also a form of monogenic diabetes. About 50% of babies with neonatal diabetes have the lifelong form called permanent neonatal diabetes mellitus. For the other half, the condition disappears within a few months from onset, but it can come back later in life. This is called transient neonatal diabetes mellitus.
• Brittle diabetes: Brittle diabetes is a form of Type 1 diabetes that’s marked by frequent and severe episodes of high and low blood sugar levels. This instability often leads to hospitalization. In rare cases, a pancreas transplant may be necessary to permanently treat brittle diabetes. (https://my.clevelandclinic.org/health/diseases/7104-diabetes) 

What is the pathophysiology of diabetes?

A patient with DM has the potential for hyperglycaemia. The pathology of DM can be unclear since several factors can often contribute to the disease. Hyperglycaemia alone can impair pancreatic beta-cell function and contributes to impaired insulin secretion. Consequentially, there is a vicious cycle of hyperglycaemia leading to an impaired metabolic state. Blood glucose levels above 180 mg/dL are often considered hyperglycaemic in this context, though because of the variety of mechanisms, there is no clear cutoff point. Patients experience osmotic diuresis due to saturation of the glucose transporters in the nephron at higher blood glucose levels. Although the effect is variable, serum glucose levels above 250 mg/dL are likely to cause symptoms of polyuria and polydipsia.

Insulin resistance is attributable to excess fatty acids and proinflammatory cytokines, which leads to impaired glucose transport and increases fat breakdown. Since there is an inadequate response or production of insulin, the body responds by inappropriately increasing glucagon, thus further contributing to hyperglycaemia. While insulin resistance is a component of T2DM, the full extent of the disease results when the patient has inadequate production of insulin to compensate for their insulin resistance. 

Chronic hyperglycaemia also causes nonenzymatic glycation of proteins and lipids. The extent of this is measurable via the glycation haemoglobin (HbA1c) test. Glycation leads to damage in small blood vessels in the retina, kidney, and peripheral nerves. Higher glucose levels hasten the process. This damage leads to the classic diabetic complications of diabetic retinopathy, nephropathy, and neuropathy and the preventable outcomes of blindness, dialysis, and amputation, respectively.

(https://www.ncbi.nlm.nih.gov/books/NBK551501/) 

What are the symptoms of Diabetes?

Diabetes symptoms depend on how high your blood sugar is. Some people, especially if they have prediabetes, gestational diabetes or type 2 diabetes, may not have symptoms. In type 1 diabetes, symptoms tend to come on quickly and be more severe.

Some of the symptoms of type 1 diabetes and type 2 diabetes are:

• Feeling more thirsty than usual.
• Urinating often.
• Losing weight without trying.
• Presence of ketones in the urine. Ketones are a byproduct of the breakdown of muscle and fat that happens when there's not enough available insulin.
• Feeling tired and weak.
• Feeling irritable or having other mood changes.
• Having blurry vision.
• Having slow-healing sores.
• Getting a lot of infections, such as gum, skin and vaginal infections.

Type 1 diabetes can start at any age, often starts during childhood or teen years. Type 2 diabetes can develop at any age, more common in people older than 40.  (https://www.mayoclinic.org/diseases-conditions/diabetes/symptoms-causes/syc-20371444)