Insulin, glucose and diabetes

What is insulin, how does it act, and why do we need it?

Insulin is a hormone that is produced in the pancreas and released to the blood in response to increasing glucose (sugar) levels after eating.

Insulin is incredibly important for us because it allows our body to store glucose, one of our main energy sources.

Insulin triggers the uptake of glucose into muscle and fat cells. Insulin actions on the liver, muscle, and fat tissue regulate the production of the major energy storage units of the human body: glycogen and fat/lipids. These energy sources are utilized by our bodies throughout the day in all kinds of activities.

What happens if the body stops producing insulin?

Without insulin, our body loses the capacity to properly manage its energy sources. Because glucose is no longer entering our muscle and fat cells, the glycogen and lipid stores inside these cells get eventually depleted. This results in loss of weight, feeling of weakness and constant hunger (polyphagia). High levels of circulating glucose (hyperglycemia) cause changes in the refractive properties of the lenses in our eyes, which leads to blurred vision. Our body attempts to bring blood glucose levels down by excreting it through the kidneys in urine. This, in turn, leads to frequent urination (polyuria) and constant feeling of thirst (polydipsia).

Is this familiar to you? It certainly is to me. This conjunction of symptoms is what makes most people go to a healthcare facility in the first place and ultimately discover they have diabetes.

In case of prolonged absence of insulin, because the body is no longer able to use glucose as an energy source, the metabolism is shifted towards using fatty acids and ketones instead. The increased production of ketone bodies reduces blood pH, which can lead to diabetic ketoacidosis (DKA). This is a potentially life-threatening complication of diabetes characterized by abdominal pain, vomiting, confusion, and loss of consciousness in addition to the symptoms described above. DKA is still unfortunately an all-too-common presentation of newly diagnosed diabetic patients, particularly children.

What is diabetes?

Diabetes is a pandemic of enormous proportions affecting more than 500 million people worldwide – that’s more than 1 in 10 human beings on the planet – and growing.

Diabetes is not one but rather a group of metabolic disorders characterized by hyperglycemia due to the body’s loss of capacity to regulate blood glucose levels. In all diabetes types the insulin hormone takes center stage – this is because in diabetes there are generally issues with insulin production, or problems with the tissues in our body responding to insulin action, or both. Broadly, the different diabetes types can be distinguished by the different causes that lead to disease onset and on its manifestation (for instance, presence of autoimmunity or not). Among the many types of diabetes, type 1 and type 2 are the most common. There is no cure for diabetes. The major goal in diabetes management is to maintain blood glucose levels within the desired target range.

One of the many dark sides of diabetes is the fact that people with diabetes are at increased risk of developing cardiovascular and neurological complications even when they are able to maintain blood glucose levels within the desired target range for years.

What are the different types of diabetes?

Type 1 diabetes (T1D)

Autoimmune disorder marked by the loss of insulin-producing beta-cells that reside in the islets of Langerhans in the pancreas. It makes 5-10% of all diabetes cases and is characterized by the inability of the body to produce sufficient insulin to regulate blood glucose levels. People with type 1 diabetes are dependent on the administration of insulin to survive – this is typically done by multiple daily injections of insulin with insulin pens or using insulin pumps that continuously release insulin into the body.

The pathophysiology of type 1 diabetes is highly complex. Many factors, including genetic, immune, and environmental influences contribute to disease development. Among the environmental influences, dietary factors, vitamin D deficiency, viral infections, and even the gut microbiome composition are implicated in triggering this disorder.

Type 1 diabetes is also known as immune-mediated diabetes, insulin-dependent diabetes, and has historically been called juvenile-onset diabetes – this term is outdated since it is now known that the incidence of type 1 diabetes in adulthood can be as high as in juveniles.

Type 2 diabetes (T2D)

The most common type, affecting around 90-95% of people with diabetes. It is caused by a combination of genetic, metabolic, and environmental factors that lead to increased resistance to insulin action, deficient pancreatic insulin secretion, and defective compensatory response for insulin secretion.

The risk of developing type 2 diabetes increases with age and is more common in people with low levels of physical activity and high levels of body fat, particularly in the abdominal region.

In contrast to type 1 diabetes, there is no autoimmune involvement in the pathophysiology of type 2 diabetes, and patients do not depend on insulin administration to survive (at least in the initial stages of the disease).

Latent Autoimmune Diabetes of Adults (LADA)

Generally described as a new diabetes diagnosis after the age of 30 where patients do not require insulin treatment for at least 6 months but are positive for anti-islet autoantibodies.

The presence of clinical features that are typically associated either with type 1 and type 2 diabetes results in a highly heterogeneous group with clinical and genetic features that are intermediate to the two classic diabetes types – this has led to LADA being known as type 1.5 diabetes. In fact, the World Health Organization has categorized the condition as a “hybrid form of diabetes” and named it “slowly evolving immune-mediated diabetes”. It is still unclear whether LADA is a disease syndrome where the pathophysiologies of type 1 and type 2 diabetes are both present in each patient, or whether it results from difficulties in disease classification.

An important concern originating from the overlapping clinical features of LADA with both type 1 and type 2 diabetes is that of misdiagnosis: some people with true type 2 diabetes are misdiagnosed as LADA and conversely, people with true LADA are misdiagnosed as type 2 diabetics. This is of particular concern in people with body-mass index (BMI) that is out of the typical range for each diabetes type.

Gestational diabetes mellitus (GDM)

During pregnancy, the increase in body fat and the growing fetus causes a natural increase in insulin resistance in women’s bodies. This triggers a natural compensatory response whereby insulin-producing beta-cell numbers and size increase and more insulin is secreted in response to glucose. Gestational diabetes mellitus occurs when this compensatory mechanism fails and insulin production is not upregulated during the second/third trimester of pregnancy.

Gestational diabetes is estimated to occur in 6-14% of all pregnancies worldwide and its risk increases with age, body weight, physical inactivity, among other factors. Gestational diabetes typically resolves after delivery, but is associated with an increased risk of developing type 2 diabetes later in life for both the mother and the child. Adoption of improved nutrition practices and higher levels of physical activity are first-line approaches to tackling gestational diabetes.

There are many other specific types of diabetes:

Among others, these can be caused by:

Mutations in genes important for the normal function of insulin-producing beta cells (which leads to maturity-onset diabetes of the young; MODY), or mutations in the insulin gene and the receptors to which insulin binds to;

Disorders that extensively affect pancreatic function, such as pancreatic carcinoma, or the surgical removal of the pancreas (pancreatectomy);

Certain viral infections;

Drugs and chemical compounds that impair insulin secretion or insulin action.

How is diabetes treated?

People with type 1 diabetes will have insufficient production of insulin and will rely on insulin injections to survive as their main line of treatment.

The amount of insulin required to maintain blood glucose levels within the desired target range will vary throughout the progression of the disease; for instance, there can be revitalization of beta-cell function during the period immediately after diagnosis that leads to low insulin requirements – this is known as the “honeymoon” period and it typically lasts longer in adults compared to children diagnosed with type 1 diabetes.

The factors that influence the insulin amounts required to cover a particular meal or even during a particular day are numerous. Among many others, aspects related to the meal composition, to the way the meal was cooked, sleep quality, social interactions, the time of day, the type, amount, and time of insulin injected prior, all of these influence the decisions implicated in diabetes management.