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What is Diabetes Mellitus?

Diabetes is a metabolic disease that is characterized by the presence of great amounts of sugar (glucose) in the blood. This high blood glucose level is the result of the body’s inability to process or metabolize carbohydrates. This glucose comes from the food that we eat that is digested and absorbed in the digestive tract. This sugar then enters the blood from the digestive system, which is then distributed throughout the body to become transported into our body cells for regular energy needs. Our body systems and organs can’t function without glucose. So, when the glucose can’t be transported to or utilized by our body organs, tissues, or cells, then most of the body becomes dysfunctional.

The hormone that regulates the transport of glucose from the blood to the inside of our cells is called insulin. Insulin is primarily secreted from special cells in the pancreas, which is responsible for regulating the blood sugar levels. When there is too much sugar in our blood, the pancreas secretes more insulin, and when there is little glucose in our blood, the pancreas secretion of insulin becomes limited.

Patients with diabetes have problems with either insulin secretion from the pancreas or because the secreted insulin is dysfunctional and can’t transport glucose to cells. That is why diabetes is divided into two main categories: type I diabetes mellitus, where there is not enough insulin secretion, and type II diabetes mellitus, where the secreted insulin does not work properly. However, in both types of diabetes, the issue remains the same, where there are high levels of sugar in our blood.

With the inability to properly get glucose inside the cells, they become to starve, and the sugar becomes deposited in the blood vessel walls. This long-term process causes very harmful effects on every organ in our bodies, including heart diseases, kidney diseases, liver problems, and many other systems.

Type I Diabetes Mellitus

In this type of diabetes, the main issue is with insulin secretion, where the pancreas can’t secrete the required amounts of insulin on a regular basis. It is also often seen in young children; that’s why it is referred to as “juvenile diabetes” or “insulin-dependent diabetes”.

The beta cells of the pancreas, which secrete insulin, become dysfunctional in this type of diabetes. Insulin then becomes secreted in very low or no amounts at all. Therefore, patients with type I diabetes are conventionally treated with insulin injections, which are used for the rest of their lives because the damage to the beta cells of the pancreas can’t be fixed.

It is important to note that patients with type I diabetes who are not treated with insulin can suffer from very harmful complications that can potentially lead to death if not properly treated. If the patient is not receiving insulin, then glucagon (a hormone that opposes the action of insulin) will stimulate the liver to provide glucose. However, this process will involve the development of many ketone bodies and acids, which will eventually result in an emergency condition called “diabetic ketoacidosis”. In this condition, the patient becomes unaware of the surroundings. His body starts to go into a shock-like state, where the kidneys, liver, heart, and other organs are severely affected. This condition, if it happens, requires immediate medical attention.

Unfortunately, cannabidiol (CBD) does only offer mild benefit for these patients and can’t be used to manage this condition. Other drugs are used, under close medical observation, to manage this condition.

Type II Diabetes mellitus

Type II diabetes, or type 2 diabetes, often occurs in adults. That is why it is often referred to as “adult-onset diabetes”. This type of diabetes is not caused by the lack of secretion of insulin from the beta cells of the pancreas. The pancreas is well-functioning and secretes regular amounts of insulin. However, the secreted insulin can’t exert its action at the target cells of the body. That is why it is referred to as “non-insulin-dependent diabetes”.

It is thought that this type of diabetes occurs due to genetic predisposition, and that is why the onset of this disease is slow and gradual. Researchers think that this type of diabetes is mainly caused by poor diet and poor lifestyle habits.

As people eat, the digestive tract starts to breakdown food into various nutrients, including sugar, which will then be absorbed into the blood. This results in a high amount of sugar in our blood, and that is why we feel energized directly after we have our meals. Then, the pancreas starts secreting insulin to get the glucose in the blood to the inside of the cells in order to maintain a normal blood sugar level: too much is harmful, and too little is bad as well.

Noteworthy, if we eat food that contains high amounts of simple sugars like candy, the food becomes digested very fast, and the secreted insulin will transport the glucose out of the blood very quickly. With the resulting low blood glucose levels, we feel fatigued. This is often referred to as a crash after a meal. Over the years, if this dietary habit is repeated, the body will get trained to ignore the insulin that is being secreted from the pancreas. The insulin has then no function. This process is also hypothesized to be modulated by other factors as well. Eventually, the person starts to develop diabetes type II, with high sugar amounts in the blood. In this stage, the patient is known to be insulin resistant (insensitive), which is the first step towards type II diabetes mellitus.

How is Diabetes Treated?

There are many drugs that can be used in patients with different types of diabetes. Occasionally, patients with type I diabetes are treated with insulin, while patients with type II diabetes are treated with antidiabetic drugs.

These drugs include the following:

  1. Diet: Mediterranean diet is known as the most evidence-based supported diet in patients with type II diabetes.
  2. Metformin: it improves the sensitivity to insulin.
  3. Sulfonylureas: it increases the release of insulin from beta-pancreatic cells.
  4. Meglitinides: they increase the release of more insulin.
  5. Thiazolidinediones: it improves the sensitivity to insulin.
  6. DPP-4 inhibitors: they increase the level of insulin.
  7. GLP-1 receptor agonists: they minimize the rate of glucose absorption by the digestive system.
  8. SGLT2 inhibitors: they prevent the kidney from reabsorbing the secreted glucose.
  9. Insulin: it is often provided to patients with type I diabetes and patients with type II diabetes in their late stages or during complications.

These drugs are prescribed based on the patient’s medical condition and his/her response to the prescribed drug. Sometimes, these drugs become ineffective, and the patient condition worsens. Therefore, researchers are investigating new drugs that may target the primary cause of diabetes and solve the life-long suffering of those patients. Cannabidiol (CBD) is being investigated as one of the options that can potentially help cure diabetes in the near future.

The Endocannabinoid System and Diabetes

Cannabinoids are present inside our bodies in the form of endocannabinoids. These endocannabinoids combine with target cannabinoid receptors type 1 (CB1) and type 2 (CB2) to form the Endocannabinoid system (ECS), which is involved in many physiological processes, including inflammation, pain, and many others.

Experimental evidence and clinical trials have clearly shown that ECS plays a key role in the development of primary diabetes and various diabetic complications.

Recent preclinical studies showed that peripherally restricted CB1 antagonists might represent a viable therapeutic strategy.

The inhibition of CB1 receptors may directly minimize the inflammatory response in diabetes and reduce the generation of reactive oxygen species (ROS) and reactive nitrogen species in endothelial cells, immune cells, and other cell types. These are key pathogenic pathways for diabetes development. CB1 inhibition is also reported to play a key role in controlling diabetes complications.

The Cannabinoid Receptors and the Development of Diabetes

It is proposed that CB1 receptor activation is involved in the development of diabetes and diabetic complications. CB1 receptor activation may indirectly (via its metabolic consequences) or directly enhance diabetes-associated inflammation and ROS generation, promoting tissue injury and the development of diabetic complications.

Current Trends in Treating Diabetes and its Complications by Cannabinoids

CB2 agonists may exert beneficial effects on diabetes and diabetic complications by attenuating inflammatory response and reducing the associated oxidative stress.

Natural cannabinoids, such as CBD and tetrahydrocannabinol (THC), have tremendous therapeutic potential in the management of diabetes and its complications.

CBD oil for sublingual use and its derivatives, which may combine the beneficial effects of simultaneous CB1 inhibition and CB2 stimulation, are still under intense preclinical investigation.

It will be of great interest to see how newly developed, peripherally restricted CB1 receptor antagonists and/or CB2 receptor agonists and certain natural cannabinoids, such as CBD and THC, will influence the clinical outcomes of diabetic patients.

CB2 receptor stimulation may exert beneficial effects against various diabetic complications by attenuating high glucose-induced endothelial cell activation and inflammatory response; chemotaxis, transmigration, adhesion, and activation of inflammatory cells; and subsequent proinflammatory responses and ROS generation.

Type II Diabetes Mellitus and Cannabidiol

In a randomized, double-blinded, placebo-controlled study, a total of 62 patients with type-2 DM were randomized to 5 treatment arms: CBD (100 mg twice daily), Δ9-tetrahydrocannabivarin (THCV) (5 mg twice daily), 1:1 ratio of CBD and THCV (5 mg/5 mg, twice daily), 20:1 ratio of CBD and THCV (100 mg/5 mg, twice daily), or matched placebo for 13 weeks.

The results showed that in comparison with placebo, THCV significantly reduced fasting plasma glucose and improved pancreatic β-cell function, adiponectin, and apolipoprotein A. However, plasma HDL was unaffected.

Compared to baseline (not placebo), CBD decreased resistin and increased glucose-dependent insulinotropic peptide. Both treatments were well tolerated.

Even though CBD failed to show any detectable metabolic effects, it produced desirable changes in some adipokines and gut hormone concentrations. Therefore, both treatments are warranted further investigation as new therapeutic agents for glycemic control in patients with type II diabetes.

Type I Diabetes Mellitus and Cannabidiol

In an experiment on non-obese diabetic (NOD) mice to investigate the impact of CBD treatment on early pancreatic inflammation in type I diabetes by intravital microscopy (IVM), seven-week-old female NOD mice were prophylactically administered daily 5 mg/kg CBD or control (five times weekly for ten weeks).

Animals underwent IVM after confirmation of T1D diagnosis by blood glucose testing. Leukocyte activation and functional capillary density (FCD) were quantified by IVM.

The results showed promising effects of CBD of markers of inflammation in the microcirculation of the pancreas, where non-treated NOD mice developed T1D earlier than CBD-treated mice. Also, CBD-treated mice showed significantly reduced leukocyte activation and increased FCD in the pancreatic microcirculation.

There have been many animal studies that investigated the effects of CBD on controlling the development and progression of diabetes. Here is a summary of the major findings of many animal models of diabetes treated with CBD.

Disease Model Dose of CBD CBD Effect Reference
Diabetes Mellitus STZ-induced diabetic SD rats 10 mg/kg for up to 4 weeks Reduction in diabetes-induced hyperpermeability El-Remessy et al., 2006
Reduction in inflammation
Reduction in oxidative stress
Reduction in vascular endothelial growth factor
High glucose treated human coronary artery endothelial cells 0-6 μM, 48 hours incubation Reduction in ICAM-1 and VCAM-1 Rajesh et al., 2007
Reduction in monocyte adhesion and trans-endothelial migration
Reduction in disruption of endothelial barrier
Reduction in superoxide production
Reduction in inflammation
STZ-induced diabetic mice 20 mg/kg for 11 weeks Reduction in left ventricular dysfunction Rajesh et al., 2010
Reduction in myocardial oxidative stress
Reduction in myocardial inflammation
Reduction in myocardial fibrosis
Reduction in myocardial nitrative stress

A Take-Home Note

Based on a recent survey of medical cannabis use for the treatment of various medical conditions, it was reported that cannabinoids were used by 16 individuals (out of 2032 surveyed people) for their diabetes condition.

Despite the low use of CBD in diabetes, there are many promising effects of CBD in controlling this condition. However, more studies are still needed to reach a final conclusion about its effectiveness in patients with diabetes compared to those treated with placebo in well-conducted randomized controlled trials.

  • https://pubmed.ncbi.nlm.nih.gov/30460546/
  • https://pubmed.ncbi.nlm.nih.gov/16849753/
  • https://pubmed.ncbi.nlm.nih.gov/24923339/
  • https://pubmed.ncbi.nlm.nih.gov/32052321/
  • https://pubmed.ncbi.nlm.nih.gov/26883879/
  • https://pubmed.ncbi.nlm.nih.gov/25503438/
  • https://pubmed.ncbi.nlm.nih.gov/23410498/

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