When I first started medical school, I remember clearly one patient among hundreds. At the time, we were studying some clinical cases in an endocrinology department. It's a branch of medicine that deals with pathological dysfunctions of endocrine glands and hormones, due to the frequency of diabetes, nearly half of our patients were suffering from unbalanced diabetic states (Ketoacidosis, hyperglycemia, hypoglycemia etc..).

All of them were asking questions about managing their symptoms and taking their treatment but there was this one patient who thought differently. He wanted to know if there is any hope of a complete remission? What do you think? Personally, I never heard of a diabetic person who returned to a non-diabetic state. The doctor's answer was of course negative, he couldn't give him false hopes but what if there is really a cure? 

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The Very Unique Hormone 

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Your pancreas is a vital organ found in your abdomen, it has a double function secreting enzymes for digestion and secreting two important hormones: Insulin and Glucagon. For the purpose of the article, we will only stick with insulin, you probably heard a couple of times in your life but why it's so damn important? Simply because it's the only hormone in the body capable of decreasing blood sugar levels.

Insulin is a hormone produced by specific cells called beta cells found in pancreas, it has so many metabolic functions, perhaps the most important is allowing the entrance of glucose to the cells by activating the synthesis of GLUT4 channels in the cell's membrane, so basically without insulin, cells cannot use glucose, therefore, they become hungry and unable to function properly.

It also stimulates the storage of glucose in the liver within a process called glycogenesis which is the synthesis of long chains of glucose called glycogens used later when blood sugar levels drop. The extra carbohydrates become fats in the adipocytes, we call this process lipogenesis. 

So many other functions deserve to be mentioned, check this link for more details. 

When we eat a meal, sugar levels rise dramatically and beta cells start releasing insulin into the bloodstream. There are two main phases of insulin secretion, a rapid phase where the stored insulin is diffused, this phase is very short and starts even before the ingestion of the meal. In fact when we see something delicious or when we know that we're going to have a meal soon, the parasympathetic nervous system takes action, saliva increases, the digestive system becomes more active and insulin production begins. The second phase is a continuous, progressive phase and can last longer, it's a direct result of the present activity of beta cells. This biphasic model of insulin production stands for the majority of healthy mammals, we will see how it can be disrupted by diabetes mellitus.

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Diabetes mellitus in a nutshell

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Diabetes is the most frequent metabolic disease all over the world, it's characterized by a chronic hyperglycemia (high levels of blood sugar) which can cause a remarkable dehydration seen in diabetic persons. The clinical traduction of this dehydration is the couple polyuria/polydipsia with variable severity depending on the levels of the blood sugar, but what causes this hyperglycemia in the first place?

Many public opinions are inaccurate, diabetes comes in different types and each one has it own treatment, we'are only going to discuss the two main types diabetes type 1 and type 2. Type 1 diabetes is rare and only 10 % of diabetic persons suffer from it, it's caused by a mass destruction of beta cells by an auto-immune process thus a lack in insulin, it hit at a young age and we don't know exactly why it happens, all we know is that our own immune system is to blame. Symptoms are only seen if more than 90 % of the cells are destroyed because at the beginning the pancreas has a capacity to substitute the lack of insulin. The basic symptomatic treatment is simply a specific administration of insulin-regulated by the time of the meals unless we invent an artificial pancreas or we restore the missing beta cells this type of diabetes is untreatable to this day.

Type 2 diabetes is the most frequent type, it's not caused by a destruction of beta cells but rather an insulino-resistance. As the name suggests, this anomaly is characterized by a cell resistance to the action of insulin, the same amount of insulin doesn't have the same effect as it used to be, fewer GLUT-4 are made thus less glucose enters the cells which stimulate cellular hunger explaining why these patients are always hungry, insulin-resistance is thought to be some kind of mitochondrial dysfunction. Also, less glucose means that the cells take a longer time to regenerate thus wounds cant heal properly or fast enough explaining the high death rate from traumas among these patients. For a treatment, these patients receive different drugs to enhance their insulin sensibility and decrease blood sugar levels, the best drug that I can think about is metformin. 

This drug decrease neoglucogenesis, a fancy word to describe the process of making sugar from non-sugar molecules and of course decreases insulin-resistance. It is used by some patients to help them lose weight but I don't recommend it. In extreme cases, these patients switch their treatment to pure insulin injections because the drug pool by that time becomes inefficient and short. Personally, I never heard of someone who suffers from type 2 diabetes and achieves a non-diabetic state without drugs, Did you? 

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What if there's a simple cure?

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Wait for the magic!

For many years we have established a link between obesity and diabetes, we have even described a clinical syndrome called the metabolic syndrome. It includes high blood pressure, abdominal obesity, hyperglycemia, and dyslipidemia. Most patients have a great risk of developing one of these anomalies if they have already a previous one, so to begin with the link is pretty strong. Note that we are not talking about any kind of obesity but rather abdominal obesity, so what's the difference? You see there are different types of obesity like gynoid obesity when the body becomes pear-shaped mostly in women or uniform obesity when the distribution of fats are ubiquitous and so on. The most dangerous type is the abdominal obesity because unlike the other types, fat cells are not only subcutaneous but have higher chances of infiltrating the internal organs and interfering with the normal function of these organs, establishing what we call visceral obesity.

For instance, let's analyze this images from an MRI for a second, what do you see? well, they are taken from men with the same waist circumference but different abdominal fat deposits are found! This means that we cannot count on waist circumference to determine the visceral fat deposit, the key is to keep a balanced weight. A couple of days before, I read an article on steemstem community talking about why following a healthy lifestyle when you are obese is better than being slim and following a bad lifestyle, well I guess visceral obesity is a part of the answer 

A study done by researchers at the University of Newcastle found that diabetes type 2 can be treated with a simple weight loss. In fact, if we take an MRI of a normal pancreas versus a pancreas of a diabetic person, we are more likely to see fat deposits inside and these fat cells disrupt the normal function of the pancreas. In type 2 diabetes, the first phase of insulin production by beta cells is diminished remarkably comparing to a normal pancreas. So, in theory, we can cure diabetes by eliminating the excess of fats, right? Well not so fast! They also found that in order to achieve complete remission, the beta cells need to be able to regenerate and re-differentiate normally. Think about it like normal DNA, at the beginning if there's an anomaly it can be fixed quickly but if the alterations become too many or too complicated, the process is no longer possible. The same principle happens with beta cells, if the mitochondrial defect alongside with other metabolic anomalies takes too long, no remission is possible by that time. This explains why pre-diabetic states (When the person is not healthy but not diabetic as well, his blood sugar is at its limits) can be cured with simple health advice.

This new discovery offers new hopes for diabetic people to cure the disease completely, unfortunately, they will be always prone for a reappearance because genetically speaking they can develop diabetes far more easily than normal people. It's not a magic solution and nothing is guaranteed for sure, nevertheless, the idea is very exciting and strongly motivates these people to pursue a healthy lifestyle. 

Sources & Useful links for further reading:

Diabetes mellitus

Diabetes-types

Weight Loss as a Cure for Type 2 Diabetes? Fact or Fantasy

Why weight loss produces remission of type 2 diabetes in some patients

Remission of Human Type 2 Diabetes Requires Decrease in Liver and Pancreas Fat Content but Is Dependent upon Capacity for  Cell Recovery

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