The star treatment -metformin- is ineffective in up to 20% of patients due to a genetic mutation, forcing treatment to be personalized.
Dr. Florez (Head of Endocrinology at Massachusetts General Hospital) and his fellow collaborators have proposed the creation of subgroups for type 2 diabetes patients: obese, insulin resistant, with pancreatic beta-cell failure, or with hypercholesterolemia. This is the first effort by the research community to distinguish each patient individually so as to take more personalized decisions about both their treatment and the necessary interventions to be made in their lifestyles.
Dr. Francisco Martínez Peñalver – Neolife Medical Team
Currently, type 2 diabetes involves the same universal treatment for everyone, usually starting with oral anti-diabetic drugs (primarily metformin).
Type 2 diabetes represents a worldwide pandemic (1), and is caused by the inability of pancreatic beta-cells to produce the right amount of insulin needed in each moment. It is a disease that evolves and responds to medication differently in each patient.
From a macro-molecular point of view, getting older, weight gain, a sedentary lifestyle etc. are all recognized factors that accelerate this process. At a molecular level, the causes of beta-cell failure are due to a fault in the production of the hormone; an error in transporting the hormone towards the cell membrane; or a failed insulin release through said cell membrane.
When it comes to treating a patient with diagnosed type 2 diabetes, doctors specializing in this field first address the existing Treatment Guidelines, e.g. those of the American Diabetes Association (ADA) (2). The star treatment, present in these guides is that of metformin, which is ineffective in up to 20% of patients in whom a genetic mutation renders the medication useless (3).
Genetic studies in order to establish the presence of such mutations may only need to be carried out once in a lifetime, with a relatively low cost considering the significance of the information obtained, since the subsequent integration of data on the patient’s genome combined with the clinical data will allow decision-making to be personalized to the extreme.
The fact that type 2 diabetes differs from patient to patient is highlighted through: the evolution of the disease; the response to medication; and differences in diet. Nevertheless, given the huge volume of patients, the disease is still treated universally, usually starting with oral anti-diabetic drugs; among which, as we have already mentioned, the star of the show is metformin. This isn’t to say that it is bad in any way, only that there are patients who do not benefit from such medication and this is why such patients must be identified and treated appropriately. It has to be admitted that metformin has earned its reputation as a baseline treatment because it is indeed capable of modifying the course of the disease in many patients, not only helping to control blood glucose levels, but also in complementing healthy lifestyle habits.
The Head of Endocrinology at Massachusetts General Hospital, Dr. Florez, recognizes that “the treatments recommended by the guides do help to control the disease, in treating the larger population; however, a more personalized approach is needed in line with the original cause of type 2 diabetes in each patient”4. Dr. Florez and his fellow collaborators have proposed the creation of subgroups for type 2 diabetes patients: obese, insulin resistant, with pancreatic beta-cell failure, or with hypercholesterolemia. These groups are not watertight compartments – surely each patient will cross over into each of them – but it is a first attempt to classify and single out each element in order to look for individual answers through modifying the patients’ lifestyle, or medication…
There are other research groups that have preferred to create these subgroups in response to the secondary complications of the disease that may occur in patients (retinopathy, nephropathy, peripheral arteriopathy…). This is just as valid as that proposed by Dr. Florez and points towards the direction of the coming years of the research community making an effort to distinguish each patient individually so as to take more personalized decisions about both their treatment and the necessary interventions to be made in their lifestyles.
At Neolife we have been advocating for some time that 21st Century Medicine should be governed by the 4 Ps (Prediction, Prevention, Proactivity and Personalization). The aspect of this axiom that provides the greatest value is that of Personalization. Every patient is unique, is different, and therefore will need diagnostic tests and treatments different to other patients; such personalization, apart from increasing quality of life, will also present higher success rates in the prevention and cure of diseases.
(1) Ginter E, Simko V. Type 2 diabetes mellitus, pandemic in 21st century. Adv Exp Med Biol. 2012;771:42-50
(2) American Diabetes Association. Diabetes Advocacy: Standards of Medical Care in Diabetes-2018. Diabetes Care. 2018 Jan;41(Suppl 1):S152-S153.
(3) Li Q et al. STK11 rs2075604 Polymorphism is associated with metformin efficacy in Chinese type 2 diabetes mellitus. Int J Endocrinol. 2017;2017:3402808
(4) Merino J, Florez JC. Precision medicine in diabetes: an opportunity for clinical translation. Ann N Y Acad Sci. 2018 Jan;1411(1):140-152.