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A New Weapon in the War Against Type 2 Diabetes

Updated: Jul 26, 2021


Diabetes Mellitus, what is it?

Diabetes mellitus (DM), also know simply as diabetes, is a condition that is caused by insufficient secretion of insulin or improperly functioning insulin leading to hyperglycemia as well as severe changes in the metabolic processing of carbohydrates, proteins, and fats. Long term hyperglycemia is known to lead to many serious and often life threatening complications.


"As of 2015, 30.3 million people in the United States, or 9.4 percent of the population, had diabetes. More than 1 in 4 of them didn’t know they had the disease. Diabetes affects 1 in 4 people over the age of 65. About 90-95 percent of cases in adults are type 2 diabetes."




Diabetic Mellitus complication


Type 2 diabetes can cause serious, potentially life-threatening complications in all parts of the body. These include:

  • Atherosclerosis — Atherosclerosis is a fat buildup in the artery walls, most commonly of the heart, brain, or legs, which impairs blood flow to all the organs.

  • Retinopathy — The rear part of the eye, called the retina, is filled with tiny blood vessels that can be damaged by extended high blood sugar. This damage, in turn, leads to blockages that starve the retina or bleeding into the retina. Both of these situations reduce the ability of the retina to detect light. If diagnosed early, this damage can be minimized by rigorously controlling blood sugar and laser surgery, but if left untreated, retinopathy will lead to blindness.

  • Eye damage - Along with the damage to the retina, diabetes increases the risk of other severe eye diseases, such as cataracts, glaucoma, etc., which potentially lead to blindness.

  • Neuropathy (a.k.a. nerve damage) - This condition typically begins in the extremities with damage to the nerves in the legs (causing pain in the feet) but is also common in arms/hands and can also affect things like digestion, sexual function, and bladder control.

  • Foot problems - Another side effect of neuropathy is that the numbness, may cause a person to not feel irritation in the foot. Of course, the reason our bodies feel irritation or pain is, so we know there is something that needs to be fixed. Without that early warning, sore and blisters may become ulcerous before being noticed. Blood circulation can also be interrupted, leading to reduced healing. This reduced healing also allows small sores or blisters to progress into more dangerous ulcers. If medical intervention cannot reverse these issues, the foot may require amputation.

  • Nephropathy - Diabetics often have high blood pressure as well as high blood sugar, if these conditions are left untreated for an extended period it may lead to severe kidney damage (nephropathy), a disease that damages the small blood vessels in the kidneys.

  • Hearing impairment - People with diabetes are more at risk of developing hearing problems than healthy individuals.

  • Skin conditions - Susceptibility to skin problems, both bacterial and fungal infections, is significantly increased amongst those who have diabetes.

  • Sleep apnea - While obesity may be the main contributing factor to both diabetes and sleep apnea, it has been shown that by treating sleep apnea, you may lower blood pressure and make you feel more rested. Although it's not clear whether it helps improve blood sugar control.

  • Alzheimer's disease - Type 2 diabetes seems to increase the risk of Alzheimer's disease, though it's not clear why. The higher your blood sugar control, the more noticeable the risk appears to be.


Treatment option Diabetes Mellitus

The backbone of diabetes management is proper diet and regular exercise, which have to be individualized. Both could be the only management needed for controlling blood glucose in type 2 diabetes in its early phase. Patients with type 2 diabetes may require oral hypoglycemic agents or insulin. The treatment plan for diabetes may include

  • diabetes education

  • meal planning and nutritional recommendations

  • exercise

  • anti-diabetic medications

  • insulin

  • management of associated conditions and complications.


The care of an individual with diabetes mellitus requires specialists from several healthcare disciplines, including a primary care provider or diabetologist, nutritionist, and a diabetes educator. When the complications arise, various sub-specialists like neurologists, podiatrists, nephrologists, vascular surgeons, cardiologists, and ophthalmologists, are essential. But ultimately, the success of all these specialists is dependent on the patient! On their participation, input, and enthusiasm when it comes to maintaining the strict treatment plans needed to ensure the best possible outcome.


Type 2 diabetes is a Disease of Aging


Metabolic conditions, including type 2 diabetes mellitus (T2DM) and cardiovascular disease, are strongly related to the aging process. While it is obesity and insulin resistance that are the initial preconditions, it’s among the elderly that the consequences related to metabolic disorders and cardiovascular diseases are frequently found. A decline in lean body mass and an increase in body fat, particularly belly fat that often accompanies aging, may actively contribute to the development of insulin resistance. As for T2DM, it is known that aging induces a decrease of insulin sensitivity and alteration or insufficient compensation of beta-cell functional mass in the face of increasing insulin resistance. When related to beta-cell functions, aging correlates with a decrease of beta-cell proliferation capacity and enhances sensitivity to apoptosis.


Recent research has stated, “It has recently been proposed that an age-associated decline in mitochondrial function contributes to insulin resistance in the elderly.”

As well as other metabolic diseases also frequently related to aging, such as coronary arterial disease, malignancies, cognitive disorders, and vitamin D deficiency.


Stem Cell Therapy Research for the Treatment of Diabetes

A review of clinical studies published in the Journal of Molecular Endocrinology discussed the following research about the use of Mesenchymal stem cells (MSCs).


In 2011, a pilot study in China involving placenta-derived MSCs to patients with long-standing diabetes mellitus type 2 revealed the transplantation was relatively simple, safe, and potentially productive. This research included ten patients who had been diagnosed with type 2 diabetes for three or more years, insulin-dependent for at least one year, and poorly controlled glucose. The subjects received placental stem cells via IV infusions. After six months of treatment, the insulin dosage and HbA1c measurements for all the patients demonstrated improvement. Also, C-peptide and insulin release were higher after MSC treatment. This study included a group of individuals who, due to other co-morbidities, including heart disease, kidney disease, and vascular complications, more closely matched actual clinical scenarios.


In 2013 Hu et al. conducted a single-center double-blind study examining the safety, feasibility, and preliminary outcomes of umbilical cord Wharton’s jelly-derived MSCs for new-onset type I diabetics. The MSC-treated group underwent two intravenous infusions separated four weeks apart. They found significant improvement in all common measurements(insulin dosage, HbA1c, C-peptide, and insulin usage) for the MSC group. The authors concluded that in their research, at least, the transplant of umbilical cord MSCs is feasible and safe.


In 2015, investigators from Sweden reported the first study aimed to evaluate the safety and efficacy of autologous MSC treatment in newly-diagnosed type 1 diabetics. Stem cells harvested from the patient’s iliac crest bone marrow did not result in adverse events in any of the ten patients.


Lately, researchers have designed insulin-secreting MSCs and delivered them, in combination with hematopoietic stem cells, to patients with type I diabetes. Rather than using donor stem cells, transplanting the patient’s own stem cells via the intra-pancreatic route tended to have improved postprandial glucose and C-peptide measurement in under 24 months. Both studies viewed the stem cell administration as a safe procedure with potential benefits; however, more extensive studies will need to be conducted to substantiate their findings.


To Learn More about MSCs visit my past article, How do Stem Cells know where to Repair


Stem Cells Treatment for Diabetes Mellitus

Recently, stem cell therapy has shown positive results in medical procedures related to the 3Rs (Replacement, Repair, and Regeneration). Of note, 3R treatment uses stem cells and progenitor cells as practical tools to prevent, repair, replace, and treat damaged organs. MSC therapy has been applied successfully in diabetes, from pre-clinical to clinical studies, and is proving to be an excellent platform for diabetes therapy because it can not only slow down the progression of diabetes but also eliminate the complications caused by long-term elevated blood glucose levels.


Umbilical Cord MSCs for More Extensive Treatment of Diabetes


It has been suggested that MSCs are not merely adult stem able to play many roles cells but also universal donor cells capable of adapting to any host due to their ability to avoid immune rejection. Due to this enormous potential, feasibility to isolate, abundance, and lack of ethical concerns regarding their harvest mesenchymal stem cells (MSCs) have been the cells most commonly evaluated.


MSCs are widely distributed throughout the body and can, therefore, be isolated from multiple sources, e.g., the bone marrow, heart, bodily fluids, skin, and perinatal tissues. MSCs react to micro-environmental changes (pH, oxygen, stress) by releasing immune-modulatory and trophic factors known to regenerate damaged cells and tissues.

Studies have established that while MSCs can be extracted from both umbilical cord blood and Wharton’s jelly (umbilical cord matrix), advantages to the isolation of MSCs from the Wharton’s jelly (WJ) include higher yield, more homogeneous stem cell population, increased likelihood of successful MSC isolation, and better ability to differentiate into insulin-producing cells.

Mesenchymal Stem Cell Transplantation for Diabetes Mellitus


MSCs play a vital role in healing damaged tissues; they differentiate and replace the dead cells as well as secrete chemicals needed to activate surrounding cells in the micro-environment, thus improving the tissue repair process. Therefore, MSCs can be applied to treat tissues impaired by chronic hyperglycemia. For Type 1 diabetes(T1DM), MSC transplantation can theoretically increase beta-cell mass through the following actions:

  1. beta cell replacement through differentiation (internally or externally);

  2. local micro-environment modification by the production of chemicals that stimulate regeneration;

  3. reduction or prevention of autoimmune reactions against beta cells. While several MSC transplantation studies have clearly shown the outcome of controlled glucose metabolism, there have also been observations of decreased insulin resistance and enhanced beta-cell function effects. Some studies have hypothesized that the immunomodulatory and inflammatory effects of MSCs are what contribute to the resulting reduction in insulin resistance.



 

by Dr. Chontirot Srikasedsarakul

Dr. Chontirot Srikasedsarakul is a specialist in Genomics, Dermatology and Aesthetics.  She has received qualifications from numerous educational institutions like Stanford University, U.S.A.; the University of Queensland, Australia; Chulalongkorn University, Thailand and the American Board of Anti-Aging Medicine.


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