Advances in Diabetes — Prevention, Interception and Reversal

Statistics relating to diabetes have never seemed more dire. The incidence and prevalence of Type 1 diabetes (T1D) are rising, with recent estimates being that more than 542,000 children worldwide have the condition. Diagnoses are increasing by 2–3 percent per year.1 Some troubling trends have also been reported for Type 2 diabetes (T2D).2 Cases of T2D have quadrupled in the last 30 years, with 23 million people in the U.S. diagnosed with diabetes; 90 percent of these have T2D. Globally, diabetes is now the seventh major cause of mortality.3

While diabetes can be effectively treated using insulin, it is also true that insulin is no “magic bullet” and patients remain dissatisfied with the quality of life that existing therapies provide. This is, however, an exciting time in terms of diabetes research beyond the framework of conventional, insulin-based therapies. Real advances are being made in relation to prevention, interception and even reversal of the disease.

Preventing diabetes

Therapeutic developments using hybrid closed-loop devices, artificial pancreas systems and continuous glucose monitoring technology have helped improve the lives of people living with T1D. There is, however, currently no way to prevent the disease, although close monitoring of high-risk patients can significantly reduce the rates of diabetic ketoacidosis.1 Islet autoantibodies are known to be highly predictive biomarkers of progression to T1D and thus could be used to screen for risk. The development of an effective preventative strategy for T1D remains a priority and would justify the implementation of such screening for all children.

For T2D, protocols for preventing development of the disease in prediabetic individuals are well-established and include:3

• Annual monitoring of patients;

• Intervention strategies involving an initial loss in body weight (7 percent) and an increase in physical activity of at least moderate intensity;

• Technology-assisted interventions to educate, raise awareness and help prevent T2D;

• Metformin therapy for patients with a body-mass index (BMI) higher than 35 kg/m2, those aged 60 years or above, and women with prior gestational diabetes;

• The monitoring of vitamin B12 levels in association with metformin therapy, as long-term use of the drug is associated with vitamin B12 deficiency. This is particularly important for patients with anemia or peripheral neuropathy;

• Identification of risk factors for cardiovascular disease that can be adjusted or treated; and,

• Development and maintenance of patient behaviors that can prevent or delay the onset of T2D, such as healthy eating and physical activity.

Stopping diabetes in its tracks

Diabetes interception relies on three key factors:

• Patients have not yet developed symptoms of the disease;

• Biomarkers for the disease can be detected before the patient develops symptoms; and,

• Medical treatment can then prevent symptoms based on the detection of these biomarkers.

Biomarkers of T1D in children may present years before the onset of clinical disease. Screening for the disease is, however, rare, and individuals often progress to T1D and insulin-dependence before T1D can be diagnosed. With the incidence of T1D rising by 2–3 percent annually,1 the development of a mechanism to intercept the disease is of crucial importance.

Janssen has developed the T1D Disease Interception Accelerator.4 This initiative is intended to identify biomarkers for T1D in children and allow gene-based risks to be profiled. It is hoped that this strategy will provide opportunities to intervene with disease progression. A team within the program is also developing epidemiological modeling and predictive biomarkers to identify women at risk of gestational diabetes mellitus.

Reversing diabetes

Some of the most exciting developments in diabetes research relate to a potential reversal of the disease. Progress has even been made in the reversal of T1D. JDRF is a T1D charity that funds research to cure, treat and prevent the disease. It is currently funding more than 80 grants around the world, totaling more than $55 million, and is working on every aspect of beta cell replacement. Dr. Esther Latres, Director of Cell Therapies for JDRF, says, “We are funding research on renewable beta cell sources so that every person with Type 1 diabetes can get this treatment. We are establishing ways to maintain oxygen and other nutrients after the beta cells have been transplanted, and to shield them from immune attack. This includes micro- and macro-encapsulation, to prevent the need for additional immunosuppressant drugs. The maintenance of oxygen and other nutrients is needed before beta cell replacement therapy can be successfully achieved in clinical studies.”

Purdue University, in collaboration with the Indiana University School of Medicine, has reported the first minimally invasive therapy to successfully reverse T1D.5 Preclinical animal trials show that this reversal occurs within 24 hours. The patented technology uses a “Trojan horse,” consisting of a collagen formulation incorporating islet cells, to evade the immune system. The technology has been shown to maintain insulin independence for at least 90 days.

For T2D, one study of particular promise uses an individualized approach to nutritional ketosis.6 Of 349 patients with T2D, 262 were provided with individualized low-carbohydrate diets. Patients were connected with a health coach and physician via a mobile app with associated educational resources. This approach prevented significant hypoglycemic events and reported the following outcomes:

• There was a 1.3 percent average reduction in hemoglobin A1C, a biomarker that indicates average blood glucose concentration over the previous three months;

• There was 12 percent average weight loss;

• As many as 94 percent of patients using insulin therapy were able to reduce or eliminate insulin use; and,

• A total of 60 percent of patients showed hemoglobin A1C levels below the threshold for diabetes.

The Diabetes Remission Clinical Trial (DiRECT) program, funded by Diabetes UK, has also looked at how an intensive, low-calorie diet-based program of weight management can reverse T2D.7 The program is led by Professor Rod Taylor from Newcastle University, who found that the avoidance of, or reduction in, weight regain can prevent T2D return.

Exciting times for diabetes care

A disease we once saw as progressive is now becoming preventable and reversible, with advances in both Type 1 and Type 2 diabetes demonstrating that the disease can potentially be prevented, intercepted and even reversed. With so much research underway, it is important to keep up to date with new insights in patient care.

Access additional resources and practical information to enhance the care and treatment of your diabetes patients.

About our expert

Nicola DaviesNicola Davies, PhD, health psychologist and author of I Can Beat Obesity! Finding the Motivation, Confidence and Skills to Lose Weight and Avoid Relapse

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