PEMF Therapy for the Management of Diabetes in Obese Patients (ProMise): A Randomized Controlled Trial

The modern lifestyle has led to the development and propagation of obesity and type 2 diabetes (T2DM) pandemics. Obesity is associated with increased morbidity and mortality due to its associated diseases such as T2DM; certain cancers; cardiovascular diseases including hypertension, coronary artery disease and stroke; as well as mental disorders. T2DM is currently the main contributor to growing healthcare costs of obesity. One in three Singaporeans is at risk of developing T2DM, and by 2050, this is estimated to cost Singapore about $1.8 billion in medical expenses and productivity lost. With a global population trend towards increased obesity, the prevalence of T2DM will also be increased, thus creating burgeoning health and socioeconomic consequences. An effective interventional strategy against these chronic diseases would not only positively impact human health, but also relieve growing socioeconomic burden.

All guidelines recommend hypocaloric diet and lifestyle interventions (e.g. exercise) to manage T2DM in overweight or obese patients. The goal is to achieve and maintain 5-10%, and 15-20% weight loss in patients with BMI 25-35 kg/m2 and BMI>35 kg/m2, respectively. This goal requires limitation of daily calorie intake to 800-1200 and up to 275 minutes of exercise per week for a moderately obese person. Anti-obesity drugs can also be prescribed for T2DM patients with BMI > 27 kg/m2. When glycaemic control is not achieved, different progressive stages of T2DM are managed by monotherapy, dual therapy and finally triple therapy of Glucose Lowering Drugs (GLDs) without or with insulin program. Invasive bariatric surgeries are also recommended for T2DM patients with BMI >35 kg/m2 (32.5 kg/m2 in Asian populations), as well as lower BMI of 30 - 35 kg/m2 (equivalent to 27.5 - 32.5 kg/m2 in Asian populations) when the metabolic response to regular treatment plans has been poor.

Patient compliance with diet and lifestyle intervention regime can often be challenging, and yet those who faithfully comply may still fail to achieve the necessary weight loss within a limited time-frame. Pharmacotherapy with GLDs also carries some risks for side effects such as hypoglycaemia, weight gain, gastrointestinal problems, infections, bone fracture, pancreatitis, etc. The most effective approach for long term weight loss of >15% and T2DM remission has been bariatric surgery. Hypertension remission rates and metabolic control are also higher with bariatric surgery versus medical treatment. However, surgically treated patients also had significantly higher risk for additional surgical procedures and other complications including abdominal pain, gastroduodenal ulcers, long-term nutrition and micronutrient deficiency, etc. There is a global urgency for patient-friendly yet effective treatment options with minimal side effects for obesity and T2DM.

T2DM remission in bariatric surgery patients has been intricately linked to weight loss. Perhaps most intriguing is the observation that glycaemic control is re-established prior to weight loss and improvement in muscle insulin sensitivity, thus suggesting that there is an earlier mechanistic juncture, potentially amenable to interventional regulation. In the Twin Cycle Hypothesis, fat accumulation in the liver and secondarily in the pancreas, leads to vicious cycles that result in the development of T2DM. Decreasing liver fat content may potentially be the tunable interventional juncture in promoting remission of T2DM in overweight and obese patients. The PROMISE pilot trial will investigate whether metabolic activation of muscle with a novel, non-invasive technology will further improve metabolic outcomes in overweight/obese patients with early T2DM who are currently given diet and/ or lifestyle (DL) interventions.

Better glycaemic control at the early stages of T2DM would