Background Pre-diabetes is a serious medical condition associated with elevated blood glucose that is higher than normal, but not high enough to be considered for a diagnosis of diabetes. An estimated 88 million adults aged 18 years and older have pre-diabetes in the United States (U.S.), yet more than 84% of those with pre-diabetes are unaware. Those with pre-diabetes are at increased risk for developing diabetes, cardiovascular disease (CVD), and stroke. Fifteen to 30% of individuals with pre-diabetes are likely to develop type 2 diabetes mellitus (T2DM) within 5 years. Pre-diabetes is a major risk factor associated with metabolic syndrome. Insulin resistance and excess body weight are common in both pre-diabetes and metabolic syndrome.
Metabolic syndrome - a cluster of risk factors that increase the risk of T2DM and CVD - affects about 35% of adults in the U.S. The risk factors for metabolic syndrome include hypertension, dyslipidemia, hyperglycemia, and excess body weight (especially due to excess central body fat). These risk factors represent an independent risk for developing T2DM, CVD, and stroke, as well as an increased risk of mortality. The risk of T2DM, CVD, and stroke increases with the number of metabolic risk factors. Persons with metabolic syndrome, when compared with healthy persons, have a 5-fold increased risk for T2DM. The combination of pre-diabetes and metabolic syndrome compared with healthy persons is associated with an even higher (i.e., 21-fold) risk for T2DM.
An inconsistent sleep schedule or a general lack of sleep has been associated with increased risk of developing T2DM. Specifically, sleep disturbance is associated with pre-diabetes and metabolic syndrome. Sleep disturbance is associated with poor cardio-metabolic control (i.e., hypertension, dyslipidemia, and a reduction in insulin level released after eating). Further, elevated stress hormones that keep the body awake have been associated with increased blood glucose level by increasing the production of glucose in the liver; decreasing glucose uptake in the muscles and fat cells; decreasing insulin secretion; and increasing insulin resistance. In addition, sleep deprivation has also been associated with increased appetite, which heightens the risk of T2DM. Again, insufficient sleep has been associated with higher levels of ghrelin, which increase appetite, and lower levels of leptin, which signals fullness. Therefore, improving sleep patterns has the potential to improve cardio-metabolic risk factors among those at risk for T2DM.
Lifestyle practices that promote good sleep hygiene and reduce stress have been associated with lower risk of T2DM and the control of cardio-metabolic risk factors among those at risk for T2DM. In addition, consistent sleep patterns have also been associated with improved glycemic control in T2DM. Phototherapy is thought to help improve sleep patterns in persons with circadian rhythm sleep disorders to normal sleeping patterns and times. Further, in a meta-analysis phototherapy therapy was shown to improve symptoms of vascular complications and quality of life that are linked to diabetes. In animal models, phototherapy has been shown to reduce abdominal fat. In addition, phototherapy has also been associated with improved insulin sensitivity in T2DM.
Phototherapy, also known as photobiomodulation (PBM), or low-level light therapy, has been known for almost 50 years but still has not gained widespread acceptance, largely due to uncertainty about the mechanisms of action. In recent years, much knowledge has been gained in this area. The primary site of light absorption in mammalian cells has been identified as the mitochondria, and more specifically, cytochrome c oxidase (CCO), an enzyme that contains both heme and copper centers and is known to reduce oxygen to water at the end of the mitochondrial respiratory chain. CCO has recently been shown to have an additional enzymatic activity: the reduction of nitrite to nitric oxide (NO) upon exposure to low-intensity light. The absorption peaks of CCO are in the visible (420-450 nm and 600-700 nm) and the near-infrared (760-980 nm) spectral region.
The leading hypothesis is that photons dissociate inhibitory NO from CCO, leading to an increase in electron transport, mitochondrial membrane potential and ATP production. Another hypothesis concerns light-sensitive ion channels that can be activated, allowing calcium to enter the cell. After the initial photon absorption events, numerous signaling pathways are activated via reactive oxygen species (ROS), cyclic AMP, NO and Ca2+, leading to activation of transcription factors. These transcription factors can lead to increased expression of genes related to protein synthesis, cell migration and proliferation, anti-inflammatory signaling, anti-apoptotic proteins, and antioxidant enzymes.
In a recent study showing that PBM reduced blood glucose and insulin resistance and reversed metabolic abnormalities in skeletal muscle in two diabetic mouse models, PBMT accelerated adenosine triphosphate (ATP) and ROS generation by elevating CCO activity. ROS-induced activation of phosphatase and tensin homolog (PTEN)/ protein kinase B (AKT) signaling after PBMT promoted glucose transporter GLUT4 translocation and glycogen synthase activation, accelerating glucose uptake and glycogen synthesis in skeletal muscle.
The effects of the non-transdermal Fos Biomedical patch system (which utilizes the concept of phototherapy) on cardio-metabolic risk factors and sleep quality in persons at risk for T2DM are unclear. Proposed is a randomized crossover placebo-controlled trial to assess the impact of the Fos Biomedical patch system use on cardio-metabolic risk factors and sleep quality among adults at risk for type 2 diabetes. Specifically, the investigators hypothesize that the use of the Fos Biomedical patch system for 12 weeks, as compared to placebo patch system, will improve glycated hemoglobin, other markers of cardio-metabolic risk factors and sleep quality in adults at risk for T2DM.
