This week is diabetes awareness week. We know that the incidence of type 2 diabetes is increasing and although diet plays a fundamental role in the onset of the disease, other aspects of modern life are also contributing and need to be addressed in conjunction with dietary changes. Therefore in this blog we investigate the association of stress and diabetes and how high stress levels can play a significant role in the progression of type 2 diabetes.
The pathogenesis of type 2 diabetes can be complicated and multi factorial. But ultimately it is due to a dysfunction of glucose metabolism leading to insulin resistance. The main driver of type 2 diabetes is a diet high in sugar and refined carbohydrates leading to high blood glucose and insulin levels. Insulin is designed to stimulate the uptake of glucose into cells, via insulin receptors, where it can be stored as glycogen. Excessive insulin levels, due to the consumption of sugary foods, can cause significant drops in blood sugar leading to fatigue, irritability and sugar cravings.
Sugar or caffeine may be used for a quick energy boost, once again triggering the insulin response. If this occurs day in, day out for prolonged periods of time it can lead to the development of insulin resistance, whereby the insulin receptors are no longer sensitive to insulin and therefore blood glucose levels remain elevated as do insulin levels.
Prolonged excessive secretion of insulin can additionally lead to fatigue of the pancreas and eventually insulin production can reduce or cease and the person may require exogenous insulin.
Diabetes is a significant risk factor for the onset of cardiovascular disease, dementia and metabolic syndrome. See our blog: Diabetes and Insulin Resistance
The stress response is fundamental to human survival and is designed to provide us with the ability to either “fight or flight” from danger, the example that is often used is when, historically, we encountered a predator such as a man-eating tiger. In today’s society we are rarely faced with such dangers, however our bodies are still programmed to react to stress in the same way. Stress is often perceived as a negative response, but appropriate levels of stress can be healthy and are helpful in stimulating motivation and achievement allowing us to rise to challenges, providing the stress response is switched off once the challenge or danger has passed.
Stress which helps us to meet a deadline, pass an exam or run a marathon is commonly experienced at an unhelpful chronic level, constantly triggered by factors such as financial worries, relationship issues, chronic pain or illness.
At a hormonal level, stress triggers the release of hormones from the adrenal glands: adrenaline and cortisol. Adrenaline is “fast acting” and initiates a response to increase energy and blood flow to the brain, muscles and cardiovascular systems quickly, thereby stimulating vasoconstriction, bronchodilation, and increased blood pressure. Cortisol provides a more sustained response and increases blood glucose levels, thus it opposes the action of insulin and it is this action of cortisol which is thought to be the main driver of insulin resistance in relation to stress.
Research has shown a correlation with increased stress and diabetes. One study found significantly higher 10pm salivary cortisol levels, post dexamethasone (drug which mimics cortisol), in newly diagnosed diabetes mellitus (NDDM) subjects compared to subjects with normal glucose tolerance (NGT). It concluded that NDDM subjects display significantly higher chronic stress and stress responses when compared to subjects with NGT. Chronic stress and endocrine stress responses are significantly associated with glucose intolerance, insulin resistance and diabetes mellitus.
Stress is not the only driver of type 2 diabetes but it plays a major role and has an effect on many pathways which are associated with the progression of insulin resistance. Stress and high cortisol levels contribute to the onset of type 2 diabetes by:
- Stimulating glycogenolysis (breakdown of glycogen into glucose)
- Stimulating gluconeogenesis (production of glucose from fat and protein)
- Increasing lipolysis, thereby increasing release of free fatty acids which induces or aggravates insulin resistance in liver and muscle through direct or indirect (from triglyceride deposits) generation of metabolites, altering the insulin signalling pathway. Alleviating the excess of free fatty acids is a target for the treatment of insulin resistance
- Increasing proteolysis, therefore causing breakdown of protein in order to create glucose
- Research shows that glucocorticoids (e.g. cortisol) have been documented to reduce the expression of the glucose transporter GLUT2, which facilitates glucose movement across cell membranes
- Long-term treatment with glucocorticoids seems to induce pancreatic beta cell dysfunction, probably as a consequence of both the inhibition of insulin synthesis and secretion, as well as apoptosis of the pancreatic beta cells induced directly and indirectly by glucocorticoids with a consequent loss of beta cell function and the development of diabetes mellitus, especially in susceptible individuals
High levels of cortisol have also been shown to impair insulin receptor signalling pathways by inducing a “post receptor defect”. A study looking at rat skeletal muscle cells, showed that administration with a glucocorticoid mimicking drug significantly impaired the intracellular pathways which uptake glucose, leading to a consequent reduction of glucose uptake. A decrease of glycogen synthase kinase (GSK)-3 phosphorylation, with a consequent decrease of glycogen synthesis was also observed. In humans, the limited number of studies on the treatment with glucocorticoid drugs in healthy subjects seem to confirm these findings. Therefore we can see from this that cortisol has a direct impact on insulin function so can play a significant role in the pathogenesis of type 2 diabetes.
Mood and depression
Stress and high cortisol can also have a significant impact on mood and depression; it is very common to see high stress and anxiety coupled with mood disorders. Low mood and depression can also have an independent effect on blood sugar control and insulin resistance. Studies show that depression increases the risk of type 2 diabetes by 60% and is associated with an increased level of cortisol. The feel good neurotransmitter serotonin plays a role in satiety and feeding control. Also, carbohydrates are required to transport tryptophan across the blood brain barrier, to then be converted into serotonin. When serotonin is low, as in depression, we can see feeding behaviours such as increased carbohydrate consumption and binge eating which can again contribute to insulin resistance.
The proteolytic effects of cortisol can reduce muscle mass by increasing the breakdown of protein from muscle and inhibiting protein synthesis, which can contribute to sarcopenia. As the muscle and the liver are the most highly metabolic organs, a reduction in muscle can have an enormous impact on the body’s sensitivity to insulin. Increasing muscle mass allows the body to improve its response to insulin and uptake glucose into the cell.
Cortisol also has been shown to increase the deposition of visceral adipose tissue, leading to a typical apple shape, which again is associated with insulin resistance and diabetes. Cortisol is able to stimulate the differentiation of pre-adipocytes into adipocytes and therefore increase adipocyte numbers and fat deposition. In addition, it can affect adipose tissue metabolism by a number of pathways which contribute to the development of insulin resistance. The occurrence of insulin resistance in adipose tissue, together with the predominance of visceral or peripheral adipose tissue, participate in the pathogenesis of type 2 diabetes and metabolic syndrome.
Excess reactive oxygen species and mitochondrial dysfunction are observed in type 2 diabetic patients and mitochondrial dysfunction is thought to play a significant role in the pathogenesis and progression of the disease. Prolonged stress and high levels of cortisol can increase reactive oxygen species and are associated with increased mitochondrial dysfunction. Reducing oxidative stress and normalising mitochondrial function are important factors in supporting patients with insulin resistance and diabetes.
Stress and excess cortisol have a significant role to play in the progression of insulin resistance, diabetes and also metabolic syndrome, and have an effect on multiple pathways which are involved in the pathogenesis of these disorders. It is therefore important to support a healthy stress response in all individuals but particularly in those who are susceptible to, or already have, this condition. Here are some suggestions that may be useful:
- Stress management techniques: look at mindfulness (there are some really useful apps), relaxation techniques and breathing exercises
- Exercise improves resistance to stress and insulin sensitivity (aim for at least the recommended 150 minutes per week of moderate exercise)
- Reduce refined carbohydrate and sugar consumption (opt for wholegrain carbohydrates with protein and healthy fat)
- Consume high amounts of antioxidants; aim for at least 6-8 portions of vegetables and 1-2 portions of fruit per day
- Consider supplementing nutrients which are important for supporting adrenal function such as vitamin C, Vitamin B5 and B6 and magnesium. Plus nutrients which are involved in mitochondrial function such as L-carnitine, CoQ10, alpha lipoic acid and N-acetyl-cysteine
- Consider adaptogenic herbs, which have been shown to modulate the stress response
- Try fasting for at least 12 hours per day and 3 hours before bed (e.g. dinner at 7pm, bed at 10pm and breakfast at 7am). A period of fasting for at least 12 hours reduces insulin levels and increases insulin sensitivity
- Aim for 8 hours sleep every night – lack of sleep increases insulin resistance
- The stress hormone cortisol directly affects insulin signalling and therefore can exacerbate the progression of insulin resistance and type 2 diabetes.
- High cortisol inhibits glycogen synthesis and increases gluconeogenesis (glucose synthesis), thereby increasing blood glucose levels and insulin.
- Cortisol can reduce muscle mass, therefore increasing sarcopenia (muscle wastage), which has an indirect negative effect on insulin sensitivity.
- High cortisol increases visceral fat tissue which further increases insulin resistance and progression of metabolic syndrome.
- High cortisol can increase oxidative stress which negatively affects mitochondrial function (mitochondria are the energy powerhouses of cells), which again is involved in the pathogenesis of insulin resistance and type 2 diabetes.
- Stress management, exercise, sleep, adrenal support, antioxidants and mitochondrial support can help support a healthy stress response.
Relevant Cytoplan Products:
Blood Glucose Support – contains magnesium, zinc, Ceylon cinnamon and GTF chromium
Adrenal Support – Herb complex containing Siberian ginseng, liquorice as well as b5, kelp (providing iodine), chromium and selenium.
Organic Ashwagandha – Used in traditional Ayurverdic medicine, Organic Ashwagandha comes at a potency of 500mg per capsule.
Phytoshield – phytonutrient flavonoid and carotenoid complex, providing antioxidants.
Cyto Renew – contains CoQ10, l-carnitine, alpha lipoic acid, N-acetyl cysteine, gingko biloba and rosemary.
Pantothenic Acid (B5) – 50mg pantothenic acid per tablet.
Cherry C – 200mg of vitamin C from acerola cherry, additionally contains naturally occurring bioflavonoids.
Biofood Magnesium – contains 100mg of elemental magnesium per tablet.
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