Can MK-677 Cause Diabetes?

Can MK-677 Cause Diabetes?

Yes, there is some evidence that MK-677 increases the release of glucose, fatty acids and insulin into the blood. This has a risk of leading to insulin insensitivity [1]. This is a common finding in metabolic syndrome, a set of symptoms preceding diabetes.

To understand whether MK-677 can cause diabetes, let’s first recap what MK-677 and diabetes are.

MK-677 or Ibutamoren

MK-677, also known as Ibutamoren, is a growth hormone secretagogue that binds to the ghrelin receptor and stimulates the growth of hormones.

Human growth hormones are released from the pituitary gland and influence many anabolic processes. They can support muscle growth, improve bone density, accelerate healing, and prevent muscle wasting in catabolic conditions (for example, chemotherapy, ageing, or individuals with short guts).

MK-677 also increases insulin-like growth factor 1 (IGF-1) levels, which impacts the release of insulin and glucose metabolism in the body [2].

What is Diabetes?

Diabetes is a chronic disease that affects the body's ability to process blood glucose, commonly called blood sugar. It is characterised by high blood sugar levels due to defects in insulin secretion, the cells’ response to insulin, or both [3, 4].

Insulin is a hormone that facilitates glucose uptake into cells, muscles and the liver. It reduces gluconeogenesis in the liver and promotes its conversion to glycogen or fat. Without enough insulin, glucose stays in your blood, leading to high blood sugar levels that are toxic to your cells [6].

Subtypes of Diabetes

There are three main subtypes of diabetes: type 1, type 2, and gestational diabetes.

Type 1 diabetes is an autoimmune condition in which immune cells destroy the beta cells that produce insulin in the pancreas. This means that the body does not make any insulin. Only about 10% of diabetes cases are type 1, and these are most commonly diagnosed in childhood [5, 7, 8].

Type 2 diabetes is when the body doesn't use insulin well. This form of diabetes is often associated with lifestyle-related factors like obesity and is more commonly undiagnosed [9, 10]. Symptoms of type 2 diabetes include increased thirst and urination, weight fluctuations, fatigue and blurred vision [11].

Gestational diabetes is a temporary condition that causes high blood sugar levels during pregnancy. It occurs in about 5-9% of pregnant women, of which roughly 50% go on to develop type 2 diabetes [12].

There is evidence that growth hormone is linked to diabetes:

What is the link between growth hormone and diabetes?

Based on the provided articles, there appears to be a significant link between growth hormone (GH) and diabetes. Here are the key points:

• [18] Up to 25% of patients with acromegaly (excess GH) develop diabetes, indicating GH's potential role in the etiology of diabetes.
• [19], [20] GH hypersecretion and reduced circulating insulin-like growth factor-1 (IGF-1) levels are prevalent in insulin-dependent diabetes mellitus (IDDM).
• [21] Growth hormone concentrations in people with diabetes are 2 to 3 times higher than in those without diabetes.
• [22] Well-controlled adolescents with IDDM show abnormalities in GH, beta-hydroxybutyrate, and IGF-I levels despite normoglycemia.
• [23] Insufficient insulin in IDDM results in hepatic GH resistance, increased IGF-binding proteins, and decreased circulating IGF-I levels, leading to GH hypersecretion.
• [24] GH deficiency is associated with insulin resistance and diabetes. GH replacement therapy in GH-deficient adults increases the incidence of diabetes by 2.6 per 100 patient-years compared to reference populations.

In summary, both excess GH (acromegaly) and GH deficiency are linked to an increased risk of developing diabetes, likely due to the counter-regulatory effects of GH on carbohydrate metabolism and its interactions with insulin and IGF-1 signaling.

MK-677 and Diabetes

MK-677 may impair blood sugar regulation and lead to symptoms of type 2 diabetes. However, it is unlikely to cause type 1 diabetes since this is an autoimmune condition. Although GH and IGF-1 influence immune cell development, this is unlikely to lead to autoimmunity [13].

On the other hand, MK-677 has been shown to elevate blood glucose levels by suppressing the inhibition of gluconeogenesis [1]. This is because MK-677 mimics the effects of ghrelin, the hunger peptide. In response to ghrelin, the body feels that energy supplies are low and releases glucose from glycogen stores in the liver [2]. In addition, MK-677 promotes the release of Free Fatty Acids (FFAs) that compete to be taken into muscles and cells for energy.

Insulin-like growth factor 1 also stimulates insulin release, which can lower blood glucose levels [14, 15, 16]. Concurrently, high insulin and blood glucose confuse the cells. After some time, cells can become insensitive to insulin signalling, also known as insulin resistance.

There is one prominent case report of a man suffering from hyperglycaemia after taking MK-677 at 25mg / five days a week for three months, alongside other performance-enhancing drugs. This case study indicates that the combination of 'supplements' was detrimental to the patient's health and warrants extreme caution when taking over-the-counter supplements [17].

To summarise, MK-677 mimics the role of ghrelin, which leads to the release of glucose and fatty acids from stores around the body. However, it also stimulates the release of IGF-1, which can reduce blood glucose levels. Therefore, whether or not MK-677 causes diabetes will be highly individual, depending on your medical and family history as well as the dose and duration for which you are taking MK-677.

Fortunately, studies have reported that elevations in fasting blood glucose caused by GH supplements were quickly reversed after stopping their intake [15]. This indicates that impaired glucose levels is a reversible side effect of MK-677, unless they develop into diabetes