Trait: Fasting Blood Glucose
Dr Haran Sivapalan
December 9, 2019
What is glucose?
Glucose is a simple sugar (or monosaccharide) that is required by the body for energy.
When you eat a meal with carbohydrates (which are molecules composed of chains of sugars), your body breaks it down into simple glucose molecules to be absorbed and used for energy.
Why is glucose important?
Glucose is rich in chemical energy. Through a process of respiration, cells in your body unlock this energy and convert it into another form of chemical energy, ATP (adenosine triphosphate).
ATP is often referred to as the ‘energy currency’ of cells. It is required for us to move, grow and carry out the multitude of biochemical processes that allow us to survive.
- Glucose is the body’s major energy source.
- Glucose is used to form ATP, the chemical energy currency used by cells.
How does glucose get into your bloodstream?
Carbohydrates in your diet
Complex carbohydrates e.g. starch and glycogen, are known as polysaccharides - they are molecules made up of long-chains of sugars. Carbohydrates such as maltose, lactose and sucrose are disaccharides – they are molecules made up of two sugars.
For cells to take in and get energy from these carbohydrate molecules, polysaccharides and disaccharides must first be broken down into simpler molecules containing just one sugar molecule: monosaccharides.
Glucose is the most important monosaccharide as it is used for energy.
Digestion of carbohydrates
When you eat a meal containing carbohydrate (e.g. starch, glycogen, maltose), your digestive system starts to breakdown these larger molecules into smaller molecules and eventually into glucose.
This process starts in the mouth, where your saliva contains an enzyme called amylase, which begins to break down starch into smaller molecules.
The main site of carbohydrate digestion, however, is in the small intestine. Enzymes located on villi (small finger-like structures lining the small intestine) break down polysaccharides and disaccharides into glucose.
Absorption of glucose
Once carbohydrates are broken down into glucose, the molecules of glucose are then absorbed into the bloodstream by the small intestine. Specifically, glucose enters into a part of circulatory system called your hepatic portal system.
Once in the circulation, glucose goes to the liver and other tissues, where it may be further metabolized or turned into energy storage molecules (e.g. glycogen).
- Carbohydrates (polysaccharides and disaccharides) are broken down into simple sugars (monosaccharides) by enzymes in the digestive system.
- Glucose (a monosaccharide) is absorbed by the small intestine into the bloodstream.
- Once in the bloodstream, glucose can be used by tissues for energy or converted into other molecules.
What is insulin?
Insulin is an important hormone that allows various tissues (particularly muscle and fat tissue) to take up and use sugar (glucose) from the bloodstream.
Insulin also has several important roles in the metabolism and storage of carbohydrates and fats for energy.
Why is insulin important?
Without insulin, glucose would not be able to leave the bloodstream and be taken up by cells in muscle and fat tissue. This would then deprive important tissues and organs of a vital energy source.
- Insulin allows cells to take up and use glucose.
- Insulin plays a number of roles in sugar and fat metabolism.
Where is insulin produced?
Insulin is made by your pancreas.
The pancreas is an organ that sits deep in the abdomen behind your stomach. A region of the pancreas called the Islets of Langerhans is responsible for producing various hormones.
Within this region, specialised cells called beta cells produce and secrete insulin.
How is insulin produced?
Insulin is made from a precursor molecule called pro-insulin. Pro-insulin is then combined with zinc and calcium to form crystals or ‘granules’ of insulin. These insulin granules are stored inside small compartments called vesicles before being secreted into the bloodstream.
Given the involvement of zinc and calcium, your intake and metabolism of both these minerals have an influence on your production and secretion of insulin.
- Insulin is produced by beta cells in the pancreas.
- The production of insulin requires zinc and calcium.
What are the effects of insulin?
Insulin plays several key roles in the uptake, storage and breakdown of carbohydrates and fat for energy.
- Insulin facilitates the entry of glucose into tissues
Several tissues in the body, especially muscle and adipose (fat) tissue, require insulin to allow them to take up glucose. Glucose can then be used for energy (for example, to generate ATP needed for the contraction in skeletal muscles) or can be built into energy storage molecules (e.g. glycogen).
- Insulin stimulates the formation of glycogen in the liver and muscle
Glycogen is polysaccharide molecule made of long chains of glucose joined together. It is useful as an energy storage molecule in muscle and liver as it can quickly be broken down into glucose for respiration.
When blood glucose levels rise, insulin causes the liver and muscles to convert glucose into glycogen for energy storage. Similarly, insulin slows down the rate at which glycogen is broken back down into glucose.
- Insulin stimulates the production of fatty acids in the liver
Fatty acids are the building blocks of fats. Insulin stimulates the liver to convert glucose into fatty acids.These fatty acids are then made available to other tissues, such as adipose (fat) tissue and muscle. The fatty acids may then be made into triglycerides (a type of fat) for storage.
- Insulin inhibits the breakdown of fat stores
Your body carries fat stores in tissue known as adipose tissue. Fat is stored here in the form of triglycerides. Triglycerides can then be broken down to release fatty acids for energy in a process known as lipolysis. Insulin inhibits this process.
Furthermore, insulin stimulates adipose (fat) and muscle tissue to take up triglycerides circulating in the blood and store them as fat.
- Insulin stimulates the formation of protein
In addition to influencing carbohydrate and fat metabolism, insulin also affects how your body uses protein.
Insulin is an anabolic hormone – it stimulates growth and the building of proteins in muscle, liver and other tissues. It also increases the uptake of amino acids (the building blocks of protein) into these tissues.
How does insulin work?
Insulin binds to specialized insulin receptors (IRs) on the surface membrane of cells.
When insulin binds to the outer part (the alpha subunit) of these receptors, it stimulates an enzyme (called tyrosine kinase) on the inner part (the beta subunit) of the receptor.
The stimulation of this enzyme causes the activation of various molecules, including molecules known as insulin receptor substrates (IRS). These, in turn, trigger a cascade of chemical reactions which activate a number of other molecules/enzymes that are ultimately responsible for insulin’s various effects.
Insulin and glucose entry
In several tissues, including muscle and fat tissue, insulin facilitates the entry of glucose into cells.
Cells in these tissues have special transporter proteins that allow glucose to pass into the cells. These proteins, called glucose transporter proteins (GLUT), are stored inside the cell in small compartments called vesicles. There are different types of GLUT proteins, but GLUT 4 is the predominant protein in muscle and fat tissue.
When insulin binds to the insulin receptor, it triggers a signalling cascade that causes the vesicles containing GLUT4 proteins to fuse with the outer membrane of the cell. The GLUT4 proteins then become inserted into the membrane and allow glucose to enter into the cell.
- Insulin binds to insulin receptors (IR) on cells.
- When insulin binds to IRs, it triggers a cascade of chemical reactions that give rise to insulin's effects.
- In muscle and fat tissue, insulin causes GLUT4 transporter proteins to the cell membrane and allow the entry of glucose.
What are your blood glucose levels?
Your blood glucose level refers to the concentration of glucose circulating in your bloodstream. The amount of glucose in your blood varies throughout the day according to when you’ve eaten food and how well your body produces and responds to insulin.
To accurately measure your blood glucose level, a blood test is required.(Note: we do not offer this service at FitnessGenes).
In this regard, there are three main blood glucose levels that are routinely measured.
Random blood glucose
This is your level of blood glucose when taken at any time during the day. This level will vary widely depending on when you last ate. Typically, however, a normal random blood glucose level is 125 mg/dL (7mmol/L) or lower.
Fasting blood glucose
This is your level of blood glucose after you have had nothing to eat or drink after at least 8 hours. A normal fasting blood glucose level is between 70 mg/dL (3.9 mmol/L) and 100 mg/dL (5.6 mmol/L).
Oral Glucose Tolerance test
In some healthcare settings, clinicians will take a blood sample at regular intervals (e.g. hourly) after you’ve consumed a drink containing 75 g of glucose.
- Your fasting blood glucose level refers to the concentration of glucose in your bloodstream after you haven't eaten for at least 8 hours.
- A blood test is required for an accurate measurement of your fasting blood glucose level.
What is the relationship between blood glucose levels and insulin function?
Recall that one of the main functions of insulin is to allow glucose move from the bloodstream into cells.
If there is a problem with the production of insulin (i.e. insulin deficiency), then glucose is less able to move into cells. Instead, glucose lingers in the bloodstream and therefore blood glucose levels become higher.
Alternatively, if your pancreas can produce enough insulin, but your tissues are not responsive or ‘sensitive’ to insulin (a phenomenon called insulin resistance), then, again, glucose will not be able to move into cells. Consequently, levels of glucose in the blood start to rise.
Your blood glucose levels are therefore an indication of how well your body produces and/or responds to insulin.
High blood glucose levels suggest that your pancreas has difficulty producing and secreting insulin and/or tissues in your body are poorly sensitive or ‘resistant’ to insulin.
Such impairment of your insulin function has several negative health effects and may be a sign of the development of metabolic diseases such as Type 2 diabetes.
- Your fasting blood glucose levels indicate how well you produce and respond to insulin.
- High fasting blood glucose levels may suggest reduced production of insulin or poor sensitivity of tissues to insulin (insulin resistance).
What are high fasting blood glucose levels?
Impaired fasting glucose
A fasting blood glucose level between 100 mg/DL (5.6 mmol/L) and 125 mg/DL (6.9 mmol/L) is known in medical terms as impaired fasting glucose.
This suggests that your tissues have started to become resistant to the effects of insulin. This, in turn, is part of a condition called ‘prediabetes’. If left untreated, this condition may develop into full diabetes.
A fasting blood glucose level over 126 mg/DL (7 mmol/L) suggests diabetes mellitus. Diabetes is a metabolic health condition characterised by the inability to effectively produce and/or respond to insulin.
IMPORTANT: Note that the figures above refer to blood glucose levels as measured directly by a blood test in a healthcare setting.
By contrast, FitnessGenes uses your genetic (i.e. your DNA results) and lifestyle data (e.g. waist circumference, BMI) to make an approximate prediction of your fasting glucose level. We do not diagnose medical conditions such as diabetes mellitus, pre-diabetes or metabolic syndrome.
If you are worried about your blood glucose levels or diabetic illness, you are strongly advised to consult a physician.
- High fasting blood glucose levels may be a sign of pre-diabetes or diabetes.
- A blood test is required to accurately measure fasting blood glucose and diagnose metabolic disease.
- FitnessGenes use your genetic and lifestyle data to roughly predict your fasting blood glucose level.
- FitnessGenes cannot and do not diagnose diabetes, pre-diabetes or any other medical condition based on your data.
- Consult a physician if you are concerned about poor blood sugar control or diabetes.
What are the consequences of high fasting blood glucose levels?
High fasting blood glucose levels which persist for a long time can have several negative effects on your health.
One reason for this is that high concentrations of sugar (glucose) in your bloodstream can inflict damage to cells. On a molecular level, high amounts of glucose (and other simple sugars) can bind (without the need for an enzyme) to proteins and lipid molecules in cells. This process is known as glycation.
Glycation can impair the function of various molecules and thereby damage cells. Furthermore, glycation leads to the formation of harmful molecules called Advanced Glycation End Products (AGEs).
AGEs can lead to inflammation, oxidative stress and ultimately cause damage to blood vessels, nerves and organs. This may also increase the risk of cardiovascular disease (e.g. heart attack and stroke).
Risk of metabolic disease
High fasting blood glucose levels are also a reflection of insulin resistance.
Insulin resistance refers to the poor sensitivity of tissues to insulin, meaning that muscle, fat and other tissues do not respond effectively to normal (or high) amounts of insulin.
Insulin resistance is associated with an increased risk of chronic health conditions such as Type II diabetes, obesity and metabolic syndrome (a cluster of high blood sugar, high blood fats, a large waistline, high blood pressure and low amounts of ‘good’ HDL cholesterol).
When your tissues are resistant to the effects of insulin, your pancreas may try to compensate by producing significantly high amounts of insulin. This is a phenomenon known as compensatory hyperinsulinemia. As your pancreas are working extra hard to produce high amounts of insulin, they may eventually become unable to keep up with the body's demands for insulin. This can lead to the development of Type II diabetes and metabolic syndrome.
As insulin promotes fat deposition, compensatory hyperinsulinemia is also linked to weight gain and obesity.
Impaired exercise performance
As established earlier, your cells require glucose for energy. If, due to impairments in insulin function, glucose cannot enter cells, then they will struggle to generate energy to function efficiently.
Your skeletal muscles are particularly reliant on insulin for the entry of glucose. Insulin resistance can therefore lead to reduced exercise performance and, more generally, tiredness and lethargy.
- High blood glucose levels can cause damage to nerves, blood vessels and organs.
- High blood glucose levels increase the risk of metabolic diseases (e.g. Type II diabetes) and cardiovascular disease (e.g. heart attack and stroke).
- High blood glucose levels can lead to accumulation of fat and weight gain.
- High blood glucose levels negatively affect your exercise performance.
How do my genes influence my blood glucose levels?
The regulation of blood glucose levels, insulin function, and carbohydrate and fat metabolism is extremely complex, with several genes and lifestyle factors all playing interacting roles.
Below are just three genes (of several thousand) we analyze at FitnessGenes when generating your fasting blood glucose trait:
As mentioned in the “How is insulin produced?” section, the production and secretion of insulin in the pancreas requires zinc and calcium.
Your SLC30A8 gene encodes a zinc transporter protein that aids with this process. Specifically, it helps move zinc during the formation of insulin granules in the vesicles of beta cells.
Variants of this gene may influence how well you form and secrete insulin, with some variants (alleles) associated with an increased risk of diabetes.
When insulin binds to its insulin receptor, it triggers signalling cascades of various chemical reactions. These reactions are carried out by different enzymes and signalling proteins.
Your TCF7L2 gene encodes a protein that is involved in one of these signalling cascades. Variants of TCF7L2 gene may affect your tissues’ sensitivity to insulin.
As we eat at different times, our production of insulin varies according to the time of the day. For example, when we’re asleep (and therefore not eating) insulin production is suppressed.
The coordination of our insulin release with day/night cycle is strongly regulated by the ‘sleep hormone’ melatonin. Melatonin exerts its effects by binding to the melatonin receptor, which is coded for by the MTNR1B gene.
Studies suggest that one variant of this gene causes people to produce less insulin during the night. If these people then eat a high-carbohydrate meal, they are more likely to experience high blood glucose levels.
How do lifestyle factors influence my blood glucose levels?
In addition to genes, environmental and lifestyle factors strongly influence your blood glucose levels and your production and sensitivity to insulin.
Excessive amounts of body fat and a higher body fat percentage are associated with poorer insulin sensitivity and higher fasting blood glucose levels. Where you deposit fat is also a major factor, with visceral fat (fat around internal organs in the abdomen) associated with worse insulin function.
By contrast, a greater lean body mass and lower body fat percentage are linked to better control of blood glucose levels.
It’s widely established that physical exercise increases insulin sensitivity and improves blood sugar levels. One potential mechanism underlying this effect is that, by regularly exercising, muscles increase the amount of GLUT4 transporter protein they produce. This allows them to take in and use more glucose for energy.
Conversely, a lack of physical activity is associated with poorer insulin sensitivity and higher blood glucose levels.
A diet high in saturated fat, trans fats and refined, high-GI carbohydrates is linked to the development of insulin resistance and high fasting blood sugar levels.
Some components of diet e.g. fiber, whole-grains, and various vitamins and minerals (e.g zinc) can help to improve blood sugar levels.
Disturbed sleep patterns increase the risk of higher fasting blood glucose levels. There are several potential reasons for this, from hormonal changes in insulin function and carbohydrate metabolism to behavioural changes e.g. binge eating in response to sleep deprivation.