November was Diabetes Awareness Month…
Diabetes has become synonymous with lifestyle disorders and is a major concern because of its increasing occurrence among age groups that were previously not affected. During November, many organisations and groups took the opportunity to raise awareness of the disease, its causes and symptoms, as well as the preventative measures that can be considered to minimise the chances or delay the onset of diabetes.
Diabetes is a chronic disease when either the pancreas does not create enough insulin, or when the body is unable to optimally utilise the insulin it produces. Because insulin regulates the sugar levels in the blood, a lack thereof can result in hyperglycemia which, when left untreated, ultimately leads to damage of the body’s systems, including nerves and blood vessels.
Type 1 (insulin-dependent) diabetes is caused by deficient insulin production and is managed by daily administration of insulin. Prevalent symptoms include excessive urine excretion, constant thirst and/or hunger, weight loss, vision change, and fatigue. Since the causes of this type of diabetes are unknown, prevention is still impossible.
Type 2 (non-insulin-dependent) diabetes is caused by the body’s ineffective use of insulin – commonly in later life (adult onset) but the disease is nowadays observed in children too. Symptoms are generally similar to those of type 1 diabetes, yet less obvious and, as a result, Type 2 diabetes is often diagnosed long after actual onset. This type of diabetes can be prevented, as its major causes are excess body weight and lack of physical activity. Insulin resistance is the result of muscle cells, body fat and the liver resisting or ignoring the signal of insulin, which leads to type 2 diabetes when left untreated. Therefore, it is vital to understand one’s own predisposition so as to ensure early detection and effective treatment
In line with diabetes awareness that recently took centre stage on World Diabetes Day (14 November), our focus in this newsletter is on specific genes that could influence a person’s risk for obesity, fat metabolism and diabetes. Moreover, these genes are part of the gene panels that are tested for in our GENEDIETTMand GENEWELLTMtest. Let’s take a closer look at six of these genes…
- ADRβ2 – Adrenoceptor beta 2 gene
The ADRβ2 gene plays an important role in a person’s weight status because of its effect on the process of fat metabolism, i.e. fat breakdown (lipolysis) and formation (lipogenesis). This gene’s functions include:
- Mobilising fat from the white adipose tissue fat cells for energy in response to exercise and energy restriction
- Promoting gluconeogenesis and glycogenolysis in the liver and skeletal muscle
- Influencing insulin secretion
- Regulating energy expenditure
- Lipid metabolism
- FABP2 – Fatty acid-binding protein 2 gene
The FABP2 gene functions in the small intestine and affects uptake, metabolism and transport of long-chain fatty acids. Individuals with the mutant genotype have a higher affinity for Omega-6 fatty acids and are considered ‘hyper-absorbers’. This gene is associated with the following:
- Increased risk of obesity, body fat and abdominal fat
- Increased risk of inflammation
- Increased risk for insulin resistance
- Higher postprandial triglycerides
- Higher cholesterol
- Leptin resistance, which in turn influences regulation of energy intake and expenditure, appetite and metabolism
- IRS1 – Insulin receptor substrate 1 gene
The IRS1 gene plays a dominant role in regulating insulin and determines how well the body can process carbohydrates and insulin. Genetic variants of the IRS1 gene have been associated with type 2 diabetes, insulin resistance and hyperinsulinemia. It also affects glucose delivery to the cell and can slow down the rate of weight loss. Insulin promotes the uptake of glucose by almost all of the body’s cells, including muscle, liver and fat cells, and is the most effective treatment for elevated blood glucose levels. At any given time, cells are also burning glucose for fuel. However, if the fuel intake (calories eaten) is greater than the energy expenditure (calories burned), glucose is being stored. Muscle and liver cells store extra glucose in the form of ‘glycogen’. Fat cells store extra glucose as fat.
- PPAR-γ– Peroxisome proliferator-activated receptor gamma gene
PPAR-γ is involved in insulin sensitivity and healthy blood glucose levels. PPAR-γ protein is abundantly expressed in fat cells where it plays a key role in the formation of fat cells and acts as a gateway for activating fat cells to store more fatty acids. The protein is activated by Omega-6 fatty acids, which causes fat cells to take fatty acids out of circulation and store them. This causes cells in the body to take up glucose (mainly from carbohydrates) and use it for energy. Normal metabolism makes use of available glucose first for energy conversion and store fats for later use when glucose levels are depleted. PPAR-γ is also involved in the natural circadian rhythm by regulating genes involved in storing fat and insulin sensitivity over a 24-hour cycle.
- SLC2A2 –Solute carrier family 2 (Facilitated Glucose Transporter), member 2 gene
The SLC2A2 gene encodes GLUT2, a carrier protein that enables glucose movement across cell membranes. GLUT2 is the main transporter of glucose between the blood and liver. GLUT2 is also required for glucose sensing by cells of the central nervous system (CNS), which means that the rate of glucose entry into CNS cells is proportional to the blood glucose levels. GLUT2 functions as a ‘glucose detection mechanism’ in direct response to changes in glucose concentrations; for example, when the taste bud cells sense the presence of sugar in food, insulin secretion is initiated.
- TCF7L2 –Transcription factor 7-like 2 gene
Type 2 diabetes is a polygenic disorder, in other words many genes affect the risk of obtaining this disease. The TCF7L2 gene has the biggest effect of all the known risk genes, and individuals who carry the risk allele (a variant form of a gene) have an impaired ability to produce sufficient insulin in response to high carbohydrate intake. Impaired insulin secretion could result from dysfunction of the specialised cells of the pancreas that produce and secrete insulin, and this can lead to higher blood sugar levels over time. Normally, food triggers insulin secretion through the production of hormones in the stomach – known as the incretin effect – and a reduction in this effect may lead to a defective response to food in the gut.
A summary of the risks associated with the mutant genotype variants are given in the table below:
Gene / SNP
Effect of risk allele on genotype
Insulin secretion and glycogenolysis
The G allele is associated with an increased risk for insulin resistance.GA or GG genotypes mobilise less cellular fat, lose less weight than expected in response to exercise and are at greater risk of rebound weight gain.
Metabolism of long-chain fatty acids, cell growth and proliferation
Carrying the threonine allele is associated with an increased sensitivity to saturated fats and refined carbohydrates. The GA and AA genotypes are associated with an increased rate of Omega-6 fatty acid absorption, which increases the risk of obesity.
Insulin-stimulated signal transduction pathways
The risk allele is associated with a moderately (CT genotype) to significantly (CC genotype) increased risk for insulin resistance, which in turn is associated with weight loss resistance.
Regulates fatty acid storage
The C allele represents one of the ‘thrifty genes’ that convert excess food into body fat for energy storage. Individuals with the CC or GC genotypeshould follow a lower-fat diet for effective weight loss.
Mediates bidirectional transfer of glucose
In general, the GA and AA genotypes are associated with high habitual consumption of sugars and usually indicate a preference for sugar (having a ‘sweet tooth’). Elevated glucose and cholesterol levels may be seen with subsequent risk for developing type 2 diabetes and cardiovascular diseases.
Influence transcription of several genes in the TCF gene family
If the correct diet is not followed, even in the absence of overweight, carriers of the risk allele (CT or TT genotypes) have a higher risk of developing type 2 diabetes.
GENEWAYTM Supplement in the spotlight:
What is Carb Support?
Carb Support contains a unique blend of nutrients that support healthy insulin and carbohydrate metabolism when used as part of a healthy diet.
Who would benefit from GENEWAYTM Carb Support?
Carb Support may assist with:
- Poorly managed blood sugar metabolism
- Insulin resistance (that makes it difficult to lose weight)
- Weight management
- PCOS (polycystic ovarian syndrome)
Benefits of supplementation with GENEWAYTM Carb Support
The unique blend of bioactive compounds functions on various pathways responsible for metabolic regulation, including carbohydrate digestion and absorption, body fat accumulation, blood insulin levels and glucose levels. The ingredients in Carb Support™ have other health benefits too, as the blend is a potent antioxidant and has anti-inflammatory, weight management and cardiovascular health advantages.
Genes supported by GENEWAYTM Carb Support
ADRβ2, FABP2, IRS1, PPAR-γ, SLC2A2, TCF7L2