Glucose is a sugar necessary for energy production and the correct functioning of many organs in the body. But blood glucose that’s too high or too low can be harmful. Read on to learn about how glucose works, about diabetes, and about the effects of having high or low levels of glucose in your blood.
What is Glucose?
Glucose, or blood sugar, is the main and most important source of energy for most living organisms. All human cells use glucose for their energy needs. The brain uses the most, and during fasting can account for up to 80% of glucose consumption in the whole body. Serum glucose is the quantity of glucose in the blood [1, 2, 3].
Glucose concentrations in the blood (serum glucose) are maintained within a narrow range through the action of various hormones (i.e. insulin and glucagon) and mechanisms (i.e. gluconeogenesis, glycogenolysis, and glycolysis). Glucose can be measured in a laboratory using blood samples or with glucose meters using reactive strips [2].
Glucose Sources
Glucose in the body comes from two distinct sources. One is through ingested food, mainly carbohydrates, and the other is through production within the body (endogenous glucose production) [1, 2].
Food
Carbs are the major sources of glucose. Carbs generally account for 45-65% of total daily caloric intake. This percentage varies depending on the specific diet. For example, a keto diet is an exception, as carbohydrates account for less than 10% of the diet. When digested, carbs are broken down into glucose in the body [4, 5].
Carbohydrate Digestion
Initial carbohydrate digestion begins in the mouth by a salivary enzyme (amylase). Digestion continues in the stomach and intestines by a variety of enzymes from the intestines and pancreas (α-amylase and brush-border enzymes). Complex carbs get broken down into simpler forms (monosaccharide) and then absorbed through the small intestine into the bloodstream, which increases blood sugar [4].
After absorption, glucose travels through the portal vein into the liver where it is stored in the form of glycogen. Glycogen is a reservoir of glucose molecules and is a source of glucose in times of need [6, 7].
Complex vs. Simple Carbs
There are two main types of carbohydrates: complex and simple. Simple carbohydrates require less digestion (the structure has fewer bonds that enzymes need to break) and cause a rapid rise in blood glucose. Examples of these are candy, carbonated drinks, corn syrup, fruit juice, honey, and table sugar [4].
Complex carbohydrates are a combination of multiple sugars that are bound together and take longer to digest (the structure has more bonds that enzymes need to break). These cause a more gradual increase in blood glucose, and examples are apples, broccoli, lentils, spinach and brown rice [4].
Between the two types, complex carbs are more healthy. This is because of their gradual effects on blood glucose [4].
Endogenous Glucose Production
Glycogen Breakdown (Glycogenolysis)
During fasting periods, glucose is released from its storage in the liver, glycogen (glycogenolysis). Glycogen contains an abundance of glucose that can be broken down by enzymes and released into the bloodstream. This process is activated when serum glucose is too low [8, 9].
Although a lot of glycogen is stored in muscles, it is mostly used as a source of energy during intense exercise. Once all the muscle glycogen is used up, new glucose is taken up by the muscles after a meal to create new stores [10, 11].
New Glucose Production (Gluconeogenesis)
During long-term periods of fasting, the glycogen stores are depleted and the production of new glucose (gluconeogenesis) becomes the predominant source of glucose [8, 12]. The main organs involved in endogenous glucose production (EGP) are the liver and the kidneys.
The liver produces glucose from fructose, lactate, amino acids, and glycerol via the gluconeogenesis pathway. Glucose is then released into the bloodstream, increasing serum glucose. This pathway is activated when serum glucose levels are too low [8, 9].
The outer layer of the kidneys can also make glucose (from lactate, glutamine, glycerol, and alanine) and release it into the bloodstream [8, 9].
Glucose Use and Breakdown
After being digested and taken up across the gut wall, glucose is distributed among the various tissues of the body. Glucose is almost the sole fuel of energy for the brain, except during prolonged starvation. It is also an important source of fuel for the muscles and most major organs [13].
Glycolysis
Most living organisms rely on glycolysis as a way to transform glucose into fuel. It involves the breakdown of glucose, which releases energy (in the form of ATP, adenosine triphosphate) that the cells can use for a variety of different functions. This process is crucial for optimal cell function [14].
Pentose Phosphate Pathway (PPP)
Some glucose is also used to make a modified sugar (pentose phosphate) in the pentose phosphate pathway (PPP). Pentose phosphate provides [15, 16, 17]:
- NADPH, a molecule is involved in energy metabolism and in antioxidant defense
- Ribose-5-phosphate, involved in carbohydrate metabolism. It helps produce other molecules involved in DNA and RNA production
Sugars Increase Body Fat
Excess carbohydrate intake from the diet increases body fat storage through the conversion of sugars into fat and less fat breakdown. Excess glucose in the body is converted into fat (fatty acids) in the liver. Fat breakdown does not occur when there is enough energy available from other sources (carbs in this case) [18, 19].
Serum Glucose Regulation
Blood glucose needs to be maintained within a certain range in order to avoid health complications. Insulin and glucagon play major roles in balancing glucose levels. Both are made by the pancreas [20, 8, 9].
Glucose levels normally rise after a meal which causes a release of insulin. This hormone increases the amount of glucose that cells take up. Glucose can then be stored (as glycogen or fats) or used for fuel, clearing it from the blood [21, 20].
When glucose levels are too low, such as during fasting or between meals, glucagon gets involved. This hormone increases storage breakdown (glycogenolysis) and the production of new glucose (gluconeogenesis), increasing glucose levels in the blood [8, 9]
When insulin is released, after eating a meal, the release of glucagon is blocked. This is the body’s way of balancing the opposite effects of these two hormones; insulin is needed after a meal, and glucagon during fasting, but they are never released at the same time [8, 9, 22, 21].
Normally, glucose cannot enter cells without assistance from insulin and transport proteins. GLUTs is the family of transport proteins that allows for glucose to cross the cell membrane and enter into cells. Activation of these transport proteins is dependent on insulin [3, 23].
During urine filtering, the kidneys reabsorb and release glucose back into the bloodstream. But when blood glucose levels are too high, the transporters cannot reabsorb glucose quickly enough, and it’ll begin appearing in the urine. This is common in diabetes [24].
Urine test strips can show if there’s glucose in urine. These rapid urine tests are available without a prescription, but should be used in consultation with your doctor [25, 26].
Read more about normal blood glucose ranges, causes of high and low levels, and ways to improve them here.
What Is Diabetes?
Diabetes is a chronic condition associated with abnormally elevated blood glucose levels. This is caused by a lack of insulin secretion, impaired response to insulin, or both [27].
There are several types of diabetes, including [27]:
- Type 1 diabetes (T1D) happens when your body doesn’t make enough insulin. It is an autoimmune disease, where the immune system damages insulin-producing cells – (beta cells) in the pancreas. Type 1 diabetic patients require insulin therapy to keep their glucose levels normal [27].
- Type 2 diabetes (T2D) is caused by the body’s inability to respond to insulin, or insulin resistance. This hinders cells in the body from absorbing glucose from the bloodstream. The main treatment for this type of diabetes is usually healthy eating, regular exercise, blood glucose monitoring, medication, and sometimes insulin therapy [27].
- Gestational diabetes mellitus (GDM) occurs during pregnancy in women who previously did not have diabetes. It causes high blood glucose levels during pregnancy [27].
- Maturity-onset diabetes of the young (MODY) is caused by genetic defects of insulin-producing cells and leads to very high glucose levels, and is characterized by hyperglycemia at an early age (before 25) [27].
Who is At Risk of Diabetes?
According to the American Diabetes risk factors for diabetes include [28]:
- Being overweight, obese, or physically inactive
- Having a close (first or second degree) relative with diabetes
- Belonging to a certain race/ethnic group (Native Americans, African-Americans, Hispanic Americans, Asians/South Pacific Islanders)
- Having signs of insulin resistance or conditions associated with insulin resistance, such as high blood pressure (hypertension), low good cholesterol and/or high triglycerides (dyslipidemia), and polycystic ovary syndrome
- Having had diabetes in pregnancy (gestational diabetes)
Health Effects of High Glucose and Diabetes
[29]
1) Blood Vessel Damage
High glucose levels in the body damage the inner lining of blood vessels. This is because high glucose increases damaging (reactive oxidative species, CRP) and inflammatory compounds (cytokines), and makes it harder for the vessels to relax (via reducing NO) [30, 31].
The resulting oxidative stress in the blood vessels causes inflammation. Proteins and leukocytes accumulate, harden blood vessels, and eventually lead to the formation of plaques that block blood flow (atherosclerosis). This is the root cause of heart disease in people with diabetes [30, 31].
If left untreated, high blood sugar can lead to stroke, heart disease, and other blood vessel disorders – the most common complication of type 2 diabetes. A recent analysis of 20 studies concluded that even in the nondiabetic range, elevated blood sugar increases the risk of heart disease [30, 32].
In a study of over 68k people without diabetes, higher blood sugar levels were associated with an increased risk of heart attacks over the next 4 years [33].
2) Nerve Damage
Diabetic neuropathy happens when high glucose causes nerve damage in people with diabetes. High glucose increases inflammation in the nerves, resulting in mild numbness and pain in the legs and feet or problems with digestion, urination, and heart function [34].
A common complication of diabetic neuropathy is called the diabetic foot, with ulcers, infections, and minimal to no feeling in feet or legs. Loss of feeling in the foot may lead to more injuries and open wounds, while a lower immune response in people with diabetes makes it harder to fight the infections off [35].
3) Kidney Damage
Kidney damage (nephropathy) is another common complication of both type 1 and type 2 diabetes. Diabetes can damage the delicate filtering system in the kidneys. Severe damage can cause kidney failure and even end-stage kidney disease, which requires dialysis and a kidney transplant [36].
3) Weakened Immune System
High blood glucose impairs white blood cells (neutrophils), reduces antioxidant activity, and reduces immunity (humoral). This increases the risk of skin disorders and infections [37].
This can be seen from studies that looked at HbA1c. In a study of over 1000 healthy people, elevated HbA1c was associated with impaired immune response (T-cell) [38].
4) Dementia
Dementia refers to memory loss, impaired brain function, and low cognitive activity [39].
In one study (meta-analysis), diabetes was associated with:
- 73% increased risk of all types of dementia,
- 56% increased risk of Alzheimer’s dementia, and
- 127% increased risk of vascular dementia
Vascular dementia is a decline in thinking skills because of reduced or blocked blood flow to the brain, causing oxygen and nutrient deficiency [40, 41, 42].
5) Impaired Vision or Hearing
Diabetic retinopathy (damage to blood vessels in the retina) is a frequent complication of diabetes, and the most common cause of blindness in the working-age population. Fluid build-up in the eyes (diabetic macular edema) also causes loss of vision in those with diabetes [43].
Blindness can be prevented by regularly monitoring and controlling both blood sugar and blood pressure [43].
In a study of 199 diabetics (type 2), 108 patients (54.3%) suffered from dry eye syndrome. This is a condition that causes irritation and blurred vision [44].
Hearing impairment is also more common in people with diabetes. This may be due to the effects of high glucose on the blood vessels and nerves in the ear [45].
6) Osteoporosis
In a meta-analysis, both types of diabetes increased the risk of hip fractures. In type 2 diabetes, bone density is increased, whereas it is decreased in type 1 diabetes [46, 47].
7) Mental Illness
Studies suggest that individuals with type 1 diabetes have a higher risk of depression, anxiety, and eating disorders [48].
If you have diabetes and are suffering from a mental health issue, don’t hesitate to ask for help and support.
8) Cancer
Studies suggest that diabetes may increase the risk of liver, pancreas, uterus, colon/rectum, breast, and bladder cancer. In a study of over 1.3 million Koreans, cancer was more common in individuals with diabetes and/or high glucose levels [49, 50].
Additionally, a meta-analysis (of 23 studies) showed that individuals with both diabetes and cancer have a higher chance of mortality than individuals with cancer alone [49, 50].
In one study, 17,860 men were categorized into three groups: non-diabetic, prediabetic and diabetic, of which 1663 got prostate cancer (after a follow-up). Diabetics were more likely to develop prostate cancer, which may be due to hormonal changes caused by elevated glucose levels. The exact causes are unknown, though [51].
A case-control study evaluated fasting blood glucose levels of around 1100 participants. Individuals with higher fasting blood glucose levels over the last 11 years had a higher risk of pancreatic cancer [52].
Health Effects of Low Glucose (Hypoglycemia)
Hypoglycemia, or very low glucose levels, has severe health effects and increases the risk of serious complications in people with diabetes.
It is a very dangerous state that can lead to coma and even death, depending on its severity or duration. The brain relies on glucose to function. Long-term, very low glucose levels could damage cognitive function, particularly in young children [53, 54].
Hypoglycemia can usually be prevented by regular glucose monitoring, as well as being consistent with your lifestyle and drug regimen [53].
1) Brain Damage
Glucose is fuel for the brain. Inadequate glucose supply over time will result in dementia. Severe episodes may even lead to coma and death [53].
2) Heart Disease
Patients with type 2 diabetes have a higher chance of getting heart disease (cardiovascular disease). But the mortality rates from heart disease are even higher in those who experience severe hypoglycemia [53].
Acute hypoglycemia activates the fight-or-flight response (sympathetic nervous system), which releases epinephrine. This increases heart rate and blood pressure, which can be especially risky for patients with a history of complications [53].
3) Impaired Vision
Hypoglycemia can cause visual disorder in individuals with diabetes and has been linked with double vision (diplopia), dizziness/blurred vision and loss of contrast sensitivity [53].
Hypoglycemia also makes your eyes more sensitive, reduces eye muscle responses, and generally heavily damages and kills cells in the eye (retinal cell dysfunction, retinal cell death, and cone cell death). All these factors can heavily impair vision, and may even cause blindness [53, 55, 56, 57].
4) Lower Quality of Life
Recurrent hypoglycemia episodes generate feelings of powerlessness, anxiety, and depression amongst patients and their families [58].
Acute hypoglycemia can result in mood swings including irritability, stubbornness, and feelings of depression [58].
Decreasing or Increasing Blood Glucose Levels
If your glucose levels are elevated or decreased, the most important thing is to work with your doctor to find out what’s causing abnormal glucose and to treat the underlying conditions!
If you have diabetes, depending on what type of diabetes you have, your doctor may prescribe blood sugar monitoring, insulin and/or other medications. A healthy diet, healthy weight and regular exercise are also important in managing diabetes.
Adherence to therapy and lifestyle and dietary modifications prescribed by your doctor will minimize your risk of diabetic complications and improve your overall quality of life.
Read about the factors that increase or decrease blood sugar levels here. This article also summarizes the best ways to:
- Prevent diabetes if you have prediabetes
- Keep your blood sugar in check if you have diabetes
