What is Glucose?
Glucose is the main and most important source of energy for most living organisms. In humans, all cells use glucose for their energy needs. The brain uses the most glucose, and during fasting can account to 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). It can be measured in a laboratory using blood samples or with glucose meters using reactive strips .
Glucose Production and Sources
Glucose supply to the body comes from two distinct pathways. One way is through production in the body (endogenous glucose production) and the other is through ingested food, mainly from carbohydrates [1, 2].
Carbohydrates are the most major sources of glucose. Carbohydrates generally make up 45-65% of the total daily caloric intake of humans. This percentage varies depending on the specific diet. For example, in a keto diet is an exception, as carbohydrates would probably be less than 10% of the diet. When digested, carbohydrates are broken down into glucose in the body [4, 5].
Initial carbohydrate digestion begins in the mouth through a salivary enzyme (amylase). Digestion continues in the stomach and intestines through a variety of enzymes from the intestines and pancreas (α-amylase and brush-border enzymes). It’s broken down into its simplest form (monosaccharide) and then absorbed through the small intestine into the bloodstream, which increases blood sugar .
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 when broken down. This is especially important when blood glucose levels fall [6, 7].
In normal conditions, a part of the digested glucose is used and the remaining part is converted into sugar storages called glycogen that serve as a reservoir in muscles and liver .
Lactase is an enzyme in the small intestine (brush-border enzyme) that is involved in the digestion of lactose, a milk sugar. Lactase breaks bonds (β-glycosidic bonds) between glucose and galactose in lactose .
People who are lactose intolerant have a deficiency in the lactase enzyme. This causes stomach irritation upon dairy consumption because lactose does not get digested in the small intestine .
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 .
Complex carbohydrates are a combination of multiple sugars bonded 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 .
Between the two types, complex carbohydrates are more healthy. This is because of their gradual effects on blood glucose. Fibers are also an important type of carbohydrate because they reduce the risk of heart disease, stroke, and digestive problems. Fibers, however, are not digested in the body, their beneficial effects are limited to the gut .
Endogenous Glucose Production
Glucose can also be released from stores or made from other nutrients in the body. The main organs involved in endogenous glucose production (EGP) are the liver and the kidneys. The human liver produces glucose that is released into the bloodstream and used by other tissues, particularly during periods of fasting .
Glucose released from the liver comes from glycogen breakdown (glycogenolysis) and direct glucose production (gluconeogenesis). During long-term periods of fasting, the glycogen store is depleted and the production of new glucose (gluconeogenesis) becomes the predominant source of glucose [10, 11].
New Glucose Production (Gluconeogenesis)
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. Glucose in the kidneys is mostly made from glutamate [10, 12].
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 [10, 12].
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 [13, 14].
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 .
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 .
Pentose Phosphate Pathway (PPP)
- 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
Can Sugars Increase Body Fat?
Excess carbohydrate intake from the diet increases body fat storages 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) [20, 21].
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 [22, 10, 12].
Glucose levels normally rise after a meal and insulin gets activated. This hormone increases the amount of glucose the cells take up. Glucose can then be stored (as glycogen or fats) or used for fuel, clearing it from the blood [23, 22].
When glucose levels are too low, such as during fasting or between meals, glucagon gets activated. This hormone increases storage breakdown (glycogenolysis) and the production of new glucose (gluconeogenesis), increasing glucose levels in the blood [10, 12]
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 [10, 12, 24, 23].
Normal 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, 25].
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 cases of undiagnosed diabetes .
Urine test strips can show whether an individual has a urinary tract infection or diabetes. These rapid urine tests are available without a prescription, but should be used in consultation with your doctor [27, 28].
This test can predict diabetes by detecting high levels of glucose and ketone bodies in the urine. Ketone bodies in the urine are most common in patients with type 1 diabetes because they are produced in response to low insulin levels [27, 28, 29].
What Is Diabetes?
Diabetes is a chronic condition normally associated with abnormally elevated blood glucose. This is caused by a lack of insulin secretion, activity, or both .
There are several types of diabetes :
- Type 1 diabetes (T1D) happens when your body does not make enough insulin. It is an autoimmune disease, where the immune system damages insulin-producing cells – beta cells – in the pancreas. It occurs once most of these cells are destroyed, leading to high blood glucose. Type 1 diabetic patients require insulin therapy to keep their glucose levels normal .
- 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 in the bloodstream, eventually causing hyperglycemia. The main treatment for this is usually healthy eating, regular exercise, blood glucose monitoring, and sometimes insulin therapy .
- Gestational diabetes mellitus (GDM) occurs during pregnancy in women who previously did not have. It causes high blood glucose levels during pregnancy .
- Other Less Common Types :
- 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). Another form is caused by genetic defects of a protein (glucokinase) also involved in the insulin-release pathway.
- Genetic defects in insulin action (receptor altered) can cause high blood sugar.
- Diseases of the pancreas can damage insulin-producing cells, ultimately stopping insulin release.
- Hormonal disorders such as an excess release of several hormones (growth hormones, cortisol, glucagon, and epinephrine) can block insulin’s function.
- Low potassium levels (hypokalemia) caused by hormone-producing tumors (somatostatinoma and aldosteronoma) block insulin release.
Health Risks of High Glucose and Diabetes
Diabetes Damages Blood Vessels
The high glucose levels in the body damage the inner lining (endothelium) 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) [32, 33].
The resulting oxidative stress in the blood vessels causes inflammation. This accumulates proteins and leukocytes that harden the blood vessels and eventually lead to the formation of plaques, which block blood vessels (atherosclerosis). This is the root of all diabetes-caused cardiovascular diseases [32, 33].
If left untreated, high blood sugar leads to a number of cardiovascular diseases such as stroke, heart disease, and other blood circulation disorders – the most common complication of type 2 diabetes. A recent meta-analysis of 20 studies on nondiabetic subjects concluded that even in the nondiabetic range, elevated glucose increases the risk for cardiovascular disease [32, 34].
Diabetes Damages Nerves
Diabetic neuropathy happens when high glucose causes nerve damage in patients with diabetes. High glucose increases inflammation in the nerves, resulting in mild numbness and pain in legs and feet or problems with digestion, urination, and the heart [35, 35].
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 can lead to more injuries and open wounds, while a lower immune response in people with diabetes can make it harder to fight the infection off .
Diabetes Increases the Risk of Dementia
Dementia refers to memory loss, impaired brain function, and low cognitive activity .
In one study (meta-analysis), people with diabetes had:
- 73% increased risk of all types of dementia,
- 56% increased risk of Alzheimer’s dementia, and
- 127% increased risk of vascular dementia compared to those without diabetes.
Diabetes May Worsen Mental Illness
Mental health is important in diabetes. Therapy for diabetes requires daily self-management (maintaining glucose levels and avoiding hypoglycemia). Mental health problems can cause people to stick to their treatment less, causing poor blood glucose control. This increases the risk of short- and long-term complications .
Individuals with type 1 diabetes have a doubled risk for depression, anxiety, and eating disorders. When untreated, this can lead to disability, unemployment, family dysfunction, homelessness, substance abuse, incarceration, and even suicide .
If you have diabetes and are suffering from a mental health issue, don’t hesitate to ask for help and support.
Diabetes Increases the Risk of Cancer
Diabetes increases the risk the of liver, pancreas, uterus, colon/rectum, breast, and bladder cancer. In a study of over 1.3 million Korean adults (prospective), cancer was more common in individuals with diabetes and/or high glucose levels. Overall, 8-18% of individuals with cancer also have diabetes [42, 43].
Diabetes May Cause Osteoporosis
Diabetes increases the risk of hip fractures in both sexes (SR). This effect is stronger in type 1 diabetes than type 2 diabetes. Type 2 diabetes is also weakly associated with fractures of other parts of the body [44, 45].
In another meta-analysis, both types of diabetes increased the risk of hip fractures. In type 2 diabetes though, bone density is increased, whereas it is decreased in type 1 diabetes .
Diabetes May Cause Hearing Impairment
Hearing impairment is more common in people with diabetes. This may be due to the effects of high glucose on the blood vessels and neurons in the ear .
Hearing impairment was about twice as prevalent in people with diabetes compared to those without, even when all other factors are considered (survey) .
Diabetes Increases the Chance of Hepatitis B
Compared with the general population, people with diabetes are more likely to get hepatitis B. This may be due to contact with infected blood or through improper equipment use (glucose monitoring devices or infected needles) [47, 48]
Diabetes Weakens the Immune Response
Diabetic individuals have a 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 .
Since type 1 diabetes (T1D) is an autoimmune disease, lymphocytes (T cells) in the body are destroying insulin-producing beta cells in the pancreas. The impaired immune response can increase the chance of various yeast, bacterial, and viral infections [49, 50].
This includes lower respiratory tract infections, liver infections, head and neck infections, urinary tract infections, and skin and mucous membrane infections. The skin can also be affected by blisters, skin lesions, bumps, rashes, and foot ulcers [49, 51].
Aside from the immune system, the blood vessel and nerve damage caused by high glucose further increases risk of infection. The antibacterial activity of urine is decreased as well .
Diabetes May Cause Vision Loss
Diabetic retinopathy (damage to blood vessels at the retina) is one of the most frequent complications 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 patients with diabetes .
Blindness can be prevented by regularly monitoring and controlling both blood sugar and blood pressure .
Health Risks of Low Glucose (Hypoglycemia)
Hypoglycemia, or very low glucose levels, increases the risk of serious complications in patients with diabetes who are on insulin. In fact, it causes a six-fold increase in death if severe. Hypoglycemia can usually be prevented by regular glucose monitoring, as well as being consistent with your lifestyle and drug regimen .
Hypoglycemia Affects the Whole Body
The fight or flight response from an episode of hypoglycemia may cause sweating and palpitations, cognitive dysfunction, and even seizures.
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 intellectual function, particularly in young children [53, 54].
Hypoglycemia And the Brain
Glucose is the fuel for the brain. Inadequate glucose supply will result in dementia, and may eventually lead to coma and death .
Severe hypoglycemia episodes in elderly patients increase the risk of dementia and brain inflammation (cerebellar ataxia) .
Hypoglycemia And the Heart
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 .
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 .
Hypoglycemia And the Eyes
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 .
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].
Hypoglycemia And Hormones
Acute hypoglycemia activates the fight-or-flight response (sympathetic nervous system), causing increases in epinephrine and norepinephrine. Hypoglycemia also increases ACTH and inflammatory markers (C-reactive protein, Il-6, Il-8, and more) .
Hypoglycemia Reduces the Quality of Life
Recurrent hypoglycemia episodes generate feelings of powerlessness, anxiety, and depression amongst patients and their families .
Everyone is different, and our bodies can be complex. If you want to increase/decrease your glucose levels, it’s best to analyze them with Lab Test Analyzer. This tool will compute, based on this and your other results, the best steps you can take that will bring you back to optimal.
What Increases Glucose?
1) Sleep Fragmentation
Stress can cause hyperglycemia by increasing hormones that raise blood sugar levels (glucagon, growth hormone, catecholamine, and glucocorticoids), cytokines (tumor necrosis factor alpha and interleukin-1) .
In normal conditions, glucose production (gluconeogenesis) is blocked during hyperglycemia. During stress, gluconeogenesis does not get blocked, leading to glucose production despite already high levels. Additionally, the effects of insulin are reduced (impaired glucose absorption into muscles), further increasing blood glucose .
Drugs and Hormones
This hormone has the opposite effects as insulin. It increases serum glucose by increasing glycogen breakdown (glycogenolysis) and glucose production (gluconeogenesis) .
Epinephrine normally boosts glucose release (both from glycogenolysis and gluconeogenesis) and blocks glucose breakdown. The body’s response to epinephrine usually results in high glucose levels .
4) Thyroid Hormones
5) Growth Hormone (GH)
Increased growth hormone levels cause insulin resistance (within 2 – 12 hrs) and decrease insulin activity, which increases serum glucose .
Steroid drugs (corticosteroids) increase glucose production by enhancing the effects of glucagon and epinephrine, which promote glucose production. Additionally, corticosteroids block production and release of insulin, causing hyperglycemia .
6) Antipsychotic Medications
Antipsychotic medications (chlorpromazine, clozapine, olanzapine and more) can cause hyperglycemia by decreasing the effect of insulin. This may lead to high glucose, predisposing people on antipsychotics to diabetes .
Thiazide diuretics are used to lower high blood pressure and edema by flushing excess fluids from the body. They can have a number of side effects, including elevated blood glucose. Thiazide diuretics can decrease insulin production and increase the risk of diabetes .
1) Niacin (Vitamin B3)
Niacin can be found in several foods like fruits, vegetables, seeds, liver, chicken, beef, eggs, and fish.
A study (RCT) showed that the use of niacin for 3 years in subjects with high blood fats and normal glucose levels increased in blood glucose. This may slightly increase the risk of developing impaired fasting glucose, but actually improved heart and blood vessel health .
Niacin is generally safe and has several health benefits. But people with a risk of diabetes or those with diabetes should consult a healthcare professional first and monitor their glucose levels closely if taking niacin.
2) White Rice
Data suggests that regular consumption of white rice increases the risk of type 2 diabetes. Replacement of white rice with brown rice or other whole grains reduces the risk of type 2 diabetes .
- Processed meat consumption increased fasting glucose
- Unprocessed meat increased both fasting glucose and insulin
- Red meat consumption increased the risk of type 2 diabetes
Non-caloric artificial sweeteners (NAS) are popular due to their low calories and perceived health benefits (weight and serum glucose reduction). A study in mice found that non-caloric artificial sweeteners actually lead to glucose intolerance – lowering the ability of the body to reduce glucose levels after a meal. They can disrupt the gut microbiome, which contributes to the negative effects .
Ways to Decrease Blood Glucose
A study of 62 patients with type 2 diabetes determined that long-term regular physical activity is helpful in blood sugar control. Additionally, resistance training is even better at preventing high glucose (decreases HbA1c) than aerobic (cardio) training in adults [75, 76].
Diet and exercise are preferred therapeutic strategies for the prevention and management of glucose intolerance and insulin resistance in overweight people .
2) Weight Loss
Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes .
Fat tissues release compounds (fatty acids, glycerol, hormones, cytokines, and other factors) that are involved in insulin resistance. Weight and fat loss will reduce these harmful effects, may improve the activity of insulin, and decrease blood glucose .
In a study in rats, alcohol increased insulin secretion and reduced glucose levels (via nitric oxide and the vagus nerve). But alcoholism, poor liver function, and poor nutrition can cause dangerously low glucose levels [79, 80].
Moderate drinking decreased the risk of diabetes in one analysis (SR), but only in Asian women. Another analysis (MA) did not find an effect of alcohol consumption on glucose in non-diabetic individuals [81, 80].
Drugs and Hormones
This is a natural hormone in the body that is produced when serum glucose levels increase. It reduces serum glucose by promoting glucose transport into insulin-sensitive cells. Insulin is the primary therapy given to individuals with type 1 diabetes, who are not able to produce it due to pancreas damage .
Since the discovery of insulin, therapy options have expanded for patients with diabetes. Many different varieties of human insulin are available, each with different effects. Unlike before, all insulin produced is now of non-animal origin (produced with recombinant DNA techniques) .
In the US, the types of commercially available insulin are :
- Short-acting Regular: The most common and generic version. Regular insulin needs to be injected about 30 minutes before a meal because it has a delayed effect (30 – 60 minutes).
- Rapid-acting: This type of insulin is designed to have a more rapid effect in the body (breaks down and is absorbed more easily). These can be taken about 15-20 minutes before a meal, making it more convenient for patients to adhere to their therapy. It has a shorter duration of action than regular insulin.
- Intermediate-acting: This type takes 2 hours to work, has a broad peak (6-14 hours), and can last up to 16 hours. It can be used at bedtime or in the morning.
- Long-acting: These provide basal insulin, to make up for a normal level of insulin outside of meals. They block glucose production (gluconeogenesis) and prevent hyperglycemia during fasting states. They also block ketone body production.
- Insulin mixtures: There can be mixtures of rapid-acting, intermediate-acting, and regular insulin. This will provide the required dosage for an upcoming meal, as well as basal coverage. However, there is an increased risk of hypoglycemia using mixed insulin preparations, as they are not individually tailored.
Somatostatin gets naturally released in the body when glucose levels rise just slightly (as low as 3 mmol/L). This hormone blocks the release of glucagon, preventing glucose levels from further increasing .
In 9 children with diabetes, somatostatin injection followed by infusion significantly reduced serum glucose levels over time .
3) Incretins (GLP-1)
Sulfonylureas are commonly used as the second-line of therapy in patients with type 2 diabetes. They cause insulin release independent of the blood glucose levels, often causing hypoglycemia as a side effect .
Meglitinides stimulate insulin release very rapidly and are quickly broken down in the liver. The fast action and quick elimination makes meglitinides a suitable therapy for patients with type 2 diabetes that like to live a more flexible lifestyle (i.e. unplanned eating behavior in elderly patients). The downside is that these drugs are rather expensive, and are not commonly used .
Tramadol is a pain medication (weak opioid) that increases the risk of hospitalization due to hypoglycemia compared to other opioids .
Pramlintide is similar to a hormone that the pancreas makes. It blocks glucagon release and reduces appetite. It is a U.S. Food and Drug Administration (FDA)-approved therapy for use in adults with type 1 diabetes. It induces weight loss and lowers the insulin dose .
8) Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors
SGLT2 inhibitors reduce glucose independently of insulin, by blocking glucose reabsorption in the kidneys. This causes more glucose to be eliminated in the urine. They are also used as a therapy for type 2 diabetes .
Fenugreek is an aromatic plant that has many uses and is a key ingredient of curries and other Indian recipes. 24 type 2 diabetic patients were treated with Fenugreek for 8 weeks. Fenugreek lowered glucose levels long-term (by decreasing HbA1c), and can potentially be used as an add-on treatment for type 2 diabetes if soaked in hot water .
Additionally, a study of 220 healthy subjects and 90 diabetic patients found that coffee consumption reduces fasting blood glucose levels and provides better glucose control long-term (decreases HbA1c) .
In a study in rats, raw garlic significantly reduced blood glucose levels, whereas boiled garlic had no effect .
Daily dietary supplementation of bioactives from freeze-dried whole blueberry powder improved insulin sensitivity over 6 weeks in 32 obese, non-diabetic participants. But it had no effect on glucose levels .
6) Cherry Juice
7) Mediterranean Diet
The Mediterranean diet improved insulin resistance study on 11 offspring of obese diabetic individuals (prospective). It may lower glucose better than carbohydrate-rich diets .
Regular consumption of mango improves blood glucose levels in obese individuals, according to a study of 22 obese individuals (pilot) .
Vinegar may have beneficial effects on diabetes risk factors, such as high glucose or high insulin (which leads to decreased insulin activity) .
Irregular Glucose Levels?
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