Glucose is a type of sugar, in the blood flow is known as serum glucose or blood sugar, and is necessary for energy production and correct functioning of the human body. Read more below to know what are the pros and cons of having higher or lower levels of serum glucose.
- What Are The Sources Of Glucose For The Human Body?
- Intake Of Glucose
- Endogenous Glucose Production
- New Glucose Production (Gluconeogenesis)
- Glycogen Breakdown (Glycogenolysis)
- Glucose Dephosphorylation After Gluconeogenesis And Glycogenolysis
- How Is Serum Glucose Regulated?
- How is The Serum Glucose Disposed of ?
- Glucose Oxidation To Carbon Dioxide
- Pentose Phosphate Pathway (PPP)
- Fatty Acid Synthesis
- Hexosamine Biosynthetic Pathway (HBP)
- Formation Of UDP-Glucuronate
- What Are The Normal Levels Of Serum Glucose?
- What Is Diabetes?
- What Are The Health Effects Of Having Higher Levels Of Glucose And/Or Diabetes?
- Diabetes And Dementia
- Diabetes Relation With Mental Illness
- Hyperglycemia And Cancer
- Diabetes And Hip Fractures
- Hyperglycemia and Hearing Impairment
- Diabetes And Hepatitis B
- Diabetes And Cutaneous Disorders
- Diabetes Increased Risk Of Common Infections
- Increased Glucose And Cardiovascular Risk
- Diabetes And Eyesight Loss
- What Are The Health Effects Of Having Lower Levels Of Glucose?
- How Can You Increase Or Decrease Serum Glucose Naturally Or Pharmacologically?
- Lifestyle to Increase Serum Glucose
- Drugs, Hormones/Pathways That Increase Serum Glucose
- Nutritional Factors That Increase Serum Glucose
- Lifestyle to Decrease Serum Glucose
- Drugs, Hormones/Pathways That Decreases Serum Glucose
- Nutritional Factors That Decrease Serum Glucose
Serum glucose is defined as the quantity of glucose in the blood. Glucose, also known as dextrose is a dextrorotatory monosaccharide (hexose) with the chemical formula of C6H12O6.
It is found in the free state in fruits and other parts of plants, and combined in glucosides, disaccharides (often with fructose in sugars),oligosaccharides, and polysaccharides; it is the product of complete hydrolysis of cellulose, starch, and glycogen (R, R1).
Glucose is an obligate metabolic energy source for some tissues and cells like muscles and erythrocytes and preferred energy for many others like central nervous system (CNS).
In the body, there are two main sources: dietary carbohydrate and endogenous production (R).
Serum Glucose concentrations are maintained within a narrow range by the action of various hormones and mechanisms. It can be measured in a laboratory using blood samples or with glucose meters using reactive stripes (R).
Another way to measure serum glucose is by measuring the glycosylation of hemoglobin. This process takes place under physiologic conditions, at a specific site on the NH2-terminal amino group of the β chains of the hemoglobin, a site usually involved in the binding of organic phosphates.
Normally, about 5% of hemoglobin in a population of normal human red cells is covalently linked to glucose, resulting in the formation of a chromatographically distinct minor component designated as HbA1c (R, R1).
These hemoglobin molecules are formed slowly and continuously throughout the 120-days lifespan of the red cell so glycosylated hemoglobin levels are a reflection of a patient’s average serum glucose for the two preceding months.
What Are The Sources Of Glucose For The Human Body?
Glucose supply to the body comes from two distinct pathways, one of them is Endogenous Glucose Production (EGP), and the other pathway consists of the intake of Glucose (EG) through ingested food, mainly from carbohydrates.
This is either in the direct form of glucose or from other sugars that once digested are converted into glucose.
Intake Of Glucose
The Americans gain carbohydrates from the diet, mostly from simple sugars (glucose and fructose), disaccharides (lactose and sucrose), and complex carbohydrates (starch and glycogen).
Carbohydrates are not really essential in the diet, but they generally make up to 40–45% of the total daily caloric intake of humans. Plant starches generally constitute 50–60% of the carbohydrate calories consumed (R).
The initial digestion of these carbohydrates starts in the mouth with a salivary enzyme denominated α-amylase. There is another α-amylase in the pancreas. Salivary α-amylase is deactivated by acid pH so it doesn’t take long to get inactivated by stomach acid.
If the salivary α-amylase is inside the bolus it can continue to digest complex carbohydrates until it is exposed and enters into contact with stomach acid. Thus, up to 30–40% of the digestion of complex carbohydrates can take place before the food reaches the small intestine (R).
Inside the small intestine, pancreatic juice enters and with its high bicarbonate concentration starts to neutralize gastric acid.
Within the pancreatic juice is the pancreatic α-amylase that enters the intestine and actively continues to break down complex carbohydrates into maltose, maltotriose(isomaltose), trisaccharides, larger oligosaccharides, and α-limit dextrins (oligosaccharides with branch points) (R).
The molecules that result from the hydrolysis of starch by α-amylase are still di, tri, and oligosaccharides, which means that they need additional digestion in order to be absorbed as monosaccharides.
There are enzymes in the brush borders of intestinal epithelial cells (enterocytes) that convert bigger molecules into smaller molecules so they can be absorbed (R).
There are several brush-border membrane enzymes like β-glucoamylase (also known as maltase), sucrase-isomaltase complex, Isomaltase (also known as limit dextrinase or debranching enzyme), sucrase, that hydrolyzes linkages between glucose and fructose molecules and thus splits sucrose.
Another of the brush-border membrane enzymes is the β-glycosidase complex, which includes lactase and glucosyl-ceramidase. Glucosyl-ceramidase splits β-glycosidic bonds between glucose or galactose. Lactase splits bonds between glucose and galactose in milk sugar (R).
Some adults have lactose intolerance because of a lactase deficiency which is known as “adult hypolactasia”, this causes that the lactase-deficient small intestine epithelial cells allow the lactose acquired from the diet to reach the colon, once it reaches the colon the bacteria ferment lactose into gas and organic acids.
This produces an osmotic gradient, increasing water in the inside of the colon, which causes a distension of the gut walls that increases gut movements (peristalsis), provoking flatulence along with diarrhea (R).
Another brush-border membrane enzyme is trehalase, which hydrolyzes the glycosidic bond in trehalose, a small disaccharide uncommon in the American diet.
After the digestion of carbohydrates by α-amylase and the brush-border membrane enzymes, the resulting simpler molecules (monosaccharides) are transported inside the enterocyte by transmembrane transport proteins that allow the transit of specific molecules.
Glucose and galactose are actively transported into the enterocyte by Na+-Glucose cotransporter SGLT1 (SLC5A1 gene on chromosome 22) via the transmembrane electrochemical Na+ gradient, and exit across the basolateral membrane by the glucose transporter GLUT2 (SLC2A2 gene on chromosome 3).
GLUT2 are found in intestinal and kidney basolateral membranes (predominantly), in the liver, and in pancreatic β-cells and mediate both the uptake and efflux of glucose, galactose, or fructose (R, R1, R2).
Another monosaccharide like Fructose is not transported by SGLT1 but rather is taken up on the brush-border side of the intestine cells by the specific facilitated diffusion transporter GLUT5 (SLC2A5 gene on chromosome 1).
Once the monosaccharides go through the cell to the basolateral membrane and into the bloodstream, they go to the Liver through the portal vein to continue with their metabolism (R).
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 muscle and liver.
To synthesize Glucose Storages (glycogen), glucose is converted into UDP-glucose that is the immediate glucose donor for glycogen synthesis (R).
Endogenous Glucose Production
The main organs involved in the EGP are the liver and the kidneys. The human liver produces glucose that is released into the systemic circulation and used by other tissues, particularly during periods of fasting.
Hepatic glucose production derives from glycogen breakdown (glycogenolysis) and from the production of glucose (gluconeogenesis). During short-term periods of fasting glycogen breakdown (glycogenolysis) is the predominant source of glucose.
The magnitude of kidney glucose release in humans is somewhat unclear because the kidney consumes and produces glucose. One analysis of 10 published studies concluded that the kidney’s contribution to total body glucose release in the postabsorptive state is approximately 20%.
Based on the assumption that the production of glucose accounts for approximately 50% of all circulatory glucose release during the fasting state, kidney production of glucose is projected, although not conclusively proven, to potentially be responsible for approximately 40% of all the glucose production (R, R).
New Glucose Production (Gluconeogenesis)
The liver synthesizes glucose from precursors such as fructose, lactate, alanine, and glycerol via the gluconeogenesis pathway.
Glutamine is a predominant precursor of gluconeogenesis in the kidney (R).
The kidney’s cortex has enzymes for the production of glucose, and it synthesizes glucose-6-phosphate from precursors like; lactate, glutamine, glycerol, alanine. Also, the kidneys are able to release glucose into the bloodstream (R, R).
Glycogen Breakdown (Glycogenolysis)
During fasting periods, in the liver, glucose is released from glycogen (glycogenolysis)by a process called hydrolysis mediated by an enzyme called glycogen phosphorylase.
This glucose becomes available to be used in other tissues, meanwhile glycogen in muscular tissue it is not available to be used in other tissues due to the deficiency of an enzyme (glucose-6-phosphatase) (R).
Glucose Dephosphorylation After Gluconeogenesis And Glycogenolysis
In the liver cell (hepatocyte) or the kidney’s cortex, glucose-6-phosphate derived from either gluconeogenesis or glycogenolysis needs to get a phosphate removed (dephosphorylation) to be able to get out of the cell (R).
The mechanisms involved in glucose exit from the liver cells to the bloodstream after dephosphorylation are not really clear.
Patients that present mutations in the SLC2A2 gene (GLUT2 transporter Gene) suffer fasting hypoglycemia and liver glycogen accumulation, indicating that GLUT2 is required for glucose to leave the hepatocyte.
GLUT2 is also available in the kidneys so is probably the mechanism involved in the exit of glucose out of the hepatocyte and in the kidney cortex (R).
How Is Serum Glucose Regulated?
After the glucose intake, the increase in serum glucose concentration triggers a series of blood sugar regulation processes to maintain optimal levels.
Specifical hormones like insulin, glucagon, incretins, and various cells and tissues (within the brain, muscle, gut, liver, kidney and fat tissue), are involved in blood glucose regulation by means of uptake, metabolism, storage, and excretion (R, R).
This highly controlled process of glucose regulation may be particularly evident during the period after eating a meal (postprandial), during which, under normal physiologic circumstances, glucose levels rarely rise beyond 140 mg/dL, even after consumption of a high-carbohydrate meal (R).
The main hormones involved in glucose regulation are insulin and glucagon, both produced in the pancreas, within the islets of Langerhans; β-cells produce insulin and α-cells produce glucagon.
Insulin (INS gene located on chromosome 11), is a potent inhibiting fat breakdown (antilipolytic) hormone, is known to reduce blood glucose levels by accelerating transport of glucose into insulin-sensitive cells and facilitating its conversion to storage compounds via conversion of glucose to glycogen (glycogenesis) and fat production (lipogenesis) (R, R).
Glucagon (GCG gene located on chromosome 2), is produced in response to glucose levels lower than normal (hypoglycemia) and acts to increase them by accelerating the breakdown of glucose storages (glycogen) and promoting the formation of new glucose (gluconeogenesis).
After a glucose-containing meal, however, glucagon secretion is inhibited by high levels of insulin, which contributes to the suppression of the hepatic glucose production and maintenance of normal levels of glucose after eating a meal. The hormone amylin also contributes to glucagon levels reduction after eating a meal (postprandial) (R, R).
Glucose can’t go through impermeable cell membranes, so it requires assistance from both insulin and the GLUTs family of transport proteins.
GLUTs act as channels, forming a pore across fat soluble cellular membranes, through which glucose can move more easily.
Of the 12 known GLUT molecules, GLUT-4 (SLC2A4 gene located on chromosome 17)is considered the major transporter for fat, muscle, and cardiac tissue, whereas GLUTs 1, 2, 3, and 8 facilitate glucose entry into other organs like brain, liver, and kidneys.
Also, the role of glucose reabsorption in kidneys is crucial for glucose regulation. Under normal circumstances, the glucose is freely filtered, if the plasma glucose normal concentration is 1 gr/L and glomerular filtration rate (renal filtration of blood rate) (GFR) is about 180 L/day, the amount of the filtered glucose is about 180 gr/day (or 125 mg/min).
Virtually, none of the filtered glucose is normally excreted in the urine; therefore, the kidneys have the ability to reabsorb over 180 gr of glucose per day (R).
This mechanism, which allows the retention of valuable substances like glucose and amino acids, is facilitated by the combination of secondary active glucose transporters and passive glucose diffusion, The SGLT-2 Na+/Glucose cotransporters that are located at the luminal membrane of the kidney tubular cells permits the transit of glucose into the cell.
After entering the cell, glucose exists across the basolateral membranes by facilitated diffusion down its electrochemical gradient to the bloodstream again. If the serum glucose overpasses the 180 mg/dL, the kidney cannot reabsorb all the glucose and it will start appearing in the urine (R).
How is The Serum Glucose Disposed of ?
After being digested and absorbed across the gut wall, glucose is distributed among the various tissues of the body.
It is required by all cells, but its main consumer is the brain in the fasting or “postabsorptive” phase, which accounts for approximately 50% of the body’s glucose use.
Another 25% of glucose disposal occurs in the splanchnic area (liver and gut tissue), and the remaining 25% takes place in insulin-dependent tissues, including muscle and fat tissue.
The glucose disposal and usage have several mechanisms (R).
Glucose Oxidation To Carbon Dioxide
The oxidation process occurs mainly in the brain and skeletal muscle, and these are the organs that consume more circulating glucose. Glucose is oxidized to carbon dioxide in a process called glycolysis or glucose breakdown (R, R).
Pentose Phosphate Pathway (PPP)
Only about 20% of glucose is directly decarboxylated to pentose phosphate. The pentose phosphate pathway is a physiological route of glucose metabolism in the cytosol that provides reducing equivalents (NADPH) and ribose 5-phosphate.
In the liver cells (hepatocytes), NADPH is required for the synthesis of fatty acids. In the red blood cells, NADPH is predominantly used to maintain glutathione in the reduced state, protecting cells from oxidative damage.
Fatty Acid Synthesis
When oxidation capacity is surpassed, additional glucose is converted into fatty acids in the liver. Excess dietary carbohydrate increases body fat storages both by suppression of the oxidation of dietary fat and by conversion of the excess carbohydrate to fat.
Among healthy subjects, carbohydrate overfeeding increases hepatic fat production compared to a control diet. The excess of fatty acids leads to the exacerbated Acetyl-CoA production through an oxidation process (R).
The Acetyl-CoA gives rise to the ketone bodies via the reactions of the HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) cycle. The enzymes involved are found in extrahepatic tissues such as heart, kidney, and intestine.
But the most important enzyme (The HMG-CoA synthase), is present in large quantities only in the liver, which marks this tissue as the primary site of ketogenesis.
The ketone bodies produced by the liver readily diffuse into the blood and are carried to extrahepatic tissues where they must be converted back into acetyl-CoA before their complete combustion to C02 and water via the reactions of the Krebs cycle (R, R).
Hexosamine Biosynthetic Pathway (HBP)
The HBP is a glucose metabolic pathway, usually accounting for only 2 – 5% of total glucose metabolism.
Formation Of UDP-Glucuronate
A minor amount of UDP-glucose is converted to UDP-glucuronate in the liver which yields glucuronate residues to a variety of external and internal compounds to allow their solubilization and excretion.
What Are The Normal Levels Of Serum Glucose?
Normal Serum Glucose levels in healthy individuals are 55 mg/dL – 100 mg/dL(3.0mmol/L – 5,6mmol/L).
Glycosylated Hemoglobin (HbA1c) normal levels go from A1C 5%–5.7% (31–39 mmol/mol)
When Serum Glucose is under 55 mg/dL in healthy individuals (3.0mmol/L) and under 70 mg/dL (3.9mmol/L) in diabetic patients being treated is called “Hypoglycemia”.
|Prediabetes (Patients with increased risk of Diabetes)|
|– Serum Glucose measured after a fasting of at least 8 hours that goes from 100 mg/dl – 125 mg/dL 5.6 mmol/L – 6.9 mmol/L|
|– Serum Glucose measured 2 hours after an oral glucose tolerance test (OGTT) 140 mg/dL – 199 mg/dL (7.8 mmol/L – 11.0 mmol/L)|
|– HbA1c 5.7–6.4% (39–46 mmol/mol)|
|Diabetes (2 Tests in a row)|
|– Serum Glucose measured after a fasting of at least 8 hours that goes ≥126 mg/dL (≥7.0 mmol/L).|
|– Serum Glucose measured 2 hours after an oral glucose tolerance test (OGTT) of ≥200 mg/dL (≥ 11.1 mmol/L)|
|– HbA1c ≥6.5% (48 mmol/mol). The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay|
|In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose of ≥200 mg/dL (11.1 mmol/L).|
*Oral Glucose Tolerance Test (OGTT): Consists in the ingestion of a sweet liquid composed of 75gr of glucose dissolved in water, glucose is measured before and 2 hours after the ingestion of the liquid (R, R).
What Is Diabetes?
Diabetes is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both (R).
Diabetes can be classified into the following general categories:
- Type 1 diabetes (T1D): Due to β-cell destruction in the pancreas, usually leading to absolute insulin deficiency.
- Type 2 diabetes (T2D): Due to a progressive loss of insulin secretion on the background of insulin resistance.
- Gestational diabetes mellitus (GDM): Diabetes diagnosed in the second or third trimester of pregnancy that is not clearly overt diabetes.
- Specific types of diabetes due to other causes; monogenic diabetes syndromes such as neonatal diabetes and maturity-onset diabetes of the young (MODY), diseases of the exocrine pancreas such as cystic fibrosis, and drug- or chemical-induced diabetes such as with glucocorticoid use, in the treatment of HIV/AIDS or after organ transplantation (R).
What Are The Health Effects Of Having Higher Levels Of Glucose And/Or Diabetes?
Diabetes And Dementia
The most severe form of cognitive dysfunction is dementia.
A recent meta-analysis of prospective observational studies in people with diabetes showed a 73% increased risk of all types of dementia, a 56% increased risk of Alzheimer dementia, and 127% increased the risk of vascular dementia compared with individuals without diabetes (R).
Diabetes Relation With Mental Illness
A severe mental disorder that includes schizophrenia, bipolar disorder, and depression is increased 1.7-fold in people with diabetes (R).
Hyperglycemia And Cancer
Diabetes is associated with increased risk of cancer of the liver, pancreas, endometrium, colon/rectum, breast, and bladder.
Diabetes And Hip Fractures
Fractures Age-specific hip fracture risk is significantly increased in both type 1 (relative risk 6.3) and type 2 (relative risk 1.7) diabetes in both sexes.
Hyperglycemia and Hearing Impairment
Hearing impairment, both in high-frequency and low/mid-frequency ranges, is more common in people with diabetes than in those without, perhaps due to neuropathy and/or vascular disease.
In a National Health and Nutrition Examination Survey (NHANES) analysis, hearing impairment was about twice as prevalent in people with diabetes compared with those without, after adjusting for age and other risk factors for hearing impairment (R).
Diabetes And Hepatitis B
Compared with the general population, people with type 1 or type 2 diabetes have higher rates of hepatitis B. This may be due to contact with infected blood or through improper equipment use (glucose monitoring devices or infected needles).
Because of the higher likelihood of transmission, hepatitis B vaccine is recommended for adults with diabetes (R).
Diabetes And Cutaneous Disorders
There are many relations between diabetes and a series of cutaneous disorders and lesions. Skin lesions may reveal diabetes in a more or less specific way.
They may also represent complications supervening in an already treated diabetic patient. Some of these dermatoses (acanthosis nigricans, purpuric and pigmented capillaritis) are markers of macrovascular complications.
The same disorders and some others (xerosis, Dupuytren’s disease) are more frequently associated with microangiopathy in Type II diabetes. Other skin diseases(alopecia areata, vitiligo) are markers of autoimmunity in Type I diabetes (R).
Diabetes Increased Risk Of Common Infections
Patients with T1D and T2D are at increased risk for lower respiratory tract infection, urinary tract infection, and skin and mucous membrane infection (R).
Increased Glucose And Cardiovascular Risk
A recent meta-analysis of 20 studies on nondiabetic subjects has demonstrated that in the nondiabetic range of glycemia (<6.1 mmol/l), increased sugar level is already associated with an increased risk for cardiovascular disease.
Also, 12 recent prospective studies have convincingly indicated that hyperglycemia contributes to cardiovascular complications in patients with type 2 diabetes (R).
Diabetes And Eyesight Loss
Data suggest that hyperglycemia and, possibly, high blood pressure are related to proliferative retinopathy. Vision-threatening retinopathy is rare in type 1 diabetic patients in the first 3–5 years of diabetes or before puberty.
During the next two decades, nearly all type 1 diabetic patients develop retinopathy.Up to 21% of patients with type 2 diabetes have retinopathy at the time of the first diagnosis of diabetes, and most develop some degree of retinopathy over time.
Vision loss due to diabetic retinopathy results from several mechanisms (R).
What Are The Health Effects Of Having Lower Levels Of Glucose?
Hypoglycemia General Body Affectation
Fight or Flight response following an episode of hypoglycemia may be associated with a range of symptoms progressing from sweating and palpitations to cognitive dysfunction and seizures.
Hypoglycemia can lead to coma and even death, depending on its severity or duration. Could cause alterations in cognitive function that can have a potentially deleterious and cumulative long-term effects on intellectual function, particularly in young children (R, R).
Hypoglycemia Association With Cardiac Ischemia
Hypoglycemia is more likely to be associated with cardiac ischemia and symptoms than normoglycemia and hyperglycemia, and it is particularly common in patients who experience considerable swings in blood glucose (R).
Hypoglycemia Effects On The Brain
Acute interruption of glucose supply may result in functional brain failure and eventually lead to coma and death. There is a possible association between repeated episodes of severe hypoglycemia and long-term cognitive dysfunction (R).
Low Serum Glucose And Visual Disorders
Hypoglycemia is can cause visual disorder in individuals with diabetes and has been linked with diplopia, dizziness/blurred vision and loss of contrast sensitivity.
A decrease in sugar concentrations was associated with reductions in retinal sensitivity, reduced viability of all retinal cell types, retinal cell death, loss of vision, reduction of retinal responses, increased retinal degeneration and cone cell death (R, R, R).
Hypoglycemia Increases Growth Hormone
In normal subjects, hypoglycemia produces an abrupt and sustained rise in levels of human growth hormone in plasma.
This effect is independent of insulin, glucagon, or epinephrine. Prolonged fasting is accompanied by a rise in the hormone level in plasma (R).
Hypoglycemia Diminishes Patients Quality of Life
Recurrent hypoglycemia episodes generate feelings of powerlessness, anxiety, and depression amongst patients and their families.
Acute hypoglycemia can result in mood swings including irritability, stubbornness, and feelings of depression (R).
How Can You Increase Or Decrease Serum Glucose Naturally Or Pharmacologically?
Lifestyle to Increase Serum Glucose
1) Sleep Fragmentation
Stress can cause hyperglycemia due to the presence of excessive counterregulatory hormones (glucagon, growth hormone, catecholamine, and glucocorticoid, either endogenous or exogenous), high circulating or tissue levels of cytokine (in particular tumor necrosis factor-α [TNα] and interleukin-1 (R).
Obesity is associated with an increased risk of developing insulin resistance and type 2 diabetes.
In obese individuals, adipose tissue releases increased amounts of non-esterified fatty acids, glycerol, hormones, pro-inflammatory cytokines and other factors that are involved in the development of insulin resistance.
When insulin resistance is accompanied by dysfunction of pancreatic islet -cells there is a failure in the control blood sugar levels (R).
Nobody should do this because of all the lung problems and diseases, also smoking acutely impaired glucose tolerance and insulin sensitivity, enhanced serum cholesterol, and triglyceride levels, and raised blood pressure and heart rate.
These findings support the pathogenetic role of cigarette smoking on cardiovascular risk factors (R).
Drugs, Hormones/Pathways That Increase Serum Glucose
Counterregulatory hormone to Insulin. To increase blood glucose, glucagon promotes hepatic glucose output by increasing glycogenolysis and gluconeogenesis and by decreasing glycogenesis and glycolysis in a concerted fashion via multiple mechanisms (R).
In physiologic conditions, catecholamines like epinephrine are associated with enhanced rates of aerobic glycolysis (resulting in adenosine triphosphate production), glucose release (both from glycogenolysis and gluconeogenesis), and inhibition of insulin-mediated glycogenesis.
Consequently, hyperglycemia and hyperlactatemia are the hallmarks of this metabolic response (R).
Data demonstrates that cortisol increases glucose production by stimulating gluconeogenesis within 3–4 h.
The stimulation of T3-sensitive neurons in the Para Ventricular Nucleus of euthyroid rats increases EGP via sympathetic projections to the liver, independently of circulating glucoregulatory hormones.
This represents a unique central pathway for modulation of hepatic glucose metabolism by thyroid hormone (R).
5) Growth Hormone (GH)
GH counteracts, in general, the effects of insulin on glucose and lipid metabolism. The physiological elevations in GH:
- induce state of insulin resistance within 2–12 h,
- only slightly impair insulin’s suppressive effect on endogenous glucose production, indicating that the primary site of insulin resistance resides in peripheral tissues,
- do not alter the plasma insulin response to hyperglycemia, and
- cause a decrease in insulin binding that results from a decrease in receptor affinity (R).
6) Peroxisome Proliferator-Activated Receptor γ Coactivator-1a (PGC-1α)
Upon fasting, the mRNA levels of PGC-1α in the liver are dramatically elevated, and under these conditions PGC-1α co-activates FoxO1 (Forkhead box protein O1) to further increase transcription of gluconeogenic genes and hepatic glucose production.
In addition to FoxO1, PGC-1α was also shown to coactivate the liver-enriched nuclear receptor hepatocyte HNF-4α. This interaction between PGC-1α and HNF-4α strongly induces expression of gluconeogenic genes and promotes hepatic glucose output (R, R1, R2).
5) External Corticosteroids
Corticosteroids potentiate the adrenergic effects of catecholamines and stimulate the synthesis of epinephrine from norepinephrine this increases glucose release.
Also, other systemic effects of high doses of glucocorticoids include adrenocortical insufficiency upon glucocorticoid removal, steroid-induced diabetes, hyperlipidemia, elevated glucagon, and hypocalcemia (R, R).
6) Antipsychotic Medications
Recent controlled studies suggest that antipsychotics can impair glucose regulation by decreasing insulin action, although effects on insulin secretion are not ruled out, this will lead to increase in the sugar levels.
Also, antipsychotic medications induce weight gain, and the potential for weight gain varies across individual agents with larger effects observed again for agents like chlorpromazine, clozapine, and olanzapine (R).
7) Thiazide Diuretics
Multiple suggest that thiazide diuretics tend to raise blood glucose. The ALLHAT study (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).
In this trial, whose results were published in 2006, participants were given one of the several different types of medicine to treat their high blood pressure, to try to determine the best type of therapy.
Based on a subgroup analysis of approximately 18,000 people without diabetes who were treated and followed for an average of five years, the risk of developing diabetes was slightly higher in those who took a thiazide diuretic (14%) compared to those who took two other types of blood-pressure-lowering drugs, a calcium channel blocker (11.1%) or an angiotensin-converting enzyme (R).
Nutritional Factors That Increase Serum Glucose
1) Niacin (Vitamin B3)
Niacin can be found in several foods like fruits and vegetables (avocados, dates, tomatoes), seeds, liver, chicken, beef, eggs, fish.
A study performed showed that the use of niacin for 3 years in subjects with normal baseline glucose levels was associated with an increase in blood glucose levels and the risk of developing impaired fasting glucose, but not diabetes mellitus.
Also, niacin remains the most effective available agent for raising HDL-C levels. On a population basis, most patients with diabetic and other forms of dyslipidemia (eg, associated with stable type 2 DM) show significant reductions in cardiovascular risk (R, R).
2) White Rice
Data suggests that regular consumption of white rice is associated with an increased risk of type 2 diabetes, whereas replacement of white rice by brown rice or other whole grains is associated with a lower risk.
The current Dietary Guidelines for Americans identifies grains, including rice, as one of the primary sources for carbohydrate intake and recommends at least half of carbohydrate intake should come from whole grains (R).
A study shows that meat intake is associated with fasting glucose and insulin concentrations in Caucasians without diabetes mellitus.
This association is not dependent on the genetic variation of loci. This study adds to the growing body of evidence that suggests that meat intake is associated with higher glucose and insulin concentrations.
Study show how Non-caloric artificial sweeteners (NAS) altered microbial metabolic pathways that are linked to host susceptibility to metabolic disease in mice and demonstrate similar NAS-induced dysbiosis and glucose intolerance in healthy human subjects.
Collectively, our results link NAS consumption, dysbiosis and metabolic abnormalities like glucose intolerance and glucose levels elevation (R).
Lifestyle to Decrease Serum Glucose
1) Resistance Exercise Lowers HbA1c Levels
Clinical trials have provided strong evidence for the A1C-lowering value of resistance training in older adults with type 2 diabetes and for an additive benefit of combined aerobic and resistance exercise in adults with type 2 diabetes (84, 88,89)
2) Aerobic Exercise
Findings suggest that weight loss induced by diet and exercise approximating 1–2 lbs per week provides an advantage with respect to improvements in insulin action by comparison with diet alone.
Also, findings support the notion that diet and exercise is a preferred therapeutic strategy for the prevention and management of glucose intolerance and insulin resistance in obese men (R).
A study demonstrates that ethanol exerts substantial influences on pancreatic microcirculation by evoking a massive redistribution of blood flow within the pancreatic gland, redirecting it into the endocrine part, evoking sustained insulin secretion and hypoglycemia.
This mechanism, which seems to involve nitric oxide and vagal pathways, may in part underlie the well-known hypoglycemic properties of alcohol in diabetic patients or in alcoholics with hepatic failure (R).
Drugs, Hormones/Pathways That Decreases Serum Glucose
Natural Hormone in the body that reduces serum glucose by accelerating transport of glucose into insulin-sensitive cells and facilitating the storage of glucose.
Also, several international guidelines on diabetes emphasize intensive insulin treatment designed to reduce the risk of long-term diabetic complications.
Higher incidence of hypoglycemia, particularly among patients treated with insulin over extended periods of time, reinforce the idea that the disease progression and increased insulin use subsequently increases the risk of hypoglycemia with clinical consequences ranging from mild discomfort to coma and even death (R, R1, R2).
Results show that somatostatin lowers blood glucose concentrations as a secondary effect of inhibition of glucagon secretion.
Somatostatin is not optimal for diabetes treatment because it has a short period of action, so this study speculates that a similar substance with a more prolonged and specific action on glucagon might prove of practical value in the treatment of diabetes mellitus (R, R).
3) Incretins (GIP and GLP-1)
Incretins, which include a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), are also involved in regulation of blood glucose, in part by their effects on insulin and glucagon.
However, both GLP-1 and GIP are only secreted when glucose levels rise above normal fasting plasma glucose levels; they do not directly stimulate insulin secretion.
The biological activities of GLP-1 include stimulation of glucose-dependent insulin secretion, lowering of blood glucose and lipids, inhibition of gastric emptying and food intake, the stimulation of β-cell proliferation and inhibition of their apoptosis.
Sulphonylureas, commonly used as second-line therapy in patients with type 2 Diabetes Mellitus, promote insulin release independent of prevailing glucose value and as a result, hypoglycemia is an expected side effect (R).
They trigger insulin secretion with a faster onset and shorter duration of action anticipating a lower risk of hypoglycemia. However, studies have shown that the risk of hypoglycemia with repaglinide was similar to second-generation sulfonylureas (R).
Tramadol is a weak opioid analgesic with an increasing use, but studies show that the initiation of tramadol therapy is associated with an increased risk of hypoglycemia requiring hospitalization. Additional studies are needed to confirm this rare but potentially fatal adverse event (R).
Pramlintide, an amylin analog, is an agent that delays gastric emptying, blunts pancreatic secretion of glucagon, and enhances satiety. It is a U.S. Food and Drug Administration (FDA)-approved therapy for use in adults with type 1 diabetes.
8) Sodium–Glucose Cotransporter 2 (SGLT2) Inhibitors
SGLT2 inhibitors provide insulin-independent glucose lowering by blocking glucose reabsorption in the proximal renal tubule by inhibiting SGLT2. These agents provide modest weight loss and blood pressure reduction (R).
Biguanides like metformin are used for treatment in the diabetic subjects, the mechanism of action consists in lower glucose production rates through a reduction in the rate of gluconeogenesis (R).
Nutritional Factors That Decrease Serum Glucose
Fenugreek is an aromatic plant that has many uses and is a key ingredient of curries and other Indian recipes. the results of 18 patients that consumed fenugreek (11 consumed fenugreek in hot water and 7 in yogurt) were studied.
Findings showed that fasting blood glucose, total glucose and VLDL-C decreased significantly (25%, 30% and 30.6% respectively) after taking fenugreek seed soaked in hot water whereas there were no significantly changes in lab parameters in cases consumed it mixed with yogurt.
BMI, Energy, Carbohydrate, Protein and fat intake remained unchanged during the study (R).
Data provide novel evidence that increasing coffee consumption over a 4 year period is associated with a lower risk of type 2 diabetes while decreasing coffee consumption is associated with a higher risk of type 2 diabetes in subsequent years.
But this data has a discrepancy with other experiments that show that acute ingestion of caffeine can cause postprandial hyperglycemia and insulin peripheral resistance.
But as the beneficial effects of coffee consumption exist for both decaffeinated and caffeinated coffee, a component of coffee other than caffeine must be responsible.So we need a better understanding of coffee components to know the exact relation between Coffee and blood glucose (R, R).
Based on the currently available literature, cinnamon may have a beneficial effect on fasting plasma glucose, LDL-C, HDL-C, and triglyceride levels in patients with type 2 diabetes.
It has been suggested that cinnamon`s effectiveness in lowering blood glucose can be attributed to its active component cinnamaldehyde.
The insulinotropic effects of cinnamaldehyde have been preliminarily investigated and are thought to be responsible for promoting insulin release, enhancing insulin sensitivity, increasing insulin disposal, and exerting activity in the regulation of protein-tyrosine phosphatase 1B (PTP1B) and insulin receptor kinase (R).
A study performed in rats showed that raw garlic had a profound effect in reducing the glucose, cholesterol, and triglyceride levels, whereas boiled garlic had little effect in controlling these parameters (R).
A study showed that daily dietary supplementation of bioactives in freeze-dried whole blueberry powder improved insulin sensitivity over 6 weeks in obese, nondiabetic, and insulin-resistant participants.
The active components in blueberries enhanced insulin sensitivity independent of any changes in inflammatory biomarkers or adiposity (R).
6) Cherry Juice
Study Indicates that the consumption of 40 gr/day of Concentrated Sour Cherry Juice (CSCJ) decreases body weight, blood pressure, and HbA1c after 6 weeks in diabetes type 2 women and improves blood lipids in diabetic patients with hyperlipidemia.
In this study, Fasting blood sugar levels decreased not significantly. However, HbA1c, which is the long-term representative of blood glucose, reduced after 6 weeks intake of CSCJ (R).
7) Mediterranean Diet
Results have shown that in prediabetic insulin resistant subjects an olive oil-enriched Mediterranean Diet taken at weight-maintenance levels improves insulin resistance and fasting proinsulin levels in insulin-resistant subjects.
A study showed that mango consumption did not induce weight loss, but findings indicate that regular consumption of mango by obese adults provides a positive effect on their blood glucose.
Further clinical trials with larger sample sizes and longer duration of mango supplementation are necessary.
But still, mango supplementation may offer an innovative dietary intervention in modulating blood glucose without negative effects on body composition (R).
There is some evidence supporting the favorable effects of vinegar on cardiovascular risk factors, such as hyperglycemia, hyperinsulinemia, hyperlipidemia, and obesity.
The majority of the data, however, are derived from animal models and/or acute experiments in a few human individuals, and the scant randomized placebo-controlled trials in humans had serious limitations and very low numbers of participants (R).
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