Diabetes: A Growing Health Concern
The International Diabetes Foundation (IDF) reported that 537 million adults between the ages of 20 and 79 years across the world had diabetes in 2021, translating to 1 in every 10 people in 2021. The IDF estimated that this number will rise to around 643 million by 2030 and 783 million by 2045.
Incidence of diabetes in children is rising as well. Researchers conducting the 2019 Global Burden of Disease Study analyzed data from 204 countries and territories throughout the world. In this study, diabetes incidence increased by almost 40% between 1990 and 2019 in children between the ages of 0 and 14 years.
Diabetes is one of the leading causes of mortality globally, accounting for 6.7 million deaths in 2021. Diabetes cost an estimated 966 billion US dollars in global healthcare expenditures – a cost that has exponentially risen by 316% over the past 15 years.
What Is Diabetes?
Diabetes mellitus (DM) is a term that comes from the Greek word “diabetes,” which means to siphon or pass through, and the Latin word “mellitus,” which means sweet. DM is a metabolic disorder characterized by the body’s inability to properly control the amount of glucose in the blood.
Glucose, a simple sugar and type of carbohydrate, is the body’s main source of energy. Glucose is obtained from food that is consumed; however, the body also produces glucose through metabolic processes, such as gluconeogenesis and glycogenolysis.
During gluconeogenesis, the body forms new glucose molecules from various other substances, such as glycerol, lactate, and pyruvate. During glycogenolysis, the body breaks down glycogen, which is the stored form of glucose in the body. The liver and muscles store glycogen as a reserve energy source to ensure that glucose concentrations in the blood meet the body’s energy demands, especially for the brain.
Under normal circumstances, glucose is the only fuel source used by brain cells since glucose is present in the blood in sufficient enough quantities to sustain optimal brain function. The adult human brain consumes around 20-25% of glucose in the body, while developing brains in babies and children require even more glucose.
However, unlike the liver and muscles, which can store large amounts of glycogen, brain cells cannot store enough glucose in the form of glycogen to serve as a sufficient energy reserve, so brain function (and therefore bodily function) depends on a steady circulation of glucose from the peripheral bloodstream. Glucose must be continuously transported through the blood brain barrier (BBB) to get into the brain.
Cause Of Diabetes
The pancreas is an organ in the abdomen responsible for making a hormone called insulin. Insulin assists the absorption of glucose from the blood into the body’s cells for use as an energy source.
When a person becomes diabetic, it means one of two things: either the pancreas doesn’t produce enough insulin, or the body is unable to use insulin effectively (a term called insulin resistance). Under either circumstance, glucose remains circulating in the bloodstream instead of being used by the cells.
When the brain’s glucose-sensing mechanisms perceive that the body’s cells are not receiving adequate supplies of glucose, it encourages the body to produce more glucose, either through increased food intake (which explains the symptom of increased hunger in people with diabetes) or through the processes of gluconeogenesis or glycogenolysis.
However, the underlying problem is not really a lack of glucose, rather the primary issue contributing to diabetes is effectively getting the glucose into the cells. The inability of the cells to use insulin to absorb glucose triggers an ongoing and progressive process because the cells continue to signal to the brain that they are not getting enough glucose. This in turn results in high concentrations of glucose in the blood (hyperglycemia), a hallmark sign of diabetes.
Signs And Symptoms Of Diabetes
While the characteristic sign of diabetes is elevated blood sugar, other diabetes-related symptoms include the following:
Increased thirst
Increased urination
Increased hunger
Unintended weight loss
Fatigue
Frequent infections
Blurry vision
Numbness, tingling, or unusual sensations in the hands and feet, also known as the stocking-glove pattern of nerve damage (neuropathy)
Skin problems, including dryness or poor wound healing
The kidneys may attempt to eliminate excess glucose from the bloodstream through the urine. This process may result in another sign of diabetes called glucosuria, in which glucose is present in the urine in quantities above the normal limit of 0.25 mg/mL. This sign explains how the term diabetes mellitus was coined because the “sweet” sugar (glucose) “passes through” the body into the urine.
Diagnosis Of Diabetes
A doctor may suspect that a person has diabetes based on their family history, current symptoms, and other health conditions. If that is the case, clinicians use several different tests to diagnose diabetes and prediabetes, including the following:
Fasting plasma glucose test, which measures blood glucose at a single point in time after fasting without food for at least 8 hours
Random plasma glucose test, which measures blood glucose without requiring a person to fast for 8 hours
Glucose challenge test, which assesses for gestational diabetes in pregnant women by measuring their blood glucose 1 hour after drinking a sweet glucose-containing liquid
A1C test, which provides an overview of the average concentration of blood glucose over during the last 3 months
Oral glucose tolerance test (OGTT), which measures blood glucose after fasting for 8 hours, measures again 2 hours after drinking a glucose-containing liquid, and, for pregnant women, every hour for 2 to 3 hours to assess for gestational diabetes
People who do not have prediabetes or diabetes will have the following results:
Fasting plasma glucose of 99 mg/dL or lower
A1C below 5.7%
OGTT of 139 mg/dL or lower
People with prediabetes will have the following results:
Fasting plasma glucose between 100 and 125 mg/dL
A1C between 5.7% and 6.4%
OGTT of 140 and 199 mg/dL
People with diabetes will have the following results:
Fasting plasma glucose of 126 mg/dL or higher
Random plasma glucose of 200 mg/dL or higher
A1C of 6.5% or above
OGTT of 200 mg/dL or higher
Doctors may use different test result values to determine if a pregnant woman has gestational diabetes because the blood glucose is also being used to help the baby grow and develop.
Types Of Diabetes
Several subtypes of diabetes have been identified – each associated with different causes and risk factors. The 3 most prevalent subtypes of diabetes include the following:
type 2 diabetes (T2D), which accounts for 90% to 95% of cases
type 1 diabetes (T1D), which accounts for 5% to 10% of cases
gestational diabetes, which occurs only in pregnant women and resolves after childbirth
T1D
T1D is an autoimmune condition in which the immune system attacks and destroys the special cells called beta cells that are located in the pancreas in the islets beta cells that are located in the pancreas in the islets of Langerhans. These beta cells produce, store, and release insulin to regulate blood glucose concentrations.
Symptoms of T1D most often occur suddenly. T1D can affect people at any age, although T1D is most prevalent among children and adolescents. T1D accounts for around 98% of all cases of diabetes occurring in children younger than the age of 10 years, and around 87% of all cases in preteens and adolescents between the ages of 10 and 19 years.
Similar to other autoimmune conditions, researchers believe that a combination of genetic susceptibility and environmental exposures, especially to certain viruses during childhood, contribute to the risk of developing T1D.
T2D
In contrast to T1D, which is a condition in which the pancreas does not produce enough insulin to regulate blood sugar, T2D is caused by the inefficient use of insulin by the muscles, liver, and fat cells. This insulin resistance triggers the pancreas to produce more and more insulin to meet the body’s demands for glucose.
Gradually, the pancreas cannot produce enough insulin to keep up with the body’s demands and progressive insulin resistance, resulting in elevated blood glucose concentrations.
T2D often is associated with physical inactivity and obesity/being overweight. Extra weight, particularly stored in the belly as abdominal fat, is associated with increased insulin resistance, T2D, and cardiovascular disease.
Similar to T1D, genetics also may contribute to the development of T2D as the condition runs in families as well as in specific racial or ethnic groups, especially those with African, Asian, and Hispanic ancestry.
Gestational Diabetes
Gestational diabetes occurs during pregnancy in women without a history of diabetes. Screening for gestational diabetes using the 50 g 1-hour oral glucose tolerance test is recommended for all pregnant women at 24 weeks gestation. Most women are able to produce enough insulin during pregnancy to overcome this hormonally-driven insulin resistance; however, some cannot and develop gestational diabetes.
Gestational diabetes is caused by dysfunction or delayed response of the pancreatic beta-cells and increased insulin resistance related to placental hormonal release, primarily the hormone, lactogen. In addition to lactogen, growth hormone, prolactin, progesterone, and corticotropin-releasing hormone are all hormones that promote insulin resistance and hyperglycemia during pregnancy.
Less Common Subtypes of Diabetes
Type 3 diabetes (T3D) describes a type of insulin resistance accompanied by insulin deficiency that is restricted to the brain. T3D may overlap with T2D and may be a contributing factor to the development of neurodegeneration seen in people with Alzheimer disease (AD).
Type 3c diabetes, also known as pancreatogenic diabetes, is a type of secondary diabetes caused by damage to pancreas that is not autoimmune in nature. The pancreas may be injured during surgery or due to illness, inflammation of the pancreas (pancreatitis) or other conditions like pancreatic cancer that affect the ability of the pancreas to produce enough insulin to support the body’s needs.
It is projected that type 3c diabetes accounts for around 9% of all cases of diabetes and is underdiagnosed due to lack of awareness of the condition amongst the public and clinicians.
Monogenic diabetes are forms of diabetes that are caused by changes to a single gene, whereas T1D and T2D are caused by changes to multiple genes (polygenic) as well as environmental factors. Most monogenic forms of diabetes affect the body’s ability to produce insulin.
Although quite rare, the most common forms of monogenic diabetes include neonatal diabetes and maturity-onset diabetes of the young (MODY). Neonatal diabetes affects newborns during the first 6 to 12 months of life. MODY typically affects adolescents or young adults (ages 20 and younger).
Other genetic disorders, such as cystic fibrosis and hemochromatosis, can cause scarring in the pancreas, which in turn affects its ability to produce insulin.
Long-Term Effects Of Diabetes
Individuals with diabetes have an increased likelihood of developing complications and chronic conditions related to their diabetes. Long-term effects of diabetes include the following:
cardiovascular disease (CVD), such as high blood pressure (hypertension), high cholesterol (hypercholesterolemia), stroke, heart disease, heart attack, and blood vessel damage, especially hardening of the arteries (atherosclerosis)
diabetic eye disease, which consists of several eye disorders that may develop due to diabetes, such as diabetic retinopathy, cataracts, glaucoma, and diabetic macular edema, and may progress to poor vision or even blindness
diabetic neuropathy, characterized by lack of sensation especially in the hands and feet
diabetic nephropathy, characterized by kidney damage that may result in kidney failure. The blood vessels in the kidneys may be damaged either due to high blood pressure or the attempt of the kidneys to remove excess glucose from the blood through the urine.
foot problems, related to nerve damage and poor blood flow resulting in increased risk of cuts, foot ulcers, infection, gangrene, amputation, and Charcot’s foot
dental problems, such as gum disease and cavities
bladder problems, such as leaking (incontinence), inability to completely empty the bladder, and increased bladder infections
sexual problems, such as erectile dysfunction, fertility problems, low libido or arousal response, painful sex, and increased yeast infections
A major complication of diabetes is low blood glucose (hypoglycemia), which occurs more commonly if people:
Have a T1D diagnosis
Have additional health problems, like kidney or heart disease or impaired understanding and memory
Take insulin or other diabetes medications that influence glucose concentration in the blood
Are over 65 years of age
Have a history of hypoglycemia
Individuals with diabetes who are prone to hypoglycemia are more at risk for severe complications, such as fainting, coma, or even death. Careful and frequent monitoring of blood glucose is required to prevent these serious complications because symptoms do not always occur during hypoglycemic episodes. Blood glucose may lower at night while sleeping (and fasting).
Modern Treatments
Treatment choices depend on the type of diabetes and range from lifestyle modifications to medications to insulin administration using advanced technologies.
Insulin Therapy
Insulin therapy is required for people with T1D and more advanced stages of T2D. Insulin can be administered in several different ways, including a needle and syringe, an insulin pen, an insulin pump, a jet injector, an inhaler, or an artificial pancreas (closed-loop systems).
Continuous glucose monitoring (CGM) and use of advanced technologies help to control blood glucose levels, especially during and after exercise, while sleeping, and during and after meals.
Some pregnant women with gestational diabetes need to use insulin to control blood glucose levels.
One of the most important factors to consider is timing of the insulin administration because different forms of insulin and different routes of administration may affect how quickly the insulin starts to work, when the insulin works best (peaks), and how long the insulin works.
Types of insulin include:
Rapid-acting (inhaled)
Rapid-acting/ultra rapid-acting
Regular (short-acting)
Intermediate-acting
Long-acting
Ultra long-acting
Rapid-acting insulin that is inhaled has the quickest effect within 10 to 15 minutes of administration and works the best after 30 minutes. Its therapeutic benefits last about 3 hours.
Rapid-acting and ultra rapid-acting forms of insulin begin to work 15 minutes after administration and work the best after 1 hour. The therapeutic benefits last between 2 to 4 hours for rapid-acting insulin and 5 to 7 hours for ultra rapid-acting insulin.
Regular, or short-acting insulin begins to work 30 minutes after administration and works the best after 2 to 3 hours. The therapeutic benefits last between 3 to 6 hours.
Intermediate-acting insulin takes a bit longer to work, typically 2 to 4 hours after administration. It works the best between 4 and 12 hours, and the therapeutic benefits last between 12 and 18 hours.
Long-acting insulin begins to work 2 hours after administration and does not have a period of time during which it works the best. The therapeutic benefits last around 24 hours.
Ultra long-acting insulin takes the longest period of time to work, typically 6 hours after administration. Similar to long-acting insulin, ultra long-acting insulin does not have a period of time during which it works the best. The therapeutic benefits last the longest for around 36 hours or more.
Lifestyle Modifications
Initial recommendations to prevent onset of T2D (for people with prediabetes) and to treat newly diagnosed T2D usually involve lifestyle modifications, including dietary changes, monitoring sugar intake, regular physical activity, and weight loss programs.
Smoking increases the risk for worsening the symptoms related to diabetes because both smoking and diabetes narrow the blood vessels, which may lead to heart disease. It is important to quit smoking to reduce this risk.
If lifestyle modifications do not improve insulin resistance, the next treatment options include oral medications, injections, or insulin to help manage T2D. People diagnosed with T2D should also check blood glucose levels daily, especially while taking insulin, so that the best decisions can be made about eating, exercising, and timing medications.
Oral Medications
A patient information booklet published in 2018 listed the following oral medications, which are most often used to treat T2D:
Alpha-glucosidase inhibitors
Glyset (miglitol)
Precose (acarbose)
Biguanides
Fortamet (metformin)
Glucophage (metformin)
Glucophage extended-release (XR) (metformin)
Glumetza (metformin)
Riomet (metformin)
Bile acid sequestrants
Welchol (colesevelam)
Dopamine receptor agonists
Cycloset (bromocriptine)
DPP-4 inhibitors
Januvia (sitagliptin)
Nesina (alogliptin)
Onglyza (saxagliptin)
Tradjenta (liagliptin)
GLP-1 receptor agonists
Rybelsus (semaglutide)
Meglitinides
Prandin (repaglinide)
Starlix (nateglinide)
SGLT2 inhibitors
Farxiga (dapagliflozin)
Invokana (canaglifozin)
Jardiance (empagliflozin)
Steglatro (ertugliflozin)
Sulfonylureas
Amaryl (glimepiride)
Diabeta glynase (glyburide)
Diabinese (chloropropamide)
Glucotrol/Glucotrol XR (glipizide)
Orinase (tolbutamide)
Tol-Tab (tolbutamide)
Tolinase (tolazamide)
Thiazolidinediones
Actos (pioglitazone)
Avandia (rosiglitazone)
Sometimes combining these oral medicines help manage symptoms for individuals with T2D with better results, including the following combination medicines:
ActoPlus Met/ActoPlus Met XR (pioglitazone and metformin)
Avadamet (rosiglitazone and metformin)
Avandaryl (rosiglitazone and glimepiride)
Duetact (pioglitazone and glimepiride)
Glucovance (glyburide and metformin)
Glyxambi (empagliflozin and linagliptin)
Invokamet/Invokamet XR (canagliflozin and metformin)
Janument/Janumet XR (sitagliptin and metformin)
Jentadueto (linagliptin and metformin)
Kazano (alogliptin and metformin)
Kombiglyze/Kombiglyze XR (saxagliptin and metformin)
Metaglip (glipizide and metformin)
Oseni (alogliptin and pioglitazone)
PrandiMet (repaglinide and metformin)
Xigduo XR (dapagliflozin and metformin)
Injections
The following medications are administered through an injection underneath the skin (subcuatenous injections) and should not be considered a replacement for insulin.
Amylin analog
Symlin (pramlintide acetate)
GLP-1 receptor agonists
Adlyxin (lixisenatide)
Bydureon (exenatide)
Byetta (exenatide)
Mounjaro (tirzepatide)
Ozempic (semaglutide)
Tanzeum (albiglutide)
Trulicity (dulaglutide)
Victoza (liraglutide)
Surgical Procedures
Weight-loss surgery, also known as bariatric or metabolic surgery, can help people lose weight by altering the way the digestive system functions. This procedure may help people with T2D and obesity to lose weight and normalize their blood glucose levels. Some individuals who undergo weight-loss surgery are able to stop taking medications for diabetes.
Pancreatic islet transplantation is an experimental surgical treatment for people with T1D during which islets containing healthy beta-cells from a donor’s pancreas are injected into the vein carrying blood to the liver in a person with T1D.
Some individuals with T1D may benefit from a whole pancreas transplant; however, the risk of complications, such as the recipient’s rejection of the donor’s pancreas, is much higher than with pancreatic islet transplantation. Individuals who receive transplants from donors must undergo lifelong immunosuppressive treatments so that their immune systems do not attack the transplant.
Routine Monitoring And Follow-Up Appointments
Individuals with diabetes should follow up with their primary care provider to make sure they are meeting treatment goals, especially for people with T2D who are attempting to manage the condition through lifestyle modifications. Sometimes, people with more complicated forms of diabetes that are resistant to lifestyle modifications may need to see an endocrinologist for comprehensive management and routine follow-up.
In addition to blood glucose checks several times a day, people with diabetes should regularly monitor blood pressure, cholesterol, and A1C. If people with diabetes have trouble consistently meeting their blood glucose goals or if the doctor changes the treatment regimen, A1C should be monitored every 3 months.
Daily checks of the feet, sometimes using a mirror if places are hard to see should be done to help catch and promptly treat cuts, sores, and infections that may develop due to diabetes. Wearing shoes and socks at all times to prevent injuries, washing the feet daily, smoothing corns and calluses with a pumice stone, trimming the toenails straight across, paying routine visits to the foot doctor (podiatrist), and exercising regularly to improve blood flow to the feet can help to prevent diabetic-associated foot complications.
If treatment goals are being met and consistently maintained, follow-ups with the doctor, including A1C tests, may only be necessary every 6 months. Dental exams should also be performed every 6 months to check for cavities, gum disease, and other dental complications due to diabetes.
Yearly check-ups for people with diabetes should include the following:
A dilated eye exam to check for diabetic retinopathy, glaucoma, macular edema, and other diabetes-related eye complications
Tests for kidney function to check for diabetic nephropathy
Hearing exams
Cholesterol tests
Complete foot check
People with diabetes should also stay current with their vaccines. The flu vaccine is needed yearly, whereas the vaccines for pneumonia (before the age of 65 years) and hepatitis B (before the age of 60 years) are only required once.
If any new symptoms or health problems appear, or if current symptoms get worse, people with diabetes should contact their doctor right away to be evaluated and treated.
Conclusion
In short, diabetes is a complex, multifaceted, metabolic disease with varying causes, long-term effects that can be quite serious, and multiple treatments options.
Some factors contributing to disease development may be outside the realm of a person’s control, such as genetics, autoimmunity, environmental exposures, or other disease processes that impair insulin production; however, some factors may allow people with diabetes to take control of their own health, such as quitting smoking and committing to a healthy diet, regular exercise, and routine appointments with their doctor.
Many daily activities affect blood glucose, including exercising, eating, and sleeping. While considering the impact of these daily activities on blood glucose, researchers, bioengineers, and clinicians are collaborating to develop novel therapeutic inventions that more precisely control the timing of insulin release and continuously monitor blood glucose concentrations to prevent the sudden onset of hypoglycemia and its serious sequelae.
Technological advancements and development of avant-garde surgical procedures are pushing the boundaries of medicine to allow people with diabetes to live their best lives and prevent diabetic complications. The future for people with diabetes along with their available treatment options looks promising indeed.
Laxxon Medical is dedicated to engineering patented 3D pharmaceutical solutions that optimize products and benefit patients. Our goal is to establish SPID®-Technology as a manufacturing process with the individual and the pharmaceutical partner in mind.
To keep up to date with SPID®-Technology and Laxxon Medical news and announcements, follow us on LinkedIn.