IVD of Diabetes & Metabolism

What is diabetes & metabolism?

Diabetes is an autoimmune disease that changes the process by which your body converts food into energy. The majority of what you eat is converted into sugar (glucose) and enters the bloodstream. When blood sugar is high, it causes your pancreas to send insulin out. It's insulin that opens the door for blood sugar to enter the cells and consume as energy. If you have diabetes, either your body doesn't produce enough insulin or your cells don't respond to insulin as well as they should. This in turn, over time leads to health issues such as heart disease, eye loss and kidney disease.

There are three main types of diabetes:

Type 1 Diabetes: Autoimmune disease wherein the immune system attacks the insulin-secreting beta cells in the pancreas.

Type 2 Diabetes: Caused by your body's inability to take insulin, or because the pancreas is not able to make enough insulin.

Gestational Diabetes: Develops during pregnancy and usually disappears after giving birth, but increases the risk of developing type 2 diabetes later in life.

Metabolism: This is the way your body uses chemical reactions to transform food into energy. These complex biochemical processes allow your body to grow, reproduce, repair damage, and respond to the environment. Metabolism is divided into two categories:

Catabolism: The breakdown of molecules for energy. It releases energy that can either be stored for later or applied immediately.

Anabolism: The synthesis of all compounds needed by the cells. It takes the energy derived from catabolic processes to construct proteins, nucleic acids and other macromolecules needed by the body.

Metabolism is a chain of enzymes and chemicals that transform molecules in food into substances and energy that are needed to perform all the bodily functions.

Relationship and Interaction with diabetes and metabolism

Glucose Metabolism: Diabetes disturbs glucose metabolism. In the absence of insulin/insulin regulation, the glucose does not reach the cells properly and ends up in the bloodstream, causing hyperglycemia (high blood sugar). The cells could become energy-starved, and stored fat and muscle would be broken down to a different form of energy, slowing metabolism.

Insulin and Metabolic Function: Insulin helps control the metabolic process by slowing down the digestion of glucose and slowing down the breakdown of fat. When insulin is not present (or not used correctly), it damages these metabolisms and alters the way your body stores and uses energy.

Impact on Other Metabolic Processes: Over time, high blood sugar creates insulin resistance because cells aren't responding to insulin. This condition exacerbates metabolic imbalances. Diabetes can affect fat and protein metabolism, raising the levels of fatty acids and amino acids in blood.

Weight and Metabolic Syndrome: Type 2 Diabetes is often linked to obesity and metabolic syndrome, which is the result of high blood pressure, high cholesterol, and high body fat. Such conditions further damage metabolism and cardiovascular health.

Long-term Effects: Over the long term, poorly controlled diabetes metabolic abnormalities lead to cardiovascular disease, neuropathy, kidney failure, and eye damage through general metabolic homeostasis failure.

What are the symptoms of diabetes?

There are several common symptoms of diabetes, which can vary depending on the type of diabetes and how high your blood sugar levels are.

Increased Thirst and Dry Mouth: The increased thirst or polydipsia is a common symptom that occurs when you lose too much water in your urine.

Frequent Urination: This is also called polyuria because too much glucose in the blood draws water from the tissues of the body.

Extreme Hunger: Also called polyphagia, it's a condition in which the body is unable to transform the sugar in the bloodstream into energy.

Unexplained Weight Loss: People suffering from diabetes might lose weight despite their increased intake because the body does not get energy from food.

Fatigue: When cells lack sugar – what they burn for fuel – humans become fatigued and depressed.

Blurred Vision: The excess of blood sugar pulls fluid from the lenses of your eyes and distorts your vision.

Slow-Healing Sores or Frequent Infections: Diabetes affects the body's ability to heal and fight infections due to impaired circulation and immune function.

Tingling, Numbness, or Pain in the Hands or Feet: These symptoms result from nerve degeneration (neuropathy) in diabetes.

Darkened Skin Patches: Certain individuals with diabetes exhibit patches of darkened skin — this is called acanthosis nigricans.

Mood Changes: Hypersensitivity or mood swings associated with fluctuating blood sugar levels.

How to Treat Diabetes?

There are several general symptoms of diabetes, which can vary depending on your diabetes type and your blood sugar level.

Lifestyle Changes:

Healthy Eating: Having a healthy diet consisting of vegetables, fruits, whole grains, and lean proteins can help to control blood sugar. Managing carbohydrate consumption also requires careful scheduling.

Regular Exercise: Exercise lowers blood sugar and promotes the ability to absorb insulin. At least 150 minutes of moderate exercise per week is also recommended.

Weight Management: Maintaining a healthy weight will increase insulin sensitivity and control blood sugar.

Monitoring Blood Sugar Levels:

Regular monitoring can help individuals keep track of their blood sugar levels and adjust their diet, activity, or medication accordingly.

Medication:

Oral Medications: Such as Metformin, a medication that regulates blood sugar levels.

Insulin Therapy: Required for Type 1 and occasionally Type 2 diabetes.

Other injectable medicines may be needed depending on the individual.

Education and Support:

Diabetes education programs can provide support and information to help manage the condition effectively.

Regular Medical Check-ups:

Constant meetings with healthcare providers are necessary to observe any complications and adjust treatment accordingly.

Managing Coexisting Conditions:

Controlling blood pressure, cholesterol and other chronic diseases that exacerbate diabetes.

Test Methods for Diabetes

There are a number of tests for diabetes, which mostly involve taking glucose and insulin levels, along with other symptoms.

Fasting Blood Glucose Test: Measures blood sugar after an overnight fast.

Oral Glucose Tolerance Test (OGTT): Tests blood sugar before and after consuming a glucose solution.

A1C Test (Glycated Hemoglobin Test): A measure of average blood glucose over the past 2-3 months.

Random Blood Sugar Test: Tests blood sugar at random time of day, regardless of the last meal.

C-Peptide Test: Tests insulin levels and can be used to distinguish type 1 and type 2 diabetes.

Urine Test for Glucose: Tests for glucose in the urine, which can be a sign of diabetes if it shows up consistently.

Fructosamine Test: Measures average glucose levels over the past 2-3 weeks.

Insulin Autoantibodies Test (IAA): Helps identify autoimmune processes that target insulin.

Blood Ketone Test: Signs of diabetic ketoacidosis when ketone levels are elevated.

Continuous Glucose Monitoring (CGM): Provides ongoing readings of glucose levels, which is helpful for managing diabetes.

Skin Prick Blood Tests (home monitoring): enables patients with diabetes to monitor glucose levels continuously by their own.

IVD markers for diabetes

Hemoglobin A1c (HbA1c): This protein is a type of hemoglobin chemically linked to a sugar. It displays average blood glucose level from the past two or three months.

Insulin: The level of insulin protein can be measured to understand how much insulin the pancreas is producing and to help in diagnosing the type of diabetes.

C-Peptide: This protein is a byproduct of insulin production and can be used to measure how much insulin the body is producing.

GAD Antibodies (Glutamic Acid Decarboxylase Antibodies): These antibodies could be a symptom of an autoimmune reaction like Type 1 diabetes.

HLAs: Specific human leukocyte antigen (HLA) genotypes are associated with susceptibility to Type 1 diabetes.

Leptin: A protein that regulates the balance of energy, also used in research on diabetes.

Adiponectin: The hormone that regulates glucose levels and fatty acid metabolism, generally reduced in diabetes.

Advantages of our IVD biomarkers

Specificity and Sensitivity: Proteins can be highly specific to certain diseases or conditions, allowing for accurate and sensitive diagnostic tests. This specificity makes it possible to distinguish between the similar conditions and thus increase test reliability.

Early Detection: Some protein biomarkers arise early in disease progression to enable early detection and treatment. It can be essential in managing disorders such as cancer, cardiovascular conditions, and metabolic diseases such as diabetes.

Dynamic Range: Proteins are present in a wide range of concentrations in biological samples, which can be quantitatively assessed to determine disease severity or progression. This dynamic range is useful when measuring therapy response or disease progression.

High Throughput Screening: Protein-based assays can typically be converted for high throughput screening that will enable mass testing and quick outcomes. It is particularly useful in a clinical setting, where decisions need to be made at a quick clip.

Multiple Analyte Detection: Proteins can be analyzed by multiplex assays, which measure multiple biomarkers at the same time. This can be beneficial for deeper profiling and a better understanding of a patient's condition.

Cost-effectiveness: Once developed, protein assays can be relatively cheap to manufacture and implement, making them affordable for clinical laboratories to adopt widely.

Integration with Existing Platforms: Protein biomarkers are typically compatible with default diagnostic platforms, so that they can be deployed in clinical trials without the need for custom-built platforms.

Non-invasive Sample Collection: Many protein biomarkers are detectable in blood, urine or saliva, making it possible to perform non-invasive or minimally invasive testing with less pain and increased compliance.

Case Study

Case 1: Wadwa RP, Reed ZW, Buckingham BA, DeBoer MD, Ekhlaspour L, Forlenza GP, Schoelwer M, Lum J, Kollman C, Beck RW, Breton MD; PEDAP Trial Study Group. Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes. N Engl J Med. 2023 Mar 16;388(11):991-1001. doi: 10.1056/NEJMoa2210834. PMID: 36920756; PMCID: PMC10082994.

Closed-loop insulin administration control systems could reduce blood glucose levels in very young type 1 diabetic children. In this study of children with early type 1 diabetes, glucose levels remained in the normal range for a greater percentage of time when using a closed loop system than standard care.

Fig2. Figure 1.. Mean Percentage of Time with the Glucose Level in the Target Range. Panel A shows the mean percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter) each week over the 13 weeks of the trial among patients who were assigned to receive treatment with either a closed-loop system or standard care. The inset shows the mean percentage of time that the glucose level was in the target range each day for the first 7 days in the closed-loop group, according to whether the patient had been using an insulin pump or receiving multiple daily injections of insulin before the trial. The circles denote the mean values, and the vertical lines extend to ±1 SE of the mean. Panel B shows an envelope plot of the same outcome, as measured by continuous glucose monitoring, according to the time of day over the 13-week period. The circles denote the hourly median values, and the lower and upper boundary of each shaded region the 25th and 75th percentiles, respectively.

Case 2: Xiao H, Sun X, Lin Z, Yang Y, Zhang M, Xu Z, Liu P, Liu Z, Huang H. Gentiopicroside targets PAQR3 to activate the PI3K/AKT signaling pathway and ameliorate disordered glucose and lipid metabolism. Acta Pharm Sin B. 2022 Jun;12(6):2887-2904. doi: 10.1016/j.apsb.2021.12.023. Epub 2022 Jan 6. PMID: 35755276; PMCID: PMC9214054.

Insulin resistance is caused by the blockage of post-insulin receptor signaling. The PI3K/AKT signalling pathway can be negatively regulated by the progestin and adipoQ receptor 3 (PAQR3), which is an important mediator of inflammation and metabolism. In it, the authors identified GPS, a blocker of PAQR3 expression that directly inhibits PAQR3 and repairs the insulin signaling pathway, as a potential therapeutic candidate for diabetes.

Fig3. GPS treatment promoted the activation of the PI3K/AKT axis to improve glucose and lipid metabolism in PA-treated HepG2 cells. (C) Lipid droplets deposition was assessed by oil red staining and glycogen synthesis was assessed by PAS staining. (D) GCK, G6Pase, LDLR and SREBP-1c protein levels in palmitate acid-induced HepG2 cells (n = 3).