Diabetes Mellitus:- Part 1 – Carbohydrate and Glucose Metabolism, Insulin and Glucagon

Carbohydrate and Glucose Metabolism

What Sample for Glucose Estimation is needed?

1. This test can be done on serum. The serum should be separated within 30 minutes of collection.
2. The Serum can be stored at 25° C for 8 hours and 72 hours at 4 °C.
3. Oxalated blood can also be used. Preservative sodium fluoride may be added.
4. The plasma can be stored at 25 °C for 24 hours (with preservative sodium fluoride).

Stability of the  sample for glucose level

1. One ml of blood in anticoagulant will be stable for 3 hours with fluoride.
2. Oxalate plasma is stable at 2 to 8 °C for 48 hours.
3. Mainly, serum is used, stable for 8 hours at 25 °C and 72 hours at 4 °C.
4. A fast of 6 to 8 hours is required for a fasting sample.

What are the Indications for glucose estimation?

1. This test is done to diagnose diabetes mellitus.
2. This test is also done to evaluate and monitor diabetes mellitus.

Pathophysiology of the Carbohydrates 

1. Carbohydrates are major components of the diet and are an essential energy source.
   1. Glucose is controlled by insulin and glucagon.
   2. Glucose is low in the fasting state.
   3. The glucose = C₆H₁₂O₆ = C₆ (H₂O)6.
   4. Lactose = C₁₂H₂₂O₁₁ = C₁₂ (H₂O)_11.
2. The capacity of the body to store the carbohydrate is limited:
   1. The liver can store only 10% of its wet weight.
   2. Muscles can store 5% of their wet weight.
   3. This store amount is only sufficient for half a day.
3. Carbohydrates include sugar and starch.
4. The salivary gland enzyme converts starch and glycogen into dextrin and maltose.
   1. The acid pH of the stomach inhibits salivary amylase.
   2. Pancreatic alkaline secretion of amylase acts mainly on maltose and the disaccharides.
   3. Maltose, lactose, and sucrose are converted into:
      1. Glucose.
      2. Galactose.
      3. Fructose.

What are the functions of carbohydrates?

1. CHO are the components of RNA and DNA.
2. CHO is the Source of energy, which is glucose.
3. Under fasting conditions, the following organs depend only upon glucose as a source of energy:
   1. The brain is the main organ dependent on glucose.
   2. Red blood cells.
   3. White blood cells.
   4. Platelets.
   5. Kidney medulla.

Carbohydrate and Glucose Metabolism: Carbohydrates function

4. Increased glucose level leads to its storage as glycogen in the liver.
   1. Decreased glucose level leads to glycogenolysis and forms glucose from the glycogen.

Glucose Metabolism:

1. The breakdown of the following forms glucose:
   1. Grains.
   2. Starchy vegetables.
   3. Legumes.
   4. Body store of glycogen.
   5. Endogenous proteins.
   6. Excess glucose is converted into fat by adipose cells and stored in the adipose tissue.

Carbohydrate and Glucose Metabolism: Glucose pathways/metabolism

2. The Triose pathway is the main junction where four pathways intersect and help to maintain the glucose level.
   1. This is a complicated enzymatic system, but the glucose level is maintained in the normal range.

Glucose metabolism

3. The following diagrams show that glucose metabolism is interlinked with fats and proteins.
4. Glucose levels are controlled by insulin and glucagon.

Insulin and glucagon role in glucose metabolism

Glucose metabolism and the role of the liver

Carbohydrate metabolism

Pathophysiology of Glucagon and Insulin

Glucagon

1. Glucagon is produced by the Alpha (α) cells of islets of Langerhans in the pancreas.

Glucose level is regulated by insulin and glucagon

2. Glucagon is 29 amino acids polypeptide.
3. The major target organ is the liver, which binds to a specific receptor and increases intracellular adenosine-5-monophosphate and calcium.
4. Glucagon stimulates the production of glucose in the liver by glycogenolysis and gluconeogenesis.
5. It also increases ketogenesis in the liver.
6. The minor target organ is fat, which causes lipolysis.
7. Glucagon secretion is controlled by glucose level.
   1. A low glucose level is stimulatory.
   2. A high glucose level is inhibitory.
8. In the case of fasting, protein, and fats are broken down into glucose under the influence of Glucagon.
9. In the case of long-standing diabetes mellitus, it impairs the glucagon response to hypoglycemia, leading to increased chances for hypoglycemia episodes.
10. Insulin inhibits glucagon secretion from the pancreas.

Insulin

1. Insulin is produced by the beta cells of islets of Langerhans in the pancreas.
2. Insulin is an anabolic hormone.
3. First, proinsulin is formed in the ribosomes of the rough endoplasmic reticulum.
4. Later on, stored in the Golgi apparatus.
5. Proteolytic cleavage forms Insulin and C-peptide.

Insulin formation

Insulin and Diabetes mellitus:

1. It results from the abnormality in the production or use of insulin.
2. β-cells of the pancreas produce insulin, and the involvement of these Β-cells abnormality leads to diabetes mellitus:
   1. β-cells insulin production is deficient.
   2. Normal synthesis but abnormal release.
   3. Extra-pancreatic factors are like peripheral tissue cell receptor dysfunction, producing resistance to the cellular action of insulin.
   4. Non-pancreatic hormones will affect insulin secretion or blood glucose metabolism.
3. C-peptide has no biological activity and has a longer life than insulin.
   1. 1. Fasting C-peptide concentration is five folds to 10 folds higher than insulin.

C-peptide and Proinsulin

Insulin action and facts:

1. Insulin attaches to the insulin receptors in muscles, the liver, and fatty cells.
2. Insulin pushes the glucose into the cells to be metabolized into glycogen, amino acids, and fatty acids.
3. Insulin lowers the plasma glucose level.

Glucose-insulin receptor role

Insulin functions and action on glucose

4. Increased insulin will lower the blood glucose level, and deficiency will increase glucose.

Insulin main functions

Insulin and glucagon role in glucose metabolism

5. Other hormones like Adreno-corticosteroids, ACTH, epinephrine, and thyroxine can affect glucose metabolism.
   1. The above hormones increase the plasma glucose level.
6. Serum glucose level is dependent upon the time and relation to food intake.
7. The glucose level is low in the fasting state.
   1. Glucose goes to the normal state after 2 hours of food intake.
8. The concentration of glucose is higher in arterial blood than in venous.
9. When fasting glucose is around 126 mg/dl, try to estimate glucose level after oral 75 grams of glucose.
   1. Now check one-hour and two-hour samples.
   2. This oral glucose test will pick up Impaired Glucose Tolerance cases, where you can prevent the development of Diabetes Mellitus.
   3. The fasting level is between 100 to 126 mg/dl, which is called fasting hyperglycemia.
   4. The glucose level of 135 mg/dL is abnormal in the fasting state but is normal after one hour of the meal.

What are Lab findings in hyperglycemia (Diabetes mellitus)?

1. Increased blood glucose.
2. Increased urine-specific gravity.
3. Decreased blood and urine pH values (acidosis).
4. Increased blood and urine osmolality.
5. Electrolytes disturbance.
6. Ketones in the blood and urine.

Questions and answers: