This is very recognizable phrase ‘diabetes’ you could have heard among the aged. They know it in a very simplified way. Sugar is the cause, insulin is the best way to resolve the disease and they are very sure that they could wolf down whatever they want to and make use of insulin to control sugar level. Is that the truth? I don’t think so.
Do not grumble that you have diabetes and do not take it too easily as well.
This post will handle with stuffs that will deal with diabetes and in the next post we will capture ideas about the treatment and complications.
Our human body is like machinery, if you handle it with care you can employ it for a long time. If you exploit it, then you will never know when it will bring to a halt.
It is the same issue with our body. Diabetes mellitus is a metabolic disorder that is motivated by environment and genetics.
Keywords
Pancreas: Produces insulin with the help of beta cells.
Insulin: Insulin is a hormone which helps in the storage of glucose for later use. It stores glucose as glycogen in skeletal muscle, fat and liver.
Glucose:
Insulin resistance: Insulin as above said helps to store glucose in skeletal muscle, fat and liver. Insulin resistance develops when there is a situation that the available insulin for unknown reason cannot take part in taking glucose into liver cells, adipocytes (fat) and muscle. As a result, glucose cannot enter cells and stays in blood leading to hyperglycaemia (increased glucose in blood) and symptoms related to it.
How does Insulin and glucose get on together?
Insulin as mentioned earlier helps in storing glucose for future use. It is synthesized in the beta cell of the pancreas. It is initially produced as a precursor pre proinsulin. Insulin is a hormone composed of amino acids. These amino acids in preproinsulin when cleaved by proteolytic enzymes (amino acids are broken down) forms into proinsulin. The proinsulin is then broken down into chain of C peptide and A and B chains of insulin connected by disulphide bonds. These are stored in beta cells of the pancreas. C peptide clears slowly, so it could be measured to detect the amount of insulin in type 1 diabetes.
Glucose is essential for the production of insulin. There is a threshold for glucose, at the point which insulin starts to secrete from pancreas (blood glucose level is >3.9mmol/L).
For glucose to enter into the beta cell, it needs a transporter. So GLUT 2 transporter exports the glucose into the beta cell. GLUT 2 is just like a bus that drops us at the required stop, the GLUT 2 receptors transports glucose into beta cell. It blocks the potassium channel by the production of ATP which in turn opens the voltage gated calcium channels which stimulates the production of insulin. Insulin secretion occur every 10mins for about 80-150mins. There are certain drugs which bind to this receptors and blocks the potassium channel and stimulates the secretion of insulin, when there is something wrong in the production of insulin.
Glucose is stored in the form of glycogen and when the blood glucose level falls, glycogen is converted into glucose with the help of glucagon. After a series of activity, glucose is stored into the cell with the help of another glucose transporter GLUT 4.
Source: Fauci As, Kasper DL, Braunwald E, HauserSL, Longo DL, Jameson JL, Loscalzo : Diabetes Mellitus in Harrison’s principles of Internal medicine, 17th edition
When there is interruption in any of the above mechanism i.e. decreased production of insulin, resistance to insulin, or increased plasma glucose could turn this into a vicious cycle.
Classification of Diabetes:
Type 1 formerly described as insulin dependent diabetes is a form which begins in a very young age with little or no production of insulin. This has genetic, environmental and immunologic factors that influence the destruction of the beta cells leading to decrease in the production of insulin or complete stopping of production of insulin. The destruction is very progressive.
Type 2 formerly defined as non-insulin dependent diabetes is a form which begins at a very later age which is mostly dependent on an individual lifestyle. Partly it might be influenced by genetics.
In type 2 diabetes mellitus, the most considerable promoting factor of the disease is insulin resistance.
What is insulin resistance? For some reason the cells in the human body becomes insensitive to the insulin. The job of insulin is to help storage of glucose in cells but when there is decreased sensitivity or complete resistance to insulin, the result is insulin will not be able to accomplish its job. It stays in blood and the glucose in the blood will not able to cross in to the cells for storage. As a consequence, when there is decreased availability of glucose to insulin sensitive cells then there is production of glucose from liver (hepatic gluconeogenesis) for energy. This together with decreased intake of glucose intake into cells results in increased plasma glucose (hyperglycaemia). There is nothing that could reason out the cause of resistance of insulin.
For some reason insulin production becomes decreased after the insulin resistance. It might be that there is failure of beta cell to produce insulin but the reason is unclear.
In addition to the amplified production of glucose by the liver, there is increased production of free fatty acids from the adipocytes. We already learnt that glucose is deposited in liver, fat and muscle. When there is insulin resistance, free fatty acids are formed which results in increase in low density lipoproteins and triglycerides (bad cholesterol that can easily deposit in the blood vessel wall) and decreased high density cholesterol(good cholesterol).
There are many other forms of diabetes mellitus caused by genetic defects, cystic fibrosis, neoplasia, hemochromatosis, fibrocalculous pancreatopathy, cushing’s syndrome, phaechromocytoma, somatostatinoma, aldosteronoma and infections like rubella, coxsackie virus, cytomegalovirus and mainly gestational diabetes (Diabetes mellitus during pregnancy)
When should you doubt a person is said to have diabetes?
Consider the following symptoms polyuria (increased urination), Polydipsia (increased thirst), polyphagia(eating too much) and weight loss. All these symptoms are detailed picture caused by the interruption in the normal physiology of insulin and glucose.
Along with increase in glucose level in blood form the criteria to diagnose diabetes mellitus.
How do you diagnose a person has got diabetes?
Plasma glucose will be measured before glucose load and two hours after 75g of glucose load.
Measuring blood glucose
Fasting plasma glucose- person does not eat or drink 12-14 hours before the test
Normal <5.6mmol/l>7.0mmol/L
2 hours after 75g of glucose load
Normal <7.8mmol/l>11.1mmol/L
Patient will be diagnosed with Diabetes mellitus if
Fasting plasma glucose value >7mmol/L
Plasma glucose value after glucose load >11.1mmol/L
Impaired glucose tolerance is the value of glucose in which the glucose value is not in a level to put the diagnosis of diabetes mellitus or to exclude it but the plasma glucose value is in the range between normal value and Diabetes mellitus. The patient must be on strict control of diet. It takes about 5years time to develop diabetes mellitus.
People diagnosed with impaired fasting plasma glucose have a high risk of developing diabetes mellitus in future and the individual has an increased risk of cardiovascular disease.
Glycosylated hemobglobin (hbA1C) can be measured to give us a picture of three months history of blood glucose.
Acute complications of Diabetes mellitus:
It is not the symptoms that cause trouble but the ignorance of the patient of their diet will lead to development of chains of complications which could have been easily prevented, if patient had a strict control over his diet.
When we speak about acute complications, the one mostly related to negligence in the usage of insulin, improper diet and fluid depletion will lead to diabetic ketoacidosis and hyperglycaemic hyperosmolar state.
Diabetic ketoacidosis is more common in type 1 DM and hyperglycaemic hyperosmolar coma in type 2 DM.
Diabetic ketoacidosis
Diabetic ketoacidosis develops when there is insulin deficiency. Patient will have symptoms of nausea, vomiting, abdominal pain, thirst, polyuria along with signs like tachycardia (increased heart rate), dehydration, kussmaul respiration(deep breathing and increased in rate), lethargy and could lead to coma.
This is happened due to change in acid base balance of the body. When there is insulin deficiency we know that there is no glucose in the cell and there is hyperglycaemia (increased glucose in the blood). When there is not enough glucose, the body as a compensatory mechanism (increase glucose in blood but glucose cannot enter the cell due to insulin deficiency) starts to produce increase in glucagon which converts stored glycogen into glucose.
Glucose is going to pile up in the blood but there is no way of exit. In addition, the body thinks that there is not enough glucose so the stored glycogen is converted to glucose in liver. The adipocytes also release free fatty acids(usually free fatty acid result into Triglycerides and very low density lipoprotein) that result in ketone body(when there is not energy through glucose in the cell, the body starts to derive energy from fatty acids) formation. They give energy to the starving human cells. They result in decreased ph (acid) but the bicarbonate helps to compensate it. When there is decreased bicarbonate, then metabolic acidosis ensues.
Ketoacidosis is diagnosed with increased glucose, ketones and metabolic acidosis.
Treatment is to begin with assessing serum electrolytes, replace lost fluid with 2-3L of 0.9% saline over first 1-3hours;later with 5% glucose and 0.45% saline and it is given till the plasma glucose reduces to 250mg/dl
Insulin is also a main component of the treatment and the patient is given short acting insulin (IV 0.1units/kg) , insulin is increased if there is no response in 2-4h . We have to take into consideration of the serum potassium level as well. If the serum potassium level is <3.3mmol/l,>55.5mmol/L, hyperosmolality(>350mosmol/L).
Same principles are followed as in ketoacidosis. Fluid replacement with 1-3L of 0.9% normal saline for the first 2-3h. The fluid should not be infused rapidly as the hyperosmolar state is usually developed in a long period and rapid reversal might worsen the neurologic function.Insulin should be infused. IV insulin of 0.1units/kg followed by IV insulin at a constant infusion rate of 0.1units/kg per hour.
Above mentioned acute complications could be prevented. Next blog will follow on with the treatment principles of Diabetes Mellitus and chronic complications.
Do not grumble that you have diabetes and do not take it too easily as well.
This post will handle with stuffs that will deal with diabetes and in the next post we will capture ideas about the treatment and complications.
Our human body is like machinery, if you handle it with care you can employ it for a long time. If you exploit it, then you will never know when it will bring to a halt.
It is the same issue with our body. Diabetes mellitus is a metabolic disorder that is motivated by environment and genetics.
Keywords
Pancreas: Produces insulin with the help of beta cells.
Insulin: Insulin is a hormone which helps in the storage of glucose for later use. It stores glucose as glycogen in skeletal muscle, fat and liver.
Glucose:
Insulin resistance: Insulin as above said helps to store glucose in skeletal muscle, fat and liver. Insulin resistance develops when there is a situation that the available insulin for unknown reason cannot take part in taking glucose into liver cells, adipocytes (fat) and muscle. As a result, glucose cannot enter cells and stays in blood leading to hyperglycaemia (increased glucose in blood) and symptoms related to it.
How does Insulin and glucose get on together?
Insulin as mentioned earlier helps in storing glucose for future use. It is synthesized in the beta cell of the pancreas. It is initially produced as a precursor pre proinsulin. Insulin is a hormone composed of amino acids. These amino acids in preproinsulin when cleaved by proteolytic enzymes (amino acids are broken down) forms into proinsulin. The proinsulin is then broken down into chain of C peptide and A and B chains of insulin connected by disulphide bonds. These are stored in beta cells of the pancreas. C peptide clears slowly, so it could be measured to detect the amount of insulin in type 1 diabetes.
Glucose is essential for the production of insulin. There is a threshold for glucose, at the point which insulin starts to secrete from pancreas (blood glucose level is >3.9mmol/L).
For glucose to enter into the beta cell, it needs a transporter. So GLUT 2 transporter exports the glucose into the beta cell. GLUT 2 is just like a bus that drops us at the required stop, the GLUT 2 receptors transports glucose into beta cell. It blocks the potassium channel by the production of ATP which in turn opens the voltage gated calcium channels which stimulates the production of insulin. Insulin secretion occur every 10mins for about 80-150mins. There are certain drugs which bind to this receptors and blocks the potassium channel and stimulates the secretion of insulin, when there is something wrong in the production of insulin.
Glucose is stored in the form of glycogen and when the blood glucose level falls, glycogen is converted into glucose with the help of glucagon. After a series of activity, glucose is stored into the cell with the help of another glucose transporter GLUT 4.
Source: Fauci As, Kasper DL, Braunwald E, HauserSL, Longo DL, Jameson JL, Loscalzo : Diabetes Mellitus in Harrison’s principles of Internal medicine, 17th edition
When there is interruption in any of the above mechanism i.e. decreased production of insulin, resistance to insulin, or increased plasma glucose could turn this into a vicious cycle.
Classification of Diabetes:
Type 1 formerly described as insulin dependent diabetes is a form which begins in a very young age with little or no production of insulin. This has genetic, environmental and immunologic factors that influence the destruction of the beta cells leading to decrease in the production of insulin or complete stopping of production of insulin. The destruction is very progressive.
Type 2 formerly defined as non-insulin dependent diabetes is a form which begins at a very later age which is mostly dependent on an individual lifestyle. Partly it might be influenced by genetics.
In type 2 diabetes mellitus, the most considerable promoting factor of the disease is insulin resistance.
What is insulin resistance? For some reason the cells in the human body becomes insensitive to the insulin. The job of insulin is to help storage of glucose in cells but when there is decreased sensitivity or complete resistance to insulin, the result is insulin will not be able to accomplish its job. It stays in blood and the glucose in the blood will not able to cross in to the cells for storage. As a consequence, when there is decreased availability of glucose to insulin sensitive cells then there is production of glucose from liver (hepatic gluconeogenesis) for energy. This together with decreased intake of glucose intake into cells results in increased plasma glucose (hyperglycaemia). There is nothing that could reason out the cause of resistance of insulin.
For some reason insulin production becomes decreased after the insulin resistance. It might be that there is failure of beta cell to produce insulin but the reason is unclear.
In addition to the amplified production of glucose by the liver, there is increased production of free fatty acids from the adipocytes. We already learnt that glucose is deposited in liver, fat and muscle. When there is insulin resistance, free fatty acids are formed which results in increase in low density lipoproteins and triglycerides (bad cholesterol that can easily deposit in the blood vessel wall) and decreased high density cholesterol(good cholesterol).
There are many other forms of diabetes mellitus caused by genetic defects, cystic fibrosis, neoplasia, hemochromatosis, fibrocalculous pancreatopathy, cushing’s syndrome, phaechromocytoma, somatostatinoma, aldosteronoma and infections like rubella, coxsackie virus, cytomegalovirus and mainly gestational diabetes (Diabetes mellitus during pregnancy)
When should you doubt a person is said to have diabetes?
Consider the following symptoms polyuria (increased urination), Polydipsia (increased thirst), polyphagia(eating too much) and weight loss. All these symptoms are detailed picture caused by the interruption in the normal physiology of insulin and glucose.
Along with increase in glucose level in blood form the criteria to diagnose diabetes mellitus.
How do you diagnose a person has got diabetes?
Plasma glucose will be measured before glucose load and two hours after 75g of glucose load.
Measuring blood glucose
Fasting plasma glucose- person does not eat or drink 12-14 hours before the test
Normal <5.6mmol/l>7.0mmol/L
2 hours after 75g of glucose load
Normal <7.8mmol/l>11.1mmol/L
Patient will be diagnosed with Diabetes mellitus if
Fasting plasma glucose value >7mmol/L
Plasma glucose value after glucose load >11.1mmol/L
Impaired glucose tolerance is the value of glucose in which the glucose value is not in a level to put the diagnosis of diabetes mellitus or to exclude it but the plasma glucose value is in the range between normal value and Diabetes mellitus. The patient must be on strict control of diet. It takes about 5years time to develop diabetes mellitus.
People diagnosed with impaired fasting plasma glucose have a high risk of developing diabetes mellitus in future and the individual has an increased risk of cardiovascular disease.
Glycosylated hemobglobin (hbA1C) can be measured to give us a picture of three months history of blood glucose.
Acute complications of Diabetes mellitus:
It is not the symptoms that cause trouble but the ignorance of the patient of their diet will lead to development of chains of complications which could have been easily prevented, if patient had a strict control over his diet.
When we speak about acute complications, the one mostly related to negligence in the usage of insulin, improper diet and fluid depletion will lead to diabetic ketoacidosis and hyperglycaemic hyperosmolar state.
Diabetic ketoacidosis is more common in type 1 DM and hyperglycaemic hyperosmolar coma in type 2 DM.
Diabetic ketoacidosis
Diabetic ketoacidosis develops when there is insulin deficiency. Patient will have symptoms of nausea, vomiting, abdominal pain, thirst, polyuria along with signs like tachycardia (increased heart rate), dehydration, kussmaul respiration(deep breathing and increased in rate), lethargy and could lead to coma.
This is happened due to change in acid base balance of the body. When there is insulin deficiency we know that there is no glucose in the cell and there is hyperglycaemia (increased glucose in the blood). When there is not enough glucose, the body as a compensatory mechanism (increase glucose in blood but glucose cannot enter the cell due to insulin deficiency) starts to produce increase in glucagon which converts stored glycogen into glucose.
Glucose is going to pile up in the blood but there is no way of exit. In addition, the body thinks that there is not enough glucose so the stored glycogen is converted to glucose in liver. The adipocytes also release free fatty acids(usually free fatty acid result into Triglycerides and very low density lipoprotein) that result in ketone body(when there is not energy through glucose in the cell, the body starts to derive energy from fatty acids) formation. They give energy to the starving human cells. They result in decreased ph (acid) but the bicarbonate helps to compensate it. When there is decreased bicarbonate, then metabolic acidosis ensues.
Ketoacidosis is diagnosed with increased glucose, ketones and metabolic acidosis.
Treatment is to begin with assessing serum electrolytes, replace lost fluid with 2-3L of 0.9% saline over first 1-3hours;later with 5% glucose and 0.45% saline and it is given till the plasma glucose reduces to 250mg/dl
Insulin is also a main component of the treatment and the patient is given short acting insulin (IV 0.1units/kg) , insulin is increased if there is no response in 2-4h . We have to take into consideration of the serum potassium level as well. If the serum potassium level is <3.3mmol/l,>55.5mmol/L, hyperosmolality(>350mosmol/L).
Same principles are followed as in ketoacidosis. Fluid replacement with 1-3L of 0.9% normal saline for the first 2-3h. The fluid should not be infused rapidly as the hyperosmolar state is usually developed in a long period and rapid reversal might worsen the neurologic function.Insulin should be infused. IV insulin of 0.1units/kg followed by IV insulin at a constant infusion rate of 0.1units/kg per hour.
Above mentioned acute complications could be prevented. Next blog will follow on with the treatment principles of Diabetes Mellitus and chronic complications.
