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Prof Ram Shankar Upadhayaya
At its core, diabetes is characterized by elevated glucose levels, commonly referred to as hyperglycemia. A myriad of metabolic disorders can contribute to this abnormal rise in glucose levels. To understand the root causes, diabetes mellitus is bifurcated into two primary categories: one involving a defect in insulin secretion and the other in insulin action. All different classifications eventually trace back to these fundamental distinctions.
Insulin secretion primarily takes place in pancreatic beta cells, where one can find defective insulin action receptors and transporters. The crucial role of receptors becomes evident in type 2 diabetes mellitus.
The structure of the insulin molecule is also of utmost importance, consisting of four components in its pre-pro-insulin state. Upon the removal of one amino acid from pre-pro-insulin, it transforms into pro-insulin, which includes A, B, and C-peptides.
Subsequently, specific enzymes cleave pro-insulin to produce mature insulin (A and B chains connected by a disulfide bond) and eliminate the C-peptide. Each mature insulin contains one C-peptide.
Measuring the C-peptide level becomes a significant indicator of the amount of insulin released, holding clinical relevance, especially in the diagnosis of polycystic ovarian syndrome. This condition is characterized by cyst formation and the release of androgenic hormones due to the heightened sensitivity of follicular cells to insulin. Confirming the presence of cysts in the ovary, it becomes imperative to assess insulin levels by measuring the C-peptide, aiding in the effective management and monitoring of patients and their progress.
When a beta cell undergoes depolarization, triggered by the ionic nature of potassium, it releases insulin. Following a meal, glucose enters the cells, initiating the internal metabolic cycle. The digestion of glucose leads to the production of Cyclic Adenosine Monophosphate (cAMP), causing depolarization. Subsequently, calcium channels open up, facilitating the release of insulin. In this process, a vesicle emerges, opens up, and expels insulin products along with other proteins.
In Type 1 diabetes mellitus, there is an antigen called islet cell antigen, and the immune system attacks in response. Beta cells release insulin and the target tissue has an insulin receptor. The attachment of insulin to the receptor initiates signal transduction, causing the emergence of GLUT receptors on the cell surface. This, in turn, makes glucose channels available, facilitating the metabolism of glucose. This outlines the mechanism through which insulin effectively transports glucose into the cells.
Pathological complications of diabetes are due to lots of glucose in the blood because it will initiate the non-enzymatic glycation that would affect the function of protein and lead to diabetic complications. That is why we must cut carbs and use the appropriate medicines to remove glucose to avoid glucose peaks.
Many other abnormalities give rise to hyperglycemia, such as the immune system attacking beta cells and destroying them, leading to Type-1 diabetes mellitus. Typically, autoimmune diseases are more common in women. However, in type 1 diabetes mellitus, the ratio is three men to two women. So, this is an autoimmune disease where the propensity for the disease is higher in men.
Some genetic issues involve the molecular structure of insulin molecules due to polymorphism that allows such molecule structure to present but not function. Some viral infections, such as coxsackievirus, CMV cytomegalovirus, and rubella, can trigger the immune system and destroy beta cells, leading to type 1 diabetes mellitus.
There are endocrine issues causing gluconeogenesis, reducing lipolysis, and increasing glucose levels. Hyperthyroidism causes hyperglycemia.
When there is increased thyroid activity, liver function increases and produces more glucose, leading to increase in GIT function and absorption of more glucose, stimulating the pituitary gland through the hypothalamus and releasing the thyroid hormones.
It also releases neuropeptides for appetite every time the hypothalamus tells the pituitary to upregulate the thyroid, which also upregulates appetite.
So, a person with hyperthyroidism will eat more because the person is receiving signals to eat more. Few drugs can cause diabetes, such as alpha and beta-receptor agonists.
Beta-receptor agonists cause insulin resistance, whereas alpha-receptor agonists reduce insulin release. So, drugs that cause beta-receptor agonism, alpha-receptor agonism, or glucocorticoid drugs can lead to hyperglycemia.
About 80% of people develop type 2 diabetes mellitus, 10% develop type 1 diabetes mellitus, and the remaining 10% develop all other types of diabetes mellitus. Of these, Maturity-Onset Diabetes of the Young (MODY) is the most important. MODY is neither type 1 nor type 2 diabetes.
It is another type of diabetes mellitus driven by genetic factors affecting hepatic nuclear factors. Imagine you have a patient presenting with hyperglycemia, and there is suspicion of either MODY or Type 1 diabetes. To differentiate and exclude Type 1 diabetes, we would examine auto-antibodies associated with the autoimmune aspect of Type 1.
In case of MODY, there is an absence of autoantibodies targeting insulin, islet cell antigens, or glutamic acid carboxylase antigens typically involved in Type 1 diabetes mellitus.
MODY lacks insulin resistance and administering insulin to such a patient results in proper functioning. Peripheral tissues in these individuals exhibit no resistance to insulin; however, there is a lower insulin production.
In these patients, insulin resistance gradually develops between 20 and 30 years. Changes in their dietary habits may necessitate increased food, requiring more insulin, ultimately leading to diabetes mellitus.
In summary, diabetes manifests in three main types: type 1, type 2, and MODY. Understanding intricate mechanisms of diabetes equips individuals to make informed decisions, underscoring the importance of early detection, proactive management, and continuous research in diabetes mellitus.
(The writer is a US-based medical scientist)
At its core, diabetes is characterized by elevated glucose levels, commonly referred to as hyperglycemia. A myriad of metabolic disorders can contribute to this abnormal rise in glucose levels. To understand the root causes, diabetes mellitus is bifurcated into two primary categories: one involving a defect in insulin secretion and the other in insulin action. All different classifications eventually trace back to these fundamental distinctions.
Insulin secretion primarily takes place in pancreatic beta cells, where one can find defective insulin action receptors and transporters. The crucial role of receptors becomes evident in type 2 diabetes mellitus.
The structure of the insulin molecule is also of utmost importance, consisting of four components in its pre-pro-insulin state. Upon the removal of one amino acid from pre-pro-insulin, it transforms into pro-insulin, which includes A, B, and C-peptides.
Subsequently, specific enzymes cleave pro-insulin to produce mature insulin (A and B chains connected by a disulfide bond) and eliminate the C-peptide. Each mature insulin contains one C-peptide.
Measuring the C-peptide level becomes a significant indicator of the amount of insulin released, holding clinical relevance, especially in the diagnosis of polycystic ovarian syndrome. This condition is characterized by cyst formation and the release of androgenic hormones due to the heightened sensitivity of follicular cells to insulin. Confirming the presence of cysts in the ovary, it becomes imperative to assess insulin levels by measuring the C-peptide, aiding in the effective management and monitoring of patients and their progress.
When a beta cell undergoes depolarization, triggered by the ionic nature of potassium, it releases insulin. Following a meal, glucose enters the cells, initiating the internal metabolic cycle. The digestion of glucose leads to the production of Cyclic Adenosine Monophosphate (cAMP), causing depolarization. Subsequently, calcium channels open up, facilitating the release of insulin. In this process, a vesicle emerges, opens up, and expels insulin products along with other proteins.
In Type 1 diabetes mellitus, there is an antigen called islet cell antigen, and the immune system attacks in response. Beta cells release insulin and the target tissue has an insulin receptor. The attachment of insulin to the receptor initiates signal transduction, causing the emergence of GLUT receptors on the cell surface. This, in turn, makes glucose channels available, facilitating the metabolism of glucose. This outlines the mechanism through which insulin effectively transports glucose into the cells.
Pathological complications of diabetes are due to lots of glucose in the blood because it will initiate the non-enzymatic glycation that would affect the function of protein and lead to diabetic complications. That is why we must cut carbs and use the appropriate medicines to remove glucose to avoid glucose peaks.
Many other abnormalities give rise to hyperglycemia, such as the immune system attacking beta cells and destroying them, leading to Type-1 diabetes mellitus. Typically, autoimmune diseases are more common in women. However, in type 1 diabetes mellitus, the ratio is three men to two women. So, this is an autoimmune disease where the propensity for the disease is higher in men.
Some genetic issues involve the molecular structure of insulin molecules due to polymorphism that allows such molecule structure to present but not function. Some viral infections, such as coxsackievirus, CMV cytomegalovirus, and rubella, can trigger the immune system and destroy beta cells, leading to type 1 diabetes mellitus.
There are endocrine issues causing gluconeogenesis, reducing lipolysis, and increasing glucose levels. Hyperthyroidism causes hyperglycemia.
When there is increased thyroid activity, liver function increases and produces more glucose, leading to increase in GIT function and absorption of more glucose, stimulating the pituitary gland through the hypothalamus and releasing the thyroid hormones.
It also releases neuropeptides for appetite every time the hypothalamus tells the pituitary to upregulate the thyroid, which also upregulates appetite.
So, a person with hyperthyroidism will eat more because the person is receiving signals to eat more. Few drugs can cause diabetes, such as alpha and beta-receptor agonists.
Beta-receptor agonists cause insulin resistance, whereas alpha-receptor agonists reduce insulin release. So, drugs that cause beta-receptor agonism, alpha-receptor agonism, or glucocorticoid drugs can lead to hyperglycemia.
About 80% of people develop type 2 diabetes mellitus, 10% develop type 1 diabetes mellitus, and the remaining 10% develop all other types of diabetes mellitus. Of these, Maturity-Onset Diabetes of the Young (MODY) is the most important. MODY is neither type 1 nor type 2 diabetes.
It is another type of diabetes mellitus driven by genetic factors affecting hepatic nuclear factors. Imagine you have a patient presenting with hyperglycemia, and there is suspicion of either MODY or Type 1 diabetes. To differentiate and exclude Type 1 diabetes, we would examine auto-antibodies associated with the autoimmune aspect of Type 1.
In case of MODY, there is an absence of autoantibodies targeting insulin, islet cell antigens, or glutamic acid carboxylase antigens typically involved in Type 1 diabetes mellitus.
MODY lacks insulin resistance and administering insulin to such a patient results in proper functioning. Peripheral tissues in these individuals exhibit no resistance to insulin; however, there is a lower insulin production.
In these patients, insulin resistance gradually develops between 20 and 30 years. Changes in their dietary habits may necessitate increased food, requiring more insulin, ultimately leading to diabetes mellitus.
In summary, diabetes manifests in three main types: type 1, type 2, and MODY. Understanding intricate mechanisms of diabetes equips individuals to make informed decisions, underscoring the importance of early detection, proactive management, and continuous research in diabetes mellitus.
(The writer is a US-based medical scientist)
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