The concentration of glucose in the blood is the net resultant of two processes.
1. Rate of glucose entrance into the bloodstream 2. Rate of glucose removal from the bloodstream.
Ways by which sugar is added to the blood 1. By absorption from the intestine 2. Breakdown of liver glycogen
3. By gluconeogenesis. The sources of gluconeogenesis are:
amino acids, propionate, lactate, glycerol, etc.
Ways by which sugar is removed from the blood 1. Conversion to liver glycogen
2. Conversion to muscle glycogen
3. In the synthesis of fats (i.e. triglycerides)
4. In the synthesis of glycoproteins such as nucleic acids (nuc-leoproteins), lactose, etc.
5. Loss in the urine.
A balance of the above two processes will keep the blood sugar level within normal limits.
These two processes are influenced by a number of factors under physiological conditions.
The blood glucose level is most efficiently regulated by a mechanism in which liver, extrahepatic tissues and several hor-mones play an important part.
Role of Liver
Liver, being the centre of all metabolic activities is mainly responsible for the regulation of blood glucose level. In liver, exists the developed mechanism for uptake of glucose from the blood, conversion of glucose to glycogen for storage (glycogenesis), release of glucose from glycogen (glycogeno-lysis) and de novo synthesis of glucose from non-carbohydrate precursors (gluconeogenesis).
Glycogenesis in liver can occur from blood glucose or any substance capable of giving rise to pyruvate. Due to the pre-sence of glucose-6-phosphatase, liver glycogen can contribute directly to blood sugar (gluconeogenesis).
Role of Extra-hepatic Tissues
a. Role of muscle: Muscle glycogen does not contribute directly to the blood sugar due to the absence of the enzyme, glucose-6-phosphatase. Glycogenolysis in muscle provides glucose to blood only through the formation of lactic acid which by Cori cycle is converted to glucose in the liver.
b. Role of kidney: Kidney also exerts a regulatory effect by reabsorbing glucose by the reabsorptive system of the renal tubules. When the blood glucose level rises above the renal threshold, the excess glucose appears in the urine.
Role of Hormones
Several hormones play an important role in the homeostatic mechanism of blood glucose level. Out of these insulin is the only hypoglycemic hormone whereas others are hyperglycemic hormones.
1. Insulin: Insulin plays an important role in the regulation of blood glucose concentration. It is secreted into the blood in response to hyperglycemia. Insulin increases the transport of glucose across the cell membranes. Insulin reduces the blood sugar level by increasing the glucose utilization by glycolysis, decreases hepatic glycogenolysis and increases glycogenesis.
Hormones which keep the blood sugar level high are:
1. Epinephrine 2. Glucagon 3. Glucocorticoids 4. Thyroxine
5. Growth hormones.
Mechanism by which these hormones increase the blood sugar level are:
1. By increasing the absorption of glucose from the intestines 2. By decreasing the oxidation of glucose at the tissue level 3. By preventing the synthesis of glycogen
4. By stimulating glycogenolysis 5. By potentiating gluconeogenesis.
Blood sugar level is kept normal by insulin, by opposing the action of these hormones.
2. Glucagon: Glucagon is also called Hyperglycemicglyco-genolytic hormone. Glucagon is secreted by the α-cells of the islets of Langerhans. Glucagon secretion is stimulated by hypo-glycemia. It causes glycogenolysis by activating liver phos-phorylase. Glucagon thus counter balances the action of insulin which is secreted into the blood when the blood glucose level is high.
Glucagon acts primarily on liver and does not affect gly-cogen breakdown in muscles. Glucagon enhances gluconeo-genesis from amino acids and lactate.
3. Epinephrine: Epinephrine stimulates glycogen breakdown in liver and muscle. The stimulation of glycogenolysis is due to its ability to activate phosphorylase. Epinephrine also inhibits muscle glycogen synthesis in liver and thus directs the production of increased blood glucose.
4. Adrenal cortex hormones: Adrenal cortex secretes glucocor-ticoids, which lead to gluconeogenesis which is the result of increased protein breakdown and stimulation of transaminase. It also inhibits glucose utilization in extra-hepatic tissues.
5. Anterior pituitary hormones: Growth hormones and ACTH elevate the blood glucose level. Growth hormones decrease glucose uptake by the tissues, whereas ACTH stimulates the secretion of hormones of the adrenal cortex.
6. Thyroid hormone: Thyroxine has a diabetogenic action. It increases blood glucose concentration by increased absorption of glucose from the intestines.
Glycosuria
The excretion of detectable amounts of reducing sugar in urine is called Glycosuria. If glucose is excreted, then the condition is called glucosuria. Glucose is filtered by the glomeruli but is completely reabsorbed by the renal tubules. The reabsorp-tion is effected by phosphorylareabsorp-tion in the tubular cells. The maximum rate of reabsorption of glucose by the tubules (TmG—Tubular maximum of glucose) is 350 mg/minute. When
the blood levels of glucose are elevated, the filtrate contain more glucose that can be reabsorbed, the excess passes into the urine and gives rise to glucosuria.
Renal Glucosuria
The blood glucose level is normal, but as a defect in the reab-sorption system in the tubules, kidney threshold is lowered and glucose appears in the urine.
Renal glucosuria is an example of benign glucosuria.
Diabetes Mellitus
Diabetes mellitus is a metabolic disorder due to the deficiency of insulin, resulting in high blood glucose level and the excretion of glucose in the urine.
The most important features of diabetes mellitus are:
1. The hyperglycemia and glucosuria persist during fasting.
2. Liver glycogen falls to a low level.
3. Excretion of large quantities of ketone bodies due to increased fatty acid metabolism giving rise to diabetic coma.
Diabetes or diabetes mellitus is a condition where in the body does not produce enough insulin or does not properly respond to the insulin that is produced, there by keeping glucose level in the blood high.
Diabetes affects nervous digestive circulatory, endocrine, urinary system but all body system are in some way affected.
There is no diabetic sure but it can only be cautted.
Classification
1. Type 1 diabetes: Also called childhood onset diabetes, juv-enile diabetes and insulin dependent diabetes mellitus (IDDM).
Type 1 diabetes is a chronic (life long) disease that occurs when the pancreas does not produce enough insulin to properly control blood glucose levels. Type 1 diabetes can occur at any age but it is most after diagnosed in children, adolescents or young adults, In this form of diabetes, the body cannot make insulin the immune system mistakenly
attacks the cells in the pancreas that make and release insulin. As these cells die, blood glucose levels rise. People with type 1 diabetes need insulin shots.
2. Type 2 diabetes: In characterized by the inability of the body to make insulin or properly use insulin as a result, cells can not take up or utilize glucose resulting in high blood glucose level.
It is a slow onset process and person having diabetes for years without knowing.
Typically with type 2 diabetes, the body still make insulin, but the cells cannot use it. This is called insulin resistance.
3. Gestational diabetes: It occurs during pregnancy, labor and delivery, women who got gestational diabetes are more likely to develop type 2 diabetes.
Prediabetes
That condition when a person have impaired glucose tolerance where blood glucose levels are higher than normal but not high enough to be classified as diabetes.
Latest autoimmune diabetes of adults (LADA) is a condition in which Type 1 diabetes develops in adults. Adults with LADA are frequently initially misdiagnosed as having type 2 diabetes based on age rather than etiology.
Maturity onset diabetes of young (MODY): Condition because of defects in β cell function.
According to the latest WHO guidelines two fasting glucose blood measurement about 126 mg/dl is considered diagnostic for diabetes mellitus.
People with testing blood glucose level from 100-125 mg/dl is considered to have impaired fasting glucose.
HbA1c given an idea about average blood glucose control over the last 120 days.
Glycosylated hemoglobin (HbA1c) test is recommended for:
a. checking blood glucose control in pre-diabetes.
b. Monitoring blood glucose control in diabetes mellitus.
The normal value of HbA1c is 4-6% correlation between HbA1c blood glucose level.
HbA1c Average blood glucose level over past
Higher the value of HbA1c poorer the blood glucose control HbA1c >6.5 = Diabetes
<6.0 = Not diabetes
in between 6-6.5 = May be pre-diabetes or risk of diabetes The extent of glycosylation of hemoglobin can be conviently monitored and used to assess the control of hyperglycemia.
Analysis of hemoglobin A (the adult form of hemoglobin) reveals the extreme of minor components called hemoglobin A1. Hemoglobin A1 forms by nonenzymatic modification of hemoglobin A by glucose. Glycosylation has only minor effect on normal hemoglobin function.
Glycosylation occurs continuously within the red cell, and the extent of glycosylation reflects the average glucose concentration to which the cell is exposed during its 120 days life-span. Measurement of glycosylated hemoglobin content provides a clinically useful means to assess the degree of hyperglycemia that existed over the previous several weeks.
HbA1c in normal individuals (without diabetes mellitus) makes up about 6% of total hemoglobin. Individuals with controlled (blood glucose levels <10 mM, or 180 mg/dl) have levels of hemoglobin A1 of about 9% of total hemoglobin.
These with less well controlled diabetes have greater than 9%, hemoglobin A1.
Glycosylated hemoglobin is formed in erythrocytes by the reaction of glucose with hemoglobin. The glycosylation of hemoglobin is nonenzymatic reactions. The reaction is virtually irreversible. Its removal from the blood proceeds very slowly.
The prime importance of the glycosylated hemoglobin estimation in diabetes diagnosis lies in the fact that HbA1c Correlation between HbA1c blood glucose level
and blood glucose values of diabetics often present a different picture. Glycosylated hemoglobin fraction is not affected by the metabolic state at a given moment whereas the blood glucose level can change very rapidly. HbA1c thus makes it possible to identify hyperglycemic states which would other-wise go unrecognized.
The main characteristic of the glycosylated hemoglobin fraction HBA1 is that it constitutes a kind of long-term retro-spective indicator of blood glucose concentrations. This is due to the fact that the stable HbA1 is not catabolized throughout the erythrocyte lifespan (100-200 days).
HbA1C gives an indication of the averaged blood glucose levels during the proceeding weeks rather than the metabolic state of the patient at the time of testing.
HbA1C test estimates the portion of hemoglobin which is glycated. Increased blood glucose levels increase the glycation of hemoglobin. Glycation of hemoglobin is nonenzymatic, irreversible addition of glucose to hemoglobin. In normal individual 5-6% of the hemoglobin molecule is glycated.
However, in uncontrolled diabetic patient the level can go up to more than 20% which indicates that the patient has uncontrolled hyperglycemia.
Since, the formation of glycated Hb is essentially reversible and the blood level of HbA1c depend on both the lifespan of red blood cell (average 120 days) and the blood glucose concentration. Since the rate of formation of HbA1c is directly proportional to the concentration of glucose in the blood, the HbA1c concentration represents the integrated values for glucose for the proceeding 6-8 weeks.
HbA1c% Degree of glucose control
<6 Nondiabetic level 6-7 Near normal glycemia
<7 Good
7-8 Good control
>8 Action suggested
Glycosylated hemoglobin (HbA1c) test gives an overview of diabetic control over proceeding 2-4 months.
HbA1C circulates in the blood for 2-4 months before being naturally broken down by the body so the level of HbA1c at any stage can show how high the blood glucose has been over the proceedings few months.
HbA1c test shows the average amount of glucose in the blood over the last three months.