Cell Metabolism, Glucose and Diabetes Mellitus

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Joined: 26 Feb 2013 09:59
Full Name: Kannivelu Badrinath
Name of Your College/Medical School: Madras Medical College, Madras, India

Cell Metabolism, Glucose and Diabetes Mellitus

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I have posted this topic mainly for the medical students and junior doctors as it is necessary to have some basic knowledge of Glucose metabolism before you start treating diseases connected with sugar.

Blood Sugar and Diabetes Mellitus

Sugar in our blood is essential for life as glucose is the primary source of energy for all living cells in the body. Glucose is absorbed and transported from the intestine to the cells. It is made available for their metabolism through the hormone insulin produced by the pancreas. What is not used by the cells is stored in organs like the liver. The body tightly regulates the blood sugar level as a part of metabolic homeostasis. When transport from the intestine is reduced or is absent as in starvation the liver and kidneys come to the rescue to maintain the level.

When glucose is absorbed from the intestine, what is not required for immediate cell metabolism is made in to a polysaccharide of glucose by the liver cells and stored as glycogen. Some glycogen is also made and stored in the muscle cells. When the blood glucose level drops liver releases the stored glycogen after converting it back to glucose. The enzymes that play a part in glycogen synthesis and degradation are glycogen synthase and glycogen phosphorylase, respectively. The action of both enzymes is regulated by the level of activity of the person as well as by circulating hormones including insulin, glucagon and epinephrine. They must be regulated in such a way that glycogen synthesis and degradation are not activated or inhibited simultaneously.

When glycogen stores are depleted and no longer available for conversion as during excessive activity or during prolonged starvation, fuel for the cells is obtained from fat or in desperate situations from protein. Fat is normally stored as triglyceride mainly in liver and between muscle fibres.

It is remarkable that despite widely variable intervals between meals or the occasional consumption of meals with a substantial carbohydrate load, human blood glucose levels tend to remain within the normal range. The delicate balance is done through catabolic hormones (such as glucagon, cortisol and catecholamines) which increase blood glucose and an anabolic hormone (insulin), which decreases blood glucose. The levels are lowest first thing in the morning before you start eating and rises 1 or 2 hours after every meal to its highest level. In a normal individual it ranges from 70 mg/dl to 120 mg/dl (4 to 6.5 mmol/L) with occasional slightly lower or higher values.

When blood sugar levels drop too low “hypoglycaemia” results. Symptoms of hypoglycaemia include lethargy, impaired mental function, irritability, weakness of muscles and seizures. It can lead to loss of consciousness and can be fatal. Hypoglycaemia is more dangerous than hyperglycaemia.

In diabetes mellitus as the cells are unable to use the circulating sugar effectively because of lack or insufficient amount of insulin, higher levels are noted (Hyperglycaemia). (Type I diabetes when the pancreas is not producing enough insulin and Type II diabetes when pancreas is producing the insulin but the cells are struggling to get the sugar in).

When diabetes mellitus is suspected in a person a fasting blood glucose level and a postprandial level (2 hours after ingesting 75gms of glucose) should be done. Impaired glucose tolerance is indicated when it is between 7.8 and 11.1 mmol/l (140 and 200 mg/dl) and Diabetes when equal or above 11.1 mmol/l (200 mg/dl). Fasting and postprandial levels of glucose indicate the level at the time when the blood sample is taken. When the sugar level is on the border line of suggesting diabetes and we need a clearer picture before we say a patient is diabetic we should check the blood for HbA1c.

HbA1c is an overall marker of what the average levels are over a period of 2 to 3 months. It is also the test done to assess whether the diabetes is properly controlled when on treatment.

What exactly is HbA1C: The term HbA1c refers to glycated haemoglobin. It develops when haemoglobin, a protein within red blood cells joins with glucose in the blood, becoming 'glycated'.The amount of glucose that combines with this protein is directly proportional to the total amount of sugar that is in your system at that time. By measuring glycated haemoglobin (HbA1c), clinicians can get an overall picture of what our average blood sugar levels have been over a period of weeks or months.
Because red blood cells in the human body survive for 8-12 weeks before renewal, measuring glycated haemoglobin (or HbA1c) reflects the average blood glucose levels over that duration, giving you a long term view of blood glucose control.

For normal people, the range is 20-41 mmol/mol (4-5.9%) For people with diabetes, an HbA1c level of 48 mmol/mol (6.5%) is considered good control. For people with diabetes this is important as the higher the HbA1c, the greater the risk of developing diabetes-related complications.

Most interventional studies have shown that achieving and maintaining near-normal glycemic levels reduces the risk for microvascular and macrovascular complications in type 2 diabetes. Long-term hyperglycemia causes many of the long-term health problems including heart disease, eye, kidney, and nerve damage.
For diabetics to maintain good control the American Diabetes Association recommends a post-meal glucose level of less than 10 mmol/L (180 mg/dL) and a fasting plasma glucose of 3.9 to 7.2 mmol/L (70–130 mg/dL).

Did you know:
When blood is collected for the lab to estimate blood sugar levels, glucose metabolism continues in the sample of blood until the blood cells are separated by centrifugation. Red blood cells, for instance, do not require insulin to consume the glucose from the blood. Higher than normal amounts of white or red blood cell counts can lead to excessive glycolysis in the sample, with substantial reduction of glucose level if the sample is not processed quickly. Ambient temperature at which the blood sample is kept prior to centrifuging and separation of plasma/serum also affects glucose levels. If the sample is kept in a refrigerator glucose remains relatively stable for a longer period of time. Loss of glucose can be prevented by using Fluoride tubes since fluoride inhibits glycolysis. This is what should be done when it takes a longer time for the blood to reach the lab for the test.

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