Diabetes monitor
Dr. Mukaila Kareem
Diabetes is a disease of civilisation and has also been aptly described as disease of inactivity. It is caused by persistent elevated blood glucose due to inability of pancreas to produce enough insulin or failure of the body to use the insulin produced effectively to control the level of blood glucose.
Insulin is a hormone produced by specialized cells in the pancreas called beta cells and this hormone helps to drive glucose into the body. This is particularly important because too much glucose in the blood stream is dangerous to health.
For this reason, the body is sensitive to blood glucose levels and the ability to keep it within normal limits involves several organs called insulin sensitive organs. These organs are the skeletal muscle, liver and fat tissue. Obviously the skeletal muscle is associated with locomotion and very few is aware that it is the largest insulin sensitive organ. As a matter of fact, literature has demonstrated that skeletal muscle is responsible for 60 per cent to 70 per cent of total glucose clearance in the blood stream.
Insulin action in fasting and fed states
Following a meal, anywhere between three to five hours, there is an increased level of plasma glucose. The pancreas responds by secreting appropriate amount of insulin which helps to drive this glucose into skeletal muscle, liver and to a smaller extent, the fat tissue.
The insulin also blocks the liver from endogenous production and facilitates the uptake of dietary fats into the fat tissue. At this same time, the plasma insulin also prevents the breaking and releasing of already stored fat in the fat tissue called triglycerides.
However, during fasting state, the skeletal muscle is metabolically flexible and thus switches to fat substrates due to low blood glucose levels. The stored triglycerides in fat tissues are broken down into free fatty acid and glycerol and are released into the blood stream in a process called lipolysis. Therefore free fatty acids are readily available in fasting state and therefore are the preferred energy substrates for most organs.
The liver is highly sensitive to blood glucose levels and because of low insulin and low blood glucose, it is able to convert stored glycogen to glucose (glycogenolysis) and in extreme situation can make glucose from the scratch (gluconeogeneis).
This so called endogenous glucose is released into the blood stream to meet the brain’s obligate need for glucose and keeps the blood glucose levels within normal limits. It should be noted that the brain relies almost exclusively on glucose at physiological fasting and fed states for its energy needs but has poor storage capability.
Insulin resistance
It is now obvious that the concentration of blood glucose and fats are regulated between the pancreas and insulin-sensitive organs. However this tight control begins to deteriorate in a pathological process called insulin resistance.
Insulin resistance is defined as metabolic derangement associated with inadequate response of insulin target tissues to the physiologic effects of circulating insulin. It is a precursor to the onset of type 2 diabetes.
While those who are at risk for diabetes inherit the gene that makes their tissues insulin resistant, it is the environmental factors of physical inactivity and chronic excess consumption that are fueling the worldwide prevalence of diabetes and Nigeria is no exception.
Medical science has revealed that obesity and physical inactivity are insulin resistant, and these conditions put the insulin producing organ in persistent stress. Therefore people who are obese and physically inactive tend to have hyperinsulinemia or too much insulin in the blood stream.
However, with poor response to high levels of insulin secreted by pancreas in insulin resistance condition, the liver goes haywire with overproduction of glucose in the fasting state and worse still; it continues to produce endogenous glucose following a carbohydrate meal.
Glucose dissolves in water and therefore cannot cross or pass the fat layer cell covering called the membrane. Insulin is therefore needed to bind to insulin receptors on the surface of cell membrane in order to “pull” a specialized transport system called glucose transporter-4 from inside the cell to the cell surface. These transporters “open” the “gate” for passage of glucose into the cell. As regards to skeletal muscle, physical inactivity reduces the expression of insulin receptors on the surface of muscle cell and less ability to “pull” the transporter to the cell surface.
Since the skeletal muscle is the largest insulin target organ, this causes excessive amount of glucose in the blood stream in what is called “glucotoxicity”. Insulin also fails to facilitate the uptake of dietary fat into the fat tissue and at the same time the stored triglycerides with fat tissue are dumped in the blood stream as free fatty acid and glycerol.
The increased dietary fats and free fatty acid in the blood stream result in deposition of fats in wrong places such as liver, skeletal muscle and pancreas which again account for insulin resistance in what is called “lipotoxicity”.
However, in spite of increased levels of glucose and fats, the pancreas would continue to respond by secreting high level of insulin to compensate for impaired insulin action. Therefore the blood glucose will remain within normal range as long as the pancreatic beta cells are able to sustain increase in insulin secretion to overcome insulin resistance. At this stage the beta cells are in overdrive even though the normal blood glucose levels do not account for the pathological process underway in insulin resistance.
Pancreas overdrive and onset of diabetes
Over time, the insulin-producing pancreatic beta cells would be incapable of compensating for insulin resistance and the tight control of plasma glucose levels would begin to falter. This leads to impaired glucose tolerance or prediabetes with possible progression to overt diabetes.
The reduced insulin sensitivity in skeletal muscle and liver along with pancreatic beta cell failure form the core metabolic defects in type 2 diabetes but the progressive pancreatic beta cell failure is the principal cause.
It is therefore fair to say that the pancreas is the ignored organ in the reversible insulin resistance and prediabetes prior to the onset of diabetes. Unfortunately, a study reported that more than 80 per cent of pancreatic beta cell function has been lost by the time diagnosis of diabetes is made!
Pharmacology management of prediabetes and diabetes
According to the American Diabetes Association’s Standards of Medical Care in Diabetes for 2016, the initial treatment of diabetes should begin with lifestyle changes which include setting physical activity goal of 150min per week at the minimum and minimum of 7 per cent weight loss.
It advised pharmacological intervention only “when lifestyle efforts alone do not achieve or maintain glycemic goals”. In Nigeria and all developing countries, the traditional pharmacological protocol for blood glucose control is to initiate treatment with metformin and then followed with sequential addition of a sulfonylurea when metformin therapy fails.
A 2013 study referred to the focus on just blood glucose control as “treat to fail” because it does not involve the reversal of impairment in pancreatic beta cells. It stands to reason that individuals with prediabetes would eventually progress to diabetes following the death of beta cells.
Metformin is a potent insulin sensitizer that blocks the increase rate of glucose production in the liver while sulfonylurea augments insulin secretion in panreactic beta cells and none of these actions is pancreas protective. In the developed countries, antidiabetes agents such pioglitazone, a thiazolidinedione (TZD) and glucagon-like-1 analog (GLP-1) are now been added to metformin. TZD and GLP-1 analog are beta cell “sympathizers” and therefore protect and preserve pancreatic beta cell function with a goal to reverse the pathological defects. However, these are very expensive in developing countries.
Lifestyle management of prediabetes and diabetes
Exercise is free and can be undertaken by almost everyone. Due to prohibitive cost of TZD, GLP-1 and other pancreas protective agents in Nigeria, regular exercise is the best antidiabetes and protect against pancreas failure.
On my day job as a clinical physiotherapist in the US, my patients, without exception always express shock to learn that skeletal muscle is an insulin sensitive organ and responsible for 60 per cent to 70 per cent blood glucose clearance. Very few are also aware that chronic excess energy consumption and physical inactivity burden the pancreatic beta cells and promote hyperinsulinimia which is associated with high blood pressure.
Reduced caloric intake helps to deplete fats in the muscles and liver and improve insulin sensitivity in these organs even without weight loss. Exercise increases the number of “gates” (glucose transporter-4) on the surface of muscle cells and inactivity reduces their expression and may lead to insulin resistance.
Several hours after a bout of exercise, a persistent increase in insulin sensitivity of glucose transport occurs in skeletal muscle. Regular activity therefore promotes whole body glucose disposal and places no burden on the pancreas. This may prevent or delay the onset of diabetes in individuals that are genetically prone to diabetes.
A 2002 study reported that lifestyle program which included moderate food consumption and regular exercise reduce progression of prediabetes to overt diabetes by 58 per cent and metformin by 31 per cent when compared with placebo over about three years of the study.
This shows that lifestyle often determines health and healthy lifestyle is health protective. If excessive food consumption and physical inactivity elicit pain on the pancreas, no one would be inactive and everyone would adhere to food moderation and probably there would be no incidence of type 2 diabetes. Eat moderately and stay active. Healthy lifestyle matters.
Dr. Kareem is a US based Physiotherapist and blogs on healthcrowonline.com
