Muscle makes its ATP in three ways, and each way trades how much it holds against how fast it delivers. The phosphocreatine system is the fastest and holds very little. The aerobic system holds the most and releases energy slowly. The lactic system sits between them. Exercise asks for energy at a rate set by how hard the work is, and for a time set by how long it lasts. So intensity and duration together decide which system runs, which fuel is burned first and which store is drawn down. That is why the exercise prescription has to be set for each patient.
What does lifestyle treatment change?
Diet and physical activity are the two main lifestyle measures prescribed in metabolic disorders such as obesity and type 2 diabetes. Both are part of treatment. Physical inactivity and excess body fat raise the risk of type 2 diabetes by increasing insulin resistance, as the risk factors note explains.
Can losing weight bring glucose back to normal?
In recent-onset type 2 diabetes, substantial weight loss through an energy-restricted diet can restore normal glucose control in a proportion of patients. This state of restored normal glucose control is called remission.
Why should weight loss do this? Expanding adipose tissue promotes insulin resistance, as the risk factors note explains. Extra fat in the liver is thought to make the liver respond less to insulin, so it keeps releasing glucose. When that fat is lost, the liver is thought to respond again. The first-phase insulin response has also been seen to return as pancreas fat fell, and a proposed explanation is that the β cells recover. Recent onset matters here because the β cells make up for a falling insulin response for years, and overt diabetes appears when that compensation stops keeping pace, as the pathophysiology note explains.
Diet changes how much fat is stored. Exercise works differently: it changes which fuel a working muscle draws on, and that depends on two decisions.
What has to be decided about exercise?
For exercise, two aspects of the prescription have to be decided: how long the patient exercises, and how hard. Both change which fuel the muscle uses. The mix of fuels depends on how fast energy is needed and how long the work lasts, so changing either one changes the fuel. Both therefore change what the exercise achieves.
Each fuel is tied to an energy system, and each system has its own store and its own speed.
Why does muscle have three energy systems?
Muscle can draw on three energy systems. Muscle stores of ATP are small, so energy has to come from pathways that run as the work goes on. The three systems differ in how much energy they hold and in how quickly they can release it. In general the anaerobic pathways give energy faster but hold less in total than the aerobic pathways.
The fastest is the anaerobic alactic system, which runs on phosphocreatine. Its store is very low, and its speed of supply is very fast. Phosphocreatine is a small, rapidly available store, and it can be depleted almost completely during exhaustive exercise. Its rate of supply is higher than glycolysis can match. The system is anaerobic, so it regenerates ATP without oxygen.
The fastest system is also the one that lasts least, so something else has to take over.
What do the aerobic and lactic systems add?
The anaerobic lactic system holds a medium amount of energy and supplies it at a medium speed. It works through glycolysis, which runs without oxygen. That makes it quicker than the aerobic route but means it holds less, and it ends in lactate.
The aerobic system has the highest stored energy and the slowest supply, but its supply is prolonged. Aerobic energy needs oxygen delivered by the breathing and circulatory systems, so it starts and runs slowly. Aerobic metabolism can draw on fat and on glycogen, and it yields far more energy per unit of fuel, which is why it lasts longest. Because fatty acid oxidation has a limited rate per unit time, the aerobic route releases its energy slowly.
Together these speeds and stores set the order in which fuels are used.
Which fuel does muscle use first?
Because the fast stores are small and run down first, the muscle moves to slower fuels as exercise continues. In the early stages of exercise, the main energy source is muscle glycogen.
Muscle glycogen is finite, so as exercise goes on the muscle must draw on circulating glucose instead. This glucose comes first from hepatic glycogenolysis. The liver is the main source of the body’s own glucose, as the normal glucose homeostasis note explains. Glucagon drives liver glucose output, as the eight-mechanisms note explains. Liver glycogen is also limited, so when it runs low the liver turns to hepatic gluconeogenesis.
Finally the muscle draws on non-esterified fatty acids (NEFAs), which are released from adipose tissue. Insulin holds back the breakdown of fat, so fatty acids reach the blood when insulin is low, as the normal glucose homeostasis note explains. Fat is the slow route, and it takes over as the work goes on and the faster stores run down.
This order follows the length of the work. The next question is what intensity does to the mix.
Why does a hard session use glycogen and an easy one fat?
Studies show that different energy sources are used at different intensities and durations. Low intensity and low duration draw more on fatty acids and triglyceride. At low intensity the muscle needs energy slowly, and fatty acid oxidation has a limited rate, so it can meet the need. High intensity and high duration call more and more on glycogen. At high intensity the muscle needs energy faster than fatty acid oxidation can supply it, so glycogen does more of the work.
Because the mix depends on intensity, the shifts in fuel use are the basis for individualising the prescription.
How does the prescription change from one patient to the next?
The exercise prescribed to different patients should differ, and the fuel rule shows why.
A patient with a high body fat percentage is asked to exercise at low intensity, so that more lipid is used. Low-intensity exercise draws more on fatty acids. As noted above, excess body fat raises insulin resistance, which is a further reason to act on it.
A patient with poor control of blood glucose should not be given high intensity and long duration exercise. Blood glucose rises during such exercise. Intense exercise is thought to make the body release more catecholamines, and these are likely to act on the liver to raise its glucose output. Glucagon adds to that by driving the liver’s glucose release. A hard, long session therefore raises blood glucose, and a patient whose glucose is already poorly controlled starts from a higher level. Insulin-driven uptake of glucose into muscle is also blunted in type 2 diabetes, as the pathophysiology note explains.
These choices fix the intensity. How much exercise to do, and how to spread it, are set separately.
How much exercise, and how is it spread over the week?
For most adults with type 2 diabetes, the general target is at least 150 minutes per week of moderate-to-vigorous aerobic activity. This is spread over at least 3 days per week, with no more than 2 consecutive days without activity.
Why spread it? A session’s effect on how muscle responds to insulin lasts for a time after the session ends. Spreading sessions across the week is therefore thought to keep that effect present on more days, and long gaps are thought to leave it absent on the days in between. This is an inference from how long the effect lasts.
A single session’s effect on muscle is limited in time, so the week matters.
What does resistance exercise add?
The general target adds resistance exercise on 2–3 non-consecutive days per week. Resistance exercise builds muscle, and a larger muscle gives more room for glucose to be taken up.
Combined aerobic and resistance training lowers HbA1c more than either alone. A proposed explanation is that the two work by different routes. Aerobic exercise raises glucose uptake into muscle even where insulin’s own action is impaired, and resistance training adds muscle that can take glucose up. Because the routes differ, combining them is proposed to lower HbA1c more than either alone.
Weight loss brings glucose back to normal in some recent-onset patients and not in others, so what decides which patients those are?