Glucose and preterm neonates.

Jamie Egan

Nearly everyone I remember from school used to say, " I hate physics." Personally, I loved it, especially double physics on a Monday morning. Maybe that gives you some idea of just how old I am.

My first and last physics teacher ( for seven years, I only had one teacher) always said that physics was nothing to be scared of; all it does is explain what it is. Not "why" it is, but what it is. He never allows anyone to ask: why? How, what, where and when are objective. Like it or not, "why" is it not. To explain hypoglycaemia (low blood glucose), I'll stick with that convention.

What are the causes of hypoglycaemia in adults? There are many causes, including medication side effects, alcohol consumption, critical illness, cortisol insufficiency, insulinomas, bariatric or gastric surgery, pancreas transplantation, glucagon deficiency, and surreptitious causes (we don't know how probably genetic). It can result from taking too much insulin for current needs, missing meals, exercising excessively, delayed or missed snacks, or inadequate carbohydrate intake. Rarely, non-diabetic individuals may experience hypoglycemia after a large meal. But we can explain most of it by saying that the substrate (glucose) is insufficient to absorb the effects of the enzymes and hormones acting upon it.

However, the theme is that certain diseases or poisons cause hypoglycaemia in adults.

To understand the method, we start with glucose. Adults can eat or make glucose. This glucose is then metabolised into energy by combining with oxygen, a process we call glycolysis.

As long as we have enough substrate or precursor, we can make glucose forever. Glucose is the smallest carbohydrate in a large family of carbohydrates. Larger carbohydrates, like fatty acids, are essentially carbohydrates ( don't tell a dietician that). Glucose and fat are made from carbon, hydrogen, and oxygen. If we add nitrogen to a carbohydrate, we get a protein. Therefore, any fat, protein, or larger carbohydrate can become glucose. We call this process gluconeogenesis.

Gluconeogenesis operates in the opposite direction of glycolysis, which breaks down glucose into smaller molecules. To allow this system to run smoothly, the liver stores about 1500 calories worth of carbohydrates in an intermediate compound called glycogen. Instant glucose with little fuss.

Hormones like glucagon, insulin, and cortisol tightly regulate gluconeogenesis to maintain blood glucose homeostasis. Hormonal signals modulate enzyme activity and substrate availability in response to metabolic demands. It is hellishly complicated, but all you need to know is that carbon, hydrogen, and oxygen are constantly in flux between many distinct chemicals in the body depending on what we eat and how all these hormones work together.

In short, gluconeogenesis is a fundamental metabolic process that generates glucose from non-carbohydrate sources to sustain energy production and support vital bodily functions during periods of low dietary carbohydrate intake or increased energy demands.

Term babies have a lot more. They also have some fat storage and the hormones to break down this fat into glucose. Term babies can live without calories for days until the mother's milk arrives. In preterm neonates, none of these hormones work very well, which is a bit of a problem. At birth, a preterm neonate has about two hours' worth of glycogen, which it got from its mother, and little or no fat.

Therefore, probably the main reason that preterm babies get hypoglycaemic a lot is because?

The adults who care for them don't give them enough glucose. If you put the right amount in the cells, you can use it up, and it won't go too high or too low. So, the treatment of hypoglycaemia in preterm neonates is pretty straightforward: Give them more glucose. If the glucose doesn't stay up, give them some more. If it still doesn't stay up, call Houston.

Hyperglycemia and persistent hypoglycemia in neonates can be caused by various factors, including conditions like sepsis, stress, pain, medications (such as inotropes ( adrenalin/ephedrine and adrenal steroids)), and very, very rarely neonatal diabetes. In other words, neonatal diabetes has entirely different causes than those of adults. Therefore, if the blood glucose falls in a neonate, you aren't giving it enough, and if it rises, you are giving too much, or the baby is under undue stress or sepsis.

Additionally, hyperglycemia (high blood sugar) is common in newborns in ICUs, particularly in preterm babies. But the causes are now of sepsis and perinatal hypoxia. The prevalence of hyperglycemia is higher in preterm infants compared to term infants and is associated with factors like relatively high glucose intake, impaired insulin production by pancreatic beta cells, insulin resistance, immaturity of the glucose transport system, and a small mass of insulin-responsive tissues. Despite the high prevalence of hyperglycemia in preterm infants, significant glycosuria (excretion of glucose in the urine) is relatively uncommon until blood glucose levels exceed a certain threshold. Hyperglycemia can lead to complications such as osmotic diuresis, dehydration, weight loss, electrolyte imbalances, and increased serum osmolarity if not managed promptly. It has been associated with neonatal mortality and morbidities. And so, neonatal glucose metabolism is like the adult kind, but without functioning hormones.

The point is that babies are not small children, and preterm babies are not small babies. The intricate background physiology that maintains glucose in a narrow range in adults does not work in neonates. That also means that the chemical tests we use to measure glucose, insulin, and other hormones in adults do not apply to neonates. An honest appraisal of either of these conditions in a neonate should never include measuring and interpreting adult hormones and applying the results to neonates; in fact, doing so is malicious and unforgivable.

So, if you leave babies without central lines, allow them to become hypoxic and develop sepsis, what are you going to see?

Persistent hypoglycemia and hypoglycaemia.

Does this remind you of anywhere?