Meanwhile, in the kidneys, a related dysfunction is brewing. Normally, the kidneys serve as filters, removing waste products and returning cleansed fluid back to the body. The return of the cleansed fluid — or reabsorption of fluid — takes place in the renal tubules, the internal structure of the million or so filtering nephrons in each kidney. However, when the glucose concentration of the fluid entering the nephrons exceeds 250 mg/dl, the reabsorption capacity of the renal tubules is blocked, triggering what is known as osmotic diuresis —a discharge of large amounts of urine. Until the glucose levels are normalized, the renal tubules can’t regain the ability to absorb fluids.
So a dual chain reaction has begun. The cells are pumping water into the bloodstream, and the kidneys, unable to reabsorb this fluid during filtering, are uncontrollably flushing water from the body. The result is runaway urination.
To meet the clinical definition of polyuria, urine output for an adult must exceed 2.5 liters per day (normal urine output is 1.5 liters per day); however, extremely high blood glucose can lead to outputs of 15 liters (about 4 gallons) per day, a fluid loss similar to that seen in cholera victims. In rare cases, polyuria can top out at 20–25 liters per day, about half the body’s total fluid volume.
The dehydrating effect of polyuria is a key player in many of the other signs and symptoms of high blood glucose, including polydipsia.
Excessive thirst. Polydipsia is a response to the dehydrating effects of polyuria; it’s the body’s attempt to rehydrate itself. Thirst signals in the brain are triggered by osmoreceptors, specialized cells in the hypothalamus that detect the level of plasma osmolality — the level of dehydration of the blood — and create the urge to drink fluids when a person is dehydrated.
The relationship between excessive urination and excessive thirst is often misinterpreted by people experiencing high blood glucose, especially before diabetes is diagnosed. Many people assume that excessive urination is caused by the excessive thirst, and not the other way around. So they are quick to discount the excessive urination, thinking “Well, I’ve been drinking a lot lately…”
Complicating matters, many people reach for a soda when they’re thirsty, and most sodas contain both some form of sugar and caffeine. The sugar raises the blood glucose level even higher, and the caffeine, a diuretic, makes the polyuria worse. Together they increase thirst rather than resolving it.
Excessive hunger. Excessive hunger isn’t really caused so much by a high blood glucose level as by a low insulin level. The low insulin level can be either an absolute shortage of insulin, as in Type 1 diabetes, or it can be a relative shortage of insulin, as in Type 2 diabetes. In either case, the amount of insulin in the blood is insufficient to move glucose molecules from the bloodstream into the cells, where they can be used as fuel for cellular processes.
If cells aren’t able to gain access to glucose, they send out hunger signals via a variety of signaling hormones, including leptin, ghrelin, orexin, and PYY 3-36. All of these hormones signal the brain’s hypothalamus to trigger the sensation of hunger. The cells have no way of knowing that they’re starving in the land of plenty: The glucose they need exists in abundance nearby in the bloodstream, but the relative deficiency of insulin makes it inaccessible. This ultimately leads to hunger pangs that, perversely, make high blood glucose worse when a person responds by eating.
Even though you may be eating like crazy when your blood glucose is chronically high, you will still lose weight, and there are three reasons for this: