The blood concentration of glucose normally lies within the range of 80–110 mg/100 mL (4.4–6.1 mM); see Table 1. Reduction in blood glucose levels below 45–55 mg/100 mL (~2.5 mM) for a continued interval of time will lead to an impairment of brain function, tremors, and convulsions due to activation of the sympathetic nervous system, resulting ultimately in death. Conversely, a prolonged elevation of blood glucose above 130 mg/100 mL generates a state of hyperglycemia, due to a relative lack of insulin. This then leads to a devastating wasting of metabolic energy, osmotic diuresis, and metabolic acidosis. Because glucose is a “small molecule,” all blood glucose is completely filtered into urine by the glomerulus of the kidney. Under normal physiological circumstances, virtually all of this filtered glucose is reabsorbed and placed in the blood compartment. However, in circumstances of excessive hyperglycemia, this reabsorptive process is saturable and it can only accommodate a finite throughput of glucose. Thus a significant fraction of the filtered blood glucose will be lost in the urine. If there is not a balanced increase in the dietary intake of glucose, there will be, of necessity, a compensatory increased catabolism of the storage forms of glucose, namely glycogen. Over an extended interval of time this can result in a significant loss of “stored” metabolic energy.
Table1. Effects of Altered Blood Glucose Levels on Several Constituents of the Blood and Urine
In a normal (70 kg) man, the 24-hr urine volume ranges from 600 to 2500 mL, with a glucose concentration of 10–20 mg/100 mL of urine; this results in a daily loss of 600–50,000 mg (6–50 grams) of glucose in one day. However in a typical untreated diabetic (without renal complications), the 24-hr urine volume may exceed 3000–3500 mL, with a glucose concentration of 500–5000 mg/100 mL of urine; see Table1.
However, the adverse consequences of a relative lack of insulin (hyperglycemia) are not restricted to a derangement of carbohydrate metabolism. In the absence of insulin, triglycerides and fatty acids will be mobilized from adipose tissue and amino acids from muscle tissue (discussed in detail later). These sub stances then proceed to the liver, where the fatty acids and branched chain amino acids are converted into ketone bodies. The ketone bodies include β-hydroxy butyrate, acetoacetate, and acetone. Eventually, this results in progressive ketonemia, and when the renal threshold for acetoacetate and β-hydroxybutyrate is exceeded, both substances will appear in the urine.
In addition to the dominant partnership of insulin and glucagon in maintaining glucose homeostasis, there is an extensive contribution of other physiological fac tors and hormones to the regulation of blood glucose and glucose homeostasis. These are summarized in Table 2.
Table2. Factors Contributing to Glucose Homeostasis
