When blood glucose levels exceed 180 mg/dl, the ability of renal sodium-dependent glucose transporters (SGLT) to reabsorb glucose is impaired, causing glucose to be excreted in the urine. This leads to the characteristic symptoms of diabetes, including increased urine output (polyuria) and excessive thirst (polydipsia) due to dehydration.

Metabolic changes in type 1 diabetes (T1D) result from a lack of insulin, which greatly affects metabolism in the liver, skeletal muscle, and white adipose tissue. The main metabolic abnormalities seen in untreated T1D are elevated blood glucose levels and increased ketone body production. Hyperglycemia occurs due to the liver producing more glucose through gluconeogenesis, while peripheral tissues, such as muscle and adipose tissue, have decreased glucose utilization due to the insulin-regulated glucose transporter GLUT-4. Ketonemia, on the other hand, is caused by increased release of fatty acids from adipose tissue, accelerated fatty acid oxidation in the liver, and the synthesis of ketone bodies (3-hydroxybutyrate and acetoacetate). Diabetic ketoacidosis (DKA), a type of metabolic acidosis, occurs in 25%-40% of newly diagnosed T1D patients and can recur during illness or non-compliance with treatment. DKA is managed by replenishing fluids and electrolytes and gradually correcting hyperglycemia with short-acting insulin to avoid hypoglycemia.

Additionally, T1D leads to elevated levels of triacylglycerols (TAG) in the blood due to the inability of the liver to fully utilize the excess fatty acids. These fatty acids are converted into TAG and packaged into very-low-density lipoproteins (VLDL) for secretion. In diabetes, lipoprotein lipase activity in adipose tissue is reduced, resulting in decreased degradation of lipoprotein TAGs and increased levels of chylomicrons and VLDL in the bloodstream, leading to hypertriacylglycerolemia.

Treatment for T1D involves managing blood glucose levels through insulin therapy, diet, and exercise.
When blood glucose is >180 mg/dl, the ability of renal sodium-dependent glucose transporters (SGLT) to reclaim glucose is impaired, and glucose “spills” into urine. The loss of glucose is accompanied by the loss of water, resulting in the characteristic polyuria (with dehydration) and polydipsia of diabetes.
B. Metabolic changes
The metabolic abnormalities of T1D result from a deficiency of insulin that profoundly affects metabolism in three tissues: liver, skeletal muscle, and white adipose (Fig. 25.3).
1.
Hyperglycemia and ketonemia: Elevated levels of blood glucose and ketone bodies are the hallmarks of untreated T1D (see Fig. 25.3). Hyperglycemia is caused by increased hepatic production of glucose via gluconeogenesis, combined with diminished peripheral utilization (muscle and adipose tissue have the insulin-regulated glucose transporter GLUT-4; see p. 97). Ketonemia results from increased mobilization of fatty acids (FA) from triacylglycerol (TAG) in adipose tissue, combined with accelerated hepatic FA β-oxidation and synthesis of 3hydroxybutyrate and acetoacetate (ketone bodies; see p. 196). [Note: Acetyl coenzyme A from β-oxidation is the substrate for ketogenesis and the allosteric activator of pyruvate carboxylase, a gluconeogenic enzyme.] Diabetic ketoacidosis (DKA), a type of metabolic acidosis caused by an imbalance between ketone body production and use, occurs in 25%–40% of those newly diagnosed with T1D and may recur if the patient becomes ill (most commonly with an infection) or does not comply with therapy. DKA is treated by replacing fluid and electrolytes and administering short-acting insulin to gradually correct hyperglycemia without precipitating hypoglycemia.
2.
Hypertriacylglycerolemia: Not all of the FA flooding the liver can be disposed of through oxidation and ketone body synthesis. These excess FA are converted to TAG, which are packaged and secreted in very-lowdensity lipoproteins ([VLDL] see p. 230). Chylomicrons rich in dietary TAG are secreted by the intestinal mucosal cells following a meal (see p. 227). Because lipoprotein TAG degradation catalyzed by lipoprotein lipase in the capillary beds of adipose tissue (see p. 228) is low in diabetes (synthesis of the enzyme is decreased when insulin levels are low), the plasma chylomicron and VLDL levels are elevated, resulting in hypertriacylglycerolemia (see Fig. 25.3).
C. Treatment