PHYSICAL EXAMINATION

LABORATORY STUDIES

DIAGNOSIS

Diabetes mellitus type 1

PATHOPHYSIOLOGY OF KEY SYMPTOMS

The patient’s major symptoms are tied to a disruption in metabolism. The loss of weight combined with an increase in appetite reflects an increase in metabolic consumption or decrease in metabolic substrate availability. The feelings of tiredness and inactivity indicate that metabolic substrate availability is the more likely explanation. The presence of glucose and ketones in a dilute, acidic urine, the elevated plasma glucose, and the low levels of C-peptide are consistent with type 1 diabetes mellitus.

Insulin is derived from a larger pre-prohormone produced by the beta cells of the pancreas. An increase in plasma glucose is the most powerful stimulus for insulin release. In addition, ingestion of a carbohydrate meal stimulates insulin release through parasympathetic nerve activity and through the increase in gastrointestinal hormones cholecystokinin (CCK) and gastrointestinal inhibitory peptide (GIP).

Insulin decreases blood glucose by stimulating glucose uptake, utilization, and storage. Insulin enhances glucose uptake by skeletal muscle and adipose tissue by increasing the number of functional GLUT-4 transport proteins on the cell membrane (Fig. 61-1). Combined elevations in insulin and growth hormone stimulate amino acid uptake and protein synthesis in a variety of tissues. The hepatic and brain glucose transport proteins (GLUT-2 and GLUT-3, respectively) are not directly impacted by insulin. Insulin, however, increases hepatic glucose uptake and glycogen formation by increasing the activity of hexokinase and the cellular metabolic conversion of glucose. The combined actions of insulin result in a marked decrease in plasma glucose concentration.

FIGURE 61–1 Insulin entry by the GLUT4 transporter requires the action of insulin. In skeletal muscle and adipose tissue, glucose enters or requires insulin binding to a cell membrane receptor (A) and translocation of the vesicular GLUT4 transporters into the cell membrane (B). In contrast, glucose entry into hepatocytes (C, D) or neurons uses different GLUT transporters, which do not require insulin for activity.