Basal insulin is provided by either a continuous subcutaneous infusion from an insulin pump or intermittent injection (daily or twice daily) of insulin formulated to be released slowly from this site (19). Replacement insulin therapy in the basal state (between meals and overnight) has the object of constraining hepatic glucose release to match glucose uptake by non-insulin-independent tissues (Figure 2).
The amount of insulin required lo this end varies from person to person (depending on hepatic insulin sensiiiviiy). Jt will also vary according to both the time of day and the duration of the fast. For example, at night insulin requirements fall but in the morning they rise. This is presumably a consequence of the Orcadian rhythm of growth hormone and Cortisol, hormones that increase the requirements of insulin by increasing the rate of gluconeogenesis (Cortisol and growth hormone) and glycogenolysis (growth hormone). The advantage of an insulin pump over injection of a sustained-release form of insulin for provision of basal insulin supply is that it can be programmed to vary according to these circadian changes.
Long-acting insulin preparations available for intermittent subcutaneous injection include NPH insulin, which requires twice-daily injections; Ultralente insulin, which results in rather variable day-to-day insulin-concentration profiles: and recently an insulin analog, insulin glargine, modified to provide a slow release from the site of injection (20). Some patients prefer not to wear a pump and prefer intermittent insulin injections. Also, an advantage of the intermit-
responses to meal ingestion are abnormal in people with diabetes (22). The postprandial increment in insulin secretion is blunted in type 2 diabetes and absent in type 1 diabetes. The basal glucagon levels tend to be higher in patents with diabetes, and the glucagon concentrations are not appropriately suppressed after meal ingestion.
In health, the postprandial glycemic response is constrained by extraction of —40% of the meal glucose by the liver, suppression of hepatic glucose release, and Stimulation of glucose uptake by insulin-sensitive tissues (muscle and fat). Theoretically any of these could contribute to the postprandial hyperglycemia in diabetes. Hepatic extraction of meal glucose is not impaired in diabetes (23). Glucose is taken up by the liver, provided that at least some insulin is present, and patients with poorly controlled diabetes tend to have increased rather than decreased liver glycogen stores.
The primary mechanism subserving postprandial hyperglycemia is failure to adequately suppress hepatic glucose release. Given the impaired insulin secretion after meal ingestion, and failure to suppress glucagon secretion, the failure to suppress hepatic gluconeogenesis and glycogenolysis is not surprising.
Provided that at least basal insulin levels are present, glucose uptake by insulin-sensitive tissues is greater in patients with diabetes than in nondiabetics after meal ingestion, and so impaired glucose uptake is not responsible for postprandial hyperglycemia. The increased rate of glucose uptake is due to the mass action effect of glucose to promote glucose uptake in insulin-sensitive tissues (skeletal muscle, fat) in the presence of some insulin.
Was this article helpful?