Insulin therapy components.
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Confounding Factors, Epidemiologic↗
Biomedical subjects
Alan Moses
Publications and source records attributed to Alan Moses.
Postprandial glucose regulation and diabetic complications.
Atherosclerotic disease accounts for much of the increased mortality and morbidity associated with type 2 diabetes. Epidemiological studies support the potential of improved glycemic control to reduce cardiovascular complications. An association between glycosylated hemoglobin (HbA(1c)) level and the risk for cardiovascular complications has frequently been reported. Most epidemiological data implicate postprandial hyperglycemia in the development of cardiovascular disease, whereas the link between fasting glycemia and diabetic complications is inconclusive. Moreover, in many studies, postprandial glycemia is a better predictor of cardiovascular risk than HbA(1c) level. Postprandial glucose may have a direct toxic effect on the vascular endothelium, mediated by oxidative stress that is independent of other cardiovascular risk factors such as hyperlipidemia. Postprandial hyperglycemia also may exert its effects through its substantial contribution to total glycemic exposure. The present review examines the hypothesis that controlling postprandial glucose level is an important strategy in the prevention of cardiovascular complications associated with diabetes.
Blood Glucose↗
Beta-cell insulin secretory response to oral hypoglycemic agents is blunted in humans in vivo during moderate hypoglycemia.
Oral hypoglycemic agents bind to the ATP-sensitive potassium channel and lower glucose levels effectively in individuals with diabetes. Although the principle mechanism of action can also promote hypoglycemia, clinically profound hypoglycemia is rare. Decreased stimulation of insulin secretion by these agents at mild hypoglycemia could provide protection from more profound hypoglycemia. Sulfonylureas and meglitinides bind to both shared and unique sites on the ATP-sensitive potassium receptor/channel complex but have different pharmacokinetic profiles. To evaluate the differential ability of both sulfonylureas and meglitinides to stimulate insulin release at modest hypoglycemia, we evaluated dextrose infusion rates necessary to maintain plasma glucose after oral administration of repaglinide (1 mg) or glipizide (5 mg) at euglycemia and again at modest hypoglycemia. Healthy subjects with no family history of diabetes underwent four clamp studies, two performed while maintaining isoglycemia (glucose levels at the fasted value) and two while maintaining modest hypoglycemia of 2.78 mmol/liter (50 mg/dl) induced by low-dose insulin infusion (3.6 pmol/kg.min). There was a marked decrease in the dextrose infusion rate with administration of either repaglinide or glipizide at hypoglycemia compared with drug administration at euglycemia (P </= 0.006). This was accompanied by a reduction in C peptide secretion (P </= 0.001). Although each drug demonstrated a unique pharmacokinetic profile, drug absorption was comparable at euglycemia and hypoglycemia. The mechanism accounting for the reduced dextrose requirement during hypoglycemia likely involves a markedly decreased insulin secretory response to the agents during hypoglycemia and suggests that at modest hypoglycemia, low glucose or other metabolite(s) or altered counterregulatory hormone levels are sufficient to inhibit insulin release in response to potent insulin secretagogues. These findings may help to explain the relatively low incidence of severe hypoglycemia with clinical administration of these drugs.
Administration, Oral↗
Prandial glucose regulation in the glucose triad: emerging evidence and insights.
While it is well established that overall glycemic control reduces the complications of diabetes, the role of fasting glycemia versus postprandial glycemia in the pathophysiology of diabetes and its complications, and the relative importance of these parameters as specific targets of therapy, remain controversial. Evidence that postprandial glucose (PPG) plays an independent, modifiable role in cardiovascular disease is accumulating, largely from epidemiological studies. A large number of epidemiological studies show that high postprandial glucose is an independent risk factor for cardiovascular disease: indeed, a more powerful risk factor than fasting glucose or HbA1c. Pathophysiological hypotheses that support these observations include the contribution of postprandial glucose to HbA1c; postprandial glucose as a surrogate marker for other cardiovascular risk factors, serum lipids and triglycerides in particular; and direct toxicity of elevated glucose levels attributed to "spikes" in glucose concentration following caloric ingestion. Early interventional data suggest that therapy targeted at postprandial glucose can have a favorable impact on cardiovascular events. While more interventional studies clearly are needed, the growing weight of evidence supports a therapeutic approach more directed at excessive prandial glycemic excursions that are characteristic of both type 1 and type 2 diabetes.
Biomarkers↗