Components of Metabolic Syndrome
Lifestyle Issues Contribute to Obesity and MetS in Saudi Arabia
A recent study in men indicated that waist size predicted death from heart attack or stroke better than any other traditional risk factors including hypercholestermia or smoking
Every 2 inch increase in waist size increased the risk of dying of CV disease by up to 17% in the next 10 years
Role of Incretin in Glucose Homeostasis
The concept of gastrointestinal hormones (The incretin concept)
The observation that in response to hyperglycemic stimuli, oral glucose elicits a greater insulin response than intravenous glucose, is termed, which accounts for up to 60% of postprandial insulin release in healthy people
Dipeptidyl-peptidase – 4 (DPP -IV ) enzyme*
In 1993 it was demonstrated that Dipeptidyl-peptidase – 4 (DPP -IV ) enzyme mediates the inactivation of GLP-1 and GIP by removing the two N-terminal amino acids of the hormones.
The incretin hormones and Pathophysiology of Type 2 DM
Consequently, in patients with Type 2 diabetes, the incretin effect is either abolished or severely reduced (From normal 60% to < 10%) resulting in inappropriately low insulin secretion following oral ingestion of nutrients.
What are Incretin Hormones?
1906: First report of antidiabetogenic effect of extract of duodenal mucosa
1932: Concept of incretin effect first proposed (ie. assumption that intestinal peptides are involved in regulation of postprandial insulin secretion)
1964: Enhancement of insulin secretion by oral glucose demonstrated in man
1971: Amino acid sequence of GIP reported
1973: Insulinotropic effect of GIP demonstrated
1979: Existence of second incretin hormone postulated
1983: Proglucagon cloned – sequence of GLP-1 predicted
1986: Insulinotropic effect of GLP-1 demonstrated
1995: Therapeutic use of DPP-4 inhibitors first suggested
2002: Clinical proof of concept – GLP-1 reduces HbA1c levels in T2DM
2005: First GLP-1 analogue launched as antihyperglycaemic agent
2006: First DPP-4 inhibitor launched as antihyperglycaemic agent
Incretin Hormones are Gastrointestinal Peptides
Incretin-based therapy with GLP-1analogues or DPP4 inhibitors is now widely used; however, understanding of their long-term safety remains incomplete.
Incretin-based therapy in adults with type 2 diabetes
Patients should carefully be monitored for the development of pancreatitis after initiation or dose increases of these drugs.
What is now required is further long-term studies using different subgroups of patients.
The results of long-term studies are also required to determine adverse effects with chronic use (such as cancer) as well as outcomes for cardiovascular events and the incidence of microvascular complications.
Careful post-marketing surveillance for adverse effects, especially among the DPP4 inhibitors.