Patient-Centered Approach to Type 2 Diabetes

Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Glycemic Targets:

1. Target HbA1c < 7.0%

• In most patients to reduce the incidence of microvascular disease
• Mean plasma glucose of ~ 8.3-8.9 mmol/L
• Fasting and premeal glucose < 7.2mmol/L
• Postprandial glucose < 10 mmol/L

2. Target more stringent HbA1c (e.g., 6.0-6.5%)

• In selected patients such as short disease duration, long life expectancy, no significant cardiovascular disease (CVD) if this can be achieved without significant hypoglycemia or other adverse effects of treatment

 

3. Target less stringent HbA1c (e.g., 7.5-8.0% or even slightly higher)

• In patients with history of severe hypoglycemia, limited life expectancy, advanced complications, extensive comorbid conditions and those in whom the target is difficult to attain despite intensive self-managment education, repeated counseling, and effective doses of multiple gluocse-lowering agents, including insulin.

 

Reference:

1. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;25:1364-79

Exendin - A New Incretin?

ADA June 2012 Conference

Alpha cells and the origin of glucagon-like sequences and their receptors

David M. Irwin, Department of Laboratory Medicine and Pathobiology, University of Toronto

Summary of presentation:

Incretin Hormones – 2 known human incretin hormones

-          Glucagon-like peptide 1 (GLP-1)

-          Glucose-dependent insulinotropic peptide (GIP)

Other incretins = Exendin

-          Long acting GLP-1 analogue

o   Acts through the GLP-1 receptor

o   Have increased circulating half-life

o   Synthetic version marketed

-          From the venom of a lizard (Gila monster)

-          No known orthologs in vertebrates, not a product of the proglucagon gene

-          Anole Lizard Exendin – sequence of peptides are not similar to GLP-1 or GIP (human genome)

-          Other animals had similar exendin to lizard (chicken, turkey, duck, zebra finch, xenopus)

-          Exendin 1, 2, 3,and 4 sequences – exendin 3 and 4 are GLP-1 like in their sequence and function; exendin 1 and 2 similar to the are GIP-like in sequence and function

-          Expression of the exendin gene in the chicken and xenopus brain – who knows what it is duing there?

-          No exendin gene in human genome!

-          Exendin genes are found in birds, reptiles and frogs

-          No obvious candidate receptor for exendin; glucagon, GLP1, GLP2, and GIP act through related receptors

-          There are novel group of receptors present in fish, reptiles, birds that are NOT present in mammals – why do mammals not have this gene?

-          GLP1 receptors not found in fish

-          GCGR – duplicated in fish (glucagon receptors)

-          GLP2R – single copy in all species

-          GIPR – no intact gene found in birds

-          GRLR – not found in mammals (glucagon-receptor-like-receptors

Conclusion

o   Genomic data useful for identifying new genes

o   Continues to yield surprises

o   Hormone and receptor families are larger and more complex

-          Open questions

o   What does exendin do in other vertebrates?

o   Is GRLR the receptor for exendin?

o   Why do humans (all mammals) not have Exendin/GRLR?

o   What ligand/receptor has replace the function of Exendin/GRLR in mammals?

ADA 2012 Part 1