I am concerned that recent posts on how to (or how not to) treat type 2 diabetes (insulin, pioglitazone, DPP IV inhibitors, etc.) have focused on the prevention of macrovascular disease-that is poorly associated with glycemic control rather than microvascular disease-that has been overwhelmingly shown to be directly related to long-term A1C concentrations.  In the UKPDS 35th paper publishing in the BMJ in 2000 the investigators concluded:

“In patients with type 2 diabetes the risk of diabetic complications was strongly associated with previous hyperglycaemia. Any reduction in HbA1c is likely to reduce the risk of complications, with the lowest risk being in those with HbA1c values in the normal range (<6.0%).”   The benefit was a 25% reduction in microvascular events in the experimental group with a mean A1C of 7.0% versus the control group with a mean A1C of 7.9%.  The benefit on macrovascular events specifically myocardial infarctions was marginal, although it became significant in the 10-year follow up.

http://www.bmj.com/content/321/7258/405

Up to date comments on this as well

http://www.uptodate.com/contents/glycemic-control-and-vascular-complications-in-type-2-diabetes-mellitus

Microvascular complications are present to a considerable degree at diagnosis

“CONCLUSIONS—Targeted screening for type 2 diabetes (with a screening questionnaire as a first step) resulted in the identification of previously undiagnosed diabetic patients with a considerable prevalence of microvascular complications.”  At diagnosis 25% of persons with type 2 diabetes had microvascular complications. .  Thus, the push for early diagnosis and prevention has a sound scientific basis.

http://care.diabetesjournals.org/content/26/9/2604.full

In his review of microvascular complications in 2005 Margolis concluded:

“In patients with type 1 and type 2 diabetes, intense therapy to lower blood glucose concentrations reduces the incidence and the rate of progression of microvascular complications.”  He goes on to emphasize the important role of other risk factors especially hypertension.

http://www.jhasim.com/files/articlefiles/pdf/XASIM_Issue_5_4A_p260_263.pdf

Finally the CDC fact sheet states:

Glucose control

“Studies in the United States and abroad have found that improved glycemic control benefits people with either type 1 or type 2 diabetes. In general, every percentage point drop in A1c blood test results (e.g., from 8.0% to 7.0%) can reduce the risk of microvascular complications (eye, kidney, and nerve diseases) by 40%. The absolute difference in risk may vary for certain subgroups of people.”

http://www.cdc.gov/diabetes/pubs/estimates11.htm

It is certainly beneficial to the doc2doc community to discuss and to express skepticism about the benefit versus the shortcomings of any study of specific pharmacologic agents and the bias that can result from economic interests of the studies’ sponsors. Such discussions will lead to further understanding and improve our use of these agents.

Nevertheless, we should also keep in mind that the evidence for preventing vascular complications by lowering A1C is mainly, if not solely, on microvascular complications, not macrovascular ones.  These complications are responsible for most of the disability and costs associated with type 2 diabetes, which in the United States are the leading cause of renal failure, blindness and amputations.