Date of Graduation

8-15-2009

Degree Type

Capstone Project

Degree Name

Master of Science in Physician Assistant Studies

First Advisor

James Ferguson, PA-C

Second Advisor

Rob Rosenow PharmD, OD

Third Advisor

Annjanette Sommers MS, PA-C

Abstract

Background: Type 2 Diabetes Mellitus (T2DM) is a chronic, progressive incurable disease affecting over 23.6 million people in the US. This disease involves the deterioration of β-cell function, which causes hyperglycemia. Early diagnosis and treatment of diabetes is essential and helps prevent long-term medical complications such as neuropathy, nephropathy and retinopathy. Treatment begins with diet, exercise and weight loss and then progresses to oral hypoglycemic agents (OHAs), combination OHAs, and finally to insulin therapy. Initial treatment with insulin may improve β-cell function, reduce glucotoxicity and increase insulin secretion when compared to the usual course of OHA treatment.

Hypothesis: What effect does insulin treatment have on β-cell function in newly diagnosed T2DM patients?

Methods: Exhaustive search of available medical literature from 1998 to present, for studies regarding newly diagnosed T2DM patients, treated with insulin as compared to metformin and/or a sulfonylurea, which included the evaluation of β-cell function. The four studies reviewed evaluated β-cell function by measuring fasting c-peptide, insulin and proinsulin levels, post-prandial c-peptide levels, HOMA B, HOMA IR or proinsulin-to-insulin ratios.

Results: Newly diagnosed T2DM patients treated with insulin had increased c-peptide, insulin, HOMA B and post-prandial c-peptide levels, and decreased proinsulin, HOMA IR and proinsulin-to-insulin ratios, all of which indicate improved β-cell function. This improvement was measured over durations of 6, 12, and 24 months, and after that point a decline was seen. Treatment with OHAs showed a similar pattern, however, insulin treatment showed greater improvement which lasted for longer periods of time.

Conclusion: Optimal improvement in β-cell function of T2DM patients is seen with early, intensive, short-term treatment with insulin vs. metformin or a sulfonylurea. Increase in β-cell function helps to improve metabolic control, increase insulin secretion, increase acute insulin response to glucose and decrease PI/IRI ratios. Due to the progressive nature of T2DM, this improvement in β-cell function deteriorates gradually with time.

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