Andrew Schneider, Dhwajbahadur Rawat, PhD, Steve Weinstein, MD, Sachin Gupte, MD PhD, William Richards, MD. University of South Alabama College of Medicine
INTRODUCTION: Glucose-6-phosphate dehydrogenase (G6PD) is an important enzyme in lipid and glucose metabolism. Participating in the rate limiting step of the pentose phosphate pathway, G6PD provides the majority of NADPH to cells for lipid biosynthesis. Over the past years, our lab (SG) found G6PD to be more active in obese diabetic animal models versus lean controls. G6PD has also been found to be up-regulated in diabetic models in both adipose tissue as well as liver. This has led us to believe that G6PD over-expression plays an important role in the development of type 2 diabetes. We hypothesized that G6PD activity levels (blood, liver, adipocyte, omentum) in morbidly obese type 2 diabetic patients would be higher than morbidly obese non-diabetic patients and that G6PD levels would fall following Laparoscopic Roux-en-Y Gastric Bypass (LRYGB).
METHODS: Patients scheduled for gastric bypass were recruited for the IRB approved study and placed in either the diabetic (n=16) or non-diabetic group (n=16) based on their 1. history, 2. medication use and 3. hemoglobin A1C percentage (Diabetic. HgBA1c > 6.5 %, Non Diabetic. HgBA1c < 6.0 %). Blood samples were collected at baseline and three months post operatively. Liver, adipose, and omental samples were taken during surgery. All results are expressed as mean + SEM and were compared statistically using the Mann-Whitney U test. P < 0.05 (*) were considered significant.
RESULTS: We found a higher (P<0.05) Triglyceride, HOMA-IR, and RBC G6PD activity, in diabetics compared to nondiabetics before surgery. There was no significant difference in BMI, or G6PD tissue levels (omentum, liver, subcutaneous fat). At three months post-operatively, the diabetic group (n=4) showed a significant decrease in RBC G6PD activity to 1.4 ± 0.6 nmol/min/mg protein, while BMI decreased 17.8%±3.0.
|BMI||Triglycerides||HOMA-IR||RBC G6PD nmol/min/mg Protein|
|Non Diabetic (18)||44.9±2.1||218±38 *||8.6±2.7 *||1.6±0.7 *|
|Diabetic (16)||45.5±2.6||301±64 *||32.5±12.7 *||6.4±3.4 *|
CONCLUSION: These preliminary results suggest morbidly obese diabetic patients have elevated levels of G6PD activity compared to non-diabetic patients and that G6PD levels decrease following LRNYGB. This opens the door to further research on G6PD over-expression as a causal mechanism of type 2 diabetes and into the mechanism of action for remission of type 2 diabetes after LRYGB.
Program Number: S063