Our previous studies have examined various aspects of splanchnic, hepatic, and peripheral glucose metabolism in normal and diabetic subjects. The present studies will extend these initial observations as follows: The effect of insulin on peripheral (femoral vein catheter), splanchnic (hepatic vein catheter), and hepatic (3H-3-glucose) glucose metabolism will be examined susing the insulin clamp technique in healthy controls, normal weight non-insulin-dependent diabetics (NIDD), obese NIDD, and IDD with varying degrees of hyperglycemia. In all subjects beta cell secretory function will also be examined with the hyperglycemic clamp technique and the oral glucose tolerance test. Abnormalities in insulin-mediated glucose metabolism will be related to existing defects in insulin secretion in the same individual. The ability of glyburide, conventional insulin treatment, insulin pump therapy, and exercise to enhance tissue sensitivity to insulin in the preceeding groups will be evaluated. Using a) insulin binding to monocytes, b) examination of the shape of the dose response curve relating the plasma insulin concentration to glucose uptake, and c) indirect calorimetry to measure glucose oxidation (and intracellular process), an attempt will be made to define the contribution of receptor versus postreceptor defects to the impairment in insulin action. It is hoped that such analysis will provide insight as to how various therapeutic modalities are capable of enhancing tissue sensitivity to insulin. Separate studies will be performed in NIDD and IDD using a double tracer technique (3H-3-glucose and 14C-glucose) in combination with hepatic vein catheterization to quantitate splanchnic glucose uptake and suppression of hepatic glucose production following oral glucose. These studies will be performed in combination with indirect calorimetry to simultaneously quantitate glucose oxidation and glucose storage. The oral glucose load will be repeated after glyburide or insulin (NIDD) and after insulin pump (IDD) therapy. In additional studies various aspects of dietary-induced thermogenesis will be examined in control, obese, and NIDD subjects before and after weight reduction.
| Shannon, Chris; Merovci, Aurora; Xiong, Juan et al. (2018) Effect of Chronic Hyperglycemia on Glucose Metabolism in Subjects With Normal Glucose Tolerance. Diabetes 67:2507-2517 |
| Abdul-Ghani, Muhammad; DeFronzo, Ralph A (2017) Is It Time to Change the Type 2 Diabetes Treatment Paradigm? Yes! GLP-1 RAs Should Replace Metformin in the Type 2 Diabetes Algorithm. Diabetes Care 40:1121-1127 |
| DeFronzo, Ralph A (2017) Combination therapy with GLP-1 receptor agonist and SGLT2 inhibitor. Diabetes Obes Metab 19:1353-1362 |
| Abdul-Ghani, Muhammad; DeFronzo, Ralph A; Del Prato, Stefano et al. (2017) Cardiovascular Disease and Type 2 Diabetes: Has the Dawn of a New Era Arrived? Diabetes Care 40:813-820 |
| Merovci, Aurora; Abdul-Ghani, Muhammad; Mari, Andrea et al. (2016) Effect of Dapagliflozin With and Without Acipimox on Insulin Sensitivity and Insulin Secretion in T2DM Males. J Clin Endocrinol Metab 101:1249-56 |
| DeFronzo, Ralph A (2016) The EMPA-REG study: What has it told us? A diabetologist's perspective. J Diabetes Complications 30:1-2 |
| Daniele, Giuseppe; Xiong, Juan; Solis-Herrera, Carolina et al. (2016) Dapagliflozin Enhances Fat Oxidation and Ketone Production in Patients With Type 2 Diabetes. Diabetes Care 39:2036-2041 |
| Abdul-Ghani, Muhammad; Del Prato, Stefano; Chilton, Robert et al. (2016) SGLT2 Inhibitors and Cardiovascular Risk: Lessons Learned From the EMPA-REG OUTCOME Study. Diabetes Care 39:717-25 |
| DeFronzo, Ralph A; Ferrannini, Ele; Groop, Leif et al. (2015) Type 2 diabetes mellitus. Nat Rev Dis Primers 1:15019 |
| Abdul-Ghani, Muhammad A; Norton, Luke; DeFronzo, Ralph A (2015) Renal sodium-glucose cotransporter inhibition in the management of type 2 diabetes mellitus. Am J Physiol Renal Physiol 309:F889-900 |
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