The Kidneys in Type 2 Diabetes

Faculty

Lawrence Blonde, MD, FACP, FACE
Director, Ochsner Diabetes Clinical Research Unit
Department of Endocrinology, Diabetes and Metabolism
Associate Internal Medicine Residency Program Director
Ochsner Medical Center
New Orleans, Louisiana

Daniel Einhorn, MD, FACE, FACP
Clinical Professor of Medicine
University of California, San Diego
Diabetes and Endocrine Associates
Medical Director, Scripps Whittier Diabetes Institute
La Jolla, California

Richard E. Pratley, MD
Medical Director
Samuel E. Crockett, MD, Chair in Diabetes Research
Florida Hospital Diabetes Institute
Senior Scientist, Florida Hospital Sanford-Burnham Translational Research Institute for Metabolism and Diabetes
Professor, Sanford-Burnham Medical Research Institute
Orlando, Florida

Intended Audience

This activity is intended for a multidisciplinary audience of clinicians and diabetes experts who are dedicated to the care of patients with type 2 diabetes.

Learning Objectives

Upon completing this activity participants should be better able to:

• Discuss the role of the kidney in glucose homeostasis
• Individualize treatment goals for patients with T2DM that reflect the degree of hyperglycemia, comorbid conditions, disease duration, and responses to therapy 
• Evaluate the mechanisms of action and clinical profiles of sodium-glucose cotransporter 2 (SGLT-2) inhibitors for the treatment of T2DM
• Construct patient-centered therapeutic regimens for T2DM to maximize efficacy and minimize hypoglycemia, weight gain, and other potential treatment-related risks
• Educate patients with T2DM about lifestyle modifications, benefits and risks of antihyperglycemic therapy, and the importance of treatment adherence 

Needs Assessment and Learner’s Gap

The kidneys are central to glucose homeostasis.^1,2 These organs filter approximately 140-160 g of glucose from the plasma each day, virtually all of which is reabsorbed and transferred back to the bloodstream via 2 classes of glucose transporter proteins: sodium-glucose cotransporters (SGLTs) and facilitated glucose transporters.^3-5 Severe hyperglycemia in individuals with diabetes can overwhelm the renal reabsorption system, causing glucose to spill over into the urine. Counterproductively, however, patients with diabetes also exhibit an increase in the maximum glucose level that can be reabsorbed from the glomerular filtrate—an effect that is mediated, in part, by increased SGLT2 expression and activity.⁶ This high-capacity, low-affinity glucose cotransporter is specifically expressed in the kidney’s early proximal tubule, where it is responsible for recapturing 80% to 90% of glucose that is filtered out of circulating blood.^7,8 Thus, a system that evolved to conserve energy between meals becomes maladaptive in diabetes, facilitating and even exacerbating the ongoing hyperglycemic state. An epidemic of type 2 diabetes—including many individuals who are not at their glycemic targets—has generated considerable interest in developing medications that inhibit renal glucose reabsorption. Much of the focus has been on SGLT2 because of its localized expression pattern and primary role in recapturing glucose from the glomerular filtrate.² This program will examine renal processes that contribute to glucose homeostasis and the development of type 2 diabetes, as well as the clinical profiles of SGLT2 inhibitors and practical recommendations on their potential roles in patient-centered multimodal care plans.⁹

References

1. Gerich JE, Meyer C, Woerle HJ, Stumvoll M. Renal gluconeogenesis: its importance in human glucose homeostasis. Diabetes Care. 2001;24(2):382-391.
2. DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab. 2012;14(1):5-14.
3. Marsenic O. Glucose control by the kidney: an emerging target in diabetes. Am J Kidney Dis. 2009;53(5):875-883.
4. Wright EM, Hirayama BA, Loo DF. Active sugar transport in health and disease. J Intern Med. 2007;261(1):32-43.
5. Abdul-Ghani MA, DeFronzo RA. Inhibition of renal glucose reabsorption: a novel strategy for achieving glucose control in type 2 diabetes mellitus. Endocr Pract. 2008;14(6):782-790.
6. Rahmoune H, Thompson PW, Ward JM, et al. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes. 2005;54(12):3427-3434.
7. Vallon V, Platt KA, Cunard R, et al. SGLT2 mediates glucose reabsorption in the early proximal tubule. J Am Soc Nephrol. 2011;22(1):104-112.
8. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev. 2011;91(2):733-794.
9. American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014;37 (suppl 1):S14-S80.

Accreditation Statement

This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Educational Review Systems, Inc., and Integritas Communications. 

Credit Designation

This program has been reviewed and is acceptable for up to 1.0 Prescribed credit hour by The American Academy of Family Physicians.  AAFP Prescribed credit is accepted by the American Medical Association (AMA) as equivalent to AMA PRA Category 1 Credit™ for AMA Physician’s Recognition Award.  When applying for the AMA PRA, Prescribed hours earned must be reported as Prescribed hours, not as Category 1. (This statement applies to all Physicians, not just Family Physicians.)

Conflict of Interest Statement

The Conflict of Interest Disclosure Policy of Educational Review Systems, Inc., requires that faculty participating in any CME activity disclose to the audience any relationship(s) with a pharmaceutical, product, or device company.  Any presenter whose disclosed relationships prove to create a conflict of interest with regard to his/her contribution to the activity will not be permitted to present. 

Educational Review Systems, Inc. also requires that faculty participating in any CME activity and anyone in a position to influence content disclose to the audience when discussing any unlabeled or investigational uses of any commercial product, or device, not yet approved for use in the United States. 

Faculty and Planning Committee Disclosures

Lawrence Blonde, MD, receives grant research support from Eli Lilly and Company, Novo Nordisk A/S and sanofi-aventis U.S. LLC.  He receives honoraria for his role as a speaker from Amylin Pharmaceuticals, LLC., AstraZeneca, Bristol-Myers Squibb Company, Janssen Pharmaceuticals, Inc., Novo Nordisk A/S, and sanofi-aventis U.S. LLC.  He receives honoraria for his role as a consultant to AstraZeneca, Bristol-Myers Squibb Company, Eisai Inc., GlaxoSmithKline, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk A/S, Quest Diagnostics, and sanofi-aventis U.S. LLC.

Daniel Einhorn, MD, receives honoraria for his role as a speaker for Eli Lilly and Company, Halozyme, Inc., Janssen Pharmaceuticals, Inc., MannKind Corporation, Novo Nordisk A/S, and sanofi-aventis U.S. LLC.

Richard Pratley, MD, receives the following research grants, honoraria, speakers bureau, and consulting fees paid directly to Florida Hospital.  Research grants from Eli Lilly and Company; Gilead Sciences Inc.; GlaxoSmithKline; Mannkind Corporation; Merck & Co., Inc.; Novo Nordisk A/S; Pfizer Inc.; and Takeda Pharmaceuticals U.S.A., Inc. He is a speaker for Boehringer Ingelheim GmbH; Merck & Co., Inc.; Novo Nordisk A/S; and Takeda Pharmaceuticals U.S.A., Inc. He receives honoraria from AstraZeneca; Bristol-Myers Squibb Company; Boehringer Ingelheim GmbH; Eisai Inc.; GlaxoSmithKline; Janssen Pharmaceuticals, Inc.; Lexicon Pharmaceuticals, Inc.; Mannkind Corporation; Merck & Co., Inc.; Novo Nordisk A/S; Profil Institute for Clinical Research, Inc.; sanofi-aventis U.S. LLC.; and Takeda Pharmaceuticals U.S.A., Inc. He is a consultant to Amylin Pharmaceuticals, LLC.; AstraZeneca; Bristol-Myers Squibb and Company; Boehringer Ingelheim GmbH; Eisai Inc.; Eli Lilly and Company; Gilead Sciences, Inc.; GlaxoSmithKline; ICON Clinical Research, Inc.; Janssen Pharmaceuticals, Inc.; Lexicon Pharmaceuticals, Inc.; Ligand Pharmaceuticals Inc.; Mannkind Corporation; Merck & Co., Inc.; Novo Nordisk A/S; Ono Pharmaceutical Co., Ltd.; Profil Institute for Clinical Research, Inc.; sanofi-aventis U.S., LLC.; and Takeda Pharmaceuticals U.S.A., Inc.

Method of Participation

Participants must complete the preactivity questionnaire, posttest, and program evaluation. Participants must also score at least 70% on the posttest.