Participating Faculty: Understanding the Mechanisms to Maintain Glucose Homeostasis: A Review for Managed Care

This supplement to The American Journal of Managed Care explores mechanisms involved in physiologic blood glucose regulation and imbalances in glucose homeostasis, including the mechanisms by which the kidneys contribute to glucose regulation and the potential impact of glucose imbalance on the kidneys. Specific pharmacologic agents are also discussed, in the context of guidelines from the American Diabetes Association and the European Association for the Study of Diabetes as well as relevant clinical studies. An extensive update on the newest drugs for the management of type 2 diabetes mellitus and managed care aspects of diabetes care is also included.Faculty

Nissa Mazzola, PharmD, CGP

Assistant Clinical Professor, Clinical Pharmacy Practice

College of Pharmacy and Allied Health Professions

St. John’s University

Queens, New York

Ambulatory Care Specialist

North Shore University Hospital

Manhasset, New York

Curtis L. Triplitt, PharmD, CDE

Assistant Professor

Department of Medicine

Division of Diabetes

University of Texas Health Science Center at San Antonio

Texas Diabetes Institute

San Antonio, Texas

Disclosures

Disclosure Policy

According to the disclosure policies of the Pharmacy Times Office of Continuing Professional Education, faculty, editors, managers, and other individuals who are in a position to control content are required to disclose any relevant financial relationships with commercial companies related to this activity. If a conflict is identified, it is the responsibility of the Pharmacy Times Office of Continuing Professional Education to initiate a mechanism to resolve the conflict(s). The existence of these interests or relationships is not viewed as implying bias or decreasing the value of the presentation. All educational materials are reviewed for fair balance, scientific objectivity of studies reported, and levels of evidence.

The faculty and planning staff have disclosed the following relevant commercial financial relationships or affiliations in the past 12 months.

Faculty

Nissa Mazzola, PharmD, CGP, has disclosed no relevant commercial financial relationships related to this activity.

Curtis L. Triplitt, PharmD, CDE

Consultant/Advisory Board: Roche, Takeda Pharmaceuticals

Speaker’s Bureau: Amylin, Eli Lilly, Pfizer

The American Journal of Managed Care

Publishing Staff—Jeff D. Prescott, PharmD, RPh; Kara Guarini, MS; Ida Delmendo; and Christina Doong have disclosed no relevant commercial financial relationships related to this activity.

Pharmacy Times Office of Continuing Professional Education

Planning Staff—Judy V. Lum, MPA; Ann C. Lichti, CCMEP; and Donna W. Fausak have disclosed no relevant commercial financial relationships related to this activity.

The contents of this supplement may include information regarding the use of products that may be inconsistent with or outside the approved labeling for these products in the United States. Physicians should note that the use of these products outside current approved labeling is considered experimental and are advised to consult prescribing information for these products.

Understanding the Mechanisms to Maintain Glucose Homeostasis: A Review for Managed Care

Release date: January 12, 2012 | Expiration date: January 12, 2014

Estimated time to complete activity: 2.5 hours

Type of activity: Knowledge | Intended audience: Pharmacists | Media: Journal supplement

This activity is supported by an educational grant from Bristol-Myers Squibb and AstraZeneca LP.

Statement of Educational Need

The core pathophysiologic defects in type 2 diabetes mellitus (T2DM) include insulin resistance in the muscle and liver and β-cell failure. However, there are other contributing defects in T2DM that affect the regulation of glucose balance in the body, and these include accelerated lipolysis in adipocytes, incretin deficiency/resistance in the gastrointestinal tract, hyperglucagonemia in α-cells, increased glucose reabsorption in the kidneys, and insulin resistance in the brain. The involvement of all these organ systems is part of a system that helps to maintain glucose balance, an important part of homeostasis. The body regulates glucose levels within a tight window, maintaining levels at around 85 to 90 mg/dL. This is a very finely tuned system, and in any given individual the fasting glucose levels change by less than 1 to 2 mg/dL. However, when this system falters, the resulting hypo- or hyperglycemia leads to adverse consequences.

Hyperglycemia is not only the biochemical marker by which the diagnosis of diabetes is made, but it is also responsible for the development of microvascular complications, as seen in the DCCT and UKPDS trials. In addition, hyperglycemia has been shown to contribute to macrovascular disease, albeit to a lesser extent, as seen in the EDIC trial. But, most importantly, it is a self-perpetuating cause of diabetes that leads to glucose toxicity, which then contributes to insulin resistance in the muscle, liver, and adipocytes, as well as impairment in insulin secretion. In such states of hyperglycemia, it is known that elevated glucose levels worsen insulin resistance in the liver, upregulate key enzymes involved in gluconeogenesis, down-regulate glucose transport in muscle, inhibit the insulin signal transduction system, and impair insulin secretion.

These defects in glucose regulation were thought to be the result of defects of only a few organs. However, new evidence has shown that the progression of hyperglycemia to the development of T2DM can be attributed to an octet of defects. One of these defects involves the kidneys. The kidneys play a vital role in normal human physiology by helping to maintain fluid and electrolyte balance, acid-base balance, excretion of metabolic waste products and foreign chemicals, regulation of arterial pressure, secretion of hormones, and glucose balance (via glucose reabsorption and/or gluconeogenesis). New research into the role of the kidneys in glucose regulation has enhanced the understanding of the process involved in glucose reabsorption and release, including the role of sodium-glucose cotransporters (SGLTs) and facilitated glucose transporters (GLUTs) in glucose reabsorption.

In light of these new understandings of the kidneys’ role in maintaining glucose balance and the pathophysiologic derangements that contribute to the development of T2DM, healthcare professionals involved in diabetes care need to be educated on these findings. A better understanding of the myriad ways whereby glucose balance is maintained should provide a platform for the rational management of hyperglycemia in the patient with diabetes. A review of the physiology and mechanisms by which the kidneys help to maintain glucose homeostasis, kidney physiology in states of hyperglycemia, and the resulting injury that can occur if balance is not restored can be of benefit to all clinicians in their daily encounters with patients with glucose imbalance, such as those with diabetes.

Overall Educational Objectives

Upon completion of the educational activity, the participant should be able to:

• Explain the pathophysiology of diabetes and the different mechanisms involved in maintaining glucose balance
• Describe the role of therapies and where they fit into the treatment paradigm based on defects of glucose homeostasis
• Examine newer and emerging agents, their potential role in diabetes management, and implications for managed care

Pharmacist Credit

Accreditation Statement / Credit Designation

Pharmacy Times Office of Continuing Professional Education is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education. This activity is approved for 2.5 contact hours (0.25 CEUs) under the ACPE universal activity number 0290-0000-12-065-H01-P. The activity is available for CE credit through January 12, 2014.

Method of Participation and Request for Credit

Participants must read each article in this supplement, complete the evaluation form, and achieve a passing score of 70% or higher on the posttest. Participants can complete the posttest and activity evaluation free of charge online at www.pharmacytimes.com.

Activity Fee

The activity is free for participants submitting evaluation forms and posttests online for Pharmacy Credit (ACPE). For participants submitting evaluation forms and posttest for Pharmacy Credit via fax or mail, there is a nominal fee of $10.00.

Faculty

Nissa Mazzola, PharmD, CGP

Assistant Clinical Professor, Clinical Pharmacy Practice, College of Pharmacy and Allied Health Professions, St. John’s University - Queens, NY

Ambulatory Care Specialist, North Shore University Hospital - Manhasset, NY

Curtis L. Triplitt, PharmD, CDE

Assistant Professor, Department of Medicine, Division of Diabetes, University of Texas Health Science Center at San Antonio, Texas Diabetes Institute - San Antonio, TX

Disclosure Policy

According to the disclosure policies of the Pharmacy Times Office of Continuing Professional Education, faculty, editors, managers, and other individuals who are in a position to control content are required to disclose any relevant financial relationships with commercial companies related to this activity. If a conflict is identified, it is the responsibility of the Pharmacy Times Office of Continuing Professional Education to initiate a mechanism to resolve the conflict(s). The existence of these interests or relationships is not viewed as implying bias or decreasing the value of the presentation. All educational materials are reviewed for fair balance, scientific objectivity of studies reported, and levels of evidence.

Faculty DisclosuresNissa Mazzola, PharmD, CGP, has disclosed no relevant commercial financial relationships related to this activity.

Curtis L. Triplitt, PharmD, CDE

Consultant/Advisory Board: Roche, Takeda Pharmaceuticals

Speaker’s Bureau: Amylin, Eli Lilly, Pfizer

The faculty and planning staff have disclosed the following relevant commercial financial relationships or affiliations in the past 12 months.

The American Journal of Managed Care

Publishing Staff—Jeff D. Prescott, PharmD, RPh; Kara Guarini, MS; Ida Delmendo; and Christina Doong have disclosed no relevant commercial financial relationships related to this activity.

Pharmacy Times Office of Continuing Professional Education

Planning Staff—Judy V. Lum, MPA; Ann C. Lichti, CCMEP; and Donna W. Fausak have disclosed no relevant commercial financial relationships related to this activity.

The contents of this supplement may include information regarding the use of products that may be inconsistent with or outside the approved labeling for these products in the United States. Physicians should note that the use of these products outside current approved labeling is considered experimental and are advised to consult prescribing information for these products.

Disclosure of Unlabeled Use

The contents of this supplement may include information regarding the use of products that may be inconsistent with or outside the approved labeling for these products in the United States. Physicians should note that the use of these products outside current approved labeling is considered experimental and are advised to consult prescribing

information for these products.

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