September 18, 2018 : DCMS #415

DISASTERS AVERTED — Near Miss Case Studies

It Doesn’t Have to Happen

EXCLUSIVE INTERVIEW — Candid Video Interviews with Top Practitioners

Scott Isaacs on Meal Replacements

HOMERUN SLIDES — Great Clinical Presentation Highlights

Practical Use of CGM To Improve Clinical Outcomes Part 1

CLINICAL GEMS — The Best from Diabetes Texts

International Textbook of Diabetes Mellitus, 4th Ed., Excerpt #143: The Genetics of Type 2 Diabetes Part 5

MOST POPULAR ARTICLES OF THE MONTH

#1 When and When Not to Use An SGLT-2
#2 Empagliflozin’s Effect on Liver Fat
#3 What Is Glucotyping?

For years, we have often attributed the relative risk of developing diabetes to the heredity component. If your parents or grandparents had diabetes, there was a greater chance you would as well. Oftentimes patients use this as an excuse for *having* diabetes. Now that we have reasonably priced genetic testing that can identify certain hereditary disease anomalies, it would seem that we should be able to get a definitive answer.

Unfortunately, it is just not that easy. This week in our Clinical Text, the authors look into the “missing heritability” of diabetes and why the current tests only account for about 15% of the possible variants. Interesting comments are shared that likely will lead to the development of better testing methods and more definitive answers.

Dave Joffe

Editor-in-chief

You may have read Dave Joffe’s Editor’s Note on the relative risk of developing diabetes and how sometimes patients use it as an excuse for having diabetes. Although we don’t like to blame patients, it is true some people do think and say, “Why try? I have a family history of diabetes. I’m sure to get it too.” Well, we know that isn’t 100% true. Hopefully we work with our patients to help prevent or delay type 2 diabetes.

Scott Isaacs, M.D., F.A.C.P., F.A.C.E. is a board-certified endocrinologist and obesity medicine specialist in Atlanta, Georgia, and a faculty member at Emory University School of Medicine. He is a medical expert for ABC Television Networks and the medical director for the HMR Program for Weight Management at Atlanta Endocrine Associates. Since 1998, Dr. Isaacs has focused his medical practice on obesity medicine and endocrinology. Dr. Isaacs attended Emory College and Emory University School of Medicine, continuing for his residency in Internal Medicine and Fellowship in Endocrinology, Lipids, Diabetes and Metabolism. Dr. Isaacs is a Fellow of the American College of Physicians and the American College of Endocrinology.  Dr. Isaacs is past president of the Georgia Chapter of the American Association of Clinical Endocrinologists and currently serves on the national AACE board of directors and chairs the patient education and awareness committee. Dr. Isaacs is past president of the Atlanta Chapter of the Atlanta Diabetes Association.

In this week’s Homerun Slides, the effectiveness of the CGM to reduce A1C and hypoglycemia.

In spite of the large number of risk variants identified, it is estimated that they explain less than 15% of the heritability of T2DM. The unexplained heritability is an intensely discussed topic in complex genetics, some claiming it as a failure of GWA studies.There are many possible explanations for the missing heritability, including assumptions made about the genetic architecture of the disease and the definitions of heritability.The estimations of heritability explained assumes that only additive affects determine disease risk and that the risk follows the liability threshold model, that is, the genetic and environmental effects sum up to form a normal distribution of liability and that disease arises in individuals surpassing a certain threshold in the distribution [58]. If these assumptions are not true, the estimate of heritability explained will not be correct. However, there are also many other potential explanations for the missing heritability: yet unmapped common variants, distorted parent-of-origin transmission of risk alleles, rare variants, structural polymorphisms (e.g. copy number variations), gene–gene and/or gene–environment interactions (in which epigenetic effects may be important).

After reviewing evidence, a tool to evaluate benefit and risk has been developed for the use of sodium-glucose cotransporter 2 (SGLT2) inhibitors.

An SGLT-2 inhibitor reduces liver fat and ALT levels in people who have type 2 diabetes.

Patients who have normoglycemia still at risk for glucose spikes and diabetes.