Exclusive interview with Dr. Andrea Dunaif
Diabetes in Control is pleased to bring you an exclusive interview with Dr. Andrea Dunaif, the Lillian and Henry M. Stratton Professor of Molecular Medicine and Chief of the J. Lester Gabrilove Division of Endocrinology, Diabetes and Bone Disease at the Icahn School of Medicine at Mount Sinai, New York, NY. Dr. Dunaif is an internationally recognized expert in endocrinology and women’s health. Her research on polycystic ovary syndrome (PCOS), the most common hormonal disorder of reproductive-age women, has shown that it is a leading risk factor for type 2 diabetes mellitus. Further, this research has revolutionized the treatment of PCOS with insulin-sensitizing drugs.
See more at: http://www.diabetesincontrol.com/?s=Andrea%20Dunaif
Steve Freed (SF), Publisher DIC: Welcome, we have Dr. Andrea Dunaif, who was one of the senior authors of a very large study on polycystic ovarian syndrome PCOS. Sometimes it’s confusing how to recognize, diagnosis and treat PCOS. I think some of the information that she is able to provide due to this recent study gives us some answers. Will you please give us a brief overview of the purpose and findings from this study?
Dr. Andrea Dunaif (AD): What this study did was combine a number of studies that had already been conducted looking for PCOS genes using modern genetic analytic techniques called genomewide association studies (GWAS). The sequencing of the human genome created a map that allows us to query the entire genome of large groups of individuals with conditions such as PCOS to identify disease-related genes. Using this approach, the larger the number of cases, the greater the ability to find genes.
By combining about seven studies, we had than 10,000 PCOS cases and about 100,000 control subjects that enable detailed mapping. We had enough cases to be able to look at the impact of the different diagnostic criteria for PCOS. This allowed us to address, for the first time, whether there were actual genetic differences among PCOS diagnosed by varying criteria. I think much to everyone’s surprise, we found that the genes were the same whether you diagnosed PCOS using the NIH criteria, which was the first diagnostic criteria, or the later Rotterdam criteria that added in how the ovaries looked on ultrasound, polycystic ovarian morphology, PCOM, to the original NIH criteria. The NIH criteria require the presence of hyperandrogenism and chronic anovulation. The Rotterdam criteria require two of the three criteria, hyperandrogenism, chronic anovulation and/or PCOM. Therefore, the Rotterdam criteria add two additional groups, hyperandrogenism and PCOM and chronic anovulation and PCOM to the diagnosis of PCOS.
The controversy over diagnostic criteria has created huge confusion among both patients and physicians. There has been ongoing debate in the field over which diagnostic criteria were best. Our genetic analysis demonstrates that genes, which reflect the underlying biology of PCOS, are similar between NIH and non-NIH Rotterdam PCOS cases. Even PCOS cases who were provided by 23andme where the PCOS diagnosis was self-reported had similar susceptibility genes to cases diagnosed by NIH and Rotterdam criteria.
SF: Interesting. So, let’s say a woman comes into your office, she has excess weight or obesity, you do an A1C which comes back showing she has diabetes. Is it important to know she has PCOS? Why not just treat her diabetes?
AD: Well, just because a woman has an elevated BMI or even PCOS doesn’t necessarily mean she’ll have diabetes right now. What we hope for in the future is that we will be able to tailor our diabetes treatments to the specific biology of diabetes subtypes. Genetic analyses of type 2 diabetes are beginning to reveal that there are multiple subtypes with different causal genes.
However, our meta-analysis suggests the way we were subtyping PCOS based on current diagnostic criteria does not appear to indicate biologically differences between the subtypes since the genes were similar. The Holy Grail is to identify disease subtypes that are genetically distinct and to develop customized diagnostic methods and therapies.
SF: So it’s important that we determine whether it’s not just type 2 diabetes but also if it’s PCOS because obviously you’re going to treat it differently I presume.
AD: Currently, everybody tends to receive similar treatments for type 2 diabetes. The hope for the future is that we will have personalized treatments based on the type of diabetes that you have. There are many reasons to believe that women with PCOS will benefit more from certain types of treatment for diabetes. We know that women with PCOS are very insulin resistant. Therefore, drugs can improve insulin sensitivity are particularly appropriate for PCOS, such as metformin. Diabetes in PCOS is very driven by body weight, so drugs that also result in weight loss such as the GLP-1 receptor agonists tend to be very good for PCOS. By understanding the different biologic pathways we can tailor treatment more appropriately.
SF: Did you learn the best way to diagnose PCOS? There are so many different attitudes as far as the best way to diagnose.
AD: Our study suggests that the original diagnostic criteria, the NIH criteria, are absolutely fine. You don’t need to perform an ovarian ultrasound to establish the diagnosis of PCOS. The belief that an ovarian ultrasound is needed is an impediment to diagnosis, especially for a lot of physicians who don’t have their own ultrasound equipment. In addition, unfortunately, in the U.S.A., clinically available ovarian ultrasounds are usually not interpreted according to the recommended criteria for the diagnosis of PCOS so the results are not useful for diagnosis.
Learn more about the study at:
For more information about PCOS, see our interview with Dr. Dunaif from ADA 2018.