About

David A. Ehrmann is a professor based in Chicago, Illinois, with a focus on endocrinology, metabolism, reproductive medicine, and related fields. His research involves the assessment and management of polycystic ovary syndrome (PCOS), sleep disturbances in relation to metabolic health, and the genetic underpinnings of reproductive conditions. Ehrmann has contributed to the understanding of how sleep disorders impact glucose metabolism and insulin resistance, as well as the genetic architecture of PCOS through large-scale genome-wide meta-analyses. His work includes evaluating the effects of medical and surgical interventions on endocrine function and metabolic responses, and he has been involved in studies examining the role of hormones such as androgens and glucagon in metabolic and reproductive health. Ehrmann's research is characterized by a focus on translating findings into clinical practice, with an emphasis on improving outcomes for women with reproductive and metabolic disorders.

Research topics

• Medicine
• Internal medicine
• Endocrinology
• Bioinformatics
• Genetics
• Biology
• Physical therapy

Selected publications

• Evaluating the Impact of Eat, Sleep, Console in Neonatal Abstinence Syndrome Treatment for Infants Exposed to Substance Use <i>In Utero</i>

  The Journal of Pediatric Pharmacology and Therapeutics · 2024-04-01 · 1 citations

  articleOpen access

  OBJECTIVE An increase in maternal use of licit or illicit substances, alcohol, and tobacco has resulted in an increased incidence of neonatal abstinence syndrome (NAS). In recent years, NAS management has shifted to initiating an Eat, Sleep, Console (ESC) approach prior to pharmacologic treatment. The objective of this study was to evaluate the impact of ESC in combination with pharmacologic treatment in the management of NAS for infants exposed to substance use in utero. METHODS This single system, multisite, retrospective cohort study evaluated infants with known exposure to substance or polysubstance use in utero or those who had signs and symptoms of withdrawal with a positive toxicology screen. The primary outcome of rate of pharmacologic therapy initiated was evaluated pre and post implementation of ESC. Secondary outcomes included hospital length of stay, day of life that pharmacologic therapy was initiated, and an evaluation of the ESC guideline. A subgroup analysis with similar outcomes was also performed for patients with maternal polysubstance use. RESULTS A total of 2843 patients were screened, and 50 patients were randomly selected for ­inclusion in both pre- and post-groups. The rate of pharmacologic therapy initiated post implementation of ESC decreased from 58% to 30% (p &amp;lt; 0.01). In the post-group, there was a decrease in the number of ­patients requiring scheduled morphine (33%, p &amp;lt; 0.01) and duration of pharmacologic therapy (14.6 days vs 6.47 days, p &amp;lt; 0.01). CONCLUSIONS Implementing an ESC guideline decreased the length of stay and rate of pharmacologic intervention needed for infants with NAS at our institution.

  PublisherOA PDFDOI

• Body mass index stratified meta-analysis of genome-wide association studies of polycystic ovary syndrome in women of European ancestry

  BMC Genomics · 2024-02-26 · 25 citations

  reviewOpen access

  Abstract Background Polycystic ovary syndrome (PCOS) is a complex multifactorial disorder with a substantial genetic component. However, the clinical manifestations of PCOS are heterogeneous with notable differences between lean and obese women, implying a different pathophysiology manifesting in differential body mass index (BMI). We performed a meta-analysis of genome-wide association study (GWAS) data from six well-characterised cohorts, using a case–control study design stratified by BMI, aiming to identify genetic variants associated with lean and overweight/obese PCOS subtypes. Results The study comprised 254,588 women (5,937 cases and 248,651 controls) from individual studies performed in Australia, Estonia, Finland, the Netherlands and United States of America, and separated according to three BMI stratifications (lean, overweight and obese). Genome-wide association analyses were performed for each stratification within each cohort, with the data for each BMI group meta-analysed using METAL software. Almost half of the total study population (47%, n = 119,584) were of lean BMI (≤ 25 kg/m 2 ). Two genome-wide significant loci were identified for lean PCOS, led by rs12000707 within DENND1A ( P = 1.55 × 10 –12 ) and rs2228260 within XBP1 ( P = 3.68 × 10 –8 ). One additional locus, LINC02905 , was highlighted as significantly associated with lean PCOS through gene-based analyses ( P = 1.76 × 10 –6 ). There were no significant loci observed for the overweight or obese sub-strata when analysed separately, however, when these strata were combined, an association signal led by rs569675099 within DENND1A reached genome-wide significance ( P = 3.22 × 10 –9 ) and a gene-based association was identified with ERBB4 ( P = 1.59 × 10 –6 ). Nineteen of 28 signals identified in previous GWAS, were replicated with consistent allelic effect in the lean stratum. There were less replicated signals in the overweight and obese groups, and only 4 SNPs were replicated in each of the three BMI strata. Conclusions Genetic variation at the XBP1, LINC02905 and ERBB4 loci were associated with PCOS within unique BMI strata, while DENND1A demonstrated associations across multiple strata, providing evidence of both distinct and shared genetic features between lean and overweight/obese PCOS-affected women. This study demonstrated that PCOS-affected women with contrasting body weight are not only phenotypically distinct but also show variation in genetic architecture; lean PCOS women typically display elevated gonadotrophin ratios, lower insulin resistance, higher androgen levels, including adrenal androgens, and more favourable lipid profiles. Overall, these findings add to the growing body of evidence supporting a genetic basis for PCOS as well as differences in genetic patterns relevant to PCOS BMI-subtype.

  PublisherOA PDFDOI

• 1693-P: Association of Sleep and OSA Severity with Neurocognitive Function in the RISE Study

  Diabetes · 2023-06-20

  article

  Poor sleep and obstructive sleep apnea (OSA) have both been associated with worsening neurocognitive function. In the Restoring Insulin Secretion (RISE) Study, we assessed the relationship between presence and severity of OSA and cognition in treatment-naïve adults (n=179) with prediabetes or early T2D. A cognitive battery (CogState™ and story recall) assessed 1) psychomotor speed; 2) visual pattern separation; 3) visual attention and working memory; and 4) verbal learning and episodic memory. Wrist accelerometers worn for 7 days measured average sleep duration and efficiency. Other sleep outcomes were measured during one night of laboratory polysomnography. Linear regression models were fit to assess independent relationships between cognition and sleep measures. The cohort consisted of 44% females, 56% males; 53% white, 33% black, 6% Hispanic; age 54.7±8.9 years and BMI 34.7±5.4 kg/m2 (mean±SD). Based on ADA criteria, 73% had prediabetes and 27% had T2D. Sleep duration was 6.5±1.0 h; sleep efficiency was 85.9±7.5%; 26% had moderate OSA, 40% had severe OSA. After adjustment for age, sex, race/ethnicity, education, and BMI, higher sleep efficiency was associated with better visual pattern separation (as measured by the One Card Learning Test; p=0.039) but not with any other neurocognitive assessment. In the RISE cohort, measures of OSA severity (apnea-hypopnea index, oxygen desaturation index, sleep duration below 90% oxygen saturation, microarousal index) were not associated with baseline cognition. This cross-sectional analysis shows a high prevalence of moderate/severe OSA in treatment-naïve adults with prediabetes or early T2D. Although higher sleep efficiency was associated with better visual pattern separation, it was not associated with other measures of cognitive function. Further, OSA severity was not associated with measures of neurocognition. Disclosure K.A.Temple: None. A.H.Tjaden: None. D.Ehrmann: None. S.Manchanda: Advisory Panel; Inspire. S.Edelstein: None. T.S.Hannon: Advisory Panel; Eli Lilly and Company. S.Craft: None. B.Mokhlesi: None. Rise consortium: n/a. Funding American Diabetes Association (1-20-RISE-01 to S.E.); National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute; U.S. Department of Veterans Affairs; Kaiser Permanente Southern California

  PublisherDOI

• 1098-P: Association of Sleep with ß-Cell Response and Insulin Sensitivity in Youth

  Diabetes · 2023-06-20

  article

  Poor sleep may be associated with reduced β-cell response or decreased insulin sensitivity in youth. We explored whether sleep duration, sleep quality or obstructive sleep apnea (OSA) risk factors were associated with measures of β-cell response or insulin sensitivity in youth. At baseline, 88 youth (10-19 yrs of age) with recently diagnosed T2D or prediabetes completed validated questionnaires (Sleep Disturbances Scale and Cleveland Adolescent Sleepiness) in the Restoring Insulin Secretion (RISE) Study. Hyperglycemic clamps measured insulin sensitivity (steady state glucose infusion rate/insulin [M/I]) and β-cell responses: acute (0-10 min) C-peptide response to glucose (ACPRg), steady-state C-peptide at a glucose of 11.1 mmol/L (SSCP), and arginine-stimulated maximum C-peptide responses at glucose &amp;gt;25 mmol/L (ACPRmax). Linear regression models explored the independent association between sleep variables and clamp measures, adjusted for age, race/ethnicity, sex, Tanner stage, metformin use and BMI. Models including β-cell responses were adjusted for M/I to account for the role of insulin sensitivity in β-cell function. The cohort was 70% female, 28% white, 25% black, 36% Hispanic; age 14.3±2.0 yrs and BMI 36.9±6.4 kg/m2 (mean±SD). Using ADA criteria, 60% had prediabetes and 40% had T2D; 27% reported metformin use. Sleep duration &amp;lt;8 h was reported in 59%; 57% reported daytime sleepiness; 28% reported poor sleep quality; 29% had high risk for OSA. Low sleep duration (&amp;lt;8 h) was associated with a trend for lower ACPRg (p=0.069). No sleep variables (sleep duration or quality, OSA risk) were associated with clamp-derived outcomes in unadjusted or adjusted linear regression models. In youth with prediabetes or T2D, subjective measures of sleep quantity, sleep quality and OSA risk were not independently associated with β-cell response or insulin sensitivity. Further research using objective measures of sleep may better delineate the relationship between sleep and β-cell function in youth. Disclosure K.A.Temple: None. A.H.Tjaden: None. S.Manchanda: Advisory Panel; Inspire. D.Ehrmann: None. K.J.Nadeau: None. S.Edelstein: None. T.S.Hannon: Advisory Panel; Eli Lilly and Company. B.Mokhlesi: None. Rise consortium: n/a. Funding American Diabetes Association (1-20-RISE-01 to S.E.); National Institute of Diabetes and Digestive and Kidney Diseases; National Heart, Lung, and Blood Institute

  PublisherDOI

• FRI458 Rare Pathogenic Missense Variants in LMNA Identified in Women with Polycystic Ovary Syndrome (PCOS)

  Journal of the Endocrine Society · 2023-10-01

  articleOpen access

  Abstract Disclosure: R. Bauer: None. L. Gorsic: None. R.S. Legro: None. M.G. Hayes: None. M. Urbanek: None. Background: Polycystic ovary syndrome (PCOS) is the most common form of anovulatory infertility among reproductive age women. In addition to experiencing reproductive symptoms, women with PCOS are at elevated risk of developing obesity, insulin resistance (IR), and type 2 diabetes. Familial partial lipodystrophy type 2 (FPLD2) is a disorder of lipid storage and insulin resistance caused by dominant missense alleles in the gene encoding the intermediate filaments lamin A/C (LMNA). Women with this Mendelian disorder of IR also experience symptoms of PCOS such as amenorrhea and hyperandrogenism. We, therefore, hypothesize that genetic variation in LMNA also contributes to PCOS, which is a common form of IR. In other words, we hypothesize that PCOS falls into the phenotypic spectrum of disorders caused by variation in LMNA.Objective: We aim to identify and evaluate variation in LMNA that underlies PCOS pathogenesis. Methods: To test our hypothesis, we sequenced the LMNA gene in 602 women with PCOS and 125 reproductively healthy women. We comprehensively screened LMNA for genetic variation that is likely to alter the lamin A/C proteins, including missense, nonsense, splicing or frameshift variants. We identified 7 missense variants in 8 cases and no variants in reproductively healthy controls (χ2= 3.1, p=0.081, OR &amp;gt; 1.78, with study controls; χ2= 46.8, p&amp;lt;1x10-8, OR= 8.5 with gnomAD non-Finnish European cohort population controls). To determine which of these variants are pathogenic, we systematically evaluated them according to criteria outlined by the American College of Medical Genetics (ACMG). These guidelines evaluate pathogenicity of variants through multiple lines of evidence, including population data, computational predictions, and functional studies. Results: We identified 5 pathogenic variants in LMNA and 2 that are likely pathogenic. When assessed individually, 6 of the 7 variants are significantly enriched in our cohort when compared to gnomAD non-Finnish European population controls (OR &amp;gt; 5.0). All of the LMNA variants are likely damaging as predicted by 3 computational methods: CADD score ≥ 15, FATHMM prediction of “Damaging”, and MutationTaster classification as “disease causing.” Additionally, many of the variants have previously been identified in individuals with lipodystrophy. Conclusion: Together with previous identification of LMNA variants in women with PCOS by our lab (Urbanek et al. 2009 JCEM) and others (Crespo et al. 2022 JES), this work further establishes LMNA variation as a pathogenic mechanism for PCOS. Presentation Date: Friday, June 16, 2023

  PublisherDOI

• Nonalcoholic fatty liver disease and obstructive sleep apnea in women with polycystic ovary syndrome

  Fertility and Sterility · 2022-05-01 · 26 citations

  reviewSenior authorCorresponding
  PublisherDOI

• The 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research (AICR) score and diabetes risk in the Diabetes Prevention Program Outcomes Study (DPPOS)

  BMC Nutrition · 2022-09-21 · 5 citations

  articleOpen access

  BACKGROUND: The 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) 3rd expert report highlights up-to-date Cancer Prevention Recommendations that may reduce burdens of many chronic diseases, including diabetes. This study examined if following a lifestyle that aligns with the recommendations - assessed via the 2018 WCRF/AICR Score - was associated with lower risk of type 2 diabetes in high-risk adults participating in the Diabetes Prevention Program Outcomes Study (DPPOS). METHODS: The Diabetes Prevention Program (DPP) randomized adults at high risk for diabetes to receive a lifestyle intervention (ILS), metformin (MET) or a placebo (PLB) (mean: 3.2 years), with additional follow-up in DPPOS for 11 years (mean: 15 years total). 2018 WCRF/AICR Scores included seven components: body weight, physical activity, plant-based foods, fast foods, red and processed meat, sugar-sweetened beverages, and alcohol; the optional breastfeeding component was excluded. Scores ranged 0-7 points (with greater scores indicating greater alignment with the recommendations) and were estimated at years 0, 1, 5, 6, 9, and 15 (N=3,147). Fasting glucose and HbA1c were measured every six months and oral glucose tolerance tests were performed annually. Adjusted Cox proportional hazard ratios (HRs) and 95% confidence intervals (CIs) were used to examine the association of both Score changes from years 0-1 and time-dependent Score changes on diabetes risk through DPP and year 15. RESULTS: Scores improved within all groups over 15 years (p<0.001); ILS Scores improved more than MET or PLB Scores after 1 year (p<0.001). For every 1-unit improvement from years 0-1, there was a 31% and 15% lower diabetes risk in ILS (95% CI: 0.56-0.84) and PLB (95% CI: 0.72-0.97) through DPP, and no significant association in MET. Associations were greatest among American Indian participants, followed by non-Hispanic White and Hispanic participants. Score changes from years 0-1 and time-dependent Score changes in ILS and PLB remained associated with lower risk through year 15. CONCLUSIONS: Score improvements were associated with long-term, lower diabetes risk among high-risk adults randomized to ILS and PLB, but not MET. Future research should explore impact of the Score on cancer risk. TRIAL REGISTRATION: Diabetes Prevention Program: NCT00004992 ; Diabetes Prevention Program Outcomes Study: NCT00038727.

  PublisherOA PDFDOI

• Polycystic Ovary Syndrome

  2022-01-28

  book-chapter1st authorCorresponding

  Abstract Insulin resistance is common among women with PCOS independent of adiposity. However, the severity of insulin resistance in these women worsens with obesity especially in those who present with the classical phenotype of PCOS (NIH criteria) consisting of hyperandrogenism and menstrual irregularity. Hence, obese women with PCOS, especially those with the classic phenotype of PCOS, are at high risk for metabolic complications. These complications include type 2 diabetes (DM2), metabolic syndrome, dyslipidaemia and obstructive sleep apnoea (OSA). Additionally, these women are at increased risk for cardiovascular disease even though the exact risk for this complication is not established. Due to heightened risk for metabolic disorders, close screening and follow-up for development of glucose intolerance, metabolic syndrome, and OSA is essential and is supported by current guidelines. Management of women with PCOS is individualized and should depend on the patient’s symptoms as well as their risk for development of various complications.

  PublisherDOI

• Risk Factors for the Development of Retinopathy in Prediabetes and Type 2 Diabetes: The Diabetes Prevention Program Experience

  Diabetes Care · 2022 · 29 citations

  • Medicine
  • Internal medicine
  • Endocrinology

  OBJECTIVE: To determine glycemic and nonglycemic risk factors that contribute to the presence of diabetic retinopathy (DR) before and after the onset of type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: During the Diabetes Prevention Program (DPP) and DPP Outcome Study (DPPOS), we performed fundus photography over time in adults at high risk for developing T2D, including after they developed diabetes. Fundus photographs were graded using the Early Treatment Diabetic Retinopathy Study (ETDRS) grading system, with DR defined as typical lesions of DR (microaneurysms, exudates, hemorrhage, or worse) in either eye. RESULTS: By DPPOS year 16 (∼20 years after random assignment into DPP), 24% of 1,614 participants who had developed T2D and 14% of 885 who remained without diabetes had DR. In univariate analyses, using results from across the entire duration of follow-up, American Indian race was associated with less frequent DR compared with non-Hispanic White (NHW) race, and higher HbA1c, fasting and 2-h plasma glucose levels during an oral glucose tolerance test, weight, and history of hypertension, dyslipidemia, and smoking, but not treatment group assignment, were associated with more frequent DR. On multivariate analysis, American Indian race was associated with less DR compared with NHW (odds ratio [OR] 0.36, 95% CI 0.20-0.66), and average HbA1c was associated with more DR (OR 1.92, 95% CI 1.46-1.74 per SD [0.7%] increase in HbA1c). CONCLUSIONS: DR may occur in adults with prediabetes and early in the course of T2D. HbA1c was an important risk factor for the development of DR across the entire glycemic range from prediabetes to T2D.

  PublisherOA PDFDOI

• Obstructive Sleep Apnea, Glucose Tolerance, and β-Cell Function in Adults With Prediabetes or Untreated Type 2 Diabetes in the Restoring Insulin Secretion (RISE) Study

  2021-02-19

  preprintOpen access

  &lt;b&gt;Objective:&lt;/b&gt; Obstructive sleep apnea (OSA) is associated with insulin resistance and has been described as a risk factor for type 2 diabetes. Whether OSA adversely impacts pancreatic islet beta-cell function remains unclear. We aimed to investigate the association of OSA and short sleep duration with beta-cell function in overweight/obese adults with prediabetes or recently-diagnosed, treatment-naïve type 2 diabetes. &lt;p&gt;&lt;b&gt;Research Design and Methods:&lt;/b&gt; 221 adults (57.5% men, age 54.5±8.7 years, BMI 35.1±5.5 kg/m&lt;sup&gt;2&lt;/sup&gt;) completed one week of wrist actigraphy and one night of polysomnography before undergoing a 3-h oral glucose tolerance test (OGTT) and a two-step hyperglycemic clamp. Associations of measures of OSA and actigraphy-derived sleep duration with HbA1c, OGTT-derived and clamp-derived outcomes were evaluated with adjusted regression models.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Mean±SD objective sleep duration by actigraphy was 6.6±1.0 hours/night. OSA defined as an apnea-hypopnea index (AHI) ≥5 events per hour was present in 89% of the participants; 20% mild, 28% moderate and 41% severe. Higher AHI was associated with higher HbA1c (p =0.007). However, OSA severity, measured by either AHI as a continuous variable or by categories of OSA severity, and sleep duration (continuous or &lt;6 h vs. ≥6 h) were not associated with fasting glucose, 2-h glucose, insulin sensitivity or beta-cell responses.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusion:&lt;/b&gt; In this baseline cross-sectional analysis of the RISE clinical trial of adults with prediabetes or recently-diagnosed, untreated type 2 diabetes, the prevalence of OSA was high. Although some measures of OSA severity were associated with HbA1c, OSA severity and sleep duration were not associated with measures of insulin sensitivity or beta-cell responses.&lt;/p&gt;

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Recent grants

• NIH Grant R01HL075079

  NIH · $1.4M · 2008

• NIH Grant U01DK094431

  NIH · $5.1M · 2020

• NIH Grant K08DK002315

  NIH · $495k · 2000

• NIH Grant P50HD057796

  NIH · $11.8M · 2013

Frequent coauthors

• Kristen J. Nadeau

  University of Colorado Anschutz Medical Campus

  37 shared

• Karla A. Temple

  37 shared

• Eve Van Cauter

  University of Chicago

  36 shared

• Kieren J. Mather

  34 shared

• Sharon L. Edelstein

  George Washington University

  33 shared

• Babak Mokhlesi

  Rush University

  32 shared

• Ashley H. Tjaden

  31 shared

• Robert L. Rosenfield

  28 shared