Dermatology: Practical and Conceptual Dermatology Practical & Conceptual Review | Dermatol Pract Concept. 2021; 11(4):e2021131 1 Diabetes Detection and Prevention in Dermatology Alexandra Ngo1, Luise Froessl2, John Wesley McWhorter3, William Brett Perkison4, Rajani Katta 2,5 1 Department of Psychiatry, Baylor College of Medicine. 2 Baylor College of Medicine. 3 Culinary Nutrition of the Nourish Program, at the Michael & Susan Dell Center for Healthy Living at The University of Texas School of Public Health. 4 Department of Epidemiology, Human Genetics, and Environmental Science at the at the University of Texas School of Public Health in Houston. 5 McGovern Medical School at the University of Texas Health Science Center at Houston. Key words: diabetes prevention, diabetes in dermatology, diabetes skin findings, psoriasis and diabetes, diabetes screening Citation: Ngo A, Froessl L, McWorther JW, Perkinson WB, Katta R. Diabetes detection and prevention in dermatology. Dermatol Pract Concept. 2021; 11(4):e2021131. DOI: https://doi.org/10.5826/dpc.1104a131 Accepted: April 23, 2021; Published: September 2021 Copyright: ©2021 Ngo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License BY- NC-4.0, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: Rajani Katta MD is the author of a book on dermatology for the general public and is on an Advisory Board of Vichy Laboratories. Dr Ngo, MD, Dr Froessl, MD, Dr Mc Worther, PhD, and Dr Perkinson, MD, report no conflicts of interest. Authorship: All authors have contributed significantly to this publication. Corresponding author: Rajani Katta, MD, McGovern Medical School at the University of Texas Health Science Center at Houston; Baylor College of Medicine. 6750 West Loop South, Suite 695, Bellaire, TX 77401. Email: info@kattamd.com We are currently in the midst of an international epidemic of diabetes mellitus (DM) and prediabetes. The prevalence of DM in the United States is estimated at 9.4% of the population across all ages, while an estimated 1 in 3 Americans (33.9%) has prediabetes. According to the WHO, about 60 million people suffer from diabetes in the European Region. Dermatologists may play an important role in tackling this epidemic via efforts to improve early detection of both diabetes and prediabetes. Dermatologists often treat patients with, or at risk of, diabetes. This includes patients who present with cutaneous manifestations such as acanthosis nigricans, as well as patient populations at increased risk, including those with psoriasis, hidradenitis suppurativa, and polycystic ovarian syndrome. Simple screening guidelines can be used to identify patients at risk, and screening can be performed via a single non- fasting blood test. The diagnosis of prediabetes is a key feature in diabetes prevention, as interventions in this group can markedly reduce progression towards diabetes. In addition to referral to a primary care physician, dermatologists may refer these patients directly to structured behavioral lifestyle intervention programs known as diabetes prevention programs. A significant portion of the population lacks routine care by a primary care physician, and current data indicates need for improvement in diabetes screening and prevention among patient groups such as those with psoriasis. These factors highlight the importance of the dermatologist’s role in the detection and prevention of diabetes. ABSTRACT 2 Review | Dermatol Pract Concept. 2021; 11(4):e2021131 Introduction We are currently facing an international epidemic of diabetes mellitus and prediabetes. The prevalence of DM in the United States is estimated at 9.4% of the population across all ages, while an estimated 1 in 3 Americans (33.9%) has prediabetes [1]. According to the World Health Organization, about 60 million people suffer from diabetes in the European Region [2]. Dermatologists may play an important role in fighting against this epidemic. Efforts to identify and screen patients at risk can improve early detection of DM, and help identify those with prediabetes. The identification and treatment of patients with prediabetes is considered a key aspect in dia- betes prevention. There are 3 main factors making the dermatologist’s potential impact on DM epidemic further possible and more important than ever. First, dermatologists often treat patients with, or at risk of, DM. This includes patients who present with cutaneous manifestations of DM, such as acanthosis nigricans, as well as patient populations at increased risk for DM, including those with psoriasis, hidradenitis suppurativa, and polycystic ovarian syndrome [3-6]. Second, dermatolo- gists can use simple screening guidelines to identify patients at risk for DM [7]. Patients at risk may then be screened via a single non-fasting blood test. Third, diagnosing prediabetes is a key feature in DM prevention, as interventions have been shown to markedly reduce progression to DM. In addition to referral to a primary care physician (PCP), dermatologists may refer patients with prediabetes to diabetes prevention programs, behavioral lifestyle intervention programs that are cost-effective and effective [8]. Although DM screening and prevention might be typically performed by the PCP, data indicates that a significant por- tion of the population lacks routine care by a PCP. According to a recent study, only 75% of American adults reported a source of primary care in 2015 [9]. Some subgroups saw an even more marked decline in coverage, specifically younger patients, less medically complex patients, and those belonging to minorities. In parallel, the prevalence of type 2 DM has been steadily increasing, particularly among adolescents and young adults. Age of onset before 40 years has been associated with more severe long-term outcomes [10], emphasizing the importance of early diagnosis and continuous management. A significant percentage of dermatology patients at increased risk for comorbidities lack care by a PCP. This draws attention to the potential role that can be played by dermatologists in diabetes detection. A recent study found that among patients suffering from psoriasis, 21.6% of men and 16.9% of women received no primary care visits within a year from their dermatologist visit. In hidradenitis suppu- rativa, 28.1% of male patients and 22% of female patients were not visited further [11]. Furthermore, current data indicates that there is space for improvement in DM screening and prevention. Although multiple large-scale studies have found that patients with psoriasis are at higher risk for DM and other systemic comor- bidities [4, 12], data indicates that healthcare providers are not adequately screening psoriasis patients for metabolic risk factors [13]. Dermatologists rarely screen their patients for risk factors such as glucose levels (1.2%), BMI (9.7%), or blood pressure (2.6%) [13]. Even among PCPs and cardiolo- gists, survey studies reveal that many do not routinely screen patients with psoriasis for cardiovascular risk factors [14]. The Importance of Early Detection Dermatologists may interact with patients with DM at all stages of the disease, including those who are not yet diag- nosed. Despite the availability of simple screening measures, DM often goes undiagnosed for years. Much of this is because patients may be asymptomatic for years. These years, how- ever, are critical. While patients are at high risk for the devel- opment of micro- and macrovascular complications, these have not yet become irreversible. Early detection of DM and institution of early treatment may profoundly impact the course of the disease [15]. DM impacts multiple organ systems, including the brain, heart, kidneys, and skin, with significant impacts on morbidity and mortality. The National Diabetes Statistics Report found DM to be the 7th leading cause of death in the United States in 2015 [1]. Skin Findings Strongly Associated with Insulin Resistance and DM Approximately 85 million Americans (1 in 4 individuals) were evaluated by a physician for a skin disease in 2013 [16]. Certain cutaneous findings should trigger a high level of sus- picion and screening for DM. In a prospective observational study conducted in a diabetes clinic, cutaneous lesions were seen in over 98% of those with type 2 DM and 34% of those with Type 1 DM [17]. While there was a higher prevalence (98%) of skin manifestations in patients with DM for more than 5 years, cutaneous manifestations were still present in 80% of patients with DM for less than 5 years [17]. Acanthosis nigricans (AN) is a classic cutaneous man- ifestation of DM that is associated with hyperinsulinemia. Studies indicate that elevated levels of insulin and insulin-like growth factor may act to increase epidermal keratinocyte and dermal fibroblast proliferation, resulting in hyperpigmented, thickened, and velvety areas of skin [18]. Cutaneous infections are particularly prevalent in those with DM. In a prospective study of 750 patients, 79% had skin man- ifestations, with the most common (in 47.5% of patients) being cutaneous infections, including bacterial, viral and fungal [19]. Review | Dermatol Pract Concept. 2021; 11(4):e2021131 3 Diabetic dermopathy (DD) warrants prompt evaluation for DM. The atrophic, hyperpigmented macules of DD are classically seen on the shins, and are considered a common cutaneous manifestation of DM [20]. Notably, the condition is also significantly associated with microangiopathic compli- cations of DM such as retinopathy [20] and cardiovascular disease. Necrobiosis lipoidica is overall rare; although estimates vary, it is believed to impact about 1% or less of patients with DM [21]. Its presence should however lead to consideration of DM, as underlying DM has been seen in anywhere from 11% [22] to 65% [23]. It may be seen prior to the develop- ment of DM as well, and reviews estimate that up to 14% of patients may later develop DM [21]. Nonspecific Dermatologic Findings with Higher Prevalence in Patients With DM It is important to note that some dermatologic conditions that are commonly seen in the general population have an even higher prevalence among those with DM. Cutaneous xerosis is a common skin complaint overall. Multiple studies examining the frequency of skin manifestations in DM have showed a high prevalence of xerosis in both type 1 and type 2 DM [24]. As xerosis often appears on the lower extremi- ties, it is also an important element in the prevention of foot complications. One study indicated that xerosis of the feet in those with DM was associated with 3 times the number of superficial fissures [25]. Similarly, acrochordons have a prevalence of about 25% in the adult population [3] and a correlation with abnormal- ities in carbohydrate metabolism has been established [26]. Skin Diseases Associated with an Increased Risk of DM In addition to the dermatologic manifestations of DM, phy- sicians must also be familiar with dermatologic diseases that are associated with a higher risk of DM. These include psoriasis, hidradenitis suppurativa, and polycystic ovarian syndrome. Research indicates a significantly increased risk for DM and other metabolic abnormalities in patients with psoria- sis.  A meta-analysis of 27 observational studies found that psoriasis is associated with both an increased prevalence and incidence of DM [4]. A 13-year study of over 52,000 patients with psoriasis in a nationwide Danish cohort, reported a sig- nificantly increased risk of new-onset DM [12]. Importantly, this risk was significantly higher for those with severe skin disease as compared to those with mild disease. This increased risk is attributed to a combination of the systemic inflamma- tion seen in those with psoriasis and the higher prevalence of obesity [12, 27]. A relationship between pro-inflammatory cytokines in psoriasis and systemic effects has been revealed, suggesting their contribution to insulin resistance, weight gain, and cardiovascular events [27]. In addition, the psycho- social impact of psoriasis may contribute to behavioral risk factors for the development of obesity and DM [28]. Recent research indicates a higher risk of DM in patients with hidradenitis suppurativa (HS) as well. A systematic review and meta-analysis conducted by Phan et al [29] iden- tified a small but statistically significant association of DM with HS. A recent cross-sectional study by Ahmad et al [30] suggests benefits of screening for DM, as even subgroups of HS patients without traditional risk factors for DM (includ- ing age and high BMI) were found to have a high incidence of abnormal screening results. Although additional research is needed, dermatologists should be aware of this association. It is important for dermatologists to diagnose polycystic ovarian syndrome (PCOS), given that these patients have a higher risk of DM and often present to the dermatologist with commonly associated dermatologic manifestations, such as hirsutism, acne, acanthosis nigricans, alopecia or seborrhea [31]. A 2020 longitudinal study of PCOS patients assessed the metabolic changes in patients with PCOS and found a high prevalence of adverse changes in glucose metabolism, with deterioration of beta-cell function. The authors emphasize the importance of early detection and intervention in this group [32]. One prospective cohort study found a DM prevalence of close to 40% in patients with PCOS, as compared to 6% in the general population of a similar age [6]. Patients who are normal weight are at higher risk as well: one long-term longitudinal study found a 3-fold increase in risk of devel- oping DM in normal-weight PCOS patients compared with normal-weight women without PCOS [33]. The Dermatologist’s Role in DM Screening and Prevention Dermatologists can expect to see patients with prediabetes and DM, some of them undiagnosed. In fact, of the approx- imately 1/3 of the US population with prediabetes, 90% are unaware of their status [1]. Risk increases with age, and DM screening is recommended for all patients over the age of 45. Dermatologists may take a more active role in DM screen- ing and prevention via three main routes. First, by identifying patients at risk for DM. Second, by ordering screening labs. And finally, by referring to PCPs and diabetes prevention programs when indicated. Identifying Patients at Risk for DM Identifying patients at risk for DM is the first step in diabe- tes prevention and represents an important opportunity for dermatologists. Many dermatology patients, especially those 4 Review | Dermatol Pract Concept. 2021; 11(4):e2021131 who are younger, may not have a primary care physician [34]. For some, a dermatologist may be their only regular contact with the healthcare system, as with patients who are seen for annual skin cancer screening exams or those who are treated for acne. Recommendations for DM screening differ based on risk factor profile. Table 1 summarizes screening recommenda- tions by the American Diabetes Association. In terms of patients with skin disease, guidelines are not yet defined, and this area needs further research and con- sensus. Certainly, many patients diagnosed with acanthosis nigricans, or recurrent cutaneous fungal infections would benefit from screening. Psoriasis patients who are overweight or obese should also be considered for screening. Even in the absence of a high BMI, however, those with severe psoriasis may require screening. Studies have demonstrated increased risk of DM even in the absence of traditional risk factors, and severity of skin disease has been linked to a higher risk for metabolic comorbidities [12, 36]. Patients with skin disease severe enough to warrant biologic therapy should therefore also be screened for DM. Screening Laboratory Tests Screening may be accomplished by several methods, including via measurement of hemoglobin A1C level. This is a single non-fasting blood test, and can be used to diagnose predia- betes or DM. Diabetes mellitus (DM) is classified into two main cate- gories: Type I and Type II. In the last 50 years Type II DM has steadily increased in prevalence and now accounts for 90-95% of cases in the US [35]. According to the American Diabetes Association (ADA), diagnostic criteria for type II diabetes includes a Hemoglobin A1C level of 6.5% or above, a fasting blood glucose test of 126 mg/dL or above, an impaired glucose tolerance test, and/or a random blood glucose test of 200 mg/dL or above [7]. Prediabetes Diagnosis While early detection of DM remains a high priority, an increased focus has been paid to prediabetes as well. Identi- fying these individuals is a key aspect of diabetes prevention, as evidence-based interventions have shown a relative risk reduction of 40-70% in adults with prediabetes [37]. The ADA defines prediabetes as a hemoglobin A1C value of 5.7% to 6.4% or a fasting plasma glucose of 100-125 mg/dL [7], while the WHO defines prediabetes as a fasting plasma glucose of 110 – 125 mg/dL or an impaired glucose tolerance test. Prediabetes is considered an intermediate state of hyper- glycemia that has not quite surpassed the DM threshold. It has been shown that conversion from prediabetes to DM occurs at a rate of up to 19% annually, with the likelihood of progression increasing with time [37,38]. Importantly, prediabetes may also revert to normoglycemia. In a Cochrane systematic review, 47 of 103 prospective cohort studies indi- cated that regression back to normoglycemia was as high as 59% within 5 years and 42% within 6-11 years [38]. Treatment of prediabetes is crucial because individuals have a window of time where lifestyle changes or medication may be successful in preventing the development of DM. The role of lifestyle change in particular has received much attention. Although the number of drugs available for DM treatment has quadrupled since 1995, there has only been an estimated 8% improvement in glycemic control nationwide. This has led to a renewed emphasis on the importance of Table1. Summary of screening recommendations by the American Diabetes Association (ADA) [35]. All patients 45 and over should be screened every 3 years Asymptomatic patients under the age of 45 with any of the following 8 risk factors AND a BMI ≥ 25 kg/m2 should undergo screening (If Asian American, then BMI ≥ 23 kg/m2) Demographics • High-risk race/ethnicity (Black, Hispanic/Latino, American Indian, Asian American, or Pacific Islander) Family and Social History • Physical inactivity • First-degree relative with diabetes Medical History • Hypertensive (≥ 140/ 90 mmHg or on therapy for hypertension) • Other clinical conditions associated with insulin resistance such as severe obesity, acanthosis nigricans • History of cardiovascular disease • Polycystic ovary syndrome (PCOS) Laboratory Values • HDL – C < 35 mg/dL and/or triglycerides >250 mg/dL Follow-up recommendations: • If results are normal, repeated screening should occur at least every 3 years • Women who were diagnosed with gestational diabetes should undergo screening every 3 years • Patients with prediabetes should undergo screening annually Review | Dermatol Pract Concept. 2021; 11(4):e2021131 5 lifestyle interventions, which can significantly reduce the risk of DM complications [39]. Interventions For patients diagnosed with prediabetes or DM, referral to primary care is required. In addition, dermatologists may directly refer patients with prediabetes to structured lifestyle intervention programs known as certified diabetes prevention programs (DPPs). These programs significantly reduce the risk of progression to DM. They also empower patients, an underappreciated yet significant benefit [40]. A randomized placebo-controlled trial documented that an individualized, structured lifestyle intervention pro- gram was able to reduce progression to DM by 58% [41]. This data led to the development of diabetes prevention programs. In the United States, the CDC has designed a diabe- tes prevention program based on this evidence that has been reformatted for small group sessions. Similarly, in Europe, the IMAGE project (Development and Imple- mentation of a European Guideline and Training Stan- dards for Diabetes Prevention) has defined standards for quality of diabetes prevention programs in the EU [42]. DPPs last 1 year, and focus on patient education and tech- niques that encourage behavioral change. Patients learn tech- niques to help encourage healthy eating, incorporate physical activity, and use healthy coping strategies. To help build and maintain the morale, trained lifestyle coaches are scheduled to meet with patients in group settings a total of 22-24 times throughout the program [8]. The CDC maintains a database of certified programs, which are administered through a variety of healthcare providers, national and local non-profits, and telehealth pro- grams. The CDC provides an online search tool to check for availability of programs in the local area. In the US, coverage is provided for Medicare patients who meet the medical qual- ifications. Some commercial insurance plans and employers may also provide coverage for the program cost. For those without such coverage, program costs will vary; according to the American Medical Association, costs to the patient for the entire 1-year program in the US were estimated at $400–$500 total [43]. In the EU, DPPs are adapted and implemented at a national level, such as, for example, in Germany, one of the leading countries in diabetes prevention [44]. A Europe-wide multi-center study showed a significant increase in health-re- lated quality of life indicators in patients across Europe, with both diabetes and prediabetes, who participated in DPPs [39]. The Benefits of Diabetes Prevention It is well-known that DM results in serious health impacts, including increased morbidity, cardiovascular complications, and increased healthcare costs [35]. For an individual patient, reducing the risk of this chronic disease may be life changing. For those who enroll in a DPP, weight loss is another ben- efit. To achieve certification, a DPP must demonstrate weight loss of at least 5% in a certain percentage of participants [43]. In patients with psoriasis, weight loss is an important benefit. The medical board of the National Psoriasis Foun- dation in 2018 published their dietary recommendations for those with psoriasis. The authors “strongly recommend” weight reduction in those who are overweight or obese [45]. Weight loss may be considered adjunct therapy in psoriasis [46-48] as it may result in improvement of skin disease, with studies demonstrating an improvement in PASI scores. Weight loss may also improve response to systemic psoriasis therapies [49]. Conclusion Dermatologists may play an important role in combating the current DM epidemic. Early detection of DM and treatment initiation may significantly improve patient outcomes and reduce the risk of serious complications. Using demographic factors and simple screening tools in the office, patients at risk for DM may be easily identified. Patients at risk may be screened via a single non-fasting blood test or referred to their PCP for further evaluation. Efforts to identify those with prediabetes is a key aspect of diabetes prevention, as lifestyle intervention programs are now accessible for many and demonstrate impressive results in reducing the risk of progression to DM. These programs also set weight loss goals, which may have additional skin disease benefits. For patients with skin diseases such as psoriasis, these measures will improve both overall health and skin health. References 1. National Diabetes Statistics Report, 2017. :20. 2. Data and statistics. Accessed February 21, 2021. https://www. euro.who.int/en/health-topics/noncommunicable-diseases/diabe- tes/data-and-statistics 3. Duff M, Demidova O, Blackburn S, Shubrook J. Cutaneous Man- ifestations of Diabetes Mellitus. Clin Diabetes. 2015;33(1):40-48. DOI:10.2337/diaclin.33.1.40. 4. Armstrong AW, Harskamp CT, Armstrong EJ. Psoriasis and the risk of diabetes mellitus: a systematic review and meta-analysis. JAMA Dermatol. 2013;149(1):84-91. DOI:10.1001/2013.jama- dermatol.406. 5. Garg A, Birabaharan M, Strunk A. Prevalence of type 2 diabetes mellitus among patients with hidradenitis suppurativa in the United States. Journal of the American Academy of Dermatology. 2018;79(1):71-76. DOI:10.1016/j.jaad.2018.01.014. 6. Gambineri A, Patton L, Altieri P, et al. Polycystic Ovary Syndrome Is a Risk Factor for Type 2 Diabetes. Diabetes. 2012;61(9):2369- 2374. DOI:10.2337/db11-1360. 6 Review | Dermatol Pract Concept. 2021; 11(4):e2021131 7. Getting Tested | Basics | Diabetes | CDC. Published June 11, 2019. Accessed September 17, 2019. https://www.cdc.gov/diabetes/ basics/getting-tested.html 8. Lifestyle Change Program Details | National Diabetes Prevention Program | Diabetes | CDC. Published August 23, 2019. Accessed September 17, 2019. https://www.cdc.gov/diabetes/prevention/ lifestyle-program/lcp-details.html 9. Levine DM, Linder JA, Landon BE. Characteristics of Ameri- cans With Primary Care and Changes Over Time, 2002-2015. JAMA Intern Med. 2020;180(3):463. DOI:10.1001/jamaint- ernmed.2019.6282. 10. Sattar Naveed, Rawshani Araz, Franzén Stefan, et al. Age at Diag- nosis of Type 2 Diabetes Mellitus and Associations With Cardio- vascular and Mortality Risks. Circulation. 2019;139(19):2228- 2237. DOI:10.1161/CIRCULATIONAHA.118.037885. 11. Barbieri JS, Mostaghimi A, Noe MH, Margolis DJ, Gelfand JM. Use of primary care services among patients with chronic skin disease seen by dermatologists. JAAD International. 2021;2:31- 36. DOI:10.1016/j.jdin.2020.10.010. 12. Khalid U, Hansen PR, Gislason GH, et al. Psoriasis and new-on- set diabetes: a Danish nationwide cohort study. Diabetes Care. 2013;36(8):2402-2407. DOI:10.2337/dc12-2330. 13. Takeshita J, Grewal S, Langan SM, et al. Psoriasis and comorbid diseases: Implications for management. J Am Acad Dermatol. 2017;76(3):393-403. DOI:10.1016/j.jaad.2016.07.065. 14. Parsi KK, Brezinski EA, Lin T-C, Li C-S, Armstrong AW. Are patients with psoriasis being screened for cardiovascular risk factors? A study of screening practices and awareness among primary care physicians and cardiologists. J Am Acad Dermatol. 2012;67(3):357-362. DOI:10.1016/j.jaad.2011.09.006. 15. Chatterjee S, Khunti K, Davies MJ. Type 2 diabetes. Lan- cet. 2017;389(10085):2239-2251. DOI:10.1016/S0140- 6736(17)30058-2. 16. Lim HW, Collins SAB, Resneck JS, et al. The burden of skin disease in the United States. Journal of the American Acade- my of Dermatology. 2017;76(5):958-972.e2. DOI:10.1016/j. jaad.2016.12.043. 17. Shahzad M, Al Robaee A, Al Shobaili HA, Alzolibani AA, Al Mar- shood AA, Al Moteri B. Skin Manifestations in Diabetic Patients Attending a Diabetic Clinic in the Qassim Region, Saudi Arabia. Med Princ Pract. 2011;20(2):137-141. DOI:10.1159/000321219. 18. Cruz PD, Hud JA. Excess Insulin Binding to Insulin-Like Growth Factor Receptors: Proposed Mechanism for Acanthosis Nigri- cans. Journal of Investigative Dermatology. 1992;98(6, Supple- ment):S82-S85. DOI:10.1111/1523-1747.ep12462293. 19. Demirseren D, Emre S, Akoglu G, et al. Relationship Between Skin Diseases and Extracutaneous Complications of Diabetes Mellitus: Clinical Analysis of 750 Patients. American Journal of Clinical Dermatology. 2014;15(1):65-70. DOI:10.1007/s40257- 013-0048-2. 20. Morgan AJ, Schwartz RA. Diabetic dermopathy: A subtle sign with grave implications. J Am Acad Dermatol. 2008;58(3):447- 451. DOI:10.1016/j.jaad.2007.11.013. 21. Sibbald C, Reid S, Alavi A. Necrobiosis Lipoidica. Dermatol Clin. 2015;33(3):343-360. DOI:10.1016/j.det.2015.03.003. 22. O’Toole EA, Kennedy U, Nolan JJ, Young MM, Rogers S, Barnes L. Necrobiosis lipoidica: only a minority of patients have diabetes mellitus. Br J Dermatol. 1999;140(2):283-286. DOI:10.1046/ j.1365-2133.1999.02663.x. 23. Lowitt MH, Dover JS. Necrobiosis lipoidica. J Am Acad Dermatol. 1991;25(5 Pt 1):735-748. DOI:10.1016/s0190-9622(08)80961-9. 24. de Macedo GMC, Nunes S, Barreto T. Skin disorders in diabetes mellitus: an epidemiology and physiopathology review. Diabe- tology & Metabolic Syndrome. 2016;8(1):63. DOI:10.1186/ s13098-016-0176-y. 25. Lechner A, Akdeniz M, Tomova-Simitchieva T, et al. Comparing skin characteristics and molecular markers of xerotic foot skin between diabetic and non-diabetic subjects: An exploratory study. J Tissue Viability. 2019;28(4):200-209. DOI:10.1016/j. jtv.2019.09.004. 26. Kahana M, Grossman E, Feinstein A, Ronnen M, Cohen M, Millet MS. Skin tags: a cutaneous marker for diabetes mellitus. Acta Derm Venereol. 1987;67(2):175-177. 27. Korman NJ. Management of psoriasis as a systemic disease: What is the evidence? Br J Dermatol. 2019. DOI:10.1111/bjd.18245. 28. Fleming P, Kraft J, Gulliver WP, Lynde C. The Relationship of Obesi- ty With the Severity of Psoriasis: A Systematic Review. J Cutan Med Surg. 2015;19(5):450-456. DOI:10.1177/1203475415586332. 29. Phan K, Charlton O, Smith SD. Hidradenitis suppurativa and diabetes mellitus: updated systematic review and adjust- ed meta-analysis. Clinical and Experimental Dermatology. 2019;44(4):e126-e132. DOI:10.1111/ced.13922. 30. Ahmad S, Riddle AO, Sayed CJ. Outcomes of Routine Diabetes Screening for Patients with Hidradenitis Suppurativa. J Invest Dermatol. 2020. DOI:10.1016/j.jid.2020.08.016 31. Gainder S, Sharma B. Update on Management of Polycystic Ovarian Syndrome for Dermatologists. Indian Dermatol Online J. 2019;10(2):97-105. DOI:10.4103/idoj.IDOJ_249_17. 32. Jacewicz-Święcka M, Kowalska I. Changes in Metabolic Profile in the Women with a History of PCOS—A Long-Term Fol- low-Up Study. Journal of Clinical Medicine. 2020;9(10):3367. DOI:10.3390/jcm9103367. 33. Et W, R C-M, Mi C, et al. Polycystic ovary syndrome and risk for long-term diabetes and dyslipidemia. Obstet Gynecol. 2011;117(1):6-13. DOI:10.1097/aog.0b013e31820209bb. 34. Han X, Zhu S, Jemal A. Characteristics of Young Adults En- rolled Through the Affordable Care Act–Dependent Coverage Expansion. Journal of Adolescent Health. 2016;59(6):648-653. DOI:10.1016/j.jadohealth.2016.07.027. 35. Association AD. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020. Diabetes Care. 2020;43(Supplement 1):S14-S31. DOI:10.2337/dc20-S002. 36. Wan MT, Shin DB, Hubbard RA, Noe MH, Mehta NN, Gelfand JM. Psoriasis and the risk of diabetes: A prospective popula- tion-based cohort study. J Am Acad Dermatol. 2018;78(2):315- 322.e1. DOI:10.1016/j.jaad.2017.10.050. 37. Bansal N. Prediabetes diagnosis and treatment: A review. World J Diabetes. 2015;6(2):296-303. DOI:10.4239/wjd.v6.i2.296. 38. Richter B, Hemmingsen B, Metzendorf M, Takwoingi Y. Devel- opment of type 2 diabetes mellitus in people with intermediate hyperglycaemia. Cochrane Database Syst Rev. 2018;2018(10). DOI:10.1002/14651858.CD012661.pub2. 39. Nemah HH, Sebert Kuhlmann AK, Tabak RG. Effectiveness of Program Modification Strategies of The Diabetes Prevention Pro- gram: A Systematic Review. Diabetes Educ. 2016;42(2):153-165. DOI:10.1177/0145721716630386. 40. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lan- Review | Dermatol Pract Concept. 2021; 11(4):e2021131 7 cet. 2009;374(9702):1677-1686. DOI:10.1016/S0140- 6736(09)61457-4. 41. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403. DOI:10.1056/ NEJMoa012512. 42. Schwarz PEH, Gruhl U, Bornstein SR, Landgraf R, Hall M, Tuomilehto J. The European perspective on diabetes prevention: development and Implementation of A European Guideline and training standards for diabetes prevention (IMAGE). Diab Vasc Dis Res. 2007;4(4):353-357. DOI:10.3132/dvdr.2007.064. 43. Can you afford to offer a diabetes prevention program? Do this math. American Medical Association. Accessed November 18, 2019. https://www.ama-assn.org/delivering-care/diabetes/ can-you-afford-offer-diabetes-prevention-program-do-math 44. Schwarz PEH, Schuppenies A, Gruhl U, et al. [Prevention of type 2 diabetes in Germany. Ideas, evidence, implementation]. Med Klin (Munich). 2006;101(9):730-736. DOI:10.1007/s00063- 006-1100-2. 45. Ford AR, Siegel M, Bagel J, et al. Dietary Recommendations for Adults With Psoriasis or Psoriatic Arthritis From the Medical Board of the National Psoriasis Foundation: A Systematic Review. JAMA Dermatol. 2018;154(8):934-950. DOI:10.1001/jamader- matol.2018.1412. 46. Debbaneh M, Millsop JW, Bhatia BK, Koo J, Liao W. Diet and Pso- riasis: Part I. Impact of Weight Loss Interventions. J Am Acad Der- matol. 2014;71(1):133-140. DOI:10.1016/j.jaad.2014.02.012. 47. Jensen P, Zachariae C, Christensen R, et al. Effect of Weight Loss on the Severity of Psoriasis: A Randomized Clinical Study. JAMA Dermatol. 2013;149(7):795-801. DOI:10.1001/jamader- matol.2013.722. 48. Aune D, Snekvik I, Schlesinger S, Norat T, Riboli E, Vatten LJ. Body mass index, abdominal fatness, weight gain and the risk of psoriasis: a systematic review and dose–response meta-analysis of prospective studies. Eur J Epidemiol. 2018;33(12):1163-1178. DOI:10.1007/s10654-018-0366-z. 49. Gisondi P, Del Giglio M, Di Francesco V, Zamboni M, Girolomoni G. Weight loss improves the response of obese patients with mod- erate-to-severe chronic plaque psoriasis to low-dose cyclosporine therapy: a randomized, controlled, investigator-blinded clinical trial. Am J Clin Nutr. 2008;88(5):1242-1247. DOI:10.3945/ ajcn.2008.26427.