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Review

Dermatological Manifestations of Diabetes Mellitus and Its Complications

by
Liana Ly
1,
Karen L. Vo
1,
Audrey C. Cruel
1 and
Jay H. Shubrook
2,*
1
College of Osteopathic Medicine, Touro University California, Vallejo, CA 94592, USA
2
Department of Clinical Sciences and Community Health, College of Osteopathic Medicine, Touro University California, Vallejo, CA 94592, USA
*
Author to whom correspondence should be addressed.
Diabetology 2025, 6(3), 18; https://doi.org/10.3390/diabetology6030018
Submission received: 20 January 2025 / Revised: 27 February 2025 / Accepted: 3 March 2025 / Published: 5 March 2025
Browse Figures
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Abstract

:
Diabetes mellitus (DM) is a chronic metabolic disorder associated with late diagnosis due to the absence of early symptoms in patients. Cutaneous manifestations of DM often serve as indicators of insulin resistance and vary with disease progression, highlighting severity and systemic involvements. With an increasing global burden and rapidly rising prevalence, skin findings associated with DM have become more crucial for the rapid identification and treatment of underlying metabolic processes. However, current challenges in identification include inaccurate or missed detection in darker-skinned populations, which may be attributed to the lack of inclusion of diverse skin types in textbooks and research studies. This review provides clinicians with comprehensive updates on the diagnosis and treatment of cutaneous signs, complications, comorbidities, medication-associated side effects associated with DM, and the treatment of these manifestations.

1. Introduction/Background

Diabetes mellitus (DM), one of the most prevalent chronic conditions of the 21st century, is a rapidly growing burden on public health systems, individuals, and families. It is estimated that one in six adults in the US has diabetes [1]. The disease burden is disproportionately high in low-income populations and in at-risk ethnic groups, with a study demonstrating higher prevalence in Black individuals than in White individuals (0.123 vs. 0.084; P = 0.03) and the highest rates in poor (0.12) and near-poor (0.127) households [2]. Etiology varies by type, with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) being the most common. T1DM is a chronically progressive autoimmune disease characterized by T-cell-mediated destruction of pancreatic beta cells, whereas T2DM results from insulin resistance. Despite these differences, disease progression may induce similar characteristics of beta cell failure and insulin resistance [3]. Early detection and prompt treatment may alleviate the burden and reduce risks of complications [4].
Diabetes mellitus presents with a variety of dermatologic manifestations, ranging from benign cosmetic concerns to potentially severe complications. Recognizing these skin changes can offer valuable clues about a patient’s current or past metabolic status. Identifying such findings may facilitate the diagnosis of diabetes or serve as an indicator of glycemic control over time. The following discussion explores the connection between diabetes and dermatologic conditions, with a focus on skin disorders closely linked to the disease. Many cutaneous manifestations of diabetes arise due to chronic hyperglycemia, the accumulation of advanced glycation end products (AGEs), vascular dysfunction, immune impairment, and neuropathy, all of which contribute to skin-related complications [5].
Enhanced recognition of complications in diabetes mellitus is crucial for timely diagnosis and treatment, whereas proper glycemic control may limit the appearance of skin findings. Cutaneous manifestations of DM are among the most common, with 30–70% of patients experiencing complications [5]. This review discusses cutaneous signs, complications, medication side effects, and other comorbidities linked with diabetes mellitus.

2. Cutaneous Signs Associated with Diabetes Mellitus

As a systemic disease with insulin resistance and dysregulation of glucose and fat metabolism at its core, type 2 diabetes mellitus (T2DM) has many skin-related findings. These findings often develop in parallel with insulin resistance and may present before, at, or after the diagnosis of diabetes. The same temporal pattern can be seen in type 1 diabetes (T1DM), an autoimmune condition, with other skin-related autoimmune conditions.

2.1. Acanthosis Nigricans (AN)

Acanthosis nigricans is a common dermatological condition characterized by velvety thickening and hyperpigmentation of the skin, often with a symmetric distribution (Figure 1) [6,7,8]. Common affected areas include the intertriginous areas of the body; however, AN may also be found on the scalp, joints, nipples, and palmar areas [9]. In a cross-sectional study, AN was found in 19.4% of patients; those with AN were found to be twice as likely to have T2DM than patients without this dermatological condition [10]. AN is also linked with obesity, hormone disorders, and internal malignancy [7,8]. AN affects both adolescent and adult populations [11], impacting darker skin of color (SOC) groups disproportionately. Despite a lack of ethnic and racial data, a review identified Fitzpatrick III-V patients as the predominate skin types affected by this condition [12]. AN develops in response to insulin-mediated cell growth stimulation. Increased IGF-1 stimulates the proliferation of fibroblasts and epidermal keratinocytes, which release melanocyte-stimulating growth factor, increasing melanin production in these patients and causing cell growth to exceed the rate of turnover [13].
There are eight subtypes of AN: benign, obesity-associated, syndromic, malignant, acral, unilateral, medication-associated, and mixed. Obesity-associated AN is the most common, and patients with this subtype often experience insulin resistance. While AN is associated with both obesity and insulin resistance (IR), obesity is still a more important determinant of IR than AN [14]. Treatment of AN varies significantly by subtype but generally involves addressing the underlying cause(s) [8]. Most people will not receive specific treatment for these cutaneous manifestations. Cosmetic treatments may involve topical or oral retinoids, vitamin D analogs, chemical peels, dermabrasion, laser, and surgical removal [6,15].

2.2. Acrochordons

Acrochordons, or skin tags, are common benign outgrowths of skin that can appear as early as the teenage years but are most commonly seen in older individuals. They tend to occur more frequently in individuals who are obese or have diabetes and are typically found in areas prone to friction, such as the neck, axilla, and groin (Figure 2) [16]. A study suggests that acrochordon growth may be linked with increased IGF-1R and IGF-2R expression, making these benign growths more likely to occur in patients with insulin metabolism disorders [17]. Acrochordons may additionally be linked to metabolic syndrome; a cross-sectional study found a significantly higher incidence of metabolic syndrome among those with acrochordons, especially when they were not limited to the axilla [18]. Regardless of skin color, skin tags generally match the individual’s skin tone, though they may be slightly darker. They usually start as small, asymptomatic growths that can become pedunculated. Treatment is not required, but common removal methods for aesthetic purposes include snip excision, cautery, and cryosurgery [16].

2.3. Xanthelasma Palpebrarum (XP)

Xanthelasma palpebrarum is a benign manifestation presenting as semi-solid yellow plaques and papules rich in cholesterol [19,20]. Lesions can be found on both the upper and lower eyelids bilaterally, and commonly appear on the inner canthus of the eyelid (Figure 3) [21]. XP is formed due to cholesterol deposits in the skin; approximately 50% of adults with XP have disruptions in lipid metabolism due to either genetic or secondary hyperlipidemia [19,21]. These manifestations may be more common in people with T2DM and pre-diabetes, with a study revealing concomitant diabetes mellitus in 18.03% and prediabetes in 26.3% of patients [21]. They are more common in female patients than male patients, with a 4.26:1 ratio [22]. While XP is benign and slow-growing, lesions do not resolve on their own [19]. The presence of XP should prompt evaluation for associated diseases in addition to treatment [22].
People with XP will have genetically related forms of hyperlipidemia. This should be evaluated and treated as the primary response. Cosmetic treatment options include chemical peels, cryotherapy, radiofrequency ablation, surgical excision, and CO2 laser [20,23].

2.4. Diabetic Dermopathy

Diabetic dermopathy, also known as “shin spots”, is a clinical diagnosis strongly associated with both T1DM and T2DM (Figure 4) [24,25]. Lesions may be associated with local thermal trauma, subcutaneous nerve degeneration, and impaired wound healing, which is described later in this review [24]. It is more commonly found in patients with a longer duration of diabetes mellitus and is associated with more serious complications, including retinopathy, neuropathy, and nephropathy [26]. Lesions of diabetic dermopathy typically present on the bilateral pretibial areas as well-demarcated hyperpigmented macules and patches. They can be up to 5 cm in diameter and may have a central depression. Other common locations include the thighs, sides of feet, and forearms [27]. Treatment is not recommended for diabetic dermopathy, as lesions typically are self-resolving within 18–24 months. It is common for new spots to appear as older ones fade [27,28]. However, a clinical diagnosis of diabetic dermopathy should prompt further evaluation for diagnosis and prevention of diabetes mellitus complications [29].

2.5. Necrobiosis Lipoidica (NL)

Necrobiosis lipoidica is a chronic granulomatous skin disease that predominantly affects young and middle-aged adults, typically presenting at 30–40 years of age [31]. Though its pathophysiology is unknown, it may be related to microvascular changes with resulting immune complex deposition and collagen degeneration [32]. It tends to manifest earlier in patients with type 1 diabetes mellitus, averaging around 26.5 years old, compared to 51.6 to 52.1 years old in those with type 2 diabetes or without diabetes [33]. Though more common in patients with T1DM, necrobiosis lipoidica occurs in only 0.3–1.2% of patients with diabetes overall and affects women at a ratio of approximately 3:1. Considered a cutaneous sign of diabetes mellitus, NL appears before diagnosis in approximately 14% of patients, after diagnosis in 62% of cases, and spontaneously in 24% of cases [32]. Additionally, a retrospective study revealed that patients with NL had notable comorbidities of obesity, hypertension, dyslipidemia, and thyroid disease [34].
NL typically presents with yellow, red, or brown atrophic plaques with telangiectasias, most commonly on the shins (Figure 5). Ulceration of the lesions may occur as a complication of the disease [32,33]. While NL can be asymptomatic, lesions may also be painful or pruritic [32,34]. Some patients additionally complain of reduced sensation or sweat over the lesions. Treatment for NL primarily involves wound care to avoid complications and the expansion of lesions [32]. Though there are few studies comparing treatment modalities, corticosteroids have sometimes been found to be an effective option for the control of NL lesions [31].

2.6. Granuloma Annulare

Granuloma annulare is a skin condition characterized histologically by a dermal lymphohistiocytic infiltrate and areas of degenerated collagen, suggesting a potential delayed hypersensitivity reaction [35]. It predominantly affects those in the fifth decade of life, with a female-to-male ratio of 3:1. The disease is more frequent in Caucasian individuals, followed by Hispanic, Black, and Asian populations [36]. Though its exact mechanism is unknown, a retrospective study found that granuloma annulare has a higher incidence in people with type 1 diabetes compared to the general population (16% vs. 0.9%) [37], and 21% of patients with the condition are likely to have diabetes, in contrast to 13% in control groups [38].
Classically, granuloma annulare begins as a small papule or nodule that gradually expands to form a 1–4 cm ring. Lesions typically maintain the same color as adjacent areas, although they may appear slightly red or hyperpigmented. They are usually found on extensor surfaces—lower legs, feet, fingers, and hands. Pre-existing lesions can coalesce and create larger annular plaques, but the overlying epidermis remains intact. Most cases are asymptomatic, with some mild pruritus. Granuloma annulare can last from months to years as lesions regress and new ones form; the condition often resolves spontaneously without treatment [39]. For symptomatic or persistent cases, topical corticosteroids, calcineurin inhibitors, and intralesional corticosteroids are common treatments. Treating generalized disease may require systemic therapies like hydroxychloroquine, phototherapy, tetracyclines, dapsone, systemic retinoids, or TNF inhibitors [36].

3. Cutaneous Complications of Diabetes Mellitus

3.1. Scleredema Diabeticorum

Scleredema diabeticorum is a rare connective tissue disorder that occurs as a complication of diabetes mellitus. It is primarily caused by the glycosylation of collagen–a process heightened in diabetic patients. This leads to an excess accumulation of collagen and mucin, resulting in thickened and hardened skin with a distinctive “peau d’orange” texture that starts at the back of the neck and progresses towards the upper back and chest while sparing the extremities [40,41]. Studies indicate that between 2.5% and 14% of patients with diabetes may be affected, with data suggesting a predominance in type 2 diabetes [40]. Scleredema diabeticorum can affect both children and adults, though a study suggests an average age of onset of 53.8 years [42]. Most cases are slow-growing and subtle, but do not typically resolve with tight glycemic control. Treatment is primarily focused on symptom relief, with UVA-1 phototherapy and psoralen combined with PUVA proving to be the most effective [40].

3.2. Slow Wound Healing

Approximately 25% of patients with diabetes experience complications with wound healing, which can lead to severe outcomes such as lower limb amputations, imposing substantial economic and psychological burdens [43]. The hyperglycemic state in patients with diabetes supports biofilm formation and complicates wound treatment, making effective management difficult. Recent advancements have shed light on the pathophysiology underlying diabetic wounds, including impaired angiogenesis, neuropathy, chronic inflammation, barrier disruption, and susceptibility to polymicrobial infections. Effective treatment strategies require a multi-faceted approach to address these pathologies. This may include managing blood glucose levels, using targeted topical treatments, and preventing secondary infections and inflammation [44].
Individuals with chronic conditions like diabetes and cardiovascular disease face a heightened risk of developing wounds, with these risks further exacerbated by disparities in healthcare access and outcomes among racial and ethnic underrepresented groups, such as African Americans, Hispanics, and Native Americans [45]. Detecting early-stage wounds in individuals with darker skin tones poses an additional challenge, leading to potential delays in diagnosis and treatment [45,46].
Furthermore, stress disrupts the neuroendocrine and immune systems, negatively impacting wound healing and complicating diabetes management [45]. In addition, experiencing stress is associated with smoking, which further complicates wound healing due to its negative effects on immune function, tissue oxygenation, and collagen synthesis. Adequate nutrition plays a crucial role in supporting skin health and effective wound healing, yet global increases in malnutrition and diet-related illnesses disproportionately affect those in food deserts or facing food insecurity [46]. Additionally, limited access to resources and transportation barriers further restricts healthcare access, hindering the prevention and management of diabetes and chronic wounds. Clinicians may benefit from awareness of these social determinants of health and can provide patient education to help prevent worsening wound healing in patients with diabetes.

3.3. Acquired Perforating Dermatosis (APD)

Perforating dermatoses are a group of skin conditions characterized by the perforation of dermal connective tissue through the epidermis, leading to lesions. Acquired perforating dermatosis (APD) is the most common type and is typically observed in middle-aged adults with underlying systemic conditions, particularly those with diabetes or chronic kidney disease [47]. One of the most significant risk factors for APD is hemodialysis, with 3–11% of hemodialysis patients affected. The exact cause of APD remains unclear, but it is believed to result from intense scratching, leading to collagen necrosis and the elimination of necrotic tissue.
APD is diagnosed based on clinical and histological features, such as the transepidermal elimination of degenerated collagen fibers. Lesions often appear as umbilicated papules or nodules with a central keratotic plug, and they may have a yellowish-green crust, representing the degenerated dermal tissue [47]. In smaller lesions, histological analysis may be required to confirm the diagnosis. Treatment primarily involves managing the underlying systemic disease, such as improving diabetes or renal function. Additionally, therapies like topical corticosteroids, intralesional corticosteroid injections, antipruritic treatments, and UVB phototherapy can help alleviate symptoms and improve healing [48,49].

3.4. Periungual Telangiectasia

Periungual telangiectasia presents as visible, red, dilated blood vessels surrounding the proximal nail folds and is associated with conditions such as diabetes and autoimmune connective tissue diseases [25]. These vascular abnormalities result from the degeneration of capillary loops and subsequent dilation of the remaining capillaries. In diabetes, this condition is prevalent in up to 49% of patients, often accompanied by nail fold erythema, fingertip tenderness, and irregular or “ragged” cuticles [50].
These changes are linked to diabetes-related microangiopathy and may indicate early capillary damage, manifesting as venous capillary tortuosity or other abnormalities [51]. While the condition is important for clinical recognition and may signal underlying vascular compromise, it generally does not require specific treatment. Identifying periungual telangiectasia can aid in the early detection and monitoring of systemic diseases, particularly diabetes and vascular-related complications such as diabetic retinopathy [52]. However, in patients, particularly those with Fitzpatrick skin types IV and V, studies show decreased visibility and nailfold capillary density due to darker skin types [53,54].

3.5. Rubeosis Faciei

Rubeosis faciei is a benign condition commonly seen in patients with diabetes. It is characterized by chronic facial erythema and visible telangiectasias, with a flushed appearance more pronounced in individuals with lighter skin tones [25]. The prevalence of rubeosis faciei in diabetes varies, with Pavlović et al. indicating it affects around 7% of patients with T1DM [55]; however, this number rises significantly in hospitalized patients, sometimes exceeding 50%, according to a study by Gitelson et al. [56]. Rubeosis faciei is commonly associated with other diabetic complications such as retinopathy, neuropathy, and nephropathy.
Recent studies suggest a strong association between rubeosis faciei and diabetes-related nephropathy, with vascular endothelial dysfunction playing a central role in the pathogenesis of these microangiopathic changes [57,58]. Rubeosis faciei is linked to venular dilation in the cheeks, exacerbated by the effects of hyperglycemia. Effective management of underlying diabetes can potentially alleviate symptoms, although the condition may persist in some individuals as part of the broader vascular dysfunction associated with chronic diabetes. The condition may improve with better glycemic control and reducing caffeine or alcohol intake [59].

4. Concomitant Disorders of DM

4.1. Vitiligo

Vitiligo is a chronic autoimmune skin and hair disorder characterized by the destruction of epidermal melanocytes, causing patches of skin depigmentation (Figure 6). Several studies have illuminated the genetic basis of vitiligo, linking this disorder to other autoimmune diseases [60]. T1DM, linked via CD8+ T-cell–mediated destruction, has been shown to have a significant positive association with vitiligo; a 2019 meta-analysis suggests an additional association between T2DM and vitiligo caused by the role of oxidative stress in both disorders [61]. While the prevalence of patients with vitiligo with concomitant DM has been estimated to be approximately 1–7% [62], there has been little research showing variation across different ethnic groups. Treatment of vitiligo, often requiring dermatology referral, is aimed at minimizing disease progression as well as re-introducing and maintaining skin pigment [63].

4.2. Eruptive Xanthomatosis (EX)

Eruptive xanthomatosis is closely associated with hypertriglyceridemia, particularly when triglyceride levels exceed 2000 mg/dL. While EX can manifest at any age, it is most commonly seen in individuals in their second decade of life who have predisposing factors like familial hypercholesterolemia. In patients with diabetes, the presence of eruptive xanthomatosis can sometimes occur with lower triglyceride levels. EX affects approximately 1% of individuals with T1DM and 2% of patients with T2DM [25]. Lesions may appear at any time in disease progression and suggest uncontrolled diabetes [64,65]. In addition to being considered as a complication of diabetes and dyslipidemia, EX also can serve as a dermatological indication of undiagnosed disorders [66].
EX is characterized by the sudden appearance of clusters of 1–5 mm yellow lipid-laden papules, often surrounded by erythematous (red) halos (Figure 7). These lesions typically develop on the extensor surfaces of the extremities and buttocks [67]. Lesions are usually asymptomatic but can be pruritic or tender. Addressing underlying issues—dyslipidemia and diabetes mellitus—is crucial for the improvement of eruptive xanthomatosis [68].

4.3. Conditions Related to Routine Diabetes Care

During the routine diabetes clinical exam, important dermatologic components are necessary. These include inspection of the sites for fingerstick glucose testing and the placement of continuous glucose monitors. These can give the clinician insight into the frequency of testing, areas used for testing, and if the patient is using multiple sites for testing (Figure 8).
Inspecting injection sites is also important. Patients who inject into one area too often can develop liophypertrophy in these areas (Figure 9). Lipoatrophy from repeated injections can also occur but is much less common with analog insulins. These areas of abnormal tissue are much less likely to allow normal absorption of the medication injected—leading to unanticipated hyperglycemia and even hypoglycemia. This is often the etiology when patients report that their medication is “no longer working”. Inspections of the injection sites are an important part of the physical exam for patients receiving injectable therapies. Lipohypertrophy and lipoatrophy can lead to significant disruption in insulin absorption and insulin kinetics [69]. Lipohypertrophy is common among people who are receiving injections, including more than 60% of those taking insulin [70]. Injection device, lack of rotating injection sites, total dose of insulin injection, and needle length have all been associated with a higher rate of lipohypertrophy [70]. Treatment includes cessation of injections in the region for at least 2 months. The resolution of the tissue will depend on the duration of repeated injections in the area and the extent of tissue damage. A recent study found high-frequency ultrasound to be a useful adjunct for diagnosing lipohypertrophy [71].

5. Skin Infections Associated with DM

The skin is the body’s largest organ and one of the first-line barriers against pathogens. However, diabetes predisposes patients to repeated infections due to increased blood sugar, decreased blood flow, and reduced leukocyte function [73,74]. Cutaneous infections can range from mild to malignant life-threatening manifestations. Diabetes-related infections commonly remain superficial and are usually treated with oral antibiotics or topical/oral antifungals. On the other hand, more serious infections such as Fournier’s gangrene and mucormycosis require immediate medical attention to prevent the further spread of infection.

5.1. Folliculitis, Furuncles, Carbuncles, Cellulitis

Skin and soft tissue infections are among the most frequently occurring cutaneous infections in patients with diabetes. Folliculitis and furuncles, commonly resulting from infiltration of Staphylococcus aureus, form from infected hair follicles. Folliculitis is a superficial infection, usually presenting as pruritic and painful small red or white bumps [73], and can be treated with topical antibiotics such as mupirocin and clindamycin [75]. Furuncles are painful, red, and often swollen bumps that may coalesce into carbuncles; they are frequently found on the face, neck armpits, buttocks, and thighs. Deeper penetration of the infection into the dermis and subcutaneous fat layer can cause cellulitis. Treatment depends on severity, with oral antibiotics as the first-line treatment for uncomplicated cellulitis and IV antibiotics for severe cellulitis [73,74,76]. Drainage and packing of furuncles or carbuncles may be performed to prevent the recurrence and development of cellulitis [76].

5.2. Tinea Pedis, Onychomycosis, and Diabetic Foot Ulcers

Foot infections are common in patients with diabetes, as their increased skin surface pH and shoes create a warm and humid environment, which is optimal for pathogens to grow. Tinea pedis and onychomycosis are common foot infections seen in patients with diabetes; both may lead to serious complications such as diabetes-related foot ulcers (DFU) [25]. Tinea pedis manifests between the toes and on the soles of feet, often causing erythema, pruritus, and scales with resulting skin fissures. The most prevalent pathogen is Trichophyton rubrum, which causes approximately 70% of tinea pedis cases [77]. People with diabetes who have tinea pedis are recommended to be treated with a combination of oral antifungals (terbinafine and itraconazole) and topical antifungals (polyenes and imidazoles) [78].
Onychomycosis, a fungal infection of the toenails, presents with yellow-brown discoloration and hyperkeratosis. T. rubrum is the most common dermatophytic pathogen, seen in more than 90% of onychomycosis cases [78]. Surgical debridement is often utilized to reduce fungal load by decreasing the length and thickness of the toenail. Surgery in conjunction with antifungals such as fluconazole, itraconazole, and terbinafine has proven effective in the treatment of onychomycosis [79]. Studies have shown that the delayed treatment of onychomycosis along with the clinical presentations of neuropathy have shown an increased risk of DFU [80].
DFUs are classified as polymicrobial infections; C. albicans, Gram-positive cocci, Gram-negative rods, and anaerobes are the most prevalent pathogens cultured from these ulcers [81]. Neuropathic DFUs are the most frequently appearing type, though other types include ischemic or mixed (neuropathic and ischemic). Neuropathic DFUs are usually painless and round, while ischemic and mixed DFUs have irregular borders. Ulcers usually appear over bony prominences such as the toes, forefoot, and ankles [82]. Early recognition and treatment of DFU are essential in the prevention of osteomyelitis and the need for lower limb amputation. Treatment includes advanced wound care, oral/IV antibiotics and antifungals, and surgical debridement. Maintenance of good foot hygiene and frequent at-home foot exams are essential in preventing tinea pedis, onychomycosis, and DFUs. Patients are advised to wash their feet daily and dry thoroughly, moisturize their feet, and wear breathable socks and footwear [82,83].
Diabetes-related foot ulcers (DFUs), a common and debilitating complication of DM, often resist conventional treatments. Photobiomodulation (PBM), a non-invasive therapy, has shown potential in promoting the healing of chronic wounds, including DFUs. However, light-tissue interactions can vary based on skin tone, and there is a lack of research on PBM’s effectiveness and safety in people with darker skin [84]. Future trials should account for skin color when evaluating PBM’s utility in DFU treatment.

5.3. Fournier’s Gangrene (FG)

Fournier’s gangrene is a slow and insidious form of necrotizing fasciitis more commonly seen in males with diabetes. Recent studies have shown an increase in FG in those prescribed SGLT2 inhibitors [85,86]. FG is a polymicrobial infection, with Escherichia coli and Bacteroides fragilis as causative agents making up more than 80% of cases [87]. Early symptoms of FG present as pain in the genital and perianal regions with erythema. Further progression causes hemorrhagic bullae, induration, darkening, and crepitus of the skin [25,88].
Survivability is assessed using the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) and Fournier’s gangrene severity index (FGSI). Due to rapid progression and high mortality, treatment protocol necessitates broad-spectrum antibiotics and emergent surgical debridement to prevent the progression of infection. Computed tomography (CT) is utilized to define the involved fascial planes before operative interventions. Adjunctive therapies such as hyperbaric oxygen therapy (HBOT) and negative pressure wound therapy or vacuum-assisted closure (VAC) can promote wound healing [74,89].

5.4. Mucormycosis (MCR)

Mucormycosis is a deadly fungal infection that commonly affects patients with diabetes and other immunocompromised patients. Spores of the fungal species Mucor and Rhizopus enter the body through inhalation, ingestion, or inoculation and develop into MCR through the germination and formation of hyphae [90]. In a healthy individual, the immune system can typically fight the infection, whereas patients with diabetes lack sufficiently functioning immune cells. These patients have decreased neutrophils and dendritic cells in circulation and increased apoptosis of natural killer (NK) cells. This results in diabetic patients being unable to neutralize MCR, allowing the infection to persist [90]. Additionally, high blood glucose levels favor fungal growth. The most common forms of the infection are rhino-orbital-cerebral and necrotizing cutaneous mucormycosis. These patients initially present with headaches, facial swelling, and eye pain. Symptoms may progress into paranasal sinusitis, the formation of black necrotic eschar around the nasal passages or roof of the mouth, cranial nerve involvement affecting sensation in the face, and even blindness [91]. Mucormycosis is a medical emergency, and surgical debridement in combination with IV administration of amphotericin B has been shown to greatly reduce mortality. Because fungi thrive in low oxygen levels, hyperbaric oxygen therapy may inhibit fungal growth and reduce its spread [90,91].

6. Cutaneous Side Effects of Diabetes Medications

The choice of medication fundamentally depends on the type of diabetes; patients with T1DM will always require insulin, whereas patients with T2DM have a wider variety of therapeutic approaches [92]. Once patients are diagnosed and therapy begins, various cutaneous manifestations may develop in response to treatment and medical devices, impacting treatment adherence, glycemic control, and morbidity [93]. These skin reactions range from mild rashes to severe conditions like Stevens–Johnson syndrome and toxic epidermal necrolysis [94]. Early recognition, detailed history, and focused physical examination are crucial for developing a comprehensive differential diagnosis. Key considerations include the timeline, morphologic features, and systemic signs. The first-line treatment for all cutaneous adverse drug reactions (CADRs) involves withdrawing the offending drug to prevent complications and improve outcomes [86].
Cutaneous reactions to antidiabetic medications including metformin, sulfonylureas, meglitinides, glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter-2 inhibitors, thiazolidinediones, DPP-4 inhibitors, and insulin have been reviewed in the literature [86].
Eruptive melanocytic nevi is a phenomenon characterized by the sudden development of multiple nevi over weeks to months, often triggered by an underlying factor [95]. It has been linked to severe blistering diseases, renal transplantation, malignancy, AIDS, and certain medications. In general, these lesions are clinically stable and are monitored for any signs of malignancy. A notable case involved its occurrence after subcutaneous insulin injections in a pediatric patient with type 1 diabetes mellitus [96].

7. Different Skin Tones in Consideration in Diagnosis and Treatment

Diabetes mellitus (DM) is linked to significant morbidity due to its microvascular and macrovascular complications, largely driven by the accumulation of advanced glycation end products (AGEs) [97]. Skin autofluorescence (AF) is a non-invasive method used to assess tissue AGE levels and predict vascular risk in patients with DM [98]. However, while effective in lighter-skinned individuals, skin AF’s accuracy is limited in darker-skinned populations, even after excluding cases with low reflectance [99]. This highlights the need for improved diagnostic tools that are reliable across diverse skin tones.
Diabetic retinopathy (DR) remains the most common microvascular complication in patients with diabetes, with nail fold capillaroscopy (NFC) traditionally used for its assessment. Patients with DR have higher occurrences of tortuous capillaries, branched capillaries, bushy capillaries, avascular areas, microhemorrhages, and precapillary edema of the nail folds [100,101].
Recent studies investigated the utility of a handheld dermatoscope for assessing diabetes-related microvascular involvement, with a positive correlation identified between DM duration, HbA1c levels, and NFC findings [55,102]. However, visualization of NFC features decreased significantly in patients with darker skin, particularly in those with Fitzpatrick skin types IV and V [53]. Due to these limitations, it is recommended that patients with DM have a dilated and comprehensive eye examination by an ophthalmologist or optometrist to detect and monitor DR [103].
Non-invasive tools like skin AF and handheld dermatoscopes show promise for detecting and monitoring diabetic complications, but their performance in darker-skinned individuals remains a limitation. Future studies should prioritize the inclusion of diverse skin types to enhance the clinical utility of these methods across all populations, ultimately improving the management of diabetes-related complications for all patients.

8. Conclusions

There are many dermatologic clues to the existence or management of diabetes mellitus and its complications. Clinicians can utilize dermatologic findings to identify those at high risk and intervene earlier. Familiarity with some of the more serious diabetes-related complications can also be lifesaving if properly diagnosed and treated earlier.

Author Contributions

Conceptualization, L.L. and K.L.V.; methodology, L.L., K.L.V., A.C.C. and J.H.S.; software, none.; validation, none.; formal analysis, L.L., K.L.V., A.C.C. and J.H.S.; investigation, L.L., K.L.V. and A.C.C.; resources, L.L., K.L.V., A.C.C. and J.H.S.; writing—original draft preparation, L.L., K.L.V. and A.C.C.; writing—review and editing, L.L., K.L.V., A.C.C. and J.H.S.; visualization, J.H.S.; supervision, J.H.S.; project administration, none; funding acquisition, none. All authors have read and agreed to the published version of the manuscript.

Funding

This research and manuscript received no external funding.

Conflicts of Interest

LL, KV, AC have no relevant disclosures or conflicts of interest. JHS has served as a consultant to Abbott, Bayer, Eli Lilly, Madrigal, NovoNordisk and Sanofi. He is an associate editor of Diabetology.

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Figure 1. Hyperpigmentation and skin thickening on the neck of a patient with T2DM (original photo from authors).
Figure 1. Hyperpigmentation and skin thickening on the neck of a patient with T2DM (original photo from authors).
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Figure 2. Pedunculated outgrowths on the lateral neck (original photo from authors).
Figure 2. Pedunculated outgrowths on the lateral neck (original photo from authors).
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Figure 3. Yellow, well-demarcated, and soft plaques located on the bilateral medial canthi of the eyes (original photo from authors).
Figure 3. Yellow, well-demarcated, and soft plaques located on the bilateral medial canthi of the eyes (original photo from authors).
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Figure 4. Brown-red patches of diabetic dermopathy on the pretibial area (not an original picture from the authors) [30].
Figure 4. Brown-red patches of diabetic dermopathy on the pretibial area (not an original picture from the authors) [30].
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Figure 5. Early well-demarcated, atrophic lesions presenting on the pretibial area (original photo from authors).
Figure 5. Early well-demarcated, atrophic lesions presenting on the pretibial area (original photo from authors).
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Figure 6. Acral distribution of depigmented patches characteristic of vitiligo (original photo from authors).
Figure 6. Acral distribution of depigmented patches characteristic of vitiligo (original photo from authors).
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Figure 7. Newly formed clusters of yellow lipid-rich papules on a patient’s back (original photo from authors).
Figure 7. Newly formed clusters of yellow lipid-rich papules on a patient’s back (original photo from authors).
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Figure 8. Scar tissue from repeated finger stick glucose measurements (original photo from authors).
Figure 8. Scar tissue from repeated finger stick glucose measurements (original photo from authors).
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Figure 9. Lipohypertrophy from repeated insulin injections into the same area—present on the left and less on the right periumbilical areas (not an original picture from the authors) [72].
Figure 9. Lipohypertrophy from repeated insulin injections into the same area—present on the left and less on the right periumbilical areas (not an original picture from the authors) [72].
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MDPI and ACS Style

Ly, L.; Vo, K.L.; Cruel, A.C.; Shubrook, J.H. Dermatological Manifestations of Diabetes Mellitus and Its Complications. Diabetology 2025, 6, 18. https://doi.org/10.3390/diabetology6030018

AMA Style

Ly L, Vo KL, Cruel AC, Shubrook JH. Dermatological Manifestations of Diabetes Mellitus and Its Complications. Diabetology. 2025; 6(3):18. https://doi.org/10.3390/diabetology6030018

Chicago/Turabian Style

Ly, Liana, Karen L. Vo, Audrey C. Cruel, and Jay H. Shubrook. 2025. "Dermatological Manifestations of Diabetes Mellitus and Its Complications" Diabetology 6, no. 3: 18. https://doi.org/10.3390/diabetology6030018

APA Style

Ly, L., Vo, K. L., Cruel, A. C., & Shubrook, J. H. (2025). Dermatological Manifestations of Diabetes Mellitus and Its Complications. Diabetology, 6(3), 18. https://doi.org/10.3390/diabetology6030018

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