Sage Journals: Discover world-class research

Abstract

Objectives

To measure the rate of Demodex folliculorum mite infestation in patients with type 2 diabetes mellitus and to investigate if it was related to blood glucose control.

Methods

Patients with type 2 diabetes were classified according to their glycosylated haemoglobin (HbA_1c) level into two groups: a well controlled blood glucose group (HbA_1c≤ 7%) and a poorly controlled blood glucose group (HbA_1c> 7%). A standardized skin surface biopsy method was used to determine if the patients had D. folliculorum infestation (>5 mites/cm² of skin).

Results

A total of 69 patients (38 female) were enrolled in the study. Seventeen (24.6%) patients had D. folliculorum infestation. There were no significant differences in age, sex or body mass index between patients with and without D. folliculorum infestations. A significantly higher proportion of patients with poor blood glucose control had D. folliculorum infestation compared with patients with well controlled blood glucose.

Conclusions

These current findings suggest that poor blood glucose regulation increases the susceptibility to D. folliculorum mite infestation in patients with type 2 diabetes.

Keywords

Diabetes mellitus blood glucose regulation

Introduction

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycaemia due to defects in insulin secretion, insulin action, or a combination of both of these metabolic disturbances.¹ Infections occur frequently in patients with diabetes mellitus and their presence can trigger acute metabolic complications.² The long-term complications of diabetes mellitus have negative effects on both the cellular and humoral immune systems. For example, the chemotactic function of polymorphonuclear leucocytes is impaired in patients with diabetes.³ Several abnormalities might contribute to the enhanced susceptibility and severity of infections in patients with diabetes: for example, reduced mastocyte function, lower neutrophil chemotactic activity, poor leukocyte–endothelial cell interactions and reduced leucocyte numbers in inflammatory lesions, low oxidant molecule production, decreased lymph node retention capacity and reduced cytokine release.^4–7

Demodex is a tiny spindle-shaped mite 0.3–0.4 mm long that lives on mammals. Although there are numerous species of Demodex, only Demodex folliculorum and D. brevis live on the hair follicles and pilosebaceous glands of humans. Demodex mites most frequently colonize the eyelids, forehead, nose, nasolabial folds, cheek and chin, but they can also be found anywhere on the skin. Although most people are colonized by Demodex mites, they rarely cause clinical symptoms. Demodex mite infestation is associated with rosacea, pityriasis folliculorum, acne vulgaris and blepharitis.^8–11 The presence of D. folliculorum infestation is associated with immune suppression and has a higher prevalence in patients with chronic renal failure, diabetes mellitus and HIV. It may cause skin conditions, including pruritis and itching, in patients with type 2 diabetes mellitus.^12–15

To our knowledge, there have not been any reports describing the relationship between blood glucose control in patients with type 2 diabetes mellitus and the presence of D. folliculorum mites. The aim of the current study was to investigate the effect of blood glucose control on the existence of opportunistic D. folliculorum mites in patients with type 2 diabetes mellitus.

Patients and methods

Patient population

Patients diagnosed with type 2 diabetes mellitus were enrolled sequentially from the Outpatient Clinic of the Department of Endocrinology and Metabolism, Medical Faculty, Mustafa Kemal University, Hatay, Turkey between January 2012 and December 2012. Type 2 diabetes mellitus was diagnosed by demonstrating any one of the following criteria: (i) fasting plasma glucose level ≥7.0 mmol/l (126 mg/dl); (ii) an oral glucose tolerance test showing a plasma glucose level ≥11.1 mmol/l (200 mg/dl) at 2 h after a 75 g oral glucose load; (iii) symptoms of hyperglycaemia such as polyuria, polydipsia and polyphagia in conjunction with a random plasma glucose level ≥11.1 mmol/l (200 mg/dl).¹ The patients were further classified according to their glycosylated haemoglobin (HbA_1c) level into two groups: a well controlled blood glucose group, HbA_1c ≤ 7% and a poorly controlled blood glucose group, HbA_1c > 7%.^1,16

The exclusion criteria for both groups of patients with type 2 diabetes were as follows: age <18 years; dermatological disease on the face (such as herpes infection, impetigo, perioral dermatitis, seborrhoeic dermatitis, lupus erythematous); pregnancy; lactation; systemic diseases (malignancy, chronic liver and renal disease); radiotherapy; chemotherapy; topical acaricidal usage; and use of oral or topical antibiotics in the previous month.

The study was approved by the Ethics Committee of Mustafa Kemal University Medical School, Hatay, Turkey (registration number: MKU-2012) and written informed consent was obtained from all patients. The study procedures complied with the current laws of the Republic of Turkey and the Declaration of Helsinki.

Laboratory measurements

Blood samples were collected after a 12-h fast from the ulnar vein of each patient for the analysis of fasting plasma glucose and whole blood HbA_1c levels. The blood was anticoagulated with ethylenediaminetetra-acetic acid to produce plasma. All of the biochemical analyses were completed on the same day as the blood collection. Fasting plasma glucose levels (ARCHITECT c8000 Analyser; Abbott Diagnostics, Lake Forest, IL, USA) and whole blood HbA_1c levels (VARIANT II System; Bio-Rad, Hercules, CA, USA) were determined routinely according to the manufacturers’ instructions. Body mass index (BMI) was determined using the ratio of weight (kg) to height squared (m²).

Analysis of D. folliculorum mite infestation

The presence of D. folliculorum mites was investigated in all patients using the standardized skin surface biopsy (SSSB) technique for measuring the density of Demodex mites.¹⁷ In this method, clinical samples were taken using cyanoacrylate-containing glue. Before taking the skin samples, the selected skin regions (nose, chin, left cheek, right cheek and forehead) were cleaned with alcohol to remove any creams and lotions and the areas were allowed to dry. A 1 cm² circle was drawn on one side of a glass slide with an appropriate pen and 1 ml of cyanoacrylate-containing glue was added to the other side of the glass slide. The adhesive-containing side of the glass slide was pressed against the skin to be sampled and left for 1 min. The slide was removed carefully from the skin at the end of this period. The slides were mounted using Hoyer’s solution¹⁸ (1 ml) and the density of D. folliculorum mites was evaluated using a light microscope (Olympus CH20; Olympus Optical, Tokyo, Japan) at magnifications of × 40 and × 100. The identification of >5 mites/cm² of skin was classified as a D. folliculorum mite infestation.

Statistical analyses

All statistical analyses were performed using the SPSS® software package, version 13.0 (SPSS Inc., Chicago, IL, USA) for Windows®. Continuous variables were analysed using the Kolmogorov–Smirnov test in terms of their normal distribution. Relationships between nominal variables were calculated using χ²-test and Fisher's Exact test. For continuous variables, Student’s t-test and Mann–Whitney U-test were used. A P-value < 0.05 was considered statistically significant.

Results

A total of 69 patients (mean ± SD age 56.6 ± 11.0 years; range 25–79 years) with type 2 diabetes were enrolled in the study. Of these, 38 (55.1%) were female and 31 (44.9%) were male. Of the 69 patients, 27 patients had well controlled blood glucose (HbA_1c≤ 7%) and 42 patients had poorly controlled blood glucose (HbA_1c> 7%). Using the SSSB technique, D. folliculorum mite infestations were found in 17 (24.6%) patients.Demodex folliculorum mite infestations were significantly more frequent in female than male patients (13 versus four, respectively; P = 0.043). There were no significant differences in age and BMI between patients with D. folliculorum mite infestation and those without D. folliculorum mite infestation (Table 1). Patients with D. folliculorum mite infestation had significantly higher HbA_1c levels compared with patients without D. folliculorum mite infestation (P = 0.035).

Table 1.

The relationship between the presence of a Demodex folliculorum infestation^a and the age, body mass index (BMI) and glycosylated haemoglobin (HbA_1c) level in patients with type 2 diabetes mellitus (n = 69).

Characteristic	D. folliculorum status	n	Mean ± SD	Range		Statistical significance^b
Characteristic	D. folliculorum status	n	Mean ± SD	Minimum	Maximum	Statistical significance^b
Age, years	Positive	17	54.2 ± 9.9	25	65	NS
Age, years	Negative	52	57.4 ± 11.3	27	79	NS
BMI, kg/m²	Positive	17	31.61 ± 5.55	21.78	39.26	NS
BMI, kg/m²	Negative	52	30.89 ± 5.38	20.07	43.85	NS
HbA_1c, %	Positive	17	9.54 ± 3.44	6.10	19.20	P = 0.035
HbA_1c, %	Negative	52	7.82 ± 1.60	5.40	12.20	P = 0.035

D. folliculorum infestation (i.e. positive) was classified as >5 mites/cm² of skin.

Mann–Whitney U-test.

NS, no statistically significant difference (P ≥ 0.05).

When patients were categorized according to their blood glucose control (HbA_1c≤ 7% versus HbA_1c > 7%), there were no significant differences in age, sex and BMI between the two groups (Table 2). Patients with poor blood glucose control (HbA_1c> 7%) had a significantly higher fasting plasma glucose concentration compared with patients who had well controlled blood glucose (HbA_1c ≤ 7%) (P = 0.047). A significantly higher proportion of patients with poor blood glucose control (HbA_1c> 7%) had D. folliculorum mite infestation compared with patients with well controlled blood glucose (HbA_1c ≤ 7%) (P = 0.038).

Table 2.

Analysis of the relationship between the presence of a Demodex folliculorum infestation^a, demographic characteristics and blood glucose regulation in patients with type 2 diabetes mellitus (n = 69).

	Blood glucose regulation
	Well controlled (HbA_1c ≤ 7%) n = 27	Poorly controlled (HbA_1c > 7%) n = 42	Statistical significance
D. folliculorum status, n (%)
Positive, n = 17	3 (17.6%)	14 (82.4%)	P = 0.038^b
Negative, n = 52	24 (46.2%)	28 (53.8%)
Sex, n (%)
Male, n = 31	10 (32.3%)	21 (67.7%)	NS^c
Female, n = 38	17 (44.7%)	21 (55.3%)
Age, years	56.70 ± 11.88	56.57 ± 10.47	NS^d
FPG, mg/dl	204.37 ± 55.11	241.66 ± 84.81	P = 0.047^d
FPG, mmol/l	11.32 ± 3.05	13.37 ± 4.66
BMI, kg/m²	31.77 ± 5.69	30.62 ± 5.22	NS^d

Data presented as mean ± SD unless otherwise stated.

D. folliculorum infestation (i.e. positive) was classified as >5 mites/cm² of skin.

Fisher's exact test.

χ²-Test.

Student's t-test.

HbA_1c, glycosylated haemoglobin; FPG, fasting plasma glucose; BMI, body mass index; NS, no statistically significant difference (P ≥ 0.05).

Discussion

The current study demonstrated that 24.6% of patients with type 2 diabetes had a D. folliculorum mite infestation as defined as >5 mites/cm² of skin and mite infestation was significantly more common in women than men. This current study also demonstrated that a significantly higher proportion of patients with poorly controlled blood glucose levels had D. folliculorum mite infestation compared with patients with well controlled blood glucose levels.

Demodex folliculorum is a saprophytic mite located at the human pilosebaceous unit with a preference for facial skin and eyelashes. Infestation is usually asymptomatic, but suppurative or granulomatous inflammation may be seen with a high mite density. Dermatological disorders including rosacea, pityriasis folliculorum and blepharitis have been attributed to Demodex parasite infestation.^8,9,11,12,19 It seems likely that there is usually a control mechanism limiting the number of follicle mites, but that local and systemic factors may cause an environment that is preferable to their growth. Immunosuppression may be related to an increase in the density of D. folliculorum, and demodicidosis has been identified in children with leukaemia who are taking chemotherapy.²⁰ Hypotheses suggest that either an immunological deficiency resulting in an increase in the number of Demodex mites or an abnormal immunological reaction of the skin to the parasites causes the dermatological lesions.¹³ An increased incidence of Demodex mites was found in subjects with human leucocyte antigen (HLA)-Cw2 and HLA-Cw4 alleles, which was related to a decrease in natural killer cells.²¹ Immunosuppression may result in an increase in the mite numbers, favouring an inflammatory reaction, or it may cause an impaired immunological response in the skin to the mite infestation.

Data regarding the prevalence of Demodex mite infestations in patients with diabetes are rare. In addition, there are no published data regarding the prevalence of Demodex mite infestations in patients with diabetes stratified according to the quality of their blood glucose control. A study of cheek biopsies from patients with diabetes found a significantly higher mean mite density and a greater mean mite size compared with cheek biopsies from control subjects.¹⁵ A study that evaluated the prevalence of Demodex mites on the eyelashes of 256 subjects also reported that the mites were more common in patients with diabetes mellitus.²²

Many studies that have investigated the association between Demodex infestation and acquired immunodeficiency syndrome and cancer chemotherapy, and studies that have reported the higher prevalence of demodicidosis in potentially immunosuppressed subjects such as pregnant women and haemodialysis patients, have proposed that immunological deficiency may cause the overgrowth of the Demodex mites.^20,23–25 Patients with diabetes mellitus have an increased risk for infections, but the exact pathophysiology of their immunocompromised state remains unknown.

Demodex infestation results in disruption of the skin barrier and the mites are responsible for epithelial erosion.²⁶ However, an increasing number of case reports and epidemiological studies show that in certain conditions the number of follicle mites increases, and this increase in mite numbers probably causes or contributes to the development of cutaneous disorders, such as granulomatous rosacea, bald papulopustular dermatosis, pustular folliculitis, blepharitis and spinulosis of the face.^27–30

Although many cases are asymptomatic, the clinical features of demodicosis can include itching, vascular (ﬂushes, erythema and telangiectasia) and inﬂammatory symptoms (folliculitis, papules and pustules) of the skin.^26–29 For example, papulopustular rosacea disease is a multifactorial skin disease involving infestation by D. folliculorum.^26–29 In some patients, the symptom of itching may be the only symptom experienced. Treatment with acaricidal agents can resolve the cutaneous symptoms of demodicosis and lead to wound healing.³⁰ Acaricidal creams and oral isotretinoin have been used to treat different cutaneous demodicosis lesions.^26–30However, there are no clinical data about the use of acaricidal agents in patients with diabetes mellitus who have the symptoms of itching without any obvious skin disorders. Based on these current findings, we would recommend the use of acaricidal creams in patients with diabetes, particularly those with poorly controlled blood glucose levels, who have clinical findings suggestive of a Demodex mite infestation.

In conclusion, type 2 diabetes is an extremely common metabolic disorder, the only clinical symptom of which in some patients is itching or pruritis, which could be caused by an undiagnosed D. folliculorum mite infestation of the skin. The findings of this current study suggest that the prevalence of D. folliculorum mite infestation is high in patients with type 2 diabetes and that those patients with poorly controlled blood glucose levels are particularly susceptible. Therefore, in addition to considering the risk of microvascular and macrovascular complications associated with poor blood glucose control, physicians may also need to consider the possibility of the presence of parasitic infestations such as D. folliculorum. Further research is required to determine the clinical implications of Demodex mite infestations in patients with type 2 diabetes, particularly those with poor blood glucose control, and how these infestations can be best treated.

Footnotes

Declaration of conflicting interest

The authors declare that there are no conflicts of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

References

American Diabetes Association. Diagnosis and classiﬁcation of diabetes mellitus. Diabetes Care 2013; 36(Suppl 1): S67–S74.

Gupta

Koirala

Khardori

. Infections in diabetes mellitus and hyperglycemia. Infect Dis Clin North Am 2007; 21: 617–638.

Delamaire

Maugendre

Moreno

. Impaired leucocyte functions in diabetic patients. Diabet Med 1997; 14: 29–34.

Mowat

Baum

. Chemotaxis of polymorphonuclear leukocytes from patients with diabetes mellitus. N Engl J Med 1971; 284: 621–627.

Bagdade

Nielson

Bulger

. Reversible abnormalities in phagocytic function in poorly controlled diabetic patients. Am J Med Sci 1972; 263: 451–456.

Sannomiya

Oliveira

Fortes

. Aminoguanidine and the prevention of leukocyte dysfunction in diabetes mellitus: a direct vital microscopic study. Br J Pharmacol 1997; 122: 894–898.

Moriguchi

Sannomiya

Lara

. Lymphatic system changes in diabetes mellitus: role of insulin and hyperglycemia. Diabetes Metab Res Rev 2005; 21: 150–157.

Yamashita

LSFF

Cariello

Geha

NMA

. Demodex folliculorum on the eyelash follicule of diabetic patients. Arq Bras Oftalmol 2011; 74: 422–424.

Rufli

Mumcuoglu

. The hair follicle mites Demodex folliculorum and Demodex brevis: biology and medical importance. A review. Dermatologica 1981; 162: 1–11.

10.

Yula

Aycan-Kaya

Atambay

. What is the importance of Demodex folliculorum and D. brevis in the etiology of blepharitis? Turkiye Klinikleri J Med Sci 2013; 33: 420–424. [in Turkish, English abstract].

11.

Erbağci

Ozgöztaşi

. The significance of Demodex folliculorum density in rosacea. Int J Dermatol 1998; 37: 421–425.

12.

Barrio

Lecona

Hernanz

. Rosacea-like demodicosis in an HIV-positive child. Dermatology 1996; 192: 143–145.

13.

Patrizi

Neri

Chieregato

. Demodicidosis in immunocompetent young children: report of eight cases. Dermatology 1997; 195: 239–242.

14.

Ozçelik

Sümer

Değerli

. The incidence of Demodex folliculorum in patients with chronic kidney deficiency. Turkiye Parazitol Derg 2007; 31: 66–68. [in Turkish, English abstract].

15.

Akdeniz

Bahceci

Tuzcu

. Is Demodex folliculorum larger in diabetic patients? J Eur Acad Dermatol Venereol 2002; 16: 539–541.

16.

Alberti

Zimmet

. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998; 15: 539–553.

17.

Aşkin

Seçkin

. Comparison of the two techniques for measurement of the density of Demodex folliculorum: standardized skin surface biopsy and direct microscopic examination. Br J Dermatol 2010; 162: 1124–1126.

18.

Anderson

. Hoyer’s solution as a rapid permanent mounting medium for bryophytes. Bryologist 1954; 57: 242–244.

19.

Kemal

Sümer

Toker

. The prevalence of Demodex folliculorum in blepharitis patients and the normal population. Ophthalmic Epidemiol 2005; 12: 287–290.

20.

Damian

Rogers

. Demodex infestation in a child with leukaemia: treatment with ivermectin and permethrin. Int J Dermatol 2003; 42: 724–726.

21.

Mumcuoglu

Akilov

. The role of HLA A2 and Cw2 in the pathogenesis of human demodicosis. Dermatology 2005; 210: 109–114.

22.

Clifford

Fulk

. Association of diabetes, lash loss, and Staphylococcus aureus with Infestation of eyelids by Demodex folliculorum (Acari: Demodicidae). J Med Entomol 1990; 27: 467–470.

23.

Nara

Katoh

Inoue

. Eosinophilic folliculitis with a Demodex folliculorum infestation successfully treated with ivermectin in a man infected with human immunodeficiency virus. Clin Exp Dermatol 2009; 34: e981–e983.

24.

Aydingöz

Dervent

Güney

. Demodex folliculorum in pregnancy. Int J Dermatol 2000; 39: 743–745.

25.

Yagdiran Düzgün

Aytekin

. Comparison of Demodex folliculorum density in haemodialysis patients with a control group. J Eur Acad Dermatol Venereol 2007; 21: 480–483.

26.

Forton

. Papulopustular rosacea, skin immunity and Demodex: pityriasis folliculorum as a missing link. J Eur Acad Dermatol Venereol 2012; 26: 19–28.

27.

Forton

. Demodex-associated folliculitis. Am J Dermatopathol 1998; 20: 536–537.

28.

Jansen

Kastner

Kreuter

. Rosacea-like demodicidosis associated with acquired immunodeﬁciency syndrome. Br J Dermatol 2001; 144: 139–142.

29.

Fariña

Requena

Sarasa

. Spinulosis of the face as a manifestation of demodicidosis. Br J Dermatol 1998; 138: 901–903.

30.

Zhao

Guo

Xun

. Sociodemographic characteristics and risk factor analysis of Demodex infestation (Acari: Demodicidae). J Zhejiang Univ Sci B 2011; 12: 998–1007.

The effect of blood glucose regulation on the presence of opportunistic Demodex folliculorum mites in patients with type 2 diabetes mellitus

Abstract

Objectives

Methods

Results

Conclusions

Keywords

Introduction

Patients and methods

Patient population

Laboratory measurements

Analysis of D. folliculorum mite infestation

Statistical analyses

Results

Discussion

Footnotes

Declaration of conflicting interest

Funding

References