Neurogenic Inflammation in Diabetes

• Induration size as a response to intracutaneous Candida albicans. [ Time Frame: 24 hours after injection. ] [ Designated as safety issue: No ]
• Induration size as a response to intracutaneous Candida albicans. [ Time Frame: 48 hours after injection. ] [ Designated as safety issue: No ]
• Induration size as a response to intracutaneous Candida albicans. [ Time Frame: 72 hours after injection. ] [ Designated as safety issue: No ]

• Temperature at the injection site of the highest concentration of Candida albicans antigen on the foot, compared to the same location on the contralateral foot. [ Time Frame: 24, 48 and 72 hours after injection. ] [ Designated as safety issue: No ]
• Nature of the induration that appears as a response to intracutaneous Candida albicans evaluated by microscopy of a skin biopsy taken at the injection site of the highest concentration of Candida albicans on the foot. [ Time Frame: 72 hours after injection. ] [ Designated as safety issue: No ]

Polyneuropathy is a complication of diabetes mellitus which leads to decreased sensation in arms and legs. This in turn can lead to the development of (infected) foot ulcers. Charcot's disease can also be a consequence of polyneuropathy. Patients with Charcot's disease suddenly develop a red, warm and swollen foot, like an infection. Charcot's disease leads to foot fractures. After these fractures have healed, the shape of the foot can be dramatically altered. This altered shape of the foot increases the risk of developing foot ulcers. Nerves are important in regulating the inflammatory response. This study aims to investigate whether the inflammatory response is different in patients with polyneuropathy with and without a history of Charcot's disease.

Community (healthy controls), primary care facilities (patients with diabetes without polyneuropathy), secondary care facilities (patients with polyneuropathy, patients with a history of Charcot's disease).

• Diabetes Mellitus
• Polyneuropathies
• Arthropathy, Neurogenic

• Other: Intracutaneous injection of Candida albicans antigen.
  Intracutaneous injection of 0.05 ml of four different concentrations of Candida albicans antigen on both the arm and foot.
• Procedure: Punch skin biopsy
  Biopsy will be taken at the site of injection of the highest concentration of Candida albicans on the foot.
• Other: Temperature measurement.
  Temperature measurement at the site of injection of the highest concentration of Candida albicans antigen on the foot and the same location on the contralateral foot using an infrared thermometer.

• Healthy controls
  Interventions:

  • Other: Intracutaneous injection of Candida albicans antigen.
  • Procedure: Punch skin biopsy
  • Other: Temperature measurement.
• Diabetes
  Patients with diabetes mellitus without polyneuropathy.
  Interventions:

  • Other: Intracutaneous injection of Candida albicans antigen.
  • Procedure: Punch skin biopsy
  • Other: Temperature measurement.
• Polyneuropathy
  Patients with diabetes and polyneuropathy.
  Interventions:

  • Other: Intracutaneous injection of Candida albicans antigen.
  • Procedure: Punch skin biopsy
  • Other: Temperature measurement.
• Charcot
  Patients with a history of Charcot's disease.
  Interventions:

  • Other: Intracutaneous injection of Candida albicans antigen.
  • Other: Temperature measurement.

Inclusion Criteria:

• Patients with type 2 diabetes with and without polyneuropathy.
• Patients with type 2 diabetes with a history of Charcot's disease.
• Healthy controls.
• Signed informed consent.

Exclusion Criteria:

• Peripheral arterial disease: toe pressure < 70 mm Hg and/or transcutaneous oxygen tension < 40 mm Hg and/or claudication.
• Renal insufficiency: MDRD creatinin clearance < 30 ml/min.
• Systemic disease such as vasculitis or rheumatoid arthritis.
• Malignancy.
• (Diabetic) foot ulcer.
• Gout.
• Bacterial infection of an extremity.
• Skin condition of the dorsal aspect of the foot or the medial side of the upper arm.
• Bleeding disorder such as hemophilia.
• Use of medication for asthma.
• Impaired immunity such as in HIV/AIDS.
• Capillary blood glucose < 3 mmol/l or > 20 mmol/l at the time of the study.
• Peripheral oedema.
• Vaccination in the two months prior to study inclusion.
• Chemotherapy or radiation therapy in the twelve months prior to study inclusion.
• Surgery in the two months prior to study inclusion.
• Previous adverse reaction to Candida albicans antigen.
• Acute infection at the time of the study or in the month prior to study inclusion.
• Transfusion in the two months prior to study inclusion.
• Use of immunosuppressants in the two months prior to study inclusion.
• Pregnancy or breastfeeding.