Necrobiosis lipodica (NL) is a recognized feature of diabetes affecting 0.3–1.2% of patients (1,2). It presents with elevated, erythematous lesions (usually on the shins), which typically become atrophic in the center over time. It is most commonly seen in patients with type 1 diabetes, but 7–30% of diabetic patients with NL have type 2 diabetes (1–3). This gives a prevalence of NL of 6.5% in patients with type 1 diabetes and 0.4% in patients with type 2 diabetes. Numerous underlying mechanisms have been proposed, including vascular dysfunction, autoimmunity, and genetic factors (4).
Maturity-onset diabetes of the young (MODY) is a subtype of non-insulin-dependent diabetes characterized by a young age of onset (usually before 25 years), autosomal dominant inheritance, and β-cell dysfunction. Mutations in five genes have been found to cause MODY: glucokinase, hepatocyte nuclear factor (HNF)-1α, HNF-4α, HNF-1β, and insulin promoter factor-1 (5). Two family members from a Chinese family with an HNF-1α mutation have been described with diabetes and NL (6). There have been no studies looking at the prevalence and course of NL in MODY.
We reviewed the records of 178 patients from 108 families referred to Exeter fitting the clinical criteria for MODY (diagnosis <25 years and three-generation history of diabetes with autosomal dominant inheritance). If evidence of a rash was noted, further details were collected from the patient and clinical records.
Five patients (three female) from five families had a rash typical of NL (confirmed on biopsy in one patient), giving a prevalence of 2.8%. The mean age of onset of NL was 19 years (range 15–25 years). Onset varied between 3 years before and 5 years after diagnosis of diabetes. The diagnosis of NL led directly to the diagnosis of diabetes in two patients. Patients had good glycemic control, and no other diabetic complications were present at diagnosis of NL. In two patients the rash resolved within 1 year, whereas there has been no improvement for the other three patients (17–43 years after diagnosis). Mutations in the HNF-1α gene have been found by direct sequencing in three patients (P291fsinsC, R159Q, and R54X), one patient declined genetic testing, and in the fifth patient direct sequencing of the full coding region and minimal promoter of the HNF-1α and HNF-4α genes has failed to identify a mutation.
We have shown that NL is a feature of MODY in 2.8% of patients, a prevalence lower than that seen in type 1 diabetes (6.5%) and higher than that found in type 2 diabetes (0.4%) (1–4). This higher prevalence of NL in MODY compared with type 2 diabetes may be caused by selection bias in a well-characterized group.
The MODY patients described here developed NL early in their disease course, often before diagnosis of diabetes; their glycemic control was good, and other diabetic complications were not present. This is in contrast with other reports that have suggested an association with microvascular complications (7,8). The finding of NL in this monogenic form of diabetes makes a specific etiology related to a type of diabetes, such as autoimmunity, unlikely.
We conclude that NL is a feature of diabetes due to MODY. If NL is found in a young nonobese diabetic patient, a diagnosis of MODY as well as type 1 diabetes should be considered, especially in the presence of a family history.
Article Information
The work in Exeter on MODY was funded by Diabetes UK. Paul Lambert is funded by a Diabetes UK Clinical Training Fellowship.
We thank our patients for their support with our research.
References
Address correspondence requests to Andrew T. Hattersley, Department of Diabetes and Vascular Medicine, Barrack Rd., Exeter, EX2 5AX, Devon, U.K. E-mail: [email protected].
