Liver adenomatosis in patients with hepatocyte nuclear factor-1 alpha maturity onset diabetes of the young (HNF1A-MODY): Clinical, radiological and pathological characteristics in a French series.

BACKGROUND: Liver adenomatosis (LA) is a rare disease resulting from biallelic inactivation of the hepatocyte nuclear factor-1 alpha (HNF1A) gene, which induces the proliferation of adenoma cells in liver parenchyma. Liver adenomatosis has only been documented in case reports from patients carrying a HNF1A germline mutation. We have evaluated the frequency of LA among a large cohort of patients with HNF1A-maturity onset diabetes of the young (MODY), previously termed "MODY3," and herein describe its clinical, radiological, and pathological characteristics. METHODS: In all, 137 HNF1A-MODY subjects from 74 families were screened by liver ultrasonography in 13 centers, and 15 additional cases of LA were later included in the series. Liver adenomatosis was confirmed by liver computed tomography, magnetic resonance imaging (MRI), and/or histopathology. RESULTS: Among 137 carriers of an HNF1A mutation, 9 patients (6.5%) from seven families were diagnosed with LA. Diabetes mellitus was present in 87.5% of patients with LA. In 25% of patients, LA was diagnosed due to intra-abdominal or intratumoral bleeding. Liver biochemistry was near normal in all patients. Liver imaging showed adenomas of various sizes and numbers. On MRI, most nodules had the radiological characteristics of steatotic adenomas. Histopathological confirmation of LA was available in 13 cases, and these adenomas were mostly steatotic. Surgery was initially performed in 37.5% of patients, and liver disease progression was observed in 30%. No disease progression was observed in 14 pregnancies. CONCLUSIONS: The frequency of LA in a cohort of screened HNF1A-MODY patients and the high incidence of LA progression and/or hemorrhage warrants systematic screening for liver adenomatosis in HNF1A-MODY families.

Potential Insulin Underdelivery from Prefilled and Reusable Insulin Pens in Cases of Premature Needle Withdrawal: A Laboratory Evaluation.

BACKGROUND: Devices for the treatment of diabetes are not always used as recommended in good practice. Our aim was to evaluate potential insulin underdelivery in cases of premature needle withdrawal after injection with insulin pens, which is a commonly observed misuse, especially in young type 1 diabetes patients. MATERIALS AND METHODS: Potential insulin underdelivery was evaluated using five prefilled insulin pens (lispro Kwikpen(®) [Eli Lilly, Indianapolis, IN], aspart Flexpen(®) [Novo Nordisk, Bagsvaerd, Denmark], glulisine Solostar(®) [Sanofi, Paris, France], detemir Flexpen(®) [Novo Nordisk], and glargine Solostar(®) [Sanofi]) and three reusable insulin pens (Humapen(®) Luxura HD with lispro cartridge [Eli Lilly], Novopen(®) Echo with aspart and detemir cartridge [Novo Nordisk], and JuniorSTAR(®) with glulisine and glargine cartridge [Sanofi]) in a laboratory. For each pen and insulin, we simulated premature needle withdrawal 2 and 3 s after an insulin injection of 5 and 10 units, respectively. RESULTS: With prefilled pens, mean potential insulin underdelivery was 0.43±0.30 and 0.44±0.32 units after injection of 5 and 10 units, respectively. With reusable pens, mean potential insulin underdelivery was lower (0.29±0.13 and 0.29±0.12 units after injection of 5 and 10 units, respectively; P<0.001). The results were heterogeneous across pens, ranging from 2.6%/1.6% to 20.2%/8.6% of the selected insulin dose for prefilled/reusable pens, respectively (P<0.001). CONCLUSIONS: Potential insulin underdelivery varies across prefilled and reusable insulin pens but may represent up to one-fifth of the total injected dose. Clinicians should be aware of the potential consequences of premature needle withdrawal and should reinforce insulin injection education.