Although Huntington’s disease (HD) is primarily considered a rare neurodegenerative disorder, it has been linked to glucose metabolism alterations and diabetes, as has been described in other neuro syndromes such as Friedreich’s ataxia or Alzheimer’s disease. This review surveys the existing literature on HD and its potential relationship with diabetes, glucose metabolism-related indexes and pancreas morphology, in humans and in animal’s models. The information is reported in chronological sequence. That is, studies performed before and after the identification of the genetic defect underlying HD (CAG: encoding glutamine ≥36 repeats located in exon 1 of the HTT gene) and with the development and evolution of HD animal models. The aim of the review is to evaluate whether impaired glucose metabolism contributes to the development of HD, and whether optimized glycemic control may ameliorate the symptoms of HD.

Scope Huntington's disease (HD) is a rare progressive neurodegenerative disorder of genetic origin, with no definitive treatment. Unintentional weight loss (UWL) is a clinical feature of symptomatic HD subjects. To prevent UWL, a customized HD diet is designed and its impact on plasma miRNA HD footprint and neurological parameters is examined. Methods and results Eleven participants are included, BMI ≤ 18 kg m–2 or UWL of 5% in 6 months or 10% in a year. Diet design is based on nutritional surveys and interviews of participants and caregivers and on published literature review. Twelve‐month dietary intervention, with follow‐up every 3 months, induces high diet adherence, which manages to curb UWL in all participants (73% gained weight). Noticeable increases in fat mass and leptin levels are obtained. The results also show significant decrease in the expression of 19 miRNAs, which are previously reported to be upregulated in HD‐patients versus healthy controls: revealing hsa‐miR‐338‐3p, hsa‐miR‐128‐3p, hsa‐miR‐23a‐3p, and hsa‐miR‐24‐3p as potential HD‐biomarkers. The diminished expression of hsa‐miR‐100‐5p reflects the general maintenance of the functional status. Cognitive status is improved in six of 11 participants, while only three present better motor‐score values. Conclusion A customized HD‐diet prevents UWL and modified miRNAs HD‐footprint. The normalization of miRNA values suggests its potentially use as HD‐biomarkers.

Mol. Nutr. Food Res. 2018, 62, https://doi.org/10.1002/mnfr.201800619 DOI: https://doi.org/10.1002/mnfr.201800619 In 11 genetic‐diagnosed Huntington's disease patients with symptoms, one year of customized dietary intervention induced A) high diet adherence, which managed to curb unintentional weight loss in all participants; B) a significantly modified miRNA footprint of the disorder, leading the system to normalization; and C) general maintenance of neurological parameters. Further details can be found in article number https://doi.org/10.1002/mnfr.201800619 by Nieves González and co‐workers.