Our research group has dealt with injection-induced lip hypertrophy (IILH) in insulin-treated subjects for over a decade, focusing on causes and consequences, education, prevention and treatment, comorbidities, and related complications. Stimulated by an excellent Review that recently appeared on the pages of this Journal, we want to contribute insight into IILH. This brief Commentary underlines some key concepts on how to identify, prevent and cure them, pointing out salient aspects derived from our research to provide the scientific community with an as complete as possible overview of evidence-based knowledge and highlight the need for further experimental insights.

Introduction: Patients with Type 1 and Type 2 diabetes mellitus (T1DM and T2DM) are at high risk of developing chronic kidney disease (CKD), i.e., diabetic nephropathy (DN), whose onset and progression are associated with a high morbidity and mortality risk. Early DN prediction is crucial. Presently it relies on albumin excretion rate (AER) and glomerular filtration rate (GFR) assessment. Nevertheless, recent literature reports that DN eventually affects patients with normal AER and GFR values. Therefore, further cost-effective biomarkers of DN onset or fast worsening are needed. Intracellular liver-type fatty acid-binding protein (L-FABP) has been associated with renal tubular-interstitial damage and could help predict and diagnose DN. Methods: we performed a systematic review of the literature to evaluate the performance of urinary excretion of such biomarker (uL-FABP) in predicting and diagnosing DN and its progression in T2DM and T1DM patients. To do so, we evaluated 635 publications on four major scientific databases, 21 of which were suited for inclusion in this review. Results: we selected twenty-one in-extenso publications, 14 reporting a cross-sectional design/arm (nine on T2DM, four on T1DM, and one on both). Ten included a longitudinal design/arm. Cross-sectional studies, primarily conducted in Asian and north-European populations, showed uL-FABP levels to correlate directly with DN severity (micro-, macro-albuminuria, and overt CKD) in T1DM and T2DM, besides being significantly higher than in healthy controls in the case of normoalbuminuria. In addition, longitudinal ones showed baseline uL-FABP to predict DN onset in normoalbuminuric patients with T1DM and DN progression independently of diabetes type. Discussion: the studies analyzed in this review suggest that uL-FABP is a marker of tubular damage detectable before increased albumin excretion and can represent the earliest sign of kidney dysfunction in diabetes. Indeed, it discloses DN onset and often predicts DN severity from start to end-stage renal disease (ESRD) in T2DM and T1DM patients. Currently, uL-FABP can be assessed on a routine basis and, being available as a point-of-care fast test kit, may also become an easy-to-handle diagnostic tool for outpatients. Conclusions: uL-FABP represents a cost-effective and user-friendly biomarker of DN and can even predict DN progression in T2DM and T1DM over time.