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Introduction: Lipohypertrophies (LHs) due to incorrect insulin injection techniques have been described in the literature for decades. Their rate averages 38%, but this is still controversial because of the vast range reported by different publications, most of which fail to describe the selected detection protocol and therefore are not entirely reliable. We still need to identify the real LH rate, and only consistently using a standardized method in a large cohort of insulin-treated (IT) patients make this possible. Methods: Our group performed thorough clinical skin examinations on patients suffering from type 2 diabetes mellitus (T2DM): 1247 IT T2DM outpatients were examined according to a standardized protocol, previously published elsewhere, as well as an ultrasound scan of the same skin areas to assess the degree of concordance between the two methods and to evaluate the demographic, clinical, and behavioral risk factors (RF) as well as metabolic consequences of identified LHs. Results: The concordance between the two methods was 99%. Identified risk factors for LHs were needle reuse, failure to rotate injection sites, and ice-cold insulin injections. High HbA1c values, wide glycemic variability, and longstanding proneness to hypoglycemia with a high rate of ongoing hypoglycemic events proved to be significantly associated with LHs, too; the same applied to cardiovascular and renal complications as well as to living alone and being retired. Conclusions: Based on a strict well-structured methodology, our data confirmed what has already been reported in the literature on factors leading to, or associated with, LHs and, for the first time in adults, indicated cryotrauma from ice-cold insulin injections and specific social conditions as factors facilitating LH occurrence. HCPs should therefore plan a yearly clinical examination of all injection sites to improve patient quality of life through better glucose control and a reduced rate of hypoglycemic events. Trial Registration: Trial registration no. 127-11.01.2019, approved by the Scientific and Ethics Committee of Campania University "Luigi Vanvitelli," Naples, Italy. [ABSTRACT FROM AUTHOR]