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      Lipohypertrophy in Elderly Insulin-Treated Patients With Type 2 Diabetes

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          The number of older adults with insulin-treated diabetes mellitus (DM) is steadily increasing worldwide. Errors in the insulin injection technique can lead to skin lipohypertrophy (LH), which is the accumulation of fat cells and fibrin in the subcutaneous tissue. While lipohypertrophic lesions/nodules (LHs) due to incorrect insulin injection techniques are very common, they are often flat and hardly visible and thus require thorough deep palpation examination and ultrasonography (US) for detection. Detection is crucial because such lesions may eventually result in poor diabetes control due to their association with unpredictable insulin release patterns. Skin undergoes fundamental structural changes with aging, possibly increasing the risk for LH. We have therefore investigated the effect of age on the prevalence of LHs and on factors potentially associated with such lesions.


          A total of 1227 insulin-treated outpatients with type 2 DM (T2DM) referred to our diabetes centers were consecutively enrolled in the study. These patients underwent a thorough clinical and US evaluation of the skin at injection sites, as previously described, with up to 95% concordance betweenthe clinical and US screening techniques. Of these 1227 patients, 718 (59%) had LH (LH+) and 509 (41%) were LH-free (LH−). These patients were then assigned to two age class groups (≤ 65 years and > 65 years), and several clinical features, diabetes complication rates, and injection habits were investigated.


          Comparison of the two age subgroups revealed that 396 (48%) and 322 (79%) patients in the younger and older groups, respectively, had LHs ( p < 0.001). Compared to the younger subgroup, the older subgroup displayed a higher LH rate in the abdomen (52.9 vs. 38.3%; p < 0.01) and a lower rate in the arms (25.4 vs. 35.8%; p < 0.05), thighs (26.7 vs. 33.4%; p < 0.05), and buttocks (4.9 vs. 26.2%; p < 0.01). In older subjects, the most relevant parameters were: habit of injecting insulin into LH nodules (56 vs. 47% [younger subjects]; p < 0.01), rate of post-injection leakage of insulin from injection site (drop-leaking rate; 47 vs. 39% [younger subjects]; p < 0.05), and rate of painful injections (5 vs. 16% [younger subjects]; p < 0.001). Multivariate analysis showed a stronger association between LH and poor habits, as well as between several clinical parameters, among which the most relevant were hypoglycemic events and glycemic variability.


          The higher rate of post-injection drop-leaking and pain-free injections might find an explanation in skin changes typically observed in older adults, including lower thickness, vascularity and elasticity, and a more prominent fibrous texture, all of which negatively affect tissue distensibility. Consequently, in addition to the well-known association between aging skin impaired drug absorption rate, aging skin displays a progressively decreasing ability to accommodate large volumes of insulin-containing fluid.


          The strong association between LH rate and hypoglycemic events plus glycemic variability suggests the need (1) to take specific actions to prevent and control the high risk of acute cardiovascular events expected to occur in older subjects in the case of hypoglycemic events, and (2) to identify suitable strategies to fulfill the difficult task of performing effective educational programs specifically targeted to the elderly.

          Trial Registration

          Trial registration number 172–11:12.2019, Scientific and Ethical Committee of Campania University “Luigi Vanvitelli”, Naples, Italy).

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          Most cited references 29

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          Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes.

          Our objective was to assess the frequency of lipohypertrophy (LH) and its relationship to site rotation, needle reuse, glucose variability, hypoglycaemia and use of insulin.
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            A 5-year randomized controlled study of learning, problem solving ability, and quality of life modifications in people with type 2 diabetes managed by group care.

            To study time course changes in knowledge, problem solving ability, and quality of life in patients with type 2 diabetes managed by group compared with individual care and education. We conducted a 5-year randomized controlled clinical trial of continuing systemic education delivered by group versus individual diabetes care in a hospital-based secondary care diabetes unit. There were 120 patients with non-insulin-treated type 2 diabetes enrolled and randomly allocated to group or individual care. Eight did not start and 28 did not complete the study. The main outcome measures were knowledge of diabetes, problem solving ability, quality of life, HbA1c, BMI, and HDL cholesterol. Knowledge of diabetes and problem solving ability improved from year 1 with group care and worsened among control subjects (P<0.001 for both). Quality of life improved from year 2 with group care but worsened with individual care (P<0.001). HbA1c level progressively increased over 5 years among control subjects (+1.7%, 95% CI 1.1-2.2) but not group care patients (+0.1%, -0.5 to 0.4), in whom BMI decreased (-1.4, -2.0 to -0.7) and HDL cholesterol increased (+0.14 mmol/l, 0.07-0.22). Adults with type 2 diabetes can acquire specific knowledge and conscious behaviors if exposed to educational procedures and settings tailored to their needs. Traditional one-to-one care, although delivered according to optimized criteria, is associated with progressive deterioration of knowledge, problem solving ability, and quality of life. Better cognitive and psychosocial results are associated with more favorable clinical outcomes.
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              Age and skin structure and function, a quantitative approach (I): blood flow, pH, thickness, and ultrasound echogenicity.

              The aging process has been studied with fervor recently, given our shifting demographics. Since age's effects are so manifest in skin's appearance, structure, mechanics, and barrier function, it is not surprising that much effort has been placed in research to better understand them. Quantitative measurements permitted by bioengineering have allowed us to objectively and precisely study aging skin. These overviews piece together the immense amounts of information that have emerged from recent technological advances in dermatological research in order to develop a unified understanding of the quantitative effects of age on the skin. We performed a literature on age-related changes in blood flow, pH, skin thickness, and ultrasound imaging data, searching Pub-med, Em-Base, Science Citation Index, and the UCSF dermatological library's collection of books on the topic of aging skin. Despite the many tools and techniques available for quantitative analysis of skin, age studies are often conflicting, especially in the areas of blood flow and skin thickness. Trends indicate that blood flow may decrease with age, especially in sites exposed to the environment. pH apparently varies little until the age of 70, after which it declines. Skin thickness data are difficult to interpret; while the stratum corneum is generally accepted to maintain its thickness during aging, dermal, epidermal, and whole skin thickness changes are controversial. Ultrasound reveals the appearance of a subepidermal low echogenic band that thickens with age, especially in environmentally exposed areas. Some studies also indicate the presence of an echogenic band in the lower dermis which thins with increased age. However, the whole dermis appears to become more echogenic in elderly people. Much remains to be done if we are to reach consensus on the effects of age on skin structure and function. Future studies would be benefited by increased standardization of skin sites tested, methodology, and increased sample size.

                Author and article information

                Diabetes Ther
                Diabetes Ther
                Diabetes Therapy
                Springer Healthcare (Cheshire )
                21 November 2020
                21 November 2020
                January 2021
                : 12
                : 1
                : 107-119
                [1 ]GRID grid.9841.4, ISNI 0000 0001 2200 8888, Department of Internal Medicine, , Campania University “Luigi Vanvitelli”, ; Naples, Italy
                [2 ]Diabetes Unit AID Stabia, Nefrocenter Research and Nyx Start-Up, Naples, Italy
                [3 ]Nutrition, Nefrocenter Research and Nyx Start-Up, Naples, Italy
                [4 ]Diabetes Unit, Italian Association for Diabetes (AID) Napoli, Naples, Italy
                [5 ]Diabetes Unit, AID Benevento, Benevento, Italy
                [6 ]Diabetes Unit, AID Nola, Nola, Italy
                [7 ]Diabetes Unit, AID Stabia, Castellammare di Stabia, Italy
                [8 ]Neuropsicology Unit, Nefrocenter Research Network, Naples, Italy
                [9 ]Diabetes Unit, AID San Cairo, Portici, Italy
                [10 ]Diabetes Unit, AID Cava dè Tirreni, Cava dè Tirreni, Italy
                [11 ]Dialysis Unit, Nefrocenter Research Network, Naples, Italy
                [12 ]GRID grid.18887.3e, ISNI 0000000417581884, Diabetes, Endocrinology and Metabotic Disease, , IRCCS San Raffaele Pisana, ; Rome, Italy
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.

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                © The Author(s) 2021

                Endocrinology & Diabetes

                skin, lipohypertrophy, insulin, diabetes, ageing


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