Lipohypertrophy in Elderly Insulin-Treated Patients With Type 2 Diabetes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. DISCUSSION: 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. CONCLUSIONS: 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).

Insulin-Induced Skin Lipohypertrophy in Type 2 Diabetes: a Multicenter Regional Survey in Southern Italy.

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.

A randomized, open-label, comparative, crossover trial on preference, efficacy, and safety profiles of lispro insulin u-100 versus concentrated lispro insulin u-200 in patients with type 2 diabetes mellitus: a possible contribution to greater treatment adherence.

BACKGROUND: Several outstanding pharmacological advances making innovative drugs sophisticateddevices available during the last few years. Nevertheless too many patients still disappointingly fail to meetthe metabolic targets suggested by current guidelines. Incorrect insulin administration techniques may greatly affect metabolic control in T2DM people. The aim of our study was to compare glycemic control associated with a concentrated insulin analog preparation (U-200 lispro) in people with T2DM to the one observed with standard U-100 lispro. The secondary endpoint of our study was patients' preference and performance ratings of U-200 lispro. METHODS: 126 patients with T2DM were enrolled. They were also assessed for limited joint mobility syndrome (LJMS),defined as limitation in at least two anatomical areas of the dominant upper extremity. After a 4-weekstructured insulin injection education period. Half of them were randomized to U-100 lispro, half to U-200 and after 12 weeks they were switched to the other preparation for 12 weeks. At the end a questionnaire was also administered to investigate patient preference. RESULTS: No significant variation in fasting blood glucose, HbA1c, severe or mild hypoglycemic rate and daily fast-acting insulin analog dose was observed with U-100 lispro while U-200 lispro treatment was associated with a significant improvement of all the above mentioned parameters and with around 20% decrease in insulin requirement. Moreover patients' answers to the questionnaire pointed out a higher preference for U-200 lispro for continuing treatment due to fewer difficulties completing injection. DISCUSSION: The explanation of better metabolic results with the U-200 device might be the lower inner piston inertia and volume and shorter duration of a complete injection. CONCLUSIONS: Checking for LJIMS before insulin prescription could be adopted as a standard practiceaimed at choosing the most suitable device for patient's specific characteristics and abilities. The use of U-200 lispro might improve treatment adherence and metabolic control. This would also result intocost reduction by saving about half the amount of pens per year and of time spent to both fill prescriptionand dump the pharmacy.

Effects of Mediterranean diet on sexual function in people with newly diagnosed type 2 diabetes: The MÈDITA trial.

AIMS: To assess the long-term effect of Mediterranean diet, as compared with low-fat diet, on sexual function in patients with newly diagnosed type 2 diabetes. METHODS: In a randomized clinical trial, with a total follow-up of 8.1years, 215 men and women with newly diagnosed type 2 diabetes were assigned to Mediterranean diet (n=108) or a low-fat diet (n=107). The primary outcome measures were changes of erectile function (IIEF) in diabetic men and of female sexual function (FSFI) in diabetic women. RESULTS: There was no difference in baseline sexual function in men (n=54 vs 52) or women (n=54 vs 55) randomized to Mediterranean diet or low-fat diet, respectively (P=0.287, P=0.815). Over the entire follow-up, the changes of the primary outcomes were significantly lower in the Mediterranean diet group compared with the low-fat group: IIEF and FSFI showed a significantly lesser decrease (1.22 and 1.18, respectively, P=0.024 and 0.019) with the Mediterranean diet. Baseline C-reactive protein levels predicted erectile dysfunction in men but not female sexual dysfunction in women. CONCLUSIONS: Among persons with newly diagnosed type 2 diabetes, a Mediterranean diet reduced the deterioration of sexual function over time in both sexes.

Treatment satisfaction and glycemic control in young Type 1 diabetic patients in transition from pediatric health care: CSII versus MDI.

To evaluate whether continuous subcutaneous insulin infusion (CSII) may have any advantage over multiple daily injections (MDI) on glycemic control and treatment satisfaction in young patients with Type 1 diabetes in transition to an adult diabetes center. The study population consisted of 125 patients on MDI; 38 out of the 43 patients considered eligible for CSII completed the study and the 82 remaining on MDI served as control group. Glycemic control and treatment satisfaction [diabetes treatment satisfaction questionnaire (DTSQ)] were evaluated in all patients at baseline and after 12 weeks. At baseline, the two groups were well matched for demographic characteristics and glycemic control. DTSQ score was lower in CSII group (21.1 ± 8.8 vs. 25.1 ± 7.1, P = 0.011). After 12 weeks, a similar decrease in HbA1C was observed in both groups [difference -0.3 % (95 % CI-0.6 to 0.1, P = 0.847)]. Mean amplitude glucose excursions,blood glucose standard deviation, and overall hypoglycemia were significantly reduced in CSII group. DTSQ overall score increased in CSII and decreased in MDI (difference between groups = 9.9, 95 % CI 8.0-12.0, P<0.001), while perceived hyperglycemia and hypoglycemia decreased in CSII compared with MDI (difference:-2.5 and -2.0, respectively, P<0.001 for both). Among young Type 1 diabetic patients in transition from Pediatrics,CSII showed a similar efficacy in reducing HbA1c compared with MDI, with less hypoglycemia and glycemic excursions, and was better in improving overall treatment satisfaction and the rate of perceived hyperglycemia and hypoglycemia.

Basal supplementation of insulin lispro protamine suspension versus insulin glargine and detemir for type 2 diabetes: meta-analysis of randomized controlled trials.

OBJECTIVE: We compared the effect of insulin lispro protamine suspension (ILPS) with that of insulin glargine and insulin detemir, all given as basal supplementation, in the treatment of patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We conducted an electronic search until February 2012, including online registries of ongoing trials and abstract books. All randomized controlled trials comparing ILPS with insulin glargine or detemir with a duration of ≥12 weeks were included. RESULTS: We found four trials lasting 24-36 weeks involving 1,336 persons: three studies compared ILPS with glargine, and one trial compared ILPS with detemir. There was no significant difference in change in HbA(1c) level between ILPS and comparators, in the proportion of patients achieving the HbA(1c) goals of ≤6.5 or <7%, in weight change, or in daily insulin doses. There was no difference in overall hypoglycemia, but nocturnal hypoglycemia occurred significantly more with ILPS than with comparator insulins (mean difference 0.099 events/patient/30 days [95% CI 0.03-0.17]). In a prespecified sensitivity analysis comparing data obtained in patients who remained on their once-daily insulin regimen, not significantly different event rates for nocturnal hypoglycemia were observed between ILPS and comparator insulins (0.063 [-0.007 to 0.13]), and ILPS was associated with lower insulin dose (0.07 units/kg/day [0.05-0.09]). CONCLUSIONS: There is no difference between ILPS and insulin glargine or detemir for targeting hyperglycemia, but nocturnal hypoglycemia occurred more frequently with ILPS than with comparator insulins. Nocturnal hypoglycemia was not significantly different in people who injected insulin once daily.