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Aims: To compare two progressive approaches [once-daily insulin glargine plus ≤3 mealtime lispro (G+L) vs. insulin lispro mix 50/50 (LM50/50) progression once up to thrice daily (premix progression, PP)] of beginning and advancing insulin in patients with type 2 diabetes (T2D) and inadequate glycaemic control on oral therapy, with the aim of showing non-inferiority of PP to G+L.Methods: Patients were randomized to PP (n = 242) or G+L (n = 242) in a 36-week, multinational, open-label trial. Dinnertime insulin LM 50/50 could be replaced with insulin lispro mix 75/25 if needed for fasting glycaemic control.Results: Baseline haemoglobin A1c (HbA1c) were 9.5% (PP) and 9.3% (G+L); p = 0.095. Change in A1C (baseline to endpoint) was −1.76% (PP) and −1.93% (G+L) (p = 0.097) [between-group difference of 0.17 (95% confidence interval: −0.03, 0.37)]. Non-inferiority of PP to G+L was not shown based on the prespecified non-inferiority margin of 0.3%. A1C was lower with G+L at weeks 12 (7.8 vs. 7.9%; p = 0.042), 24 (7.4 vs. 7.6%; p = 0.046), but not at week 36 (7.5 vs. 7.6%; p = 0.405). There were no significant differences in percentages of patients achieving A1C ≤7%, overall hypoglycaemia incidence and rate or weight change. Total daily insulin dosages at endpoint were higher with PP vs. G+L (0.57 vs. 0.51 U/kg; p = 0.017), likely due to more injections (1.98 vs. 1.79; p = 0.011).Conclusions: Both treatments progressively improved glycaemic control in patients with T2D on oral therapy, although non-inferiority of PP to G+L was not shown. Higher insulin doses were observed with PP with no between-treatment differences in overall hypoglycaemia or weight gain.

Aims/IntroductionDysregulated inflammatory response is believed to be an important factor in the pathogenesis of several late complications of diabetes mellitus. β‐Glucans are potent inducers of immune function. The present randomized, double blind, two‐center, placebo‐controlled study was undertaken to explore safety, tolerability and efficacy of soluble β‐1,3/1,6‐glucan (SBG) as a local treatment of diabetic foot ulcers.Materials and MethodsA total of 60 patients with type 1 or 2 diabetes and lower extremity ulcers (Wagner grade 1–2, Ankle/Brachial Index ≥0.7) received SBG or a comparator product (methylcellulose) locally three times weekly up to 12 weeks in addition to conventional management scheme. A total of 54 patients completed the study.ResultsA tendency for shorter median time to complete healing in the SBG group was observed (36 vs 63 days, P = 0.130). Weekly percentage reduction in ulcer size was significantly higher in the SBG group than in the methylcellulose group between weeks 1–2, 3–4 and 5–6 (P < 0.05). The proportion of ulcers healed by week 12 was also in favor of SBG (59% vs 37%, P = 0.09), with a significantly higher healing incidence in the SBG group at week 8 (44% vs 17%, P = 0.03). SBG was safe and well tolerated. There was a clinically significant difference regarding the incidence of serious adverse events in favor of the SBG treatment.ConclusionsLocal treatment of diabetic lower extremity ulcers with β‐1,3/1,6‐polyglucose shows good safety results. This β‐glucan preparation shows promising potential as a treatment accelerating cutaneous healing. Further studies are required to confirm this effect. This trial was registered with ClinicalTrials.gov (no. NCT00288392).

Urinary steroid profiling (USP) was studied using high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) methods in 108 patients with adrenocortical adenoma (ACA) and in 31 patients with adrenocortical carcinoma (ACC). Thirteen ACC and Cushing's syndrome (ACC-CS) patients had two types of USP as well as 18 ACC patients without hypercortisolism. These four types differed by androgen and glucocorticoid secretion of the adrenal cortex. Fifteen main ACC features were observed by GC-MS. Urinary excretion of dehydroepiandrosterone (DHEA) was increased in 67.7 % of ACC patients and tetrahydro-11-deoxycortisol (THS) in 74.2 %. By combination of the following parameters: THS >900 μg/24 h and/or DHEA >1500 μg/24 h with ratios of 3α,16,20-pregnentriol/3β,16,20-pregnentriol (3α,16,20dP3/3β,16,20dP3) less than 6.0 and 3α,17,20dP3/3β,17,20dP3 less than 9.0 and the detection of "non-classical" 5-en-pregnens, not found in ACA and healthy persons, 100 % sensitivity and specificity of ACC and ACA differential diagnosis were achieved. Features of 21-hydroxylase and 11β-hydroxylase deficiency were observed by GC-MS in 32.2 and 61.3 % of the ACC patients, respectively. Additional features for ACC-CS diagnostic were increased urinary excretion of 6β-hydroxycortisol, 18-hydroxycorticosterone, the sum (UFF + UFE) obtained by HPLC, tetrahydrocorticosterone, and the sum (THF + THE + allo-THF) obtained by GC-MS.

Lixisenatide before the main meal was noninferior to lixisenatide before breakfast in patients insufficiently controlled on metformin. Lixisenatide treatment allows flexibility in administration timing.