Lack of persistent remission following initial recovery in patients with type 1 diabetes treated with autologous peripheral blood stem cell transplantation.

AIMS: To assess metabolic control in patients with newly diagnosed type 1 diabetes mellitus who underwent immunoablation followed by autologous peripheral blood stem cell transplantation (APBSCT) as a treatment of diabetes. METHODS: APBSCT was performed in 23 patients. Control group comprised 8 non-APBSCT patients in whom after diagnosis insulin therapy was initiated. Fasting plasma glucose, glycated hemoglobin, fasting and postprandial C-peptide were assessed in all subjects and continuous glucose monitoring was performed at 6th, 12th, 24th, 36th, 48th month after transplantation. The APBSCT group was observed for 72 months. RESULTS: Six months after the procedure, 22 of 23 transplant patients remained insulin-free, but after 6 years, there was only one APBSCT insulin-free patient. Good glycemic control was observed in all patients throughout the observation period, although fasting plasma glucose in control group was significantly higher in comparison with the both transplanted groups up to the 36th month. HbA1c values were significantly lower in the insulin-free group only at the 24th and 36th month. Fasting and postprandial C-peptide concentrations were higher in APBSCT group as compared with control group. The most serious adverse event was a fatal case of Pseudomonas aeruginosa sepsis. CONCLUSIONS: The effectiveness of APBSCT as a treatment for newly diagnosed DM1 seems to be limited in time. The metabolic control of APBSCT patients is similar to conventionally treated patients. The lower fasting plasma glucose and higher C-peptide achieved with APBSCT seem to not exceed the risks associated with the procedure.

Efficacy and Safety of Biosimilar SAR342434 Insulin Lispro in Adults with Type 1 Diabetes Also Using Insulin Glargine-SORELLA 1 Study.

BACKGROUND: SAR342434 is a biosimilar follow-on of insulin lispro-Humalog®. This study aimed to show similar efficacy, safety, and immunogenicity of SAR342434 (SAR-Lis) versus insulin lispro-Humalog (Ly-Lis) in adult patients with type 1 diabetes (T1DM) treated with multiple daily injections while using basal insulin glargine (Lantus®; GLA-100). MATERIALS AND METHODS: SORELLA-1 was a randomized, open-label phase 3 study (NCT02273180). Patients completing the 6-month main study continued on SAR-Lis or Ly-Lis, as randomized, for a 6-month safety extension. Assessments included change in HbA1c, fasting plasma glucose (FPG), seven-point self-monitored plasma glucose (SMPG) profiles, hypoglycemic events, treatment-emergent adverse events (TEAEs), and anti-insulin antibodies (AIAs). RESULTS: Five hundred seven patients were randomized (SAR-Lis n = 253; Ly-Lis n = 254). Least square (LS) mean (SEM) change in glycosylated hemoglobin (HbA1c) (baseline to week 26; primary endpoint) was similar in both treatment groups (SAR-Lis: -0.42% [0.051]; Ly-Lis: -0.47% [0.050]). Noninferiority at prespecified 0.3% noninferiority margin and inverse noninferiority were demonstrated (LS mean difference of SAR-Lis vs. Ly-Lis: 0.06% [95% confidence interval: -0.084 to 0.197]). At week 52 (end of extension period) versus week 26, a small HbA1c increase was observed in both groups. FPG and seven-point SMPG profile changes, including postprandial glucose excursions, were similar between groups. At week 52, similar changes in mean daily mealtime and basal insulin doses were observed. Hypoglycemia, TEAEs, and AIAs (incidence, prevalence) did not differ between groups. CONCLUSIONS: Results from this controlled study in patients with T1DM also using GLA-100 support similar efficacy and long-term safety (including immunogenicity) of SAR-Lis and Ly-Lis.

Intima-media thickness and other markers of atherosclerosis in patients with type 2 diabetes and periodontal disease.

BACKGROUND: Periodontal disease is an inflammatory process which results in increased cardiovascular risk in patients with type 2 diabetes mellitus (DM2). It is not clear, however, whether periodontal inflammation may be associated with increased markers of atherosclerosis in these patients. AIM: This cross-sectional study aimed to answer the question of whether periodontal disease in DM2 is associated with increased markers and risk factors of atherosclerosis. METHODS: One hundred and twenty one patients were included in the study. Sixteen were classified as periodontally healthy (BGI-H), 87 as having gingivitis (BGI-G), and 18 as having periodontitis with moderate bleeding (BGI-P2), according to the new Offenbacher classification. In all patients, intima-media thickness (IMT), pulse wave velocity (PWV), lipids, and C-reactive protein (CRP) were assessed. RESULTS: Patients with periodontitis and gingivitis had a higher IMT value compared to the BGI-H group (0.804 ± 0.112 and 0.772 ± 0.127 vs 0.691 ± 0.151 mm, p < 0.01 and p < 0.05, respectively, odds ratio 5.25 for having IMT ≥ 0.8 mm, 95% CI 1.1; 25). Patients from the BGI-P2 group also had higher blood pressure (BP) compared to the BGI-G and BGI-H groups, and higher CRP compared to the BGI-G group (4.6 ± 2.3 vs 3.8 ± 4.8 mg/L, p < 0.01). Lipid parameters and PWV were comparable in all the groups. CONCLUSIONS: Periodontal inflammation in patients with DM2 seems to be associated with increased IMT and BP, but not with greater arterial stiffness. These results support the hypothesis that periodontal disease may be associated with a vascular pathology.

Blood pressure and left ventricular mass in subjects with type 2 diabetes and gingivitis or chronic periodontitis.

INTRODUCTION: This study aimed to answer the question of whether chronic periodontitis in subjects with type 2 diabetes mellitus is associated with increased left ventricular mass (LVM) and systemic and central blood pressure (CBP). MATERIAL AND METHODS: One hundred and fifty-five subjects with type 2 diabetes (67 F, 88 M, mean age 61.1±6.9 years, BMI 32.7±5.7 kg/m(2)) were divided according to their periodontal status into biofilm-gingival interface - healthy (BGI-H, 14 subjects), BGI-gingivitis (BGI-G, 119 subjects) and BGI-periodontitis (BGI-P, 22 subjects) groups. In all subjects, LVM, systemic and CBP were measured. The LVM index (LVMI) was calculated. RESULTS: (1) BGI-P and BGI-G subjects, respectively, had higher (mean; 95% CI) LVM (238.6 g; 206.6-267.4 and 222.8 g; 207.0-238.2) versus BGI-H subjects (170.3 g; 125.5-217.8).(2) BGI-P and BGI-G subjects, respectively, had higher (mean; 95% CI) LVM1 (95.2 g/m(2) ; 82.9-107.4) and 87.8 g/m(2) ; 81.5-94.1) versus BGI-H subjects (63.7 g/m(2) ; 45.2-62.3).(3) BGI-P subjects had higher central and systemic systolic and diastolic blood pressure than subjects from BGI-G and BGI-H groups. CONCLUSION: In subjects with type 2 diabetes, periodontitis and gingivitis are associated with increased LVM and periodontitis is associated with increased central and systemic blood pressure.

Alleviation of exogenous insulin requirement in type 1 diabetes mellitus after immunoablation and transplantation of autologous hematopoietic stem cells.

An essential component of type 1 diabetes mellitus is autoaggression of the immune system against insulin-secreting pancreatic cells. It is thought that early destruction of the autoaggressive mechanism prior to the complete damage of beta cells should halt this process. In a 28-year-old male patient with a 4-week history of type 1 diabetes mellitus, three courses of plasmapheresis had been performed before cyclophosphamide, 2 g/m2 body surface area, was administered and hematopoietic cells were obtained. Six weeks after the diagnosis, 4 doses of cyclophosphamide 50 mg/kg body weight were again administered together with antithymocyte globulin, and autologous hematopoietic cells were transplanted. The procedure was associated with no significant side effects. Insulin requirement started to drop from the first course of plasmapheresis, and the patient has remained normoglycemic with no need of exogenous insulin or other hypoglycemic agents since the third week after the procedure, which has been 5 months until publication of this report. Independence from exogenous insulin is associated with the implemented therapy (a gradual decrease in insulin requirement has been observed after consecutive stages of the immunosuppressive treatment, with total discontinuation after bone marrow transplantation). The course of the disease and the type of treatment may suggest that such medical procedures could eliminate autoaggressive mechanism in diabetes and prevent further degeneration of insulin-producing cells, thus becoming a new therapeutic option for patients with type 1 diabetes mellitus.

[Acute painful neuropathy at the initial period of effective insulin therapy]. / Ostra neuropatia bólowa w poczatkowym okresie skutecznej insulinoterapii.

We report on three patients (two men with recently discovered type 1 diabetes and one woman with type 2 diabetes and secondary failure of oral antidiabetic drugs) who developed acute painful neuropathy after the institution of effective insulintherapy and rapid drop of glycemia. The EMG disclosed in them traits of mixed lesions of motor-sensory neurons at the level of nerve fibres, more evident in sensory nerves of low extremities. In one patient (A) observed for 5 years, in spite of progressive partial remission of clinical symptoms and signs, no improvement in successive EMG was found. The evident therapeutic effect of alpha-lipoic acid in the presented cases needs to be confirmed in appropriate prospective studies.