Dynamic monitoring of HbA1c in Russian regions: data comparison of mobile medical center (Diamodul) and national diabetes register of Russian Federation

BACKGROUND: Glikogemoglobin (HbA1c) is a key clinical marker for evaluating the effectiveness of glucose-lowering therapy for patients with diabetes mellitus (DM) and the quality of diabetic care. AIMS: to conduct dynamic monitoring of the quality of glycemic control in DM patients based on a comprehensive examination in mobile medical center (Diamodul) during repeated visits to the regions in 2019 compared with visits of Based Federal program “Diabetes Mellitus” (2005–2010) and data of the National diabetes register (NDR). MATERIALS AND METHODS: The object of the study: patients with T1DM and T2DM examined in Diamodul in 2019 in Voronezh region (Vr), Krasnodar region (Kr) (n = 600), there were “dynamic” group of re-examined (Vr n = 224; Kr n = 113), “random” group of new patients (Vr n = 72; Kr n = 191); group of adult patients from NDR with indicated HbA1c in 2019 (n = 2410067). RESULTS: According to Diamodul, the HbA1c levels are significantly worse than they were reported to NDR: the proportion of patients achieved HbA1c <7% for T1DM is 13.3% and 11.7%; T2DM – 25.1% and 28.6%, in Kr and Vr, respectively; in NDR: T1DM – 37.4%, T2DM – 52.2%. The average HbA1c values in the Diamodul are higher than in NDR by 0.95% for T1DM, 1.41% for T2DM patients. The proportion of patients with HbA1c≥9% decrease in dynamic of examinations through years in T1: in Vr from 53.1% in 2005 and 55.8% in 2010 to 42.9% in 2019, in Kr from 53.2% in 2006 to 43.8% in 2019; also there were decreases in the average HbA1c values in Vr from 9.3% in 2005 and 9.4% in 2010 to 8.8% in 2019; in Kr from 9.1% in 2006 to 8.7% in 2019. In T2DM patients with the best parameters of DM control in a whole, the positive trends were less pronounced and are assessed as non-deterioration: the proportion of HbA1c≥9 % in Vr: 34.7%–34.7%–36.4%, in Kr 40.1%–28.4%; average values of HbA1c: 8.2%–8.4%–8.5% and 8.6%–8.4%, respectively. CONCLUSIONS: The data of the research clearly indicates the need for 100% inclusion of HbA1c in the examination standards in all DM patients at the primary level at least 1 time per year, in order to monitor the real clinical situation, the effectiveness of glucose-lowering therapy and its timely intensification to prevent development of complications

Trends in the epidemiology of diabetic foot and lower limb amputations in Russian Federation according to the Federal Diabetes Register (2013–2016)

BACKGROUND: The epidemiological study of diabetic foot (DF) is very important because of high risk lower limbs amputations in patients with diabetes mellitus (DM). AIMS: The aim of the study was to evaluate the DF prevalence in adult patients with type 1 (T1) and 2 (T2) diabetes in Russian Federation for period 201316years. METHODS: We have used the database of the Russian Federal Diabetes register, 81st regions included in the online register. Indicators were estimated per 10,000 adult DM patients (18years). RESULTS: In 2016, the prevalence of DF in RF was T1 4,7%, T2 1,9%, with marked interregional differences: 0,1519,9%, 0,0710,3%, respectively. The DF prevalence in RF decreased: T1 506,3473,6, T2 214,60194,8. The incidence of new DF cases/per year was stable in adults with T1: 20,820,4/; increased in T2 13.214.2. The mean age of DF diagnosis increased by 2years for both DM types. The average DM duration of DF determine increased T1 15.419.0years, T2 7.410.1years. Proportion of DF forms: neuropathic with trophic ulcer 41.6%, neuropathic form (Charcot's foot) 17.9%, the neuroischemic 28.3%, ischemic 12.2%, in T2: 41.6%, 7,4%, 32,4%, 18,5%, respectively. The amount of new cases of amputations/per year in dynamics: T1 10,512,4, T2 9,610,9, with marked interregional differences 0.132.9% in T1, 0.04-6.0% in T2. The mean DM duration before amputation increased in T1 18.421.3years, in T2 9.19.9. The average amputation age: T1 51.7years, T2 66.2years. There was marked decrease in proportion of major amputations: T1 43,637,0%, T2 52.245.5 by redistribution in one toe amputations T14,010.0%, in T22,89.1%. CONCLUSIONS: The dynamic of new DF cases in adult patients in Russian Federation is stable at T1, in T2 tends to increase. The interregional differences in frequency of DF and amputations may be due to differences in the quality of specialized care, the lack or shortage of diabetic foot cabinets, treatment of patients with DF in general surgical practice in a number of regions, which is recognized as a less effective strategy. A positive fact that proportion of high amputations declines, DF develops in later age and longer diabetes duration, that may reflect the increasing effectiveness of preventive lower limbs in diabetes

Bis-Amiridines as Acetylcholinesterase and Butyrylcholinesterase Inhibitors: <i>N</i>-Functionalization Determines the Multitarget Anti-Alzheimer’s Activity Profile

Using two ways of functionalizing amiridine—acylation with chloroacetic acid chloride and reaction with thiophosgene—we have synthesized new homobivalent bis-amiridines joined by two different spacers—bis-N-acyl-alkylene (3) and bis-N-thiourea-alkylene (5) —as potential multifunctional agents for the treatment of Alzheimer’s disease (AD). All compounds exhibited high inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) with selectivity for BChE. These new agents displayed negligible carboxylesterase inhibition, suggesting a probable lack of untoward drug–drug interactions arising from hydrolytic biotransformation. Compounds 3 with bis-N-acyl-alkylene spacers were more potent inhibitors of both cholinesterases compared to compounds 5 and the parent amiridine. The lead compounds 3a–c exhibited an IC50(AChE) = 2.9–1.4 µM, IC50(BChE) = 0.13–0.067 µM, and 14–18% propidium displacement at 20 μM. Kinetic studies of compounds 3a and 5d indicated mixed-type reversible inhibition. Molecular docking revealed favorable poses in both catalytic and peripheral AChE sites. Propidium displacement from the peripheral site by the hybrids suggests their potential to hinder AChE-assisted Aβ42 aggregation. Conjugates 3 had no effect on Aβ42 self-aggregation, whereas compounds 5c–e (m = 4, 5, 6) showed mild (13–17%) inhibition. The greatest difference between conjugates 3 and 5 was their antioxidant activity. Bis-amiridines 3 with N-acylalkylene spacers were nearly inactive in ABTS and FRAP tests, whereas compounds 5 with thiourea in the spacers demonstrated high antioxidant activity, especially in the ABTS test (TEAC = 1.2–2.1), in agreement with their significantly lower HOMO-LUMO gap values. Calculated ADMET parameters for all conjugates predicted favorable blood–brain barrier permeability and intestinal absorption, as well as a low propensity for cardiac toxicity. Thus, it was possible to obtain amiridine derivatives whose potencies against AChE and BChE equaled (5) or exceeded (3) that of the parent compound, amiridine. Overall, based on their expanded and balanced pharmacological profiles, conjugates 5c–e appear promising for future optimization and development as multitarget anti-AD agents