Vitamin B12 deficiency in metformin-treated type-2 diabetes patients, prevalence and association with peripheral neuropathy

BACKGROUND : The association between long-term metformin use and low vitamin B12 levels has been proven. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed considerable variation among the studies. The potential of the deficiency to cause or worsen peripheral neuropathy in type-2 diabetes mellitus (T2DM) patients has been investigated with conflicting results. The aim of the study was to investigate: 1) the prevalence of vitamin B12 deficiency in T2DM patients on metformin; 2) the association between vitamin B12 and peripheral neuropathy; 3) and the risk factors for vitamin B12 deficiency in these patients. METHODS : In this cross-sectional study, consecutive metformin-treated T2DM patients attending diabetes clinics of two public hospitals in South Africa were approached for participation. Participation included measuring vitamin B12 levels and assessing peripheral neuropathy using Neuropathy Total Symptom Score-6 (NTSS-6) questionnaire. The prevalence of vitamin B12 deficiency (defined by concentrations <150 pmol/L) was determined. Those with NTSS-6 scores >6 were considered to have peripheral neuropathy. The relationship between vitamin B12 and peripheral neuropathy was investigated when the two variables were in the binary and continuous forms. Multiple logistic regression was used to determine risk factors for vitamin B12 deficiency. RESULTS : Among 121 participants, the prevalence of vitamin B12 deficiency was 28.1 %. There was no difference in presence of neuropathy between those with normal and deficient vitamin levels (36.8 % vs. 32.3 %, P = 0.209). Vitamin B12 levels and NTSS-6 scores were not correlated (Spearman’s rho =0.056, P = 0.54). HbA1c (mmol/mol) (OR = 0.97, 95 % CI: 0.95 to 0.99, P = 0.003) and black race (OR = 0.34, 95 % CI: 0.13 to 0.92, P = 0.033) were risk factors significantly associated with vitamin B12 deficiency. Metformin daily dose (gram) showed borderline significance (OR = 1.96, 95 % CI: 0.99 to 3.88, P = 0.053). CONCLUSIONS : Close to third of metformin-treated T2DM patients had vitamin B12 deficiency. The deficiency was not associated with peripheral neuropathy. Black race was a protective factor for vitamin B12 deficiency.The Department of Pharmacology, University of Pretoriahttp://bmcpharmacoltoxicol.biomedcentral.comam2017Internal MedicinePharmacolog

Retrofitting controlled dynamic reconfiguration into the architecture description language MontiArcAutomaton

Component & connector architecture description languages (C&C ADLs) provide hierarchical decomposition of system functionality into components and their interaction. Most ADLs fix interaction configurations at design time while some express dynamic reconfiguration of components to adapt to runtime changes. Implementing dynamic reconfiguration in a static C&C ADL by encoding it into component behavior creates implicit dependencies between components and forfeits the abstraction of behavior paramount to C&C models. We developed a mechanism for retrofitting dynamic reconfiguration into the static C&C ADL MontiArcAutomaton. This mechanism lifts reconfiguration to an architecture concern and allows to preserve encapsulation and abstraction of C&C ADLs. Our approach enables efficient retrofitting by a smooth integration of reconfiguration semantics and encapsulation. The new dynamic C&C ADL is fully backwards compatible and well-formedness of configurations can be statically checked at design time. Our work provides dynamic reconfiguration for the C&C ADL MontiArcAutomaton

Automatic refinement and vacuity detection for symbolic trajectory evaluation

Abstract. Symbolic Trajectory Evaluation (STE) is a powerful technique for model checking. It is based on 3-valued symbolic simulation, using 0,1 and X (”unknown”). The X value is used to abstract away parts of the circuit. The abstraction is derived from the user’s specification. Currently the process of abstraction and refinement in STE is performed manually. This paper presents an automatic refinement technique for STE. The technique is based on a clever selection of constraints that are added to the specification so that on the one hand the semantics of the original specification is preserved, and on the other hand, the part of the state space in which the ”unknown ” result is received is significantly decreased or totally eliminated. In addition, this paper raises the problem of vacuity of passed and failed specifications. This problem was never discussed in the framework of STE. We describe when an STE specification may vacuously pass or fail, and propose a method for vacuity detection in STE.