Clinical inertia is the enemy of therapeutic success in the management of diabetes and its complications: A narrative literature review

Diabetes mellitus is a chronic disease characterized by high social, economic and health burden, mostly due to the high incidence and morbidity of diabetes complications. Numerous studies have shown that optimizing metabolic control may reduce the risk of micro and macrovascular complications related to the disease, and the algorithms suggest that an appropriate and timely step of care intensification should be proposed after 3 months from the failure to achieve metabolic goals. Nonetheless, many population studies show that glycemic control in diabetic patients is often inadequate. The phenomenon of clinical inertia in diabetology, defined as the failure to start a therapy or its intensification/de-intensification when appropriate, has been studied for almost 20 years, and it is not limited to diabetes care, but also affects other specialties. In the present manuscript, we have documented the issue of inertia in its complexity, assessing its dimensions, its epidemiological weight, and its burden over the effectiveness of care. Our main goal is the identification of the causes of clinical inertia in diabetology, and the quantification of its social and health-related consequences through the adoption of appropriate indicators, in an effort to advance possible solutions and proposals to fight and possibly overcome clinical inertia, thus improving health outcomes and quality of care

A Combination of Nutriments Improves Mitochondrial Biogenesis and Function in Skeletal Muscle of Type 2 Diabetic Goto–Kakizaki Rats

BACKGROUND: Recent evidence indicates that insulin resistance in skeletal muscle may be related to reduce mitochondrial number and oxidation capacity. However, it is not known whether increasing mitochondrial number and function improves insulin resistance. In the present study, we investigated the effects of a combination of nutrients on insulin resistance and mitochondrial biogenesis/function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that defect of glucose and lipid metabolism is associated with low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle of the diabetic Goto-Kakizaki rats. The treatment of combination of R-alpha-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin effectively improved glucose tolerance, decreased the basal insulin secretion and the level of circulating free fatty acid (FFA), and prevented the reduction of mitochondrial biogenesis in skeletal muscle. The nutrients treatment also significantly increased mRNA levels of genes involved in lipid metabolism, including peroxisome proliferator-activated receptor-alpha (Ppar alpha), peroxisome proliferator-activated receptor-delta (Ppar delta), and carnitine palmitoyl transferase-1 (Mcpt-1) and activity of mitochondrial complex I and II in skeletal muscle. All of these effects of mitochondrial nutrients are comparable to that of the antidiabetic drug, pioglitazone. In addition, the treatment with nutrients, unlike pioglitazone, did not cause body weight gain. CONCLUSIONS/SIGNIFICANCE: These data suggest that a combination of mitochondrial targeting nutrients may improve skeletal mitochondrial dysfunction and exert hypoglycemic effects, without causing weight gain

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Is Climate Change Time-Reversible?

This paper proposes strategies to detect time reversibility in stationary stochastic processes by using the properties of mixed causal and noncausal models. It shows that they can also be used for non-stationary processes when the trend component is computed with the Hodrick-Prescott filter rendering a time-reversible closed-form solution. This paper also links the concept of an environmental tipping point to the statistical property of time irreversibility and assesses fourteen climate indicators. We find evidence of time irreversibility in greenhouse gas emissions, global temperature, global sea levels, sea ice area, and some natural oscillation indices. While not conclusive, our findings urge the implementation of correction policies to avoid the worst consequences of climate change and not miss the opportunity window, which might still be available, despite closing quickly

A model for glucose control of insulin secretion during 24 h of free living

The aim of this work was to develop a mathematical model describing the functional dependence of insulin secretion on plasma glucose concentrations during 24 h of free living. We obtained hourly central venous blood samples from a group of healthy volunteers who spent 24 h in a calorimetric chamber, where they consumed standardized meals. Insulin secretory rates were reconstructed from plasma C-peptide concentrations by deconvolution. The relationship between insulin release and plasma glucose concentrations was modeled as the sum of three components: a static component (describing the dependence on plasma glucose concentration itself, with an embedded circadian oscillation), a dynamic component (modeling the dependence on glucose rate of change), and a residual component (including the fraction of insulin secretion not explained by glucose levels). The model fit of the individual 24-h secretion profiles was satisfactory (within the assigned experimental error of glucose and C-peptide concentrations). The static component yielded a dose-response function in which insulin release increased quasi-linearly (from 40 to 400 pmol/min on average) over the range of 4-9 mmol/l glucose. The dynamic component was significantly different from zero in coincidence with meal-related glucose excursions. The circadian oscillation and the residual component accounted for the day/night difference in the ability of glucose to stimulate insulin release. Over 24 h, total insulin release averaged 257 ± 58 nmol (or 43 ± 10 U). The static and dynamic component together accounted for ∼80% of total insulin release. The model proposed here provides a detailed robust description of glucose-related insulin release during free-living conditions. In nondiabetic subjects, non-glucose-dependent insulin release is a small fraction of total insulin secretion

Enhanced optical and electrical gas sensing response of sol-gel based NiO-Au and ZnO-Au nanostructured thin films

NiO and ZnO thin films of about 40-50 nm thickness with embedded Au nanoparticles have been synthesized with a simple and reliable sol-gel procedure. The nanocomposites films are crystalline and porous and they show optical absorptions in the visible range according to Au nanoparticles concentration. These films have been tested as optical and electrical sensors for pollutant gases detection. A fast and reversible response has been detected for hydrogen, CO and NO 2. Au nanoparticles have been found to improve the optical sensing properties of both NiO and ZnO films over the Au surface plasmon resonance peak wavelength range, but also to enhance the ZnO optical response in the near UV range, where Au nanoparticles are optically inactive. Moreover, combining the observed shift in the surface plasmon resonance peak and the different semiconductive type of the two oxides, it has been proved that reducing gases inject electrons into the oxide and then afterward the charge variation is detected by Au nanoparticles. Electrical tests confirm the n-type behavior of ZnO and p-type behavior of NiO, and show good performances at lower temperatures. Moreover, an enhancing effect of Au nanoparticles in the overall sensing performances is observed also in electrical tests

The influence of thermal and visible light activation modes on the NO2 response of WO3 nanofibers prepared by electrospinning

The paper reports on the influence of visible light at different wavelengths (red, λ = 630 nm; green, λ = 570 nm; purple–blue, λ = 430 nm), light irradiance conditions (from 30 to 770 μW/cm2) and operating temperatures (from 25 °C to 100 °C) on the electrical response of WO3 electrospun nanofibers (NFs) to 100–400 ppb NO2 gas in dry air. WO3 NFs were prepared by mixing a W–O sol–gel transparent solution (WCl6 in ethanol) with a polymeric solution made of polyvinylpyrrolidone (PVP) and dimethylformamide (DMF). Electrospun NFs were annealed between 300 °C and 500 °C and the their microstructures features investigated by SEM and XRD. Room temperature (25 °C) gas responses of the 450 °C annealed NFs have shown that, beside a slight reduction of the relative gas response (RRs), a decrease of the light wavelength (toward the purple–blue) and an increase of its irradiance, greatly improve the base line recovery and the response time with respect to dark conditions. At operating temperatures ranging from 25 °C to 100 °C, sensor relative responses in dark always resulted to be higher as respect to the ones displayed under purple–blue light illumination. The combined action of purple-blue light with an irradiance of 770 μW/cm2 and of mild operating temperature of 75 °C, relative responses (RRs) of 12.4 and base line recovery percentages (RPs) of 97% were attained at 400 ppb NO2. The capability to tune the response of WO3 NFs to NO2 by combining light and mild thermal gas sensors activations is addressed and discussed also considering the involved response mechanisms