Relationship between autonomic function and parameters of beta cell secretion across the entire spectrum of glucose homeostasis

Background: type 2 diabetes is determined by a reduction of β cell mass and function besides a defect in insulin sensitivity. It was demonstrated that pancreatic islets are innervated by sympathetic nervous system (SNS) and parasympathetic nervous system (PNS) fibers and autonomic function contributes to the regulation of glucose homeostasis. An alteration in neuronal control of β cell function could be involved in the pathogenesis of the type 2 diabetes. Aim: we focused on finding a possible association between autonomic function and the different parameters that describe β cell function in The Maastricht Study, a population-based cohort. We sought this association also in the population of Verona Newly Diagnosed Type 2 Diabetes Study (VNDS), a study of patients with newly diagnosed type 2 diabetes. Research design and Methods: in the Maastricht study population from 24-h electrocardiogram we derived Heart Rate Variability (HRV) time and frequency domains (individual z-scores, based upon seven and six variables, respectively). From a standard 2-hour 75 g OGTT we estimated different aspects of β cell function, i.e. C-peptidogenic index t0-30, overall insulin secretion, β cell glucose sensitivity, β cell potentiation factor, and β cell rate sensitivity, using formula-based methods and mathematical modeling. In the VNDS study cardiovascular autonomic function was assessed by a computerized system which analyzed heart rate and blood pressure variations during lying to standing (LS), deep breathing (DB), and Valsalva maneuver (VM), following the criteria presented by Ewing and Clarke. From a 5-hour 75g OGTT we estimated through mathematical modelling two main parameters of beta cell glucose sensitivity: derivative (first phase) and proportional control (second phase) of insulin secretion. Results: in the Maastricht study we analyzed 2007 individuals with a mean standard deviation (SD) age of 59.8 8.2 years, of whom 52% were men and 24% with type 2 diabetes (oversampled by design). After adjustment for age, sex, educational level and Matsuda index, time and frequency domain HRV were significantly and directly associated with C-peptidogenic index, β cell glucose sensitivity and β cell potentiation factor, but not with overall insulin secretion. Then, further adjustment for cardiovascular risk factors (model 4) did not materially alter these associations, though only the association of HRV with C-peptidogenic remained statistically significant (standardized β [95%CI] per 1-SD increment in HRV TIME domain, for respectively C-peptidogenic index, overall insulin secretion, β cell glucose sensitivity, and β cell potentiation, 0.05 [0.00; 0.09]; 0.04 [-0.00; 0.08]; 0.04 [0.00; 0.08] ; and 0.04 [-0.00; 0.08]; standardized β [95%CI] per 1-SD increment in HRV FREQUENCY domain, for respectively C-peptidogenic index, overall insulin secretion, β cell glucose sensitivity, and β cell potentiation, 0.05 [0.00; 0.09]; 0.04 [-0.00; 0.08]; 0.04 [0.00; 0.08] ; and 0.04 [-0.00; 0.08]). HRV time and frequency domain weren’t significantly associated with rate sensitivity. Furthermore, we evaluated data of 537 patients with newly diagnosed type 2 diabetes with a mean ± SD age of 58.3 ± 9.6 of whom 66.3% were male. 91 subjects (16.9%) showed at least one abnormal test used to evaluate cardiovascular autonomic function (CAN). We found a worse derivative control of beta cell function in people with signs of cardio autonomic neuropathy as compared to the other group. This difference however did not reach statistical significance (p=0.063). Conclusion: In summary, in the present research we analyzed a possible association between autonomic function and β cell secretion, estimated from OGTT. We found that autonomic dysregulation could contribute to β-cell dysfunction, in particular affecting the first phase of insulin secretion. This mechanism could add to the other factors that lead to the impairment of glucose homeostasis

Country rankings on the scientific production in endocrinology and diabetology

Diabetes represents a major global health problem. It was estimated that the global prevalence of diabetes in 2019 was approximately 9%, with the worrying projection to increase up to 11% by 2045 [1]. Importantly, it was also calculated that in 2016 worldwide nearly 1.6 million deaths were directly related to diabetes or high blood glucose [1]. In parallel, other important endocrinological diseases, such as obesity, thyroid diseases (i.e., hyperthyroidism, hypothyroidism, and cancer), polycystic ovary syndrome, and infertility, have a relevant clinical and socio-economic impact worldwide [2, 3]. These data strongly suggest that an additional uplift in research efforts is necessary in this area

Budget impact of pneumococcal vaccination in adults and elderly in Italy

BackgroundStreptococcus pneumoniae or pneumococcus, is responsible for severe invasive infections (IPD) in high risk groups and in the elderly. Moreover the pneumococcus is the most common cause of..

Development of EIS cell chips and their application for cell analysis

International audience; We report the development of EIS cell chips able to monitor cell growth and adhesion. They are made of transparent or semitransparent materials to allow complementary analysis of cell behaviour during the measurements through optical microscopy. Our approach is cheap both in fabrication and usage, it is not invasive for cells and it does not require any additional reagent. Our devices are particular suitable to count cells or to evaluate cell morphology and changes as a consequence of different treatments

A nanobiosensor to detect single hybridization events

An economical nanoarray method to electrically detect hybridization events is demonstrated. As a proof of concept, we fabricated a sensor for DNA sequencing, in which targets are oligonucleotides conjugated to gold nanoparticles. As a consequence of target–probe binding events, a conductive bridge forms between two electrodes, resulting in a quantized change in conductivity. This enables a robust detection of a few (down to single) hybridization events and can be potentially applied also to other binding events (like specific interactions between proteins, antibodies, ligands and receptors). Moreover, target amplification techniques (such as PCR) are no longer necessary

Towards pancreatic cancer diagnosis using EIS biochips

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Trans-synaptic degeneration in the optic pathway. A study in clinically isolated syndrome and early relapsing-remitting multiple sclerosis with or without optic neuritis

Increasing evidence suggest that neuronal damage is an early and diffuse feature of Multiple Sclerosis (MS) pathology. Analysis of the optic pathway may help to clarify the mechanisms involved in grey matter damage in MS. Purpose of our study was to investigate the relationship between inflammation and neurodegeneration and to achieve evidence of trans-synaptic degeneration in the optic pathway in MS at clinical onset

Impact of a multidisciplinary management team on clinical outcome in ICU patients affected by Gram-negative bloodstream infections: a pre-post quasi-experimental study

Background: Bloodstream infections (BSIs) by Gram-negative pathogens play a major role in intensive care patients, both in terms of prevalence and severity, especially if multi-drug resistant pathogens are involved. Early appropriate antibiotic therapy is therefore a cornerstone in the management of these patients, and growing evidence shows that implementation of a multidisciplinary team may improve patients' outcomes. Our aim was to evaluate the clinical and microbiological impact of the application of a multidisciplinary team on critically ill patients. Methods: Pre-post study enrolling critically ill patients with Gram negative bloodstream infection in intensive care unit. In the pre-intervention phase (from January until December 2018) patients were managed with infectious disease consultation on demand, in the post-intervention phase (from January until December 2022) patients were managed with a daily evaluation by a multidisciplinary team composed of intensivist, infectious disease physician, clinical pharmacologist and microbiologist. Results: Overall, 135 patients were enrolled during the study period, of them 67 (49.6%) in the pre-intervention phase and 68 (50.4%) in the post-intervention phase. Median age was 67 (58-75) years, sex male was 31.9%. Septic shock, the need for continuous renal replacement therapy and mechanical ventilation at BSI onset were similar in both groups, no difference of multidrug-resistant organisms (MDRO) prevalence was observed. In the post-phase, empirical administration of carbapenems decreased significantly (40.3% vs. 62.7%, p = 0.02) with an increase of appropriate empirical therapy (86.9% vs. 55.2%, p < 0.001) and a decrease of overall antibiotic treatment (12 vs. 16 days, p < 0.001). Despite no differences in delta SOFA and all-cause 30-day mortality, a significant decrease in microbiological failure (10.3% vs. 29.9%, p = 0.005) and a new-onset 30-day MDRO colonization (8.3% vs. 36.6%, p < 0.001) in the post-phase was reported. At multivariable analysis adjusted for main covariates, the institution of a multidisciplinary management team (MMT) was found to be protective both for new MDRO colonization [OR 0.17, 95%CI(0.05-0.67)] and microbiological failure [OR 0.37, 95%CI (0.14-0.98)]. Conclusions: The institution of a MMT allowed for an optimization of antimicrobial treatments, reflecting to a significant decrease in new MDRO colonization and microbiological failure among critically ill patients

The tumor suppressor gene KCTD11REN is regulated by Sp1 and methylation and its expression is reduced in tumors

A hallmark of several human cancers is loss of heterozygosity (LOH) of chromosome 17p13. The same chromosomal region is also frequently hypermethylated in cancer. Although loss of 17p13 has been often associated with p53 genetic alteration or Hypermethylated in Cancer 1 (HIC1) gene hypermethylation, other tumor suppressor genes (TSGs) located in this region have critical roles in tumorigenesis. A novel TSG mapping on human chromosome 17p13.2 is KCTD11REN (KCTD11). We have recently demonstrated that KCTD11 expression is frequently lost in human medulloblastoma (MB), in part by LOH and in part by uncharacterized epigenetic events. Using a panel of human 177 tumor samples and their normal matching samples representing 18 different types of cancer, we show here that the down-regulation of KCTD11 protein level is a specific and a diffusely common event in tumorigenesis. Additionally, in order to characterize the regulatory regions in KCTD11 promoter, we identified a CpG island and several Sp1 binding sites on this promoter, and demonstrated that Sp1 transcription factor and DNA methylation contribute, at least in part, to regulate KCTD11 expression. Our findings identify KCTD11 as a widely down-regulated gene in human cancers, and provide a basis to understand how its expression might be deregulated in tumor cells