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The Cochrane Database of Systematic... Apr 2022Glycaemic control is a key component in diabetes mellitus (diabetes) management. Periodontitis is the inflammation and destruction of the underlying supporting tissues... (Review)
Review
BACKGROUND
Glycaemic control is a key component in diabetes mellitus (diabetes) management. Periodontitis is the inflammation and destruction of the underlying supporting tissues of the teeth. Some studies have suggested a bidirectional relationship between glycaemic control and periodontitis. Treatment for periodontitis involves subgingival instrumentation, which is the professional removal of plaque, calculus, and debris from below the gumline using hand or ultrasonic instruments. This is known variously as scaling and root planing, mechanical debridement, or non-surgical periodontal treatment. Subgingival instrumentation is sometimes accompanied by local or systemic antimicrobials, and occasionally by surgical intervention to cut away gum tissue when periodontitis is severe. This review is part one of an update of a review published in 2010 and first updated in 2015, and evaluates periodontal treatment versus no intervention or usual care. OBJECTIVES: To investigate the effects of periodontal treatment on glycaemic control in people with diabetes mellitus and periodontitis.
SEARCH METHODS
An information specialist searched six bibliographic databases up to 7 September 2021 and additional search methods were used to identify published, unpublished, and ongoing studies. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) of people with type 1 or type 2 diabetes mellitus and a diagnosis of periodontitis that compared subgingival instrumentation (sometimes with surgical treatment or adjunctive antimicrobial therapy or both) to no active intervention or 'usual care' (oral hygiene instruction, education or support interventions, and/or supragingival scaling (also known as PMPR, professional mechanical plaque removal)). To be included, the RCTs had to have lasted at least 3 months and have measured HbA1c (glycated haemoglobin).
DATA COLLECTION AND ANALYSIS
At least two review authors independently examined the titles and abstracts retrieved by the search, selected the included trials, extracted data from included trials, and assessed included trials for risk of bias. Where necessary and possible, we attempted to contact study authors. Our primary outcome was blood glucose levels measured as glycated (glycosylated) haemoglobin assay (HbA1c), which can be reported as a percentage of total haemoglobin or as millimoles per mole (mmol/mol). Our secondary outcomes included adverse effects, periodontal indices (bleeding on probing, clinical attachment level, gingival index, plaque index, and probing pocket depth), quality of life, cost implications, and diabetic complications.
MAIN RESULTS
We included 35 studies, which randomised 3249 participants to periodontal treatment or control. All studies used a parallel-RCT design and followed up participants for between 3 and 12 months. The studies focused on people with type 2 diabetes, other than one study that included participants with type 1 or type 2 diabetes. Most studies were mixed in terms of whether metabolic control of participants at baseline was good, fair, or poor. Most studies were carried out in secondary care. We assessed two studies as being at low risk of bias, 14 studies at high risk of bias, and the risk of bias in 19 studies was unclear. We undertook a sensitivity analysis for our primary outcome based on studies at low risk of bias and this supported the main findings. Moderate-certainty evidence from 30 studies (2443 analysed participants) showed an absolute reduction in HbA1c of 0.43% (4.7 mmol/mol) 3 to 4 months after treatment of periodontitis (95% confidence interval (CI) -0.59% to -0.28%; -6.4 mmol/mol to -3.0 mmol/mol). Similarly, after 6 months, we found an absolute reduction in HbA1c of 0.30% (3.3 mmol/mol) (95% CI -0.52% to -0.08%; -5.7 mmol/mol to -0.9 mmol/mol; 12 studies, 1457 participants), and after 12 months, an absolute reduction of 0.50% (5.4 mmol/mol) (95% CI -0.55% to -0.45%; -6.0 mmol/mol to -4.9 mmol/mol; 1 study, 264 participants). Studies that measured adverse effects generally reported that no or only mild harms occurred, and any serious adverse events were similar in intervention and control arms. However, adverse effects of periodontal treatments were not evaluated in most studies.
AUTHORS' CONCLUSIONS
Our 2022 update of this review has doubled the number of included studies and participants, which has led to a change in our conclusions about the primary outcome of glycaemic control and in our level of certainty in this conclusion. We now have moderate-certainty evidence that periodontal treatment using subgingival instrumentation improves glycaemic control in people with both periodontitis and diabetes by a clinically significant amount when compared to no treatment or usual care. Further trials evaluating periodontal treatment versus no treatment/usual care are unlikely to change the overall conclusion reached in this review.
Topics: Diabetes Mellitus, Type 2; Glycated Hemoglobin; Glycemic Control; Humans; Periodontal Index; Periodontitis
PubMed: 35420698
DOI: 10.1002/14651858.CD004714.pub4 -
Diabetes Care Aug 2008The A1C assay, expressed as the percent of hemoglobin that is glycated, measures chronic glycemia and is widely used to judge the adequacy of diabetes treatment and...
OBJECTIVE
The A1C assay, expressed as the percent of hemoglobin that is glycated, measures chronic glycemia and is widely used to judge the adequacy of diabetes treatment and adjust therapy. Day-to-day management is guided by self-monitoring of capillary glucose concentrations (milligrams per deciliter or millimoles per liter). We sought to define the mathematical relationship between A1C and average glucose (AG) levels and determine whether A1C could be expressed and reported as AG in the same units as used in self-monitoring.
RESEARCH DESIGN AND METHODS
A total of 507 subjects, including 268 patients with type 1 diabetes, 159 with type 2 diabetes, and 80 nondiabetic subjects from 10 international centers, was included in the analyses. A1C levels obtained at the end of 3 months and measured in a central laboratory were compared with the AG levels during the previous 3 months. AG was calculated by combining weighted results from at least 2 days of continuous glucose monitoring performed four times, with seven-point daily self-monitoring of capillary (fingerstick) glucose performed at least 3 days per week.
RESULTS
Approximately 2,700 glucose values were obtained by each subject during 3 months. Linear regression analysis between the A1C and AG values provided the tightest correlations (AG(mg/dl) = 28.7 x A1C - 46.7, R(2) = 0.84, P < 0.0001), allowing calculation of an estimated average glucose (eAG) for A1C values. The linear regression equations did not differ significantly across subgroups based on age, sex, diabetes type, race/ethnicity, or smoking status.
CONCLUSIONS
A1C levels can be expressed as eAG for most patients with type 1 and type 2 diabetes.
Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Male; Middle Aged; Models, Theoretical; Monitoring, Ambulatory; Reference Values; Regression Analysis
PubMed: 18540046
DOI: 10.2337/dc08-0545 -
Angewandte Chemie (International Ed. in... Jul 2020Miniaturization and acceleration of synthetic chemistry is an emerging area in pharmaceutical, agrochemical, and materials research and development. Herein, we describe...
Miniaturization and acceleration of synthetic chemistry is an emerging area in pharmaceutical, agrochemical, and materials research and development. Herein, we describe the synthesis of iminopyrrolidine-2-carboxylic acid derivatives using chiral glutamine, oxo components, and isocyanide building blocks in an unprecedented Ugi-3-component reaction. We used I-DOT, a positive-pressure-based low-volume and non-contact dispensing technology to prepare more than 1000 different derivatives in a fully automated fashion. In general, the reaction is stereoselective, proceeds in good yields, and tolerates a wide variety of functional groups. We exemplify a pipeline of fast and efficient nanomole-scale scouting to millimole-scale synthesis for the discovery of a useful novel reaction with great scope.
Topics: Automation; Crystallography, X-Ray; Drug Discovery; Imines; Miniaturization; Molecular Structure; Nanotechnology; Pyrrolidines
PubMed: 32048418
DOI: 10.1002/anie.202000887 -
International Journal of Molecular... Dec 2022Astrocytes are the most abundant glial cells in the central nervous system (CNS) mediating a variety of homeostatic functions, such as spatial K buffering or... (Review)
Review
Astrocytes are the most abundant glial cells in the central nervous system (CNS) mediating a variety of homeostatic functions, such as spatial K buffering or neurotransmitter reuptake. In addition, astrocytes are capable of releasing several biologically active substances, including glutamate and GABA. Astrocyte-mediated GABA release has been a matter of debate because the expression level of the main GABA synthesizing enzyme glutamate decarboxylase is quite low in astrocytes, suggesting that low intracellular GABA concentration ([GABA]) might be insufficient to support a non-vesicular GABA release. However, recent studies demonstrated that, at least in some regions of the CNS, [GABA] in astrocytes might reach several millimoles both under physiological and especially pathophysiological conditions, thereby enabling GABA release from astrocytes via GABA-permeable anion channels and/or via GABA transporters operating in reverse mode. In this review, we summarize experimental data supporting both forms of GABA release from astrocytes in health and disease, paying special attention to possible feedback mechanisms that might govern the fine-tuning of astrocytic GABA release and, in turn, the tonic GABA receptor-mediated inhibition in the CNS.
Topics: Astrocytes; gamma-Aminobutyric Acid; Neuroglia; Receptors, GABA-A; Glutamic Acid
PubMed: 36555501
DOI: 10.3390/ijms232415859 -
Journal of Lipid Research Mar 2019Gallstone (GS) formation requires that bile is supersaturated with cholesterol, which is estimated by a cholesterol saturation index (CSI) calculated from gallbladder... (Review)
Review
Gallstone (GS) formation requires that bile is supersaturated with cholesterol, which is estimated by a cholesterol saturation index (CSI) calculated from gallbladder (GB) total lipids and the mol% (mole percent) of bile acids (BAs), cholesterol, and phospholipids (PLs). Whereas CSI indicates GS risk, we hypothesized that additional comparisons of GB lipid mol% data are inappropriate to identify why CSI is increased in GS disease. We anticipated that GB lipid mmol/l (millimole per liter) levels should instead identify that, and therefore retrieved GB mmol/l data for BAs, cholesterol, and PLs from a study on 145 GS and 87 GS-free patients and compared them with the corresponding mol% data. BA and PL mmol/l levels were 33% and 31% lower in GS patients, while cholesterol was unaltered. CSI was higher in GS patients and correlated inversely with GB levels of BAs and PLs, but not with cholesterol. A literature search confirmed, in 13 studies from 11 countries, that GB BA levels and, to a certain extent, PLs are strongly reduced in GS patients, while cholesterol levels are not elevated. Our findings show that a shortage of BAs is a major reason why GB bile is supersaturated with cholesterol in GS patients. These results are sustainable because they are also valid from a global perspective.
Topics: Adult; Bile Acids and Salts; Cholesterol; Female; Gallbladder; Gallstones; Humans; Male
PubMed: 30610083
DOI: 10.1194/jlr.S091199 -
Drug Testing and Analysis Aug 2022New biomarkers indicating the abuse of drugs and alcohol are still of major interest for clinical and forensic sciences. The endogenous neurotransmitter and approved...
New biomarkers indicating the abuse of drugs and alcohol are still of major interest for clinical and forensic sciences. The endogenous neurotransmitter and approved drug, gamma-hydroxybutyric acid (GHB), is often illegally used for drug-facilitated crimes by spiking GHB into alcoholic beverages. Analytical detection windows of only 6 h in blood and 12 h in urine are often too short to provide reliable proof of GHB ingestion. Therefore, new biomarkers are needed to prove exogenous GHB administration. Previously, amino acid GHB conjugates were discovered in an untargeted metabolomics screening and fatty acid esters with GHB were recently discussed as promising biomarkers to enlarge the analytical detection time windows. However, the development of analytical methods is still slowed down since reference compounds for targeted screenings are still missing. In this paper, we describe simple procedures for the rapid synthesis and purification of amino acid GHB conjugates as well as fatty acid esters, which can be adopted in analytical and clinical/forensic laboratories. Structural characterization data, together with IR, H-nuclear magnetic resonance (NMR), C-NMR, high-resolution mass spectra (MS), and MS/MS spectra in positive and negative ionization mode are reported for all obtained GHB conjugates and GHB conjugate precursors.
Topics: Amino Acids; Biomarkers; Hydroxybutyrates; Laboratories; Sodium Oxybate; Tandem Mass Spectrometry
PubMed: 35415886
DOI: 10.1002/dta.3273 -
Nature Communications Jan 2024Industrial hydrogen peroxide (HO) is synthesized using carbon-intensive H gas production and purification, anthraquinone hydrogenation, and anthrahydroquinone oxidation....
Industrial hydrogen peroxide (HO) is synthesized using carbon-intensive H gas production and purification, anthraquinone hydrogenation, and anthrahydroquinone oxidation. Electrochemical hydrogenation (ECH) of anthraquinones offers a carbon-neutral alternative for generating HO using renewable electricity and water instead of H gas. However, the HO formation rates associated with ECH are too low for commercialization. We report here that a membrane reactor enabled us to electrochemically hydrogenate anthraquinone (0.25 molar) with a current efficiency of 70% at current densities of 100 milliamperes per square centimeter. We also demonstrate continuous HO synthesis from the hydrogenated anthraquinones over the course of 48 h. This study presents a fast rate of electrochemically-driven anthraquinone hydrogenation (1.32 ± 0.14 millimoles per hour normalized per centimeter squared of geometric surface of electrode), and provides a pathway toward carbon-neutral HO synthesis.
PubMed: 38278793
DOI: 10.1038/s41467-024-44741-1 -
JAMA Network Open Dec 2022There have been major advances in insulin delivery and formulations over the past several decades. It is unclear whether these changes have resulted in improved glycemic...
IMPORTANCE
There have been major advances in insulin delivery and formulations over the past several decades. It is unclear whether these changes have resulted in improved glycemic control for patients with diabetes.
OBJECTIVE
To characterize trends and disparities in glycemic control and severe hyperglycemia in US adults with diabetes using insulin.
DESIGN, SETTING, AND PARTICIPANTS
This serial population-based cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) between 1988-1994 and 1999-2020. Participants were nonpregnant US adults aged 20 years or older who had a diagnosis of diabetes and were currently using insulin.
EXPOSURES
Diabetes diagnosis and use of insulin.
MAIN OUTCOMES AND MEASURES
Trends in glycemic control (glycated hemoglobin [HbA1c] level <7%) and severe hyperglycemia (HbA1c level >10%; to convert percentage of total hemoglobin to proportion of total hemoglobin, multiply by 0.01; to convert to millimoles per mole, multiply by 10.93 and subtract by 23.50) overall and by age, race and ethnicity, and indicators of socioeconomic status were evaluated using logistic regression. Analyses incorporated sample weights to account for oversampling of certain populations and survey nonresponse.
RESULTS
There were 2482 participants with diabetes using insulin included in the analyses (mean [SD] age, 59.8 [0.4] years); 51.3% were men, 7.0% were Mexican American individuals, 17.9% were non-Hispanic Black individuals, and 65.2% were non-Hispanic White individuals. From 1988-1994 to 2013-2020, the proportion of patients with diabetes who received insulin and achieved glycemic control did not significantly change, from 29.2% (95% CI, 22.6%-36.8%) to 27.5% (95% CI, 21.7%-34.2%). Mexican American adults who received insulin were less likely than non-Hispanic White adults to achieve glycemic control, and disparities increased during the study period. The proportion of adults with severe hyperglycemia did not significantly change and was 14.6% (95% CI, 12.0-17.5) in 2013-2020. Adults who were Mexican American or non-Hispanic Black, were uninsured, or had low family income had the highest prevalence of severe hyperglycemia.
CONCLUSIONS AND RELEVANCE
In this population-based cross-sectional study of NHANES data over the past 3 decades, glycemic control stagnated and racial and ethnic disparities increased among US adults with diabetes who received insulin. Efforts to improve access to insulin may optimize glycemic control and reduce disparities in this population.
Topics: Male; Adult; Humans; Middle Aged; Female; Insulin; Nutrition Surveys; Glycated Hemoglobin; Cross-Sectional Studies; Glycemic Control; Diabetes Mellitus; Insulin, Regular, Human; Hyperglycemia
PubMed: 36538330
DOI: 10.1001/jamanetworkopen.2022.47656 -
Metallomics : Integrated Biometal... Feb 2019Gadolinium-based contrast agents (GBCAs) are widely used with clinical magnetic resonance imaging (MRI), and 10 s of millions of doses of GBCAs are administered annually... (Review)
Review
Gadolinium-based contrast agents (GBCAs) are widely used with clinical magnetic resonance imaging (MRI), and 10 s of millions of doses of GBCAs are administered annually worldwide. GBCAs are hydrophilic, thermodynamically stable and kinetically inert gadolinium chelates. In clinical MRI, 5-10 millimoles of Gd ion is administered intravenously and the GBCA is rapidly eliminated intact primarily through the kidneys into the urine. It is now well-established that the Gd3+ ion, in some form(s), is partially retained in vivo. In patients with advanced kidney disease, there is an association of Gd retention with nephrogenic systemic fibrosis (NSF) disease. However Gd is also retained in the brain, bone, skin, and other tissues in patients with normal renal function, and the presence of Gd can persist months to years after the last administration of a GBCA. Regulatory agencies are restricting the use of specific GBCAs and inviting health care professionals to evaluate the risk/benefit ratio prior to using GBCAs. Despite the growing number of studies investigating this issue both in animals and humans, the biological distribution and the chemical speciation of the residual gadolinium are not fully understood. Is the GBCA retained in its intact form? Is the Gd3+ ion dissociated from its chelator, and if so, what is its chemical form? Here we discuss the current state of knowledge regarding the issue of Gd retention and describe the analytical and spectroscopic methods that can be used to investigate the Gd speciation. Many of the physical methods that could be brought to bear on this problem are in the domain of bioinorganic chemistry and we hope that this review will serve to inspire this community to take up this important problem.
Topics: Contrast Media; Gadolinium; Magnetic Resonance Imaging; Molecular Structure
PubMed: 30516229
DOI: 10.1039/c8mt00302e