Impact of Impaired Glucose Metabolism on Periodontitis Progression over Three Years

We evaluated the relationship between glucose abnormalities and periodontitis in overweight/obese individuals. Eight hundred and seventy (870) diabetes-free participants aged 40–65 years completed the three-year follow-up in the San Juan Overweight Adults Longitudinal Study. The ADA thresholds for fasting and 2-h post-load glucose and HbA1c were used to define prediabetes. The NHANES methods were used to assess periodontitis. Multivariable linear regression was used to evaluate the relationship between baseline glucose metabolism measures and periodontitis at follow-up, adjusting for potential confounders. There was no association between impaired glucose measures and mean pocket depth (PD), mean clinical attachment loss (CAL), or mean percent of sites ≥5 mm PD. Impaired glucose tolerance (IGT) was associated with a lower mean percent of sites ≥5 mm CAL (β = −1.6, p = 0.037). Prediabetes and impaired fasting glucose (IFG) were associated with improvement in mean percent of sites ≥5 mm PD (β = −1.4, p = 0.022; β = −1.6, p = 0.032; respectively). IFG and IGT were associated with improvement in mean percent of sites with ≥5 mm CAL (β = −1.6, p = 0.038; β = −1.9, p = 0.020; respectively). In conclusion, there were no consistent associations between baseline prediabetes or insulin resistance and periodontitis progression over a three-year period.

An integrative transcriptional logic model of hepatic insulin resistance

Abnormalities of lipid/lipoprotein and glucose metabolism are hallmarks of hepatic insulin resistance in type 2 diabetes. The former antedate the latter, but the latter become progressively refractory to treatment and contribute to therapeutic failures. It’s unclear whether the two processes share a common pathogenesis and what underlies their progressive nature. In this study, we investigated the hypothesis that genes in the lipid/lipoprotein pathway and those in the glucose metabolic pathway are governed by different transcriptional regulatory logics that affect their response to physiologic (fasting/refeeding) as well as pathophysiologic cues (insulin resistance and hyperglycemia). To this end, we obtained genomic and transcriptomic maps of the key insulin-regulated transcription factor, FoxO1, and integrated them with those of CREB, PPAR-α, and glucocorticoid receptor. We found that glucose metabolic genes are primarily regulated by promoter and intergenic enhancers in a fasting-dependent manner, while lipid genes are regulated through fasting-dependent intron enhancers and fasting-independent enhancerless introns. Glucose genes also showed a remarkable transcriptional resiliency (i.e., the ability to compensate following constitutive FoxO1 ablation through an enrichment of active marks at shared PPAR-α/FoxO1 regulatory elements). Unexpectedly, insulin resistance and hyperglycemia were associated with a “spreading” of FoxO1 binding to enhancers and the emergence of unique target sites. We surmise that this unusual pattern correlates with the progressively intractable nature of hepatic insulin resistance. This transcriptional logic provides an integrated model to interpret the combined lipid and glucose abnormalities of type 2 diabetes.

HbA1c Screening for Diabetes in Patients with Acute Coronary Syndrome: A Worthwhile Test or a Pitfall?

Background: Diagnostic concordance between HbA1c and other glucose-based tests is imperfect, and data on this problem in acute coronary syndrome (ACS) are still lacking. The aim of this study was to identify undiagnosed glucose abnormalities in ACS patients, and to compare the effectiveness and consistency of the diagnostic screening based on HbA1c to the oral glucose tolerance test (OGTT). Methods: The study group consisted of 121 ACS patients, mean age 62.3 ± 11.6 years, without known glucose abnormalities. HbA1c, admission and fasting plasma glucose in the first days of hospitalization were assessed and referred to the results of OGTT performed two weeks after discharge. Results: OGTT identified normoglycemia in 45%, pre-diabetes in 39.4%, and diabetes in 15.6%, while HbA1c revealed these categories in 39.7%, 51.2%, and 9.1%, respectively. With an HbA1c cut-off ≥6.5% (48 mmol/mol) diagnostic for diabetes, the sensitivity of the method was 41%, while specificity was 98%, compared to the OGTT. The optimal HbA1c cut-off value at the crossing of sensitivity and specificity curves was 5.9%. The HbA1c value recommended for the diagnosis of pre-diabetes and optimal cut-off point were the same (5.7%). Conclusions: Using HbA1c without OGTT in an early but stable phase of ACS may result in a significant underdiagnosis of diabetes.

Detection and Management of Early Glucose Abnormalities in Cystic Fibrosis

With advances in technology, it is now possible to detect the emergence of glucose abnormalities in cystic fibrosis with improved sensitivity, and from a very early age. These abnormalities are increasingly recognized as predictors of clinical decline, raising the possibility that early intervention may slow or prevent this deterioration. In this chapter, we will review the available literature on methods of detecting glucose abnormalities in cystic fibrosis (random and fasting glucose, HbA1c, oral glucose tolerance testing, and continuous glucose monitoring), and detail their advantages and possible limitations in the interpretation of glycemic data. We will also discuss treatment outcomes of early intervention, prior to the diagnosis of diabetes as currently defined.

GP73 is a glucogenic hormone regulating SARS-CoV-2-induced hyperglycemia

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces new-onset diabetes and severe metabolic complications of pre-existing diabetes. The pathogenic mechanism underlying this is incompletely understood. Here, we provided evidence linking circulating GP73 with the exaggerated gluconeogenesis triggered by SARS-CoV-2 infection. We found that SARS-CoV-2 infection or glucotoxic condition increased the cellular secretion of GP73. Secreted GP73 trafficked to the liver and kidney to stimulate gluconeogenesis through cAMP/PKA pathway. By using global phosphoproteomics, we found a drastic remodeling of PKA kinase hub exerted by GP73. Notably, COVID-19 patients showed pathologically elevated plasma GP73, and neutralization of the secreted GP73 inhibited enhanced PKA signaling and glucose production associated with SARS-CoV-2 infection. GP73 blockade also reduced gluconeogenesis and lowered hyperglycemia in type 2 (T2D) diabetic mice. Therefore, our findings provide novel insight into the roles of GP73 as a key glucogenic hormone and mechanistic clues underlying the development of SARS-CoV-induced glucose abnormalities.

An integrative transcriptional logic model of hepatic insulin resistance

Abnormalities of lipid/lipoprotein and glucose metabolism are hallmarks of hepatic insulin resistance in type 2 diabetes. The former antedate the latter, but the latter become progressively refractory to treatment and contribute to therapeutic failures. It's unclear whether the two processes share a common pathogenesis and what underlies their progressive nature. In this study, we investigated the hypothesis that genes in the lipid/lipoprotein pathway and those in the glucose metabolic pathway are governed by different transcriptional logics that affect their response to physiologic (fasting/refeeding) as well as pathophysiologic cues (insulin resistance and hyperglycemia). To this end, we obtained genomic and transcriptomic maps of the key insulin-regulated transcription factor, FoxO1, and integrated them with those of CREB, PPARα, and glucocorticoid receptor. We found an enrichment of glucose metabolic genes among those regulated by intergenic and promoter enhancers in a fasting-dependent manner, while lipid genes were enriched among fasting-dependent intron enhancers and fasting-independent enhancer-less introns. Glucose genes also showed a remarkable transcriptional resiliency, i.e., an enrichment of active marks at shared PPARα/FoxO1 regulatory elements when FoxO1 was inactivated. Surprisingly, the main features associated with insulin resistance and hyperglycemia were a ″spreading″ of FoxO1 binding to enhancers, and the emergence of target sites unique to this condition. We surmise that this unusual pattern correlates with the progressively intractable nature of hepatic insulin resistance. This transcriptional logic provides an integrated model to interpret the combined lipid and glucose abnormalities of type 2 diabetes.

Incidence of glucose level abnormalities in neonatal sepsis and its association with mortality

Background: Plasma glucose abnormalities were previously noted in neonatal sepsis, but data in neonates is limited and the association with mortality is not established. The aim of the study was to determine the incidence of plasma glucose abnormalities among newborns with sepsis and their association with mortality.Methods: This was a prospective observational study including 50 neonates with suspected, probable and proven sepsis. Plasma glucose level was measured within 2 hours of admission and the patients were monitored till discharge or death. The patients were divided into hyperglycaemic, hypoglycaemic and normoglycemic subgroups as per the serum glucose levels.Results: Majority (56%) were noted to have normoglycemia, followed by hypoglycaemia in 32% and 12% had hyperglycaemic. Mortality in the hypoglycemic, hyperglycemic, and normoglycemic subgroups were 50.0, 33.3, and 7.2% respectively. Mortality was high in hyperglycemic patients compared to normoglycemic patients but the difference was not statistically significant between two groups, whereas the mortality was high in hypoglycemic patients compared to normoglycemic patients and the difference was statistically significant between two groups. A significant association was noted between hypoglycemia in neonatal sepsis with mortality.Conclusions: Altered glycemic status is common in neonatal sepsis. Mortality is higher among septic neonates with hypoglycemia. We conclude that majority of septic neonates had high mortality rate when plasma glucose levels were either >145 mg/dl or <45 mg/dl. This signifies the importance of plasma glucose estimation in cases of neonatal sepsis to improve mortality outcome.