Mechanisms Linking COPD to Type 1 and 2 Diabetes Mellitus: Is There a Relationship between Diabetes and COPD?

Park, Sangmi S.; Perez, Jessica L. Perez; Gandara, Brais Perez; Agudelo, Christina W.; Ortega, Romy Rodriguez; Ahmed, Huma; García-Arcos, Itsaso; McCarthy, Cormac; Geraghty, Patrick

doi:10.3390/medicina58081030

Cited by 28 publications

(25 citation statements)

References 225 publications

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“…Additionally, the inflammation within adipose tissue leads to a systemic pro‐inflammatory state and metabolic dysfunction in NAFLD (Ma et al, 2021). Leptin and lipocalin levels in adipose tissue act as adipokines and their secretion promotes systemic inflammation (Park et al, 2022). In this study, it was confirmed that LQ significantly suppressed the circulating pro‐inflammatory factors expression, inhibited leptin, and increased the concentration of lipocalin in mice, implying that LQ improved the inflammatory response in NAFLD.…”

Section: Discussionmentioning

confidence: 99%

Liquiritigenin regulates insulin sensitivity and ameliorates inflammatory responses in the nonalcoholic fatty liver by activation PI3K/AKT pathway

Bao¹,

Hao

Jiang³

et al. 2023

Chem Biol Drug Des

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Nonalcoholic fatty liver disease (NAFLD) is a prevalent long‐term disease in the world. Liquiritigenin (LQ) is protective against a variety of hepatotoxins. Herein, we report the potential mechanism of LQ on a high‐fat diet (HFD) induced NAFLD. NAFLD mice model was established by HFD for 12 weeks, and LQ treatment for 1 week. Commercially available assay kits measure liver triglycerides (TG) and total cholesterol (TC) levels. Plasm TC, TG, high‐density‐lipoprotein (HDL‐C), and low‐density‐lipoprotein cholesterol (LDL‐C) levels were also monitored by biochemistry. Enzyme linked immunosorbent assay (ELISA) kits were performed to analyze the pro‐inflammatory factors, and intraperitoneal glucose tolerance test (IPGTT), insulin tolerance test (IPITT), and serum insulin were also determined. GO and KEGG pathway enrichment analysis was employed to analyze the overlapping genes of LQ targets and NAFLD development‐related targets. Western blot was performed on key proteins of the enriched signaling pathway. HFD mice showed significant increases in hepatic TG and TC, and plasm TC, TG, and LDL‐C in blood lipids, while HDL‐C significantly decreased, and LQ treatment reversed their levels (p < 0.05). LQ also alleviated HFD‐induced elevated levels of IPGTT, IPITT, and homeostasis model assessment of insulin resistance (HOMA‐IR). And serum levels of the pro‐inflammatory factor were also suppressed by LQ. PI3K/AKT pathway was enriched by KEGG pathway enrichment, and its key proteins p‐PI3K and p‐AKT were elevated after LQ treatment (p < 0.05). We found for the first time that LQ improves lipid accumulation, alleviates insulin resistance, and suppresses inflammatory responses in NAFLD mice, which might be associated with the activation of the PI3K/AKT pathway.

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Section: Discussionmentioning

confidence: 99%

Liquiritigenin regulates insulin sensitivity and ameliorates inflammatory responses in the nonalcoholic fatty liver by activation PI3K/AKT pathway

Bao¹,

Hao

Jiang³

et al. 2023

Chem Biol Drug Des

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“…Previous studies have reported that hyperinsulinaemia plays an important role in the association between diabetes and COPD. 26,27 Hyperinsulinaemia has a negative impact on COPD and lung function by adversely affecting airways structure and function. 28 An experimental study showed that high concentrations of insulin can reduce cellular senescence in human airway epithelial cells through the autophagy pathway, which is implicated in COPD progression.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have reported that hyperinsulinaemia plays an important role in the association between diabetes and COPD 26,27 . Hyperinsulinaemia has a negative impact on COPD and lung function by adversely affecting airways structure and function 28 .…”

Section: Discussionmentioning

confidence: 99%

Association between glycated haemoglobin and the risk of chronic obstructive pulmonary disease: A prospective cohort study in UK biobank

Li,

Wan,

Zhu

et al. 2023

Diabetes Obesity Metabolism

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AimsTo investigate the association between glycated haemoglobin (HbA1c) levels and chronic obstructive pulmonary disease (COPD) incidents in the general population, and the association between HbA1c levels and mortality in patients with COPD.Materials and MethodsWe investigated the association of HbA1c levels with COPD risk in the general population in the UK Biobank, using data from 420 065 participants. Survival analysis was conducted for 18 854 patients with COPD. We used restricted cubic spline analysis to assess the dose‐response relationship between HbA1c levels and COPD risk and survival. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs).ResultsDuring a median follow‐up of 12.3 years, 11 556 COPD cases were recorded. HbA1c had a non‐linear relationship with COPD risk (p for non‐linearity < .05). Compared with the quintile 2 (32.2‐<34.3 mmol/mol), those with HbA1c levels above 38.7 mmol/mol (quintile 5) had a 22% (HR, 1.22, 95% CI: 1.15‐1.30) higher risk of COPD. Compared with the HbA1c decile 2 (30.5‐<32.2 mmol/mol), the HRs (95% CI) of COPD risk were 1.16 (1.03‐1.30) and 1.36 (1.24‐1.50) in the lowest HbA1c decile (<30.5 mmol/mol) and highest decile (≥41.0 mmol/mol), respectively. The increased COPD risk associated with HbA1c was more pronounced in younger, current smokers, passive smokers, and participants with a higher Townsend deprivation index (all p for interaction < .05). Among patients with COPD, 4569 COPD cases died (488 because of COPD) during a median follow‐up of 5.4 years. Regarding COPD survival, HbA1c had a non‐linear relationship with all‐cause death (p for non‐linearity < .05). Those with HbA1c quintile 5 (≥38.7 mmol/mol) had a 23% (HR, 1.23, 95% CI: 1.10‐1.37) higher risk of all‐cause death compared with the quintile 2 (32.2‐<34.3 mmol/mol). Compared with the HbA1c decile 4 (33.3‐<34.3 mmol/mol), those in the lowest HbA1c decile (<30.5 mmol/mol) and highest HbA1c decile (≥41.0 mmol/mol) had 22% (HR, 1.22; 95% CI: 1.01‐1.47) and 28% (HR, 1.28; 95% CI: 1.11‐1.48) higher risk for overall death. However, no significant association was observed between HbA1c levels and the risk of COPD‐specific death.ConclusionsOur findings indicated that lower and higher HbA1c levels were associated with a higher risk of COPD. In COPD cases, lower and higher HbA1c levels were associated with a higher COPD all‐cause death risk.

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“… 28 Possible common causal mechanisms for both are chronic systemic inflammation, oxidative stress, hypoxia, obesity and hyperglycaemia. 29 , 30 Patients with COPD combined with diabetes have a significantly higher rate of hospitalization, and diabetes increases the risk of infection, and progression of disease course, leading to poor prognosis and increased mortality in COPD patients. 31 , 32 Conversely, the inflammatory process, impaired lung function and/or the use of glucocorticoids in COPD patients may increase the risk of developing diabetes.…”

Section: Chronic Obstructive Pulmonary Diseasementioning

confidence: 99%

The Role of Glucagon-Like Peptide-1 Receptor Agonists in Chronic Obstructive Pulmonary Disease

Wang¹,

Mei²,

Qian³

et al. 2023

COPD

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Chronic obstructive pulmonary disease (COPD) is one of the common diseases of the respiratory system. As the disease recurs, damage to the airways and lung tissue gradually worsens, leading to a progressive decline in lung function, affecting the patient’s workforce and quality of life, and causing a huge social and economic burden. Diabetes is a common comorbidity of COPD and patients with COPD are at increased risk of developing diabetes, while hyperglycemia can also reduce lung function and contribute to the progression and poor prognosis of COPD. Glucagon-like peptide-1 receptor agonist (GLP-1RA) is a new type of hypoglycemic agent that has been shown to regulate blood glucose levels, reduce inflammatory responses and oxidative stress, and regulate lipid metabolism, among other effects. GLP-1RAs may benefit COPD patients by acting directly on the lung from mechanisms such as reducing the inflammatory response, improving oxidative stress, regulating protease/anti-protease imbalance, improving airway mucus homeostasis, and reducing airway remodeling. This study provides a review of the potential role of GLP-1RAs in COPD and offers new ideas for the prevention and treatment of COPD.

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Mechanisms Linking COPD to Type 1 and 2 Diabetes Mellitus: Is There a Relationship between Diabetes and COPD?

Cited by 28 publications

References 225 publications

Liquiritigenin regulates insulin sensitivity and ameliorates inflammatory responses in the nonalcoholic fatty liver by activation PI3K/AKT pathway

Liquiritigenin regulates insulin sensitivity and ameliorates inflammatory responses in the nonalcoholic fatty liver by activation PI3K/AKT pathway

Association between glycated haemoglobin and the risk of chronic obstructive pulmonary disease: A prospective cohort study in UK biobank

The Role of Glucagon-Like Peptide-1 Receptor Agonists in Chronic Obstructive Pulmonary Disease

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