Integrative traditional Chinese medicine treatment for children with obstructive sleep apnea.

Purpose: Obstructive sleep apnea (OSA) is a chronic disease that affects 1%-6% of children. Our study aims to explore the effectiveness and clinical characteristics of integrative Traditional Chinese Medicine (ITCM) for pediatric OSA. Materials and methods: In this retrospective cohort study, we assessed differences of polysomnography (PSG) parameters and clinical characteristics between 2009 and 2020. Children <12 years old diagnosed with OSA (n = 508) were included and were categorized into ITCM cohort, western medicine (WM) cohort ,and surgery cohort. Outcomes were apnea-hypopnea index (AHI), respiratory disturbance index (RDI), and body mass index (BMI). Results: There were 56 (11%), 324 (63.8%), and 128 (25.2%) patients in the ITCM, WM, and surgery cohorts. Among 17, 26, and 33 patients in the ITCM, WM, and surgery cohorts underwent follow-up PSG studies, respectively. In the ITCM follow-up cohort, AHI were significantly reduced (9.59 to 5.71, p < 0.05). BMI significantly increased in the WM follow-up cohort (19.46 to 20.50, p < 0.05) and the surgery follow-up cohort (18.04 to 18.85, p < 0.01). Comparing ITCM to WM cohort, a significant difference was found between the changes in RDI (ITCM: -6.78, WM: 0.51, p < 0.05) after treatment. Among ITCM follow-up cohort, the most prescribed TCM formula was Forsythia and Laminaria Combination. The most prescribed TCM herb was Ephedrae Herba. Conclusions: ITCM therapy can significantly reduce RDI and control BMI. We identified potential TCM treatments for pediatric OSA. Further study of the pharmacological mechanisms and clinical efficacy is warranted.

Effects of glucagon-like peptide-1 receptor agonists on liver-related and cardiovascular mortality in patients with type 2 diabetes.

BACKGROUND: Patients with type 2 diabetes (T2D) tend to have nonalcoholic fatty liver disease (NAFLD) with poorer prognosis. We performed this research to compare the risks of cardiovascular diseases, cirrhosis, liver-related mortality, and cardiovascular mortality between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and no-use in patients with T2D without viral hepatitis. METHODS: From January 1, 2008, to December 31, 2018, we used propensity-score matching to identify 31,183 pairs of GLP-1 RA users and nonusers from Taiwan's National Health Insurance Research Database. Multivariable-adjusted Cox proportional hazards models were used to examine the outcomes between the study and control groups. RESULTS: The median (Q1, Q3) follow-up time for GLP-1 RA users and nonusers were 2.19 (1.35, 3.52) and 2.14 (1.19, 3.68) years, respectively. The all-cause mortality incidence rate was 5.67 and 13.06 per 1000 person-years for GLP-1 RA users and nonusers, respectively. Multivariable-adjusted analysis showed that GLP-1 RA use had significantly lower risks of all-cause mortality (aHR 0.48, 95%CI 0.43-0.53), cardiovascular events (aHR 0.92, 95%CI 0.86-0.99), cardiovascular death (aHR 0.57, 95%CI 0.45-0.72), and liver-related death (aHR 0.32, 95%CI 0.13-0.75). However, there was no significant difference in the risk of liver cirrhosis development, hepatic failure, and hepatocellular carcinoma compared to GLP-1 RA no-use. CONCLUSIONS: This nationwide cohort study showed that GLP-1 RA use was associated with a significantly lower risk of all-cause mortality, cardiovascular events, and cardiovascular death in patients with T2D among Taiwan population. More prospective studies are warranted to verify our results.

Risk of Diabetic Retinopathy in Patients With Type 2 Diabetes After SGLT-2 Inhibitors: A Nationwide Population Cohort Study.

Diabetic retinopathy (DR) accounts for 80% of cases of vision loss in patients with type 2 diabetes mellitus (T2DM). Interventional treatments are only indicated in advanced DR and are ineffective in some patients. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are used to attenuate T2DM-associated cardiovascular complications. We conducted the cohort study to investigate the effect of SGLT2is on DR development. Data (May 2016-December 2018) obtained from the Taiwan National Health Insurance Research Database were analyzed in this nationwide retrospective cohort study. After propensity score matching, a total of 31,764 patients receiving SGLT2is and another 31,764 patients receiving dipeptidyl peptidase 4 inhibitors (DPP4is) were included in this study. Multiple Cox proportional-hazards regression models were used to evaluate DR risk. Overall DR incidence among SGLT2i or DPP4i users was 10.9 or 15.6 per 10,000 patient-years, respectively. After covariate adjustment, DR (both early and late stage) risk was substantially lower in SGLT2i users (adjusted hazard ratio: 0.68, 95% confidence interval: 0.6-0.78) than in DPP4i users. DR risk appears to be considerably lower in SGLT2i users than in DPP4i users. Glycemic control measurement with HbA1C level was unavailable in this claim database.

Glucagon-like Peptide-1 Receptor Agonist Use in Patients With Liver Cirrhosis and Type 2 Diabetes.

BACKGROUND AND AIMS: Liver cirrhosis is often associated with type 2 diabetes (T2D), but research on treatment of T2D in cirrhotic patients is scarce. We investigated the long-term outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with T2D and cirrhosis. METHODS: Using propensity score matching, we selected 467 matched pairs of GLP-1 RA users and nonusers from the National Health Insurance Research Database of Taiwan from January 1, 2008, to December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to compare the outcomes between GLP-1 RA users and nonusers. RESULTS: The mean follow-up time was 3.28 and 3.06 years for GLP-1 RA users and nonusers, respectively. The rates of death were 27.46 and 55.90 per 1000 person-years for GLP-1 RA users and nonusers, respectively. The multivariable-adjusted models showed that GLP-1 RA users had lower risks of mortality (adjusted hazard ratio [aHR], 0.47; 95% confidence interval [CI], 0.32-0.69), cardiovascular events (aHR, 0.6; 95% CI, 0.41-0.87), decompensated cirrhosis (aHR, 0.7; 95% CI, 0.49-0.99), hepatic encephalopathy (aHR, 0.59; 95% CI, 0.36-0.97), and liver failure (aHR, 0.54; 95% CI, 0.34-0.85) than nonusers. A longer cumulative duration of GLP-1 RA use had a lower risk of these outcomes than GLP-1 RA nonuse. CONCLUSIONS: This population-based cohort study showed that GLP-1 RA users exhibited a significantly lower risk of death, cardiovascular events, decompensated cirrhosis, hepatic encephalopathy, and liver failure in patients with T2D and compensated liver cirrhosis. Additional studies are needed to confirm our results.

LipoCol Forte capsules reduce the risk of liver cancer: A propensity score-matched, nationwide, population-based cohort study.

BACKGROUND: Liver cancer is among the top five most common cancers globally. Lipid-lowering drugs such as statins can lower the risk of liver cancer, but may also cause liver damage. LipoCol Forte capsules (LFC), a red yeast rice product, have demonstrated significant antihypercholesterolemic effects and a good safety profile in clinical studies. AIM: To evaluate whether LFC lowers the risk of liver cancer in adults in this propensity score-matched, nationwide, population-based cohort study. METHODS: We used data from Taiwan's National Health Insurance Research Database, which includes electronic medical records for up to 99.99% of Taiwan's population. LFC users and LFC non-users were matched 1:1 by propensity scores between January 2010 and December 2017. All had follow-up data for at least 1 year. Statistical analyses compared demographic distributions including sex, age, comorbidities, and prescribed medications. Cox regression analyses estimated adjusted hazard ratios (aHRs) after adjusting for potential confounders. RESULTS: We enrolled 33231 LFC users and 33231 non-LFC users (controls). No significant differences between the study cohorts were identified regarding comorbidities and medications [standardized mean difference (SMD) < 0.05]. At follow-up, the overall incidence of liver cancer was significantly lower in the LFC cohort compared with controls [aHR 0.91; 95% confidence interval (CI): 0.86-0.95; P < 0.001]. The risk of liver cancer was significantly reduced in both females (aHR 0.87; 95%CI: 0.8-0.94; P < 0.001) and males (aHR 0.93; 95%CI: 0.87-0.98; P < 0.01) in the LFC cohort compared with their counterparts in the non-LFC cohort. The antitumor protective effects applied to patients with comorbidities (including hypertension, ischemic stroke, diabetes mellitus, hyperlipidemia, hepatitis B infection and hepatitis C infection). Those using LFC for more than 84 drug days had a 0.64-fold lower risk of liver cancer compared with controls (P < 0.001). Compared with controls, the risk of developing liver cancer in the LFC cohort progressively decreased over time; the lowest incidence of liver cancer occurred in LFC users followed-up for more than 6 years (27.44 vs 31.49 per 1,000 person-years; aHR 0.75; 95%CI: 0.68-0.82; P < 0.001). CONCLUSION: This retrospective cohort study indicates that LFC has a significantly protective effect on lowering the risk of liver cancer, in a dose-dependent and time-dependent manner.

Respiratory Outcomes of Insulin Use in Patients with COPD: A Nationwide Population-Based Cohort Study.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) with severe hyperglycemia may require insulin to lower glucose levels in people with coexisting type 2 diabetes (T2D) and COPD. We conducted this study to examine the risk of hospitalization for COPD, pneumonia, ventilator use, lung cancer, hypoglycemia, and mortality with and without insulin use in people with T2D and COPD. We adopted propensity-score-matching to identify 2370 paired insulin users and non-users from Taiwan's National Health Insurance Research Database between 1 January 2000 and 31 December 2018. Cox proportional hazards models and the Kaplan-Meier method were utilized to compare the risk of outcomes between study and control groups. The mean follow-up for insulin users and non-users was 6.65 and 6.37 years. Compared with no insulin use, insulin use was associated with a significantly increased risk of hospitalization for COPD (aHR 1.7), bacterial pneumonia (aHR 2.42), non-invasive positive pressure ventilation (aHR 5.05), invasive mechanical ventilation (aHR 2.72), and severe hypoglycemia (aHR 4.71), but with no significant difference in the risk of death. This nationwide cohort study showed that patients with T2D and COPD requiring insulin therapy may have an increased risk of acute COPD exacerbations, pneumonia, ventilator use, and severe hypoglycemia without a significant increase in the risk of death.

Impact of individual microvascular disease on the risks of macrovascular complications in type 2 diabetes: a nationwide population-based cohort study.

BACKGROUND: This study compared the risks of cardiovascular morbidity and mortality between patients with type 2 diabetes (T2D) with and without microvascular diseases, and between matched patients with microvascular diseases. METHODS: We identified newly diagnosed type 2 diabetes patients from National Health Insurance Research Database in Taiwan from January 1, 2008, to December 31, 2019. Propensity score matching was applied to construct matched pairs of patients with diabetic kidney disease, retinopathy, or neuropathy. Multivariable Cox proportional-hazard models were adopted to compare the risks of cardiovascular morbidity and mortality. RESULTS: Patients with microvascular disease had a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. Among the matched cohorts, patients with diabetic retinopathy had a significantly higher risk of stroke development than those with diabetic kidney disease (aHR 1.11, 95%CI 1.03-1.2). Diabetic neuropathy showed a significantly higher risk of stroke development than diabetic kidney disease (aHR 1.17, 95%CI 1.1-1.25) and diabetic retinopathy (aHR 1.12, 95%CI 1.03-1.21). Diabetic retinopathy had a significantly higher risk of incident heart failure than diabetic kidney disease (aHR 1.43, 95%CI 1.3-1.57), and diabetic neuropathy had a significantly lower risk of incident heart failure than diabetic retinopathy (aHR 0.79, 95%CI 0.71-0.87). CONCLUSIONS: T2D patients with microvascular disease have a significantly higher risk of cardiovascular morbidities and mortality than those without microvascular disease. In the matched cohorts, diabetic neuropathy was significantly associated with stroke development, and diabetic retinopathy had a significant association with heart failure compared to other microvascular diseases.

The risk of ischemic stroke significantly increases in individuals with blepharitis: A population-based study involving 424,161 patients.

INTRODUCTION: To investigate the association of blepharitis and ischemic stroke. METHODS: This nationwide retrospective cohort study used population-based data in Taiwan. Individuals aged 20 and above with diagnosis of blepharitis was included based on electrical medical records. After exclusion of ineligible cases, 424,161 patients were identified between 2008 and 2018. The blepharitis and non-blepharitis cohorts were matched based on sex, age, and comorbidities. Multivariable-adjusted Cox proportional hazards model was adopted to calculate the hazard ratio and 95% confidence interval (CI) between blepharitis and non-blepharitis cohorts. The incidence of ischemic stroke was estimated by Kaplan-Meier analysis. RESULTS: 424,161 pairs of blepharitis cohort and non-blepharitis cohort were 1:1 propensity score matched for statistical analysis. Patients with blepharitis had significantly increased risk of ischemic stroke compared with the individuals without blepharitis (adjusted hazard ratio 1.32, 95% CI 1.29-1.34, P < 0.001). A significantly higher risk of ischemic stroke was observed in blepharitis cohort with a previous diagnosis of cancer than in those without cancer (P for interaction < 0.0001). Kaplan-Meier survival analysis revealed the cumulative incidence of ischemic stroke increased in the blepharitis cohort compared with that in the non-blepharitis cohort in 10 years (log-rank P < 0.001). The follow-up period analysis further indicated 1.41-fold adjusted hazard (95% CI 1.35-1.46, P < 0.001) of ischemic stroke within a year after blepharitis diagnosis. CONCLUSIONS: Patients with blepharitis had an elevated risk of developing ischemic stroke. Early treatment and active surveillance are suggested for patients with chronic blepharitis. Further research is required to determine the casual relationship between blepharitis and ischemic stroke, as well as the underlying mechanism.

Acupuncture Is Effective at Reducing the Risk of Stroke in Patients with Migraines: A Real-World, Large-Scale Cohort Study with 19-Years of Follow-Up.

Migraines are common headache disorders and risk factors for subsequent strokes. Acupuncture has been widely used in the treatment of migraines; however, few studies have examined whether its use reduces the risk of strokes in migraineurs. This study explored the long-term effects of acupuncture treatment on stroke risk in migraineurs using national real-world data. We collected new migraine patients from the Taiwan National Health Insurance Research Database (NHIRD) from 1 January 2000 to 31 December 2017. Using 1:1 propensity-score matching, we assigned patients to either an acupuncture or non-acupuncture cohort and followed up until the end of 2018. The incidence of stroke in the two cohorts was compared using the Cox proportional hazards regression analysis. Each cohort was composed of 1354 newly diagnosed migraineurs with similar baseline characteristics. Compared with the non-acupuncture cohort, the acupuncture cohort had a significantly reduced risk of stroke (adjusted hazard ratio, 0.4; 95% confidence interval, 0.35-0.46). The Kaplan-Meier model showed a significantly lower cumulative incidence of stroke in migraine patients who received acupuncture during the 19-year follow-up (log-rank test, p < 0.001). Acupuncture confers protective benefits on migraineurs by reducing the risk of stroke. Our results provide new insights for clinicians and public health experts.

Immune thrombocytopenia and risk of stroke: Evidence from a nationwide population-based cohort study.

BACKGROUND: Research investigating differences in the overall stroke risk between individuals with and without immune thrombocytopenia (ITP) is lacking. METHODS: This real-world study used the National Health Insurance Research Database (NHIRD). Risk of stroke was compared between 13,085 individuals with ITP enrolled between 1 January 2000 and 31 December 2015 and a control cohort of 52,340 individuals without ITP (1:4 ratio propensity score-matched by age, sex, index year, relevant comorbidities, and medications). Sub-distribution hazards models were used to estimate adjusted sub-distribution hazard ratio (SHR) and 95% confidence intervals (CIs), with the non-ITP group as the control group. RESULTS: Of the 65,425 participants, 13,085 had ITP, 63.3% were women, and the mean age was 52.59 years. The risk of both ischemic and hemorrhagic stroke was 1.14 times (adjusted SHR 1.14, 95% CI, 1.07-1.22) and 1.93 times (adjusted SHR 1.93, 95% CI, 1.70-2.20) higher in the ITP group than in controls. Patients with ITP in the 20- to 29-year subgroup had a higher risk of new-onset stroke (adjusted SHR, 4.06 (95% CI, 2.72-6.07), p value for interaction <0.01) than those aged 20-29 years without ITP. Individuals with severe ITP with splenectomy had a 1.79 times higher overall stroke risk than those without. CONCLUSIONS: ITP is associated with increased risk of both ischemic and hemorrhagic stroke.

Metformin Use before Influenza Vaccination May Lower the Risks of Influenza and Related Complications.

Older adults are more likely to have influenza and respond less well to the flu vaccine. We conducted this study to investigate whether pre-influenza vaccination metformin use had an effect on influenza and relevant complications in older adults with type 2 diabetes mellitus. Propensity score matching was used to identify 28,169 pairs of metformin users and nonusers from Taiwan's National Health Insurance Research Database from 1 January 2000 to 31 December 2018. We used Cox proportional hazards models to calculate the risks of hospitalization for influenza, pneumonia, cardiovascular disease, ventilation, and mortality between metformin users and nonusers. Compared with metformin nonusers, the aHRs (95% CI) for metformin users at risk of hospitalization for influenza, pneumonia, cardiovascular disease, invasive mechanical ventilation, death due to cardiovascular disease, and all-cause mortality were 0.60 (0.34, 1.060), 0.63 (0.53, 0.76), 0.41 (0.36, 0.47), 0.56 (0.45, 0.71), 0.49 (0.33, 0.73), and 0.44 (0.39, 0.51), respectively. Higher cumulative duration of metformin use was associated with lower risks of these outcomes than no use of metformin. This cohort study demonstrated that pre-influenza vaccination metformin use was associated with lower risks of hospitalizations for influenza, pneumonia, cardiovascular disease, mechanical ventilation, and mortality compared to metformin nonusers.

Metformin and the Development of Asthma in Patients with Type 2 Diabetes.

We conducted this study to compare the risks of asthma development and exacerbation between metformin users and nonusers. Overall, 57,743 propensity score-matched metformin users and nonusers were identified from Taiwan's National Health Insurance Research Database between 1 January 2000, and 31 December 2017. We used the Cox proportional hazards model with robust standard error estimates to compare the risks of asthma onset, exacerbation, and hospitalization for asthma in participants with type 2 diabetes (T2D). Compared with metformin nonuse, the aHRs (95% CI) for metformin use in asthma development, exacerbation, and hospitalization for asthma were 1.13 (1.06−1.2), 1.62 (1.35−1.95), and 1.5 (1.22−1.85), respectively. The cumulative incidences of asthma development, exacerbation, and hospitalization for asthma were significantly higher in metformin users than nonusers (p < 0.001). A longer cumulative duration of metformin use for more than 728 days was associated with significantly higher risks of outcomes than metformin nonuse. Our study demonstrated that metformin users showed significantly higher risks of asthma development, exacerbation, and hospitalization for asthma than metformin nonusers. Moreover, metformin use for more than 728 days was associated with higher risks of outcomes. A randomized control study is warranted to verify our results.

Role of Metformin in Morbidity and Mortality Associated with Urinary Tract Infections in Patients with Type 2 Diabetes.

We conducted this study to compare the morbidity and mortality associated with UTI and sepsis, between metformin users and nonusers in patients with diabetes. As such, 40,774 propensity score-matched metformin users and nonusers were identified from Taiwan's National Health Insurance Research Database, between 1 January 2000 and 31 December 2017. We adopted the Cox proportional hazards model with robust standard error estimates for comparing the risks of UTI, sepsis, and death due to UTI or sepsis, in patients with T2DM. Compared with the nonuse of metformin, the aHRs (95% CI) for metformin use in UTI, recurrent UTI, sepsis, and death due to UTI or sepsis were 1.06 (0.98, 1.15), 1.08 (0.97, 1.2), 1.01 (0.97, 1.06), and 0.58 (0.42, 0.8), respectively. The cumulative incidence of death due to UTI or sepsis was significantly lower in metformin users than in nonusers (p = 0.002). A longer cumulative duration of metformin use had a lower aHR in the risk of death due to UTI or sepsis than metformin nonuse. In patients with T2DM, metformin use showed no significant differences in the risks of UTI, recurrent UTI, or sepsis. However, it was associated with a lower risk of death due to UTI or sepsis than metformin nonuse.

Corrigendum: Decreased Risk of Anxiety in Diabetic Patients Receiving Glucagon-Like Peptide-1 Receptor Agonist: A Nationwide, Population-Based Cohort Study.

[This corrects the article DOI: 10.3389/fphar.2022.765446.].

Metformin use and the risk of bacterial pneumonia in patients with type 2 diabetes.

Persons with type 2 diabetes (T2D) have neutrophil dysfunction with a higher risk of infection than those without diabetes. We conducted this study aiming to compare the risk of pneumonia between metformin use and nonuse in persons with T2D. We identified 49,012 propensity score-matched metformin users and nonusers from Taiwan's National Health Insurance Research Database between January 1, 2000, and December 31, 2017. We used the Cox proportional hazards model to compare the risks of pneumonia and respiratory death. The mean (SD) age of the participants was 57.46 (12.88) years, and the mean follow-up time for metformin users and nonusers was 5.47 (3.71) years and 5.15 (3.87) years, respectively. Compared with the nonuse of metformin, the adjusted hazard ratios (95% CI) for metformin use in bacterial pneumonia, invasive mechanical ventilation, and respiratory cause of death were 0.89 (0.84-0.94), 0.77 (0.73-0.82), and 0.64 (0.56-0.74), respectively. A longer cumulative duration of metformin use had further lower adjusted hazard ratios in these risks compared with nonuse. In patients with T2D, metformin use was associated with significantly lower risks of bacterial pneumonia, invasive mechanical ventilation, and respiratory cause of death; moreover, longer metformin use duration was associated with lower hazard ratios of these risks.

Decreased Risk of Anxiety in Diabetic Patients Receiving Glucagon-like Peptide-1 Receptor Agonist: A Nationwide, Population-Based Cohort Study.

Background: Previous findings on using Glucagon-like peptide-1 receptor agonist (GLP1-RA) as an antidepressant were conflicting, lacking large-scale studies. We used population-based data to investigate depression and anxiety risk in diabetic patients receiving the medication. Methods: From claims records of the National Health Insurance Research Database (NHIRD) of Taiwan, we identified cohorts of 10,690 GLP1-RA users and 42,766 propensity score-matched patients without GLP1-RA use from patients with diabetes mellitus (DM) diagnosed in 2011-2017, matched by age, gender, index year, occupation, urbanization, comorbidities, and medications. Incidence, hazard ratios (HR) and 95% confidence interval (CI) of depression and/or anxiety were estimated by the end of 2017. Results: The overall combined incidence of anxiety and/or depression was lower in GLP1-RA users than in non-users (6.80 versus 9.36 per 1,000 person-years), with an adjusted HR adjusted hazard ratio (aHR) of 0.8 (95% CI: 0.67-0.95) after controlling for covariates. The absolute incidence reduction was greater in anxiety (2.13 per 1,000 person-years) than in depression (0.41 per 1,000 person-years). The treatment effectiveness was significant for women. Patients taking GLP1-RA for longer than 180 days had the incidence of anxiety reduced to 2.93 per 1,000 person-years, with an aHR of 0.41 (95%CI: 0.27-0.61), compared to non-users. Dulaglutide could significantly decrease risks of both anxiety and depression. Conclusion: Patients with DM receiving GLP1-RA therapy have a greater reduction of the risk of anxiety than that of depression. Our findings strengthen previous research that advocated possible anti-depressant or anxiolytic effects of GLP1-RA and may lead to improved treatment adherence among patients with DM.

Familial aggregation and shared genetic loading for major psychiatric disorders and type 2 diabetes.

AIMS/HYPOTHESIS: Psychiatric disorders, such as schizophrenia (SCZ), major depressive disorder (MDD) and bipolar disorder (BPD), are highly comorbid with type 2 diabetes. However, the mechanisms underlying such comorbidity are understudied. This study explored the familial aggregation of common psychiatric disorders and type 2 diabetes by testing family history association, and investigated the shared genetic loading between them by testing the polygenic risk score (PRS) association. METHODS: A total of 105,184 participants were recruited from the Taiwan Biobank, and genome-wide genotyping data were available for 95,238 participants. The Psychiatric Genomics Consortium-derived PRS for SCZ, MDD and BPD was calculated. Logistic regression was used to estimate the OR with CIs between a family history of SCZ/MDD/BPD and a family history of type 2 diabetes, and between the PRS and the risk of type 2 diabetes. RESULTS: A family history of type 2 diabetes was associated with a family history of SCZ (OR 1.23, 95% CI 1.08, 1.40), MDD (OR 1.19, 95% CI 1.13, 1.26) and BPD (OR 1.26, 95% CI 1.15, 1.39). Compared with paternal type 2 diabetes, maternal type 2 diabetes was associated with a higher risk of a family history of SCZ. SCZ PRS was negatively associated with type 2 diabetes in women (OR 0.92, 95% CI 0.88, 0.97), but not in men; the effect of SCZ PRS reduced after adjusting for BMI. MDD PRS was positively associated with type 2 diabetes (OR 1.04, 95% CI 1.00, 1.07); the effect of MDD PRS reduced after adjusting for BMI or smoking. BPD PRS was not associated with type 2 diabetes. CONCLUSIONS/INTERPRETATION: The comorbidity of type 2 diabetes with psychiatric disorders may be explained by shared familial factors. The shared polygenic loading between MDD and type 2 diabetes implies not only pleiotropy but also a shared genetic aetiology for the mechanism behind the comorbidity. The negative correlation between polygenic loading for SCZ and type 2 diabetes implies the role of environmental factors.

Liver-related long-term outcomes of alpha-glucosidase inhibitors in patients with diabetes and liver cirrhosis.

Background: Adequate management of diabetes in patients with liver cirrhosis can be challenging. We conducted this study to investigate the liver-related long term outcomes of alpha-glucosidase inhibitors (AGIs) in patients with diabetes and cirrhosis. Methods: From National Health Insurance Research Database (NHIRD) in Taiwan, we recruited propensity-score matched alpha-glucosidase inhibitor users and non-users from a cohort of type 2 diabetes mellitus (T2DM) with compensated liver cirrhosis between 1 January 2000, and 31 December 2017, and followed them until 31 December 2018. Cox proportional hazards models with robust sandwich standard error estimates were used to assess the risk of main outcomes for alpha-glucosidase inhibitor users versus non-users. Results: The incidence rates of mortality during follow-up were 65.56 vs. 96.06 per 1,000 patient-years for alpha-glucosidase inhibitor users and non-users, respectively. The multivariable-adjusted model shows that alpha-glucosidase inhibitor users had significantly lower risks of all-cause mortality (aHR 0.63, 95% CI 0.56-0.71), hepatocellular carcinoma (aHR 0.55, 95% CI 0.46-0.67), decompensated cirrhosis (aHR 0.74 95% CI 0.63-0.87), hepatic encephalopathy (aHR 0.72, 95% CI 0.60-0.87), and hepatic failure (aHR 0.74, 95% CI 0.62-0.88) than alpha-glucosidase inhibitor non-users. Patients who received alpha-glucosidase inhibitors for a cumulative duration of more than 364 days had significantly lower risks of these outcomes than non-users. Conclusion: Alpha-glucosidase inhibitor use was associated with a lower risk of mortality, hepatocellular carcinoma, decompensated cirrhosis, and hepatic failure in patients with diabetes and compensated cirrhosis. alpha-glucosidase inhibitors may be useful for the management of diabetes in patients with compensated liver cirrhosis. Large-scale prospective studies are required to verify our results.

The Risk of Nephropathy, Retinopathy, and Leg Amputation in Patients With Diabetes and Hypertension: A Nationwide, Population-Based Retrospective Cohort Study.

Purpose: To compare the risks of chronic kidney disease (CKD), end-stage renal disease (ESRD), sight-threatening retinopathy, and leg amputation between patients with diabetes or hypertension. Methods: From January 1, 2000, to December 31, 2015, we identified 28943 matched pairs of patients with diabetes with and without subsequent hypertension, 89102 pairs of patients with hypertension with and without subsequent diabetes, and 145294 pairs of patients with coexisting diabetes and hypertension with a previous history of diabetes or hypertension from Taiwan's National Health Insurance Research Database. Cox proportional-hazard models were used for calculating the risks of CKD, sight-threatening retinopathy, and leg amputation. Results: The mean follow-up time of this study in different cohorts was between 3.59 and 4.28 years. In diabetes patients with vs. without subsequent hypertension, hypertension patients with vs. without subsequent diabetes, and comorbid diabetes and hypertension patients with previous diabetes vs. with previous hypertension, the adjusted HRs (95% CIs) for CKD were 2.77 (2.61-2.94), 1.73 (1.68-1.77), and 1.04 (1.02-1.07); for ESRD were 42.38 (22.62-79.4), 2.76 (2.43-3.13), and 0.72 (0.66-0.79); for sight-threatening retinopathy were 2.07 (1.85-2.3), 3.41 (3.14-3.71), and for leg amputation were 1.51 (1.43-1.58); and 4.74 (3.02-7.43), 6.27(4.72-8.31), and 1.19(1.03-1.38). Conclusions: This study demonstrated that both diabetes and hypertension are risk factors for the development of CKD, retinopathy, and amputation. Tracing subsequent diabetes for patients with hypertension, and hypertension for patients with diabetes are important in clinical settings.