Pub Date : 2025-02-01DOI: 10.1016/j.jdiacomp.2024.108910
Assim A. Alfadda , Adel N. Alqutub , Suphia M. Sherbeeni , Abdullah S. Aldosary , Saleh A. Alqahtani , Arthur Isnani , Rukhsana Gul , Mohammad S. Khaleel , Sara M. Alqasim , Abdulrahman M. Almaghamsi
Aim
To investigate predictors of liver fibrosis progression in patients with type 2 diabetes mellitus (T2DM) over a minimum follow-up duration of three years.
Methods
Two hundred and thirty-three patients completed the follow-up period and their clinical, laboratory and liver FibroScan data are reported. Patients were categorized into progressors 42 (18.0 %) and non-progressors 191 (82.0 %) based on liver fibrosis progression. Factors influencing fibrosis progression were identified by comparing these groups.
Results
Progressors showed significantly increased aspartate aminotransferase (AST) (p = 0.010), increased alkaline phosphatase (ALP) (p = 0.001) and decreased platelet count (p = 0.002). Non-progressors exhibited significant decreases in diastolic blood pressure (DBP) (p = 0.050), body mass index (BMI) (p < 0.001), waist circumference (p < 0.001), gamma-glutamyl transferase (GGT) (p < 0.001), albumin (p < 0.001), alanine aminotransferase (ALT) (p = 0.022), glycosylated haemoglobin (HbA1c) (p = 0.002) and fasting blood sugar (FBS) (p = 0.030) with increase in HDL-cholesterol (p < 0.001), creatinine (p < 0.001), bilirubin (p < 0.001), and ALP (p = 0.007). Baseline parameters predictive of liver fibrosis progression included elevated AST and reduced platelet count. Delta changes from baseline to follow-up revealed that increases in ALP, BMI, waist circumference, and reduction in platelet count were correlated with fibrosis progression. Use of GLP-1 receptor agonist was associated with reduced progression.
Conclusion
In conclusion, increase in ALP and waist circumference and reduction in platelet count are predictive of liver fibrosis progression in patients with T2DM. GLP-1 receptor agonists use seems to have a promising protective effect against liver fibrosis progression.
{"title":"Predictors of liver fibrosis progression in cohort of type 2 diabetes mellitus patients with MASLD","authors":"Assim A. Alfadda , Adel N. Alqutub , Suphia M. Sherbeeni , Abdullah S. Aldosary , Saleh A. Alqahtani , Arthur Isnani , Rukhsana Gul , Mohammad S. Khaleel , Sara M. Alqasim , Abdulrahman M. Almaghamsi","doi":"10.1016/j.jdiacomp.2024.108910","DOIUrl":"10.1016/j.jdiacomp.2024.108910","url":null,"abstract":"<div><h3>Aim</h3><div>To investigate predictors of liver fibrosis progression in patients with type 2 diabetes mellitus (T2DM) over a minimum follow-up duration of three years.</div></div><div><h3>Methods</h3><div>Two hundred and thirty-three patients completed the follow-up period and their clinical, laboratory and liver FibroScan data are reported. Patients were categorized into progressors 42 (18.0 %) and non-progressors 191 (82.0 %) based on liver fibrosis progression. Factors influencing fibrosis progression were identified by comparing these groups.</div></div><div><h3>Results</h3><div>Progressors showed significantly increased aspartate aminotransferase (AST) (p = 0.010), increased alkaline phosphatase (ALP) (p = 0.001) and decreased platelet count (p = 0.002). Non-progressors exhibited significant decreases in diastolic blood pressure (DBP) (p = 0.050), body mass index (BMI) (p < 0.001), waist circumference (p < 0.001), gamma-glutamyl transferase (GGT) (p < 0.001), albumin (p < 0.001), alanine aminotransferase (ALT) (p = 0.022), glycosylated haemoglobin (HbA1c) (p = 0.002) and fasting blood sugar (FBS) (p = 0.030) with increase in HDL-cholesterol (p < 0.001), creatinine (p < 0.001), bilirubin (p < 0.001), and ALP (p = 0.007). Baseline parameters predictive of liver fibrosis progression included elevated AST and reduced platelet count. Delta changes from baseline to follow-up revealed that increases in ALP, BMI, waist circumference, and reduction in platelet count were correlated with fibrosis progression. Use of GLP-1 receptor agonist was associated with reduced progression.</div></div><div><h3>Conclusion</h3><div>In conclusion, increase in ALP and waist circumference and reduction in platelet count are predictive of liver fibrosis progression in patients with T2DM. GLP-1 receptor agonists use seems to have a promising protective effect against liver fibrosis progression.</div><div><span><span><strong>ClinicalTrials.gov</strong></span><svg><path></path></svg></span> <strong>ID:</strong> <span><span>NCT05697991</span><svg><path></path></svg></span></div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108910"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142828737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jdiacomp.2024.108901
Zhaohui Zheng, Bin Cao, Jing Ke, Dong Zhao
Background
This study aimed to examine the association between mean cumulative glycemic burden (MCGB) and variability cumulative glycemic burden (VCGB) with diabetic foot ulcers (DFUs).
Methods
Participants were followed up at least 4 times with 4 recorded glycosylated hemoglobin (HbA1c) measurements. Glycemic burden during follow-up period was defined as the trapezoidal areas enclosed by the HbA1c measurements taken during two consecutive visits and the responding time interval. MCGB was calculated by dividing sum of total trapezoidal areas by the period of follow-up. VCGB was defined as the standard deviation of the trapezoidal areas divided to the mean of trapezoidal areas. To identify the association between MCGB and VCGB with DFUs, a Cox regression analysis was conducted.
Results
Among 1876 diabetic patients, 138 (7.4 %) developed foot ulcers. As MCGB increased across quartiles, DFUs incidence also rose significantly (3.2 % to 16.0 %, P < 0.001). Similarly, the prevalence of DFUs increases with increasing quartiles of mean HbA1c level (3.2 % to 16.2 %; P < 0.001). When assessing VCGB, ulcer incidence gradually increased with the quartiles increased (P = 0.040), but HbA1c variability did not follow a similar trend (P = 0.133).
Multivariable Cox regression analysis indicates that compared to the first quartile, both MCGB and VCGB in the fourth quartile significantly increase the risk of DFUs (HR = 2.99 and 5.29, respectively).
Conclusions
Elevated MCGB and VCGB correlate positively with DFUs. In clinical practice, lowering blood glucose levels and reducing glycemic variability are both crucial for reducing the occurrence of diabetic foot ulcers.
{"title":"The effect of long-term glycemic burden on the incidence of diabetic foot ulcers: A retrospective study","authors":"Zhaohui Zheng, Bin Cao, Jing Ke, Dong Zhao","doi":"10.1016/j.jdiacomp.2024.108901","DOIUrl":"10.1016/j.jdiacomp.2024.108901","url":null,"abstract":"<div><h3>Background</h3><div>This study aimed to examine the association between mean cumulative glycemic burden (MCGB) and variability cumulative glycemic burden (VCGB) with diabetic foot ulcers (DFUs).</div></div><div><h3>Methods</h3><div>Participants were followed up at least 4 times with 4 recorded glycosylated hemoglobin (HbA1c) measurements. Glycemic burden during follow-up period was defined as the trapezoidal areas enclosed by the HbA1c measurements taken during two consecutive visits and the responding time interval. MCGB was calculated by dividing sum of total trapezoidal areas by the period of follow-up. VCGB was defined as the standard deviation of the trapezoidal areas divided to the mean of trapezoidal areas. To identify the association between MCGB and VCGB with DFUs, a Cox regression analysis was conducted.</div></div><div><h3>Results</h3><div>Among 1876 diabetic patients, 138 (7.4 %) developed foot ulcers. As MCGB increased across quartiles, DFUs incidence also rose significantly (3.2 % to 16.0 %, <em>P</em> < 0.001). Similarly, the prevalence of DFUs increases with increasing quartiles of mean HbA1c level (3.2 % to 16.2 %; <em>P</em> < 0.001). When assessing VCGB, ulcer incidence gradually increased with the quartiles increased (<em>P</em> = 0.040), but HbA1c variability did not follow a similar trend (<em>P</em> = 0.133).</div><div>Multivariable Cox regression analysis indicates that compared to the first quartile, both MCGB and VCGB in the fourth quartile significantly increase the risk of DFUs (HR = 2.99 and 5.29, respectively).</div></div><div><h3>Conclusions</h3><div>Elevated MCGB and VCGB correlate positively with DFUs. In clinical practice, lowering blood glucose levels and reducing glycemic variability are both crucial for reducing the occurrence of diabetic foot ulcers.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108901"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Patients with type 1 diabetes (DM1), even in the setting of adequate glycaemic control, have an excess risk for developing cardiovascular disease. Residual insulin secretion (RIS), measured by detectable C-peptide levels in patients with DM1, might protect against diabetes-related complications. This study aimed to examine the relationship between residual insulin secretion and prognostic markers of cardiovascular complications in patients with DM1.
Methods
A total of 137 patients with DM1 were included in this analysis. They were of young age (<45 years), with an established diagnosis of over two years before the study entry and without a history of cardiovascular complications. All patients underwent complete clinical and laboratory evaluation. A c-peptide measurement of ≥0.05 ng/ml was used to identify the presence of RIS. Pulse wave velocity (PWV), cardiac autonomic function assessed both at rest, by total power of heart rate variability and dynamically, by the expiration to inspiration (e/i) index, albumin to creatinine ratio (ACR), and high sensitivity CRP (hs-CRP) were used as predictive biomarkers of cardiovascular complications.
Results
Female participants represented 63.5% of the population [mean age: 29.7 (±8.1) years, mean HbA1c: 7.6% (±1.4), median diabetes duration:15 (10-21) years, median age at diabetes diagnosis: 13 (8-17) years]]. The median value of fasting c-peptide was 0.04 (0.03-0.05) ng/ml, and RIS was detected in 32 patients (23.4%). Patients with RIS had a shorter diabetes duration, an older age at diagnosis and a lower BMI, while no significant association was found between residual c-peptide and age or HbA1c. RIS was significantly associated with lower PWV values [8.1 m/s² (7-8.7) vs 9.2 m/s² (7.8-10.1), p <0,001], higher total power values [1124 Hz (600-3277) vs 577 Hz (207-2091), p <0,001], and higher E/I measurements [1.4 (1.2-1.5) vs. 1.3 (1.2-1.4), p=0.01]. No significant association was noted between RIS and either ACR or hs-CRP. In multivariable linear regression analysis, the association between RIS and lower PWV values remained significant (p= 0.007) regardless of age, sex, diabetes duration or age of diagnosis, blood pressure and BMI. Similarly, residual insulin secretion retained a significant independent association with total power (p= 0.032) and E/I (p=0.045).
Conclusion
In young patients with DM1, free of macrovascular complications, residual insulin secretion is independently associated with more favorable prognostic markers of subclinical atherosclerosis and cardiac autonomic function.
{"title":"The relationship between residual insulin secretion and subclinical cardiovascular risk indices in young adults with type 1 diabetes","authors":"Aikaterini Barmpagianni, Georgios Karamanakos, Ioanna A. Anastasiou, Aikaterini Kountouri, Vaia Lambadiari, Stavros Liatis","doi":"10.1016/j.jdiacomp.2024.108946","DOIUrl":"10.1016/j.jdiacomp.2024.108946","url":null,"abstract":"<div><h3>Background</h3><div>Patients with type 1 diabetes (DM1), even in the setting of adequate glycaemic control, have an excess risk for developing cardiovascular disease. Residual insulin secretion (RIS), measured by detectable C-peptide levels in patients with DM1, might protect against diabetes-related complications. This study aimed to examine the relationship between residual insulin secretion and prognostic markers of cardiovascular complications in patients with DM1.</div></div><div><h3>Methods</h3><div>A total of 137 patients with DM1 were included in this analysis. They were of young age (<45 years), with an established diagnosis of over two years before the study entry and without a history of cardiovascular complications. All patients underwent complete clinical and laboratory evaluation. A c-peptide measurement of ≥0.05 ng/ml was used to identify the presence of RIS. Pulse wave velocity (PWV), cardiac autonomic function assessed both at rest, by total power of heart rate variability and dynamically, by the expiration to inspiration (e/i) index, albumin to creatinine ratio (ACR), and high sensitivity CRP (hs-CRP) were used as predictive biomarkers of cardiovascular complications.</div></div><div><h3>Results</h3><div>Female participants represented 63.5% of the population [mean age: 29.7 (±8.1) years, mean HbA1c: 7.6% (±1.4), median diabetes duration:15 (10-21) years, median age at diabetes diagnosis: 13 (8-17) years]]. The median value of fasting c-peptide was 0.04 (0.03-0.05) ng/ml, and RIS was detected in 32 patients (23.4%). Patients with RIS had a shorter diabetes duration, an older age at diagnosis and a lower BMI, while no significant association was found between residual c-peptide and age or HbA1c. RIS was significantly associated with lower PWV values [8.1 m/s² (7-8.7) vs 9.2 m/s² (7.8-10.1), p <0,001], higher total power values [1124 Hz (600-3277) vs 577 Hz (207-2091), p <0,001], and higher E/I measurements [1.4 (1.2-1.5) vs. 1.3 (1.2-1.4), p=0.01]. No significant association was noted between RIS and either ACR or hs-CRP. In multivariable linear regression analysis, the association between RIS and lower PWV values remained significant (p= 0.007) regardless of age, sex, diabetes duration or age of diagnosis, blood pressure and BMI. Similarly, residual insulin secretion retained a significant independent association with total power (p= 0.032) and E/I (p=0.045).</div></div><div><h3>Conclusion</h3><div>In young patients with DM1, free of macrovascular complications, residual insulin secretion is independently associated with more favorable prognostic markers of subclinical atherosclerosis and cardiac autonomic function.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108946"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142894737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jdiacomp.2024.108947
Simo Liu , Jing Ke , Xiaotong Feng , Yongsong Xu , Lin Zhu , Longyan Yang , Dong Zhao
Background
Left ventricular hypertrophy (LVH) is an important and common pathologic change in the heart of patients with diabetes mellitus. Microvascular complications have been reported to be involved in the development and process of LVH. This study aimed to explore the association between diabetic microvascular complications and LVH in patients with type 2 diabetes mellitus (T2DM).
Material and methods
This is a cross-sectional study. A total of 2912 patients with T2DM were enrolled, including 360 patients with LVH and 2552 patients without LVH. Demographic data, medical history and laboratory indices were collected, along with information on diabetic microvascular complications and results from cardiac ultrasonography. The study utilized multivariable logistic regression to evaluate the independent effects of microvascular complications (DR, DPN, or DKD) and the cumulative number of these complications on the presence of LVH, while adjusting for potential confounding factors.
Result
In patients with T2DM, those with LVH were older and had higher body mass index, waist circumference and hip circumference than those without LVH. Additionally, the proportion of patients with diabetic retinopathy (DR) and diabetic kidney disease (DKD) was larger among those with LVH compared to those without LVH. After adjusting for potential confounding factors, DR and DKD were associated with increased odds of LVH (odds ratio [OR] = 1.351 and OR = 1.404, respectively). The risk of LVH also increased progressively in patients with two or more diabetic microvascular conditions compared to those with only one. In subgroup analysis, the risk of LVH increased with the number of microvascular conditions in male patients with T2DM.
Conclusions
Diabetic microvascular complications were significantly associated with LVH in T2DM. Moreover, the risk of LVH increased with the number of microvascular complications, particularly in males with T2DM.
{"title":"Diabetic microvascular complications are associated with left ventricular hypertrophy in patients with type 2 diabetes mellitus","authors":"Simo Liu , Jing Ke , Xiaotong Feng , Yongsong Xu , Lin Zhu , Longyan Yang , Dong Zhao","doi":"10.1016/j.jdiacomp.2024.108947","DOIUrl":"10.1016/j.jdiacomp.2024.108947","url":null,"abstract":"<div><h3>Background</h3><div>Left ventricular hypertrophy (LVH) is an important and common pathologic change in the heart of patients with diabetes mellitus. Microvascular complications have been reported to be involved in the development and process of LVH. This study aimed to explore the association between diabetic microvascular complications and LVH in patients with type 2 diabetes mellitus (T2DM).</div></div><div><h3>Material and methods</h3><div>This is a cross-sectional study. A total of 2912 patients with T2DM were enrolled, including 360 patients with LVH and 2552 patients without LVH. Demographic data, medical history and laboratory indices were collected, along with information on diabetic microvascular complications and results from cardiac ultrasonography. The study utilized multivariable logistic regression to evaluate the independent effects of microvascular complications (DR, DPN, or DKD) and the cumulative number of these complications on the presence of LVH, while adjusting for potential confounding factors.</div></div><div><h3>Result</h3><div>In patients with T2DM, those with LVH were older and had higher body mass index, waist circumference and hip circumference than those without LVH. Additionally, the proportion of patients with diabetic retinopathy (DR) and diabetic kidney disease (DKD) was larger among those with LVH compared to those without LVH. After adjusting for potential confounding factors, DR and DKD were associated with increased odds of LVH (odds ratio [OR] = 1.351 and OR = 1.404, respectively). The risk of LVH also increased progressively in patients with two or more diabetic microvascular conditions compared to those with only one. In subgroup analysis, the risk of LVH increased with the number of microvascular conditions in male patients with T2DM.</div></div><div><h3>Conclusions</h3><div>Diabetic microvascular complications were significantly associated with LVH in T2DM. Moreover, the risk of LVH increased with the number of microvascular complications, particularly in males with T2DM.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108947"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143006490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Type 2 diabetes is a chronic disease requiring comprehensive pharmacological and non-pharmacological interventions to slow its progression and prevent or delay its micro- and macrovascular complications. Oxidative stress contributes to the development and progression of type 2 diabetes as well as to the development of its complications through several mechanisms. Therefore, therapeutic targeting of oxidative stress could aid in managing this disease and its complications. In our study, we have collected information on the most frequently used antidiabetic drugs (metformin, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors) in the EU and the USA based on their antioxidant effects.
Based on our results, we can conclude that the antioxidant effects of the investigated antidiabetics may contribute significantly to the management of the disease and its complications and may open new therapeutic perspectives in their prevention.
{"title":"Diabetes mellitus therapy in the light of oxidative stress and cardiovascular complications","authors":"Alaa A.M. Osman, Adrienn Seres-Bokor, Eszter Ducza","doi":"10.1016/j.jdiacomp.2024.108941","DOIUrl":"10.1016/j.jdiacomp.2024.108941","url":null,"abstract":"<div><div>Type 2 diabetes is a chronic disease requiring comprehensive pharmacological and non-pharmacological interventions to slow its progression and prevent or delay its micro- and macrovascular complications. Oxidative stress contributes to the development and progression of type 2 diabetes as well as to the development of its complications through several mechanisms. Therefore, therapeutic targeting of oxidative stress could aid in managing this disease and its complications. In our study, we have collected information on the most frequently used antidiabetic drugs (metformin, glucagon-like peptide 1 receptor agonists and sodium-glucose cotransporter 2 inhibitors) in the EU and the USA based on their antioxidant effects.</div><div>Based on our results, we can conclude that the antioxidant effects of the investigated antidiabetics may contribute significantly to the management of the disease and its complications and may open new therapeutic perspectives in their prevention.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108941"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jdiacomp.2024.108927
Sabina Chaudhary Hauge , Henrik Øder Hjortkjær , Frederik Persson , Simone Theilade , Morten Frost , Niklas Rye Jørgensen , Peter Rossing , Ditte Hansen
Aim
To explore the association between bone disorder and the risk for progression of diabetic kidney disease (DKD) in persons with type 1 diabetes mellitus (T1DM).
Methods
In this prospective cohort study the association between bone mineral density (BMD), bone-derived factors (sclerostin, Dickkopf-1, and osteoprotegerin (OPG)), and four outcomes were investigated: 1) progression of albuminuria; 2) decline in estimated glomerular filtration rate (eGFR) ≥30 %; 3) kidney failure (KF); and 4) a composite kidney outcome consisting of at least one of the outcomes.
Results
In 318 participants (median follow-up time 5.5 years) patients with osteoporosis (BMD with T-score < −2.5) had increased risk of eGFR decline: hazard ratio (HR) 2.56 (95 % CI 1.06–6.19, p = 0.04), KF: HR 9.92 (95 % CI 1.16–84.95, p = 0.04), and the composite kidney outcome: HR 2.42 (95 % CI 1.18–4.96, p = 0.02). Patients with high OPG had increased risk of eGFR decline, KF, and the composite outcome, compared to patients with low OPG in unadjusted analysis. No bone-derived factor was associated with any outcome in adjusted analyses.
Conclusions
In patients with T1DM low BMD was associated with progression of DKD, suggesting an interaction between bone and kidney.
{"title":"Bone mineral density and the risk of kidney disease in patients with type 1 diabetes","authors":"Sabina Chaudhary Hauge , Henrik Øder Hjortkjær , Frederik Persson , Simone Theilade , Morten Frost , Niklas Rye Jørgensen , Peter Rossing , Ditte Hansen","doi":"10.1016/j.jdiacomp.2024.108927","DOIUrl":"10.1016/j.jdiacomp.2024.108927","url":null,"abstract":"<div><h3>Aim</h3><div>To explore the association between bone disorder and the risk for progression of diabetic kidney disease (DKD) in persons with type 1 diabetes mellitus (T1DM).</div></div><div><h3>Methods</h3><div>In this prospective cohort study the association between bone mineral density (BMD), bone-derived factors (sclerostin, Dickkopf-1, and osteoprotegerin (OPG)), and four outcomes were investigated: 1) progression of albuminuria; 2) decline in estimated glomerular filtration rate (eGFR) ≥30 %; 3) kidney failure (KF); and 4) a composite kidney outcome consisting of at least one of the outcomes.</div></div><div><h3>Results</h3><div>In 318 participants (median follow-up time 5.5 years) patients with osteoporosis (BMD with T-score < −2.5) had increased risk of eGFR decline: hazard ratio (HR) 2.56 (95 % CI 1.06–6.19, <em>p</em> = 0.04), KF: HR 9.92 (95 % CI 1.16–84.95, <em>p</em> = 0.04), and the composite kidney outcome: HR 2.42 (95 % CI 1.18–4.96, <em>p</em> = 0.02). Patients with high OPG had increased risk of eGFR decline, KF, and the composite outcome, compared to patients with low OPG in unadjusted analysis. No bone-derived factor was associated with any outcome in adjusted analyses.</div></div><div><h3>Conclusions</h3><div>In patients with T1DM low BMD was associated with progression of DKD, suggesting an interaction between bone and kidney.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108927"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jdiacomp.2024.108945
Ashley Raudanskis , Shohinee Sarma , Tor Biering-Sørensen , Katarina Zorcic , Fahad Razak , Amol Verma , Magnus Thorsten Jensen , Bruce A. Perkins , Michael Colacci , Michael Fralick
Aims
To identify factors associated with use of novel diabetes medications among patients hospitalized under general internal medicine.
Methods
We conducted a cohort study of patients with type 2 diabetes mellitus (T2DM) hospitalized in Ontario, Canada between 2015 and 2020. We evaluated the patient- and physician-level factors associated with sodium-glucose cotransporter 2 inhibitor (SGLT2) and glucagon-like peptide 1 receptor agonist (GLP1R) use using a multivariable logistic regression model.
Results
There were 253,152 hospitalizations and 68,126 involved patients who had T2DM. Prior to discharge, 3.7 % (N = 2490) of patients with T2DM received an SGLT2 and 0.2 % (N = 121) received a GLP1R. The strongest predictors for receiving a novel diabetes medication were hemoglobin A1C > 9.0 % (Odds Ratio (OR) = 1.81, 95 % Confidence Interval (CI) 1.28, 2.60) and patients aged 40–60 compared with patients <40 years old (OR = 1.81, 95 % CI 1.33, 2.68). The strongest predictors for not receiving a novel diabetes medication were dementia (OR = 0.47, 95 % CI 0.39, 0.56) and creatinine ≥200 μmol/L (OR = 0.11, 95 % CI 0.08, 0.15). Overall, 46.8 % of patients hospitalized with T2DM not receiving a novel diabetes medication would potentially benefit from an SGLT2 inhibitor.
Conclusions
Novel diabetes medications were rarely continued or initiated during hospitalization despite a high prevalence of cardiovascular disease, raising the concern for systematic under-utilization after discharge.
{"title":"Identifying predictors of sodium-glucose cotransporter 2 inhibitor and glucagon-like peptide 1 receptor agonist use in hospital among adults with diabetes","authors":"Ashley Raudanskis , Shohinee Sarma , Tor Biering-Sørensen , Katarina Zorcic , Fahad Razak , Amol Verma , Magnus Thorsten Jensen , Bruce A. Perkins , Michael Colacci , Michael Fralick","doi":"10.1016/j.jdiacomp.2024.108945","DOIUrl":"10.1016/j.jdiacomp.2024.108945","url":null,"abstract":"<div><h3>Aims</h3><div>To identify factors associated with use of novel diabetes medications among patients hospitalized under general internal medicine.</div></div><div><h3>Methods</h3><div>We conducted a cohort study of patients with type 2 diabetes mellitus (T2DM) hospitalized in Ontario, Canada between 2015 and 2020. We evaluated the patient- and physician-level factors associated with sodium-glucose cotransporter 2 inhibitor (SGLT2) and glucagon-like peptide 1 receptor agonist (GLP1R) use using a multivariable logistic regression model.</div></div><div><h3>Results</h3><div>There were 253,152 hospitalizations and 68,126 involved patients who had T2DM. Prior to discharge, 3.7 % (<em>N</em> = 2490) of patients with T2DM received an SGLT2 and 0.2 % (<em>N</em> = 121) received a GLP1R. The strongest predictors for receiving a novel diabetes medication were hemoglobin A1C > 9.0 % (Odds Ratio (OR) = 1.81, 95 % Confidence Interval (CI) 1.28, 2.60) and patients aged 40–60 compared with patients <40 years old (OR = 1.81, 95 % CI 1.33, 2.68). The strongest predictors for not receiving a novel diabetes medication were dementia (OR = 0.47, 95 % CI 0.39, 0.56) and creatinine ≥200 μmol/L (OR = 0.11, 95 % CI 0.08, 0.15). Overall, 46.8 % of patients hospitalized with T2DM not receiving a novel diabetes medication would potentially benefit from an SGLT2 inhibitor.</div></div><div><h3>Conclusions</h3><div>Novel diabetes medications were rarely continued or initiated during hospitalization despite a high prevalence of cardiovascular disease, raising the concern for systematic under-utilization after discharge.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108945"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jdiacomp.2025.108952
Yuling Yang , Fengxia Li , Yankun Li , Xue Li , Zhonghua Zhao , Nong Zhang , Hui Li
Aims
We aim to explore the potential of nicotinamide n-methyltransferase (NNMT) as a sensitive marker of renal tubular injury and the possibility of an NNMT inhibitor to combine with sodium-glucose cotransporter 2 (SGLT2) inhibitor to protect proximal tubular epithelium in vivo and in vitro model of Type 2 diabetes mellitus (T2DM), respectively.
Methods
In vivo, immunohistochemical staining, Masson's trichrome staining and Sirius red staining were used to observe the changes of NNMT expression, renal tubular injury and interstitial fibrosis in renal tissue from the db/db mice. Bioinformatic analysis was also conducted to broaden the range of data validation. In vitro, Western Blot and quantitative RT-PCR were used to measure the degree of damage of HK-2 cells.
Results
Our in vivo data showed upregulation of NNMT expression paralleled renal tubular damage and interstitial fibrosis. Our in vitro data revealed both NNMT inhibitors and SGLT2 inhibitors can protect against the injury as assessed by extracellular matrix (ECM) synthesis and profibrotic phenotype transition of HK-2 cells, and the combination of these two agents can further reduce these injuries.
Conclusions
The present study is the first to show that NNMT is a promising marker of renal tubular injury in diabetic nephropathy (DN) and NNMT inhibitors can synergize with SGLT2 inhibitors to protect HK-2 better. Our findings will provide the insight and pave the way of developing novel therapeutic strategies for chronic renal tubular injury associated with T2DM.
{"title":"Nicotinamide n-methyltransferase inhibitor synergizes with sodium-glucose cotransporter 2 inhibitor to protect renal tubular epithelium in experimental models of type 2 diabetes mellitus","authors":"Yuling Yang , Fengxia Li , Yankun Li , Xue Li , Zhonghua Zhao , Nong Zhang , Hui Li","doi":"10.1016/j.jdiacomp.2025.108952","DOIUrl":"10.1016/j.jdiacomp.2025.108952","url":null,"abstract":"<div><h3>Aims</h3><div>We aim to explore the potential of nicotinamide <em>n</em>-methyltransferase (NNMT) as a sensitive marker of renal tubular injury and the possibility of an NNMT inhibitor to combine with sodium-glucose cotransporter 2 (SGLT2) inhibitor to protect proximal tubular epithelium in vivo and in vitro model of Type 2 diabetes mellitus (T2DM), respectively.</div></div><div><h3>Methods</h3><div>In vivo, immunohistochemical staining, Masson's trichrome staining and Sirius red staining were used to observe the changes of NNMT expression, renal tubular injury and interstitial fibrosis in renal tissue from the db/db mice. Bioinformatic analysis was also conducted to broaden the range of data validation. In vitro, Western Blot and quantitative RT-PCR were used to measure the degree of damage of HK-2 cells.</div></div><div><h3>Results</h3><div>Our in vivo data showed upregulation of NNMT expression paralleled renal tubular damage and interstitial fibrosis. Our in vitro data revealed both NNMT inhibitors and SGLT2 inhibitors can protect against the injury as assessed by extracellular matrix (ECM) synthesis and profibrotic phenotype transition of HK-2 cells, and the combination of these two agents can further reduce these injuries.</div></div><div><h3>Conclusions</h3><div>The present study is the first to show that NNMT is a promising marker of renal tubular injury in diabetic nephropathy (DN) and NNMT inhibitors can synergize with SGLT2 inhibitors to protect HK-2 better. Our findings will provide the insight and pave the way of developing novel therapeutic strategies for chronic renal tubular injury associated with T2DM.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108952"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jdiacomp.2024.108942
Kristine Stoltenberg Addington , Maria Kristiansen , Nana F. Hempler , Marie Frimodt-Møller , Victor M. Montori , Marleen Kunneman , Stine H. Scheuer , Lars J. Diaz , Gregers S. Andersen
Aims
Early-onset type 2 diabetes (T2DM) (18–45 years) is rising globally, yet complication incidence in this group remains unclear. We investigated the incidence of early-onset T2DM, the incidence of micro- and macrovascular complications, and how comorbidities (e.g., severe mental illness) and sociodemographic factors (e.g., education level) influence complication risk and timing in Denmark.
Methods
Using nationwide registers, we followed 8,129,005 individuals from 1996 to 2020 to estimate the incidence rate (IR) of early-onset T2DM. 49,850 individuals with early-onset T2DM were followed to calculate IRs for microvascular (nephropathy, retinopathy) and macrovascular (cardiovascular disease, amputation) complications. Incidence rate ratios (IRRs) assessed associations between comorbidities, sociodemographic factors, and complications. Poisson regression models calculated IRs and IRRs.
Results
From 1996 to 2020, the IR of early-onset T2DM more than doubled in men and tripled in women, with women dominating younger age groups. During follow-up (7.9–9.8 years), 37.6 % developed complications. Higher complication IRs were observed in men, those with sociodemographic disadvantages, and individuals with comorbidities. Early complications (≤5 years) were more common among the unemployed, single individuals, and those with comorbidities.
Conclusions
The rising IR of early-onset T2DM in younger women, and complications disproportionately affecting men and those with comorbidities or sociodemographic disadvantages, highlight the need for targeted interventions.
{"title":"Incidence of early-onset type 2 diabetes and sociodemographic predictors of complications: A nationwide registry study","authors":"Kristine Stoltenberg Addington , Maria Kristiansen , Nana F. Hempler , Marie Frimodt-Møller , Victor M. Montori , Marleen Kunneman , Stine H. Scheuer , Lars J. Diaz , Gregers S. Andersen","doi":"10.1016/j.jdiacomp.2024.108942","DOIUrl":"10.1016/j.jdiacomp.2024.108942","url":null,"abstract":"<div><h3>Aims</h3><div>Early-onset type 2 diabetes (T2DM) (18–45 years) is rising globally, yet complication incidence in this group remains unclear. We investigated the incidence of early-onset T2DM, the incidence of micro- and macrovascular complications, and how comorbidities (e.g., severe mental illness) and sociodemographic factors (e.g., education level) influence complication risk and timing in Denmark.</div></div><div><h3>Methods</h3><div>Using nationwide registers, we followed 8,129,005 individuals from 1996 to 2020 to estimate the incidence rate (IR) of early-onset T2DM. 49,850 individuals with early-onset T2DM were followed to calculate IRs for microvascular (nephropathy, retinopathy) and macrovascular (cardiovascular disease, amputation) complications. Incidence rate ratios (IRRs) assessed associations between comorbidities, sociodemographic factors, and complications. Poisson regression models calculated IRs and IRRs.</div></div><div><h3>Results</h3><div>From 1996 to 2020, the IR of early-onset T2DM more than doubled in men and tripled in women, with women dominating younger age groups. During follow-up (7.9–9.8 years), 37.6 % developed complications. Higher complication IRs were observed in men, those with sociodemographic disadvantages, and individuals with comorbidities. Early complications (≤5 years) were more common among the unemployed, single individuals, and those with comorbidities.</div></div><div><h3>Conclusions</h3><div>The rising IR of early-onset T2DM in younger women, and complications disproportionately affecting men and those with comorbidities or sociodemographic disadvantages, highlight the need for targeted interventions.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108942"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.jdiacomp.2025.108954
Francisca Obianuju Okoro, Victor Markus
While artificial sweeteners are Generally Regarded as Safe (GRAS), the scientific community remains divided on their safety status. The previous assumption that artificial sweeteners are inert within the body is no longer valid. Artificial sweeteners, known for their high intense sweetness and low or zero calories, are extensively used today in food and beverage products as sugar substitutes and are sometimes recommended for weight management and Type 2 Diabetes Mellitus (T2DM) patients. The general omission of information about the concentration of artificial sweeteners on market product labels makes it challenging to determine the amounts of artificial sweeteners consumed by people. Despite regulatory authorization for their usage, such as from the United States Food and Drug Administration (FDA), concerns remain about their potential association with metabolic diseases, such as T2DM, which the artificial sweeteners were supposed to reduce. This review discusses the relationship between artificial sweetener consumption and the risk of developing T2DM. With the increasing number of recent scientific studies adding to the debate on this subject matter, we assessed recent literature and up-to-date evidence. Importantly, we highlight future research directions toward furthering knowledge in this field of study.
{"title":"Artificial sweeteners and Type 2 Diabetes Mellitus: A review of current developments and future research directions","authors":"Francisca Obianuju Okoro, Victor Markus","doi":"10.1016/j.jdiacomp.2025.108954","DOIUrl":"10.1016/j.jdiacomp.2025.108954","url":null,"abstract":"<div><div>While artificial sweeteners are Generally Regarded as Safe (GRAS), the scientific community remains divided on their safety status. The previous assumption that artificial sweeteners are inert within the body is no longer valid. Artificial sweeteners, known for their high intense sweetness and low or zero calories, are extensively used today in food and beverage products as sugar substitutes and are sometimes recommended for weight management and Type 2 Diabetes Mellitus (T2DM) patients. The general omission of information about the concentration of artificial sweeteners on market product labels makes it challenging to determine the amounts of artificial sweeteners consumed by people. Despite regulatory authorization for their usage, such as from the United States Food and Drug Administration (FDA), concerns remain about their potential association with metabolic diseases, such as T2DM, which the artificial sweeteners were supposed to reduce. This review discusses the relationship between artificial sweetener consumption and the risk of developing T2DM. With the increasing number of recent scientific studies adding to the debate on this subject matter, we assessed recent literature and up-to-date evidence. Importantly, we highlight future research directions toward furthering knowledge in this field of study.</div></div>","PeriodicalId":15659,"journal":{"name":"Journal of diabetes and its complications","volume":"39 2","pages":"Article 108954"},"PeriodicalIF":2.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143039320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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