Diabetes Medication Metformin Inhibits Osteoclast Formation and Activity in In Vitro Models for Periodontitis

Diabetes and periodontitis are comorbidities and may share common pathways. Several reports indicate that diabetes medication metformin may be beneficial for the periodontal status of periodontitis patients. Further research using appropriate cell systems of the periodontium, the tissue that surrounds teeth may reveal the possible mechanism. Periodontal ligament fibroblasts anchor teeth in bone and play a role in the onset of both alveolar bone formation and degradation, the latter by inducing osteoclast formation from adherent precursor cells. Therefore, a cell model including this type of cells is ideal to study the influence of metformin on both processes. We hypothesize that metformin will enhance bone formation, as described for osteoblasts, whereas the effects of metformin on osteoclast formation is yet undetermined. Periodontal ligament fibroblasts were cultured in the presence of osteogenic medium and 0.2 or 1 mM metformin. The influence of metformin on osteoclast formation was first studied in PDLF cultures supplemented with peripheral blood leukocytes, containing osteoclast precursors. Finally, the effect of metformin on osteoclast precursors was studied in cultures of CD14+ monocytes that were stimulated with M-CSF and receptor activator of Nf-κB ligand (RANKL). No effects of metformin were observed on osteogenesis: not on alkaline phosphatase activity, Alizarin red deposition, nor on the expression of osteogenic markers RUNX-2, Collagen I and Osteonectin. Metformin inhibited osteoclast formation and accordingly downregulated the genes involved in osteoclastogenesis: RANKL, macrophage colony stimulating factor (M-CSF) and osteoclast fusion gene DC-STAMP. Osteoclast formation on both plastic and bone as well as bone resorption was inhibited by metformin in M-CSF and RANKL stimulated monocyte cultures, probably by reduction of RANK expression. The present study unraveling the positive effect of metformin in periodontitis patients at the cellular level, indicates that metformin inhibits osteoclast formation and activity, both when orchestrated by periodontal ligament fibroblasts and in cytokine driven osteoclast formation assays. The results indicate that metformin could have a systemic beneficiary effect on bone by inhibiting osteoclast formation and activity.

Concurrent Metformin Use and Survival Among Finnish Non-Small Cell Lung Cancer Patients Treated With EGFR TKIs

Purpose Many studies have shown correlation between metformin use and lower incidence and improved outcomes of lung cancer. We investigated the potential association between metformin use and survival among Finnish non-small cell lung cancer (NSCLC) patients treated with EGFR TKIs. Methods Nationwide registries were utilized to identify all the patients with use of EGFR TKIs in NSCLC between 2011–2016, and 1242 patients were included in further analyses. Data related to cancer, survival, and drug purchases were combined with personal identity codes. Concurrent use of diabetes medications was defined as their purchase +/-120 days from the first purchase of EGFR TKI. The impact of diabetes medication use was investigated separately in the whole and in the EGFR mutant type cohort (n = 481). Results Concurrent metformin use was found in 10 % (n = 124) and use of other diabetes medication in 5 % (n = 60) of the patients. In the whole patient cohort, metformin use did not associate with survival but in the EGFR mutant type cohort a non-significant trend for higher mortality was found (HR 1.42, 95% CI 0.99–2.02). Metformin use associated also with a shorter EGFR TKI treatment duration (HR 1.26, 95 % CI 1.04–1.52). The use of other diabetes medication than metformin did not associate with survival or EGFR TKI treatment duration. Conclusion Concomitant metformin use associated with a shorter EGFR TKI treatment duration, however, no statistically significant correlation with survival was found. Ethnicity, comorbidities, and metformin dosage may influence on the associations found between metformin use and EGFR TKI treatment responses.

Complexity of antidiabetic medication regimen is associated with increased diabetes-related distress in persons with type 2 diabetes mellitus

IntroductionDiabetes-related distress is present in a high proportion of people with type 2 diabetes mellitus. We hypothesized that complexity of the antidiabetic medication regimen is a factor that is associated with diabetes-related distress.Research design and methodsThis was a retrospective study including a group of 74 patients managed at a tertiary care center. Patients with type 1 diabetes mellitus, steroid-induced diabetes, post-transplant diabetes, and other types of diabetes were excluded. Patients were screened using the Diabetes Distress Scale-2 (DDS-2). A Diabetes Medication Complexity Scoring (DMCS) system was developed to objectively assess the diabetes medication complexity. Based on DMCS, participants were categorized into three groups: low (n=26), moderate (n=22), and high (n=26) medication complexity.ResultsComplexity groups were similar in sociodemographic characteristics, diabetes duration, body mass index, and blood pressure as well as the prevalence of hypertension, hyperlipidemia and hypoglycemic episodes. However, there were significant differences for HbA1c with higher HbA1c in the high and moderate complexity groups than in the low group (p=0.006). The microvascular complications were also more common in higher complexity groups (p=0.003). The prevalence of diabetes-related distress (DDS-2 ≥6) was 34.6% in the low, 36.4% in the moderate and 69.2% in the high complexity groups (p=0.021). There were significant differences in DDS-2 score among complexity groups (p=0.009), with higher DDS-2 score in the high complexity group compared with the moderate (p=0.008) and low complexity groups (p=0.009). The difference in DDS-2 score remained significant after adjusting for HbA1c (p=0.024) but did not reach statistical significance after controlling for both HbA1c and microvascular complications (p=0.163).ConclusionsA complex antidiabetic medication regimen may be associated with high levels of diabetes-related distress.

Smartphone Apps for Diabetes Medication Adherence: A Systematic Review (Preprint)

BACKGROUND Diabetes is one of the leading noncommunicable chronic diseases globally. Since there is no cure, blood glucose levels need to be monitored regularly and managed. In addition, patients must live a healthy lifestyle and use regular medication to maintain their health and wellbeing. However, various factors contribute to poor adherence to medication. OBJECTIVE This study aims to systematically review and evaluate applications (apps) available for diabetes medication adherence, identify and analyze high-quality apps that are freely available to the public in the Android and Apple app stores, and present the technical features of the apps. METHODS Applying predefined selection criteria, we systematically searched the Apple App Store and Google Play Store for apps to assist in diabetes medication adherence. We assessed high-quality apps using the Mobile App Rating Scale. Apps that achieved a total mean quality score greater than 4 out of 5 in our study were considered high quality. RESULTS We selected eight apps for analysis in this study and discussed them in detail under three main categories: characteristics of the included apps, app features, and diabetes medication adherence. We formulated a task-technology fit matrix to evaluate the apps for diabetes medication adherence. On evaluation, we observed that 25% of the apps promoted high adherence and another 25% of the apps promoted moderate adherence. Finally, we found that 50% of the apps provided low adherence to diabetes medication. CONCLUSIONS Our framework to evaluate smartphone apps in promoting diabetes medication adherence considered physiological factors influencing diabetes and app features. Therefore, our findings could have positive implications for the design and development of apps for diabetes patients. Additionally, available apps can be evaluated according to our framework, and those promoting higher medication adherence could be prescribed for better health outcomes.

Identification and Predictors for Cardiovascular Disease Risk Equivalents among Adults With Diabetes Mellitus

Objective: We examined diabetes mellitus (DM) as a cardiovascular disease (CVD) risk equivalent based on diabetes severity and other CVD risk factors. <p>Research Design and Methods: We pooled 4 US cohorts (ARIC, JHS, MESA, FHS-Offspring) and classified subjects by baseline DM/CVD. CVD risks between DM+/CVD- vs. DM-/CVD+ were examined by diabetes severity and in subgroups of other CVD risk factors. We developed an algorithm to identify subjects with CVD risk equivalent diabetes by comparing the relative CVD risk of being DM+/CVD- vs. DM-/CVD+. </p> <p>Results: The pooled cohort included 27,730 subjects (mean age of 58.5 years, 44.6% male). CVD rates per 1000 person-years were 16.5, 33.4, 43.2 and 71.4 among those with DM-/CVD-, DM+/CVD-, DM-/CVD+ and DM+/CVD+, respectively. Compared to those with DM-/CVD+, CVD risks were similar or higher for those with HbA1c≥7%, diabetes duration ≥10 years, or diabetes medication use while those with less severe diabetes had lower risks. Hazard ratios for DM+/CVD- vs. DM-/CVD+ were 0.96(0.86-1.07), 0.97(0.88-1.07), 0.96(0.82-1.13), 1.18(0.98-1.41), 0.93(0.85-1.02) and 1.00(0.89-1.13) among women, white race, age <55 years, triglycerides ≥2.26mmol/L, CRP≥2mg/L and eGFR<60mL/min/1.73m², respectively. In DM+/CVD- group, 19.1% had CVD risk equivalent diabetes with a lower risk score but a higher observed CVD risk. </p> <p>Conclusion: Diabetes is a CVD risk equivalent in one-fifth of CVD-free adults living with diabetes. High HbA1c, long diabetes duration, and diabetes medication use were predictors of CVD risk equivalence. Diabetes is a CVD risk equivalent for women, white people, those of younger age, with higher triglycerides or CRP, or reduced kidney function. </p>

Identification and Predictors for Cardiovascular Disease Risk Equivalents among Adults With Diabetes Mellitus

Objective: We examined diabetes mellitus (DM) as a cardiovascular disease (CVD) risk equivalent based on diabetes severity and other CVD risk factors. <p>Research Design and Methods: We pooled 4 US cohorts (ARIC, JHS, MESA, FHS-Offspring) and classified subjects by baseline DM/CVD. CVD risks between DM+/CVD- vs. DM-/CVD+ were examined by diabetes severity and in subgroups of other CVD risk factors. We developed an algorithm to identify subjects with CVD risk equivalent diabetes by comparing the relative CVD risk of being DM+/CVD- vs. DM-/CVD+. </p> <p>Results: The pooled cohort included 27,730 subjects (mean age of 58.5 years, 44.6% male). CVD rates per 1000 person-years were 16.5, 33.4, 43.2 and 71.4 among those with DM-/CVD-, DM+/CVD-, DM-/CVD+ and DM+/CVD+, respectively. Compared to those with DM-/CVD+, CVD risks were similar or higher for those with HbA1c≥7%, diabetes duration ≥10 years, or diabetes medication use while those with less severe diabetes had lower risks. Hazard ratios for DM+/CVD- vs. DM-/CVD+ were 0.96(0.86-1.07), 0.97(0.88-1.07), 0.96(0.82-1.13), 1.18(0.98-1.41), 0.93(0.85-1.02) and 1.00(0.89-1.13) among women, white race, age <55 years, triglycerides ≥2.26mmol/L, CRP≥2mg/L and eGFR<60mL/min/1.73m², respectively. In DM+/CVD- group, 19.1% had CVD risk equivalent diabetes with a lower risk score but a higher observed CVD risk. </p> <p>Conclusion: Diabetes is a CVD risk equivalent in one-fifth of CVD-free adults living with diabetes. High HbA1c, long diabetes duration, and diabetes medication use were predictors of CVD risk equivalence. Diabetes is a CVD risk equivalent for women, white people, those of younger age, with higher triglycerides or CRP, or reduced kidney function. </p>