Associations among diabetes medication use, serum magnesium, and insulin resistance in a cohort of older Puerto Rican adults.

BACKGROUND: Hypomagnesemia is commonly observed in individuals with diabetes, but how diabetes medications alter magnesium (Mg) status remains unclear. OBJECTIVES: We aimed to examine the association between diabetes medication and hypomagnesemia and evaluate whether serum Mg mediates the association between diabetes medication and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in a prospective cohort. METHODS: Adults from the Boston Puerto Rican Health Study were included (n = 1106). Multivariable logistic regression models were used to estimate odds ratio (OR) and 95% confidence interval (CI) for cross-sectional association between diabetes medication and hypomagnesemia (serum Mg <0.75 mmol/L). Longitudinal mediation analysis was performed to evaluate the direct and indirect (via serum Mg) associations between diabetes medication and 4-y HOMA-IR in 341 participants with baseline hemoglobin A1c (HbA1c) of ≥6.5%. RESULTS: Mean age at baseline was 59.0 ± 7.6 y, with 28.0% male and 45.8% with hypomagnesemia. Use of metformin [OR (95% CI) = 3.72 (2.53, 5.48)], sulfonylureas [OR (95% CI) = 1.68 (1.00, 2.83)], and glitazones [OR (95% CI) = 2.09 (1.10, 3.95)], but not insulin, was associated with higher odds of hypomagnesemia. Use of multiple diabetes medications and longer duration of use were associated with higher odds of hypomagnesemia. Serum Mg partially mediated the association between metformin and HOMA-IR [indirect association: ß (95% CI) = 1.11 (0.15, 2.07)], which weakened the direct association [ß (95% CI) = -5.16 (-9.02, -1.30)] by 22% [total association: ß (95% CI) = -4.05 (-7.59, -0.51)]. Similarly, serum Mg mediated 17% of the association between sulfonylureas and elevated HOMA-IR. However, the mediation by serum Mg was weak for insulin and glitazones. CONCLUSIONS: Diabetes medication, especially metformin, was associated with elevated odds of hypomagnesemia, which may weaken the association between metformin and lowering of HOMA-IR. The causal inference needs to be confirmed in further studies.

Non-use of diabetes medication and its associated factors: a comparative analysis of female and male patients in four Sub-Saharan African countries.

BACKGROUND: Globally, the burden of disease is shifting towards non-communicable diseases (NCDs), including diabetes. Sub-Saharan Africa (SSA) faces an increasing prevalence of diabetes, hindering the achievement of global health goals. This study investigates the determinants of non-use of diabetes medication, specifically exploring potential sex differences in four SSA countries. METHODS: This cross-sectional study analyzed recent Demographic and Health Survey (DHS) data (2017-2021) from four SSA countries (Benin, Cameroon, Madagascar, and Mauritania). Samples included 23,695 women and 25,339 men, focusing on individuals with diabetes not using medication (248 women, 162 men). Descriptive and inferential analyses, including chi-square tests and binary logistic regression models, were conducted using Stata version 14. Odds ratios were calculated with a 95% confidence interval to determine the associations. RESULTS: This study found that a larger proportion of female patients with diabetes (64.1%) were not using diabetes medication compared to their male counterparts (59.4%). Age influenced medication non-use in males, with older individuals exhibiting lower odds of non-usage. Higher wealth status was associated with lower odds of non-use of diabetes medications. The presence of heart disease was associated with a lower likelihood of medication non-use among females. CONCLUSIONS: This study demonstrates sex disparities, age differences, wealth status, heart disease, and country-specific variations in medication non-use. Tailored interventions for different age groups, as well as socioeconomic support, are critical, as is integrated cardiovascular and diabetes care. These actions can improve medication use and adherence, quality of life, and long-term diabetes management outcomes.

Association of Metformin, Dipeptidyl Dipeptidase-4 Inhibitors, and Insulin with Coronavirus Disease 2019-Related Hospital Outcomes in Patients with Type 2 Diabetes.

OBJECTIVE: The effects of diabetes medications on COVID-19 hospitalization outcomes have not been consistent. We sought to determine the effect of metformin, dipeptidyl peptidase-4 inhibitors (DPP-4i), and insulin on admission to the intensive care unit (ICU), need for assisted ventilation, development of renal insufficiency, and mortality in patients admitted with COVID-19 infection after controlling for clinical variables and other relevant diabetes-related medications in patients with type 2 diabetes mellitus (DM). METHODS: This was a retrospective study of patients hospitalized with COVID-19 from a single hospital system. Univariate and multivariate analyses were performed that included demographic data, glycated hemoglobin, kidney function, smoking status, insurance, Charlson comorbidity index, number of diabetes medications, and use of angiotensin-converting enzyme inhibitors and statin prior to admission and glucocorticoids during admission. RESULTS: A total of 529 patients with type 2 DM were included in our final analysis. Neither metformin nor DPP4i prescription was associated with ICU admission, need for assisted ventilation, or mortality. Insulin prescription was associated with increased ICU admission but not with need for assisted ventilation or mortality. There was no association of any of these medications with development of renal insufficiency. CONCLUSIONS: In this population, limited to type 2 DM and controlled for multiple variables that have not been consistently studied (such as a measure of general health, glycated hemoglobin, and insurance status), insulin prescription was associated with increased ICU admission. Metformin and DPP4i prescriptions did not have an association with the outcomes.

Compliance with Medication amongst Persons with Diabetes Mellitus during the COVID-19 Pandemic, Kerala, India: A Cross Sectional Study.

Compliance with medication in persons with diabetes mellitus (DM) has been a challenge during the COVID-19 pandemic, leading to poor glycemic control and higher risk of complications. In the state of Kerala, India, 20−25% of adults have DM. Our cross-sectional study aimed to assess medication compliance and factors associated with poor compliance in DM persons attending selected primary care government facilities in Kerala during the COVID-19 pandemic. Persons registered with DM for >6 months were consecutively interviewed between August and September 2021. Poor compliance was defined as answering "No" to one or more of three questions related to access and intake of medication two weeks prior to and the day before the interview. Factors independently associated with poor compliance were assessed using adjusted prevalence ratios (aPr) and 95% confidence intervals. Of the 560 DM persons included, 209 (37%) exhibited poor compliance. Factors associated with poor compliance were age 19−45 years (aPr 1.4, 1.1−1.9); inability to be blood glucose tested during the COVID-19 pandemic (aPr 3.6, 2.9−4.3); not having COVID-19 (aPr 1.4, 1.0−1.9); and being double vaccinated against COVID-19 (aPr 1.4, 1.1−2.0). Focused attention must be paid to these groups to improve medication compliance and prevent DM complications and severe COVID-19-related disease.

Association between different diabetes medication classes and risk of Parkinson's disease in people with diabetes.

PURPOSE: Diabetes has been associated with increased risk of Parkinson's disease (PD). Diabetes medications have been suggested as a possible explanation, but findings have been inconsistent. More information on the role of exposure in different time windows is needed because PD has long onset. We assessed the association between use of different diabetes medication categories and risk of PD in different exposure periods. METHODS: A case-control study restricted to people with diabetes was performed as part of nationwide register-based Finnish study on PD (FINPARK). We included 2017 cases (diagnosed 1999-2015) with PD and 7934 controls without PD. Diabetes medication use was identified from Prescription Register (1995-2015) and categorized to insulins, biguanides, sulfonylureas, thiazolidinediones (TZDs), dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues and glinide. Exposure for each medication class was determined as none, at least 3 years before outcome and only within the three-year lag time before PD outcome. RESULTS: The use of insulins, biguanides, sulfonylureas, DPP-4 inhibitors, GLP-1 analogues or glinides was not associated with PD. Use of TZDs before lag time compared to non-use of TZDs (adjusted odds ratio (OR) 0.78; 95% Confidence interval (CI) 0.64-0.95) was associated with decreased risk of PD. CONCLUSIONS: Our nationwide case-control study of people with diabetes found no robust evidence on the association between specific diabetes medication classes and risk of PD. Consistent with earlier studies, TZD use was associated with slightly decreased risk of PD. The mechanism for this should be verified in further studies.

Work-related factors related to forgetting to take oral diabetes medication during the working day among Japanese male employees with diabetes.

AIM: This study aimed to explore the work-related factors related to forgetting to take oral diabetes medication during the working day among Japanese employees with diabetes. METHODS: This worksite-based study was designed to clarify the important work-related factors for preventing the aggravation of diabetes among working-age people and support for coexisting diabetes treatment and work (Ryoritsu Shien). This cross-sectional survey was conducted in 2018. The participants were full-time employees with type 2 diabetes aged over 40 years who took oral diabetes medication during the working day. The participants were classified into forgetting and non-forgetting groups. Their characteristics and work-related factors were evaluated using a self-administered questionnaire and specific health checkup data. RESULTS: Of the 93 employees with diabetes, 22 (23.7%) were classified into the forgetting group. After adjusting for confounding factors, irregular meal times during the working day was positively associated with forgetting to take oral diabetes medication during the working day [multivariable-adjusted odds ratio (OR), 7.08; 95% confidence interval (CI): 1.38-36.32, irregular vs. regular]. Skipping meals during the working day was positively associated with forgetting to take oral diabetes medication during the working day (multivariable-adjusted OR 3.55, 95% CI 1.14-11.09 presence vs. absence). CONCLUSIONS: Our findings suggest that irregular meal times and skipping meals during the working day are important factors related to forgetting to take oral diabetes medication during the working day among Japanese male employees with diabetes.

Type 2 diabetes reversal with digital twin technology-enabled precision nutrition and staging of reversal: a retrospective cohort study.

BACKGROUND: Type 2 diabetes reversal has been viewed in the literature primarily as a dichotomous event (reversed or not reversed), even though this viewpoint may not be optimal for clinicians or patients. This cohort study's objectives were to define stages of type 2 diabetes reversal and measure changes in reversal stages before and after 90 days of digital twin-enabled precision nutrition therapy. METHODS: This study defines seven stages of diabetes reversal. The study is a retrospective pre/post comparison of changes in reversal stage, hemoglobin A1c (HbA1c), weight, body mass index (BMI), and other metrics measured before and after precision nutrition therapy. Reversal stages were defined as Stage 0: HbA1c < 5.7% without medication for > 1 year, Stage 1: HbA1c < 5.7% without medication for < 1 year, Stage 2: HbA1c < 6.5% without medication, Stage 3: estimated HbA1c (eA1c) between 5.7 and 6.4% without medication, Stage 4: estimated HbA1c (eA1c) between 5.7 and 6.4% with metformin monotherapy, Stage 5: dual oral therapy, Stage 6: > = 3 medications. RESULTS: Reversal stage information was available for 463 patients at baseline and 90 days. At baseline, the proportions of patients in each reversal stage were Stages 1 and 2: 0%, Stage 3: 1%, Stage 4: 8%, Stage 5: 6%, and Stage 6: 85%. After 90 days, the proportions in each reversal stage were Stage 1: 2%, Stage 2: 9%, Stage 3: 32%, Stage 4: 39%, Stage 5: 7%, and Stage 6: 11%, indicating significant progress. Reversal stage progression rates varied by patient subgroup. CONCLUSIONS: Type 2 diabetes patients reached differing reversal stages during 90 days of precision nutrition therapy. Use of reversal stages may benefit patients during therapy. TRIAL REGISTRATION: This was a retrospective study that was approved by the Medisys Clinisearch Ethical Review Board (without registration number) in 2019.

Patient-physician interpersonal processes of care at the time of diabetes treatment intensification and their links to patient outcomes.

OBJECTIVE: To investigate how patient-physician interpersonal processes of care are related to levels of diabetes-related distress, diabetes medication-taking behavior, and HbA1c during conversations with patients about intensifying medication. METHODS: We randomly recruited 1270 patients from diabetes specialty clinics in Tehran, Iran who were taking an additional oral diabetes medication or starting insulin during the prior 3 months. This interviewer-administered cross-sectional survey assessed multiple aspects of patient-physician interpersonal processes, diabetes-related distress, and diabetes medication-taking. Clinical history and HbA1c were collected from electronic medical records. Regression estimates and Structural Equation Modeling were used to test associations. RESULTS: Some communication scales indicated a significant relationship with total diabetes distress (P < 0.001). Diabetes medication-taking was associated with less diabetes distress (adjusted odds ratio [aOR]=0.45, P < 0.001), lower Hurried Communication (aOR=0.72, P = 0.013), higher Elicited Concerns (aOR=1.30, P = 0.012), and higher Explained Results (aOR=1.41, P < 0.001) scores. SEM analyses showed medication-taking behavior was associated with a 0.68 decrease in HbA1c. Hurried Communication and diabetes distress were directly associated with HbA1c. CONCLUSION: Aspects of patient-physician interpersonal processes at the time of intensifying diabetes treatment may be related to experiencing less distress, effective medication-taking, and improved HbA1c. PRACTICE IMPLICATIONS: The results are intended to inform communication strategies that physicians might incorporate into practice.

Reducing HbA1c in Type 2 Diabetes Using Digital Twin Technology-Enabled Precision Nutrition: A Retrospective Analysis.

INTRODUCTION: The objective of this study was to examine changes in hemoglobin A1c (HbA1c), anti-diabetic medication use, insulin resistance, and other ambulatory glucose profile metrics between baseline and after 90 days of participation in the Twin Precision Nutrition (TPN) Program enabled by Digital Twin Technology. METHODS: This was a retrospective study of patients with type 2 diabetes who participated in the TPN Program and had at least 3 months of follow-up. The TPN machine learning algorithm used daily continuous glucose monitor (CGM) and food intake data to provide guidelines that would enable individual patients to avoid foods that cause blood glucose spikes and to replace them with foods that do not produce spikes. Physicians with access to daily CGM data titrated medications and monitored patient conditions. RESULTS: Of the 89 patients who initially enrolled in the TPN Program, 64 patients remained in the program and adhered to it for at least 90 days; all analyses were performed on these 64 patients. At the 90-day follow-up assessment, mean (± standard deviation) HbA1c had decreased from 8.8 ± 2.2% at baseline by 1.9 to 6.9 ± 1.1%, mean weight had decreased from 79.0 ± 16.2 kg at baseline to 74.2 ± 14.7 kg, and mean fasting blood glucose had fallen from 151.2 ± 45.0 mg/dl at baseline to 129.1 ± 36.7 mg/dl. Homeostatic model assessment of insulin resistance (HOMA-IR) had decreased by 56.9% from 7.4 ± 3.5 to 3.2 ± 2.8. At the 90-day follow-up assessment, all 12 patients who were on insulin had stopped taking this medication; 38 of the 56 patients taking metformin had stopped metformin; 26 of the 28 patients on dipeptidyl peptidase-4 (DPP-4) inhibitors discontinued DPP-4 inhibitors; all 13 patients on alpha-glucosidase inhibitors discontinued these inhibitors; all 34 patients on sulfonylureas were able to stop taking these medications; two patients stopped taking pioglitazone; all ten patients on sodium-glucose cotransporter-2 (SGLT2) inhibitors stopped taking SGLT2 inhibitors; and one patient stopped taking glucagon-like peptide-1 analogues. CONCLUSION: The results provide evidence that daily precision nutrition guidance based on CGM, food intake data, and machine learning algorithms can benefit patients with type 2 diabetes. Adherence for 3 months to the TPN Program resulted in patients achieving a 1.9 percentage point decrease in HbA1c, a 6.1% drop in weight, a 56.9% reduction in HOMA-IR, a significant decline in glucose time below range, and, in most patients, the elimination of diabetes medication use.

Adherence to multiple medications in the TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) cohort: effect of additional medications on adherence to primary diabetes medication.

Background Non-adherence to diabetes medication leads to poor outcomes and increased healthcare costs. Multiple factors affecting adherence in adults with type 2 diabetes (T2D) have been identified, but pediatric data is sparse. We aimed to determine whether initiation of additional oral medications or insulin affects adherence to primary study medication (PSM) in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study. Methods Six hundred and ninety-nine youth (aged 10-17 years) with recent-onset T2D were randomized in the TODAY study. Participants were categorized as adherent (≥80% taken by pill count) or non-adherent (<80%), and adherence was compared between those on additional medications or not. Subgroup analyses to assess influence of race/ethnicity, gender, medication type, or depression were performed. Results At 36 months, 46.3% of participants were taking additional oral medications and 31.9% were on insulin. There was no difference in study medication adherence with additional oral medications (55.1%, 67.1%, and 56.7% at month 36 in those prescribed 0, 1, or 2+ additional medications; p = 0.16). Girls on oral contraceptives (OC) had higher adherence (65.2% vs. 55.8% at month 36; p = 0.0054). Participants on insulin had lower adherence (39.7% vs. 59.3% at 36 months; p < 0.0001). There was decreased adherence in participants with baseline depression (p = 0.008). Conclusions Additional oral medications did not influence adherence to diabetes medications in TODAY. Addition of insulin led to reduced adherence. In subgroup analyses, OC use was associated with higher adherence in girls, while baseline depression was associated with lower adherence overall. Further studies examining potentially modifiable risk factors of adherence in pediatric T2D are needed.

Validation of diabetes medication adherence scale in the Lebanese population.

AIM: To validate the Diabetes Medication Adherence Scale (DMAS-7), determine its concordance with another validated scales and to assess factors affecting medication adherence. METHODS: A cross-sectional study was conducted on a sample of Lebanese patients with diabetes using a questionnaire. The level of adherence was measured using the DMAS-7 and the Lebanese Medication Adherence Scale (LMAS-14). Bivariate and multivariate analyses were conducted, and the scale was validated in terms of reliability, predictive ability, and construct validity using SPSS version 19. RESULTS: Out of 300 eligible patients, the rate of adherence was 33.7%. Measures of validity showed good reliability (Cronbach alpha = 0.627), and good construct validity with LMAS-14 (Spearman's rho = 0.846; Cohen's kappa = 0.711). DMAS-7 was found to be both correlated with LMAS-14 (ICC average measure = 0.675; p-value <0.001) in addition to possessing a better predictive value. Thus, DMAS-7 showed to have good concordance and increased validity compared to LMAS-14. Having an optimal glycated hemoglobin (HbA1C) (OR = 0.779; p = 0.001) and performing regular physical activity (OR 2.328; p = 0.002) increased medication adherence. CONCLUSION: The DMAS-7 showed to be reliable and valid instrument superior to LMAS-14 in predicting adherence levels to oral anti-diabetic medications, and thus can be used to achieve better glycemic outcomes.

Evaluation of antidiabetic medication adherence in the Lebanese population: development of the Lebanese Diabetes Medication Adherence Scale.

OBJECTIVE: To evaluate factors affecting adherence to oral antidiabetic treatment in the Lebanese population and to develop the Diabetes Medication Adherence Scale (DMAS) based on these factors. METHODS: A cross-sectional study was conducted on a sample of Lebanese diabetic patients. Data were collected using a structured questionnaire. The level of adherence was measured using the Lebanese Medication Adherence Scale (LMAS-14). Bivariate analyses and multivariable analysis was done using SPSS. Psychometric evaluation of DMAS included an assessment of internal consistency, factor analysis, evaluation of sensitivity and specificity. Criterion-related validity was assessed by comparison with LMAS-14 measure of adherence. KEY FINDINGS: A total of 500 patients were recruited. 39.2% were adherent to treatment. Long working hours, increased number of oral antidiabetic medication per day, drug discontinuation when travelling, longer duration of diabetes and treatment burden were among factors that decreased adherence. While understanding the treatment regimen, following up physician recommendations and following up the recommended diet contributed to good medication adherence. The final 7-item scale (DMAS) had a good internal consistency (Cronbach's α = 0.612) and a good correlation and agreement with LMAS-14 (Spearman's rho = 0.699, Cohen's kappa = 0.566). Patients with high DMAS scores were significantly more likely to have controlled glycaemia (P < 0.05). Sensitivity and specificity reached 70.39% and 51.47%, respectively. CONCLUSION: Adherence to oral antidiabetic treatment is suboptimal in Lebanon. The DMAS is a reliable instrument for assessing adherence and predicting poor glycaemic control in clinical practice, but requires further validation in other populations.

Role of and Recent Evidence for Antiplatelet Therapy in Prevention of Cardiovascular Disease in Diabetes.

PURPOSE OF REVIEW: When treating patients with diabetes mellitus (DM), the benefits of antiplatelet therapy in preventing cardiovascular disease must be weighed against an increased risk of bleeding. Recent trials have sought to determine both the optimal anti-platelet regimen for patients with DM, and who specifically requires medication among the DM population. This paper will review recent trials and evidence recommending the use of antiplatelet therapy in the prevention of cardiovascular disease in patients with diabetes. RECENT FINDINGS: Seven notable trials assessed the effectiveness of antiplatelet therapy in the DM population. The ASCEND trial concluded 100 mg aspirin/day reduced rates of serious vascular events (OR 0.88, p < 0.01) but also increased rates of major bleeding events (OR 1.29, p < 0.01). The DAPT study revealed a longer dual antiplatelet regimen (30 months vs. 18 months) after coronary stent placement was more effective in reducing rates of stent thrombosis (0.5% vs. 1.1%, p = 0.06) and rates of myocardial infarction (3.5% vs. 4.8%, p = 0.06). DECLARE DIABETES showed that adding cilostazol to dual antiplatelet therapy after a coronary stent procedure reduced rates of in-stent and in-segment late loss and increased rates of revascularization (p < 0.04). In PEGASUS-TIMI, daily ticagrelor demonstrated reduced rates of major adverse cardiovascular and cerebrovascular events (OR 0.84, p < 0.04). The DAVID trial compared daily picotamide with daily aspirin therapy, finding reduced mortality rates in the picotamide group (OR 0.55, p < 0.05). Lastly, ACUITY found bivalirudin monotherapy resulted in lower rates of major bleeding events when compared to a glycoprotein IIb/IIa inhibitor and heparin or bivalirudin combination regimen (p < 0.01). Dual antiplatelet therapy guidelines still typically revolve around aspirin, but an increasing number of studies have demonstrated other drugs that may have a role in preventing atherosclerotic cardiovascular disease while decreasing the risk of major bleeding. Overall, it is wise to weigh the cardiovascular risk of a DM patient before prescribing antiplatelet medication. More research is necessary to determine a universal drug or combination of drugs that is safe and effective for DM patients.

Diabetes Medication Use in Association with Survival among Patients of Breast, Colorectal, Lung, or Gastric Cancer.

PURPOSE: Studies suggest that regular use of metformin may decrease cancer mortality. We investigated the association between diabetes medication use and cancer survival. MATERIALS AND METHODS: The current study includes 633 breast, 890 colorectal, 824 lung, and 543 gastric cancer cases identified from participants of two population-based cohort studies in Shanghai. Information on diabetes medication use was obtained by linking to electronic medical records. The associations between diabetes medication use (metformin, sulfonylureas, and insulin) and overall and cancer-specific survival were evaluated using time-dependent Cox proportional hazards models. RESULTS: After adjustment for clinical characteristics and treatment factors, use of metformin was associated with better overall survival among colorectal cancer patients (hazards ratio [HR], 0.55; 95% confidence interval [CI], 0.34 to 0.88) and for all four types of cancer combined (HR, 0.75; 95% CI, 0.57 to 0.98). Ever use of insulin was associated with worse survival for all cancer types combined (HR, 1.89; 95% CI, 1.57 to 2.29) and for the four cancer types individually. Similar associations were seen for diabetic patients. Sulfonylureas use was associated with worse overall survival for breast or gastric cancer (HR, 2.87; 95% CI, 1.22 to 6.80 and HR, 2.05; 95% CI, 1.09 to 3.84, respectively) among diabetic patients. Similar association patterns were observed between diabetes medication use and cancer-specific survival. CONCLUSION: Metformin was associated with improved survival among colorectal cancer cases, while insulin use was associated with worse survival among patients of four major cancers. Further investigation on the topic is needed given the potential translational impact of these findings.

Diabetes Medication Use in Association with Survival among Patients of Breast, Colorectal, Lung, or Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Studies suggest that regular use of metformin may decrease cancer mortality. We investigated the association between diabetes medication use and cancer survival. MATERIALS AND METHODS: The current study includes 633 breast, 890 colorectal, 824 lung, and 543 gastric cancer cases identified from participants of two population-based cohort studies in Shanghai. Information on diabetes medication use was obtained by linking to electronic medical records. The associations between diabetes medication use (metformin, sulfonylureas, and insulin) and overall and cancer-specific survival were evaluated using time-dependent Cox proportional hazards models. RESULTS: After adjustment for clinical characteristics and treatment factors, use of metformin was associated with better overall survival among colorectal cancer patients (hazards ratio [HR], 0.55; 95% confidence interval [CI], 0.34 to 0.88) and for all four types of cancer combined (HR, 0.75; 95% CI, 0.57 to 0.98). Ever use of insulin was associated with worse survival for all cancer types combined (HR, 1.89; 95% CI, 1.57 to 2.29) and for the four cancer types individually. Similar associations were seen for diabetic patients. Sulfonylureas use was associated with worse overall survival for breast or gastric cancer (HR, 2.87; 95% CI, 1.22 to 6.80 and HR, 2.05; 95% CI, 1.09 to 3.84, respectively) among diabetic patients. Similar association patterns were observed between diabetes medication use and cancer-specific survival. CONCLUSION: Metformin was associated with improved survival among colorectal cancer cases, while insulin use was associated with worse survival among patients of four major cancers. Further investigation on the topic is needed given the potential translational impact of these findings.

[Type 2 Diabetes and Vascular Endothelial Dysfunction].

Vascular endothelial function is important for maintaining the homeostasis of the living body. Especially, nitric oxide (NO) produced in vascular endothelial cells regulates blood vessel tone and has an antiatherosclerotic effect. Type 2 diabetes is a typical disease that causes impaired vascular endothelial function, resulting in various vascular complications and damage to organs. Cardiovascular disease associated with type 2 diabetes is a chronic inflammatory disease that starts with endothelial dysfunction (ED), and vascular ED is important as an initial change in arteriosclerotic lesions. Vascular ED in type 2 diabetes is thought to be caused by hyperglycemia, hyperinsulinemia associated with insulin resistance, and hypoglycemia, in which elevated oxidative stress accompanying postprandial hyperglycemia and blood glucose fluctuation are involved. Vascular ED is also caused by postprandial metabolic abnormalities, so correcting postprandial metabolic abnormalities is also important. Meanwhile, Glucagon-like peptide-1 (GLP-1) receptor agonist, thiazolidine, biguanide and Dipeptidyl peptidase-4 (DPP-4) inhibitor have an effect of protecting vascular endothelial function beyond glycemic control. In order to promote a healthy lifestyle for diabetes patients, it is important not only to lower HbA1c but also to avoid postprandial hyperglycemia, blood glucose fluctuation, and hypoglycemia. It is also important to conduct treatment with a view to suppressing vascular complications, such as the selection of antiarteriosclerosis medications.

Work-loss years among people diagnosed with diabetes: a reappraisal from a life course perspective.

AIMS: Early exit from the workforce has been proposed to be one of the unfavorable consequences of diabetes. We examined whether early exit from the workforce differed between persons who were and were not diagnosed with diabetes during their work career. METHODS: The cohort included 12,726 individuals of the Helsinki Birth Cohort Study, born between 1934 and 1944. Using data from nationwide registers, the cohort was followed up from early adulthood until they transitioned into retirement or died. Work-loss years were estimated using the restricted mean work years method. RESULTS: During a follow-up of 382,328 person-years for men and 349 894 for women, 36.8% transitioned into old age pension and 63.2% exited workforce early. Among men, 40.5% of those with and 32.8% of those without diabetes transitioned into old age pension (p=0.003). The corresponding numbers for women were 48.6% and 40.4% (p = 0.013), respectively. Mean age at exit from the workforce was 60.1 (95% confidence interval [CI], 59.6 to 60.7) years among men with diabetes and 57.6 (95% CI, 57.2 to 58.0) years among men without diabetes (p = 0.016). Among women, corresponding ages were 61.4 (95% CI, 60.8 to 61.9) years for those with diabetes and 59.5 (95% CI, 59.3 to 59.7) years for those without diabetes (p < 0.001). The difference in mean restricted work-loss years according to diabetes was 2.5 (95% CI 0.5 to 4.6) for men and 1.9 (95% CI 1.0 to 2.8) for women. CONCLUSION: Among individuals followed up throughout their work career, those with a diabetes diagnosis exited the workforce approximately two years later compared to those without diabetes.

Diabetes medication associates with DNA methylation of metformin transporter genes in the human liver.

BACKGROUND: Given that metformin is the most common pharmacological therapy for type 2 diabetes, understanding the function of this drug is of great importance. Hepatic metformin transporters are responsible for the pharmacologic action of metformin. However, epigenetics in genes encoding metformin transporters has not been fully elucidated. We examined the DNA methylation of these genes in the liver of subjects with type 2 diabetes and tested whether epigenetic alterations associate with diabetes medication, i.e., metformin or insulin plus metformin treatment. RESULTS: DNA methylation in OCT1 encoded by SLC22A1, OCT3 encoded by SLC22A3, and MATE1 encoded by SLC47A1 was assessed in the human liver. Lower average and promoter DNA methylation of SLC22A1, SLC22A3, and SLC47A1 was found in diabetic subjects receiving just metformin, compared to those who took insulin plus metformin or no diabetes medication. Moreover, diabetic subjects receiving just metformin had a similar DNA methylation pattern in these genes compared to non-diabetic subjects. Notably, DNA methylation was also associated with gene expression, glucose levels, and body mass index, i.e., higher SLC22A3 methylation was related to lower SLC22A3 expression and to insulin plus metformin treatment, higher fasting glucose levels and higher body mass index. Importantly, metformin treatment did also directly decrease DNA methylation of SLC22A1 in hepatocytes cultured in vitro. CONCLUSIONS: Our study supports that metformin decreases DNA methylation of metformin transporter genes in the human liver. Moreover, higher methylation levels in these genes associate with hyperglycaemia and obesity.

Diabetes treatment and hypoglycaemic episodes in elderly patients at nursing homes in Uppsala County.

AIM: The aim of this study was to examine the situation for elderly patients with diabetes living in nursing homes with regard to diabetes treatment, clinical variables, and vascular complications associated with diabetes. A second aim was to evaluate if the patients were at risk of hypoglycaemia. METHODS: This was a cross-sectional study including diabetes patients from all 30 nursing homes in Uppsala County, Sweden. Current antidiabetic medications, HbA1c, hypoglycaemic events, and diabetes complications were registered from the medical records. The patients were stratified into a general group and divided into three groups according to HbA1c (<52, 52-73, and >73 mmol/mol). RESULTS: Of 1,350 individuals, 218 patients were identified with diabetes mellitus. The diabetes duration was 11.2 ± 9.4 years and their serum HbA1c concentration 56.0 ± 1.2 mmol/mol. Hypoglycaemic events were reported in 24% of the diabetic individuals, and 43.1% of them had HbA1c <52 mmol/mol (mean value 44.0 ± 1.1 mmol/mol). Of these, 36% were taking antidiabetic drugs. Another 35.8% of the patients had HbA1c values between 52-73 mmol/mol (mean value 60.0 ± 1.1 mmol/mol), and 82% of these patients were taking antidiabetic drugs. Almost 80% of the diabetic patients had either micro- or macrovascular complications, with diabetes duration as an association for both micro- or macrovascular complications and hypoglycaemic events. CONCLUSIONS: A reduction of the use of antidiabetic drugs with follow-up of HbA1c level should be considered, especially for multimorbid elderly patients with low HbA1c and hypoglycaemia.