Serum selenium concentrations and risk of all-cause and heart disease mortality among individuals with type 2 diabetes.

BACKGROUND: The impact of selenium status on the long-term health of people with type 2 diabetes (T2D) remains unclear. OBJECTIVES: To prospectively examine the association of serum selenium concentrations with all-cause and heart disease mortality among individuals with T2D. METHODS: This analysis included 3199 adults with T2D from the third NHANES (NHANES III) and NHANES (2003-2004, 2011-2014). Mortality from heart disease and all causes was linked to National Death Index mortality data. Cox proportional hazard models were used to estimate HRs and 95% CIs. RESULTS: The median (IQR) concentration of serum selenium was 127.0 (115.0, 139.1) µg/L. During an average 12.6-y follow-up, 1693 deaths were documented, including 425 heart disease deaths. Compared with participants in the lowest quartile of selenium, the multivariate-adjusted HRs (95% CIs) for participants in the highest quartile were 0.69 (0.54, 0.89) for all-cause mortality (P-trend = 0.002) and 0.66 (0.45, 0.99) for heart disease mortality (P-trend = 0.03). In addition, a linear dose-response relation between serum selenium (range: 89-182 µg/L) and mortality was observed. For per-unit increment in natural log-transformed serum selenium, there was a 64% lower risk of all-cause mortality and a 66% lower risk of heart disease mortality (both P < 0.05). Similar results were observed when stratifying by age, sex, race, smoking status, BMI, physical activity, diabetes duration, and HbA1c concentrations. CONCLUSIONS: Our study suggested that higher selenium concentration was associated with lower all-cause and heart disease mortality among individuals with T2D. More studies are needed to confirm these findings.

Chocolate consumption and risk of coronary artery disease: the Million Veteran Program.

Background: Although previous studies have suggested cocoa products may promote cardiovascular health in the general population, no public data are available from patients receiving care in a national integrated health care system. Objectives: We tested the hypothesis that regular chocolate consumption is associated with a lower risk of coronary artery disease (CAD) events among participants of the Million Veteran Program (MVP). Secondary analysis examined if the main hypothesis was observed among participants with type 2 diabetes. Methods: We analyzed data from MVP participants who completed the food frequency section of the MVP Lifestyle Survey and were free of CAD at the time of survey completion. CAD events during follow-up (International Statistical Classification of Diseases Ninth Revision codes 410-411 and 413-414, and Tenth Revision codes I20-I25 except I25.2) were assessed using electronic health records. We fitted a Cox proportional hazard model to estimate the RR of CAD. Results: Of 188,447 MVP enrollees with survey data, mean ± SD age was 64 ± 12.0 y and 90% were men. For regular chocolate (28.3 g/serving) consumption of <1 serving/mo, 1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and ≥5 servings/wk, crude incidence rates (per 1000 person-years) for fatal and nonfatal CAD events or coronary procedures were 20.2, 17.5, 16.7, 17.1, and 16.9, respectively, during a mean follow-up of 3.2 y. After adjusting for age, sex, race, and lifestyle factors, the corresponding HRs (95% CIs) were 1.00 (ref), 0.92 (0.87, 0.96), 0.88 (0.83, 0.93), 0.89 (0.84, 0.95), and 0.89 (0.84, 0.96), respectively (P for linear trend < 0.0001). In a secondary analysis of 47,265 diabetics, we did not observe a decreasing trend in CAD mortality among those who consumed ≥1 serving of chocolate a month compared with those who consumed <1 serving/mo. Conclusions: Regular chocolate consumption was associated with a lower risk of CAD among veterans, but was not associated with cardiovascular disease risk in veterans with type 2 diabetes.

Coffee consumption and cardiovascular diseases and mortality in patients with type 2 diabetes: A systematic review and dose-response meta-analysis of cohort studies.

AIMS: To evaluate the long-term consequences of coffee drinking in patients with type 2 diabetes. DATA SYNTHESIS: PubMed, Scopus, and Web of Sciences were searched to November 2020 for prospective cohort studies evaluating the association of coffee drinking with risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes. Two reviewers extracted data and rated the certainty of evidence using GRADE approach. Random-effects models were used to estimate the hazard ratios (HRs) and 95% CIs. Dose-response associations were modeled by a one-stage mixed-effects meta-analysis. Ten prospective cohort studies with 82,270 cases were included. Compared to those with no coffee consumption, the HRs for consumption of 4 cups/d were 0.79 (95%CI: 0.72, 0.87; n = 10 studies) for all-cause mortality, 0.60 (95%CI: 0.46, 0.79; n = 4) for CVD mortality, 0.68 (95%CI: 0.51, 0.91; n = 3) for coronary heart disease (CHD) mortality, 0.72 (95%CI: 0.54, 0.98; n = 2) for CHD, and 0.77 (95%CI: 0.61, 0.98; n = 2) for total CVD events. There was no significant association for cancer mortality and stroke. There was an inverse monotonic association between coffee drinking and all-cause and CVD mortality, and inverse linear association for CHD and total CVD events. The certainty of evidence was graded moderate for all-cause mortality, and low or very low for other outcomes. CONCLUSIONS: Drinking coffee may be inversely associated with the risk of mortality in patients with type 2 diabetes. However, more research is needed considering type of coffee, sugar and cream added to coffee, and history of CVD to present more confident results. REGISTRY AND REGISTRY NUMBER: The protocol of this systematic review was registered at Open Science Framework (https://osf.io/8uaf3, registered form: osf.io/xur76, registration DOI: 10.17605/OSF.IO/8UAF3).

The effects of acarbose therapy on reductions of myocardial infarction and all-cause death in T2DM during 10-year multifactorial interventions (The Beijing Community Diabetes Study 24).

To investigate the potential benefits of acarbose therapy on cardiovascular events (CVD) in Type 2 diabetes (T2DM) in an urban community over 10-year follow-up. The study population of Beijing Community Diabetes Study (BCDS) were type 2 diabetes (T2DM) living in 21 communities in Beijing. All patients received comprehensive intervention in accordance with the Chinese guidelines for the prevention and treatment of diabetes. Professors in endocrinology from top tier hospitals regularly visited the communities for consultations, which was a feature of this study. A total of 1797 T2DM in BCDS study had complete screening data, including blood glucose, blood pressure, lipid profiles and acarbose continuous therapy. After 10-year follow-up, the risks of CVD outcomes were assessed according to whether patients had received acarbose therapy or not. All patients were followed-up to assess the long-term effects of the multifactorial interventions. At baseline, compared with the acarbose therapy free in T2DM, there was no significant difference in achieving the joint target control in patients with acarbose therapy. From the beginning of 8th year follow-up, the joint target control rate in patients with acarbose therapy was significantly higher than that of acarbose therapy free. During the 10-year follow-up, a total of 446 endpoint events occurred, including all-cause death, cardiovascular events, cerebrovascular events. The incidences of myocardial infarction (from the 4th year of follow-up) and all-cause death (from the 2nd year of follow-up) in patients who received acarbose therapy were significantly lower than that of acarbose therapy free respectively. In Cox multivariate analyses, there were significant differences in incidences of myocardial infarction and all-cause death between afore two groups during the 10-year follow-up, and the adjusted HRs were 0.50 and 0.52, respectively. After multifactorial interventions, T2DM with acarbose therapy revealed significant reductions of myocardial infarction and all-cause death. The long-term effects of with acarbose therapy on improving joint target control might be one of the main reasons of myocardial infarction and all-cause death reduction.Trial Registration: ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.

Thromboembolism, bleeding and vascular death in nonvalvular atrial fibrillation patients with type 2 diabetes receiving rivaroxaban or warfarin.

BACKGROUND: Diabetes increases a patient's risk of developing atrial fibrillation by 49%. Patients with nonvalvular atrial fibrillation are at a fivefold increased risk of stroke and die more frequently from vascular causes. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular atrial fibrillation patients with type 2 diabetes. METHODS: This was an analysis of Optum® De-Identified electronic health record data from 11/2010 to 12/2019. We included adults with nonvalvular atrial fibrillation and type 2 diabetes, newly started on rivaroxaban or warfarin and with ≥ 12-months of prior electronic health record activity. Patients who were pregnant, had alternative indications for oral anticoagulation or valvular heart disease were excluded. We evaluated the incidence rate (%/year) of developing the composite outcome of stroke/systemic embolism or vascular death and major or clinically relevant nonmajor bleeding as well as each endpoint individually. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted proportional hazards regression. RESULTS: We included 32,078 rivaroxaban (31% initiated on 15 mg dose) and 83,971warfarin users (time-in-therapeutic range = 47 ± 28%). Rivaroxaban was associated with a reduced risk of stroke/systemic embolism or vascular death (3.79 vs. 4.19; hazard ratio = 0.91, 95% confdience interval = 0.88-0.95), driven mostly by reductions in vascular death (2.81 vs 3.18, hazard ratio = 0.90, 95% confidence interval = 0.86-0.95) and systemic embolism (0.13 vs. 0.16; hazard ratio = 0.82, 95% confidence interval = 0.66-1.02). Major/clinically relevant nonmajor bleeding was less frequent with rivaroxaban versus warfarin (2.17 vs. 2.31; hazard ratio = 0.94, 95% confidence interval = 0.89-0.99) due to decreased critical organ bleeding (including intracranial hemorrhage) (0.35 vs. 0.54; hazard ratio = 0.63, 95% confidence interval = 0.55-0.72). CONCLUSIONS: In nonvalvular atrial fibrillation patients with type 2 diabetes, rivaroxaban was associated with an ~ 10% relative reduction in vascular mortality and fewer bleeding-related hospitalizations versus warfarin.

Association of Acupuncture Treatment with Mortality of Type 2 Diabetes in China: Evidence of a Real-World Study.

The prevalence and mortality rates of diabetes are increasing globally, posing severe challenges to health systems. Acupuncture is used worldwide as a non-drug treatment for diabetes. However, empirical evidence of the effect of combined acupuncture and drug treatments on diabetic-associated mortality is limited. This study aimed to examine this association of acupuncture treatment with mortality of type 2 diabetes based on real-world data. A four-year cohort study was conducted in Shanghai between 2015 and 2018, The database consisted of 37,718 patients (acupuncture group: 6865 type 2 diabetes mellitus (T2DM) patients, non-acupuncture (control) group: 30,853 T2DM patients) in 2016. The objective was to analyze the impact of receiving acupuncture prescriptions for diabetes in 2016 on all-cause mortality in 2018 based on real-world data. An Inverse Probability Weighted Regression Adjustment (IPWRA) and Propensity Score Matching (PSM) were used to minimize the bias due to potential confounding variables to increase the reliability of differences in comparisons between the two groups. Our inverse probability weighted regression results suggest that the coefficient of the key dependent variable of accepted acupuncture in 2016 was negative (coefficient: -0.0002; 95% CI: -0.0024-0.0019, p = 0.857), but it is not statistically significant. In robustness check, PSM with the nearest-neighbor method with replacement at a 1:4 ratio and 1:3 ratio and kernel matching showed that the average treatment effect was negative. Therefore, there was a negative correlation between acupuncture combined with other drugs and the mortality of diabetic patients, but it was not statistically significant.

Impact of Quality Improvement (QI) Program on 5-Year Risk of Diabetes-Related Complications: A Simulation Study.

OBJECTIVE: We successfully implemented the American Diabetes Association's (ADA) Diabetes INSIDE (INspiring System Improvement with Data-Driven Excellence) quality improvement (QI) program at a university hospital and safety-net health system (Tulane and Parkland), focused on system-wide improvement in poorly controlled type 2 diabetes (HbA1c >8.0% [64 mmol/mol]). In this study, we estimated the 5-year risk reduction in complications and mortality associated with the QI program. RESEARCH DESIGN AND METHODS: The QI implementation period was 1 year, followed by the postintervention period of 6 months to evaluate the impact of QI on clinical measures. We measured the differences between the baseline and postintervention clinical outcomes in 2,429 individuals with HbA1c >8% (64 mmol/mol) at baseline and used the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes model to project the 5-year risk reduction of diabetes-related complications under the assumption that intervention benefits persist over time. An alternative assumption that intervention benefits diminish by 30% every year was also tested. RESULTS: The QI program was associated with reductions in HbA1c (-0.84%) and LDL cholesterol (LDL-C) (-5.94 mg/dL) among individuals with HbA1c level >8.0% (64 mmol/mol), with greater reduction in HbA1c (-1.67%) and LDL-C (-6.81 mg/dL) among those with HbA1c level >9.5% at baseline (all P < 0.05). The implementation of the Diabetes INSIDE QI program was associated with 5-year risk reductions in major adverse cardiovascular events (MACE) (relative risk [RR] 0.78 [95% CI 0.75-0.81]) and all-cause mortality (RR 0.83 [95% CI 0.82-0.85]) among individuals with baseline HbA1c level >8.0% (64 mmol/mol), and MACE (RR 0.60 [95% CI 0.56-0.65]) and all-cause mortality (RR 0.61 [95% CI 0.59-0.64]) among individuals with baseline HbA1c level >9.5% (80 mmol/mol). Sensitivity analysis also identified a substantially lower risk of diabetes-related complications and mortality associated with the QI program. CONCLUSIONS: Our modeling results suggest that the ADA's Diabetes INSIDE QI program would benefit the patients and population by substantially reducing the 5-year risk of complications and mortality in individuals with diabetes.

Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort study.

BACKGROUND: Diabetes has been associated with increased COVID-19-related mortality, but the association between modifiable risk factors, including hyperglycaemia and obesity, and COVID-19-related mortality among people with diabetes is unclear. We assessed associations between risk factors and COVID-19-related mortality in people with type 1 and type 2 diabetes. METHODS: We did a population-based cohort study of people with diagnosed diabetes who were registered with a general practice in England. National population data on people with type 1 and type 2 diabetes collated by the National Diabetes Audit were linked to mortality records collated by the Office for National Statistics from Jan 2, 2017, to May 11, 2020. We identified the weekly number of deaths in people with type 1 and type 2 diabetes during the first 19 weeks of 2020 and calculated the percentage change from the mean number of deaths for the corresponding weeks in 2017, 2018, and 2019. The associations between risk factors (including sex, age, ethnicity, socioeconomic deprivation, HbA1c, renal impairment [from estimated glomerular filtration rate (eGFR)], BMI, tobacco smoking status, and cardiovascular comorbidities) and COVID-19-related mortality (defined as International Classification of Diseases, version 10, code U07.1 or U07.2 as a primary or secondary cause of death) between Feb 16 and May 11, 2020, were investigated by use of Cox proportional hazards models. FINDINGS: Weekly death registrations in the first 19 weeks of 2020 exceeded the corresponding 3-year weekly averages for 2017-19 by 672 (50·9%) in people with type 1 diabetes and 16 071 (64·3%) in people with type 2 diabetes. Between Feb 16 and May 11, 2020, among 264 390 people with type 1 diabetes and 2 874 020 people with type 2 diabetes, 1604 people with type 1 diabetes and 36 291 people with type 2 diabetes died from all causes. Of these total deaths, 464 in people with type 1 diabetes and 10 525 in people with type 2 diabetes were defined as COVID-19 related, of which 289 (62·3%) and 5833 (55·4%), respectively, occurred in people with a history of cardiovascular disease or with renal impairment (eGFR <60 mL/min per 1·73 m2). Male sex, older age, renal impairment, non-white ethnicity, socioeconomic deprivation, and previous stroke and heart failure were associated with increased COVID-19-related mortality in both type 1 and type 2 diabetes. Compared with people with an HbA1c of 48-53 mmol/mol (6·5-7·0%), people with an HbA1c of 86 mmol/mol (10·0%) or higher had increased COVID-19-related mortality (hazard ratio [HR] 2·23 [95% CI 1·50-3·30, p<0·0001] in type 1 diabetes and 1·61 [1·47-1·77, p<0·0001] in type 2 diabetes). In addition, in people with type 2 diabetes, COVID-19-related mortality was significantly higher in those with an HbA1c of 59 mmol/mol (7·6%) or higher than in those with an HbA1c of 48-53 mmol/mol (HR 1·22 [95% CI 1·15-1·30, p<0·0001] for 59-74 mmol/mol [7·6-8·9%] and 1·36 [1·24-1·50, p<0·0001] for 75-85 mmol/mol [9·0-9·9%]). The association between BMI and COVID-19-related mortality was U-shaped: in type 1 diabetes, compared with a BMI of 25·0-29·9 kg/m2, a BMI of less than 20·0 kg/m2 had an HR of 2·45 (95% CI 1·60-3·75, p<0·0001) and a BMI of 40·0 kg/m2 or higher had an HR of 2·33 (1·53-3·56, p<0·0001); the corresponding HRs for type 2 diabetes were 2·33 (2·11-2·56, p<0·0001) and 1·60 (1·47-1·75, p<0·0001). INTERPRETATION: Deaths in people with type 1 and type 2 diabetes rose sharply during the initial COVID-19 pandemic in England. Increased COVID-19-related mortality was associated not only with cardiovascular and renal complications of diabetes but, independently, also with glycaemic control and BMI. FUNDING: None.

Estimating the number of preventable cardiovascular disease events in the United States using the EMPA-REG OUTCOME trial results and National Health and Nutrition Examination Survey.

AIM: We examined eligibility and preventable cardiovascular disease events in US adults with diabetes mellitus from the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME). METHODS: We identified adults with diabetes mellitus eligible for EMPA-REG OUTCOME based on trial eligibility criteria available from the National Health and Nutrition Examination Surveys, 2007-2016. We estimated composite cardiovascular disease endpoints, as well as all-cause deaths, death from cardiovascular disease and hospitalizations for heart failure from trial treatment and placebo event rates, the difference indicating the preventable events. RESULTS: Among 29,629 US adults aged ⩾18 years (representing 231.9 million), 4672 (27.3 million) had diabetes mellitus, with 342 (1.86 million) meeting eligibility criteria of EMPA-REG OUTCOME. We estimated from trial primary endpoint event rates of 10.5% and 12.1% in the empagliflozin and placebo groups, respectively, that based on the 'treatment' of our 1.86 million estimated EMPA-REG OUTCOME eligible subjects, 12,066 (95% confidence interval: 10,352-13,780) cardiovascular disease events could be prevented annually. Estimated annual preventable deaths from any cause, cardiovascular causes and hospitalizations from heart failure were 17,078 (95% confidence interval: 14,652-19,504), 14,479 (95% confidence interval: 12,422-16,536) and 9467 (95% confidence interval: 8122-10,812), respectively. CONCLUSION: Empagliflozin, if provided to EMPA-REG OUTCOME eligible US adults, may prevent many cardiovascular disease events, cardiovascular and total deaths, as well as heart failure hospitalizations.

LEADER Trial Eligibility and Preventable Cardiovascular Events in US Adults with Diabetes: the National Health and Nutrition Examination Surveys 2007-2016.

PURPOSE: The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial showed the cardiovascular disease (CVD) benefits of liraglutide therapy among patients with type 2 diabetes mellitus (T2DM). We applied this trial to US adults with T2DM in terms of eligibility and preventable CVD events. METHODS: We included US adults with T2DM from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. Eligibility criteria from LEADER primary and secondary prevention cohorts were applied to determine potentially eligible US adults. We estimated the number of primary composite and secondary CVD endpoints that would occur based on LEADER treated and placebo published event rates, with the difference indicating the number of preventable events. RESULTS: Among 4672 (projected to 27.3 million [M]) adults we identified with T2DM, we estimated 800 (4.2 million) (15.4%) to fit LEADER eligibility criteria, including 205 (0.9 M) primary prevention 595 (3.3 M) secondary prevention subjects. Compared to LEADER trial participants, our sample had higher proportions of women and minorities, prior angina, chronic kidney disease, and lipid-lowering medication use. We estimated 21,209 primary composite CVD events, 29,691 extended CVD composite outcomes, 16,967 all-cause deaths, 16,967 cardiovascular deaths, 12,725 myocardial infarctions, and 12,725 microvascular events would be prevented annually if our eligible T2DM subjects were on liraglutide. CONCLUSION: Liraglutide may prevent many fatal and non-fatal CVD events if provided to US adults meeting LEADER eligibility criteria. More efforts are needed to educate the healthcare providers on the CVD benefits from newer diabetes therapies, including liraglutide.

Association of types of dietary fats and all-cause and cause-specific mortality: A prospective cohort study and meta-analysis of prospective studies with 1,164,029 participants.

BACKGROUND: Associations between dietary fats and mortality are unclear. METHODS: We evaluated the relationship between quartiles of total fat, mono-unsaturated (MUFA), polyunsaturated (PUFA) and saturated fatty acid (SFA) consumption, and all-cause, coronary heart disease (CHD), stroke, and type 2 diabetes (T2D)-associated mortality in 24,144 participants from the National Health and Nutrition Examination Surveys (NHANES) 1999-2010. We added our results to a meta-analysis based on searches until November 2018. RESULTS: In fully adjusted Cox-proportional hazard models in our prospective study, there was an inverse association between total fat (HR: 0.90, 95% confidence interval 0.82, 0.99, Q4 vs Q1) and PUFA (0.81, 0.78-0.84) consumption and all-cause mortality, whereas SFA were associated with the increased mortality (1.08, 1.04-1.11). In the meta-analysis of 29 prospective cohorts (n = 1,164,029) we found a significant inverse association between total fat (0.89, 0.82-0.97), MUFA (0.94, 0.89-0.99) and PUFA (0.89, 0.84-0.94) consumption and all-cause mortality. No association was observed between total fat and CVD (0.93, 0.80-1.08) or CHD mortality (1.03 0.99-1.09). A significant association between SFA intake and CHD mortality (1.10, 1.01-1.21) was observed. Neither MUFA nor PUFA were associated with CVD or CHD mortality. Inverse associations were observed between MUFA (0.80, 0.67-0.96) and PUFA (0.84, 0.80-0.90) intakes and stroke mortality. CONCLUSIONS: We showed differential associations of total fat, MUFA and PUFA with all-cause mortality, but not CVD or CHD mortalities. SFA was associated with higher all-cause mortality in NHANES and with CHD mortality in our meta-analysis. The type of fat intake appears to be associated with important health outcomes.

Incidence and characteristics of childhood- and youth-onset diabetes in the Qalandarabad area in northern Pakistan.

OBJECTIVES: Determine the types, incidence, mortality rate, and clinical status of youth diabetes at Bach Christian Hospital (BCH), Qalandarabad, Pakistan. METHODS: Analysis of incidence and mortality data of all patients (<25 year (y)) diagnosed from January 2014-June 2019, and also analysis of clinical status of patients < 25y seen in 2018/2019. RESULTS: Ninety-three patients were seen over the study period. Eighty-eight were type 1 diabetes (T1D), 51.1% female. Age of diagnosis was 0.8-24.5 years (y) (mean = 11.4 y, SD = 6.2y). 15.1% were 0-4y, 31.4% 5-9 y, 24.4% 10-14y, 19.8% 15-19y, and 9.3% 20-24y. Minimum incidence for the Mansehra tehsil administrative district was calculated as 1.0 per 100,000 population <15y/y, 1.2 per 100,000 < 20y/y and 1.1 per 100,000 < 25y/y; the degree of ascertainment could not be assessed. A further four patients were diagnosed with thiamine-responsive megaloblastic anaemia (TRMA), all male, three from the same consanguineous family, and were treated with high-dose thiamine. One other patient was diagnosed with type 2 diabetes. Three T1D and one TRMA patient died during the study period. The standardised mortality rate for T1D was 9.4, but vital status was unknown for 13 patients. The mean/median HbA1c of T1D patients seen in 2018/2019 was 9.1%/9.2% (76/77 mmol/mol). CONCLUSIONS: Minimum T1D incidence in Mansehra tehsil is double the previously reported value for Pakistan (from 1990 to 1999), although is still low compared to most other countries. Considering the limited resources available, patients attending BCH are achieving fair glycemic control. The TRMA cases show the importance of genetic testing in atypical cases.

Type 2 Diabetes Mellitus, Insulin Resistance, and Vitamin D.

PURPOSE OF REVIEW: There is a growing, largely inconsistent, literature on the role of vitamin D in association with type 2 diabetes, insulin resistance/insulin secretion, glycemic indices, and complications of type 2 diabetes. Pathophysiologic, bystander, preventive, and treatment roles of vitamin D have all been proposed. In this focused review, we attempt to organize and clarify our current information in this area. RECENT FINDINGS: Clinical study interpretation is difficult because of variability in dosage, dosage form, study duration, and populations studied, as well as recently reported normal human polymorphisms in vitamin D synthesis and catabolism, vitamin D-binding protein, and vitamin D receptors in addition to a host of potential epigenetic confounders. Low vitamin D status appears to be associated with type 2 diabetes and most other insulin resistance disorders reported to date. The extraskeletal benefits of supplementation/repletion in these disorders in our species, with a few highlighted exceptions, remain to be established. This focused review attempts to summarize our current knowledge in this burgeoning area through a review of key meta-analyses, observational studies, randomized control trials, and Mendelian randomization studies and will hopefully serve as a guide to indicate future research directions and current best practice.

Metformin Prolongs Survival in Type 2 Diabetes Lung Cancer Patients With EGFR-TKIs.

Background: Metformin use reportedly reduces cancer risk and improves survival in lung cancer patients. This study aimed to investigate the effect of metformin use in patients with diabetes mellitus (DM) and lung cancer receiving epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) therapy. Methods: A nationwide, population-based cohort study was conducted using the Taiwan National Health Insurance Research Database. From January 1, 2004, to December 31, 2012, a total of 373 metformin and 1260 non-metformin lung cancer cohorts with type 2 DM and EGFR-TKI treatment were studied. Results: Metformin use was significantly associated with a reduced risk of death (hazard ratio: 0.73, 95% confidence interval [CI]: 0.62-0.85, P < .001), as well as a significantly longer median progression-free survival (9.2 months, 95% CI: 8.6-11.7, vs 6.4 months, 95% CI: 5.9-7.2 months, P < .001) and median overall survival (33.4 months, 95% CI: 29.4-40.2, vs 25.4 months, 95% CI: 23.7-27.2 months, P < 0.001). Conclusions: In conclusion, metformin may potentially enhance the therapeutic effect and increase survival in type 2 DM patients with lung cancer receiving EGFR-TKI therapy.

Projected number of people with diagnosed Type 2 diabetes in Germany in 2040.

AIMS: To project the number of people with Type 2 diabetes in Germany between 2015 and 2040. METHODS: Based on data from 65 million insurees of the German statutory health insurance, we projected the age-specific prevalence of diabetes using mathematical relations between prevalence, incidence rate and mortality. We compared several scenarios regarding temporal trends in the incidence and mortality rate. The projected age-specific prevalence was applied to the projected age structure of the German population between 2015 and 2040 to calculate the number of people with Type 2 diabetes. RESULTS: Application of current age-specific prevalence estimates to the projected age structure in 2040, although ignoring temporal trends in incidence and mortality, yielded an increase in the number of Type 2 diabetes cases from 6.9 million in 2015 to 8.3 million (+21%) in 2040. More realistic scenarios that account for decreasing mortality rates and different trends in the incidence rates project between 10.7 million (+54%) and 12.3 million (+77%) Type 2 diabetes cases in 2040. CONCLUSIONS: For the first time, we projected the number of future Type 2 diabetes cases for the whole adult population in Germany. The results indicate a relative increase in the number of Type 2 diabetes cases of between 54% and 77% from 2015 to 2040. Temporal trends in the incidence rate are the main drivers of this increase. Simply applying current age-specific prevalence to the future age structure probably underestimates the future number of Type 2 diabetes cases.

Associations between multimorbidity, all-cause mortality and glycaemia in people with type 2 diabetes: A systematic review.

INTRODUCTION: Type 2 diabetes (T2D) is a major health priority worldwide and the majority of people with diabetes live with multimorbidity (MM) (the co-occurrence of ≥2 chronic conditions). The aim of this systematic review was to explore the association between MM and all-cause mortality and glycaemic outcomes in people with T2D. METHODS: The search strategy centred on: T2D, MM, comorbidity, mortality and glycaemia. Databases searched: MEDLINE, EMBASE, CINAHL Complete, The Cochrane Library, and SCOPUS. Restrictions included: English language, quantitative empirical studies. Two reviewers independently carried out: abstract and full text screening, data extraction, and quality appraisal. Disagreements adjudicated by a third reviewer. RESULTS: Of the 4882 papers identified; 41 met inclusion criteria. The outcome was all-cause mortality in 16 studies, glycaemia in 24 studies and both outcomes in one study. There were 28 longitudinal cohort studies and 13 cross-sectional studies, with the number of participants ranging from 96-892,223. Included studies were conducted in high or upper-middle-income countries. Fifteen of 17 studies showed a statistically significant association between increasing MM and higher mortality. Ten of 14 studies showed no significant associations between MM and HbA1c. Four of 14 studies found higher levels of MM associated with higher HbA1c. Increasing MM was significantly associated with hypoglycaemia in 9/10 studies. There was no significant association between MM and fasting glucose (one study). No studies explored effects on glycaemic variability. CONCLUSIONS: This review demonstrates that MM in T2D is associated with higher mortality and hypoglycaemia, whilst evidence regarding the association with other measures of glycaemic control is mixed. The current single disease focused approach to management of T2D seems inappropriate. Our findings highlight the need for clinical guidelines to support a holistic approach to the complex care needs of those with T2D and MM, accounting for the various conditions that people with T2D may be living with. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews CRD42017079500.

Reducing chronic disease through changes in food aid: A microsimulation of nutrition and cardiometabolic disease among Palestinian refugees in the Middle East.

BACKGROUND: Type 2 diabetes mellitus and cardiovascular disease and have become leading causes of morbidity and mortality among Palestinian refugees in the Middle East, many of whom live in long-term settlements and receive grain-based food aid. The objective of this study was to estimate changes in type 2 diabetes and cardiovascular disease morbidity and mortality attributable to a transition from traditional food aid to either (i) a debit card restricted to food purchases, (ii) cash, or (iii) an alternative food parcel with less grain and more fruits and vegetables, each valued at $30/person/month. METHODS AND FINDINGS: An individual-level microsimulation was created to estimate relationships between food aid delivery method, food consumption, type 2 diabetes, and cardiovascular disease morbidity and mortality using demographic data from the United Nations (UN; 2017) on 5,340,443 registered Palestinian refugees in Syria, Jordan, Lebanon, Gaza, and the West Bank, food consumption data (2011-2017) from households receiving traditional food parcel delivery of food aid (n = 1,507 households) and electronic debit card delivery of food aid (n = 1,047 households), and health data from a random 10% sample of refugees receiving medical care through the UN (2012-2015; n = 516,386). Outcome metrics included incidence per 1,000 person-years of hypertension, type 2 diabetes, atherosclerotic cardiovascular disease events, microvascular events (end-stage renal disease, diabetic neuropathy, and proliferative diabetic retinopathy), and all-cause mortality. The model estimated changes in total calories, sodium and potassium intake, fatty acid intake, and overall dietary quality (Mediterranean Dietary Score [MDS]) as mediators to each outcome metric. We did not observe that a change from food parcel to electronic debit card delivery of food aid or to cash aid led to a meaningful change in consumption, biomarkers, or disease outcomes. By contrast, a shift to an alternative food parcel with less grain and more fruits and vegetables was estimated to produce a 0.08 per 1,000 person-years decrease in the incidence of hypertension (95% confidence interval [CI] 0.05-0.11), 0.18 per 1,000 person-years decrease in the incidence of type 2 diabetes (95% CI 0.14-0.22), 0.18 per 1,000 person-years decrease in the incidence of atherosclerotic cardiovascular disease events (95% CI 0.17-0.19), and 0.02 decrease per 1,000 person-years all-cause mortality (95% CI 0.01 decrease to 0.04 increase) among those receiving aid. The benefits of this shift, however, could be neutralized by a small (2%) increase in compensatory (out-of-pocket) increases in consumption of refined grains, fats and oils, or confectionaries. A larger alternative parcel requiring an increase in total food aid expenditure by 27% would be more likely to have a clinically meaningful improvement on type 2 diabetes and cardiovascular disease incidence. CONCLUSIONS: Contrary to the supposition in the literature, our findings do not robustly support the theory that transitioning from traditional food aid to either debit card or cash delivery alone would necessarily reduce chronic disease outcomes. Rather, an alternative food parcel would be more effective, even after matching current budget ceilings. But compensatory increases in consumption of less healthy foods may neutralize the improvements from an alternative food parcel unless total aid funding were increased substantially. Our analysis is limited by uncertainty in estimates of modeling long-term outcomes from shorter-term trials, focusing on diabetes and cardiovascular outcomes for which validated equations are available instead of all nutrition-associated health outcomes, and using data from food frequency questionnaires in the absence of 24-hour dietary recall data.

Diabetes Shared Care Program (DSCP) and risk of infection mortality: a nationwide cohort study using administrative claims data in Taiwan.

OBJECTIVE: The Diabetes Shared Care Program (DSCP) is an integrated care model in Taiwan that has been proven to improve the care quality of patients with diabetes. We aimed to evaluate the efficacy of DSCP in decreasing the hospital mortality of infectious diseases. METHODS: From 1 662 929 patients with type 2 diabetes newly diagnosed between 1999 and 2013, we retrieved a total of 919 patients who participated in the DSCP with the first hospitalisation for an infectious disease as the study cohort and 9190 propensity score-matched patients with type 2 diabetes who did not participate as the comparison.The efficacy of DSCP was evaluated via the following comparisons between the DSCP and non-DSCP cohorts: hospital mortality, 1-year medical cost prior to and during the hospitalisation, and complications, such as receiving mechanical ventilation and intensive care unit admission. The ratio (OR) for hospital mortality of the DSCP participants was calculated by logistical regression. Further stratification analyses were conducted to examine which group of patients with type 2 diabetes benefited the most from the DSCP during hospitalisation for infectious diseases. RESULTS: The DSCP cohort had a lower hospital mortality rate than the non-DSCP participants (2.18% vs 4.82%, p<0.001). The total medical cost during the hospitalisation was lower in the DSCP cohort than in the non-DSCP cohort (NT$72 454±30 429 vs NT$86 385±29 350) (p=0.006). In the logistical regression model, the DSCP participants exhibited a significantly decreased adjusted OR for hospital mortality (adjusted OR=0.42, 95% CI 0.26 to 0.66, p=0.0002). The efficacy of the DSCP was much more prominent in male patients with type 2 diabetes and in patients with lower incomes. CONCLUSION: Participation in the DSCP was associated with a lower risk of hospital mortality for infectious diseases.

Diabetes, Frequency of Exercise, and Mortality Over 12 Years: Analysis of the National Health Insurance Service-Health Screening (NHIS-HEALS) Database.

BACKGROUND: The goal of this study was to analyze the relationship between exercise frequency and all-cause mortality for individuals diagnosed with and without diabetes mellitus (DM). METHODS: We analyzed data for 505,677 participants (53.9% men) in the National Health Insurance Service-National Health Screening (NHIS-HEALS) cohort. The study endpoint variable was all-cause mortality. RESULTS: Frequency of exercise and covariates including age, sex, smoking status, household income, blood pressure, fasting glucose, body mass index, total cholesterol, and Charlson comorbidity index were determined at baseline. Cox proportional hazard regression models were developed to assess the effects of exercise frequency (0, 1-2, 3-4, 5-6, and 7 days per week) on mortality, separately in individuals with and without DM. We found a U-shaped association between exercise frequency and mortality in individuals with and without DM. However, the frequency of exercise associated with the lowest risk of all-cause mortality was 3-4 times per week (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.65-0.73) in individuals without DM, and 5-6 times per week in those with DM (HR, 0.93; 95% CI, 0.78-1.10). CONCLUSION: A moderate frequency of exercise may reduce mortality regardless of the presence or absence of DM; however, when compared to those without the condition, people with DM may need to exercise more often.