Impact of herpes zoster vaccination on incident dementia: A retrospective study in two patient cohorts

Background Herpes zoster (HZ) infection increases dementia risk, but it is not known if herpes zoster vaccination is associated with lower risk for dementia. We determined if HZ vaccination, compared to no HZ vaccination, is associated with lower risk for incident dementia. Methods and findings Data was obtained from Veterans Health Affairs (VHA) medical records (10/1/2008–9/30/2019) with replication in MarketScan® commercial and Medicare claims (1/1/2009-12/31/2018). Eligible patients were ≥65 years of age and free of dementia for two years prior to baseline (VHA n = 136,016; MarketScan n = 172,790). Two index periods (either start of 2011 or 2012) were defined, where patients either had or did not have a HZ vaccination. Confounding was controlled with propensity scores and inverse probability of treatment weighting. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between HZ vaccination and incident dementia in all patients and in age (65–69, 70–74, ≥75) and race (White, Black, Other) sub-groups. Sensitivity analysis measured the association between HZ vaccination and incident Alzheimer’s dementia (AD). HZ vaccination at index versus no HZ vaccination throughout follow-up. VHA patients mean age was 75.7 (SD±7.4) years, 4.0% were female, 91.2% white and 20.2% had HZ vaccination. MarketScan patients mean age was 69.9 (SD±5.7) years, 65.0% were female and 14.2% had HZ vaccination. In both cohorts, HZ vaccination compared with no vaccination, was significantly associated with lower dementia risk (VHA HR = 0.69; 95%CI: 0.67–0.72; MarketScan HR = 0.65; 95%CI:0.57–0.74). HZ vaccination was not related to dementia risk in MarketScan patients aged 65–69 years. No difference in HZ vaccination to dementia effects were found by race. HZ vaccination was associated with lower risk for AD. Conclusions HZ vaccination is associated with reduced risk of dementia. Vaccination may provide nonspecific neuroprotection by training the immune system to limit damaging inflammation, or specific neuroprotection that prevents viral cytopathic effects.

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Lower Risk for Dementia Following Adult Tetanus, Diphtheria and Pertussis (Tdap) Vaccination

The Journals of Gerontology Series A ◽

10.1093/gerona/glab115 ◽

2021 ◽

Author(s):

Jeffrey F Scherrer ◽

Joanne Salas ◽

Timothy L Wiemken ◽

Christine Jacobs ◽

John E Morley ◽

...

Keyword(s):

Lower Risk ◽

Protective Effects ◽

Proportional Hazard ◽

Veterans Health ◽

Cox Proportional Hazard ◽

Dementia Risk ◽

Incident Dementia ◽

Nonspecific Effects ◽

Reduce Risk

Abstract Background Adult vaccinations may reduce risk for dementia. However it has not been established whether tetanus, diphtheria, pertussis (Tdap) vaccination is associated with incident dementia. Methods Hypotheses were tested in a Veterans Health Affairs (VHA) cohort and replicated in a MarketScan medical claims cohort. Patients were ≥65 years of age and free of dementia for 2 years prior to index date. Patients either had or did not have a Tdap vaccination by the start of either of two index periods (2011 or 2012). Follow-up continued through 2018. Controls had no Tdap vaccination for the duration of follow-up. Confounding was controlled using entropy balancing. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between Tdap vaccination and incident dementia in all patients and in age sub-groups (65-69, 70-74, ≥75 years of age). Results VHA patients were, on average, 75.6 (SD±7.5) years of age, 4% female, and 91.2% were white race. MarketScan patients were 69.8 (SD±5.6) years of age, on average and 65.4% were female. After controlling for confounding, patients with, compared to without Tdap vaccination, had a significantly lower risk for dementia in both cohorts (VHA: HR=0.58; 95%CI:0.54 - 0.63 and MarketScan: HR=0.58; 95%CI:0.48 - 0.70). Conclusions Tdap vaccination was associated with a 42% lower dementia risk in two cohorts with different clinical and sociodemographic characteristics. Several vaccine types are linked to decreased dementia risk, suggesting that these associations are due to nonspecific effects on inflammation rather than vaccine-induced pathogen-specific protective effects.

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Dose-response association between device-measured physical activity and incident dementia: a prospective study from UK Biobank

BMC Medicine ◽

10.1186/s12916-021-02172-5 ◽

2021 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Fanny Petermann-Rocha ◽

Donald M. Lyall ◽

Stuart R. Gray ◽

Jason M. R. Gill ◽

Naveed Sattar ◽

...

Keyword(s):

Physical Activity ◽

Lower Risk ◽

Hazard Models ◽

Proportional Hazard ◽

Uk Biobank ◽

Proportional Hazard Models ◽

Cox Proportional Hazard ◽

Incident Dementia ◽

Cox Proportional Hazard Models

Abstract Background Previous cohort studies have investigated the relationship between self-reported physical activity (PA) and dementia. Evidence from objective device-measured PA data is lacking. This study aimed to explore the association of device-measured PA with the risk of dementia incidence and common subtypes (Alzheimer’s disease [AD] and vascular dementia) using the UK Biobank study. Methods 84,854 participants (55.8% women), invited to participate in the device-measured PA between 2013 and 2015, were included in this prospective cohort study. Wrist accelerometers were used to measure light, moderate, vigorous, moderate-to-vigorous PA (MVPA) and total PA intensity and duration (MET/min/week). Incident dementia (fatal and non-fatal) was extracted from hospital episodes records for incidence and death register for mortality. Incidence follow-up was carried out until the end of March 2021in England and Scotland and the end of March 2018 in Wales. Mortality data were available until February 2021. Nonlinear associations were first investigated using penalised cubic splines fitted in the Cox proportional hazard models. In addition, using MVPA, five categories were created. Associations of these categories with the outcomes were investigated using Cox proportional hazard models. Analyses were adjusted for sociodemographic, lifestyle and health-related factors. Results After a median follow-up of 6.3 years, 678 individuals were diagnosed with dementia. Evidence of nonlinearity was observed for all PA modes and all-cause dementia. For categories of MVPA, there was a significant trend towards a low risk of overall dementia when higher levels of MVPA were achieved (HRtrend 0.66 [95% CI 0.62 to 0.70]. The lowest risk was identified in individuals who performed more than 1200 MET/min/week, those who had 84% (95% CI 0.12 to 0.21) lower risk of incident dementia compared to those who performed < 300 MET/min/week. Conclusions Participants with higher PA levels had a lower risk of incident dementia than those less active, independently of sociodemographic, lifestyle factors and comorbidity. Considering that the majority of previous studies have reported this association using self-reported data, our findings highlight the strong inverse association between PA objectively measured and incident dementia.

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Histologic Remission Is Associated With Lower Risk of Treatment Failure in Patients With Crohn Disease in Endoscopic Remission

Inflammatory Bowel Diseases ◽

10.1093/ibd/izaa301 ◽

2020 ◽

Author(s):

Hyuk Yoon ◽

Sushrut Jangi ◽

Parambir S Dulai ◽

Brigid S Boland ◽

Vipul Jairath ◽

...

Keyword(s):

Treatment Failure ◽

Crohn Disease ◽

Lower Risk ◽

Hazard Analysis ◽

Cumulative Risk ◽

Treatment Optimization ◽

Cox Proportional Hazard ◽

Endoscopic Remission ◽

Risk Of Treatment

Abstract Background Although achieving histologic remission in ulcerative colitis is established, the incremental benefit of achieving histologic remission in patients with Crohn disease (CD) treated to a target of endoscopic remission is unclear. We evaluated the risk of treatment failure in patients with CD in clinical and endoscopic remission by histologic activity status. Methods In a single-center retrospective cohort study, we identified adults with active CD who achieved clinical and endoscopic remission through treatment optimization. We evaluated the risk of treatment failure (composite of clinical flare requiring treatment modification, hospitalization, and/or surgery) in patients who achieved histologic remission vs persistent histologic activity through Cox proportional hazard analysis. Results Of 470 patients with active CD, 260 (55%) achieved clinical and endoscopic remission with treatment optimization; 215 patients with histology were included (median age, 33 years; 46% males). Overall, 132 patients (61%) achieved histologic remission. No baseline demographic, disease, or treatment factor was associated with achieving histologic remission. Over a 2-year follow-up, patients with CD in clinical and endoscopic remission who achieved histologic remission experienced a 43% lower risk of treatment failure (1-year cumulative risk: 12.9% vs 18.2%; adjusted hazard ratio, 0.57 [95% confidence interval, 0.35-0.94]) as compared with persistent histologic activity. Conclusions Approximately 61% of patients with active CD who achieved clinical and endoscopic remission with treatment optimization simultaneously achieved histologic remission, which was associated with a lower risk of treatment failure. Whether histologic remission should be a treatment target in CD requires evaluation in randomized trials.

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Bi-directional association between epilepsy and dementia

Neurology ◽

10.1212/wnl.0000000000011077 ◽

2020 ◽

Vol 95 (24) ◽

pp. e3241-e3247 ◽

Cited By ~ 1

Author(s):

Maria Stefanidou ◽

Alexa S. Beiser ◽

Jayandra Jung Himali ◽

Teng J. Peng ◽

Orrin Devinsky ◽

...

Keyword(s):

Proportional Hazards ◽

Secondary Analysis ◽

Cox Proportional Hazards ◽

Dementia Risk ◽

Incident Dementia ◽

Heart Study ◽

Allele Status ◽

Ε4 Allele ◽

Nested Case Control

ObjectiveTo assess the risk of incident epilepsy among participants with prevalent dementia and the risk of incident dementia among participants with prevalent epilepsy in the Framingham Heart Study (FHS).MethodsWe analyzed prospectively collected data in the Original and Offspring FHS cohorts. To determine the risk of developing epilepsy among participants with dementia and the risk of developing dementia among participants with epilepsy, we used separate, nested, case–control designs and matched each case to 3 age-, sex- and FHS cohort–matched controls. We used Cox proportional hazards regression analysis, adjusting for sex and age. In secondary analysis, we investigated the role of education level and APOE ε4 allele status in modifying the association between epilepsy and dementia.ResultsA total of 4,906 participants had information on epilepsy and dementia and dementia follow-up after age 65. Among 660 participants with dementia and 1,980 dementia-free controls, there were 58 incident epilepsy cases during follow-up. Analysis comparing epilepsy risk among dementia cases vs controls yielded a hazard ratio (HR) of 1.82 (95% confidence interval 1.05–3.16, p = 0.034). Among 43 participants with epilepsy and 129 epilepsy-free controls, there were 51 incident dementia cases. Analysis comparing dementia risk among epilepsy cases vs controls yielded a HR of 1.99 (1.11–3.57, p = 0.021). In this group, among participants with any post–high school education, prevalent epilepsy was associated with a nearly 5-fold risk for developing dementia (HR 4.67 [1.82–12.01], p = 0.001) compared to controls of the same educational attainment.ConclusionsThere is a bi-directional association between epilepsy and dementia. with either condition carrying a nearly 2-fold risk of developing the other when compared to controls.

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Association of Angiotensin II–Stimulating Antihypertensive Use and Dementia Risk

Neurology ◽

10.1212/wnl.0000000000010996 ◽

2020 ◽

Vol 96 (1) ◽

pp. e67-e80

Author(s):

Jan Willem van Dalen ◽

Zachary A. Marcum ◽

Shelly L. Gray ◽

Douglas Barthold ◽

Eric P. Moll van Charante ◽

...

Keyword(s):

Angiotensin Ii ◽

Calcium Channel ◽

Calcium Channel Blockers ◽

Excess Mortality ◽

Population Sample ◽

Community Dwelling ◽

Channel Blockers ◽

Dementia Risk ◽

Incident Dementia

ObjectiveTo assess whether angiotensin II–stimulating antihypertensives (thiazides, dihydropyridine calcium channel blockers, and angiotensin I receptor blockers) convey a lower risk of incident dementia compared to angiotensin II–inhibiting antihypertensives (angiotensin-converting enzyme inhibitors, β-blockers, and nondihydropyridine calcium channel blockers), in accordance with the “angiotensin hypothesis.”MethodsWe performed Cox regression analyses of incident dementia (or mortality as competing risk) during 6–8 years of follow-up in a population sample of 1,909 community-dwelling individuals (54% women) without dementia, aged 70–78 (mean 74.5 ± 2.5) years.ResultsAfter a median of 6.7 years of follow-up, dementia status was available for 1,870 (98%) and mortality for 1,904 (>99%) participants. Dementia incidence was 5.6% (27/480) in angiotensin II–stimulating, 8.2% (59/721) in angiotensin II–inhibiting, and 6.9% (46/669) in both antihypertensive type users. Adjusted for dementia risk factors including blood pressure and medical history, angiotensin II–stimulating antihypertensive users had a 45% lower incident dementia rate (hazard ratio [HR], 0.55; 95% CI, 0.34–0.89) without excess mortality (HR, 0.86; 95% CI, 0.64–1.16), and individuals using both types had a nonsignificant 20% lower dementia rate (HR, 0.80; 95% CI,0.53–1.20) without excess mortality (HR, 0.97; 95% CI, 0.76–1.24), compared to angiotensin II–inhibiting antihypertensive users. Results were consistent for subgroups based on diabetes and stroke history, but may be specific for individuals without a history of cardiovascular disease.ConclusionsUsers of angiotensin II–stimulating antihypertensives had lower dementia rates compared to angiotensin II–inhibiting antihypertensive users, supporting the angiotensin hypothesis. Confounding by indication must be examined further, although subanalyses suggest this did not influence results. If replicated, dementia prevention could become a compelling indication for older individuals receiving antihypertensive treatment.

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Effect of adherence to monthly zoledronic acid treatment on risk and frequency of skeletal complications and follow-up duration in breast cancer patients

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9593 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 9593-9593

Author(s):

H. T. Hatoum ◽

S. Lin ◽

M. R. Smith ◽

A. Lipton

Keyword(s):

Breast Cancer ◽

Zoledronic Acid ◽

Cancer Patients ◽

Lower Risk ◽

Propensity Scores ◽

Female Breast Cancer ◽

Breast Cancer Patients ◽

Skeletal Complications ◽

Comorbidity Index

9593 Background: Bone is the most common site of metastasis in breast cancer patients (pts). Clinical trials and outcome studies have demonstrated benefit of zoledronic acid (ZA) in reducing risk of skeletal complications (SC). This study explored relationships between persistency on ZA and the intended treatment (TX) outcomes. Methods: Female breast cancer pts with first bone metastasis (BM) diagnosed between Jan 03 to Oct 06 were identified from PharMetrics database. Persistency was defined as duration from initiating ZA TX to date of first TX gap of >45 days. Pts were divided into short (≤90 days, 230 pts), medium (91–180, 171 pts) and long (>180, 313 pts) persistency groups. TX selection bias was handled by calculating propensity scores using year of first BM diagnosis, having other metastases or >1 BM claim, use of opioids and oral bisphoshonate before BM. Propensity scores, age and Charlson's Comorbidity Index (CCI) were included in multiple regressions to investigate impact of ZA persistency on follow-up duration, risk and rate of SC. Results: 2394 pts were enrolled, with 714 (29.72%) ZA treated. Three persistency groups had similar age. Short group had higher CCI than long group (mean 8.53 vs 8.34, p<0.05). Frequency of ZA TX decreased over time in all groups. For short, medium and long persistency groups, means of follow-up durations were 9.8 (median, 7.0), 13.0 (9.0), 19.3 (18.1) months, and means of time to first SC after BM were 249 (median: 167), 323 (217), 418 (365) days. Means of SC rates were 0.27, 0.21, and 0.12 per month for patients who experienced at least 1 SC among the three groups. Medium and long persistency groups had 41% and 139% longer follow-up than short group (p<0.05). Long group had lower risk of SC than short group (HR=0.576, p<0.05). In patients who developed at least 1 SC, long group experienced 39% less SCs (p<0.005) than short group. Conclusions: TX with zoledronic acid in breast cancer pts with BM positively impacts the risk, frequency of SC and follow-up duration. Also, longer persistency on ZA TX is associated with significantly longer follow-up and lower risk of SC. [Table: see text]

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Weight loss and incident dementia in elderly Yoruba Nigerians: a 10-year follow-up study

International Psychogeriatrics ◽

10.1017/s1041610210001390 ◽

2010 ◽

Vol 23 (3) ◽

pp. 387-394 ◽

Cited By ~ 18

Author(s):

Adesola Ogunniyi ◽

Su Gao ◽

Frederick W. Unverzagt ◽

Olusegun Baiyewu ◽

Oyewusi Gureje ◽

...

Keyword(s):

Weight Loss ◽

Normal Subjects ◽

Smoking History ◽

Close Monitoring ◽

Cognitive Assessments ◽

Mixed Effect ◽

Mixed Effect Models ◽

Dementia Risk ◽

Incident Dementia

ABSTRACTBackground: The relationship between weight and dementia risk has not been investigated in populations with relatively low body mass index (BMI) such as the Yoruba. This study set out to achieve this objective using a prospective observational design.Methods: The setting was Idikan Ward in Ibadan City, Nigeria. The participants were all aged 65 years or older and were enrolled in the Indianapolis-Ibadan Dementia Project. Repeated cognitive assessments and clinical evaluations were conducted to identify participants with dementia or MCI during 10 years of follow-up (mean duration: 5.97 years). BMI measures, information on alcohol, smoking history, cancer, hypertension, diabetes, heart attack, stroke and depression were collected at each follow-up evaluation. Mixed effect models adjusted for covariates were used to examine the differences in BMI among participants who developed dementia or MCI and those who remained cognitively normal during the follow-up.Results: This analysis included 1559 participants who had no dementia at their first BMI measurements. There were 136 subjects with incident dementia, 255 with MCI and 1168 with normal cognition by the end of the study. The mean BMI at baseline was higher for female participants (22.31; SD = 4.39) than for male (21.09; SD = 3.61, p < 0.001). A significantly greater decline in BMI was found in those with either incident dementia (p < 0.001) or incident MCI (p < 0.001) compared to normal subjects.Conclusion: Decline in BMI is associated with incident MCI and dementia in elderly Yoruba. This observation calls for close monitoring of weight loss in elderly individuals which may indicate future cognitive impairment for timely detection and tailored interventions.

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Metformin vs sulfonylurea use and risk of dementia in US veterans aged ≥65 years with diabetes

Neurology ◽

10.1212/wnl.0000000000004586 ◽

2017 ◽

Vol 89 (18) ◽

pp. 1877-1885 ◽

Cited By ~ 41

Author(s):

Ariela R. Orkaby ◽

Kelly Cho ◽

Jean Cormack ◽

David R. Gagnon ◽

Jane A. Driver

Keyword(s):

Lower Risk ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Confounding By Indication ◽

Cox Proportional Hazards Models ◽

Incident Dementia ◽

Us Veterans

Objective:To determine whether metformin is associated with a lower incidence of dementia than sulfonylureas.Methods:This was a retrospective cohort study of US veterans ≥65 years of age with type 2 diabetes who were new users of metformin or a sulfonylurea and had no dementia. Follow-up began after 2 years of therapy. To account for confounding by indication, we developed a propensity score (PS) and used inverse probability of treatment weighting (IPTW) methods. Cox proportional hazards models estimated the hazard ratio (HR) of incident dementia.Results:We identified 17,200 new users of metformin and 11,440 new users of sulfonylureas. Mean age was 73.5 years and mean HbA1c was 6.8%. Over an average follow-up of 5 years, 4,906 cases of dementia were diagnosed. Due to effect modification by age, all analyses were conducted using a piecewise model for age. Crude hazard ratio [HR] for any dementia in metformin vs sulfonylurea users was 0.67 (95% confidence interval [CI] 0.61–0.73) and 0.78 (95% CI 0.72–0.83) for those <75 years of age and ≥75 years of age, respectively. After PS IPTW adjustment, results remained significant in veterans <75 years of age (HR 0.89; 95% CI 0.79–0.99), but not for those ≥75 years of age (HR 0.96; 95% CI 0.87–1.05). A lower risk of dementia was also seen in the subset of younger veterans who had HbA1C values ≥7% (HR 0.76; 95% CI 0.63–0.91), had good renal function (HR 0.86; 95% CI 0.76–0.97), and were white (HR 0.87; 95% CI 0.77–0.99).Conclusions:After accounting for confounding by indication, metformin was associated with a lower risk of subsequent dementia than sulfonylurea use in veterans <75 years of age. Further work is needed to identify which patients may benefit from metformin for the prevention of dementia.

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Association of Type 2 Diabetes, According to the Number of Risk Factors Within Target Range, With Structural Brain Abnormalities, Cognitive Performance, and Risk of Dementia

10.2337/figshare.14806743 ◽

2021 ◽

Author(s):

April C.E. van Gennip ◽

Coen D.A. Stehouwer ◽

Martin P.J. van Boxtel ◽

Frans R.J. Verhey ◽

Annemarie Koster ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Cognitive Performance ◽

Target Range ◽

Brain Abnormalities ◽

Brain Volumes ◽

Dementia Risk ◽

Incident Dementia

Objective Type 2 diabetes is associated with increased risks of cognitive dysfunction and brain abnormalities. The extent to which risk factor modification can mitigate these risks is unclear. We investigated the associations between incident dementia, cognitive performance and brain abnormalities among individuals with type 2 diabetes, according to the number of risk factors on target, compared to controls without diabetes. <div>Research Design and Methods Prospective data from UK Biobank of 87,856 individuals (n=10,663 diabetes/n=77,193 controls; baseline 2006-2010; dementia follow-up until February, 2018). Individuals with diabetes were categorized according to the number of seven selected risk factors within guideline-recommended target range (nonsmoking; guideline-recommended levels of HbA1c, blood pressure, BMI, albuminuria, physical activity, diet). Outcomes were incident dementia, domain-specific cognitive performance, white matter hyperintensities and total brain volume. Results After a mean follow-up of 9.0 years, 147(1.4%) individuals with diabetes and 412(0.5%) controls had incident dementia. Among individuals with diabetes, excess dementia risk decreased stepwise for a higher number of risk factors on target. Compared to controls (incidence rate per 1,000 person-years 0.62(95%CI:0.56;0.68)), individuals with diabetes who had 5-7 risk factors on target had no significant excess dementia risk (absolute rate difference per 1,000 person-years 0.20(-0.11;0.52); HR:1.32(0.89;1.95)). Similarly, differences in processing speed, executive function, and brain volumes were progressively smaller for a higher number of risk factors on target; these results were replicated in the Maastricht Study. Conclusions Among individuals with diabetes, excess dementia risk, lower cognitive performance and brain abnormalities decreased stepwise for a higher number of risk factors on target.</div>

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Abstract 3737: The Association Between Therapy With Insulin Glargine Versus Nph And The Risk Of Myocardial Infarction In Patients With Type 2 Diabetes

Circulation ◽

10.1161/circ.116.suppl_16.ii_849-c ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Mikhail Kosiborod ◽

Quanwu Zhang ◽

JoAnne Foody

Keyword(s):

Myocardial Infarction ◽

Type 2 Diabetes ◽

Insulin Glargine ◽

Lower Risk ◽

Administrative Database ◽

Medical Claim ◽

Cox Proportional Hazard ◽

Cox Proportional Hazard Models

Background: Prior studies have demonstrated that insulin glargine produces less hypoglycemia, as compared with NPH. Whether these results translate into better long-term cardiovascular outcomes in patients with Type 2 diabetes is unknown. Methods: Using a national managed care administrative database, we evaluated patients with Type 2 diabetes who were on oral antiglycemic agents within 6 months prior to initiating either insulin glargine (n=15,039) or NPH (n=5,666) and had at least 12 months of subsequent continuous plan enrollment during 03/2001–03/2005. Cox proportional hazard models were used to compare the rate of subsequent myocardial infarction (MI) events (defined by ICD-9 codes) following initiation of glargine vs NPH, after adjusting for demographic characteristics, comorbidities, other medications, insulin adherence and baseline Hemoglobin A1C (A1C). Results: Mean age was 56 years, 49% were women; mean duration of follow up was 24 months. Among patients who had available A1C (n=2514), those in glargine group had higher A1C at baseline vs. NPH (9.3 vs 8.9 respectively, p<0.0001). During the 1 st year following insulin initiation, 8.7% patients in NPH vs. 7.5% in glargine group had at least one medical claim for hypoglycemia (OR=1.17, 95% CI: 1.05–1.31). In unadjusted analysis, the rate of MI events was 4.4% in glargine group vs. 7.7% in the NPH group (p<0.0001). After multivariable adjustment, risk of MI events remained lower in glargine group (HR: 0.78, 95% CI: 0.64–0.95). Although hypoglycemic events were associated with higher MI risk (HR 1.3, 95% CI 1.18–1.44 for each quarter with a medical claim for hypoglycemia during 1 st year of follow up), the association between glargine use and lower risk of MI events remained significant even after adjusting for hypoglycemia (HR: 0.79, 95% CI 0.65–0.96). Conclusion: Initiation of insulin glargine in patients with Type 2 diabetes is associated with lower risk of subsequent MI events, as compared with NPH. Lower rate of hypoglycemia associated with glargine use does not completely account for this difference in outcomes. Further studies are needed to validate these results and provide insights into potential physiologic mechanisms.

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