Sex Differences in Autoimmune Multimorbidity in Type 1 Diabetes Mellitus and the Risk of Cardiovascular and Renal Disease: A Longitudinal Study in the United States, 2001-2017.

Background: Autoimmune diseases are usually more prevalent in women. The risks of cardiovascular and renal disease in those with multiple autoimmune diseases have not been fully described. Materials and Methods: Using a national database from a large health insurer in the United States (years 2001-2017) containing ∼75 million members, we calculated age- and sex-specific co-prevalence of 12 autoimmune disorders for individuals with type 1 diabetes. We then evaluated whether concomitant autoimmune diseases were associated with renal failure, ischemic stroke, and myocardial infarction. Results: Of the 179,248 people diagnosed with type 1 diabetes, 1 in 4 had a concomitant autoimmune disease (27.03%; 95% confidence interval [CI] = 26.83%-27.24%), with hypothyroidism, rheumatoid arthritis, and celiac disease being the most common. The prevalence of autoimmune disease was 1.9 times greater in female than male patients (p < 0.001). In female patients with type 1 diabetes, one in three had another autoimmune disease (35.62%; 95% CI = 35.30%-35.94%) compared with one in five male patients (19.17%; 95% CI = 18.92%-19.42%). The risk of renal failure, ischemic stroke, and myocardial infarction increased with a greater number of concomitant autoimmune diseases (p < 0.001, test for trend for both female and male patients). Patients with type 1 diabetes who had multiple sclerosis or myasthenia gravis experienced an approximate threefold increase in risk of ischemic stroke (odds ratio [OR] = 3.57, OR = 3.22, respectively). Patients with type 1 diabetes and Addison's disease had a threefold increased risk of renal failure. Conclusions: Patients with type 1 diabetes, particularly women, frequently have coexisting autoimmune diseases that are associated with higher rates of renal failure, ischemic stroke, and myocardial infarction. Additional study is warranted, as are preventive efforts in this high-risk population.

Congenital infections as contributors to the onset of diabetes in children: A longitudinal study in the United States, 2001-2017.

BACKGROUND: Maternal infections during pregnancy, particularly with rubella virus, were reported to increase the risk of diabetes in children. Widespread vaccination has decreased the number of infants with congenital rubella syndrome in the United States, although it remains a problem in developing countries. Because vaccine hesitancy has recently increased, we investigated the association between congenital infections with subsequent diabetes risk in children in the United States. METHODS: Using data from a nationwide private health insurer for years 2001-2017, 1 475 587 infants were followed for an average of 3.9 years (maximum 16.5 years). Information was obtained regarding congenital infections (rubella, cytomegalovirus, other congenital infections) and perinatal infections, as well as for the development of diabetes mellitus and diabetic ketoacidosis. RESULTS: There were 781 infants with congenital infections and 73 974 with perinatal infections. Diabetes developed in 3334 children. The odds of developing diabetes for infants with congenital rubella infection were 12-fold greater (P = .013) and, for infants with congenital cytomegalovirus infection, were 4-fold greater (P = .011) than infants without congenital or perinatal infection. Infants with other congenital infections had 3-fold greater odds of developing diabetes (P = .044). Results were similar for diabetes ketoacidosis. Infants with other perinatal infections had 49% greater odds of developing diabetes during the follow-up period (P < .001). CONCLUSION: Congenital and other perinatal infections are associated with elevated risks of developing diabetes mellitus during childhood. Vaccination for rubella remains an important preventive action to reduce the incidence of diabetes in children.

Geospatial Variation in Rotavirus Vaccination in Infants, United States, 2010-2017.

We evaluated rotavirus vaccination rates in the United States by using records from a nationwide health database. From data on 519,697 infants, we found 68.6% received the entire rotavirus vaccine series. We noted pockets of undervaccination in many states, particularly in the Northeast and in some western states.

Onset of type 1 diabetes mellitus in rural areas of the USA.

BACKGROUND: In the USA, the epidemiologic features of type 1 diabetes are not well-defined across all 50 states. However, the advent of large nationwide insurance databases enables the investigation of where type 1 diabetes cases occur throughout the country. METHODS: An integrated database from a large nationwide health insurer in the USA (Clinformatics Data Mart Database) was used, from 2001 to 2017. The database contained longitudinal information on approximately 77 million people. RESULTS: The incidence of type 1 diabetes was greatest in areas of low population density across the 50 states. Individuals in the lowest population density areas had rates that were 2.28 times (95% CI 2.08 to 2.50) that of persons living in high-density areas. This association was consistent across various measures of rural status (p<0.001 for population density; p<0.001 for per cent rural as defined by the US Census Bureau; p=0.026 for farmland). The association between rural areas and the incidence of type 1 diabetes was evident across all four general regions of the USA. CONCLUSIONS: The predilection of type 1 diabetes in rural areas provides clues to potential factors associated with the onset of this autoimmune disease.

Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia: A Multihospital Cohort Study.

Background: Randomized trials demonstrate no benefit from antibiotic treatment exceeding the shortest effective duration. Objective: To examine predictors and outcomes associated with excess duration of antibiotic treatment. Design: Retrospective cohort study. Setting: 43 hospitals in the Michigan Hospital Medicine Safety Consortium. Patients: 6481 general care medical patients with pneumonia. Measurements: The primary outcome was the rate of excess antibiotic treatment duration (excess days per 30-day period). Excess days were calculated by subtracting each patient's shortest effective (expected) treatment duration (based on time to clinical stability, pathogen, and pneumonia classification [community-acquired vs. health care-associated]) from the actual duration. Negative binomial generalized estimating equations (GEEs) were used to calculate rate ratios to assess predictors of 30-day rates of excess duration. Patient outcomes, assessed at 30 days via the medical record and telephone calls, were evaluated using logit GEEs that adjusted for patient characteristics and probability of treatment. Results: Two thirds (67.8% [4391 of 6481]) of patients received excess antibiotic therapy. Antibiotics prescribed at discharge accounted for 93.2% of excess duration. Patients who had respiratory cultures or nonculture diagnostic testing, had a longer stay, received a high-risk antibiotic in the prior 90 days, had community-acquired pneumonia, or did not have a total antibiotic treatment duration documented at discharge were more likely to receive excess treatment. Excess treatment was not associated with lower rates of any adverse outcomes, including death, readmission, emergency department visit, or Clostridioides difficile infection. Each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse events reported by patients after discharge. Limitation: Retrospective design; not all patients could be contacted to report 30-day outcomes. Conclusion: Patients hospitalized with pneumonia often receive excess antibiotic therapy. Excess antibiotic treatment was associated with patient-reported adverse events. Future interventions should focus on whether reducing excess treatment and improving documentation at discharge improves outcomes. Primary Funding Source: Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships program.

Lower Incidence Rate of Type 1 Diabetes after Receipt of the Rotavirus Vaccine in the United States, 2001-2017.

We evaluated whether rotavirus vaccination is associated with the incidence of type 1 diabetes among children. We designed a cohort study of 1,474,535 infants in the United States from 2001-2017, using data from a nationwide health insurer. There was a 33% reduction in the risk of type 1 diabetes with completion of the rotavirus vaccine series compared to the unvaccinated (95% CI: 17%, 46%). Completion of the pentavalent vaccine series was associated with 37% lower risk of type 1 diabetes (95% CI: 22%, 50%). Partial vaccination (incompletion of the series) was not associated with the incidence of type 1 diabetes. There was a 31% reduction in hospitalizations in the 60-day period after vaccination (95% CI: 27%, 35%) compared to unvaccinated children. Overall, there was a 3.4% decrease in incidence annually in children ages 0-4 in the United States from 2006-2017 which coincides with the vaccine introduction in 2006. We conclude that rotavirus vaccination is associated with a reduced incidence of type 1 diabetes. Rotavirus vaccination may be the first practical measure that could play a role in the prevention of this disease.

Duration of Insulin Supply in Type 1 Diabetes: Are 90 Days Better or Worse Than 30 Days?

OBJECTIVE: There have been few studies regarding the duration of insulin prescriptions and patient outcomes. This study evaluated whether A1C varied with the duration of insulin prescription in patients with type 1 diabetes. METHODS: We conducted a longitudinal investigation (from 2001 to 2015) within a nationwide private health insurer. A cohort study was first used to compare A1C after 30-day only, 90-day only, and a combination (30-day and 90-day) of insulin prescriptions. Second, a self-controlled case series was used to compare A1C levels after 30-day versus 90-day prescriptions for the same person. RESULTS: In the cohort study, there were 16,725 eligible patients. Mean A1C was 8.33% for patients with 30-day prescriptions compared to 7.69% for those with 90-day prescriptions and 8.05% for those who had a combination of 30- and 90-day prescriptions (P <0.001). Results were similar when stratified by age and sex. Mean A1C was 7.58% when all prescriptions were mailed versus 8.21% when they were not. In the self-controlled case series, there were 1,712 patients who switched between 30- and 90-day prescriptions. Mean A1C was 7.87% after 30-day prescriptions and 7.69% after 90-day prescriptions (P <0.001). Results were similar when stratified by sex. For this within-person comparison, the results remained significant for those ≥20 years of age (n = 1,536, P <0.001), but not for youth (n = 176, P = 0.972). CONCLUSION: There was a statistically significant but clinically modest decrease in A1C with 90-day versus 30-day insulin prescriptions in adults. A mailed 90-day insulin prescription may be a reasonable choice for adults with type 1 diabetes.

Use of Peripherally Inserted Central Catheters in Patients With Advanced Chronic Kidney Disease: A Prospective Cohort Study.

Background: Existing guidelines, including Choosing Wisely recommendations, endorse avoiding placement of peripherally inserted central catheters (PICCs) in patients with chronic kidney disease (CKD). Objective: To describe the frequency of and characteristics associated with PICC use in hospitalized patients with stage 3b or greater CKD (glomerular filtration rate [GFR] <45 mL/min/1.73 m2). Design: Prospective cohort study. Setting: 52 hospitals participating in the Michigan Hospital Medicine Safety Consortium. Participants: Hospitalized medical patients who received a PICC between November 2013 and September 2016. Measurements: Percentage of patients receiving PICCs who had CKD, frequency of PICC-related complications, and variation in the proportion of PICCs placed in patients with CKD. Results: Of 20 545 patients who had PICCs placed, 4743 (23.1% [95% CI, 20.9% to 25.3%]) had an estimated GFR (eGFR) less than 45 mL/min/1.73 m2 and 699 (3.4%) were receiving hemodialysis. In the intensive care unit (ICU), 30.9% (CI, 29.7% to 32.2%) of patients receiving PICCs had an eGFR less than 45 mL/min/1.73 m2; the corresponding percentage in wards was 19.3% (CI, 18.8% to 19.9%). Among patients with an eGFR less than 45 mL/min/1.73 m2, multilumen PICCs were placed more frequently than single-lumen PICCs. In wards, PICC-related complications occurred in 15.3% of patients with an eGFR less than 45 mL/min/1.73 m2 and in 15.2% of those with an eGFR of 45 mL/min/1.73 m2 or higher. The corresponding percentages in ICU settings were 22.4% and 23.9%. In patients with an eGFR less than 45 mL/min/1.73 m2, PICC placement varied widely across hospitals (interquartile range, 23.7% to 37.8% in ICUs and 12.8% to 23.7% in wards). Limitation: Nephrologist approval for placement could not be determined, and 2.7% of eGFR values were unknown and excluded. Conclusion: In this sample of hospitalized patients who received PICCs, placement in those with CKD was common and not concordant with clinical guidelines. Primary Funding Source: Blue Cross Blue Shield of Michigan and Blue Care Network.

Nationwide cohort study of independent risk factors for acute respiratory distress syndrome after trauma.

BACKGROUND: The primary objective of this study was to evaluate the effect of specific direct and indirect factors that accounted, in trauma patients, for the development of acute respiratory distress syndrome (ARDS) and mortality in patients with ARDS. METHODS: We performed a retrospective cohort study of patients from the National Trauma Data Bank. Multilevel mixed-effects logistic regression was used with the development of ARDS as the primary and mortality in patients with ARDS as the secondary outcome measures. We compared trauma patients with versus without thoracic (direct) and extrathoracic (indirect) risk factors, using patient demographics, physiologic, and anatomic injury severity as covariates. Subset analysis was performed for patients with trauma-induced lung contusion (TILC) and for patients with minor (Injury Severity Score [ISS] ≤15) injury. RESULTS: A total of 2 998 964 patients were studied, of whom 28 597 developed ARDS. From 2011 to 2014, the incidence of ARDS decreased; however, mortality in patients with ARDS has increased. Predictors of ARDS included direct thoracic injury (TILC, multiple rib fractures, and flail chest), as well as indirect factors (increased age, male gender, higher ISS, lower Glasgow Coma Scale motor component score, history of cardiopulmonary or hematologic disease, and history of alcoholism or obesity). Patients with ARDS secondary to direct thoracic injury had a lower risk of mortality compared with patients with ARDS due to other mechanisms. DISCUSSION: Despite the decreasing incidence of trauma-induced ARDS, mortality in patients with ARDS has increased. Direct thoracic injury was the strongest predictor of ARDS. Knowing specific contributors to trauma-induced ARDS could help identify at-risk patients early in their hospitalization and mitigate the progression to ARDS and thereby mortality. LEVEL OF EVIDENCE: Prognostic study, level III.

Private Insurance Coverage for Diabetes Before and After Enactment of the Preexisting Condition Mandate of the Affordable Care Act, 2005-2016.

OBJECTIVES: To examine private insurance coverage for persons with diabetes before and after enactment of the preexisting condition mandate of the Affordable Care Act (ACA) in the United States. METHODS: We conducted a nationwide study in adults aged 20 to 59 years with private health insurance with the Clinformatics Data Mart Database (2005-2016). We used fixed-effects negative binomial regression to evaluate differences in pre-post mandate trends. RESULTS: There was a 4% decline in prevalence rates of type 1 diabetes in adults with private health insurance before the mandate and an 11% increase afterward (P < .001). Coverage increased to the greatest extent (-6% before, +20% after) in those aged 50 to 59 years (P < .001). For type 2 diabetes, there was a significant decline in prevalence before the mandate, which increased afterward in those aged 40 to 49 years (-4% before, 3% after; P = .031) and 50 to 59 years (-6% before, 15% after; P < .001). CONCLUSIONS: Adults with diabetes may have benefited in obtaining private health insurance after implementation of the preexisting condition mandate of the ACA. Public Health Implications. Efforts to limit enforcement of these protections are likely to contribute to setbacks in access to care.

The fear of needles: A systematic review and meta-analysis.

AIMS: The aim of this study was to evaluate the prevalence of needle fear and summarize the characteristics of individuals who exhibit this fear. BACKGROUND: Injections are among the most common medical procedures, yet fear of needles can result in avoidance of preventive measures and treatment. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE (1966-2017), Embase (1947-2017), PsycINFO (1967-2017), and CINAHL (1961-2017) were searched, with no restrictions by age, gender, race, language, or country. REVIEW METHODS: The prevalence of needle fear was calculated and restricted maximum likelihood random effects models were used for meta-analysis and meta-regression. RESULTS: The search yielded 119 original research articles which are included in this review, of which 35 contained sufficient information for meta-analysis. The majority of children exhibited needle fear, while prevalence estimates for needle fear ranged from 20-50% in adolescents and 20-30% in young adults. In general, needle fear decreased with increasing age. Both needle fear and needle phobia were more prevalent in females than males. Avoidance of influenza vaccination because of needle fear occurred in 16% of adult patients, 27% of hospital employees, 18% of workers at long-term care facilities, and 8% of healthcare workers at hospitals. Needle fear was common when undergoing venipuncture, blood donation, and in those with chronic conditions requiring injection. CONCLUSIONS: Fear of needles is common in patients requiring preventive care and in those undergoing treatment. Greater attention should be directed to interventions which alleviate fear in high-risk groups.

Role of transfusions in the development of hospital-acquired urinary tract-related bloodstream infection among United States Veterans.

BACKGROUND: Urinary tract-related bloodstream infection (BSI) is associated with substantial morbidity, mortality, and financial costs. We examined the role of red blood cell (RBC) transfusions on developing this condition among US Veterans. METHODS: We conducted a matched case-control study among adult inpatients admitted to 4 Veterans Affairs hospitals. Cases were patients with a positive urine culture result obtained 48hours or longer after admission and a blood culture obtained within 14days of the urine culture, which grew the same organism. Controls included patients with a positive urine culture result who were at risk for but did not develop BSI (control group 1) and patients without a positive urine culture result who were present in the facility at the time of case diagnosis (control group 2). RESULTS: Compared with the findings in control group 1, receipt of RBCs was not significantly associated with urinary tract-related BSI (odds ratio, 1.03; 95% confidence interval, 1.00-1.07; P = .07). However, we found increased odds of urinary tract-related BSI compared with the results in patients without infection (control group 2) (odds ratio, 1.11; 95% confidence interval, 1.06-1.17; P < .001). CONCLUSIONS: Given the heightened risk of urinary tract-related BSI associated with receiving a greater number of RBC transfusions, adhering to recommendations to transfuse the minimum amount of blood products necessary may minimize the risk of this infection among Veterans.

Mixed messages to consumers from Medicare: Hospital Compare grades versus value-based payment penalty.

OBJECTIVES: To (1) compare the 2015 hospital grades reported on Medicare's Hospital Compare website for heart failure (HF) and acute myocardial infarction (AMI) readmissions with the HF- and AMI-specific scores for excess readmissions used to assess Medicare readmission penalties and (2) assess how often hospitals were penalized for excess readmissions in only 1 or 2 conditions, given that hospitals received a penalty impacting all Medicare payments based on an overall readmission score calculated from 5 conditions (HF, AMI, pneumonia, chronic obstructive pulmonary disease, and total hip/knee arthroplasty). STUDY DESIGN: Retrospective secondary data analysis. METHODS: Descriptive analyses of hospital-specific, condition-specific grades and excess readmission scores and hospital-level penalties downloaded from Hospital Compare. RESULTS: Of the 2956 hospitals that had publicly reported HF grades on Hospital Compare, 91.9% (2717) were graded as "no different" than the national rate for HF readmissions, which included 48.6% that were scored as having excessive HF admissions, and 87% received an overall readmission penalty. Of 120 (4.1%) hospitals graded as "better" than the national rate for HF, none were scored as having excessive HF readmissions and 50% were penalized. AMI data yielded similar results. Among 2591 hospitals penalized for overall readmissions, 26.6% had only 1 condition with excess readmissions and 27.5% had 2 conditions. CONCLUSIONS: Many hospitals with an HF and AMI readmission grade of "no different" than the national rate on Hospital Compare received penalties for excessive readmissions under the Hospital Readmissions Reduction Program. The value signal to consumers and hospitals communicated by grades and penalties is therefore weakened because the methods applied to the same hospital data produce conflicting messages of "average grades" yet "bad enough for penalty."

Interruptions In Private Health Insurance And Outcomes In Adults With Type 1 Diabetes: A Longitudinal Study.

Type 1 diabetes mellitus, which often originates during childhood, is a lifelong disease that requires intensive daily medical management. Because health care services are critical to patients with this disease, we investigated the frequency of interruptions in private health insurance, and the outcomes associated with them, for working-age adults with type 1 diabetes in the United States in the period 2001-15. We designed a longitudinal study with a nested self-controlled case series, using the Clinformatics Data Mart Database. The study sample consisted of 168,612 adults ages 19-64 with type 1 diabetes who had 2.6 mean years of insurance coverage overall. Of these adults, 24.3 percent experienced an interruption in coverage. For each interruption, there was a 3.6 percent relative increase in glycated hemoglobin. The use of acute care services was fivefold greater after an interruption in health insurance compared to before the interruption and remained elevated when stratified by age, sex, or diabetic complications. An interruption was associated with lower perceived health status and lower satisfaction with life. We conclude that interruptions in private health insurance are common among adults with type 1 diabetes and have serious consequences for their well-being.

The epidemiology of hospital-acquired urinary tract-related bloodstream infection in veterans.

BACKGROUND: Hospital-acquired urinary tract-related bloodstream infections are rare but often lethal. Recent epidemiology of this condition among the United States veteran population is poorly described. METHODS: We conducted a retrospective review of hospital-acquired urinary tract-related bloodstream infections of adult inpatients admitted to 4 Veterans Affairs hospitals over 15 years. Electronic medical records were used to obtain clinical, demographic, and microbiologic information. Descriptive statistical analyses were conducted using chi-square tests of association. Test for trend was performed by genus of organism and for case fatality rate over time. RESULTS: While the most commonly isolated organisms were Staphylococcus spp. (36.5%), the incidence of infections caused by Escherichia and Klebsiella increased over time (P = .02 and P = .03, respectively). The overall in-hospital case fatality rate was 24.2% in 499 patients. The case fatality rate was 25.8% for patients with Staphylococcus infections and 20.7% for patients with enterococcal infections. CONCLUSIONS: Hospital-acquired urinary tract-related bloodstream infection is commonly due to Staphylococcus spp. and is related to the high fatality among United States veterans. Focused infection control efforts could decrease the incidence of this fatal infection.

Fluctuations in airway bacterial communities associated with clinical states and disease stages in cystic fibrosis.

Bacteria that infect the airways of persons with cystic fibrosis (CF) include a group of well-described opportunistic pathogens as well as numerous, mainly obligate or facultative anaerobic species typically not reported by standard sputum culture. We sequenced the V3-V5 hypervariable region of the bacterial 16S rRNA gene in DNA derived from 631 sputum specimens collected from 111 CF patients over 10 years. We describe fluctuations in the relative abundances of typical CF pathogens, as well as anaerobic species, in relation to changes in patients' clinical state and lung disease stage. Both bacterial community diversity and the relative abundance of anaerobes increased during exacerbation of symptoms (prior to antibiotic treatment), although this trend was not observed uniformly across disease stages. Community diversity and the relative abundance of anaerobic species decreased during antibiotic treatment. These results support current hypotheses regarding the role of anaerobes in CF pulmonary exacerbations and lung disease progression.

Longitudinal study of short-term corticosteroid use by working-age adults with diabetes mellitus: Risks and mitigating factors.

BACKGROUND: This study assessed the frequency of short-term oral corticosteroid use in adults with diabetes, examined the incidence of fractures, venous thromboembolism (VTE), and hospitalization for sepsis after corticosteroid use, and evaluated whether preventative medications mitigated adverse events. METHODS: A longitudinal study (2012-14) was conducted of 1 548 945 adults (aged 18-64 years) who received healthcare coverage through a large national health insurer. Incidence rate ratios (IRR) were calculated using conditional Poisson regression. RESULTS: Short-term oral corticosteroids were used by 23.9%, 20.8%, and 20.9% of adults with type 2 diabetes, type 1 diabetes, and no diabetes, respectively, during the 3-year period (P < 0.001). Baseline risks of fracture, VTE, and sepsis were greater for individuals with than without diabetes (P < 0.001). The combined effect of having diabetes and using corticosteroids was greater than the sum of the individual effects (synergy indices of 1.17, 1.23, 1.30 for fracture, VTE, and sepsis, respectively). The IRR for VTE in the 5-30 days after corticosteroid use was 3.62 (95% confidence interval [CI] 2.41-5.45). Fractures increased in the 5-30 days after corticosteroid use (IRR 2.06; 95% CI 1.52, 2.80), but concomitant use of ergocalciferol mitigated this risk (IRR 1.13; 95% CI 0.12, 11.07). The risk of hospitalization for sepsis was elevated with corticosteroid use (IRR 3.79; 95% CI 2.05, 7.01), but was mitigated by the concomitant use of statins. CONCLUSIONS: Short-term oral corticosteroid use is common in adults with diabetes and is associated with an elevated, but low, risk of adverse events. The findings suggest that preventative medications may mitigate risk.

Fluctuations in the incidence of type 1 diabetes in the United States from 2001 to 2015: a longitudinal study.

BACKGROUND: While the United States has the largest number of children with type 1 diabetes mellitus, less is known regarding adult-onset disease. The present study utilizes nationwide data to compare the incidence of type 1 diabetes in youth (0-19 years) to that of adults (20-64 years). METHODS: In this longitudinal study, the Clinformatics® Data Mart Database was used, which contains information from 61 million commercially insured Americans (years 2001-2015). Incidence rates and exact Poisson 95% confidence intervals were calculated by age group, sex, census division, and year of diagnosis. Changes in rates over time were assessed by negative binomial regression. RESULTS: Overall, there were 32,476 individuals who developed type 1 diabetes in the cohort. The incidence rate was greatest in youth aged 10-14 years (45.5 cases/100,000 person-years); however, because adulthood spans over a longer period than childhood, there was a greater number of new cases in adults than in youth (n = 19,174 adults; n = 13,302 youth). Predominance in males was evident by age 10 and persisted throughout adulthood. The male to female incidence rate ratio was 1.32 (95% CI 1.30-1.35). The incidence rate of type 1 diabetes in youth increased by 1.9% annually from 2001 to 2015 (95% CI 1.1-2.7%; P < 0.001), but there was variation across regions. The greatest increases were in the East South Central (3.8%/year; 95% CI 2.0-5.6%; P < 0.001) and Mountain divisions (3.1%/year; 95% CI 1.6-4.6%; P < 0.001). There were also increases in the East North Central (2.7%/year; P = 0.010), South Atlantic (2.4%/year; P < 0.001), and West North Central divisions (2.4%/year; P < 0.001). In adults, however, the incidence decreased from 2001 to 2015 (-1.3%/year; 95% CI -2.3% to -0.4%; P = 0.007). Greater percentages of cases were diagnosed in January, July, and August for both youth and adults. The number of new cases of type 1 diabetes (ages 0-64 years) in the United States is estimated at 64,000 annually (27,000 cases in youth and 37,000 cases in adults). CONCLUSIONS: There are more new cases of type 1 diabetes occurring annually in the United States than previously recognized. The increase in incidence rates in youth, but not adults, suggests that the precipitating factors of youth-onset disease may differ from those of adult-onset disease.