INTRODUCTION: Defining type of diabetes using survey data is challenging, although important, for determining national estimates of diabetes. The purpose of this study was to compare the percentage and characteristics of US adults classified as having type 1 diabetes as defined by several algorithms. RESEARCH DESIGN AND METHODS: This study included 6331 respondents aged ≥18 years who reported a physician diagnosis of diabetes in the 2016-2017 National Health Interview Survey. Seven algorithms classified type 1 diabetes using various combinations of self-reported diabetes type, age of diagnosis, current and continuous insulin use, and use of oral hypoglycemics. RESULTS: The percentage of type 1 diabetes among those with diabetes ranged from 3.4% for those defined by age of diagnosis <30 years and continuous insulin use (algorithm 2) to 10.2% for those defined only by continuous insulin use (algorithm 1) and 10.4% for those defined as self-report of type 1 (supplementary algorithm 6). Among those defined by age of diagnosis <30 years and continuous insulin use (algorithm 2), by self-reported type 1 diabetes and continuous insulin use (algorithm 4), and by self-reported type 1 diabetes and current insulin use (algorithm 5), mean body mass index (BMI) (28.6, 27.4, and 28.5 kg/m(2), respectively) and percentage using oral hypoglycemics (16.1%, 11.1%, and 19.0%, respectively) were lower than for all other algorithms assessed. Among those defined by continuous insulin use alone (algorithm 1), the estimates for mean age and age of diagnosis (54.3 and 30.9 years, respectively) and BMI (30.9 kg/m(2)) were higher than for other algorithms. CONCLUSIONS: Estimates of type 1 diabetes using commonly used algorithms in survey data result in varying degrees of prevalence, characteristic distributions, and potential misclassification.

OBJECTIVE: The use of emergency medical services (EMS) for diabetes-related events is believed to be substantial but has not been quantified nationally despite the diverse acute complications associated with diabetes. We describe diabetes-related EMS activations in 2015 among people of all ages from 23 U.S. states. METHODS: We used data from 23 states that reported >/=95% of their EMS activations to the U.S. National Emergency Medical Services Information System (NEMSIS) in 2015. A diabetes-related EMS activation was defined using coded EMS provider impressions of "diabetes symptoms" and coded complaints recorded by dispatch of "diabetic problem." We described activations by type of location, urbanicity, U.S. Census Division, season, and time of day; and patient-events by age category, race/ethnicity, disposition, and treatment with glucose. Crude and age-adjusted diabetes-related EMS patient-level event rates were calculated for adults >/=18 years of age with diagnosed diabetes using the Behavioral Risk Factor Surveillance System to estimate the population denominator. RESULTS: Of 10,324,031 relevant EMS records, 241,495 (2.3%) were diabetes-related activations, which involved over 235,000 hours of service. Most activations occurred in urban or suburban environ- ments (86.4%), in the home setting (73.5%), and were slightly more frequent in the summer months. Most patients (72.6%) were >/=45 years of age and over one-half (55.4%) were transported to the emergency department. The overall age-adjusted diabetes-related EMS event rate was 33.9 per 1,000 persons with diagnosed diabetes; rates were highest in patients 18-44 years of age, males, and non-Hispanic blacks and varied by U.S. Census Division. CONCLUSIONS: Diabetes results in a substantial burden on EMS resources. Collection of more detailed diabetes complication information in NEMSIS may help facilitate EMS resource planning and prevention strategies.

OBJECTIVE: Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults, and although screening with eye exams is effective, screening rates are low. We evaluated eye exam visits over a 5-year period in a large population of insured patients 10-64 years of age with diabetes. RESEARCH DESIGN AND METHODS: We used claims data from IBM Watson Health to identify patients with diabetes and continuous insurance coverage from 2010 to 2014. Diabetes and DR were defined using ICD-9 Clinical Modification codes. We calculated eye exam visit frequency by diabetes type over a 5-year period and estimated period prevalence and cumulative incidence of DR among those receiving an eye exam. RESULTS: Among the 298,383 insured patients with type 2 and no diagnosed DR, almost half had no eye exam visits over the 5-year period and only 15.3% met the American Diabetes Association (ADA) recommendations for annual or biennial eye exams. For the 2,949 patients with type 1 diabetes, one-third had no eye exam visits and 26.3% met ADA recommendations. The 5-year period prevalence and cumulative incidence of DR was 24.4% and 15.8% for patients with type 2 diabetes, respectively, and 54.0% and 33.4% for patients with type 1 diabetes. CONCLUSIONS: The frequency of eye exams was alarmingly low, adding to the abundant literature that systemic changes in health care may be needed to detect and prevent vision-threatening eye disease among people with diabetes.

As noted by de Miguel-Yanes et al. (1), we reported a decline in hospitalization rates from 1998 to 2014 for several cardiovascular disease (CVD) conditions in the U.S. population with diabetes (2). Similar to their report on cardiovascular events in people with diabetes in Spain (3), we found that during the study period hospitalization rates for acute coronary syndrome decreased in the U.S. population with diabetes. In seeming contrast with their findings, we reported in this population overall significant declines in hospitalization rates for ischemic stroke and hemorrhagic stroke. However, consistent with their findings and of particular concern, we noted in the latter part of the period increases in hospitalization rates for ischemic stroke in several subgroups, including those aged 35–74 years, men, women, non-Hispanic whites, and non-Hispanic blacks. Although specific reasons for the observed heterogeneity in our study cannot be determined from surveillance data, shifting patterns of case finding or declines in diabetes incidence (4) and decreases in mortality (5) in the U.S. may be changing the epidemiologic characteristics of the U.S. population with diabetes to a more high-risk population susceptible to the development of diabetes complications. More years of data and continued surveillance of CVD hospitalizations in the U.S. population with diabetes will be needed to confirm these trends. | | Furthermore, as de Miguel-Yanes et al (1) pointed out, differences in the impact of treatment, preventive treatment, or risk factor control between populations of different countries may account for differences in CVD trends.

OBJECTIVE: To examine changes in diabetes-related preventable hospitalization costs and to determine the contribution of each underlying factor to these changes. RESEARCH DESIGN AND METHODS: We used data from the 2001-2014 U.S. National Inpatient Sample for adults (>/=18 years old) to estimate the trends in hospitalization costs (2014 USD) in total and by condition (short-term complications, long-term complications, uncontrolled diabetes, and lower-extremity amputation). Using regression and growth models, we estimated the relative contribution of following underlying factors: total number of hospitalizations, rate of hospitalization, the number of people with diabetes, mean cost per admission, length of stay, and cost per day. RESULTS: During 2001-2014, the estimated total cost of diabetes-related preventable hospitalizations increased annually by 1.6% (92.9 million USD; P < 0.001). Of this 1.6% increase, 75% (1.2%) was due to the increase in the number of hospitalizations, which is a result of a 3.8% increase in diabetes population and a 2.6% decrease in the hospitalization rate, and 25% (0.4%) was due to the increase in cost per admission, for a net result of a 1.6% increase in cost per day and a 1.3% decline in mean length of stay. By component, the cost of short-term complications, lower-extremity amputations, and long-term complications increased annually by 4.2, 1.9, and 1.5%, respectively, while the cost of uncontrolled diabetes declined annually by 2.6%. CONCLUSIONS: The total cost of diabetes-related preventable hospitalizations had been increasing during 2001-2014, mainly resulting from increases in number of people with diabetes and cost per hospitalization day. The underlying factors identified in our study could lead to efforts that may lower future hospitalization costs.

OBJECTIVES: To determine whether declining trends in lower extremity amputations have continued into the current decade. RESEARCH DESIGN AND METHODS: We calculated hospitalization rates for nontraumatic lower extremity amputation (NLEA) for the years 2000-2015 using nationally representative, serial cross-sectional data from the Nationwide Inpatient Sample on NLEA procedures and from the National Health Interview Survey for estimates of the populations with and without diabetes. RESULTS: Age-adjusted NLEA rates per 1,000 adults with diabetes decreased 43% between 2000 (5.38 [95% CI 4.93-5.84]) and 2009 (3.07 [95% CI 2.79-3.34]) (P < 0.001) and then rebounded by 50% between 2009 and 2015 (4.62 [95% CI 4.25-5.00]) (P < 0.001). In contrast, age-adjusted NLEA rates per 1,000 adults without diabetes decreased 22%, from 0.23 per 1,000 (95% CI 0.22-0.25) in 2000 to 0.18 per 1,000 (95% CI 0.17-0.18) in 2015 (P < 0.001). The increase in diabetes-related NLEA rates between 2009 and 2015 was driven by a 62% increase in the rate of minor amputations (from 2.03 [95% CI 1.83-2.22] to 3.29 [95% CI 3.01-3.57], P < 0.001) and a smaller, but also statistically significant, 29% increase in major NLEAs (from 1.04 [95% CI 0.94-1.13] to 1.34 [95% CI 1.22-1.45]). The increases in rates of total, major, and minor amputations were most pronounced in young (age 18-44 years) and middle-aged (age 45-64 years) adults and more pronounced in men than women. CONCLUSIONS: After a two-decade decline in lower extremity amputations, the U.S. may now be experiencing a reversal in the progress particularly in young and middle-aged adults.

Accurately quantifying undiagnosed type 2 diabetes is an important challenge for conducting diabetes surveillance and identifying the potential missed opportunities for preventing complications. However, there has been little focused attention on how undiagnosed diabetes is defined in epidemiologic surveys and how limitations in methods used to ascertain undiagnosed diabetes may impact our understanding of the magnitude of this important public health problem. This Perspective highlights weaknesses in how undiagnosed diabetes is quantified in epidemiologic research and the biases and caveats that should be considered when using estimates of undiagnosed diabetes to influence public health policy.

OBJECTIVE: Cardiovascular disease (CVD) mortality has declined substantially in the U.S. The aims of this study were to examine trends and demographic disparities in mortality due to CVD and CVD subtypes among adults with and without self-reported diabetes. RESEARCH DESIGN AND METHODS: We used the National Health Interview Survey (1985-2014) with mortality follow-up data through the end of 2015 to estimate nationally representative trends and disparities in major CVD, ischemic heart disease (IHD), stroke, heart failure, and arrhythmia mortality among adults >/=20 years of age by diabetes status. RESULTS: Over a mean follow-up period of 11.8 years from 1988 to 2015 of 677,051 adults, there were significant decreases in major CVD death (all P values <0.05) in adults with and without diabetes except adults 20-54 years of age. Among adults with diabetes, 10-year relative changes in mortality were significant for major CVD (-32.7% [95% CI -37.2, -27.9]), IHD (-40.3% [-44.7, -35.6]), and stroke (-29.2% [-40.0, -16.5]), but not heart failure (-0.5% [-20.7, 24.7]), and arrhythmia (-12.0% [-29.4, 77.5]); the absolute decrease of major CVD among adults with diabetes was higher than among adults without diabetes (P < 0.001). Men with diabetes had larger decreases in CVD death than women with diabetes (P < 0.001). CONCLUSIONS: Major CVD mortality in adults with diabetes has declined, especially in men. Large reductions were observed for IHD and stroke mortality, although heart failure and arrhythmia deaths did not change. All race and education groups benefitted to a similar degree, but significant gaps remained across groups.

BACKGROUND: Large reductions in diabetes complications have altered diabetes-related morbidity in the USA. It is unclear whether similar trends have occurred in causes of death. METHODS: Using data from the National Health Interview Survey Linked Mortality files from 1985 to 2015, we estimated age-specific death rates and proportional mortality from all causes, vascular causes, cancers, and non-vascular, non-cancer causes among US adults by diabetes status. FINDINGS: From 1988-94, to 2010-15, all-cause death rates declined by 20% every 10 years among US adults with diabetes (from 23.1 [95% CI 20.1-26.0] to 15.2 [14.6-15.8] per 1000 person-years), while death from vascular causes decreased 32% every 10 years (from 11.0 [9.2-12.2] to 5.2 [4.8-5.6] per 1000 person-years), deaths from cancers decreased 16% every 10 years (from 4.4 [3.2-5.5] to 3.0 [2.8-3.3] per 1000 person-years), and the rate of non-vascular, non-cancer deaths declined by 8% every 10 years (from 7.7 [6.3-9.2] to 7.1 [6.6-7.5]). Death rates also declined significantly among people without diagnosed diabetes for all four major mortality categories. However, the declines in death rates were significantly greater among people with diabetes for all-causes (pinteraction<0.0001), vascular causes (pinteraction=0.0214), and non-vascular, non-cancer causes (pinteration<0.0001), as differences in all-cause and vascular disease death between people with and without diabetes were reduced by about a half. Among people with diabetes, all-cause mortality rates declined most in men and adults aged 65-74 years of age, and there was no decline in death rates among adults aged 20-44 years. The different magnitude of changes in cause-specific mortality led to large changes in the proportional mortality. The proportion of total deaths among adults with diabetes from vascular causes declined from 47.8% (95% CI 38.9-58.8) in 1988-94 to 34.1% (31.4-37.1) in 2010-15; this decline was offset by large increases in the proportion of deaths from non-vascular, non-cancer causes, from 33.5% (26.7-42.1) to 46.5% (43.3-50.0). The proportion of deaths caused by cancer was relatively stable over time, ranging from 16% to 20%. INTERPRETATION: Declining rates of vascular disease mortality are leading to a diversification of forms of diabetes-related mortality with implications for clinical management, prevention, and disease monitoring. FUNDING: None.

Diabetes is a common chronic condition and as of 2015, approximately 30 million persons in the United States had diabetes (23 million with diagnosed and 7 million with undiagnosed) (1). Diabetic ketoacidosis (DKA) is a life-threatening but preventable complication of diabetes characterized by uncontrolled hyperglycemia (>250 mg/dL), metabolic acidosis, and increased ketone concentration that occurs most frequently in persons with type 1 diabetes (2). CDC's United States Diabetes Surveillance System* (USDSS) indicated an increase in hospitalization rates for DKA during 2009-2014, most notably in persons aged <45 years. To explore this finding, 2000-2014 data from the Agency for Healthcare Research and Quality's National Inpatient Sample (NIS)(dagger) were assembled to calculate trends in DKA hospitalization rates and in-hospital case-fatality rates. Overall, age-adjusted DKA hospitalization rates decreased slightly from 2000 to 2009, then reversed direction, steadily increasing from 2009 to 2014 at an average annual rate of 6.3%. In-hospital case-fatality rates declined consistently during the study period from 1.1% to 0.4%. Better understanding the causes of this increasing trend in DKA hospitalizations and decreasing trend in in-hospital case-fatality through further exploration using multiple data sources will facilitate the targeting of prevention efforts.

Currently 23 million U.S. adults have been diagnosed with diabetes (1). The two most common forms of diabetes are type 1 and type 2. Type 1 diabetes results from the autoimmune destruction of the pancreas's beta cells, which produce insulin. Persons with type 1 diabetes require insulin for survival; insulin may be given as a daily shot or continuously with an insulin pump (2). Type 2 diabetes is mainly caused by a combination of insulin resistance and relative insulin deficiency (3). A small proportion of diabetes cases might be types other than type 1 or type 2, such as maturity-onset diabetes of the young or latent autoimmune diabetes in adults (3). Although the majority of prevalent cases of type 1 and type 2 diabetes are in adults, national data on the prevalence of type 1 and type 2 in the U.S. adult population are sparse, in part because of the previous difficulty in classifying diabetes by type in surveys (2,4,5). In 2016, supplemental questions to help distinguish diabetes type were added to the National Health Interview Survey (NHIS) (6). This study used NHIS data from 2016 to estimate the prevalence of diagnosed diabetes among adults by primary type. Overall, based on self-reported type and current insulin use, 0.55% of U.S. adults had diagnosed type 1 diabetes, representing 1.3 million adults; 8.6% had diagnosed type 2 diabetes, representing 21.0 million adults. Of all diagnosed cases, 5.8% were type 1 diabetes, and 90.9% were type 2 diabetes; the remaining 3.3% of cases were other types of diabetes. Understanding the prevalence of diagnosed diabetes by type is important for monitoring trends, planning public health responses, assessing the burden of disease for education and management programs, and prioritizing national plans for future type-specific health services.

Objective: To examine recent trends in type 2 diabetes detection among adults in the USA. Research design and methods: We used data from the 1999-2014 National Health and Nutrition Examination Surveys on non-pregnant adults (aged >/=18 years) not reporting a diagnosis of diabetes (n=16 644 participants, averaging about 2000 for each 2-year cycle). We defined undiagnosed diabetes as a fasting plasma glucose >/=126 mg/dL or a hemoglobin A1c >/=6.5% (48 mmol/mol). We measured case detection as the probability of finding undiagnosed type 2 diabetes among the population without diagnosed diabetes. Linear regression models were used to examine trends overall and by sociodemographic characteristics (ie, age, gender, race/ethnicity, education, poverty-income ratio (PIR)). Results: Age-standardized probability of finding undiagnosed type 2 diabetes was 3.0% (95% CI 2.1% to 4.2%) during 1999-2000 and 2.8% (2.2%-3.6%) during 2013-2014 (P for trend=0.52). Probability increased among Mexican-Americans (P for trend=0.01) but decreased among adults aged 65 years or older (P for trend=0.04), non-Hispanic (NH) white (P for trend=0.02), and adults in the highest PIR tertile (P for trend=0.047). For all other sociodemographic groups, no significant trends were detected. Conclusions: We found little evidence of increased detection of undiagnosed type 2 diabetes among adults in the USA during the past 15 years. Although improvements were seen among NH white, older, and wealthy adults, these improvements were not large. As the scope of primary prevention efforts increases, case detection may improve.

PURPOSE: Health and administrative systems are facing spatial clustering in chronic diseases such as diabetes. This study explores how geographic distribution of diabetes in the United States is associated with socioeconomic and built environment characteristics and health-relevant policies. METHODS: We compiled nationally representative county-level data from multiple data sources. We standardized characteristics to a mean = 0 and a SD = 1 and modeled county-level age-adjusted diagnosed diabetes incidence in 2013 using 2-level hierarchical linear regression. RESULTS: Incidence of age-standardized diagnosed diabetes in 2013 varied across U.S. counties (n = 3109), ranging from 310 to 2190 new cases/100,000, with an average of 856.4/100,000. Socioeconomic and health-related characteristics explained approximately 42% of the variation in diabetes incidence across counties. After accounting for other characteristics, counties with higher unemployment, higher poverty, and longer commutes had higher incidence rates than counties with lower levels. Counties with more exercise opportunities, access to healthy food, and primary care physicians had fewer diabetes cases. CONCLUSIONS: Features of the socioeconomic and built environment were associated with diabetes incidence; identifying the salient modifiable features of counties can inform targeted policies to reduce diabetes incidence.

OBJECTIVE: Reductions in heart attack and stroke hospitalizations are well documented in the U.S. population with diabetes. We extended trend analyses to other cardiovascular disease (CVD) conditions, including stroke by type, and used four additional years of data. RESEARCH DESIGN AND METHODS: Using 1998-2014 National (Nationwide) Inpatient Sample data, we estimated the number of discharges having acute coronary syndrome (ACS) (ICD-9 codes 410-411), cardiac dysrhythmia (427), heart failure (428), hemorrhagic stroke (430-432), or ischemic stroke (433.x1, 434, and 436) as first-listed diagnosis and diabetes (250) as secondary diagnosis. Hospitalization rates for adults aged ≥35 years were calculated using estimates from the population with and the population without diabetes from the National Health Interview Survey and age-adjusted to the 2000 U.S. standard population. Joinpoint regression was used to analyze trends and calculate an average annual percentage change (AAPC) with 95% confidence limits (CLs). RESULTS: From 1998 to 2014, in the population with diabetes, age-adjusted hospitalization rates declined significantly for ACS (AAPC -4.6% per year [95% CL -5.3, -3.8]), cardiac dysrhythmia (-0.7% [-1.1, -0.2]), heart failure (-3.6% [-4.6, -2.7]), hemorrhagic stroke (-1.1% [-1.4, -0.7]), and ischemic stroke (-2.9% [-3.9, -1.8]). In the population without diabetes, rates also declined significantly for these conditions, with the exception of dysrhythmia. By 2014, rates in the population with diabetes population remained two to four times as high as those for the population without diabetes, with the largest difference in heart failure rates. CONCLUSIONS: CVD hospitalization rates declined significantly in both the population with diabetes and the population without diabetes. This may be due to several factors, including new or more aggressive treatments and reductions in CVD risk factors and CVD incidence.

States bear substantial responsibility for addressing the rising rates of diabetes and prediabetes in the United States. However, accurate state-level estimates of diabetes and prediabetes prevalence that include undiagnosed cases have been impossible to produce with traditional sources of state-level data. Various new and nontraditional sources for estimating state-level prevalence are now available. These include surveys with expanded samples that can support state-level estimation in some states and administrative and clinical data from insurance claims and electronic health records. These sources pose methodologic challenges because they typically cover partial, sometimes nonrandom subpopulations; they do not always use the same measurements for all individuals; and they use different and limited sets of variables for case finding and adjustment. We present an approach for adjusting new and nontraditional data sources for diabetes surveillance that addresses these limitations, and we present the results of our proposed approach for 2 states (Alabama and California) as a proof of concept. The method reweights surveys and other data sources with population undercoverage to make them more representative of state populations, and it adjusts for nonrandom use of laboratory testing in clinically generated data sets. These enhanced diabetes and prediabetes prevalence estimates can be used to better understand the total burden of diabetes and prediabetes at the state level and to guide policies and programs designed to prevent and control these chronic diseases.

During 2014, 120,000 persons in the United States and Puerto Rico began treatment for end-stage renal disease (ESRD) (i.e., kidney failure requiring dialysis or transplantation) (1). Among these persons, 44% (approximately 53,000 persons) had diabetes listed as the primary cause of ESRD (ESRD-D) (1). Although the number of persons initiating ESRD-D treatment each year has increased since 1980 (1,2), the ESRD-D incidence rate among persons with diagnosed diabetes has declined since the mid-1990s (2,3). To determine whether ESRD-D incidence has continued to decline in the United States overall and in each state, the District of Columbia (DC), and Puerto Rico, CDC analyzed 2000-2014 data from the U.S. Renal Data System and the Behavioral Risk Factor Surveillance System. During that period, the age-standardized ESRD-D incidence among persons with diagnosed diabetes declined from 260.2 to 173.9 per 100,000 diabetic population (33%), and declined significantly in most states, DC, and Puerto Rico. No state experienced an increase in ESRD-D incidence rates. Continued awareness of risk factors for kidney failure and interventions to improve diabetes care might sustain and improve these trends.

Infectious cDNA clones allow for genetic manipulation of a virus, thus facilitating work on vaccines, pathogenesis, replication, transmission and viral evolution. Here we describe the construction of an infectious clone for Zika virus (ZIKV), which is currently causing an explosive outbreak in the Americas. To prevent toxicity to bacteria that is commonly observed with flavivirus-derived plasmids, we generated a two-plasmid system which separates the genome at the NS1 gene and is more stable than full-length constructs that could not be successfully recovered without mutations. After digestion and ligation to join the two fragments, full-length viral RNA can be generated by in vitro transcription with T7 RNA polymerase. Following electroporation of transcribed RNA into cells, virus was recovered that exhibited similar in vitro growth kinetics and in vivo virulence and infection phenotypes in mice and mosquitoes, respectively.

Diabetes is a common chronic disease of childhood affecting approximately 200,000 children and adolescents in the United States (1). Children and adolescents with diabetes are at increased risk for death from acute complications of diabetes, including hypoglycemia and diabetic ketoacidosis (2,3); in 2012, CDC reported that during 1968-2009, diabetes mortality among U.S. persons aged ≤19 years declined by 61% (4). CDC observed disparities by race during 1979-2004, with black children and adolescents dying from diabetes at twice the rate of white children and adolescents (5). However, no previous study has examined Hispanic ethnicity. CDC analyzed data from the National Vital Statistics System for deaths among persons aged 1-19 years in the United States during 2000-2014, with diabetes listed as the underlying cause of death overall, and for Hispanic, non-Hispanic white (white), and non-Hispanic black (black) children and adolescents. During 2012-2014, black children and adolescents had the highest diabetes death rate (2.04 per 1 million population), followed by whites (0.92) and Hispanics (0.61). There were no statistically significant changes in diabetes death rates over the study period, but disparities persisted among racial/ethnic groups. Death from diabetes in children and adolescents is potentially preventable through increased awareness of diabetes symptoms (including symptoms of low blood sugar), earlier treatment and education related to diabetes, and management of diabetes ketoacidosis. Continued measures are needed to reduce diabetes mortality in children and understand the cause of racial and ethnic disparities.

Structured lifestyle interventions can reduce diabetes incidence and cardiovascular disease (CVD) risk among persons with impaired glucose tolerance (IGT), but it is unclear whether they should be implemented among persons without IGT. We conducted a systematic review and meta-analyses to assess the effectiveness of lifestyle interventions on CVD risk among adults without IGT or diabetes. We systematically searched MEDLINE, EMBASE, CINAHL, Web of Science, the Cochrane Library, and PsychInfo databases, from inception to May 4, 2016. We selected randomized controlled trials of lifestyle interventions, involving physical activity (PA), dietary (D), or combined strategies (PA+D) with follow-up duration ≥12 months. We excluded all studies that included individuals with IGT, confirmed by 2-hours oral glucose tolerance test (75g), but included all other studies recruiting populations with different glycemic levels. We stratified studies by baseline glycemic levels: (1) low-range group with mean fasting plasma glucose (FPG) <5.5mmol/L or glycated hemoglobin (A1C) <5.5%, and (2) high-range group with FPG ≥5.5mmol/L or A1C ≥5.5%, and synthesized data using random-effects models. Primary outcomes in this review included systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Totally 79 studies met inclusion criteria. Compared to usual care (UC), lifestyle interventions achieved significant improvements in SBP (-2.16mmHg[95%CI, -2.93, -1.39]), DBP (-1.83mmHg[-2.34, -1.31]), TC (-0.10mmol/L[-0.15, -0.05]), LDL-C (-0.09mmol/L[-0.13, -0.04]), HDL-C (0.03mmol/L[0.01, 0.04]), and TG (-0.08mmol/L[-0.14, -0.03]). Similar effects were observed among both low-and high-range study groups except for TC and TG. Similar effects also appeared in SBP and DBP categories regardless of follow-up duration. PA+D interventions had larger improvement effects on CVD risk factors than PA alone interventions. In adults without IGT or diabetes, lifestyle interventions resulted in significant improvements in SBP, DBP, TC, LDL-C, HDL-C, and TG, and might further reduce CVD risk.

Recent studies suggest that prevalence of diagnosed diabetes in the United States reached a plateau or slowed around 2008, and that this change coincided with obesity plateaus and increases in physical activity. However, national estimates can obscure important variations in geographic subgroups. We examine whether a slowing or leveling off in diagnosed diabetes, obesity, and leisure time physical inactivity prevalence is also evident across the 3143 counties of the United States. We used publicly available county estimates of the age-adjusted prevalence of diagnosed diabetes, obesity, and leisure-time physical inactivity, which were generated by the Centers for Disease Control and Prevention (CDC). Using a Bayesian multilevel regression that included random effects by county and year and applied cubic splines to smooth these estimates over time, we estimated the average annual percentage point change (APPC) from 2004 to 2008 and from 2008 to 2012 for diabetes, obesity, and physical inactivity prevalence in each county. Compared to 2004-2008, the median APPCs for diabetes, obesity, and physical inactivity were lower in 2008-2012 (diabetes APPC difference = 0.16, 95%CI 0.14, 0.18; obesity APPC difference = 0.65, 95%CI 0.59, 0.70; physical inactivity APPC difference = 0.43, 95%CI 0.37, 0.48). APPCs and APPC differences between time periods varied among counties and U.S. regions. Despite improvements, levels of these risk factors remained high with most counties merely slowing rather than reversing, which suggests that all counties would likely benefit from reductions in these risk factors. The diversity of trajectories in the prevalence of these risk factors across counties underscores the continued need to identify high risk areas and populations for preventive interventions. Awareness of how these factors are changing might assist local policy makers in targeting and tracking the impact of efforts to reduce diabetes, obesity and physical inactivity.

This study systematically assessed the effectiveness of lifestyle interventions on glycemic indicators among adults (18years) without IGT or diabetes. Randomized controlled trials using physical activity (PA), diet (D), or their combined strategies (PA+D) with follow-up 12months were systematically searched from multiple electronic-databases between inception and May 4, 2016. Outcome measures included fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting insulin (FI), homeostasis model assessment-estimated insulin resistance (HOMA-IR), and bodyweight. Included studies were divided into low-range (FPG <5.5mmol/L or HbA1c <5.5%) and high-range (FPG 5.5mmol/L or HbA1c 5.5%) groups according to baseline glycemic levels. Seventy-nine studies met inclusion criteria. Random-effect models demonstrated that compared with usual care, lifestyle interventions achieved significant reductions in FPG (-0.14mmol/L [95%CI, -0.19, -0.10]), HbA1c (-0.06% [-0.09, -0.03]), FI (%change: -15.18% [-20.01, -10.35]), HOMA-IR (%change: -22.82% [-29.14, -16.51]), and bodyweight (%change: -3.99% [-4.69, -3.29]). The same effect sizes in FPG reduction (0.07) appeared among both low-range and high-range groups. Similar effects were observed among all groups regardless of lengths of follow-up. D and PA+D interventions had larger effects on glucose reduction than PA alone. Lifestyle interventions significantly improved FPG, HbA1c, FI, HOMA-IR, and bodyweight among adults without IGT or diabetes, and might reduce progression of hyperglycemia to type 2 diabetes mellitus.

Zika virus (ZIKV; Family Flaviviridae, genus Flavivirus) is a rapidly expanding global pathogen that has been associated with severe clinical manifestations, including devastating neurological disease in infants. There are currently no molecular clones of a New World ZIKV available, hindering progress toward understanding determinants of transmission and pathogenesis. Here we report the development and characterization of a novel ZIKV reverse genetics system based on a 2015 isolate from Puerto Rico (PRVABC59). We generated a two-plasmid infectious clone system from which infectious virus was rescued that replicates in human and mosquito cells with growth kinetics representative of wild-type ZIKV. Infectious clone-derived virus initiated comparable infection and transmission rates in Aedes aegypti mosquitoes compared to the primary isolate and displayed similar pathogenesis in AG129 mice. This infectious clone system provides a valuable resource to the research community to explore ZIKV molecular biology, vaccine development, antiviral development, diagnostics, vector competence, and disease pathogenesis. IMPORTANCE: ZIKV is a rapidly spreading mosquito-borne pathogen that has been linked to Guillain-Barre syndrome in adults and congenital microcephaly in developing fetuses and infants. ZIKV can also be sexually transmitted. The viral molecular determinants of any of these phenotypes are not well understood. There is no reverse genetics system available for the current epidemic virus that will allow researchers to study ZIKV immunity, develop novel vaccines, or develop antiviral drugs. Here we provide a novel infectious clone system generated from a recent ZIKV isolated from a patient infected in Puerto Rico. This infectious clone produces virus with similar in vitro and in vivo characteristics to the primary isolate, providing a critical tool to study ZIKV infection and disease.

BACKGROUND: In recent decades, the United States experienced increasing prevalence and incidence of diabetes, accompanied by large disparities in county-level diabetes prevalence and incidence. However, whether these disparities are widening, narrowing, or staying the same has not been studied. We examined changes in disparity among U.S. counties in diagnosed diabetes prevalence and incidence between 2004 and 2012. METHODS: We used 2004 and 2012 county-level diabetes (type 1 and type 2) prevalence and incidence data, along with demographic, socio-economic, and risk factor data from various sources. To determine whether disparities widened or narrowed over the time period, we used a regression-based beta-convergence approach, accounting for spatial autocorrelation. We calculated diabetes prevalence/incidence percentage point (ppt) changes between 2004 and 2012 and modeled these changes as a function of baseline diabetes prevalence/incidence in 2004. Covariates included county-level demographic and, socio-economic data, and known type 2 diabetes risk factors (obesity and leisure-time physical inactivity). RESULTS: For each county-level ppt increase in diabetes prevalence in 2004 there was an annual average increase of 0.02 ppt (p<0.001) in diabetes prevalence between 2004 and 2012, indicating a widening of disparities. However, after accounting for covariates, diabetes prevalence decreased by an annual average of 0.04 ppt (p<0.001). In contrast, changes in diabetes incidence decreased by an average of 0.04 ppt (unadjusted) and 0.09 ppt (adjusted) for each ppt increase in diabetes incidence in 2004, indicating a narrowing of county-level disparities. CONCLUSIONS: County-level disparities in diagnosed diabetes prevalence in the United States widened between 2004 and 2012, while disparities in incidence narrowed. Accounting for demographic and, socio-economic characteristics and risk factors for type 2 diabetes narrowed the disparities, suggesting that these factors are strongly associated with changes in disparities. Public health interventions that target modifiable risk factors, such as obesity and physical inactivity, in high burden counties might further reduce disparities in incidence and, over time, in prevalence.

INTRODUCTION: Hospitalization data typically cannot be used to estimate the number of individuals hospitalized annually because individuals are not tracked over time and may be hospitalized multiple times annually. We examined the impact of repeat hospitalizations on hospitalization rates for various conditions and on comparison of rates by diabetes status. METHODS: We analyzed hospitalization data for which repeat hospitalizations could be distinguished among adults aged 18 or older from 12 states using the 2011 Agency for Healthcare Research and Quality's State Inpatient Databases. The Behavioral Risk Factor Surveillance System was used to estimate the number of adults with and without diagnosed diabetes in each state (denominator). We calculated percentage increases due to repeat hospitalizations in rates and compared the ratio of diabetes with non-diabetes rates while excluding and including repeat hospitalizations. RESULTS: Regardless of diabetes status, hospitalization rates were considerably higher when repeat hospitalizations within a calendar year were included. The magnitude of the differences varied by condition. Among adults with diabetes, rates ranged from 13.0% higher for stroke to 41.6% higher for heart failure; for adults without diabetes, these rates ranged from 9.5% higher for stroke to 25.2% higher for heart failure. Ratios of diabetes versus non-diabetes rates were similar with and without repeat hospitalizations. CONCLUSION: Hospitalization rates that include repeat hospitalizations overestimate rates in individuals, and this overestimation is especially pronounced for some causes. However, the inclusion of repeat hospitalizations for common diabetes-related causes had little impact on rates by diabetes status.

Asians and Native Hawaiians or other Pacific Islanders (NHPIs) are fast-growing U.S. minority populations*(,dagger) at high risk for type 2 diabetes (1-4). Although national studies have described diabetes prevalence, incidence, and risk factors among Asians (2-5) and NHPIs (2,5) compared with non-Hispanic whites, little is known about state-level diabetes prevalence among these two racial groups, or about how they differ from one another with respect to diabetes risk factors. To examine state-level prevalence of self-reported, physician-diagnosed (diagnosed) diabetes and risk factors among Asians and NHPIs aged ≥18 years, CDC analyzed data from the 2011-2014 Behavioral Risk Factor Surveillance System (BRFSS). Among five states and Guam with sufficient data about NHPIs for analysis, the age-adjusted diabetes prevalence estimate for NHPIs ranged from 13.4% (New York) to 19.1% (California). Among 32 states, the District of Columbia (DC), and Guam that had sufficient data about Asians for analysis, diabetes prevalence estimates for Asians ranged from 4.9% (Arizona) to 15.3% (New York). In the five states and Guam with sufficient NHPI data, NHPIs had a higher age-adjusted prevalence of diabetes than did Asians, and a higher proportion of NHPIs were overweight or obese and had less than a high school education compared with Asians. Effective interventions and policies might reduce the prevalence of diabetes in these growing, high-risk minority populations.

IMPORTANCE: Previous studies have shown increasing prevalence of diabetes in the United States. New US data are available to estimate prevalence of and trends in diabetes. OBJECTIVE: To estimate the recent prevalence and update US trends in total diabetes, diagnosed diabetes, and undiagnosed diabetes using National Health and Nutrition Examination Survey (NHANES) data. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional surveys conducted between 1988-1994 and 1999-2012 of nationally representative samples of the civilian, noninstitutionalized US population; 2781 adults from 2011-2012 were used to estimate recent prevalence and an additional 23,634 adults from 1988-2010 were used to estimate trends. MAIN OUTCOMES AND MEASURES: The prevalence of diabetes was defined using a previous diagnosis of diabetes or, if diabetes was not previously diagnosed, by (1) a hemoglobin A1c level of 6.5% or greater or a fasting plasma glucose (FPG) level of 126 mg/dL or greater (hemoglobin A1c or FPG definition) or (2) additionally including 2-hour plasma glucose (2-hour PG) level of 200 mg/dL or greater (hemoglobin A1c, FPG, or 2-hour PG definition). Prediabetes was defined as a hemoglobin A1c level of 5.7% to 6.4%, an FPG level of 100 mg/dL to 125 mg/dL, or a 2-hour PG level of 140 mg/dL to 199 mg/dL. RESULTS: In the overall 2011-2012 population, the unadjusted prevalence (using the hemoglobin A1c, FPG, or 2-hour PG definitions for diabetes and prediabetes) was 14.3% (95% CI, 12.2%-16.8%) for total diabetes, 9.1% (95% CI, 7.8%-10.6%) for diagnosed diabetes, 5.2% (95% CI, 4.0%-6.9%) for undiagnosed diabetes, and 38.0% (95% CI, 34.7%-41.3%) for prediabetes; among those with diabetes, 36.4% (95% CI, 30.5%-42.7%) were undiagnosed. The unadjusted prevalence of total diabetes (using the hemoglobin A1c or FPG definition) was 12.3% (95% CI, 10.8%-14.1%); among those with diabetes, 25.2% (95% CI, 21.1%-29.8%) were undiagnosed. Compared with non-Hispanic white participants (11.3% [95% CI, 9.0%-14.1%]), the age-standardized prevalence of total diabetes (using the hemoglobin A1c, FPG, or 2-hour PG definition) was higher among non-Hispanic black participants (21.8% [95% CI, 17.7%-26.7%]; P < .001), non-Hispanic Asian participants (20.6% [95% CI, 15.0%-27.6%]; P = .007), and Hispanic participants (22.6% [95% CI, 18.4%-27.5%]; P < .001). The age-standardized percentage of cases that were undiagnosed was higher among non-Hispanic Asian participants (50.9% [95% CI, 38.3%-63.4%]; P = .004) and Hispanic participants (49.0% [95% CI, 40.8%-57.2%]; P = .02) than all other racial/ethnic groups. The age-standardized prevalence of total diabetes (using the hemoglobin A1c or FPG definition) increased from 9.8% (95% CI, 8.9%-10.6%) in 1988-1994 to 10.8% (95% CI, 9.5%-12.0%) in 2001-2002 to 12.4% (95% CI, 10.8%-14.2%) in 2011-2012 (P < .001 for trend) and increased significantly in every age group, in both sexes, in every racial/ethnic group, by all education levels, and in all poverty income ratio tertiles. CONCLUSIONS AND RELEVANCE: In 2011-2012, the estimated prevalence of diabetes was 12% to 14% among US adults, depending on the criteria used, with a higher prevalence among participants who were non-Hispanic black, non-Hispanic Asian, and Hispanic. Between 1988-1994 and 2011-2012, the prevalence of diabetes increased in the overall population and in all subgroups evaluated.

BACKGROUND: Despite concerns about hypoglycemia events from overly aggressive glycemic reduction, population trends in hypoglycemia and hyperglycemic crisis incidence are unclear. To address this gap, we examined changes in emergency department (ED) visit rates for hypoglycemia and hyperglycemic crisis 2006-2011. METHODS: Using data from the Nationwide Emergency Department Sample, we estimated the number of ED visits for hypoglycemia and hyperglycemic crisis via ICD-9-CM among adults with diabetes. Using data from the National Health Interview Survey, we estimated the population of adults with diabetes and calculated ED visit rates. RESULTS: From 2006 to 2011, ED visit rates for hypoglycemia declined by 22% from 1.8 to 1.4 per 100 adults (p = 0.003). The rates decreased in all age groups (all P<0.05) except those aged 18 to 44 years (P = 0.31). Hypoglycemia rates displayed a J-shaped curve across age, with the highest rates among adults aged 75 years or older (P <0.001). ED visit rates for hyperglycemic crisis did not change overall but increased 17% for adults aged 65 to 74 years (P = 0.02) and 29% for women (P = 0.01). Hyperglycemic crisis rates were highest among adults aged 18 to 44 years (P <0.001). CONCLUSIONS: Hypoglycemia rates have declined for all adults but persons aged 18-44 years while rates for hyperglycemic crisis remained stable. Future preventive efforts should target on the susceptible population of adults aged 18 to 44 years and those aged 75 years or older.

INTRODUCTION: Diabetes is one of the most common and fastest-growing comorbidities of pregnancy. Temporal trends in gestational diabetes mellitus (GDM) have not been examined at the state level. This study examines GDM prevalence trends overall and by age, state, and region for 19 states, and by race/ethnicity for 12 states. Sub-analysis assesses trends among GDM deliveries by insurance type and comorbid hypertension in pregnancy. METHODS: Using the Agency for Healthcare Research and Quality's National and State Inpatient Databases, deliveries were identified using diagnosis-related group codes for GDM and comorbidities using ICD-9-CM diagnosis codes among all community hospitals. General linear regression with a log-link and binomial distribution was used in 2014 to assess annual change in GDM prevalence from 2000 through 2010. RESULTS: The age-standardized prevalence of GDM increased from 3.71 in 2000 to 5.77 per 100 deliveries in 2010 (relative increase, 56%). From 2000 through 2010, GDM deliveries increased significantly in all states (p<0.01), with relative increases ranging from 36% to 88%. GDM among deliveries in 12 states reporting race and ethnicity increased among all groups (p<0.01), with the highest relative increase in Hispanics (66%). Among GDM deliveries in 19 states, those with pre-pregnancy hypertension increased significantly from 2.5% to 4.1% (relative increase, 64%). The burden of GDM delivery payment shifted from private insurers (absolute decrease of 13.5 percentage points) to Medicaid/Medicare (13.2-percentage point increase). CONCLUSIONS: Results suggest that GDM deliveries are increasing. The highest rates of increase are among Hispanics and among GDM deliveries complicated by pre-pregnancy hypertension.

Vision loss and blindness are among the top 10 disabilities in the United States, causing substantial social, economic, and psychological effects, including increased morbidity, increased mortality, and decreased quality of life. There are disparities in vision loss based on age, sex, race/ethnicity, socioeconomic status, and geographic location. Current surveillance activities using national and state surveys have characterized vision loss at national and state levels. However, there are limited data and research at local levels, where interventions and policy decisions to reduce the burden of vision loss and eliminate disparities are often developed and implemented. CDC analyzed data from the American Community Survey (ACS) to estimate county-level prevalence of severe vision loss (SVL) (being blind or having serious difficulty seeing even when wearing glasses) in the United States and to describe its geographic pattern and its association with poverty level. Distinct geographic patterns of SVL prevalence were found in the United States; 77.3% of counties in the top SVL prevalence quartile (≥4.2%) were located in the South. SVL was significantly correlated with poverty (r = 0.5); 437 counties were in the top quartiles for both SVL and poverty, and 83.1% of those counties were located in southern states. A better understanding of the underlying barriers and facilitators of access and use of eye care services at the local level is needed to enable the development of more effective interventions and policies, and to help planners and practitioners serve the growing population with and at risk for vision loss more efficiently.

BACKGROUND: Screening guidelines are used to help identify prediabetes and diabetes before implementing evidence-based prevention and treatment interventions. We examined screening practices benchmarking against two US guidelines, and the capacity of each guideline to identify dysglycemia. METHODS: Using 2007-2012 National Health and Nutrition Examination Surveys, we analyzed nationally-representative, cross-sectional data from 5,813 fasting non-pregnant adults aged ≥20 years without self-reported diabetes. We examined proportions of adults eligible for diagnostic glucose testing and those who self-reported receiving testing in the past three years, as recommended by the American Diabetes Association (ADA) and the US Preventive Services Task Force (USPSTF-2008) guidelines. For each screening guideline, we also assessed sensitivity, specificity, and positive (PPV) and negative predictive values in identifying dysglycemia (defined as fasting plasma glucose ≥100 mg/dl or hemoglobin A1c ≥5.7%). RESULTS: In 2007-2012, 73.0% and 23.7% of US adults without diagnosed diabetes met ADA and USPSTF-2008 criteria for screening, respectively; and 91.5% had at least one major risk factor for diabetes. Of those ADA- or USPSTF-eligible adults, about 51% reported being tested within the past three years. Eligible individuals not tested were more likely to be lower educated, poorer, uninsured, or have no usual place of care compared to tested eligible adults. Among adults with ≥1 major risk factor, 45.7% reported being tested, and dysglycemia yields (i.e., PPV) ranged from 45.8% (high-risk ethnicity) to 72.6% (self-reported prediabetes). ADA criteria and having any risk factor were more sensitive than the USPSTF-2008 guideline (88.8-97.7% vs. 31.0%) but less specific (13.5-39.7% vs. 82.1%) in recommending glucose testing, resulting in lower PPVs (47.7-54.4% vs. 58.4%). CONCLUSION: Diverging recommendations and variable performance of different guidelines may be impeding national diabetes prevention and treatment efforts. Efforts to align screening recommendations may result in earlier identification of adults at high risk for prediabetes and diabetes.