The Undiagnosed Diseases Network: Characteristics of solvable applicants and diagnostic suggestions for nonaccepted ones.

PURPOSE: Can certain characteristics identify as solvable some undiagnosed patients who seek extensive evaluation and thorough record review, such as by the Undiagnosed Diseases Network (UDN)? METHODS: The UDN is a national research resource to solve medical mysteries through team science. Applicants provide informed consent to access to their medical records. After review, expert panels assess if applicants meet inclusion and exclusion criteria to select participants. When not accepting applicants, UDN experts may offer suggestions for diagnostic efforts. Using minimal information from initial applications, we compare features in applicants who are not accepted with those who are accepted and either solved or still not solved by the UDN. The diagnostic suggestions offered to nonaccepted applicants and their clinicians were tallied. RESULTS: Nonaccepted applicants were more often female, older at first symptoms and application, and longer in review compared with accepted applicants. The accepted and successfully diagnosed applicants were younger, shorter in review time, more often non-White, of Hispanic ethnicity, and presenting with nervous system features. Half of nonaccepted applicants were given suggestions for further local diagnostic evaluation. A few seemed to have 2 major diagnoses or a provocative environmental exposure history. CONCLUSION: Comprehensive UDN record review generates possibly helpful advice.

High proportion of undiagnosed diabetes in patients surgically treated for infrarenal abdominal aortic aneurysm: findings from the multicentre Norwegian Aortic Aneurysm and Diabetes (ABANDIA) Study.

BACKGROUND: The aim was to investigate the total prevalence of known and undiagnosed diabetes mellitus (DM), and the association of DM with perioperative complications following elective, infrarenal, open surgical (OSR) or endovascular (EVAR), Abdominal Aortic Aneurysm (AAA) repair. METHODS: In this Norwegian prospective multicentre study, 877 patients underwent preoperative screening for DM by HbA1c measurements from November 2017 to December 2020. Diabetes was defined as screening detected HbA1c ≥ 48 mmol/mol (6.5%) or previously diagnosed diabetes. The association of DM with in-hospital complications, length of stay, and 30-day mortality rate were evaluated using adjusted and unadjusted logistic regression models. RESULTS: The total prevalence of DM was 15% (95% CI 13%,17%), of which 25% of the DM cases (95% CI 18%,33%) were undiagnosed upon admission for AAA surgery. The OSR to EVAR ratio was 52% versus 48%, with similar distribution among DM patients, and no differences in the prevalence of known and undiagnosed DM in the EVAR versus the OSR group. Total 30-day mortality rate was 0.6% (5/877). Sixty-six organ-related complications occurred in 58 (7%) of the patients. DM was not statistically significantly associated with a higher risk of in-hospital organ-related complications (OR 1.23, 95% CI 0.57,2.39, p = 0.57), procedure-related complications (OR 1.48, 95% CI 0.79,2.63, p = 0.20), 30-day mortality (p = 0.09) or length of stay (HR 1.06, 95% CI 0.88,1.28, p = 0.54). According to post-hoc-analyses, organ-related complications were more frequent in patients with newly diagnosed DM (n = 32) than in non-DM patients (OR 4.92; 95% CI 1.53,14.3, p = 0.005). CONCLUSION: Twenty-five percent of all DM cases were undiagnosed at the time of AAA surgery. Based on post-hoc analyses, undiagnosed DM seems to be associated with an increased risk of organ related complications following AAA surgery. This study suggests universal DM screening in AAA patients to reduce the number of DM patients being undiagnosed and to improve proactive diabetes care in this population. The results from post-hoc analyses should be confirmed in future studies.

Association Between Rental Assistance Programs and Undiagnosed Diabetes Among U.S.

BACKGROUND: Rental assistance programs have been linked to better housing quality, stability, healthcare access, and reduced likelihood of uncontrolled diabetes. However, its direct association with diabetes screening is uncertain. OBJECTIVE: To determine whether federal rental assistance programs are associated with lower odds of undiagnosed diabetes. DESIGN: We used a quasi-experimental approach, comparing outcomes among adults receiving rental assistance to those who entered assisted housing within 2 years after their health data were collected. We test the a priori hypothesis that rental assistance will be associated with decreased odds of undiagnosed diabetes. PARTICIPANTS: Participants in the National Health and Nutrition Examination Survey 1999-2018 who received rental assistance and who had diabetes. INTERVENTION: Current rental assistance participation, including specific housing programs. MAIN MEASURES: Undiagnosed diabetes based on having hemoglobin A1c ≥ 6.5% but answering no to the survey question of being diagnosed with diabetes. KEY RESULTS: Among 435 eligible adults (median age 54.5 years, female 68.5%, non-Hispanic white 32.5%), 80.7% were receiving rental assistance programs at the time of the interview, and 19.3% went on to receive rental assistance within 2 years. The rates of undiagnosed diabetes were 15.0% and 25.3% among those receiving rental assistance programs vs. those in the future assistance group (p-value = 0.07). In an adjusted logistic regression model, adults receiving rental assistance had lower odds of undiagnosed diabetes (OR 0.52, 95% CI 0.28-0.94) than those in future assistance groups. Sex, race and ethnic group, educational level, and poverty ratio were not significantly associated with having undiagnosed diabetes, but individuals aged 45-64 years had significantly lower odds of undiagnosed diabetes (OR 0.21, 95% CI 0.08-0.53) compared with those aged 18-44. CONCLUSIONS: Rental assistance was linked to lower odds of undiagnosed diabetes, suggesting that affordable housing programs can aid in early recognition and diagnosis, which may improve long-term outcomes.

Comparing Rates of Undiagnosed Hypertension and Diabetes in Patients With and Without Substance Use Disorders.

BACKGROUND: Individuals with substance use disorders (SUDs) have increased risk for developing chronic conditions, though few studies assess rates of diagnosis of these conditions among patients with SUDs. OBJECTIVE: To compare rates of undiagnosed hypertension and diabetes among patients with and without an SUD. DESIGN: Cross-sectional analysis using electronic health record (EHR) data from 58 primary care clinics at a large, urban, healthcare system in New York. PARTICIPANTS: Patients who had at least two primary care visits from 2019-2022 were included in our patient sample. Patients without an ICD-10 hypertension diagnosis or prescribed hypertension medications and with at least two blood pressure (BP) readings ≥ 140/90 mm were labeled 'undiagnosed hypertension,' and patients without a diabetes diagnosis or prescribed diabetes medications and with A1C/hemoglobin ≥ 6.5% were labeled 'undiagnosed diabetes.' MAIN MEASURES: We calculated the mean number of patients with and without an ICD-10 SUD diagnosis who were diagnosed and undiagnosed for each condition. We used multivariate logistic regression to assess the association between being undiagnosed for each condition, and having an SUD diagnosis, patient demographic characteristics, clinical characteristics (body mass index, Elixhauser comorbidity count, diagnosed HIV and psychosis), the percentage of visits without a BP screening, and the total number of visits during the time period. KEY RESULTS: The percentage of patients with undiagnosed hypertension (2.74%) and diabetes (22.98%) was higher amongst patients with SUD than patients without SUD. In multivariate models, controlling for other factors, patients with SUD had significantly higher odds of having undiagnosed hypertension (OR: 1.81; 95% CI: 1.48, 2.20) and undiagnosed diabetes (OR: 1.93; 1.72, 2.16). Being younger, female, and having an HIV diagnosis was also associated with significantly higher odds for being undiagnosed. CONCLUSIONS: We found significant disparities in rates of undiagnosed chronic diseases among patients with SUDs, compared with patients without SUDs.

A seroprevalence study indicates a high proportion of clinically undiagnosed MPXV infections in men who have sex with men in Berlin, Germany.

INTRODUCTION: During the mpox outbreak in 2022, the highest number of cases in Germany were registered in Berlin, almost all of them in men who have sex with men (MSM). However, the frequency of clinically undiagnosed infections is unknown. METHODS: A cross-sectional study was conducted among MSM in Berlin, Germany. Participants were recruited from private practices and community-based checkpoints specialised in HIV and STI care for MSM. They were asked to complete an online questionnaire on socio-demographic data, mpox diagnosis, vaccination history and sexual behaviour, and to provide a blood sample for serological analysis. The samples were tested for antibodies against a range of antigens to distinguish between antibodies induced by mpox infection and MVA vaccination, with pre-immune sera from childhood smallpox vaccination as a confounding factor. Associations of behavioural variables with reported and suspected mpox diagnosis as the outcome were tested using univariable and multivariable logistic regression models. RESULTS: Between the 11th April and 1st July 2023, 1,119 participants were recruited in eight private practices and two community-based checkpoints in Berlin. All participants provided a blood sample for serological testing. Information for the online questionnaire was provided by 728 participants; core data on age and mpox history for participants who did not provide questionnaire data were provided by the practices for an additional 218 participants. A previous diagnosis of mpox was reported for/by 70 participants (7.4%). Using a conservative and strict case definition, we serologically identified an additional 91 individuals with suspected undiagnosed mpox infection. Individuals with reported or suspected mpox infections reported more condomless anal sex partners in the past 3 months (OR = 5.93; 95% CI 2.10-18.35 for 5-10 partners; OR = 9.53; 95% CI 2.72-37.54 for > 10 partners) and were more likely to report sexual contact with partners diagnosed with mpox (OR = 2.87; 95% CI 1.39-5.84). CONCLUSION: A substantial proportion of mpox infections were clinically undiagnosed. The number of condomless anal sex partners was strongly associated with both confirmed and suspected undiagnosed mpox infection. Therefore, mpox control measures based on clinical diagnosis of mpox are likely to have limited effectiveness in preventing mpox transmission in outbreak situations because many infections remain unrecognised and undiagnosed.

Occult liver disease: A multinational perspective.

Occult liver disease refers to the presence of unrecognized chronic liver disease and cirrhosis. Liver disease is currently the eleventh cause of death globally, representing 4% of all deaths in the world. Alcohol consumption is the leading cause of cirrhosis globally, accounting for approximately 60% of cases. The estimated global prevalence of non-alcoholic fatty liver disease (NAFLD) is 32.4% and has been steadily increasing over the last years. Viral hepatitis B and C accounted for 1.3 million deaths in 2020. Several studies in populations at high risk of chronic liver disease (elevated liver enzymes, type 2 diabetes, excessive alcohol consumption) have found an elevated prevalence of occult liver disease. Attempts should be made to assess the prevalence of occult liver disease in Latin America, a region with one of the highest rates of metabolic diseases and excessive alcohol consumption. Screening for NAFLD in high-risk subjects and screening for excessive drinking and alcohol use disorders at every level of medical care is relevant. Efforts should also focus on the early treatment of occult liver disease to try to reduce liver disease burden and, in the case of occult viral hepatitis infection, prevent further spreading.

Prevalence of undiagnosed hypertension and associated factors in Ndera sector, Gasabo district of Rwanda: a cross-sectional study.

BACKGROUND: Hypertension remains a major global health challenge, including in low- and middle-income countries. In Rwanda, a lack of adequate information and healthcare services impacts healthcare-seeking behaviors, contributing to undiagnosed hypertension in rural areas. Therefore, the need to determine its prevalence and associated factors. METHODS: A cross-sectional study was conducted with 393 adults in the Ndera Sector, of Rwanda's Gasabo District, through a multistage sampling technique. Data was gathered using the WHO STEP-wise approach to non-communicable disease risk factor surveillance (STEPS) questionnaire; physical examination was done to determine blood pressure and body-mass index (BMI), after which the data collected was analyzed using SPSS. Newly diagnosed hypertension was determined when on two different intervals, systolic blood pressure readings was > 140 mmHg, and/or the diastolic blood pressure readings was > 90 mmHg, in the absence of previous hypertension diagnosis. RESULTS: The overall prevalence of hypertension among patients at Ndera sector was 15%, all of which were newly diagnosed. The mean (SD) age of the participants was 37 (13.7) years and half (53%) were women. The mean systolic blood pressure for men was 124.3 mmHg compared to 120.9 mmHg for women (p = 0.043, 95%CI: 0.12-6.74). Women had a significantly higher mean BMI (26.0) compared to men (22.8) (p < 0.001, 95%CI: -4.18 - -2.31). Age (χ² = 37.400, p < 0.001), residence (χ² = 10.200, p < 0.001), BMI (χ² = 22.1, p < 0.001), and lack of knowledge about hypertension (χ² = 25.1, p < 0.001) were the factors with significantly undiagnosed hypertension. CONCLUSIONS: The high prevalence of undiagnosed hypertension in Ndera Sector is linked to gender, older age, higher BMI, location, and lack of hypertension knowledge. These findings call for multifaceted approaches, combining educational initiatives, geographical targeting, lifestyle modifications, and policy implementations, all aimed at mitigating the burden of undiagnosed hypertension and enhancing community health within the Ndera Sector.

Exome and genome sequencing in adults with undiagnosed disease: a prospective cohort study.

BACKGROUND: Exome and genome sequencing have been demonstrated to increase diagnostic yield in paediatric populations, improving treatment options and providing risk information for relatives. There are limited studies examining the clinical utility of these tests in adults, who currently have limited access to this technology. METHODS: Patients from adult and cancer genetics clinics across Toronto, Ontario, Canada were recruited into a prospective cohort study evaluating the diagnostic utility of exome and genome sequencing in adults. Eligible patients were ≥18 years of age and suspected of having a hereditary disorder but had received previous uninformative genetic test results. In total, we examined the diagnostic utility of exome and genome sequencing in 47 probands and 34 of their relatives who consented to participate and underwent exome or genome sequencing. RESULTS: Overall, 17% (8/47) of probands had a pathogenic or likely pathogenic variant identified in a gene associated with their primary indication for testing. The diagnostic yield for patients with a cancer history was similar to the yield for patients with a non-cancer history (4/18 (22%) vs 4/29 (14%)). An additional 24 probands (51%) had an inconclusive result. Secondary findings were identified in 10 patients (21%); three had medically actionable results. CONCLUSIONS: This study lends evidence to the diagnostic utility of exome or genome sequencing in an undiagnosed adult population. The significant increase in diagnostic yield warrants the use of this technology. The identification and communication of secondary findings may provide added value when using this testing modality as a first-line test.

Online questionnaire on genetic testing for intractable diseases in Japan: response to and issues associated with the revised medical care act.

In Japan, most genetic testing for intractable diseases has been conducted in research laboratories in the past. However, since the Revised Medical Care Act came into effect on December 1, 2018, genetic testing in compliance with this act has become a major issue. To collect information on this topic, we conducted an online survey of members of the research groups for intractable diseases, which play a central role in medical care and research on intractable diseases with the support of the Ministry of Health, Labor and Welfare, five months after the enactment of the act. We separated the surveyed facilities into those that conducted genetic testing in their own laboratories ("testing facilities") and those that outsourced genetic testing ("outsourcing facilities"). Ninety-five and 66 responses regarding genetic testing were obtained from the testing and outsourcing facilities, respectively. Genetic analysis was the most commonly conducted genetic testing method, accounting for 60% or more of the tests. At the testing facilities that conducted comprehensive analysis with a next-generation sequencer, the number of target diseases for genetic testing was observed to be higher. In these testing facilities, more than 70% were research laboratories. In contrast, at the outsourcing facilities, testing was outsourced to registered clinical laboratories in many cases or to research laboratories. The proportion of genetic testing covered by public medical insurance at the outsourcing facilities was two times higher than that at the testing facilities. The importance of quality control for genetic testing was generally well acknowledged, but there was apprehension regarding the increased cost and burden on staff of quality control assurance, and many testing facilities viewed genetic testing as difficult. The research groups could handle the examination and interpretation of the genetic testing results, and many groups gathered and registered patient information. Within the intractable disease medical support network, there was a relatively large number of collaborations, with studies supported by the Japan Agency for Medical Research and Development (AMED) and Initiative on Rare and Undiagnosed Diseases (IRUD) projects. There were many requests for genetic testing to be covered by public medical insurance. In the future, the implementation of genetic testing using a next-generation sequencer at clinical laboratories with guaranteed quality control and the development of a system for collaboration with research groups will be necessary.

Hyper-prevalence of submicroscopic Plasmodium falciparum infections in a rural area of western Kenya with declining malaria cases.

BACKGROUND: The gold standard for diagnosing Plasmodium falciparum infection is microscopic examination of Giemsa-stained peripheral blood smears. The effectiveness of this procedure for infection surveillance and malaria control may be limited by a relatively high parasitaemia detection threshold. Persons with microscopically undetectable infections may go untreated, contributing to ongoing transmission to mosquito vectors. The purpose of this study was to determine the magnitude and determinants of undiagnosed submicroscopic P. falciparum infections in a rural area of western Kenya. METHODS: A health facility-based survey was conducted, and 367 patients seeking treatment for symptoms consistent with uncomplicated malaria in Homa Bay County were enrolled. The frequency of submicroscopic P. falciparum infection was measured by comparing the prevalence of infection based on light microscopic inspection of thick blood smears versus real-time polymerase chain reaction (RT-PCR) targeting P. falciparum 18S rRNA gene. Long-lasting insecticidal net (LLIN) use, participation in nocturnal outdoor activities, and gender were considered as potential determinants of submicroscopic infections. RESULTS: Microscopic inspection of blood smears was positive for asexual P. falciparum parasites in 14.7% (54/367) of cases. All of these samples were confirmed by RT-PCR. 35.8% (112/313) of blood smear negative cases were positive by RT-PCR, i.e., submicroscopic infection, resulting in an overall prevalence by RT-PCR alone of 45.2% compared to 14.7% for blood smear alone. Females had a higher prevalence of submicroscopic infections (35.6% or 72 out of 202 individuals, 95% CI 28.9-42.3) compared to males (24.2%, 40 of 165 individuals, 95% CI 17.6-30.8). The risk of submicroscopic infections in LLIN users was about half that of non-LLIN users (OR = 0.59). There was no difference in the prevalence of submicroscopic infections of study participants who were active in nocturnal outdoor activities versus those who were not active (OR = 0.91). Patients who participated in nocturnal outdoor activities and use LLINs while indoors had a slightly higher risk of submicroscopic infection than those who did not use LLINs (OR = 1.48). CONCLUSION: Microscopic inspection of blood smears from persons with malaria symptoms for asexual stage P. falciparum should be supplemented by more sensitive diagnostic tests in order to reduce ongoing transmission of P. falciparum parasites to local mosquito vectors.

Diet quality in adults with cerebral palsy: a modifiable risk factor for cardiovascular disease prevention.

AIM: To assess diet quality and its relationship with cardiovascular health measures for adults with cerebral palsy (CP). METHOD: A convenience sample of 45 adults with CP (26 females, 19 males; mean age 35y 10mo [SD 14y 9mo]). were recruited for this cross-sectional study. Demographic, medical, and Gross Motor Function Classification System (GMFCS) information were obtained through in-person visits. Participants completed two 24-hour dietary recalls using the Automated Self-Administered 24-hour Dietary Assessment Tool. Specific macronutrient intake was compared to 2015 to 2020 US Department of Agriculture (USDA) guidelines. Other data included body mass index (BMI), waist-to-hip ratio (WHR), blood pressure, and hemoglobin A1c (HgA1c;n=43). RESULTS: Adults across GMFCS levels I to V were enrolled, 20 participants were in GMFCS levels IV or V. Mean calorie intake was 1777.91/day (SD 610.54), while sodium intake was 3261.75mg/day (SD 1484.92). Five participants met USDA vegetable and seven fruit guidelines. None met whole grain targets. Sixteen were overweight/obese by BMI. Sixteen participants without hypertension diagnoses had elevated blood pressure and nine had abnormal HgA1c without prediabetes/diabetes history. Percent calories from saturated fat was inversely associated with WHR in unadjusted and adjusted models (p=0.002 and p=0.003 respectively); all other dietary recommendations assessed (total calories, sodium, and sugar) were non-significant. Post hoc analyses were unchanged using 2020 to 2025 USDA guidelines. INTERPRETATION: Assessment of nutrient intake and diet quality is feasible and warrants further study in adults with CP, as USDA guidelines are largely unmet. What this paper adds Adults with cerebral palsy (CP) do not meet US Department of Agriculture dietary quality recommendations. Prediabetes and hypertension may be common, but unrecognized, in adults with CP. Screening for nutrient intake and diet quality should be performed to facilitate nutritional counseling.

Early Detection of Public Health Emergencies of International Concern through Undiagnosed Disease Reports in ProMED-Mail.

We conducted a retrospective analysis of all reports in ProMED-mail that were initially classified as undiagnosed diseases during 2007-2018. We identified 371 cases reported in ProMED-mail; 34% were later diagnosed. ProMED-mail could be used to supplement other undiagnosed disease surveillance systems worldwide.

Long-term Consequences of Undiagnosed Celiac Seropositivity.

INTRODUCTION: Diagnosed celiac disease (CD) is associated with lymphoproliferative malignancy and gastrointestinal cancer, but little is known about the long-term consequences of undiagnosed CD. We aimed to investigate long-term consequences of undiagnosed CD for mortality and incidence of cancer and other chronic diseases. METHODS: We screened biobank serum samples for immunoglobulin (Ig) A and IgG tissue transglutaminase (TTG) and IgG deamidated gliadin peptide in a study of 8 population-based cohort studies comprising 16,776 participants examined during 1976-2012 and followed with >99% complete follow-up in Danish nationwide registries until December 31, 2017, regarding vital status and incidence of diseases. Undiagnosed CD was defined as antibody positivity (IgA-TTG or IgG-TTG ≥ 7 U/mL and/or IgG deamidated gliadin peptide ≥ 10 U/mL) in individuals without a diagnosis of CD recorded in the National Patient Register. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox regression analyses with age as the underlying time scale. RESULTS: The prevalence of undiagnosed CD was 1.0% with no statistically significant increase over time. Undiagnosed CD was associated with increased risk of cancer overall (HR, 1.57; 95% CI, 1.16-2.11), gastrointestinal cancer (HR, 2.33; 95% CI, 1.35-4.04), cancer of the uterus (HR, 3.95; 95% CI, 1.46-10.69), breast cancer (HR, 1.98; 95% CI, 1.02-3.82), head and neck cancer (HR, 3.12; 95% CI, 1.15-8.43), and cardiovascular disease (HR, 1.37; 95% CI, 1.01-1.85). We found no statistically significant association between undiagnosed CD and mortality (HR, 1.19; 95% CI, 0.87-1.61). DISCUSSION: Undiagnosed CD was associated with increased risk of cardiovascular disease and cancer suggesting that untreated CD has serious long-term health consequences not only affecting the gastrointestinal tract (see Visual Abstract, Supplementary Digital Content, http://links.lww.com/AJG/B566).

Consistent high prevalence of undiagnosed blood-borne virus infection in patients attending large urban emergency departments in England.

Understanding local viral hepatitis and HIV epidemiology is essential if WHO elimination targets are to be achieved. We demonstrate a consistently high prevalence of undiagnosed active infection in urban emergency department attendees in England, with variations in local risk groups crucial to informing targeted testing initiatives.

Thirteen-year trends in the prevalence of diabetes in an urban region of Switzerland: a population-based study.

AIM: To assess trends in prevalence of total and diagnosed diabetes, and in the probability of detecting undiagnosed diabetes in the Swiss population. METHODS: The Bus Santé study is an annual cross-sectional study of adults residing in Geneva state, Switzerland. We included 8532 participants (51% women) from the years 2005 to 2017, when fasting plasma glucose data became available. Total diabetes was defined as the sum of diagnosed and undiagnosed diabetes, while diagnosed diabetes was defined as having a previous diagnosis, and undiagnosed diabetes as having fasting plasma glucose level of ≥7 mmol/l and no previous diagnosis. We calculated the probability of finding undiagnosed diabetes among participants without a diagnosis. We examined for linear and quadratic trends, grouping survey years into five survey periods. RESULTS: In total, 711 diabetes cases were identified over 13 years. The age- and gender-standardized prevalence of total diabetes decreased between the periods 2005-2009 and 2012-2013 from 9.6% (95% CI 8.3, 10.9) to 7.1% (95% CI 5.8, 8.4), but increased to 8.6% (95% CI 7.3%, 9.9%) by 2016-2017 (P-quadratic <0.01). For diagnosed diabetes, the prevalence decreased between 2005-2009 and 2014-2015 from 8.3% (95% CI 7.0%, 9.5%) to 6.1% (95% CI 5.0%, 7.2%), but increased slightly again to 7.0% (95% CI 5.8%, 8.2%) by 2016-2017 (P-quadratic = 0.01). Men generally had a higher prevalence of total and diagnosed diabetes than women, except in 2016-2017, when the prevalence of total diabetes was 9.5% (95% CI 7.6, 11.5) among men and 7.7% (95% CI 6.0, 9.5) among women (P >0.05). The probability of finding undetected diabetes among participants without a diabetes diagnosis decreased slightly between 2005-2009 and 2012-2013 from 1.5% (95% CI 0.9, 2.0) to 1.0% (95% CI 0.5, 1.5), but increased afterwards to 1.7% (95% CI 1.0, 2.3) by 2016-2017 (P-quadratic = 0.06); in 2016-2017, it was 2.6% (95% CI 1.5, 3.7) among men and 0.7% (95% CI 0.1, 1.3) among women (P <0.01). CONCLUSION: The prevalence of diabetes has remained relatively constant over time. However, the probability of finding undetected cases of diabetes in the population without diabetes may be increasing among men.

Prevalence of diabetes and impaired fasting glucose in Poland in 2005-2014: results of the WOBASZ surveys.

AIMS: To evaluate the prevalence of diabetes and impaired fasting glucose in Poland in 2013-2014 and to determine the temporal trends between 2003-2005 and 2013-2014. METHODS: A questionnaire survey was conducted in a representative sample of Polish adults, complemented by anthropometric and fasting plasma glucose measurements. The research was part of the national cross-sectional WOBASZ study. Diabetes was assessed as self-reported or screened (fasting plasma glucose level ≥ 7 mmol/l, based on one blood sample). RESULTS: In the years 2013-2014 among 5694 participants aged 20-74 years, 6.0% (95% CI 5.4-6.6) reported a previous diagnosis of diabetes (5.8% in women and 6.2% in men). In addition, 2.4% of the participants (95% CI 2.0-2.8) without a previous diagnosis of diabetes (1.8% of women and 3.1% of men) had a fasting blood glucose level ≥7.0 mmol/l in a single measurement. In a single measurement, 18.4% of the participants (95% CI 17.4-19.4; 13.2% of women and 23.8% of men) had impaired fasting glucose. The prevalence of dysglycaemia in the WOBASZ II study was significantly higher compared to the WOBASZ I study findings from 2003-2005, increased from 6.6% to 8.4% for diabetes and from 9.3% to 18.4% for impaired fasting glucose (after age and sex standardization to the 2013 Polish population). CONCLUSIONS: The prevalence of diabetes in Poland is similar to that observed in other European populations and has increased significantly over the last decade.

Alternative type 2 diabetes screening tests may reduce the number of U.S. adults with undiagnosed diabetes.

AIM: To evaluate the U.S. population-level impact of two alternatives for initial type 2 diabetes screening [opportunistic random plasma glucose (RPG) > 6.7 mmol/l and a 1-h 50-g glucose challenge test (GCT) > 8.9 mmol/l] compared with American Diabetes Association (ADA)-recommended tests. METHODS: Using a sample (n = 1471) from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 that represented 145 million U.S. adults at high risk for developing type 2 diabetes, we simulated a two-test screening process. We compared ADA-recommended screening tests [fasting plasma glucose (FPG), 2-h 75-g oral glucose tolerance test (OGTT), HbA1c ] vs. initial screening with opportunistic RPG or GCT (followed by FPG, OGTT or HbA1c ). After simulation, participants were entered into an individual-level Monte Carlo-based Markov lifetime outcomes model. Primary outcomes were representative number of U.S. adults correctly identified with type 2 diabetes, societal lifetime costs and quality-adjusted life years (QALYs). RESULTS: In NHANES 2013-2014, 100 individuals had undiagnosed diabetes [weighted estimate: 8.4 million, standard error (se): 1.1 million]. Among ADA-recommended screening tests, FPG followed by OGTT (FPG-OGTT) was most sensitive, identifying 35 individuals with undiagnosed diabetes (weighted estimate: 3.2 million, se: 0.9 million). Four alternative screening strategies performed superior to FPG-OGTT, with RPG followed by OGTT being the most sensitive overall, identifying 72 individuals with undiagnosed diabetes (weighted estimate: 6.1 million, se: 1.0 million). There was no increase in average lifetime costs and comparable QALYs. CONCLUSIONS: Initial screening using opportunistic RPG or a GCT may identify more U.S. adults with type 2 diabetes without increasing societal costs.

Diabetes in the UK: 2019.

AIM: Diabetes impairs the quality of life of people living with the condition and is a major public health concern. The aim of this paper is to create a state of the nation report of diabetes in the UK. METHODS: Diabetes UK collates information about diabetes from diverse sources. This paper synthesizes these data to create a national report. RESULTS: Some 7% of the UK population are now living with diabetes; approximately one million people have undiagnosed type 2 diabetes, 40 000 children have diabetes and more than 3000 children are diagnosed every year. Forty-nine per cent of people with type 1 diabetes were offered structured education, but only 7.6% attended; the corresponding figures for type 2 diabetes were 90% and 10.4%, respectively. Among people with diabetes, 28% reported having issues obtaining medication or equipment for self-management. Fifty-seven per cent of people with type 1 diabetes and 42% with type 2 diabetes do not receive all eight annual health checks. Around 40% of people with diabetes have diminished psychological well-being. One-third of people have a microvascular complication at the time of diagnosis of type 2 diabetes. Diabetes is responsible for 530 myocardial infarctions and 175 amputations every week. The National Health Service spends at least £10 billion a year on diabetes, equivalent to 10% of its budget; 80% is spent treating complications. One in six hospital inpatients has diabetes. CONCLUSION: Diabetes continues to place a significant burden on the individual with diabetes and wider UK society. This report will be updated annually to understand how diabetes is changing across the UK.

Undiagnosed type 2 diabetes during pregnancy is associated with increased perinatal mortality: a large population-based cohort study in Ontario, Canada.

AIM: To compare perinatal outcomes in women with undiagnosed diabetes with gestational diabetes alone, pre-existing diabetes and women without diabetes, and to identify risk factors which distinguish them from women with gestational diabetes alone. METHODS: This population-based cohort study included administrative data on all women who gave birth in Ontario, Canada, during 2002-2015. Maternal/neonatal outcomes were compared across groups using logistic regression, adjusting for confounders. A nested case control study compared women with undiagnosed type 2 diabetes with women with gestational diabetes alone to determine risk factors that would help identify these women. RESULTS: Among 995 990 women, 68 163 had gestational diabetes (6.8%) and, of those women with gestational diabetes,1772 had undiagnosed type 2 diabetes (2.6%). Those with undiagnosed type 2 diabetes were more likely to be older, from a lower income area, have parity > 3 and BMI ≥ 30 kg/m2 compared with gestational diabetes alone. Infants had a higher risk of perinatal mortality (OR 2.3 [1.6-3.4]), preterm birth (OR 2.6 [2.3-2.9]), congenital anomalies (OR 2.1 [1.7-2.5]), neonatal intensive care unit admission (OR 3.1 [2.8-3.5]) and neonatal hypoglycaemia (OR 406.0 [357-461]), which were similar to women with pre-existing diabetes. The strongest predictive risk factors included early gestational diabetes diagnosis, previous gestational diabetes and chronic hypertension. CONCLUSIONS: Women diagnosed with gestational diabetes who develop diabetes within 1 year postpartum are at higher risk of adverse pregnancy outcomes, including perinatal mortality. This highlights the need for earlier diagnosis, preferably pre-pregnancy, and more aggressive treatment and surveillance of suspected type 2 diabetes during pregnancy.

Limitations of exome sequencing in detecting rare and undiagnosed diseases.

While exome sequencing (ES) is commonly the final diagnostic step in clinical genetics, it may miss diagnoses. To clarify the limitations of ES, we investigated the diagnostic yield of genetic tests beyond ES in our Undiagnosed Diseases Network (UDN) participants. We reviewed the yield of additional genetic testing including genome sequencing (GS), copy number variant (CNV), noncoding variant (NCV), repeat expansion (RE), or methylation testing in UDN cases with nondiagnostic ES results. Overall, 36/54 (67%) of total diagnoses were based on clinical findings and coding variants found by ES and 3/54 (6%) were based on clinical findings only. The remaining 15/54 (28%) required testing beyond ES. Of these, 7/15 (47%) had NCV, 6/15 (40%) CNV, and 2/15 (13%) had a RE or a DNA methylation disorder. Thus 18/54 (33%) of diagnoses were not solved exclusively by ES. Several methods were needed to detect and/or confirm the functional effects of the variants missed by ES, and in some cases by GS. These results indicate that tests to detect elusive variants should be considered after nondiagnostic preliminary steps. Further studies are needed to determine the cost-effectiveness of tests beyond ES that provide diagnoses and insights to possible treatment.