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Background: There are two primary phenotypic models of comorbidity between post-traumatic stress disorder (PTSD) and drug use disorder (DUD), i.e. self-medication (PTSD precedes and causes DUD) and susceptibility (DUD precedes and causes PTSD). We sought to clarify the longitudinal relationship between PTSD and DUD, while examining sex differences.Method: We used approximately 23 years of longitudinal data from Swedish population registries to conduct two complementary statistical models: Cox proportional hazard models (N ≈ 1.5 million) and a cross-lagged panel model (N ≈ 3.8 million).Results: Cox proportional hazards models, adjusting for cohort and socioeconomic status, found strong evidence for the self-medication hypothesis, as PTSD predicted increased risk for DUD among both women [hazard ratio (HR) = 5.34, 95% confidence interval (CI) 5.18, 5.51] and men (HR = 3.65, 95% CI 3.54, 3.77), and moreover, that the PTSD to DUD association was significantly higher among women (interaction term 0.68, 95% CI 0.65, 0.71). The results of the susceptibility model were significant, but not as strong as the self-medication model. DUD predicted risk for PTSD among both women (HR = 2.43, 95% CI 2.38, 2.50) and men (HR = 2.55, 95% CI 2.50, 2.60), and HR was significantly higher in men (interaction term 1.05, 95% CI 1.02, 1.08). Investigating the pathways simultaneously in the cross-lagged model yielded support for both pathways of risk. The cross-paths instantiating the susceptibility model (0.10-0.22 in females, 0.12-0.19 in males) were mostly larger than those capturing the self-medication model (0.01-0.16 in females, 0.04-0.22 in males).Conclusions: We demonstrate that the relationship between PTSD and DUD is bidirectional, with evidence that future research should prioritize examining specific pathways of risk that may differ between men and women.

Post-traumatic stress disorder (PTSD) and drug use disorder (DUD) are highly comorbid, and few large population-based longitudinal studies have been conducted to better understand why these disorders co-occur at a rate far greater than chance.We used approximately 23 years of longitudinal data from the Swedish National Registries, in a sample of over 1.5 million people, to look at the prospective relationships between PTSD and DUD, and vice versa.We found evidence for bidirectional risk such that having one disorder increased the future risk for the other disorder, although the effect sizes were higher for PTSD's risk on future DUD, and some patterns differed by sex.

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BACKGROUND: To provide estimates of the nationwide prevalence of type 1 diabetes (T1D) and type 2 diabetes (T2D) in individuals younger than 20 years of age in Germany from 2002 to 2020 and to identify trends. METHODS: Data were obtained from the electronic health record "Diabetes Prospective Follow-up Registry (DPV)" specific to diabetes care. Prevalence was estimated based on prevalent cases at the end of each year for the years 2002, 2008, 2014, and 2020 per 100 000 persons assuming a Poisson distribution and directly age- and/or sex-standardized to the population in 2020. Individuals younger than 20 years of age with a clinical diagnosis of T1D or 10-19-year-olds with T2D were eligible for inclusion in the study. RESULTS: The standardized T1D prevalence per 100 000 persons was 138.9 (95% CI: 137.1; 140.6) in 2002 and 245.6 (243.1; 248.0) in 2020. The standardized T2D prevalence per 100 000 persons was 3.4 (3.1; 3.8) in 2002 and 10.8 (10.1; 11.5) in 2020. The annual percent change (APC) in prevalence declined over the three periods 2002-2008/2008-2014/2014-2020 (T1D: 6.3% [3.6%; 9.0%]/3.1% [0.7%; 5.5%]/0.5% [-1.7%; 2.85], T2D: 12.3% [5.3%; 20.8%]/4.7% [-0.6%; 10.3%]/3.0% [-1.8%; 8.0%]). From 2014 to 2020, the highest APCs were observed among 15-19-year-olds (T1D: 2.5% [1.3%; 3.6%], T2D: 3.4% [-0.5%; 7.5%]). CONCLUSIONS: The increase in diabetes prevalence has slowed, but medical care should be prepared for an increase in adolescents with diabetes.

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BACKGROUND: The study aimed to explore the associations of nonalcoholic fatty liver disease (NAFLD) with the remission and progression along the glycemic continuum. METHODS: This prospective cohort study was performed among the general population in 2010-2015. NAFLD was defined as ultrasound-detected hepatic steatosis with absence of excessive alcohol consumption and other hepatic diseases. Remission of type 2 diabetes referred to glycated hemoglobin <6.5% without hypoglycemic agents for ≥3 months. Prediabetes remission referred to normalization of blood glucose. Multivariable logistic analysis was applied to identify the risk of glycemic metabolic transition. RESULTS: During a median follow-up of 4.3 years, participants with NAFLD had a significantly higher risk of progressing from normal glucose tolerance to diabetes (3.36 [1.60-7.07]) and lower likelihood of diabetes remission (0.48 [0.30-0.78]). Associations in participants with overweight or obesity and higher probability of hepatic fibrosis remained consistent. Results related to the effect of NAFLD on the specific glucose parameters were generally in line with the changes of glycemic status. NAFLD improvement decreased the risk of prediabetes progressing to diabetes (0.50 [0.32-0.80]) and increased the probability of prediabetes remission (2.67 [1.49-4.79]). NAFLD tended to show the most significant association with glycemic progression and decreased the likelihood in remission of prediabetes and diabetes. CONCLUSIONS: Presence of NAFLD increased risk of glycemic progression and decreased likelihood of remission. NAFLD improvement mitigated glycemic deterioration, whereas NAFLD progression impeded the chance of remission. The results emphasized joint management of NAFLD and diabetes and further focused on liver-specific subgroups of diabetes to tailor early intervention.

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INTRODUCTION: In patients with peripheral artery disease (PAD) the presence of diabetes mellitus (DM) is associated with higher morbidity and mortality. Because huge efforts are made to improve medical care of patients with DM including chronic disease programs, the aim of the present study was to investigate temporal trends regarding the clinical burden of DM on PAD patients within a 15-year observational period. METHODS: We analyzed all patients hospitalized because of PAD between 2005 and 2019 in Germany stratified regarding DM. RESULTS: Overall, 2 654 871 hospitalizations of PAD patients (865 823 with DM) were included. Hospitalizations based on PAD inclined from 142 778 in 2005 to 190 135 in 2019 (ß 3956 per year; 95% confidence interval [CI] 3034-4878, p < .001) with simultaneous increase of hospitalizations of PAD patients with DM (2005: 41609 (29.1%) versus 2019: 65 302 (34.3%); ß 2019 per year [95% CI 1593-2446], p < .001). Amputation rates (ß -0.42 [95% CI -0.44 to -0.40]; p < .001) as well as in-hospital case-fatality rate (2005: 4.7%, 2019: 2.8%; ß -0.64 [95% CI -0.69 to -0.59]; p < .001) decreased in diabetic PAD patients during the observational time. In spite of improved morbidity and mortality in the last years of the observational period, patients with DM still suffered from an increased risk for morbidity and mortality during the observational period compared to nondiabetic PAD patients. CONCLUSIONS: Despite the progress in DM treatments, DM still was associated with an unfavorable clinical patient profile and remained a substantial risk factor for morbidity and mortality in hospitalized patients with PAD and DM in Germany between 2005 and 2019.

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BACKGROUND: The evidence for the association between metabolic score for insulin resistance (METS-IR) and type 2 diabetes mellitus (T2DM) is limited. We aimed to explore the association of METS-IR and its 6-year change with risk of incident T2DM in a rural Chinese population. METHODS: We analyzed data for 12 107 participants (mean age 50.48 years). A Cox proportional-hazard model was used to estimate the association of METS-IR with incident T2DM by using hazard ratios (HRs) and 95% confidence intervals (CIs); a logistic regression model was used to assess the association of 6-year METS-IR change with incident T2DM by using odds ratios (ORs) and 95% CIs. We used subgroup analyses of the association of METS-IR and its 6-year change with incident T2DM by sex, age, and baseline fasting plasma glucose (FPG) level as well as restricted cubic splines to describe the dose-response association. RESULTS: The association of METS-IR and 6-year METS-IR change with incident T2DM was significant (per SD unit increase: HR = 1.80, 95% CI: 1.60-2.02 for METS-IR, OR = 1.42, 95% CI: 1.28-1.57 and OR = 1.59, 95% CI: 1.44-1.76 for relative and absolute METS-IR change). The significant association remained on subgroup analyses by sex, age, and baseline FPG level. Dose-response analysis demonstrated that the probability of incident T2DM was significantly increased with increasing METS-IR and 6-year METS-IR change. CONCLUSIONS: Increased METS-IR and 6-year METS-IR change were positively associated with risk of incident T2DM in a rural Chinese population. METS-IR may be a vital indicator for identifying T2DM.

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BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset neurodevelopmental disorder that usually persists into adulthood. However, limited evidence is available regarding its influence on adult health outcomes beyond neuropsychiatric comorbidities. This study aimed to examine the association of ADHD with diabetes in US adults. METHODS: We analyzed data from the National Health Interview Survey (NHIS), a leading health survey of a nationally representative sample in the United States. We included adults aged 20-79 years who participated in the NHIS 2007 and 2012. Physician-diagnosed ADHD and diabetes were reported during an in-person household interview. Logistic regression with survey sampling weights was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of diabetes. RESULTS: This analysis included 52 821 adults (weighted mean age 45.5 years; 48.6% males). Among them, 1642 participants reported a diagnosis of ADHD and 4631 reported a diagnosis of diabetes. In the multivariable analysis adjusting for age, sex, race/ethnicity, education level, family income level, smoking, alcohol drinking, physical activity, and body mass index, the OR of diabetes among adults with ADHD vs those without ADHD was 1.54 (95% CI, 1.16-2.04). In the stratified analyses, the significant association of ADHD with diabetes remained in most strata, and the associations were not significantly modified by age, sex, race/ethnicity, or obesity status. CONCLUSIONS: In a nationally representative sample of US adults, we found a significant association between a history of ADHD diagnosis and diabetes.

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BACKGROUND: The relationship between alcohol intake and end-stage kidney disease (ESKD) risk is controversial. Moreover, while evidence has shown that the relationship between alcohol and atherosclerosis may be modified by diabetes, whether this applies to ESKD is unknown. METHODS: We examined these associations in the Singapore Chinese Health Study, a prospective cohort of 63 257 adults aged 45 to 74 years. Information on alcohol intake, diet, lifestyle factors, and medical history was collected at recruitment. We identified 1217 ESKD cases via linkage with the Singapore Renal Registry after a mean follow-up of 17.5 years. Cox regression models were used to estimate hazard ratios (HRs) and 95% CI of ESKD. RESULTS: Among the participants without diabetes at baseline, monthly to weekly drinking was associated with a decreased risk of ESKD (HR 0.69; 95% CI, 0.54-0.87) compared to nondrinkers. In contrast, this association was attenuated and not significant among those with diabetes (HR 0.82; 95% CI, 0.58-1.16; Pinteraction = .19). Comparatively, alcohol intake of ≥2 drinks per day was significantly associated with an increased risk of ESKD compared to nondrinkers among those with diabetes (HR 2.00; 95% CI, 1.14-3.53) but not among those without diabetes (HR 0.91; 95% CI, 0.53-1.56; Pinteraction = .01). The risk of ESKD among those with diabetes and who also consumed ≥2 drinks per day was increased by nearly 12-fold compared to nondrinkers without diabetes (HR 11.6; 95% CI, 6.73-19.9). CONCLUSION: Low-dose drinking is associated with a reduced risk of ESKD among individuals without diabetes. However, joint exposure to heavy drinking and diabetes is associated with a substantially higher risk of ESKD.

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BACKGROUND: Patients with type 1 diabetes (T1D) are at risk for other autoimmune diseases (ie, polyautoimmunity). The prevalence and risk factors of this phenomenon have been underreported in adults and ethnic minorities, and data are lacking regarding non-endocrine autoimmune diseases. METHODS: Study population data were gathered from HealthFacts, a deidentified patient database compiled from electronic medical records systems in the US. Patients with an International Classification of Diseases diagnosis code specifying T1D were included in the study, whereas those with a diagnosis of type 2 diabetes were excluded. RESULTS: The cross-sectional study cohort comprised 158 865 adults with T1D (mean [±SD] age 51.4 ± 18.9 years, 52.5% female). The most common autoimmune diseases were thyroid disease (20.1%), systemic rheumatic diseases (3.4%), rheumatoid arthritis specifically (2.0%), and gastrointestinal autoimmune diseases (1.4%). Most of the autoimmune diseases were more common in women (eg hypothyroidism, hyperthyroidism, celiac disease, rheumatoid arthritis, lupus, and Sjögren syndrome). Caucasians were more likely than other ethnicities to have an additional autoimmune disease. The prevalence of autoimmune diseases increased with increasing age, significantly in women, such that 38.5% of women over 80 years of age had an additional autoimmune disease, compared with 17.9% of women aged ≤29 years. CONCLUSIONS: Additional autoimmunity represents a significant comorbidity in patients with T1D. Autoimmune diseases are more common in Caucasians and in women, and increase with age. Clinicians treating patients with T1D should be aware of the risk factors for additional autoimmune diseases.

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BACKGROUND: The relationship of cotinine-verified vs self-reported smoking status with the incidence of metabolic syndrome (MetS) is not known. This study investigated the effect of urinary cotinine-verified vs self-reported smoking status on incident MetS. METHODS: In all, 47 379 participants without MetS enrolled in the Kangbuk Samsung Health Study and Kangbuk Samsung Cohort Study between 2011 and 2012 (baseline) were included in this study and followed-up in 2014; median follow-up duration was 25 months. Cotinine-verified current smoking was defined as urinary cotinine concentrations >50 ng/mL. According to cotinine-verified smoking status at baseline and follow-up, individuals were divided into four groups: never, new, former, and sustained smokers. RESULTS: The incidence of MetS in the never, former, new, and sustained smoking groups was 9.9%, 19.4%, 21.4%, and 18.7%, respectively. Multivariate Cox hazard regression analyses revealed that the relative risk (RR) for incident MetS in cotinine-verified former smokers was significantly increased compared with that in cotinine-verified never smokers (RR 1.27; 95% confidence interval [CI] 1.16-1.37), especially in individuals exhibiting weight gain (≥2 kg). These results were consistent with those of self-reported smoking status. Baseline cotinine-verified current smoking (RR 1.09; 95% CI 1.03-1.15) and self-reported former (RR 1.10; 95% CI 1.02-1.18) and current (RR 1.15; 95% CI 1.07-1.23) smoking were also significantly associated with incident MetS. CONCLUSIONS: This large observational study showed that cotinine-verified and self-reported former smoking during follow-up increased the risk for incident MetS, especially in individuals exhibiting weight gain (≥2 kg). This suggests that weight control in former smokers would be very important to reduce the development of MetS.

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BACKGROUND: Animal studies indicate that chronic exposure to certain tin compounds induces pancreatic islet cell apoptosis and glucose intolerance. However, little is known about the health effects of environmental tin exposure in humans. Therefore, we evaluated the association of tin exposure with diabetes in a nationally representative sample of US adults. METHODS: We used data from a nationally representative population (n = 3371) in the National Health and Nutrition Examination Survey 2011-14. Diabetes (n = 605) was defined as self-reported physician's diagnosis, HbA1c ≥6.5%, fasting plasma glucose ≥126 mg/dL, or 2-h plasma glucose ≥200 mg/dL. Tin concentrations in urine samples were determined by inductively coupled plasma mass spectrometry. Logistic regression with sample weights was used to estimate the odds ratios (ORs) of diabetes and 95% confidence intervals (CIs). RESULTS: Urinary tin concentrations were higher in individuals with diabetes (weighted median 0.58 µg/L) than those without diabetes (0.39 µg/L). After adjustment for urinary creatinine and other diabetes risk factors, the OR of diabetes comparing the highest with lowest quartile of urinary tin concentrations was 1.6 (95% CI 1.0-2.6; Ptrend = 0.02). CONCLUSIONS: Environmental tin exposure was positively and significantly associated with diabetes in US adults.

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BACKGROUND: In people with chronic kidney disease (CKD), HbA1c may be a problematic measure of glycemic control. Glycated albumin and fructosamine have been proposed as better markers of hyperglycemia in CKD. In the present study we investigated associations of HbA1c, glycated albumin, and fructosamine with fasting glucose by CKD categories. METHODS: A cross-sectional analysis was performed of 1665 Atherosclerosis Risk in Communities Study participants with diagnosed diabetes aged ≥65 years. Spearman's rank correlations (r) were compared and Deming regression was used to obtain root mean square errors (RMSEs) for the associations across CKD categories defined using estimated glomerular filtration rate and urine albumin:creatinine ratio. RESULTS: Correlations of HbA1c, glycated albumin, and fructosamine with fasting glucose were lowest in people with severe CKD (HbA1c r = 0.52, RMSE = 0.91; glycated albumin r = 0.39, RMSE = 1.89; fructosamine r = 0.41, RMSE = 1.87) and very severe CKD (r = 0.48 and RMSE = 1.01 for HbA1c; r = 0.36 and RMSE = 2.14 for glycated albumin; r = 0.36 and RMSE = 2.22 for fructosamine). Associations of glycated albumin and fructosamine with HbA1c were relatively similar across CKD categories. CONCLUSIONS: In older adults with severe or very severe CKD, HbA1c, glycated albumin, and fructosamine were not highly correlated with fasting glucose. The results suggest there may be no particular advantage of glycated albumin or fructosamine over HbA1c for monitoring glycemic control in CKD.

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BACKGROUND: The aim of the present study was to determine the prevalence of metabolic syndrome and its individual components among the Iranian adult population in 2011 and to investigate changes between 2007 and 2011. METHODS: Data from two rounds of the Surveillance of Risk Factors of Non-communicable Diseases national surveys conducted in 2007 and 2011 were pooled. Metabolic syndrome was defined according to International Diabetes Federation criteria. RESULTS: In 2007, the prevalence of metabolic syndrome among adults aged 25-64 years was 35.95 (95% confidence interval [CI] 34.27-37.63), which decreased to 32.96 (95% CI 30.73-35.18) in 2011 (P = 0.0108). Despite this overall decline, the prevalence of central obesity (P = 0.1383), raised triglycerides (P = 0.3058), and reduced high-density lipoprotein cholesterol (HDL-C; P = 0.5595) remained constant. There was a trend towards a decline in the proportion of individuals with increased blood pressure (P = 0.0978), and the proportion of adults with increased fasting plasma glucose (FPG) increased (P < 0.0001). In 2011, the prevalence of central obesity, raised triglycerides, reduced HDL-C, increased blood pressure and increased FPG was 51.88 (95% CI 48.97-54.79), 36.99 (95% CI 34.52-39.45), 54.72 (95% CI 50.87-58.57), 38.92 (95% CI 36.19-41.64), and 24.97 (95% CI 22.02-27.93) respectively. CONCLUSIONS: Over the period 2007-11, the prevalence of metabolic syndrome has decreased slightly in Iran, although prevalence of increased FPG has increased significantly. One-third of the Iranian adult population is diagnosed with metabolic syndrome.

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BACKGROUND: We assessed the prevalence and pregnancy outcomes of pre-existing diabetes mellitus (pre-DM) and gestational diabetes mellitus (GDM) in Alberta, Canada, 2005-11. METHODS: 327 198 singleton and 5552 twin pregnancies resulting in live births or stillbirths were included. The odds ratios of adverse outcomes were evaluated comparing pre-DM with no diabetes and GDM with no diabetes, controlling for maternal characteristics. RESULTS: Diabetes complicated 6.3% of pregnancies, with 88% being GDM. In singleton pregnancies, pre-DM and GDM were associated with increased risks of pre-eclampsia (adjusted odds ratio [aOR] = 3.38 and 1.83, respectively), cesarean delivery (aOR 2.53, 1.55), spontaneous preterm (aOR 4.20, 1.71), and labor-induced preterm (aOR 3.82, 2.00) in the mother, and macrosomia (aOR 2.11, 1.30), shoulder dystocia (aOR 1.54, 1.32), congenital anomalies (aOR 1.61, 1.20), and neonatal intensive care unit (NICU) admissions (aOR 3.81, 1.60) in the infants. In addition, pre-DM was associated with an increased likelihood of stillbirth (aOR 3.73) and neonatal death (aOR 2.00) compared with non-diabetic pregnancies. In twin pregnancies, pre-DM was associated with increased risks of spontaneous (aOR 3.54) and labor-induced (aOR 3.57) preterm births, large for gestational age (LGA) infants (aOR 3.73), congenital anomalies (aOR 3.05) and NICU admissions (aOR 2.91); GDM was associated with an increased risk of pre-eclampsia (aOR 1.54), cesarean delivery (aOR 1.57), and LGA infants (aOR 1.63). CONCLUSIONS: Pre-existing diabetes confers higher risks than GDM. Diabetes is associated with adverse outcomes in singleton and twin pregnancies, and the increased risks are generally similar or less in twins, probably due to their higher "baseline" risks and closer clinical monitoring.

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BACKGROUND: The PREDATORR (PREvalence of DiAbeTes mellitus, prediabetes, overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in Romania) study is the first national study analyzing the prevalence of diabetes mellitus (DM) and prediabetes, and their association with cardiometabolic, sociodemographic, and lifestyle risk factors in the Romanian population aged 20-79 years. METHODS: This was an epidemiological study with a stratified, cross-sectional, cluster random sampling design. Sociodemographic, lifestyle, and anamnestic data were collected through self- and interviewer-administered questionnaires, and biochemical assays and oral glucose tolerance tests were performed. RESULTS: In all, 2728 participants from 101 clinics of general practitioners were randomly selected, with a probability proportional to population size according to the 2002 Romanian Census. The participation rate was 99.6%. Impaired glucose regulation (prediabetes, known and unknown DM) was found in 28.1% of the study population. The overall age- and sex-adjusted prevalence of DM was 11.6% (95% CI 9.6%-13.6%), of which 2.4% (95% CI 1.7%-3.1%) had unknown DM. The prevalence of DM increased with age and was higher in men than in women. The age- and sex-adjusted prevalence of prediabetes was 16.5% (95%CI 14.8%-18.2%), with the highest percentage in the 60-79 year age group and in women. Obesity, abdominal obesity, dyslipidemia, low education level, and a family history of diabetes were associated with glucose metabolism disorders. CONCLUSIONS: The PREDATORR study shows a high prevalence of impaired glucose regulation in the adult Romanian population, providing data on the prevalence of DM and prediabetes and their association with several risk factors.

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BACKGROUND: A lack of demographic and clinical data hinders efforts of health care providers in China to support patients with type 1 diabetes mellitus (T1D). Therefore, the aim of the present retrospective study was to provide an overview of the demographic and clinical characteristics of Chinese patients with T1D. METHODS: Hospital medical records of patients with T1D (diagnosed between January 2000 and December 2011) in 105 secondary and tertiary hospitals across Guangdong province were reviewed. Data were collected on patient age at diagnosis, presentations at onset, physical examination, and diabetes management. RESULTS: In all, 3173 patients diagnosed with T1D between January 2000 and December 2011 were included in the study (46.2% female). The median age at diagnosis was 27.5 years (interquartile range [IQR] 18.0-38.0) years and the median body mass index (BMI) at onset was 19.6 kg/m2 (IQR 17.4-21.8 kg/m2 ). Among adult patients, 0.9% were obese, 6.6% were overweight, 62.3% were normal weight, and 30.3 % were underweight. The prevalence of diabetic ketoacidosis (DKA) at onset was 50.1%. The proportion of patients with retinopathy, nephropathy, and neuropathy was 8.1%, 20.7 %, and 11.1%, respectively. CONCLUSION: The adult-onset form of T1D is not rare in China. The registry participants were characterized by older age at onset, lower BMI, and a higher prevalence of DKA at onset compared with those in regions with a high incidence of T1D, such as northern Europe. These findings contribute to a better understanding of the heterogeneity of T1D in different populations and so will help healthcare providers to develop management models that are more suitable for these patients.

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