Association Between Incident Type 2 Diabetes and Opium Use: Mediation by Body Mass and Adiposity.

Opiates can affect glucose metabolism and obesity, but no large prospective study (to our knowledge) has investigated the association between long-term opium use, body mass index (BMI; weight (kg)/height (m)2), and incident type 2 diabetes mellitus (T2DM). We analyzed prospective data from 50,045 Golestan Cohort Study participants in Iran (enrollment: 2004-2008). After excluding participants with preexisting diseases, including diabetes, we used adjusted Poisson regression models to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for T2DM in opium users compared with nonusers, using mediation analysis to assess the BMI-mediated association of opium use with incident T2DM. Of 40,083 included participants (mean age = 51.4 (standard deviation, 8.8) years; 56% female), 16% were opium users (median duration of use, 10 (interquartile range), 4-20) years). During follow-up (until January 2020), 5,342 incident T2DM cases were recorded, including 8.5% of opium users and 14.2% of nonusers. Opium use was associated with an overall decrease in incident T2DM (IRR = 0.83, 95% CI: 0.75, 0.92), with a significant dose-response association. Most (84.3%) of this association was mediated by low BMI or waist circumference, and opium use did not have a direct association with incident T2DM (IRR = 0.97, 95% CI: 0.87, 1.08). Long-term opium use was associated with lower incidence of T2DM, which was mediated by low body mass and adiposity.

Opium use and risk of colorectal cancer: a multi-center case-referent study in Iran.

BACKGROUND: Opium use has been associated with an increased risk of cancers of the lung, oesophagus, and pancreas, and it was recently classified by the International Agency for Cancer Research as carcinogenic to humans. It is not clear whether opium also increases the risk of colorectal cancer (CRC). The aim of our study was to assess the association between various metrics of opium use and the risk of CRC. METHODS: This case-referent study from seven provinces in Iran comprised 848 CRC cases and 3215 referents. Data on opium use (duration, amount, frequency) and potential confounders were collected by trained interviewers. Multivariable unconditional logistic regression models were used to measure odds ratios (OR) adjusted for age, gender, province, marital status, family history of CRC-linked cancers, consumption of red meat, fruits and vegetables, body shape, occupational physical activity, and socioeconomic status. RESULTS: Regular opium consumption was not associated with the risk of CRC (OR 0.9, 95% confidence interval, CI: 0.7, 1.2) compared to subjects who never used opium. However, frequent opium use more than twice a day was associated with an increased risk of CRC compared to non-users of opium (OR: 2.0, 95% CI: 1.1, 3.8; p for quadratic trend 0.008). CONCLUSION: There seems to be no overall association between opium use and CRC, but the risk of CRC might be increased among persons who use opium many times a day.

Encephalopathy following ingestion of Lead-contaminated opium; magnetic resonance imaging findings.

BACKGROUND: Encephalopathy is an uncommon but serious presentation of lead toxicity. OBJECTIVE: We aimed to determine and follow-up the brain magnetic resonance imaging (MRI) abnormalities in the patients with lead encephalopathy due to ingestion of lead contaminated opium. METHODS: In a cross-sectional study during lead-contaminated opium outbreak, all lead-poisoned patients with any signs/symptoms of encephalopathy were included. RESULTS: Of 19 patients with lead encephalopathy, five died early and other five could not be sent to MRI during their hospitalization period. Mean age was 51 ± 11 years and males were dominant (89%). Median [IQR] blood lead level (BLL) was 101 [81, 108] µg/dL (range; 50 to 200 µg/dL). There was no correlation between MRI findings and signs/symptoms. MRI was normal in six and abnormal in three. Bilateral symmetric involvement of parieto-occipital lobes was observed. Gray matter, gray-white matter junction, and subcortical white matter were also affected. Follow-up MRI was performed in two with abnormal MRI which showed complete and near complete resolution of the abnormalities after cessation of opium use and treatment. CONCLUSION: There was no correlation between MRI findings and BLL. Complete recovery of brain MRI lesions was detected after cessation of opium use.

Evaluating the association between opium abuse, blood lead levels, and the complexity of coronary artery disease.

Opium abuse and exposure to heavy metals elevate the risk of coronary artery disease (CAD). Therefore, we aimed to determine the association between opium abuse and blood lead levels (BLLs) and the CAD complexity. We evaluated patients with acute coronary symptoms who underwent coronary angiography, and those with >50% stenosis in at least one of the coronary arteries were included. Furthermore, Synergy between PCI with Taxus and Cardiac Surgery I (SYNTAX I) score and BLLs were measured. Based on the opium abuse, 95 patients were subdivided into opium (45) and control (50) groups. Differences in demographics and CAD risk factors were insignificant between the two groups. The median BLLs were remarkably higher in the opium group than in controls (36 (35.7) and 20.5 µg/dL (11.45), respectively, p = 0.003). We also revealed no significant differences in SYNTAX score between the two groups (15.0 (9.0) and 17.5 (14.0), respectively, p = 0.28). Additionally, we found no significant correlation between BLLs and the SYNTAX scores (p = 0.277 and r = -0.113). Opium abuse was associated with high BLLs. Neither opium abuse nor high BLLs were correlated with the complexity of CAD. Further studies are warranted to establish better the relationship between opium abuse, BLLs, and CAD.

Opium Use and the Risk of Liver Cancer: A Case-Control Study.

Limited evidence is available to acknowledge the association between opium use and liver cancer. In a case-control study, we recruited 117 cases of primary liver cancer (PLC) and 234 age and sex-matched neighborhood controls from 2016 to 2018. We calculated odds ratios (OR) for opium use and 95% confidence intervals (95% CI), using conditional logistic regressions. Compared with non-users the adjusted OR (AOR, 95% CI) for opium use was 6.5 (95% CI, 2.87-13.44). Compared with people who had no history of use, a strong dose-response effect of opium use was observed by amount of use (AOR, 10.70; 95% CI, 3.92-28.70). Cumulative use of opium also indicated that using over 30 gr-year could increase the PLC risk dramatically (AOR, 11.0; 95% CI, 3.83-31.58). Those who used opium for more than 21 years were highly at risk of PLC (AOR, 11.66; 95% CI, 4.43-30.67). The observed associations were significant even among never tobacco smokers (including cigarette and water-pipe smoking). PREVENTION RELEVANCE: The results of this study indicate that opium use dramatically increased the risk of liver cancer. Because opioids are increasing for medical and non-medical use globally; accordingly, severe health consequences such as liver cancer have to be investigated widely.

Opium as a risk factor for early-onset coronary artery disease: Results from the Milano-Iran (MIran) study.

The spreading of opium use poses new health related concerns. In some areas of Asia its use is believed to protect from cardiovascular disorders, such as coronary artery disease (CAD). However, whether opium use has an association with CAD is unclear. We aimed to investigate the association between non-medical opium use and CAD. We set up a case-control analysis, i.e., the Milano-Iran (MIran) study by enrolling consecutive young patients who underwent a coronary angiography at the Tehran Heart Center, between 2004 and 2011. Incident cases with CAD were contrasted with controls for opium use. Relative risks were calculated in terms of odds ratios (ORs) by logistic regression models adjusted for age, sex, cigarette smoking, body mass index, hypertension, hyperlipidaemia, and diabetes. Interaction analyses were performed between opium and major cardiovascular risk factors. 1011 patients with CAD (mean age 43.6 years) and 2002 controls (mean age 54.3 years) were included in the study. Habitual opium users had a 3.8-fold increased risk of CAD (95%CI 2.4-6.2) compared with non-users. The association was strongest for men, with a fully adjusted OR of 5.5 (95%CI 3.0-9.9). No interaction was observed for the combination of opium addiction and hypertension, or diabetes, but an excess in risk was found in opium users with hyperlipidaemia (OR 16.8, 95%CI 8.9-31.7, expected OR 12.2), suggesting supra-additive interaction. In conclusion, despite common beliefs, we showed that non-medical opium use is associated with an increased risk of CAD, even when other cardiovascular risk factors are taken into account.

Interleukin-33 and Soluble ST2 as Potential Biomarkers of Cancer in Opium Users: A Nested Case-Control Study.

Background: Opium abuse is one of the social hazards in the Middle Eastern countries. Opium consumption attributes to various malignancies. However, the exact molecular mechanism of this correlation still remains unclear. Cancer and inflammation are closely correlated. Interleukin-33 (IL-33) and its receptors, transmembrane ST2 (ST2L) and soluble ST2 (sST2), have been significantly associated with tumorigenicity. The present study aimed to investigate whether IL-33 and sST2 levels serve as cancer biomarkers in opium users. Methods: Serum samples were collected from 100 opium users and 100 healthy non-opium users in a nested case-control design. The subjects with over five years of history of opium abuse were enrolled. To assess the incidence of malignancies, the opium users were followed up from 2014 to 2019. Serum levels of IL-33 and sST2 were measured using an ELISA kit. For comparison of IL-33 and sST2 levels between the groups, two-tailed Student's t test and Mann-Whitney U test were utilized, accordingly. Logistic regression analysis was performed to evaluate the influence of confounders on the incidence of cancer. Results: During the five-year follow-up, eight opium users were diagnosed with cancer. Cancer was developed by 9.3 folds in the individuals abusing opium compared to that in the non-opium users (P=0.040, OR=9.3; 95%CI [1.1-79.4]). Serum levels of IL-33 were found to be significantly higher in the opium users than those in the healthy control group (P=0.001). The sST2 levels were significantly lower in the opium users (P=0.001). The opium users with cancer exhibited significantly higher levels of IL-33 and lower levels of sST2 than the cancer-free ones (P=0.001). Conclusion: Decline in sST2 levels and rise in the level of IL-33 are valuable biomarkers in predicting cancers. Regarding the significant alterations in the levels of these biomarkers in the opium users, as well as those in the opium users diagnosed with cancer, IL-33 and sST2 may serve as potential biomarkers in the early prediction of cancer.

Does Opium Consumption Have Shared Impact on Atherosclerotic Cardiovascular Disease and Cancer?

Although atherosclerotic cardiovascular disease (ASCVD) and cancer are seemingly different types of disease, they have multiple shared underlying mechanisms and lifestyle-related risk factors like smoking, unhealthy diet, excessive alcohol consumption, and inadequate physical activity. Opium abuse is prevalent in developing countries, especially the Middle East region and many Asian countries. Besides recreational purposes, many people use opium based on a traditional belief that opium consumption may confer protection against heart attack and improve the control of the risk factors of ASCVD such as diabetes mellitus, hypertension, and dyslipidemia. However, scientific reports indicate an increased risk of ASCVD and poor control of ASCVD risk factors among opium abusers compared with nonusers. Moreover, there is accumulating evidence that opium consumption exerts potential carcinogenic effects and increases the risk of developing various types of cancer. We conducted a review of the literature to review the current evidence on the relationship between opium consumption and ASCVD as well as various kinds of cancer. In addition, we will discuss the potential shared pathophysiologic mechanisms underlying the association between opium abuse and both ASCVD and cancer.

Trends in the Prevalence and Incidence of Opium Abuse and its Association with Coronary Artery Risk Factors in Adult Population in Iran: Findings from Kerman Coronary Artery Disease Risk Factors Study.

Background: The prevalence of opium addiction in Iran is high probably due to the belief that opium has preventive effects against cardiovascular diseases. In the second phase of Kerman coronary artery disease risk factors study, the prevalence, incidence rate, and the association between opium use and other coronary artery disease risk factors (CADRFs) were assessed. Methods: In a cross-sectional study (2014-2018), 9996 inhabitants of Kerman, southeastern Iran, aged 15-80 years were recruited to the study. After taking fasting blood samples, the participants were examined or interviewed for demographic data and CADRFs, including opium use. The participants were categorized into "never", "occasional", and "dependent" users. The association between opium use and CADRFs was assessed with adjusted regression analysis (Stata v.11 software). Results: The overall prevalence of opium consumption was lower than that of five years earlier (P<0.01). The prevalence was currently higher in men than women and decreased in men between the two phases (P<0.001). There was a positive correlation between opium use and depression (P<0.001), anxiety (P<0.05), and a negative association with the level of physical activity (P<0.001). The five-year incident rate of dependent and occasional opium use was 4.2 and 3.9 persons/100 person-years, respectively. The incidence of opium use was higher in diabetic, hypertensive, depressed, anxious, and obese subjects. Conclusion: The study did not demonstrate any protective effects of opium on CADRFs. Considering the higher rate of opium use in subjects with hypertension, diabetes, obesity, and psychological disorders, the health authorities should implement educational programs to warn and correct the unsafe belief.

A Rapid Mercury Droplet Electrode Polarography Method for Determination of Blood Lead Level in Lead Poisoned People.

BACKGROUND: Lead is a hazardous heavy metal, which causes many problems in the human body. Unfortunately, recent reports showed that smugglers and opium sellers add lead to drugs during the production procedure in order to increase its weight and cost. PURPOSE: The aim of this study was development of a rapid and accurate method for measurement of blood lead levels (BLL) in the oral and inhaled opiate abuser people. METHODS: BLL in samples obtained from the oral and inhaled opium addicted patients referring to Sina Hospital in Tabriz, Iran, during 2017 was compared with healthy control group (N=15). The wet digestion method was used to prepare whole blood and Mercury Droplet Electrode Polarography (MDEP) method was utilized for measurement of the lead content of digested samples. RESULTS: Results showed that there were significant differences between the BLL of samples obtained from oral (17.12±74.61 µg/dL, p<0.0003) and inhaled (19.33±2.257 µg/dL, p<0.0001) opium addicted groups in comparison with healthy control group (4.669±0.3367 µg/dL). CONCLUSION: Based on the results of this study it was observed that BLL in opium addicted people needs to be measured as soon as possible. Furthermore, screening of blood lead concentrations in opium-addicted people with a rapid and accurate MDEP method is very necessary and important.

The marginal causal effect of opium consumption on the upper gastrointestinal cancer death using parametric g-formula: An analysis of 49,946 cases in the Golestan Cohort Study, Iran.

Upper gastrointestinal (UGI) cancer, including esophageal and gastric, is one of the most common cancers in the world. Hence, the determination of risk factors of UGI helps to reduce the economic and social burden of this cancer in communities. In Iran, the consumption of opium because of its neighborhood with Afghanistan are considerable. In this study, we examine the causal effect of opium use on the time to UGI cancer death. Based on the Golestan Cohort Study (GCS) in northeastern of Iran, about 50000 adults were enrolled to the study for four years (2004-2008) and followed annually until July 2018. We used "parametric g-formula" to study the causal effect of opium use on the time to death due to UGI. In this study, the information of 49946 individuals due to missingness were analyzed. So the median of follow-up time was 144 months and the prevalence of opium use was 17% (about 8489 persons). During the follow-up period, 593 (1.2%) death from upper gastrointestinal cancer were reported. The study showed that the effect of opium use on the time to UGI death was statistically significant (adjusted risk-ratio based on parametric g-formula = 1.31, 95% CI: [1.04, 1.65]). Additionally, the Population Attributable Fraction (PAF) in UGI cancer deaths of opium use was estimated 5.3% (95% CI: [0.6%, 11.3%]). Our results showed a causal effect of opium use on the intensity of upper gastrointestinal cancer death.

Smoking Water-Pipe, Opium Use and Prevalence of Heart Disease: A Cross-sectional Analysis of Baseline Data from the Pars Cohort Study, Southern Iran.

BACKGROUND: Associations between hookah and opium use and an increased risk of ischemic heart disease (IHD) have been suggested in a few studies, but more research is needed on the nature of these associations. We aimed to investigate the association between hookah and opium use and the prevalence of IHD in a population with relatively high prevalence of these exposures in Iran. METHODS: Using baseline data from the Pars Cohort Study (PCS), a prospective study of individuals aged 40-75 years in Fars province, southern Iran, we calculated adjusted and crude odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the independent association of hookah and opium use with prevalence of IHD. RESULTS: Of 9248 participants, 10.2% (95% CI: 9.5, 10.9) had self-reported IHD. Prevalence of ever use of hookah and opium was 48.9% (95% CI: 44.6, 53.6) and 10.2% (95% CI: 8.3, 12.5) among those with IHD, and 37.0% (95% CI: 35.7, 38.3) and 8.1% (95% CI: 7.5, 8.7) among those without IHD, respectively. Adjusted OR for the association with prevalence of IHD was 1.26 (95% CI: 1.08, 1.46) for hookah use and 1.71 (95% CI: 1.30, 2.24) for opium abuse. No dose-response association was found between hookah and prevalence of IHD. CONCLUSION: Hookah and opium abuse were associated with prevalent IHD in this study. Although more research is needed on these associations, particularly in prospective settings, reducing hookah and opium use could potentially reduce IHD risk.

Lead Toxicity due to Ingestion of Lead-Contaminated Opium in a Patient Presenting with Motor Neuropathy and Upper Limb Paresis: A case report.

Opium users may present with central or peripheral nervous system-related symptoms, gastrointestinal complications and anaemia; in such cases, lead poisoning should be suspected and chelation therapy initiated as soon as possible. We report a 64-year-old male patient with a 20-year history of opium addiction who was referred to the Imam Reza Hospital, Birjand, Iran, in 2017 with severe motor neuropathy and paresis in both upper limbs. His primary symptoms were generalised weakness, abdominal and bone pain, constipation and lower limb paraesthesia that had started several months prior. In addition, he reported severe progressive bilateral paresis of the upper limbs of one month's duration. A diagnosis of lead poisoning was confirmed by a blood lead level of 140 µg/dL. The patient underwent chelation therapy after which he improved significantly. At a one-year follow-up visit, he was neurologically intact and symptom-free.