Smokeless and combustible tobacco use among 148,944 South Asian adults: a cross-sectional study of South Asia Biobank.

INTRODUCTION: Tobacco use, in both smoking and smokeless forms, is highly prevalent among South Asian adults. The aims of the study were twofold: (1) describe patterns of SLT and combustible tobacco product use in four South Asian countries stratified by country and sex, and (2) assess the relationships between SLT and smoking intensity, smoking quit attempts, and smoking cessation among South Asian men. METHODS: Data were obtained from South Asia Biobank Study, collected between 2018 and 2022 from 148,944 men and women aged 18 years and above, living in Bangladesh, India, Pakistan, or Sri Lanka. Mixed effects multivariable logistic and linear regression were used to quantify the associations of SLT use with quit attempt, cessation, and intensity. RESULTS: Among the four South Asian countries, Bangladesh has the highest rates of current smoking (39.9% for male, 0.4% for female) and current SLT use (24.7% for male and 23.4% for female). Among male adults, ever SLT use was associated with a higher odds of smoking cessation in Bangladesh (OR, 2.88; 95% CI, 2.65, 3.13), India (OR, 2.02; 95% CI, 1.63, 2.50), and Sri Lanka (OR, 1.36; 95% CI, 1.14, 1.62). Ever SLT use and current SLT use was associated with lower smoking intensity in all countries. CONCLUSIONS: In this large population-based study of South Asian adults, rates of smoking and SLT use vary widely by country and gender. Men who use SLT products are more likely to abstain from smoking compared with those who do not.

Ferritin screening and Iron treatment for maternal anemia and fetal growth restriction prevention - A multicenter randomized controlled trial (FAIR Study).

Background: Non-anemic iron deficiency precedes iron deficiency anaemia and has an estimated prevalence of 1-2 billion worldwide. Few studies have comprehensively researched the idea of treating non-anemic iron deficiency (NAID) with iron to improve the outcome of the mother and the offspring. Methods and Analysis: FAIR will be a multicenter randomized controlled trial that will be conducted in multiple clinical academic obstetrics units in Lahore (including Services Institute of Medical Sciences, Lahore, Allama Iqbal Medical College, Lahore and Fatima Jinnah Medical University). Pregnant women at gestational age <20 weeks with hemoglobin 11-13 g/L and ferritin below the threshold (<30 ng/ml) will be invited to take part in the study. Randomization will be done by computer based generated random numbers. One group (usual care or oral group) will be offered routine care prophylactic dose of oral iron (30-45 mg/day) and the other group (intervention arm or IV group) will be offered therapeutic dose of IV iron (dose calculated by Ganzoni formula) in addition to usual care. All patients will be followed up till delivery. Primary maternal outcome will be hemoglobin at 36 weeks' gestation. Secondary outcomes are fetal birthweight or small for gestational age, preterm birth, preeclampsia, multidimensional fatigue inventory, breast feeding initiation, blood transfusion, and fetal cord ferritin and hemoglobin. Discussion: The study will generate evidence as to whether screening serum ferritin in non-anemic pregnant women and replenishing their iron stores will likely reduce the rate of predelivery anemia in pregnant women, improve birthweight and preventing perinatal complications. Roles and responsibilities: Tayyiba Wasim is principal Investigator and other members of data management team are Natasha Bushra, Shamsa Humayoun, Khalid Saeed Khan, Fatima Shehbaz, Saba Rasool, Anam Riaz and Sonia Irshad. Principal investigator will assume the full responsibility of Fair trial including training of research assistants, administration of informed consent and protecting participants confidentiality. Data management team will help in the management, development and execution of trial. Khadija Irfan Khawaja is the operational lead for fair trial´s technology team comprising of Aziz Fatima and Zubia Zafar, responsible for gathering requirements from study teams and supporting the operational implementation of technology to drive the collection of high-quality study data. Protocol contributors are Gynae unit I of Services Institute of Medical Sciences/ Services hospital, Lahore, Gynae Unit II of Allama Iqbal Medical College/ Jinnah hospital, Lahore and Gynae unit 1 of Fatima Jinnah Medical College/ Sir Ganga Ram hospital, Lahore. These coordinating centres will recruit patients (sample size=600) and will discuss their progress in trial management meetings quarterly. Steering committee: has an independent chair Prof Samia Malik, one expert member Prof Faiza Bashir and Ms Neelam to represent patients, public and consumers. Trial steering committee with independent chair and member with a patient representative will oversee the study. Chair of steering committee has the authority to stop the trial whenever needed in case of positive or negative results. Steering committee meetings will be held on annual basis. Independent Data monitoring committee: comprises of Dr. Shehnoor Azhar as chair and Prof Ejaz Hussain and Dr. Shehla Javed Akram as members. Data monitoring committee will assess the progress, data safety and if needed critical efficacy points of the clinical study and will show their results quarterly in data interim meetings. The committee will focus on integrity of the whole process and compliance of all sites with all aspects of the protocol. It will perform confidential interim analyses quarterly, which may be used to determine if an effect is observed and if the study should continue to its planned sample size. Data monitoring committee will report to the Chair of the steering committee.

Phenotypic and metabolic dichotomy in obesity: clinical, biochemical and immunological correlates of metabolically divergent obese phenotypes in healthy South Asian adults.

INTRODUCTION: Metabolic heterogeneity among obese individuals is thought to translate into variations in cardiovascular risk. Identifying obese people with an unfavourable metabolic profile may allow preventive strategies to be targeted at high-risk groups. This study aimed to identify clinical, biochemical and immunological differences between insulin-sensitive and insulin-resistant obese subgroups, to understand the population-specific pathophysiological basis of the adverse cardiovascular risk profile in the latter group. METHODS: Cardiovascular risk indicators, including anthropometric parameters, blood pressure, acanthosis nigricans area, and related biochemical, endocrine and inflammatory markers, were determined in 255 healthy South Asian volunteers aged 18-45 years, with a 2:1 ratio of obese/overweight to normal-weight individuals. Lifetime atherosclerotic cardiovascular disease (ASCVD) risk was also calculated. RESULTS: Body mass index (BMI) and insulin sensitivity-based tertiles independently showed incremental trends in waist-hip ratio, skinfold thickness, acanthosis nigricans area, blood pressure, serum lipids, hepatic enzymes, adipokines, inflammatory markers and ten-year ASCVD risk. The anthropometric, biochemical and inflammatory parameters of obese insulin-sensitive and obese insulin-resistant groups differed significantly. Extreme group analysis after excluding the middle tertiles of both insulin resistance and BMI also showed significant difference in anthropometric indicators of cardiovascular risk and estimated lifetime ASCVD risk between the two obese subgroups. CONCLUSION: Obese insulin-sensitive individuals had a favourable metabolic profile compared to the obese insulin-resistant group. The most consistent discriminative factor between these phenotypic classes was anthropometric parameters, which underscores the importance of clinical parameters as cardiovascular risk indicators in obesity.

Estimation of body fat in Pakistani adult: A comparison of equations based upon skinfold thickness measurements.

OBJECTIVE: To compare three different body fats estimation equations using skin fold measurements with bioelectrical impedance analysis. METHODS: A total of 130 subjects were included from Department of Endocrinology and Metabolism, Services Hospital, Lahore from 1st April 2016 to 30th Sep. 2016. The triceps, biceps, subscapular, chest, thigh, abdominal, suprailiac skinfold thickness of the subjects was measured with skin-fold calipers (Harpenden) on non-dominant side. The percentage fat mass (%FM) predicted by using each skin-fold-thickness equations namely Durnin & Womersley, Jackson & Pollock and Sloan was compared with %FM measured using a bioelectrical impedance analyzer (BIA). RESULTS: The mean age of subjects was 48.75±10.7 years, mean BMI was 29.08±6.09 kg/m2. The mean %FM calculated by Durnin & Womersley (32.408±0.584), Jackson & Pollock (24.658±0.527), Sloan (20.40±0.545). The %FM by BIA was 38.182±0.529. All three equations showed positive correlation but underestimated %FM as compared to BIA. CONCLUSION: All three BF estimation equations underestimate body fat percentage compared to BIA. Among the three, Durnin & Womersley equation shows best positive correlation and hence it can be used for estimation of percentage fat mass as an alternate to BIA.

Metformin and pancreatic cancer: Is there a role?

Pancreatic cancer is the fourth leading cause of cancer-related deaths in the USA, with a 5-year survival rate of 6 %. Anti-hyperglycemic treatments for type 2 diabetes mellitus that induce hyperinsulinemia (i.e., sulfonylureas) are thought to increase cancer risk, whereas treatments that lower insulin resistance and hyperinsulinemia (i.e., metformin) are considered cancer prevention strategies. Metformin is a cornerstone in the treatment of diabetes mellitus type 2. Retrospective studies have shown a survival benefit in diabetic patients with many solid tumors including pancreatic cancer that have been treated with metformin compared with patients treated with insulin or sulfonylureas. Metformin influences various cellular pathways, including activation of the LKB1/AMPK pathway, inhibition of cell division, promotion of apoptosis and autophagy, down-regulation of circulating insulin, and activation of the immune system. Ongoing research is redefining our understanding about how metformin modulates the molecular pathways implicated in pancreatic cancer. The authors review the topic critically and also give their opinion. Further studies investigating the effect of metformin in combination with chemotherapy, targeted agents, or radiation therapy are undergoing. In addition, the role of metabolic and other biomarkers is needed.

PERFORMANCE OF TWO DIFFERENT CLINICAL SCORING SYSTEMS IN DIAGNOSING DISTAL SENSORY POLYNEUROPATHY IN PATIENTS WITH TYPE-2 DIABETES.

BACKGROUND: Early diagnosis of distal peripheral neuropathy (DSPN) the commonest diabetes complications, helps prevent significant morbidity. Clinical parameters are useful for detection, but subjectivity and lack of operator proficiency often results in inaccuracies. Comparative diagnostic accuracy of Diabetic Neuropathy Symptom (DNS) score and Diabetic Neuropathy Examination (DNE) score in detecting DSPN confirmed by nerve conduction studies (NCS) has not been evaluated. This study compares the performance of these scores in predicting the presence of electro physiologically proven DSPN. The objective of this, study was to compare the diagnostic accuracy of DNS and DNE scores in detecting NCS proven DSPN in type-2 diabetics, and to determine the frequency of sub-clinical DSPN among type-2 diabetics. METHODS: In this cross-sectional study the DNS score and DNE score were determined in 110 diagnosed type-2 diabetic patients. NCS were carried out and amplitudes, velocities and latencies of sensory and motor nerves in lower limb were recorded. RESULTS: Comparison between the two clinical diagnostic modalities and NCS using Pearson's chi square test showed a significant association between NCS and DNE scores (p-value =.003, specificity 93%). The DNS score performed poorly in comparison (p-value = .068, specificity 77%). When the two scores were taken in combination the specificity in diagnosing DSPN was greater (p-value = .018, specificity 96%) than either alone. 33% of patients had subclinical neuropathy. CONCLUSION: DNE score alone and in combination with DNS score is reliable in predicting DSPN and is more specific than DNS score in evaluating DSPN. Both tests lack sensitivity. Patients without any evidence of clinical neuropathy manifest abnormalities on NCS.

Chemotherapy and metformin in pancreatic adenocarcinoma and neuroendocrine tumors.

Pancreatic cancer, despite being a relatively less commonly occurring cancer is among the deadliest ones, leading to a grave prognosis. Surgery stands as the mainstay of treatment of pancreatic cancer but is an option in less than 15% patients owing to the late presentation of the tumor. Chemotherapy offers an important part of treatment but can adversely affect the quality of life because of devastating side effects and has limited survival benefit. Unavailability of effective and less toxic treatment options for pancreatic cancer has prompted the search for new treatment strategies. One such drug being considered for its potential anti-neoplastic role is the time-tested and widely used oral hypoglycemic drug, metformin. Metformin is proposed to target metabolic pathways involved in tumorigenesis, specifically the AMPK-mTOR complex. Epidemiological evidence is mounting in favor of its role in various cancers both for treatment and prophylaxis. Herein, we aim to summarize the epidemiological data on metformin as a potential anti-cancer drug in various cancers followed by a look at some of the abstracts relating to this topic that were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2014.

Type 1 and type 2 diabetes mellitus: are they mutually exclusive?

INTRODUCTION: With advancement in the understanding of the pathogenesis underlying diabetes mellitus (DM), the boundary between type 1 and type 2 DM (T1DM and T2DM) does not seem to be as clear cut as previously thought. This study was designed to test the possibility of overlap between the spectra of immune-mediated DM and insulin resistance. METHODS: To test for the possibility of overlap, we looked for autoantibodies typical of T1DM in patients with classical T2DM, and insulin resistance in patients with T1DM. Autoantibodies against islet cell antigen, glutamic acid decarboxylase-65 and insulinoma-associated antigen-2 were tested in 82 patients with T2DM and 27 patients with T1DM. The patients had been diagnosed on clinical criteria using standard laboratory techniques. Clinical parameters of diagnostic importance were noted, and homeostatic model assessment of insulin resistance (HOMA-IR) was calculated using fasting insulin and fasting blood glucose ratio. RESULTS: Autoantibodies against one or more beta cell antigens were detected in 12.19% of patients clinically diagnosed to have T2DM, and insulin resistance (HOMA-IR > 2.5) was diagnosed in 37.03% of patients with T1DM. It was not possible to identify any combination of clinical or biochemical markers that could predict autoantibody positivity in T2DM patients. T1DM patients with insulin resistance had a significantly higher body mass index than their insulin-sensitive counterparts (p = 0.02). CONCLUSION: Autoantibodies against beta cell antigens are detectable in insulin-resistant T2DM patients, and insulin resistance may be present in relatively overweight T1DM patients. No differentiating clinical features that might predict autoantibody positivity in T2DM patients were found.

Periodontal disease in type 2 diabetes mellitus.

OBJECTIVE: To determine the periodontal status in well controlled and poorly controlled type 2 diabetic patients compared with normal healthy individuals. STUDY DESIGN: Cross-sectional comparative study. PLACE AND DURATION OF STUDY: Diabetes Management Centre, Services Hospital, Lahore, from November 2009 to January 2010. METHODOLOGY: Forty well controlled and forty poorly controlled type 2 diabetic subjects having good oral hygiene (scored according to simplified oral hygiene index) were compared with a control group of forty normal healthy individuals. Probing depth (PD), gingival recession (GR), and attachment loss (AL) were recorded to obtain the periodontal status of each tooth, using a Michigan probe "0" with Williams marking. Glycemic control was evaluated by glycated Hb value. Using ANOVA and independent sample t-test, mean probing depth and attachment loss in each tooth type (incisors, canines, premolars and molars) were compared. RESULTS: Mean age of diabetic subjects was 58.86 ± 6.21 years and that of control group was 56.92 ± 6.91 years; 60% were females. Probing depth was greater in patients with poorly controlled diabetes compared to well controlled diabetic patients and non-diabetic controls (4.21 mm vs. 3.72 mm and 2.93 mm respectively, p < 0.001). Attachment loss also increased in poorly controlled diabetes (p < 0.001) compared to the control group and well controlled diabetes, however, the difference was not statistically significant when comparing well controlled to the control group (p > 0.05). Number of sites and mean percentage of sites with attachment loss of ³ 4 and ³ 6 mm was also significantly higher in poorly controlled diabetes compared to the control group (p < 0.05 and p < 0.001 respectively). CONCLUSION: Periodontal status as estimated by probing depth and degree of attachment loss deteriorates significantly with poor glycemic control in diabetes.

A new approach for estimation of body mass index using waist and hip circumference in type 2 diabetes patients.

BACKGROUND: Body mass index (BMI), derived by dividing weight (Kg) by the square of height (m), is a useful anthropometric parameter, with multiple applications. It is dependent upon accurate measurement of its component parameters. Where measurement of height and weight with calibrated instruments is not possible, other objective parameters are required to maintain accuracy. OBJECTIVES: We aimed to propose an alternate prediction model for the estimation of BMI based on statistical linear regression equation using hip and waist circumferences. Our objective was to ascertain the accuracy of estimated BMI when compared with observed BMI of patients, and to propose a model for BMI prediction which would overcome problems encountered in the prediction of body mass index of critically ill or immobile patients, needed for applications such as BMI based calculations in ventilation protocols in ICUs. METHODS: This cross sectional survey was done by reviewing hospital records of adult subjects of both genders (n=24,485; 10,687 males and 13,798 females), aged 20 years and above, who were diagnosed with type 2 diabetes. Two different prediction models were designed for males and females keeping morphological and physiological differences in gender. The measured waist and hip circumference values were used to estimate BMI. RESULTS: Data analysis revealed a significant linear relationship between BMI, waist and hip circumference in all categories [waist circumference (r=0.795, p=0.000), hip circumference (r=0.838, p=0.000)]. Estimated regression models for males and females were BMI=-10.71+0.212 (hip cir)+0.170 (waist circumference); and BMI=-15.168+0.143 (hip circumference)+0.30 (waist circumference) respectively. CONCLUSION: Estimation of BMI using this prediction model based upon measured waist and hip circumferences, is an alternate and reliable method for the calculation of BMI.