Insulin resistance, ethnicity and cardiovascular risk

Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality. The literature supports a series of established risk factors for CVD: age, gender, family history of CVD, ethnicity (un-modifiable); and high blood pressure, blood cholesterol, TGs, LDL, diabetes, pre-diabetes, obesity, smoking, physical inactivity, stress and unhealthy diet (modifiable). High blood pressure (hypertension) shares many of these risk factors. However, much of the variance/risk in both conditions cannot be explained. This has led to a search for novel risk factors, including insulin resistance and subclinical inflammation, the significance of which at present are controversial, particularly in relation to hypertension. There are also ethnic differences in the incidence, prevalence, risk factors and progression of cardiovascular disease. In some populations CVD occurs at an earlier age and progresses more rapidly. In this thesis I worked on two datasets in relation to hypertension, cardiovascular disease and their risk factors: (i) the RISC (Relationship between Insulin Sensitivity and Cardiovascular disease) study (chapters 2, 3, 5 and 6); and (ii) routinely-collected national data in Scotland via the SDRN (Scottish Diabetes Research Network) and SCI-Diabetes (chapter 2 and 7). Work on data from the RISC cohort focused on the relation between clamp-measured insulin sensitivity (its unique feature), inflammatory markers and hypertension; the SDRN work addressed ethnic differences in relation to diabetes and CVD. The first study (Chapter 3) examined the importance of insulin sensitivity/resistance in the development of hypertension and change in blood pressure over three years of follow-up in the healthy European (EU) RISC population. Systolic BP (SBP) was higher at baseline in insulin resistant (IR) women. There was no difference in BP in relation to IR in men. After adjustment for age, BMI, baseline BP and other covariates, low insulin sensitivity (M/I) predicted a longitudinal rise in SBP in women but not men, and SBP over time did not increase in insulin sensitive women. The second study (Chapter 4) was a systematic review of the relationships between two markers of low grade inflammation (IL-6 and CRP) and BP/hypertension, considering the roles of adiposity and insulin resistance. The systematic review showed evidence of considerable variation in the relationships amongst low grade inflammation, adiposity, insulin resistance and the development of hypertension. There appeared to be a positive association in the literature between CRP and DBP in younger individuals, although none of the studies were adjusted for insulin sensitivity determined by clamp technique. This association was further explored using RISC study data in Chapter 5 with stratification by sex and adjusting for clamp-derived insulin sensitivity. The third study (Chapter 5) examined the relationship of inflammatory markers with the development of hypertension and change in blood pressure over three years in the same healthy European population and whether any relationship was independent of clamp-measured insulin sensitivity (IS). High sensitivity C reactive protein (hsCRP) predicted prospective change in diastolic BP independent of insulin sensitivity and BMI whereas IL-6 had no relation with BP (both systolic and diastolic) or the incidence of hypertension. The fourth study (Chapter 6) evaluated all available predictors of BP rise over time (both systolic and diastolic) in a healthy EU population; moreover the significance of different predictors was examined within subgroups defined by age and sex. This analysis showed that baseline BP was the principal determinant of follow-up BP in all age and sex groups. Obesity was the second most important predictor (BMI in adults aged 30-44 years; percent change in BMI in middle age people aged 45-60 years). Lifestyle factors influenced BP via their effect on BMI. People who maintained their BMI during the three year follow-up did not exhibit a rise in BP (whether systolic or diastolic). Other important predictors identified in this analysis were insulin sensitivity in middle aged women and hsCRP in adult men. The fifth study (chapter 7) evaluated the role of ethnicity in the development of cardiovascular disease in people with type 2 diabetes living in Scotland. Over a follow-up of seven years, Pakistani people had increased risk of CVD and Chinese people had decreased risk of CVD as compared to White population. Pakistanis had an increased risk of CVD at a younger age independent of other conventional risk factors. In summary, insulin sensitivity and inflammation influence blood pressure, but their role is not generalised across different age and sex groups. BMI and change in BMI are important predictors of follow-up BP in adults and middle age healthy people, supporting a role for maintenance of BMI in preserving cardiovascular health. In addition to the known ethnic differences in the development of diabetes, I identified ethnic differences in the development of CVD

Endostatin concentration in plasma of healthy human volunteers

Background: Angiogenesis is involved in many cardiovascular and cancerous diseases, including atherosclerosis and is controlled by a fine balance between angiogenic and angiostatic mediators. Endostatin is one of the main angiostatic mediators, and inhibits angiogenesis and prevents progression of atherosclerosis. The available literature shows a broad range of concentrations in relatively small samples of healthy controls and is calculated by using different techniques. This study was aimed to determine the basal endostatin concentration in plasma of healthy volunteers, to fully understand its physiological role. Methods: Fifty healthy adult volunteers were recruited to the study. Participants were advised not to participate in any physical activity on the day before the blood sampling. The volunteers’ physical activity, height, weight, heart rate and blood pressure were recorded. The samples were analysed for plasma endostatin concentration, using ELISA. The participants were divided by gender and ethnic groups to calculate any difference. Results: Endostatin and other variables were normally distributed. Most of the participants had a moderate level of physical activity with no gender related difference (p=0.370). The mean value for plasma endostatin in all samples was 105±12 ng/ml with range of 81–132 ng/ml. For males, it was 107±13 ng/ml, while for females; 102±12 ng/ml. There were no significant gender or ethnicity related differences in endostatin concentration. Moreover, endostatin was not significantly related with any anthropometric and physical variable. Conclusion: This study gives endostatin levels in normal healthy people and show no gender and ethnicity related differences in endostatin levels. Endostatin was not related with any anthropometric and physical variable

Empowerment of primary health care in an Outreach resource-limited district in Punjab: A strategy for improving adherence to Antiepileptic drug treatment in children with Epilepsy.

There is wide acknowledgement of the need for community involvement in the optimal management of children with epilepsy (CWE) in outreach financially constrained districts of the developing countries, but there is scarce data on comprehensive community-based childhood epilepsy treatment programs assessment

Celiac Disease and Glycemic Control Among Patients with Type 1 Diabetes Mellitus

Objective: To determine the frequency of celiac disease among type 1 diabetic patients and to compare the frequency of adequate glycemic control in patients having T1DM plus CD and T1DM alone. Study Design: Cross-sectional study. Place and Duration: Unit-II, Department of Medicine, Foundation University Medical College, Islamabad. from 16th June 2016 to 16th December 2016 Methodology: Patients were recruited through medical and diabetes OPDs and medical wards. All the relevant information was recorded on a Proforma. In all type 1 diabetics a sample of blood was sent to AFIP for the determination of Anti-tTG (IgA) antibodies; using a commercially available ELISA technique (Pharmacia Upjohn, Sweden) based on recombinant human tTG as antigen. The measuring range of this test is 0.1 - 100 U/ml. We used the cut-offs: anti-tTG IgA ≤ 10 U/ml were considered negative, > 10 U/ml was considered positive. The assay was a quantitative assay. On the same visit, another blood sample was sent for HbA1C estimation.  Results: Total 160 patients were included according to the inclusion criteria of the study. Mean age (years) in the study was 26.58+9.13. There were 83 (51.9) male and 77 (48.1) female patients who were included in the study according to the inclusion criteria. The frequency of celiac disease among type 1 diabetic patients was 42 (26.3) in the study whereas the frequency of adequate glycemic control in patients having T1DM plus CD and T1DM alone was 26 (61.9) and 31 (26.3) respectively. Conclusion: The study concludes that the prevalence of celiac disease in type 1 diabetes mellitus in our own population is high. Furthermore, gluten-free diet effects on glycemic control of type 1 diabetic patients which in screening for celiac disease in type 1 diabetes mellitus patients and to decreased risk of complication of diabetes.&nbsp

Device discovery in D2D communication: A survey

Device to Device (D2D) communication was first considered in out-band to manage energy issues in the wireless sensor networks. The primary target was to secure information about system topology for successive communication. Now the D2D communication has been legitimated in in-band by the 3rd Generation Partnership Project (3GPP). To initiate D2D communication, Device Discovery (DD) is a primary task and every D2D application benefits from DD as an end to end link maintenance and data relay when the direct path is obstructed. The DD is facing new difficulties because of the mobility of the devices over static systems, and the mobility makes it more challenging for D2D communication. For in-band D2D, DD in a single cell and multi-cell, and dense area is not legitimated properly, causing latency, inaccuracy, and energy consumption. Among extensive studies on limiting energy consumption and latency, DD is one of the essential parts concentrating on access and communication. In this paper, a comprehensive survey on DD challenges, for example single cell/multi-cell and dense area DD, energy consumption during discovery, discovery delay, and discovery security, etc., has been presented to accomplish an effective paradigm of D2D networks. In order to undertake the device (user) needs, an architecture has been projected, which promises to overwhelm the various implementation challenges of DD. The paper mainly focuses on DD taxonomy and classification with an emphasis on discovery procedures and algorithms, a summary of advances and issues, and ways for potential enhancements. For ensuring a secure DD and D2D, auspicious research directions have been proposed, based on taxonomy

The global, regional, and national burden of adult lip, oral, and pharyngeal cancer in 204 countries and territories:A systematic analysis for the Global Burden of Disease Study 2019

Importance Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning.Objective To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates.Evidence Review The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019.Findings In 2019, 370 000 (95% uncertainty interval [UI], 338 000-401 000) cases and 199 000 (95% UI, 181 000-217 000) deaths for LOC and 167 000 (95% UI, 153 000-180 000) cases and 114 000 (95% UI, 103 000-126 000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia.Conclusions and Relevance In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global burden of chronic respiratory diseases and risk factors, 1990–2019: an update from the Global Burden of Disease Study 2019

Background: Updated data on chronic respiratory diseases (CRDs) are vital in their prevention, control, and treatment in the path to achieving the third UN Sustainable Development Goals (SDGs), a one-third reduction in premature mortality from non-communicable diseases by 2030. We provided global, regional, and national estimates of the burden of CRDs and their attributable risks from 1990 to 2019. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated mortality, years lived with disability, years of life lost, disability-adjusted life years (DALYs), prevalence, and incidence of CRDs, i.e. chronic obstructive pulmonary disease (COPD), asthma, pneumoconiosis, interstitial lung disease and pulmonary sarcoidosis, and other CRDs, from 1990 to 2019 by sex, age, region, and Socio-demographic Index (SDI) in 204 countries and territories. Deaths and DALYs from CRDs attributable to each risk factor were estimated according to relative risks, risk exposure, and the theoretical minimum risk exposure level input. Findings: In 2019, CRDs were the third leading cause of death responsible for 4.0 million deaths (95% uncertainty interval 3.6–4.3) with a prevalence of 454.6 million cases (417.4–499.1) globally. While the total deaths and prevalence of CRDs have increased by 28.5% and 39.8%, the age-standardised rates have dropped by 41.7% and 16.9% from 1990 to 2019, respectively. COPD, with 212.3 million (200.4–225.1) prevalent cases, was the primary cause of deaths from CRDs, accounting for 3.3 million (2.9–3.6) deaths. With 262.4 million (224.1–309.5) prevalent cases, asthma had the highest prevalence among CRDs. The age-standardised rates of all burden measures of COPD, asthma, and pneumoconiosis have reduced globally from 1990 to 2019. Nevertheless, the age-standardised rates of incidence and prevalence of interstitial lung disease and pulmonary sarcoidosis have increased throughout this period. Low- and low-middle SDI countries had the highest age-standardised death and DALYs rates while the high SDI quintile had the highest prevalence rate of CRDs. The highest deaths and DALYs from CRDs were attributed to smoking globally, followed by air pollution and occupational risks. Non-optimal temperature and high body-mass index were additional risk factors for COPD and asthma, respectively. Interpretation: Albeit the age-standardised prevalence, death, and DALYs rates of CRDs have decreased, they still cause a substantial burden and deaths worldwide. The high death and DALYs rates in low and low-middle SDI countries highlights the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for tobacco control, enhancing air quality, reducing occupational hazards, and fostering clean cooking fuels are crucial steps in reducing the burden of CRDs, especially in low- and lower-middle income countries