Intekhab Ahmed

The emerging role of oxylipins in thrombosis and diabetes

The prevalence of cardiovascular disease (CVD), the leading cause of death in the US, is predicted to increase due to the shift in age of the general population and increase in CVD risk factors such as obesity and diabetes. New therapies are required to decrease the prevalence of CVD risk factors (obesity and diabetes) as well as reduce atherothrombosis, the major cause of CVD related mortality. Oxylipins, bioactive metabolites derived from the oxygenation of polyunsaturated fatty acids, play a role in the progression of CVD risk factors and thrombosis. Aspirin, a cyclooxygenase-1 inhibitor, decreases atherothrombotic associated mortality by 25%. These potent effects of aspirin have shown the utility of modulating oxylipin signaling pathways to decrease CVD mortality. The role of many oxylipins in the progression of CVD, however, is still uncertain or controversial. An increased understanding of the role oxylipins play in CVD risk factors and thrombosis could lead to new therapies to decrease the prevalence of CVD and its associated mortality.

Dual Ppar α/γ Agonists: Promises and Pitfalls in Type 2 Diabetes

Type 2 diabetes mellitus is a disease of complex pathogenesis and pleiotropic clinical manifestations. The greatest clinical challenge in this disease is the prevention of the long-term complications, many of which involve cardiovascular outcomes. The peroxisome proliferator-activated receptor (PPAR) α and γ isoforms of the family of nuclear transcription factors are pharmaceutical targets for therapeutic intervention because they can potentially ameliorate not only the hyperglycemia of diabetes, but also the dyslipidemia that is characteristic of this disorder (low high-density lipoprotein cholesterol, high triglycerides, small, dense low-density lipoprotein particles). Novel drugs with dual PPAR α and γ activity have been under clinical development for type 2 diabetes, and they have shown promise in early studies with regard to glucose lowering and improved lipid profile when compared with the PPAR-γ-specific thiazolidinediones. Unfortunately, the dual PPARs available to date have some of the PPAR-γ-associated side effect profile, including fluid retention and weight gain, which have limited the further clinical development of higher doses that show improved efficacy. This review will briefly summarize our understanding of the pathogenesis of type 2 diabetes, the role of the PPAR family of receptors, and the potential for clinical use of this novel emerging class of agents that serve as dual activators of both PPAR-α and PPAR-γ.

Is above age 45 appropriate for upstaging well-differentiated papillary thyroid cancer?

OBJECTIVE Age greater than 45 years old is a prognostic marker in well-differentiated papillary thyroid cancer (PTC) using the American Joint Cancer Committee/Union Internationale Contre le Cancer Tumor Nodes Metastasis (AJCC/UICC TNM) staging system. Our clinical observation has been that patients aged 45 to 64 years have similar outcomes when compared to patients younger than 45 years, and we questioned the origin and accuracy of this prognostic variable. METHODS Using SEERstat software, we analyzed the Surveillance, Epidemiology, and End Result (SEER) database for PTC using the following International Classification of Diseases for Oncology (ICD-O) codes: 8050, 8260, 8340, 8341, 8342, 8243, and 8344. Data were stratified in 5-year categories by age at diagnosis from 20 to 84 years old, with patients 85 years old and above categorized together. Survival is reported as cause specific. RESULTS A total of 53,581 patients were identified. The 5-year survival rate decreased with each increasing age category with no inflection point at age 45 in the survival curve. While the prognosis was less favorable in each advancing age group, survival remained above 90% for all age groups under 65 years. CONCLUSION A review of the literature reveals a lack of data supporting the use of age 45 as a prognostic variable. Our SEER database review revealed a continuum of disease-specific mortality for each incremental 5-year time period above age 45. We conclude that the current use of age 45 as a single prognostic age marker does not accurately reflect the progressive mortality risk that is apparent with each 5-year increment in age.

Sodium–glucose cotransporter 2 inhibitors: an evidence-based practice approach to their use in the natural history of type 2 diabetes

Abstract Objective The sodium–glucose cotransporter 2 (SGLT-2) inhibitors are an important addition to available treatments for patients with type 2 diabetes (T2D) as an adjunct to modifications in diet and exercise. SGLT-2 inhibitors may be prescribed alone or as add-on treatment in patients receiving metformin, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, and/or insulin across the natural history of the disease. Inhibition of SGLT-2, which is responsible for approximately 90% of renal glucose reabsorption, increases urinary glucose excretion and lowers blood glucose concentrations. The objective of this review is to discuss the pathophysiology of diabetes and the contribution of the kidney to glucose homeostasis and to provide an evidence-based practice approach to clinical applications of SGLT-2 inhibitors in the treatment of T2D. Methods PubMed and Google Scholar databases were searched to identify literature published from 1990 through September 2015 examining the pathophysiology of T2D, the role of the kidney in regulating glucose concentrations, and clinical evidence for the efficacy and safety of SGLT-2 inhibitors in T2D. Results There is a need for early treatment in patients with T2D to minimize the risk of cardiovascular complications that increase morbidity and mortality. SGLT-2 inhibitors improve glycemic control, reduce body weight and blood pressure, and are associated with a low risk of hypoglycemia. Adverse events associated with SGLT-2 inhibitors include mild to moderate urinary tract and genital infections and mild dehydration potentially leading to orthostatic hypotension. Conclusions An evidence-based practice approach to examining the importance of early, proactive treatment of T2D using SGLT-2 inhibitors from initiation of pharmacotherapy to increasingly more complicated combination therapy regimens, including insulin, suggests that this treatment strategy maximizes benefits and minimizes potential side effects. The SGLT-2 inhibitors augment the arsenal of available antidiabetes agents, facilitating the ability of clinicians to design tailored treatment regimens that help patients achieve therapeutic goals.

Subclinical hyperthyroidism: current concepts and scintigraphic imaging.

Subclinical hyperthyroidism is defined as normal serum free thyroxine and a free triiodothyronine level, with a thyroid-stimulating hormone level suppressed below the normal range and is usually undetectable. Although patients with this diagnosis have no or few signs and symptoms of overt thyrotoxicosis, there is sufficient evidence that it is associated with a relatively higher risk of supraventricular arrhythmias as well as the acceleration or the development of osteoporosis. Consequently, the approach to the patient with subclinical hyperthyroidism is controversial, that is, therapeutic intervention versus watchful waiting. Regardless, it is imperative for the referring physician to identify the causative thyroid disorder. This is optimally accomplished by a functional study, namely scintigraphy. Recognition of the scan findings of the various causes of subclinical hyperthyroidism enables the imaging specialist to help in diagnosing the underlying condition causing thyroid-stimulating hormone suppression thereby facilitating the workup and management of this thyroid disorder.

Insulin and endothelial function: A brief review

Abstract Background: In recent years, the novel effects of insulin beyond control of glucose metabolism have been appreciated, especially those that impact vascular function. A better understanding of insulins protective interactions with the endothelium has provided clinicians with a justification for more aggressive use of insulin—not only to control glucose levels, but also to potentially reduce the progression of atherosclerosis and its pathogenic sequelae. Objective: In this brief review, we provide a snapshot of the available research and clinical findings signifying beneficial effects of insulin on the endothelium. Methods: We conducted a MEDLINE search of articles published in English from 1965 through 2007 using the search terms insulin, endothelium, and anti-inflammatory. Articles with a focus on “insulin resistance” per se were excluded from this review. Results: The literature search identified 200 articles that addressed the effects of insulin on endothelium and the interaction between insulin and the vasculature. Conclusions: In addition to mitigating hyperglycemic toxicity, insulin has multiple beneficial interactions with the endothelium in physiologic and disease states. The anti-inflammatory actions of insulin confer beneficial effects in preventing and minimizing morbidity and mortality due to atherosclerosis, especially in acute settings like myocardial infarction.

Denosumab: do we need another of the same?

Religious festivals should focus our minds on the good aspects of life and there are many to recognise and respect. They are, however, like a veneer of happiness temporarily painting over the equally many negative moments that influence our lives on a day to day basis. Over a full year the scales tip one way then the other as events determine the goodness and badness of each moment in time. Austerity this year will colour Christmas for many families. We know it is necessary for the future of our children, but the pain is here and now. We also know that it is impacting on the service aspect of living – health care, education, social support – and invariably on relationships and self esteem. ‘Suicide is painless’ said the movie theme song, but only to those committing suicide, arguably the most selfish act a human being can succeed in. The subsequent pain and bewilderment for those closest or adjacent is palpable. This year has seen male suicides committed after the completely unforgivable murdering of their children – almost the ultimate evil – ‘If I can’t have them then nobody can’. Yet we need to question our support systems, are they there when the individual asks who can he or she turn to when it appears they are not needed? To rely on charity (no matter how good and dedicated) is simply not good enough. Central and regional service cut-backs are compounding the problems. The abject waste of resources rather than the intelligent and caring channelling of funds to those most in need (not necessarily the poor) is a measure of political incompetence and insensitivity, tragically transmitted to everyday life. Abuse still discolours lives, whether it is child abuse, verbal abuse, racial abuse or religious abuse. At times it is difficult to comprehend the individual or collective abuse based on colour, as witnessed at soccer matches – it may be the ‘beautiful game’ but it is not always the beautiful players or spectators. Religious abuse reached new depths with the deliberate shooting of children because they questioned the bigotry of extremism. Intolerance as a benchmark of worship devalues the entire principle, not just the subsidiary principles of the faith. But it is not really faith, because that implies trust and confidence in others and ⁄ or god, and not scheming hatred and murder. Child abuse in whatever form is, put simply, the violation of innocence. Whether it be parental, a stranger, a trusted relative or friend, or a media personality, it is the degradation of the less powerful by those who incorrectly see themselves as superior. The newspapers in the UK are beside themselves discussing privilege and ‘plebs’. None of them can see that it is a privilege to be good parents (most are) and it is a privilege to worship safely according to ones beliefs. It is also a privilege to live in a society which values caring and freedom rather than persecution and vindictiveness. As so this is Christmas again. Sentences need to begin ‘What is good about ... ’ as in what is good about health care, and what is good about being a parent. There is certainly a dark side of the moon, but once more let the season of goodwill be just that. What is good about it – we have nothing to lose and a world to gain.

Ramadan: type 2 diabetes and risk of hypoglycaemia

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Insulin Therapy in the Management of Diabetes Mellitus Type 2

A 58-year-old African-American woman who has had type 2 diabetes mellitus for the last eight years presented saying, “My blood sugars are staying high.” At the time of diagnosis she presented with symptoms of polyuria, polydipsia, and weight loss. She was prescribed metformin 500 mg to be taken twice a day. A nutritional consult was also scheduled for the patient. Due to gradually rising hemoglobin A1c values, into the 8% range, over the years she has tried to increase the dose of metformin, but this has been limited by diarrhea and upset stomach symptoms. She also tried rosiglitazone at some point, but discontinued it because of weight gain and mild peripheral edema. Glimepiride, first 2 mg per day, then gradually increasing to 8 mg per day, has helped her maintain good glycemic control in addition to the metformin 500 mg b.i.d. However, during the past 2 years, her A1c began to gradually rise above 8% and then above 9%. She has been compliant with her regimen, and has been trying to exercise (walking) and to watch her diet. She checks her blood sugars frequently, and states that most of her fasting and postprandial blood sugars have been below 150 mg/dL, except that for the last 6 months her blood sugars have shown a progressive increase up to 350 mg/dL at random times. She denies any hospitalization secondary to hyperglycemia. These elevated blood sugars have also resulted in recurrence of polyuria, nocturia, and blurry vision. Her weight has remained stable over the past year

Coronary artery disease screening in patients with diabetes

Coronary artery disease (CAD) is the most common cause of death in patients with diabetes. Many diabetics have asymptomatic CAD, and may benefit from early diagnosis. We review the recent literature to evaluate whether the current evidence supports screening for CAD in asymptomatic diabetics. Currently, no single screening modality has shown sufficient accuracy to determine which patients will have significant CAD. The combination of imaging modalities may show promise in improving the accuracy of screening, and limited data suggest that screening in this population may be associated with improved outcomes. However, based on the current evidence we presently do not recommend screening for CAD in this population.