Ali A. Rizvi

Bergamot Reduces Plasma Lipids, Atherogenic Small Dense LDL, and Subclinical Atherosclerosis in Subjects with Moderate Hypercholesterolemia: A 6 Months Prospective Study.

Background: Some patients experience statin-induced side effects or prefer nutraceutical approaches for the treatment of dyslipidemia. This has led to a search for alternative therapeutic approaches for dyslipidemia management. In recent studies Citrus bergamia (known as Bergamot) juice was able to reduce serum levels of lipids. Such benefit may be attributed to high amounts of flavonoids contained in Bergamot fruit juice (neoeriocitrin, neohesperidin, naringin). The aim of the present study was to fully investigate the effects of a Bergamot extract on cardio-metabolic parameters, including plasma lipids, atherogenic lipoproteins and subclinical atherosclerosis. Methods: Eighty subjects (42 men and 38 women, mean age: 55 ± 13 years) with moderate hypercholesterolemia [e.g., with plasma LDL-cholesterol concentrations between 160 and 190 mg/dl (between 4.1 and 4.9 mmol/l)] were included. A Bergamot-derived extract (Bergavit R®) was given at a fixed dose daily (150 mg of flavonoids, with 16% of neoeriocitrin, 47% of neohesperidin and 37% of naringin) for 6 months. Lipoprotein subfractions were assessed by gel electrophoresis. With this methodology low density lipoprotein (LDL) subclasses are distributed as seven bands (LDL-1 and -2 as large LDL, and LDL-3 to -7 as atherogenic small, dense LDL). Subclinical atherosclerosis was assessed by carotid intima-media thickness (cIMT) using B-mode ultrasound. Results: After 6 months, Bergavit R® reduced total cholesterol (from 6.6 ± 0.4 to 5.8 ± 1.1 mmol/l, p < 0.0001), triglycerides (from 1.8 ± 0.6 to 1.5 ± 0.9 mmol/l, p = 0.0020), and LDL-cholesterol (from 4.6 ± 0.2 to 3.7 ± 1.0 mmol/l, p < 0.0001), while HDL- cholesterol increased (from 1.3 ± 0.2 to 1.4 ± 0.4 mmol/l, p < 0.0007). In addition, a significant increase in LDL-1 (from 41.2 ± 0.2 to 49.6 ± 0.2%, p < 0.0001) was accompanied by decreased small, dense LDL-3, -4, and 5 particles (from 14.5 ± 0.1 to 9.0 ± 0.1% p < 0.0001; 3.2 ± 0.1 to 1.5 ± 0.1% p = 0.0053; 0.3 ± 0.0% to 0.1 ± 0.0% p = 0.0133, respectively). cIMT also decreased from 1.2 ± 0.4 to 0.9 ± 0.1 mm (p < 0.0001). Conclusion: This is the first study investigating the effects of Bergamot flavonoids supplementation on cardio-metabolic risk in dyslipidemic subjects. Bergavit R® (Bergamot juice extract) supplementation significantly reduced plasma lipids and improved the lipoprotein profile. cIMT was also reduced significantly over a relatively short time frame of 6 months.

Cytokine Biomarkers, Endothelial Inflammation, and Atherosclerosis in the Metabolic Syndrome: Emerging Concepts

In recent years, an explosion of research related to the cellular and vascular accompaniments of the metabolic syndrome has generated intense interest and controversy. Attention has focused on the vascular endothelium, where heightened, low-grade inflammatory processes lead to a continuum of vascular insults ranging from early endothelial derangements to advanced atherosclerosis. Inflammatory biocytokines, such as C-reactive protein, have been speculated to be both markers and mediators of oxidative stress and endovascular toxicity. Adipocytokines originating from fatty tissue have reinforced the concept that fat is a metabolically active organ rather than inert tissue. To fully elucidate its complex pathogenetic mechanisms, further inquiry into the inflammatory components of the metabolic syndrome is warranted. Unraveling the role of emerging proinflammatory markers has the promising potential to shed light into the underlying pathophysiology of the epidemic of obesity and the metabolic syndrome and thus help devise effective therapies.

Glucose lowering and anti-atherogenic effects of incretin-based therapies: GLP-1 analogues and DPP-4-inhibitors

Background: Type 2 diabetes is a chronic, progressive disease with a multi-faceted pathophysiology. Beyond the known defects of insulin resistance and β-cell insufficiency, derangement of incretin hormones normally produced from the gut wall in response to food intake play an important role. In recent years, the ‘incretin-based’ therapies (IBTs) have been developed to address hyperglycemia through either mimicking the action of the endogenous incretin glucagon-like polypeptide (GLP-1) (GLP-1 receptor agonists) or by inhibiting the activity of the enzyme that degrades GLP-1 (the dipeptyl peptidase-4 inhibitors). Objective: We reviewed available evidence on the glucose lowering and anti-atherogenic effects of IBT. Results: In addition to their glucose-lowering and weight-neutral or weight-reducing actions, IBT decrease systolic blood pressure and improve fasting and postprandial lipid parameters by reducing total-cholesterol, low-density lipoprotein-cholesterol and triglycerides concentrations, and increasing high-density lipoprotein-cholesterol values. Reduced high-sensitivity C-reactive protein levels and improved endothelial dysfunction have been reported too. Conclusions: IBT have several beneficial effects on cardiovascular risk factors and, for this reason, it has been recently suggested to extend the use of these drugs in diabetic patients with cardiovascular complications. Yet, the long-term effects of IBT on subclinical or clinical atherosclerosis remain to be established by future studies.

Perioperative management of diabetes and hyperglycemia in patients undergoing orthopaedic surgery.

Abstract Persons with diabetes undergo more surgical procedures, have a higher perioperative risk of complications, and have longer hospital stays than do persons who do not have diabetes. Persons with diabetes are frequently overweight, have a high prevalence of cardiovascular risk factors, and are more likely to suffer from chronic musculoskeletal conditions and traumatic injuries that require orthopaedic attention. Surgery frequently disrupts usual diabetes management, requiring adjustments to the treatment regimen. Suboptimal perioperative glucose control may contribute to increased morbidity, and it aggravates concomitant illnesses. Many patients undergoing elective or urgent orthopaedic surgery may have unrecognized diabetes or may develop stress‐related hyperglycemia in the hospital. The challenge is to minimize the effects of metabolic derangements on surgical outcomes, reduce glycemic excursions, and prevent hypoglycemia. Recent guidelines advocate evidence‐based glucose targets in the inpatient setting, and regimens for intravenous and subcutaneous insulin are gaining in popularity. Individualized treatment should be based on the ambient level of glycemic control, outpatient treatment regimen, presence of complications, nature of the surgical procedure, and type of anesthesia administered. Management by a multidisciplinary team and attention to discharge planning are key aspects of care during and after orthopaedic surgery.

Severe Primary Hypothyroidism Manifesting with Torsades De Pointes

Hypothyroidism can manifest with myriad cardiac abnormalities, often consisting of a combination of morphologic and functional changes. Low voltage, sinus bradycardia, and slowed conduction are usually found on electrocardiography. We describe a patient with severe hypothyroidism who presented with presyncope, prolongation of the QT interval, and polymorphic ventricular tachycardia (torsades de pointes). No other cause for the malignant ventricular ectopy was evident. With levothyroxine therapy, the QT interval normalized and the ventricular tachycardia was abolished. In addition to its commonly known cardiac effects, myxedema can predispose to the potentially life-threatening arrhythmia of torsades de pointes. Conversely, in patients presenting with QT interval prolongation and polymorphic ventricular tachycardia, hypothyroidism should be considered in the differential diagnosis.

A collaborative approach to the recruitment and retention of minority patients with diabetes in rural community health centers

CONTEXT Recruiting and retaining minorities from rural, community health centers is a challenge. Collaboration between the researchers and health center personnel and activities to enhance trust may improve results. PURPOSE To describe recruitment and retention strategies and report results of a 12-month clinical trial of a telemedicine-based diabetes self-management intervention, conducted within a rural community health center. METHODS Multi-level, multi-staged recruitment process including collaborative planning, data extraction, medical record review, telephone screen, 2 in-person enrollment visits and randomization. Target sample was adults >or=35 years of age with type 2 diabetes, glycated hemoglobin (GHb)>7% with no significant comorbidities to prevent safe participation. Follow-up visits occurred at 6 and 12 months post-randomization. FINDINGS Of those eligible from medical record review, 65% were African-American(AA)/other and female. Approximately 33% of those successfully contacted by telephone were randomized (n=165), yielding a predominately AA/other (73.9%) and female (74.5%) sample. Among those eligible at the Telephone Screen, a greater percentage of Non-Hispanic Whites (NHW) refused participation than AA/other (54.2% vs 45.8%), while a greater percentage of women refused compared to men (64.4% vs 35.6%). Significant baseline differences were found by ethnicity for education, insurance, transportation and diastolic blood pressure; by gender for income, transportation, weight, and home monitoring of blood glucose. Overall 6 and 12 month retention rates were 90.9% and 82.4%, respectively, with a greater percentage of AA/Other and female participants retained. CONCLUSIONS Our collaborative approach was successful in recruiting and retaining ethnically diverse study participants who reside in a rural underserved area of South Carolina. Differences in baseline characteristics and retention by ethnicity and gender were found. Successful translational research must allow for a collaborative approach addressing factors at the level of the community health center, key personnel, and patients in an effort to build trust for the purpose of advancing the science of translating research to practice.

Combined Dyslipidemia: Should the Focus be LDL Cholesterol or Atherogenic Dyslipidemia?

As the population becomes more obese and the prevalence of diabetes and the metabolic syndrome increases, low-density lipoprotein-cholesterol (LDL-C) may lose its value as a sole predictor for cardiovascular risk among lipids. Combined dyslipidemia is typically characterized by elevations in LDL-C and triglyceride levels, often accompanied by decreased high-density lipoproteincholesterol (HDL-C) concentrations and increased levels of small, dense LDL. This common disorder results from overproduction of hepatically synthesized apolipoprotein B in very low-density lipoproteins. In the last few years most of the international scientific guidelines as well as several expert panels have confirmed that LDL-C represents the primary or even the only target of treatment. Yet, increasing evidence suggests moving away from a LDL-C target-based approach to a more tailored treatment approach. For example, non- HDL-C has been introduced in the last few years as a target of treatment.

Management of Diabetes in Older Adults

Enhanced life expectancy and the aging of society have conspired with rising rates of obesity and physical inactivity to cause an unprecedented increase in diabetes prevalence worldwide. The disease and its chronic complications have unique presentations and challenges in the elderly. Postprandial hyperglycemia may be the predominant manifestation, comorbid health conditions are often present, and the risk of cardiovascular disease is vastly increased. Periodic screening is essential for early diagnosis and proper treatment. The principles of multidisciplinary management emphasizing nutrition, exercise, education, psychosocial care, attention to concomitant metabolic risk factors, and prudent use of pharmacologic agents are the mainstay of therapy for older adults. Treatment should be tailored to the individual patient, and the assistance of family and caregivers should be combined with rational utilization of community resources. An evidence-based, comprehensive, and proactive approach is needed to reduce the burden of morbidity and mortality from diabetes in the elderly.

Incidence of diabetes mellitus in a population-based cohort of HIV-infected and non-HIV-infected persons: the impact of clinical and therapeutic factors over time.

To examine incidence density rate and correlates of incident diabetes mellitus in a cohort of HIV‐infected individuals compared with matched non‐HIV‐infected persons.

Hypertension, Obesity, and Inflammation: The Complex Designs of a Deadly Trio

Hypertension is a powerful risk factor for cardiovascular disease and frequently occurs in conjunction with obesity and the metabolic syndrome. Recent research into the underlying pathophysiologic processes common to these entities has uncovered the role of a heightened inflammatory state signified by a host of circulating biocytokines. Systemic and local hormonal effectors, such as angiotensin II and aldosterone, interact with inflammatory and oxidative stress to augment endothelial damage in a complex manner. The kidneys play a prominent role in the renin-angiotensin cascade and the abnormal pressor response that ensues. Insulin resistance underlies the pathogenesis of obesity and the metabolic syndrome. The interplay of hypertension, insulin resistance, and obesity vastly enhances the noxious influence of inflammation on the vasculature, promoting deleterious immune adaptations and ultimately increasing atherosclerotic risk. Although certain classes of available pharmacologic agents already address the altered endovascular and humoral dynamics in hypertension, a better understanding of the proinflammatory picture holds promise of targeted treatment modalities in future.