Dyslipidemia is one of the major risk factors for cardiovascular disease in diabetes mellitus. The characteristic features of diabetic dyslipidemia are a high plasma triglyceride concentration, low ...HDL cholesterol concentration and increased concentration of small dense LDL-cholesterol particles. The lipid changes associated with diabetes mellitus are attributed to increased free fatty acid flux secondary to insulin resistance. The availability of multiple lipid-lowering drugs and supplements provides new opportunities for patients to achieve target lipid levels. However, the variety of therapeutic options poses a challenge in the prioritization of drug therapy. The prevalence of hypercholesterolemia is not increased in patients with diabetes mellitus, but mortality from coronary heart disease increases exponentially as a function of serum cholesterol levels, and lowering of cholesterol with statins reduces diabetic patients' relative cardiovascular risk. Although drug therapy for dyslipidemia must be individualized, most people with diabetes mellitus are candidates for statin therapy, and often need treatment with multiple agents to achieve therapeutic goals.
One of the hallmarks of health is the integrity of barriers at the cellular and tissue levels. The two cardinal functions of barriers include preventing access of deleterious elements of the ...environment (barrier function) while facilitating the transport of essential ions, signaling molecules and nutrients needed to maintain the internal milieu (transport function). There are several cellular and subcellular barriers and some of these barriers can be interrelated. The principal physiologic barriers include blood-retinal barrier, blood-brain barrier, blood-testis barrier, renal glomerular/tubular barrier, intestinal barrier, pulmonary blood-alveolar barrier, blood-placental barrier and skin barrier. Tissue specific barriers are the result of the vasculature, cellular composition of the tissue and extracellular matrix within the tissue. Uncontrolled diabetes and acute hyperglycemia may disrupt the integrity of physiologic barriers, primarily through altering the vascular integrity of the tissues and may well contribute to the clinically recognized complications of diabetes. Although diabetes is a systemic disease, some of the organs display clinically significant deterioration in function while others undergo subclinical changes. The pathophysiology of the disruption of these barriers is not entirely clear but it may be related to diabetes-related cellular stress. Understanding the mechanisms of diabetes related dysfunction of various physiologic barriers might help identifying novel therapeutic targets for reducing clinically significant complications of diabetes.
•One of the hallmarks of health is the integrity of physiologic barriers•The principal physiologic barriers are blood-retinal barrier, blood-brain barrier and renal glomerular/tubular barrier.•The barriers prevent access of deleterious elements while facilitating the transport of essential ions, signaling molecules and nutrients.•Understanding diabetes related dysfunction of physiologic barriers might help identifying novel therapeutic targets.
Summary The rapid increase in the prevalence of obesity worldwide has been partially attributed to the overconsumption of added sugars. Recent guidelines call for limiting the consumption of simple ...sugars to less than 10% of daily caloric consumption. High intensity sweeteners are regulated as food additives and include aspartame, acesulfame-k, neotame, saccharin, sucralose, cyclamate and alitame. Steviol glycosides and Luo Han Guo fruit extracts are high intensity sweeteners that are designated as generally recognized as safe (GRAS). Commonly used non-caloric artificial sweeteners may have unfavorable effect on health including glucose intolerance and failure to cause weight reduction. The nutritive sweeteners include sugar alcohols such as sorbitol, xylitol, lactitol, mannitol, erythritol, trehalose and maltitol. Naturally occurring rare sugars have recently emerged as an alternative category of sweeteners. These monosaccharides and their derivatives are found in nature in small quantities and lack significant calories. This category includes d -allulose ( d -psicose), d -tagatose, d -sorbose and d -allose. Limiting consumption of any sweetener may well be the best health advice. Identifying natural sweeteners that have favorable effects on body weight and metabolism may help achieving the current recommendations of restricting simple sugar consumption.
The number of older adults with diabetes is rapidly increasing worldwide. A variety of factors contribute to the age-related increase in the incidence of diabetes. The lack of empiric evidence in the ...field has limited the management guidelines to mostly expert opinion. Given uncertainty over the rate at which to lower blood glucose levels and the optimal method of doing so, the goals of diabetes control in older people must be individualized. If the patient requires insulin therapy, the newer insulins, with their improved pharmacodynamic consistency and reduced risk of hypoglycemia, should be preferred. Several oral agents are preferable for people with sufficient endogenous insulin because they do not cause hypoglycemia when used as monotherapy. Some of these oral agents have been found to have cardioprotective effects. Older people with diabetes also require management of the other risk factors for cardiovascular disease, with antihypertensive drugs, cholesterol-lowering agents and low-dose aspirin. However, the precise targets for blood pressure control and low-density lipoprotein (LDL) cholesterol levels continue to evolve as more data become available. Diabetes care in older adults should focus on enhancing the individual's quality of life rather than trying to normalize blood glucose levels or reach predetermined blood pressure and LDL cholesterol targets.
Dyslipidemia is one of the key risk factors for cardiovascular disease (CVD) in diabetes mellitus. Despite the mounting clinical trial data, the management of dyslipidemia other than lowering the low ...density lipoprotein cholesterol (LDL-c) continues to be controversial. The characteristic features of diabetic dyslipidemia are high plasma triglyceride concentration, reduced high density lipoprotein cholesterol (HDL-c) concentration, and increased concentration of small dense LDL particles. These changes are caused by increased free fatty acid flux secondary to insulin resistance and aggravated by increased inflammatory adipokines. The availability of several lipid-lowering drugs and nutritional supplements offers novel and effective options for achieving target lipid levels in people with diabetes. While initiation of drug therapy based on differences in the lipid profile is an option, most practice guidelines recommend statins as first-line therapy. Although the evidence for clinical utility of combination of statins with fibrates or nicotinic acid in reducing cardiovascular events remains inconclusive, the preponderance of evidence suggests that a subgroup who have high triglycerides and low HDL-c levels may benefit from combination therapy of statins and fibrates. The goal of therapy is to achieve at least 30-40 % reduction in LDL-c levels. Preferably the LDL-c should be less than 100 mg/dL in low-risk people and less than 70 mg/dL in those at high risk, including people with established CVD.
Despite the advances made in preventing complications of diabetes, there is still substantial residual risk. Hence the need for developing new therapeutic agents that target the various facets of the ...pathogenesis of complications in people with diabetes. Traditionally four general biochemical pathways had been recognized as major contributors to glucotoxicity. These include the polyol pathway, the protein kinase C (PKC) pathway, glycosylation pathway, and oxidative stress. The latter has been proposed as a common impetus of the other pathways of glucotoxicity. More recently, the cross talk between oxidative stress and other recognized cellular stresses such as endoplasmic reticulum (ER), inflammatory, and mitochondrial stresses has emerged as an important additional mechanism of glucotoxicity. The observation that targeting oxidative stress with antioxidants has been associated with unfavorable clinical outcomes and the recognition that in cell cultures antioxidants may aggravate ER stress, suggests that selective targeting of individual cellular stresses may not be sufficient for preventing glucotoxicity. Future efforts should focus on developing therapeutic agents that can ameliorate cellular stress globally by simultaneously targeting the oxidative, ER, mitochondrial, and inflammatory stresses.
The age-related resistance to thyroid hormones (THs) explains the paucity of symptoms and signs of hyperthyroidism in older adults and may partly explain the myriad of symptoms and signs of ...hypothyroidism in biochemically euthyroid older people. This review considers the available data on the mechanisms underlying TH resistance with aging and compares these physiologic changes with the changes observed in congenital TH resistance syndromes. Aging is associated with alterations in TH economy along with a host of changes in the responsiveness of various tissues to THs. The age-related resistance to THs can be attributed to decreased TH transport to tissues, decreased nuclear receptor occupancy, decreased activation of thyroxine to triiodothyronine, and alterations in TH responsive gene expression. Although an increase in serum TH levels is expected in syndromes of TH resistance, unchanged serum TH levels in the euthyroid elderly is the result of increased sensitivity to TH negative feedback with increased suppression of thyroid-stimulating hormone, decreased thyroidal sensitivity to thyroid-stimulating hormone, and decreased TH production and secretion. The current clinical evidence suggests that the age-related TH resistance is mostly an adaptive response of the aging organism. It is tempting to speculate that similar changes can occur prematurely in a group of younger people who present with signs and symptoms of hypothyroidism despite normal serum thyroid function tests.
Low carbohydrate diets (LCD) may help body weight loss and glycemic control in diabetes but their long-term consequences are not known. The aim of this review is to highlight the contrast between the ...potential benefits of short term LCD and the adverse health effects of long-term consumption of LCD. LCD can enhance weight loss in the short term although its effect is small and not sustainable. In people with diabetes and insulin resistance, LCD is helpful in achieving glycemic control. However, there are untoward side effects especially when carbohydrates are severely restricted (< 50 gm a day) to induce ketosis. The latter curbs appetite but also may cause nausea, fatigue water and electrolyte losses and limits exercise capacity. In addition, observational studies suggest that low carbohydrate diets (< 40% energy form carbohydrates) as well as very high carbohydrate diets (> 70% energy from carbohydrate) are associated with increased mortality. The available scientific evidence supports the current dietary recommendations to replace highly processed carbohydrates with unprocessed carbohydrates as well as limiting added sugars in the diet.
The increasing incidence of type 2 diabetes in the general population as well as enhanced life expectancy has resulted in a rapid rise in the prevalence of diabetes in the older population. Diabetes ...causes significant morbidity and impairs quality of life. Managing diabetes in older adults is a daunting task due to unique health and psychosocial challenges. Medical management is complicated by polypharmacy, cognitive impairment, urinary incontinence, injurious falls, and persistent pain. Health care providers now have several traditional and contemporary pharmacologic agents to manage diabetes. Avoidance of hypoglycemia is critical; however, evidence-based guidelines are lacking due to the paucity of clinical trials in older adults. For many in this population, maintaining independence is more important than adherence to published guidelines to prevent diabetes complications. The goal of diabetes care in older adults is to enhance the quality of life without subjecting these patients to intrusive and complicated interventions. Recent technological advancements such as continuous glucose monitoring systems can have crucial supplementary benefits in the geriatric population.
Cellular stress, notably oxidative, inflammatory, and endoplasmic reticulum (ER) stress, is implicated in the pathogenesis of cardiovascular disease. Modifiable risk factors for cardiovascular ...disease such as diabetes, hypercholesterolemia, saturated fat consumption, hypertension, and cigarette smoking cause ER stress whereas currently known cardioprotective drugs with diverse pharmacodynamics share a common pleiotropic effect of reducing ER stress. Selective targeting of oxidative stress with known antioxidative vitamins has been ineffective in reducing cardiovascular risk. This "antioxidant paradox" is partially attributed to the unexpected aggravation of ER stress by the antioxidative agents used. In contrast, some of the contemporary antihyperglycemic drugs inhibit both oxidative stress and ER stress in human coronary artery endothelial cells. Unlike sulfonylureas, meglitinides, α glucosidase inhibitors, and thiazolidinediones, metformin, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors are the only antihyperglycemic drugs that reduce ER stress caused by pharmacological agents (tunicamycin) or hyperglycemic conditions. Clinical trials with selective ER stress modifiers are needed to test the suitability of ER stress as a therapeutic target for cardiovascular disease.
