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By: M. Avogadro, M.A., M.D.

Associate Professor, University of New Mexico School of Medicine

These were slightly higher than the rates in the Framingham study [37] treatment of bronchitis buy atripla in united states online, presumably because of the older age of the Oxford patients treatment quality assurance unit discount 300mg atripla with mastercard. Retinopathy occurred at a rate of 60 cases and cataract at 29 cases per 1000 person-years medicine grace potter atripla 300 mg otc, while the rate of proteinuria (albumin concentration >300 mg/L) was 19 per 1000 person-years medications while breastfeeding generic 300mg atripla otc. Logistic regression demonstrated a significant rise in the prevalence of retinopathy with aging, independent of the effects of metabolic control, duration of disease and other risk variables. Age also increased the prevalence of peripheral neuropathy, hypertension and erectile dysfunction. An independent contribution of age per se to retinopathy, however, was not reported by Ballard et al. Diabetic retinopathy may be the presenting feature of the disease in older people. Elderly people with diabetes need annual measurements of visual acuity and retinal photography; where the latter may not be available or feasible, patients should undergo dilated-pupil fundoscopy by experienced observers. Exudative maculopathy (hard exudates at or within one disc diameter of the macula) is easy to detect, but macular edema is practically impossible to detect by routine ophthalmoscopy; instead, slit-lamp stereoscopic fundoscopy is required to measure retinal thickness. Mydriasis is usually a short-term intervention and, in the great majority of cases, is not associated with any major problems, even in older people. It is always important to know whether patients have a history of glaucoma before mydriasis, as this requires a different approach, often under specialist supervision. This highlights the importance of measuring the corrected visual acuity, which is decreased by maculopathy (see Chapter 36). Indications for referral to an ophthalmologist 926 Diabetes in Old Age Chapter 54 are generally identical to those in younger patients (see Table 36. As well as the common symptoms of numbness, neurogenic pain, "pins and needles" and hyperesthesia (all typically worse at night), peripheral neuropathy often causes gait disturbances, falls and other foot injuries. A trivial foot injury in a patient with severe neuropathy can eventually lead to Charcot arthropathy; most of these patients have had diabetes for at least 10 years, and many are elderly (see Chapter 44). Alternative treatments include transcutaneous nerve stimulation or acupuncture, as described in Chapter 38. As discussed in Chapter 39, atheromatous lesions in diabetes are more diffuse and involve vessels below the knee more often than in individuals without diabetes. Medial arterial calcification is common, especially in association with somatosensory and autonomic neuropathy; this change can affect Doppler ultrasound measurements of blood pressure in the foot and cause a misleadingly high ankle pressure index. As in younger patients, many older people with diabetes and critical or worsening limb ischemia, or ischemic ulcers that are slow to heal, will benefit from surgical revascularization (angioplasty or arterial reconstruction). Appropriate cases should be referred early for surgery, ideally through joint protocols developed by the diabetes specialist and the vascular surgeon [58]. A reasonable life expectancy is considered important by surgeons, as concomitant cardiac and cerebrovascular disease kill 50% of patients within 5 years [59]. Following proximal arterial reconstruction, the 5-year patency averages 70% and may exceed life expectancy in patients with major co-morbidities; for distal reconstruction surgery, 5-year limb salvage rates approach 85% [59]. Strategies to prevent diabetic foot ulceration are based on a multidisciplinary approach to identifying, educating and treating high-risk patients; as discussed in Chapter 44, these measures can effectively reduce diabetes-related amputation rates. Many elderly patients have great difficulty in performing the most basic routine foot care [60], often because of poor vision and reduced mobility. In such cases, spouses and other carers must be involved to prevent and treat foot lesions. Education needs to be concise and repeated regularly; video presentations may also be helpful. Problems with hypoglycemia and postural hypotension, however, prevent many elderly subjects from achieving tight glycemic and blood pressure control. Laser photocoagulation should be used as indicated in Chapter 36; it halves the risk of severe visual loss with macular edema and exudative maculopathy (if visual acuity is 6/9 or better), which otherwise reaches 50­70% after 5 years [48­50]. It has been calculated that screening and treating diabetic retinopathy would prevent 56% of blind registrations resulting from this condition. Diabetic foot disease Amputation of a limb remains an important and expensive health problem in the diabetic population, with the elderly being particularly affected [51]. A Dutch study [52] identified increasing age and a higher level of amputation as important factors that increased both the duration and costs of hospitalization (estimated at over Ј10 000 per hospitalization, lasting an average of 42 days). The 3-year survival following lower-extremity amputation is about 50% [53]; in about 70% of cases, amputation is precipitated by foot ulceration [54]. The principal antecedents include peripheral vascular disease, sensorimotor and autonomic neuropathy, limited joint mobility (which especially prevents older people from inspecting their feet) and high foot pressures (Table 54.


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However treatment 2 go quality atripla 300 mg, the benefits of -adrenergic blockers in reducing cardiac mortality in patients with diabetes mellitus usually outweigh their potential limitations (33) 10 medications doctors wont take purchase cheap atripla on line. Diuretics Thiazide diuretics more effectively lower blood pressure than loop diuretics in patients with normal renal function treatment of lyme disease generic atripla 200mg with mastercard. Peripheral vascular resistance is reduced by these agents because they reduce interstitial fluid volume and smoothmuscle sodium concentration (29) medicine identifier buy 600 mg atripla with mastercard. Historically, diuretics have been considered superior first-line agents in African American patients; however, this concept has recently been challenged by an extensive review of the literature (35). Patients taking -adrenergic blockers have a marked risk of orthostatic hypotension and an increased risk of congestive heart failure (24). This agent is also beneficial in reducing the risk of microalbuminuria in the presence of renin-angiotensin system blockade. Deterioration of lipid parameters has not been reported with use of carvedilol (37). Results from long-term, randomized clinical outcome studies of carvedilol treatment in patients with hypertension and diabetes mellitus are not yet available. Calcium Channel Blockers Calcium channel blockers decrease peripheral resistance by inhibiting transmembrane movement of calcium ions. Reflex sympathetically mediated tachycardia may occur in patients treated with calcium channel blockers, but this finding is absent with verapamil and diltiazem because of their direct negative chronotropic effects. Dihydropyridine agents increase proteinuria; nondihydropyridines are less likely to have this effect (29). However, the nondihydropyridine verapamil confers no protection in patients with diabetes mellitus, hypertension, and no previous history of microalbuminuria when compared with an angiotensin-converting enzyme inhibitor (38). Angiotensin-Converting Enzyme Inhibitors and Calcium Channel Blockers Combination therapy with angiotensin-converting enzyme inhibitors and calcium channel blockers is superior in efficacy compared with -adrenergic blockers and diuretics. The significant reduction in cardiovascular mortality and morbidity prompted an early discontinuation of the trial (39). Effect of diureticbased antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. Comparison of antihypertensive treatments in preventing cardiovascular events in elderly diabetic patients: results from the Swedish Trial in Old Patients with Hypertension-2. Oxidation of tetrahydrobiopterin by peroxynitrite: implications for vascular endothelial function. Randomised trial of a perindopril-based blood-pressure-lowering regimen among 6,105 individuals with previous stroke or transient ischaemic attack [erratum in Lancet. The costeffectiveness of treating all patients with type 2 diabetes with angiotensin-converting enzyme inhibitors. A summary of the effects of antihypertensive medications on measured blood pressure. Combined hypertension and orthostatic hypotension in older patients: a treatment dilemma for clinicians. Preventive pharmacologic interventions have proved beneficial (eg, lipid-modifying agents, aspirin), and findings from randomized controlled 37. Certain lipid-modifying agents may be preferred in patients with diabetes mellitus because of the underlying pathophysiology and comorbidities. Lifestyle modifications including diet, weight management, exercise (7), and tobacco avoidance are of utmost importance. Compared with individuals without diabetes, the longterm and short-term prognoses following a coronary event are worse in patients with diabetes mellitus. The rates of reinfarction, congestive heart failure, and death are increased compared with the general population, and risk of coronary disease is directly related to duration of diabetes (8,9). Revascularization procedures are less successful in patients with diabetes mellitus than in patients without diabetes (9). Diabetes blunts the beneficial effects of female sex, and the prognosis following an acute cardiovascular event is worse in women than in men (7). Ethnic differences in the risk of clinical coronary artery disease may exist in individuals with diabetes mellitus (10). Cardiovascular markers such as C-reactive protein and lipoprotein-associated phospholipase A2 may potentially assist in identifying high-risk patients and in instituting preventive measures (11-13).

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Even within the healthy non-diabetic population symptoms white tongue discount atripla 300mg visa, however treatment dynamics florham park discount atripla 600 mg with mastercard, there is substantial variation in fasting glucose levels; around one-third of this variation is genetic permatex rust treatment order generic atripla. These pathogenic effects are likely to be exerted via a direct inhibitory effect on -cells treatment research institute cheap atripla 200mg visa. Whether the differences in hemoglobin glycation associated with genetic polymorphisms are paralleled by differences in glycation in other tissues that are thought to underlie long-term complications of diabetes remains an open question. Serum lipids are important determinants of cardiovascular diseases and are related to morbidity [187]. The high heritability of circulating lipid levels is well established, and earlier studies of individuals with extreme lipid values or families with Mendelian forms of dyslipidemias have reported the involvement of numerous genes and respective proteins in lipid metabolism [188]. Many of these have also been consistently associated with lipid levels in candidate gene studies reported over the past 30 years; many of the same loci with common variants have already been shown to lead to monogenic lipid disorders in humans and/or mice, suggesting that a spectrum of common and rare alleles at each validated locus contributes to blood lipid concentrations [188]. The construction of genetic risk profiles suggests that the cumulative effect of multiple common variants contributes to polygenic dyslipidemia [191]. A possible clinical use of this novel information is to identify individuals at high risk of developing the disease in the general population, so that preventative measures may be more effectively targeted (Figure 12. The study was performed in 4232 patients with diabetes and 4595 normoglycemic adult subjects. They also showed that -cell function adjusted for insulin resistance (using the disposition index) was the strongest predictor of future diabetes, although subjects in the prediabetic stage presented with many features of insulin resistance. It is also noteworthy that many of the variants that were genotyped appear to influence -cell function. Identifying subgroups of the population at substantially different risk of disease is important to target these subgroups of individuals with more effective preventative measures. As more genetic variants are now identified, tests with better predictive performance should become available with a valuable addition to clinical practice. Knowledge of allelic variation at this locus does not seem to offer a rationale for therapeutic choices. In addition, K23K homozygotes randomized to metformin did not show the expected improvement in insulin sensitivity at 1 year [201]. Heritability of insulin secretion, peripheral and hepatic insulin action, and intracellular glucose partitioning in young and old Danish twins. Clustering of hypertension, diabetes, and obesity in adult male twins: same genes or same environments? Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50­60 years. The fetal insulin hypothesis: an alternative explanation of the association of low birthweight with diabetes and vascular disease. A genome-wide search for human non-insulindependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. Likewise, the contribution of structural variants, such as copy number variants, insertions, deletions and duplications, could also contribute to genetic susceptibility not explained by single nucleotide substitutions. Further more novel approaches looking at epigenetic sites, multitissue genome expression related to genetic traits, metabonomics and metagenomics should bring even more knowledge in the near future. Together, these discoveries will continue to improve our understanding of the biologic mechanisms that maintain glucose homeostasis, and of still hidden molecular defects leading to chronic hyperglycemia, and could also lead to the development of more specifically targeted antidiabetic drugs or even genebased therapies. Moreover, pharmacogenetic testing might then be used to predict, for each patient, the therapeutic response to different classes of drugs. Hyperproinsulinaemia in obese fat/fat mice associated with a carboxypeptidase E mutation which reduces enzyme activity. Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in T2D. Close linkage of glucokinase locus on chromosome 7p to early-onset non-insulin-dependent diabetes mellitus. Familial hyperglycaemia due to mutations in glucokinase: definition of a subtype of diabetes mellitus. A genome-wide scan in families with maturityonset diabetes of the young: evidence for further genetic heterogeneity. Identification of a locus for maturity-onset diabetes of the young on chromosome 8p23. Genetic and clinical characterisation of maturity-onset diabetes of the young in Spanish families.

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