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Rapid Responses: Rapid Responses published:
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Incorrect characterisation of Framingham risk score
- Anthony N Glaser (18 November 2005)
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Lowering body iron stores in patients with metabolic syndrome.
- Luca Mascitelli, Francesca Pezzetta, MD (19 November 2005)
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What risk is relevant?
- Matthew P Doogue (20 November 2005)
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Quiche in our time
- Des Spence (21 November 2005)
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The procoagulant nature of the metabolic syndrome
- Arun Natarajan, Azfar G. Zaman, Sally M. Marshall (21 November 2005)
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Dietary guidelines for metabolic syndrome need a rethink
- Katharine M Morrison (24 November 2005)
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When will they ever learn ?
- Dr. Herbert H. Nehrlich (24 November 2005)
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NAFLD: the hepatic manifestation of insulin resistance
- Emily A Johns, David Gorard, Alistair McIntyre and Sue Cullen. (30 November 2005)
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Metabolic syndrome and catecholamimnes
- John A Lee (15 December 2005)
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Potential impact of metabolic syndrome on liver transplant services
- Alastair D Smith (19 December 2005)
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Anthony N Glaser, Private practice of family medicine Summerville, SC 29483, USA
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The Framingham risk score does not include LDL cholesterol as one of its parameters - it uses total cholesterol, not LDL, and HDL cholesterol, as well as the other parameters mentioned in the article. Competing interests: None declared |
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Luca Mascitelli, MD, Chief of Sanitary Service Comando Brigata alpina Julia, Udine 33100 Italy, Francesca Pezzetta, MD
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Dietary modification aimed at reducing body iron stores in subjects with metabolic syndrome might be added to the lifestyle interventions suggested in the editorial by Khunti and Davies.(1) There is a growing body of evidence that serum ferritin, a good indicator of body iron stores, is positively associated with metabolic syndrome.(2,3) Consequently, awaiting specific prospective and interventional studies, it might be wise advising individuals with metabolic syndrome to modify their diets(4) by minimizing consumption of red meat (a rich source of heme iron), avoiding unnecessary iron supplementation, supplementation of vitamin C (an enhancer of nonheme iron absorption), and heavy intake of alcohol, and not discouraging consumption of coffee and low-fat dairy foods (inhibitors of iron absorption). Luca Mascitelli, MD Sanitary Service, Comando Brigata alpina “Julia”, Udine, Italy 33100 Francesca Pezzetta, MD Cardiology Service, Ospedale di San Vito al Tagliamento, San Vito al Tagliamento, Italy 33078 REFERENCES 1. Khunti K, Davies M. Metabolic syndrome. [Editorial]. BMJ 2005;331:1153-4. 2. Jehn M, Clark JM, Guallar E. Serum ferritin and risk of the metabolic syndrome in U.S. adults. Diabetes Care 2004;27: 2422-8. 3. Choi KM, Lee KW, Kim HY, et al. Association among serum ferritin, alanine aminotransferase levels, and metabolic syndrome in Korean postmenopausal women. Metabolism 2005;54:1510-4. 4. Fleming DJ, Tucker KL, Jacques PF, Dallal GE, Wilson PWF, Wood RJ. Dietary factors associated with the risk of high iron stores in the elderly Framingham Heart Study cohort. Am J Clin Nutr 2002;76:1375-1384. Competing interests: None declared |
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Matthew P Doogue, Endocrinology Registrar Christchurch Hospital
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The editorial states "Framingham risk score—based on age, serum concentrations of both LDL and HDL cholesterol, blood pressure, cigarette smoking, and diabetes mellitus—predicts full development only of cardiovascular disease whereas the presence of metabolic syndrome predicts both diabetes and cardiovascular disease". This implies added value of predicting diabetes. However the importance of diabetes is as a risk for cardiovascular disease. The value of a diagnosis is provision of prognosis and effective treatment. The best predictors of cardiovascular disease have the most value when weighing the risks and benefits of treatment. And the treatments are neither risk free nor benign. Competing interests: None declared |
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Des Spence, GP Glasgow G20
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Metabolic Syndrome has a prevalence of 22-39% pf the adult population. Presumably the rest of the population is in pre-metabolic syndrome state. Goodbye wellness and hello a disease of the everyman. This article is staggering in its assumptions, use of surrogate endpoints, lack of perspective outcome data and an assertion that it’s all a question of simple lifestyle advice . With smokers now demonized watch out the obese ( BMI greater than 25) it is your turn next. The health propaganda machines and the health Bolsheviks are gearing up a terrible repression in our one party health state. We in primary care are the agents of this new health terror – reporting and watching all those who might be subversely eating fatty and salty foods. Dissents sent to the health gulag and tortured with prescription diets. Finally Succumbing to overwhelming boredom –some months later than predicted by the flawed Framingham equation – a blessed release from this state of the living death. There is an organic tofu curtain descending across our continent and society – let the health war begin! Competing interests: Nofreelunch |
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Arun Natarajan, Clinical Research Associate School of Clinical Medical Sciences, University of Newcastle, Azfar G. Zaman, Sally M. Marshall
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Dear Editor--The prothrombotic profile present in individuals with the metabolic syndrome may contribute independently to cardiovascular risk in addition to the factors already mentioned in the editorial by Khunti and Davies (1). High levels of plasminogen activator inhibitor-1 (PAI-1) are present in individuals with obesity and in insulin resistant states such as the metabolic syndrome and type 2 diabetes (2). PAI-1 produced by vascular endothelial and smooth muscle cells and adipocytes, is a major physiological antifibrinolytic agent. High levels of PAI-1 can therefore promote clot formation and persistence. Visceral fat, in particular, is an important source of PAI-1, potentially explaining the observation that visceral adiposity is associated with increased plasma PAI-1 levels and the metabolic syndrome (3). In an analysis of the Framingham population, levels of PAI-1 were found to be consistently 2-fold higher in individuals with impaired glucose tolerance and with previously undiagnosed diabetes than in those with normal glucose tolerance (2). Clinical studies have demonstrated a strong correlation between circulating PA1-1 levels and the risk of myocardial infarction and ischaemic stroke (4). Reaven goes as far as including a raised PAI-1 level as an integral component of the metabolic syndrome alongside conventional criteria (2). Therapeutic approaches that have been demonstrated to prevent diabetes, such as diet and exercise or administration of agents such as metformin or thiazolidinediones, can also decrease plasma PAI-1 concentrations (5). The deleterious nature of excessive PAI-1 and its close link with abdominal obesity further underscores the importance of intensive lifestyle changes and weight reduction in obese individuals with the metabolic syndrome. References: 1. Khunti K, Davies M. Metabolic syndrome. BMJ 2005;331:1153-4. 2. Reaven GM. Multiple CHD risk factors in type 2 diabetes: beyond hyperglycaemia. Diabetes Obes Metab 2002;4 Suppl 1:S13-8. 3. Kockx M, Leenen R, Seidell J, Princen HM, Kooistra T. Relationship between visceral fat and PAI-1 in overweight men and women before and after weight loss. Thromb Haemost 1999;82(5):1490-6. 4. Thogersen AM, Jansson JH, Boman K, Nilsson TK, Weinehall L, Huhtasaari F, et al. High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. Circulation 1998;98(21):2241-7. 5. Colwell JA. Treatment for the procoagulant state in type 2 diabetes. Endocrinol Metab Clin North Am 2001;30(4):1011-30. Competing interests: None declared |
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Katharine M Morrison, General Practitioner Ballochmyle Medical Group Mauchline KA5 5BL
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Drs Davies and Khunti's editorial on the 19th November on the importance of metabolic syndrome and its consequences makes highly relevant reading for the General Practitioners who are aiming to modify the adverse cardiovascular effects of this condition. They correctly state that the Mediteranean diet shows benefits over our standard western diet for this set of adverse risk factors. They have not mentioned that there are also demonstrable benefits to be had from low carbohydrate diets or that their are problems with the popular recommendation to replace saturated fats with polyunsaturated fats. I believe these factors deserve closer consideration. Carbohydrate restriction has been shown to improve body mass, reduce high fasting insulin and glucose, reduce triglycerides, raise HDL and lower blood pressure. Some of these factors are improved independently of weight loss. (ref 1.) At the present time in the UK if someone has features of metabolic syndrome they are likely to be strongly advised to go on a high carbohydrate/low fat diet. Drugs for hypertension and high cholesterol will also be initiated if relevant. If insulin resistance is present however the high carb/low fat diet will worsen hyperinsulinaemia leading to a higher triglyceride concentration, raised post meal lipids in the blood, smaller and denser LDL particles and lower HDL-C concentration. Thus failure to focus on the central role of insulin resistance in the metabolic syndrome will increase rather than decrease the cardiovascular risk. It has been estimated that up to 25% of the US population may be suffering from the consequences of insulin resistance. (ref 2) The rest of the developed world will not be far behind. Should we not therefore be making an effort to give people dietary advice that will be the most helpful? Israel has one of the highest dietary polyunsaturated/saturated fat ratios in the world. They eat 8% more omega six polyunsaturated fatty acids than in the US and 12% more than in most European countries. Yet there is a very high prevalence of cardiovascular diseases, hypertension, type 2 diabetes and obesity. These conditions are all associated with hyperinsulinaemia and insulin resistance. There is also an increased cancer incidence and mortality rate, especially with women, compared to western countries. (ref 3) Perhaps our diets which are high in saturated fat are protecting us in certain ways? Yours sincerely, Katharine Morrison 1. Volek JS, Feinman RD, Carbohydrater restriction improves the features of metabolic syndrome. Metabolic syndrome may be defined by the response to carbohydrate restriction. Nutrition and Metabolism 2005. 2:31 16th November 2005. 2. Reaven MD, Clinician Update, Metabolic Syndrome. Pathophysiology and implications for management of cardiovascular disease.Circulation. 2002; 106;286 3. Yam D, Eliraz A, Berry EM. Diet and disease-the Israeli paradox: possible dangers of a high omega-6 polyunsaturated fatty acid diet. Isr J Med Sci 1996 Nov; 32(11):1134-43 Competing interests: type one diabetic son is following restricted carbohydrate, moderate protein, high fat diet. Hbaic 5.1. Hypos are rare and mild. |
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Dr. Herbert H. Nehrlich, Private Practice Bribie Island, Australia 4507
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I fully agree with Dr.Katharine M Morrison and would like to go several steps further. Perhaps we could say that one reason for the blatantly false dietary advice given to patients might be the abysmal lack of nutrition education in medical schools. Myocardial infarction (MI) did not exist before the 1920's. Paul Dudley White, physician to Eisenhower and prominent cardiologist in the fifties remarked about the "strange coincidence" of a new disease appearing at the time that vegetable oils took over from the more traditional fats like butter, lard and tallow. It should be clear by now, to any thinking and halfway informed person that the belief that fat causes high cholesterol in the blood, that high cholesterol causes heart disease and that the interventional strategies such as giving statins to lower cholesterol save cause better health and save lives is poppycock. Space does not permit to list the studies that have shown what I just touched upon. Beginning with the Framington Study, often (mis-)quoted, the Tecumseh Study,the International Atherosclerosis Project and a host of other studies in many countries, there has never been any proof for the lipid hypothesis. Prominent lipid researcher Mary Enig, the one who fought the good fight to have trans fats recognised as the bad guys, is currently one loud and sensible voice in the wilderness of false and health-damaging information that is handed out with the prescription for statins or other medications. Yes, saturated fats are a very healthful and absolutely essential part of any good diet. Butter, eggs, meat fat, lard, coconut oil, palm oil are all excellent foods that support and maintain good health. Dr. Morrison points to the wrong advice making things worse and the patient sicker. That is, unfortunately nothing new in today's sickness industry. Just look at the example of giving statins, which cause a deficiency of Coenzyme Q- 10, a substance the heart (and the rest of the body) desperately needs. One reason that Medicine is now the number one cause of death is that it is common practice to treat the patient with (and to) intervention rather than with common sense and the accumulated wisdom a physician is expected to possess. When anyone asks me about the ratio of macronutrients I recommend, my answer is try to get 60 % of your diet as fat, mostly saturated and monounsaturated (in that order) and don't worry about the proteins and the carbohydrates. But, as the song goes "when will they ever learn..." Competing interests: None declared |
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Emily A Johns, specialist registrar Wycombe Hospital, High Wycombe, HP11 2TT, David Gorard, Alistair McIntyre and Sue Cullen.
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Dear Sir, We read with interest the editorial from Khunti and Davies on the metabolic syndrome and were surprised that there was no mention of non- alcoholic fatty liver disease (NAFLD), the hepatic manifestation of insulin resistance. This spectrum of disease, ranging from non-alcoholic fatty liver (NAFL), via non-alcoholic steato-hepatitis (NASH), may progress to severe liver disease, including cirrhosis(1) and hepatocellular carcinoma.(2) The prevalence of NAFL and NASH in the general population remains unknown, however a study from Sorrentino et al suggested a prevalence of 72.5% of NAFLD in patients with the metabolic syndrome.(3) Insulin resistance is clearly related to the development of hepatic steatosis and has been the subject of an extensive review.(4) The clear and consistent evidence that NAFLD is associated with obesity has yet to be supplemented by adequate evidence that weight loss arrests the progression of the disease.(5) A number of trials of drugs designed to increase insulin sensitivity in the liver (metformin) or in the periphery (thiazolidinediones) suggest liver function tests improve and hepatic fat is reduced though no effect on outcome has yet been demonstrated.(6) Randomised double blind studies are still awaited. As Khunti and Davies rightly point out, strategies to combat coronary heart disease and type 2 diabetes should focus on preventing and intervening early in the metabolic syndrome. This may also help to prevent NAFLD and its progression to cirrhosis. References 1. Buginaesi et al. Expanding the natural history of non-alcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002; 123: 134-40 2. Caldwell et al. Obesity and hepatocellular carcinoma. Gastroenterology 2004; 127:S97-103 3. Sorrentino et al. Silent non-alcoholic fatty liver disease – a clinical histological study. J Hepatol 2004;41:751-7 4. Bugianesi et al. Insulin Resistance: A metabolic pathway to chronic liver disease. Hepatology 2005;42(5):987-1000 5. Bellantini S et al. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med 2000;132:112-117 6. Marchenisi et al. Review article: the treatment of fatty liver disease associated with the metabolic syndrome. Aliment Pharmacol Ther. 2005;22 (Suppl 2):37-9 Competing interests: None declared |
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John A Lee, Retired consultant in public health 1 Lugg View Close Hereford HR1 1JF
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A key to understanding the metabolic syndrome(1)is the relationship between insulin and the catecholamines. They are antagonistic to each other, insulin being essential to anabolism (growth) and the catecholamines to catabolism (breakdown).For example, the catecholamines inhibit the insulin mediated cellular uptake of sugar (2), while insulin antagonises the harmful actions of nor-adrenaline on the heart muscle and vascular reactivity (3,4), and prevents the catecholamine-triggered release of fatty acids from adipose tissue (5). Catecholamines are secreted by the sympathetic nervous system (s.n.s.)while the parasympathetic nervous sysytem (p.n.s.)activates digestive processes including insulin release.(2).Although both are part of the body's stress effector systems, the activities of the s.n.s and p.n,s are opposed to each other(2) Every described risk factor and epidemiological feature of ischaemic heart disease(i.h.d.)is associated with enhanced activity of the catecholamines or s.n.s.and the hormones under it's control(5)There is also convincing evidence that the catecholamines directly cause i.h.d. by a number of mechanisms.(5) The metabolic syndrome probably arises from an imbalance between the s.n.s. and p.n.s.and between insulin and the catecholamines.Treatment should involve reduction of known cardiovascular and type 2 diabetes risk factors and promoting parasympathetic activity by exercise,mental relaxation, sleep and social and family support 1. Kamlesh Khunti, Melanie Davies Metabolic Syndrome Editorial B.M J Vol 331 p.1153 2. David S. Goldstein Stress, Catecholamines and Cardiovascular Disease. Oxford University Press (1995) 3. Lee, J.A.. Downing, S.E. . Effects of insulin on cardiac muscle contraction and responsiveness to norepinephrine Amer. J. Physiol 1976(230) 1360-1365 4 Alexander, W.D Oake R.J The effect of insulin on vascular reactivity to norepinephrine.Diabetes 1977, (26), 611-614. 5. Lee.J.A. The Role of the sympathetic nervous system in ischaemic heart disease Activ Nerv, Sup (Praha) (25)No. 2 110-121 (1983). Competing interests: None declared |
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Alastair D Smith, Assistant Professor of Medicine, Division of Gastroenterology and Hepatology Room 105, Bell Research Building, Duke University Medical Center, Trent Drive, Durham, NC 27710. USA
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Editor – The points made by Dr. Johns and her colleagues in response to Drs. Khunti and Davies are timely.1 Furthermore, it is very possible that end-stage liver disease (ESLD) as the result of non-alcoholic steatohepatitis (NASH), and its complications may overwhelm already stretched liver transplant services.2 For example, NASH may have been the more appropriate diagnosis in a significant proportion of patients who underwent orthotopic liver transplantation for what was believed to have been cryptogenic cirrhosis.3 Therefore, in addition to improved understanding of the pathophysiology of non-alcoholic fatty liver disease, e.g. which patients with uncomplicated steatosis may develop inflammation and fibrosis, it is vital that the potential impact of NASH, subsequent ESLD and its complications be appreciated and accepted by non-liver physicians in both primary and secondary care. Otherwise, it may be the case that the burden of NASH upon liver transplant services will exceed that of chronic hepatitis C virus liver disease.4 References: 1. Khunti K, Davies M. Metabolic syndrome. (Editorial) BMJ 2005;331:1153- 4. 2. Williams R. Services for liver disease in the United Kingdom. (Editorial) BMJ 2005;331:858-859. 3. Contos MJ, Cales W, Sterling RK, Luetic VA, Shiffman ML, Mills AS, et al. Development of nonalcoholic fatty liver disease after orthotopic liver transplantation for cryptogenic cirrhosis. Liver Transpl 2001;7:363-73. 4. Charlton M. Nonalcoholic fatty liver disease: A review of current understanding and future impact. (Review; 117 references). Clin Gastroenterol Hepatol 2004;2:1048-58. Competing interests: None declared |
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