A21 book

INCLUDES GUIDELINES ON • Annual review after surgery • Drug therapy during weight-loss
David W Haslam
Colin Waine
Anthony R Leeds
Medical Management
During Effective Weight-loss
National Obesity Forum
www.nationalobesityforum.org.uk
Medical Management During
Effective Weight-loss

National Obesity Forum
2010
Reprinted with corrections 2010
Medical Management During Effective Weight-Loss
Medical Management During Effective Weight-Loss
Foreword
Since the advent in the UK of surgery for obesity, and with an increasingly strong evidence base Options for achieving weight-loss in medical practice for use of formula low calorie and very low calorie diets, more healthcare practitioners in bothprimary and secondary care are seeing patients who are losing larger amounts of weight than Medical management after bariatric surgery The patient undergoing therapeutic weight-loss requires management of all the other aspects of bodily function that are affected by reduced dietary energy, modified gut function (after surgery), and altered hormonal and metabolic processes.
The healthcare practitioner needs a clearly presented set of guidelines, based on sound science Metabolic complications after bariatric surgery (bypass) and medical evidence, to enable changes to drug therapy and guidance on diet and lifestyle tobe made, and advice to be given with confidence.
The purpose of this publication is twofold: • To provide outline guidance for healthcare practitioners caring for patients after bariatric surgery, following discharge from the surgical unit.
Changes in therapy for other conditions during weight-loss • To provide outline guidance on management of other medical conditions during effective weight-loss, whether following surgery or following non-surgical methods, such as very low calorie diets, part-formula low calorie diets and drugs. This short handbook is based on current guidelines, published research and current practice, but may change as new information becomes available. Practitioners are advised to check for later versions at www.nationalobesityforum.org.uk for any recent revisions.
Acknowledgements, biographical notes and declarations of interest Medical Management During Effective Weight-Loss
Medical Management During Effective Weight-Loss
Options for achieving weight-loss in medical practice
Body weight reduction can be achieved by reducing dietary energy intake, increasingactivity and by altering a number of behaviours relating to eating and activity andinactivity. In practice this means following an energy restricted diet and increasing physicalactivity as a first step. When first reviewed by the dietitian, there may be scope for changeor the patient may already have learned from many sources over many years. Behavioursassociated with being overweight, such as comfort eating, may be acknowledged by thepatient or may be denied. Drug therapy in the UK is at present limited to the use of onedrug: orlistat (Xenical®). Many other drugs are under investigation and within five yearsseveral others will be available. Drug types which are known to limit dietary energy intakein some patients, but for which the licensing is not yet specifically for weight-loss, such asGLP-1 analogues, may become available. Special diets for which there is scientificevidence for effective weight-loss have a place in practice – among these are formulavery low calorie diets (VLCD) and part-food-part-formula low calorie diets (Riecke BF et al.
2010, Johansson K et al. 2009). For the patient who meets NICE criteria (or the patient whoarranges a procedure privately), bariatric surgery is now increasingly available.
During effective weight-loss the amounts of weight lost may have appreciable effects on other conditions and the need for therapy. Following bariatric surgery there is arequirement for long-term follow-up and the account below outlines some of the needs.
Weight-loss with formula diets will be used increasingly in the coming years, and peoplewho achieve weight-loss in this way require medical reviews at intervals and reappraisalof their medication needs.
Medical management after bariatric surgery
Bariatric surgery is undertaken in order to achieve clinically meaningful weight-loss toreduce obesity-related conditions to more manageable levels. A range of metabolicchanges occurs after surgery, including increased insulin sensitivity, increased adiponectinlevels (an indicator of reduced risk of vascular disease) and decreased pro-inflammatorycytokines. Decreased amounts of fat in specific places may improve or ‘cure’ specificconditions: obstructive sleep apnoea, gastro-oesophageal reflux and urinaryincontinence. Decreased total body weight reduces cardiac work, load on joints andimproves posture and walking ability. Procedures which bypass the foregut adjust therelease of gut hormones, which stimulate (ghrelin) and suppress appetite (GLP-1 and PYY),resulting in improved appetite control. Psychological status and social status oftenimprove, as do measures of quality of life.
In practice, the variety of procedures and the absence of guidelines for long-term management present difficulties in primary care. Ultimately, all patients will be dischargedback into the general practitioner’s care, whether from a UK NHS bariatric unit or followinga procedure in the private sector abroad or in the UK.
Medical Management During Effective Weight-loss
Medical Management During Effective Weight-loss
Types of surgery
Roux-en-Y gastric bypass
Gastric banding
Figure 2. Roux-en-Y bypass Dugal Heath FRCS reproduced with permission.
A small 30ml gastric pouch is created by cutting across the stomach and is connected to Figure 1. Laparoscopic band procedure Dugal Heath FRCS reproduced with permission.
the small bowel, which has been divided 80-100 cm below the pylorus. The ‘blind loop’,with the remaining stomach at its head and with bile and pancreatic juice draining into A gastric band creates a small pouch with a narrow outlet. The band is adjustable (it is the duodenum followed by about 50-60 cm of jejunum, is then connected via a new usually not filled until six weeks after surgery). The patient needs to be fully prepared for jejuno-jejunostomy about 80cm below the gastro-jejunostomy. The effect is to divert the the reduction of food intake and educated about choices needed to achieve an adequate food-stream, bypassing important absorptive areas and creating a possible mistiming dietary intake. The patient needs to work with the procedure to eat appropriately and of substrate and enzyme mixing after the jejuno-jejunostomy. follow exercise and lifestyle choices appropriate for a weight-losing regimen, rather than try to follow the former lifestyle and eating habits.
The efficiency of absorption is reduced, but there are also specific risks of iron, B12 and calcium deficiency. There are also risks of early and late dumping syndrome. Since this procedure does not interfere with digestion and absorption, nutritional status Early dumping syndrome may occur if hypertonic food leaves the gastric pouch rapidly ought not to be impaired, but commonly occurring problems (iron, vitamin D and calcium (thus a sugar-containing drink may cause this), and results in a rapid rise of glucose deficiency) may still occur. If the quality of the diet is believed to be poor after surgery, followed by a rebound hypoglycaemia, causing nausea, sweating and faintness. there may well be an inadequate intake of micronutrients.
The hypertonic gut content may draw fluid from the vascular space into the gut causingtransient tachycardia. Rapid movement of this meal through the gut may then cause an During weight-loss, medications which are continued (see below) may need to be given in liquid form, since tablets and capsules may not pass easily through the stricture.
Biliopancreatic diversion (BPD)
The gut is dynamic and does change in response to the reduced food intake, but themajor changes of gut hormones seen after bypass surgery do not occur and there maybe little effect on appetite control. Patients may not feel full after eating. They may betroubled by hunger after gastric banding and may need help to overcome this.
Figure 3. Duodenal switch procedure Dugal Heath FRCS reproduced with permission.
Medical Management During Effective Weight-loss
Medical Management During Effective Weight-loss
As with Roux-en-Y, this procedure combines both restrictive (creation of a gastric pouch) After Roux-en-Y bypass, 80-90% of people with type 2 diabetes may go into remission, and malabsorptive components, but creates a greater reduction of absorptive efficiency while after banding 40-80% may enter remission. Hypertension and sleep apnoea may by leaving a much shorter length of small gut (50-60cm), within which digestion and go into remission in some patients and dyslipidaemias, especially secondary absorption occurs. After BPD, patients are more likely to show overt features of malabsorption, diarrhoea and offensive stools. The range of potential long-term effects after BPD is similar to that following Roux-en-Y, but more so.
Drug therapy after bariatric surgery
A review of drug therapy for co-morbidities in 114 patients treated with gastric bypass Duodenal switch
showed that the greatest changes in medication use occurred in drugs for diabetes Duodenal switch is a modified biliopancreatic diversion, where a long gastric sleeve and and hypertension (Malone and Alger-Mayer 2005). Out of 28 patients using insulin the first part of the duodenum act as the proximal pouch and are connected to the ileum.
preoperatively, 22 discontinued its use by two years. Metformin and sulphonylurea use was The remaining duodenum and jejunum, the bypassed loop, is connected at the ileum.
reduced from 25 to four cases, and 27 to one case from preoperative to two years post-op.
This procedure severely restricts digestion and absorption and 80% of patients achieve Thiazolidinedione use was halved. ACE inhibitor or receptor blocker use was reduced from 33 to 15 cases, beta-blocker use from 21 to 11 cases, calcium channel blocker use from 21 to ten cases and diuretic use from 54 to 19 cases from preoperative to two years Sleeve gastrectomy
post-op. Most of these changes appear to have been made by the three-month review.
In other areas the patterns were different. For depression, SSRI use was reduced from 49 to 35 cases, but tricyclic antidepressants and benzodiazepine use was down from 19 to six cases from preoperative to two years post-op. For osteoarthritis, use of NAIDsand COX-2inhibitors was down from 59 to 33 cases from preoperative to two years post-op.
Drugs for surgery related problems were, not surprisingly, increased. Gastric acidityreducing drugs (H2 receptor anatagonists and proton-pump inhibitors) increased fourfold. In this series of US cases, ursodeoxycholic acid (to inhibit cholesterol gallstoneformation or reduce stone size) was not used preoperatively, but was used in 45 casesaround the time of surgery and in only ten cases at two years. Allopurinol to reduce uric Figure 4. Sleeve gastrectomy Dugal Heath FRCS reproduced with permission.
acid levels, used in 24 cases preoperatively, was used by only ten cases by two years.
Nutritional supplements were increased fourfold from preop to two years post-op, This reduction of stomach volume is usually done as the first of two stages offered to though surprisingly nearly 10% were not taking a supplement at two years.
super-obese patients. Stomach volume is reduced, but the small gut is left intact at this first stage. This is thus a restrictive procedure. Subsequently a bypass procedure is added.
This particular US pattern of drug use change after surgery may not be replicated in other By the time the patient is followed up in primary care, the issues will be the same as for settings but, with the exception of use of ursodeoxycholic acid, there are likely to be similarities between US and UK experience.
Gastric balloons and gastric and duodenal sleeves
Metabolic Complications after bariatric surgery (bypass)
Gastric balloon insertion is not a common procedure in the UK. The insertion of gastric The risk of complications is dependent on the nature of the surgery and the degree and duodenal sleeves to bypass the upper gut internally are experimental procedures of bypass and the relative lengths of the small intestinal loops, either bypassed or at the present time and are not yet approved by regulatory agencies.
functioning for absorption. All are likely to develop vitamin B12 and iron deficiency. Many UK patients have low or deficient vitamin D status preoperatively, due to low Effects of bariatric surgery
exposure to sunlight (between October and March most people in the UK do not Weight reduction is likely to be greatest after BPD, followed by Roux-en-Y bypass, where synthesise vitamin D, unless they take a winter holiday in the sun), low dietary intake and up to 80% of excess weight may be lost by four years post-operatively. Gastric banding effects of their previous experience of weight-losing regimens. Vitamin D status and bone generally can result in up to 60% of excess weight-loss.
health, therefore, need to be watched. Serum trace elements such as Zinc, Selenium andCopper levels have been shown to fall in the majority of patients post-bariatric surgery.
Effects of surgery on co-morbidities are also weight-loss and procedure dependent. The serum levels of trace elements may not accurately reflect tissue and organ stores, so reliance on blood levels may be misleading.
Medical Management During Effective Weight-loss
Medical Management During Effective Weight-loss
Table 1: Metabolic complications of bypass bariatric surgery Post-operative follow-up
From one year and onwards, all bariatric surgery patients should be followed up annually, Complication
Clinical features
Management
even where there are metabolic co-morbidities (the exception is the post BPD patient who should be seen six-monthly: AACE/TOS/ASMBS Bariateric Surgery guidelines). After two years this care would usually be transferred to primary care, provided that the primary care setting can supply adequate support.
Table 2: Recommended investigations of nutritional status after bypass and band procedures at annual review after two years post-op Roux-en-Y gastric bypass
Gastric band
(and duodenal switch)
Adapted (in part) from Table 13 AACE/TOS/ASMBS Bariatric Surgery guidelines, Endocr Pract 2008; 14 (Suppl 1) 1-83.
For BPD, an extended list of investigations is suggested (see the AACE/TOSA/ASMBS guidelines). *the frequency of DEXA scans should be annual after BPD, but the frequency after gastric bypass Adapted from Table 8 AACE/TOS/ASMBS Bariatric Surgery guidelines, Endocr Pract 2008; 14 (Suppl 1) 1-83.
Post-operative guidance on diet
Each surgical unit will give guidance on the diet to be followed in stages after surgery. By the time of return to primary care at the two years post-operative time point, the lowfood intake is selected from a healthy balanced diet chosen from adequate proteinsources, fruits, vegetables and whole grains. Use of small plates may help to controlportion size. The energy (calorie) needs are based on height, weight and age. Since totalfood intake is relatively low, a vitamin and mineral supplement has to be taken dailyindefinitely. Medical Management During Effective Weight-loss
Medical Management During Effective Weight-loss
Table 3: Routine nutrient supplementation after bypass surgery For patients who have had a bypass procedure: Supplement
Product examples
A medical review, a referral to the dietitian (particularly where there is a known history of eating disorder) and measurement of a limited list of variables is indicated (Table 2). A reassessment of cardiac risk factors (it must be remembered that conventional formulae for calculation of risk are not valid following bariatric surgery) and a reappraisal of needfor drug therapy are indicated. A check on aspects of lifestyle, including physical activity, is indicated. At a suitable point in time, referral for plastic surgery may be appropriate.
The medical review should include questions about eating habits, speed of eating, dysphagia, hunger and difficulty with eating particular types of foods.
The patient should be referred back to the specialist unit if there is: Adapted from Table 14 AACE/TOS/ASMBS Bariatric Surgery guidelines, Endocr Pract 2008; 14 (Suppl 1) 1-83 and from material prepared by Ella Segaran of NLOSS for BOSS Dietitians, November 2008.
*recommendations for B12 and iron are higher in the US than in the UK, for B12 1mg/3mo may be Patients who become pregnant after bariatric surgery should be managed within an regarded as sufficient and iron up to 45mg/d may be sufficient.
obstetric unit in a centre which also has a bariatric surgical unit.
As the number of people treated with bariatric surgery in the UK rises, the numberspassing the two-year follow-up in secondary care will rise and there will be a need forannual follow-up in primary care. Formal protocols will be developed by individualbariatric units and national guidelines will be published. In the meantime, the followingpoints of guidance may be useful at the annual review at two and three years andsubsequently.
Does the surgical unit issue guidelines for management beyond two years? Do you have the report and final set of biochemical tests at two years? Have any problems developed during that time? What percentage of excess body weight has been lost? Have all adjustments to therapy for co-morbidities been made? For patients who have had gastric banding: A medical review, a referral to the dietitian (particularly where there is a known history of eating disorder) and measurement of a limited list of variables is indicated. A reassessment of cardiac risk factors (it must be remembered that conventional formulaefor calculation of risk are not valid following bariatric surgery) and a reappraisal of needfor drug therapy are indicated. A check on aspects of lifestyle, including physical activity, is indicated. At a suitable point in time, referral for plastic surgery may be appropriate.
Medical Management During Effective Weight-loss
Medical Management During Effective Weight-loss
be as good as they were immediately after weight-loss (Lanz et al. 2003). There is a Weight-loss using non-surgical methods
developing scientific literature on the potential role for chronic dietary energy restriction on Body weight reductions are characteristically of the order of 8-10 kg following drug prolonged improvement of disease risk factors and weight maintenance (with implications therapy in responders after six months of treatment and of the order of 18kg after for prolonged longevity). New drug, dietary and surgical methods to achieve chronic six months of a formula diet programme beginning with VLCD (Franz et al. 2007). dietary energy intake restriction will be used to help achieve weight maintenance.
VLCD (400-800 kcal/d) are diets formulated to provide the daily requirement of vitamins,minerals, essential fatty acids and dietary fibre. Low energy diets (800-1200 kcal/d) may Changes in therapy for other conditions during weight-loss
be food-based or part-formula-part-food-based, or may be liquid formula diets. There isa place for removal of all conventional food in some patients (who have previously Diabetes (Type 2)
struggled to comply with a food-based restricted diet) and substitution with formula diet Following bariatric surgery
for a period of time prior to the gradual reintroduction of conventional food, with education about healthy eating and lifestyle as energy intake rises to a new lower After gastric banding oral medications for diabetes are continued at the preoperative maintenance level [25kcal/d lower than the baseline dietary energy intake for each dose and then reduced according to indicators of glucose control. The immediate kilogram of weight lost]. The NICE guidance on use of VLCD recommends that reduction of dietary energy intake is likely to reduce glucose levels and hypoglycaemia uninterrupted use should not continue for more than 12 weeks. Many individuals following needs to be avoided. Self-testing of blood glucose and recording of values in a diary a VLCD develop a physiological ketosis which may help to suppress hunger, improve and making a note of any episode of hypoglycaemia (with a request for a check on mood and facilitate dietary compliance. VLCD formula diets contain all required blood glucose levels at the time of the hypo, where this is possible) are essential during micronutrients so nutritional status may be improved after weight-loss, especially in those weight-loss after surgery. During weight-loss the patient should be in close contact with with marginal baseline status, in contrast to the impairment of nutritional status seen after the managing team and the diabetes specialist nurse or practice nurse must be made fully aware of the patient’s surgical timetable.
Weight reductions of this order of magnitude [8-18kg and above] cause improvement As dietary energy intake falls, the drugs most likely to cause episodes of hypoglycaemia in insulin sensitivity, reduction of blood pressure and symptom improvement in should be reduced in dose and stopped first (e.g. sulphonylureas), whereas metformin can be left in place. The need for metformin to be left in place can be reviewed two tothree months after surgery.
Other medical conditions need to be reviewed and medication requirements need to be reassessed during effective weight-loss. Medications for diabetes require regular review After a gastric bypass or following BPD, all oral medications for diabetes would be and adjustment. Therapy for hypertension may likewise change and practitioners should stopped at the time of surgery and the need for any therapy to be reinstated judged some look out for symptoms of hypotension. Other forms of therapy are likely to remain months later. Whether this is good practice is yet to be determined. Glucose monitoring unchanged or possibly reduced in dose.
gives an important record for judging response to surgery.
Change of body weight versus reduced dietary energy intake
Patients on insulin therapy ought, depending on dose and the duration of the disease(time since diagnosis of diabetes), to reduce dose according to blood glucose response. A weight-reducing regimen reduces two primary variables: body weight and dietary A big drop in insulin requirement can be anticipated with the drop in dietary energy energy intake. Metabolic effects of weight-loss may be related to weight-loss or reduced supply immediately following surgery, although some of this reduction ought to have dietary intake or both. A reduction of dietary energy intake increases flux along some occurred preoperatively during the preoperative dietary preparation when energy is pathways and reduces it along others. There is little doubt that pro-inflammatory cytokine restricted in order to achieve liver shrinkage. Where the preoperative dose was low, it is production is reduced during energy intake restriction and clinicians know that caloric likely that this could be stopped altogether at the time of surgery. Patients on much higher restriction reduces pain in both rheumatoid and osteo-arthritis. Chronic caloric restriction doses ought perhaps to be prepared preoperatively for a longer period to achieve some improves biomarkers of longevity and oxidative stress (Heilbronn et al. 2006) as well as loss of visceral adipose tissue as well as liver mass and reduced insulin resistance. Blood classical cardiac risk factors. Reduced energy supply to the liver reduces triglyceride glucose monitoring and close contact and monitoring by the diabetes team is essential.
synthesis, in turn reducing plasma triglyceride and LDL cholesterol.
GLP-1 analogues and related drugs would be discontinued at the time of surgery.
At the end of a three or six month weight-loss programme, blood lipids and bloodpressure may well be lower than at baseline and adjustment of therapy may beappropriate (see below). At two years body weights may be significantly reduced belowbaseline and the patient may have fewer symptoms, but risk factors need to be reviewedagain at one year and two years since some patients may be on a slow weight regainwith a slightly higher dietary energy intake than is desirable and markers of risk may not Medical Management During Effective Weight-Loss
Medical Management During Effective Weight-Loss
During weight-loss with VLCD, LED and drugs
but also by indicators of renal function (in the patient who is also diabetic), includingserum creatinine and urine albumin-creatinine ratio. The fall in dietary energy supply would usually be expected to reduce requirement forboth oral therapy and insulin if these are being used. It is essential to avoid episodes of A recently published meta-analysis on blood pressure responses to drug therapy hypoglycaemia. Sulphonylureas and thiazolidendiones would best be reduced in dose indicates that there is benefit in lowering blood pressure in anyone at sufficient and discontinued as soon as possible, in line with blood glucose results, but it is wise to cardiovascular risk, regardless of blood pressure (Law et al. 2009). Hypertension therapy drop the dose of sulphonylureas or discontinue them altogether at the time of after weight-loss is therefore probably best judged on the basis of home monitoring of commencement of the diet, rather than wait for episodes of hypoglycaemia.
blood pressure, rather than doctor’s office measurements (if possible) and presence orabsence of side effects or symptoms of hypotension. There is no lower threshold below Insulin requirements are likely to be reduced rapidly when patients follow formula low
which lowering blood pressure gives no further benefit in terms of cardiovascular risk energy diets or VLCD, and pre-emptive reduction of dosage by 25% at the time of (within the ranges studied and currently reported in the literature). commencement may be appropriate. However, it is important to note that a gradualtitration of dietary energy intake downwards, through a series of steps (1500, 1200, 1000, Thyroxine
maybe 800 kcal/d) with daily monitoring of blood glucose and regular contact with thediabetes management team to determine a gradual reduction of dosage, may be Weight-loss influences thyroid hormone levels, but in routine practice no replacement preferred by some physicians over a sudden drop in dietary energy requiring a rapid therapy is introduced, unless biochemical hypothyroidism is demonstrated. Functional hypothyroidism with high levels of reverse T3 may occur, but in the UK we have nostandard approach in place to address this. It is likely that clinical trials currently underway There are no formal guidelines on the use of metformin at low dietary energy intake
in the US may provide an indication of when and how any thyroid adaptation to weight- levels, but even at baseline, some patients may be using a relatively high and possibly loss can be corrected pharmacologically, but in the meantime conventional criteria must ineffective dose above 2g/d and may be taking it when markers of renal function suggest be used. Any existing thyroid medications must remain in place and unchanged after that it should be discontinued. Hydration state may influence the potential threat to renal bariatric surgery and during weight-loss with VLCD, low energy diets or drugs. A review function posed by metformin and it may be wise to discontinue metformin below of thyroid status at three, six and/or nine months after commencement of the weight-loss 800kcal/d or when, after surgery, there may be concern about adequate hydration. The need for metformin could then be reassessed afresh two or three months aftercommencement of the diet or after surgery.
Blood lipid lowering drugs
Total blood cholesterol, LDL cholesterol and blood triglyceride often improve after weight- Hypertension
loss, but careful examination of the published literature shows that the lipid lowering Following bariatric surgery
effect is often not sustained at six months or one year after treatment, perhaps becauseof weight gain or perhaps because dietary energy intake has risen sufficiently to drive up Body weight reduction and reduced dietary energy intake lower blood pressure.
Medications for hypertension should remain in place after surgery, except when dosereduction is indicated by repeated blood pressure measurements or where electrolyte A conservative approach is to leave lipid-lowering therapy in place and remeasure blood measurements suggest reduction of diuretic use. Beta-blocker use may be reduced or lipids three and/or six months later, before withdrawing any drugs.
stopped fairly soon, if not at the time of surgery, especially if it is believed to be limitingphysical activity. This is subject to satisfactory blood pressure readings, which ought to Statins are probably best left in place, but fibrates and other triglyceride lowering drugs be done weekly during the early phases of weight-loss after bypass (more frequently might be withdrawn if a sustained adequate reduction of triglyceride to low levels is if needed), but perhaps every two to three weeks after banding.
achieved following weight-loss. Even partial weight regain or a return to higher dietaryenergy intake levels may result in a rebound of triglyceride levels.
During weight-loss with VLCD, LED and drugs
The electrolyte and water changes on commencement of a VLCD can be quite marked, Conventional formulae for calculation of cardiac risk are not valid after bariatric surgery.
and if the patient is only using a diuretic, there may be merit in stopping this or reducingdosage on commencement of the diet. Frequent (weekly) measurements of blood Aspirin, anti-platelet drugs, warfarin and heparin
pressure are indicated (more frequently if there is concern), falling to fortnightly when the Aspirin should be continued but the inhibitory effects of aspirin and ketones on The longer-term need for therapy can be reassessed at three and/or six months, when the renal uric acid handling need to be considered for those on very low calorie merits of continuing ACE inhibitors and AR blockers can be judged, not just by blood pressure, Medical Management During Effective Weight-Loss
Medical Management During Effective Weight-Loss
Anti-platelet drugs
There is no evidence that oral contraceptives are less effective after weight-loss, but the patient should be advised of these possible changes and may care to make appropriate Clopidogrel and related drugs should be continued.
choices, and consider other methods of contraception.
Warfarin
Drugs for arthritis
Warfarin dose response is influenced by dietary vitamin K. There are few Reduced dietary energy intake or absorption often results in an improvement in reported cases of problems arising during weight-loss and these relate to symptoms in rheumatoid arthritis, possibly due to a reduction of inflammatory cytokine extreme changes of diet not usually seen (see below).
production. Recently published evidence suggests that similar changes may occur inosteoarthritis with symptom reduction after effective weight-loss.
No RDA was given in EU Council Directive 90/496/EEC, but the generally accepted requirement for vitamin K is about 1µg/kg. Thus an 80kg man would Drug regimens may need to be changed on a case-by-case basis, according to require 80µg/d and a 65kg woman about 65µg/d. Vitamin K requirement in symptoms and markers of disease activity. Some patients may be able to stop or reduce morbidly obese individuals or during weight-loss has not been determined Drugs for gastric hyperacidity
If intake or absorption of vitamin K were to change significantly, the dose of warfarin may need to change. Measurement of the INR at baseline and a few Proton pump inhibitors and H2 receptor antagonists may be continued as previously. days after each major dietary change is recommended. Where formula diets With medical and dietary weight reduction, gastro-oesophageal reflux may be reduced, are used (usually containing 40µg vitamin K per portion or sachet of product), but the evidence for a benefit in reducing risk of oesophageal carcinoma needs to be each change of dietary level with consequent change of vitamin K intake ought considered before therapy is stopped. After surgery there may be a greater need for to be followed by an INR test a few days later. Consistency of intake from proton pump inhibitors in some cases.
day to day is important and those using formula diets should not change the amount of formula product consumed from day to day.
Antipsychotics
Medication should continue unchanged unless adjusted in consultation with the patient’s A case report (Quereshi GD et al. 1981) described warfarin resistance in someone following a vegetable-rich weight reducing diet (calculated to contain 1270µg/d of vitamin K), who became less resistant to warfarin when moved to Antidepressants
a ‘regular’ diet (containing 360µg/d vitamin K).
Antidepressants should continue unchanged until a relatively stable steady state has been achieved, when gradual dose reduction and cessation may be possible in somecases.
Indications for heparin use remain unchanged.
Contraceptive pill
Blood lithium levels are likely to change and measurement of blood levels is indicated, Weight-loss alters the hormonal milieu, often reduces insulin resistance and often allows especially during rapid weight-loss.
pregnancy to occur in those who have long failed to achieve this. Any womancommencing an effective weight-loss programme, whether surgical or medical, needs to Corticosteroids
be aware that fertility may change and that long-held assumptions about contraceptiveefficacy may no longer apply.
The effect of dietary energy restriction and/or weight reduction on suppression of pro-inflammatory signals may allow gradual dose-reduction.
Anticonvulsants
Loss of abdominal fat may change pelvic anatomy – if barrier methods are used, reassessment of size and fit may be needed.
Anticonvulsant therapy must continue throughout weight reduction, following either Liver steatosis may be decreased with a change of hepatic capacity for drug surgery or diet. Changed body weight and hepatic function may change the dose requirement and this may be judged by measuring blood levels or observing clinical The dynamics of oestrogen cycling within the gut may change and the response. Asking the patient to keep a diary of clinical events (fits) and notes on causes efficacy of oral contraceptives may also change.
Medical Management During Effective Weight-Loss
Medical Management During Effective Weight-Loss
References
of these (infections, life-stresses, sleep deprivation) may be helpful during an effective AACE/TOS/ASMBS Bariatric Surgery guidelines, Endocr Pract 2008; 14 (Suppl 1) 1-83. Franz MJ et al. Weight-loss outcomes: a systematic review and a meta-analysis of weight-loss clinical trials with aminimum 1-year follow-up. J Am Dietetic Assoc 2007; 107: 1755-1767.
Other effects of weight-loss
Heilbronn LK, de Jonge L, Frisard MI et al. Effect of 6 month calorie restriction on biomarkers of longevity, metabolicadaptation, and oxidative stress in overweight individuals: a randomized trial. JAMA 2006; 295: 1539-48.
Uric Acid and Gout
Johansson K, Neovius M, Lagerros YT, Harlid R, Rossner S, Granath F, Hemmingsson E. Effect of a very low-energydiet on moderate and severe obstructive sleep apnoea in obese men: Blood uric acid is influenced by dietary purine intake, endogenous uric acid production a randomised controlled trial. BMJ 2009; 339: b4609 doi 10.1136/bmj.b4609.
and renal excretion. Genetic factors influence absorption of purines and uric acid http://www.bmj.com/cgi/reprint/339/dec03_1/b4609 metabolism. Blood uric acid levels tend to be higher in overweight and obese people and Johnson JB, Summer W, Cutler RG et al. Alternate day calorie restriction improves clinical findings and reduces the process of weight-loss raises uric acid further. Any ketosis occurring during weight- markers of oxidative stress and inflammation in overweight adults with moderate asthma. Free Radic Biol Med2007; 42: 665-674.
loss after surgery or when following a formula VLCD may reduce renal excretion of uric Lantz H, Peltonen M, Ågren L, Torgerson JS. Intermittent versus on-demand use of a very low-calorie diet: acid, further raising blood levels and increasing the risk of acute clinical gout.
a randomized 2-year clinical trial. J Internal Medicine 2003; 253: 483-471.
Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: Blood uric acid should be measured and the patient questioned about personal and meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. family history of gout. Patients should be warned of the risk of possible development of BMJ 2009; 338; b1665; doi: 10.1136/bmj.b1685.
gout during weight-loss. Where appropriate, uric acid lowering therapy should be Malone M, Alger-Mayer SA. Medication use patterns after gastric bypass surgery for weight management. National Institute for Clinical Excellence Clinical Guidline 43 Obesity at:http://www.nice.org.uk/guidance/index.jsp?action=download&o=30365 Gallstones
Many overweight and obese patients have already developed gallstones, which in many Qureshi GD, Reinders TP, Swint JJ, Slate MB. Acquired Warfarin Resistance and Weight-Reducing Diet.
cases may be asymptomatic. In many cases the gall bladder may be non-functioning.
During weight-loss the litho-genicity of the bile may increase, though scientific evidence Riecke BF, Christensen R, Christensen P, Leeds AR, Boesen M, Lohmander LS, Astrup A, Bliddal H. Comparing two supporting this idea is weak. An effective weight-loss regimen, whether surgical or low-energy diets for the treatment of knee osteoarthritis symptoms in obese patients: a pragmatic randomized medical, will perturb the physiological dietary fat-induced gall bladder filling and draining clinical trial. Osteoarthritis and Cartilage 2010; 10/1016/j.joca.
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WP3-4YDKK1R- cycle and patients should be warned that there is an increased risk of developing 1&_user=10&_coverDate=02%2F17%2F2010&_rdoc=1&_fmt=high&_orig=search&_sort=d&_docanchor=&view=c&_ symptoms due to gallstones during an effective weight-loss programme. acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=bf12a25f9d871fb66a8cc335eaed74bb Sjöström L et al. Lifestyle, Diabetes and Cardiovascular Risk Factors 10 years after Bariatric Surgery.
Vitamin D status
New England Journal of Medicine 2004; 351: 2683-93 [Swedish Obesity Subjects (SOS) Study].
See also:
A proportion of people entering the surgical pathway or about to commence a medical Aills L et al., ASMBS Allied Health Nutritional guidelines for the surgical weight-loss patient. Surgery for Obesity and weight-loss programme may be vitamin D deficient or have low-normal levels, possibly Related diseases 2008; 4: S 73-S108.
due in part to repeated weight-loss attempts with dietary regimens, which result ininsufficient dietary vitamin D intake. At UK latitudes, vitamin D is not synthesised in the Websites and resources
skin during autumn and winter (October to March). There may be merit in measuring The National Obesity Forum is not responsible for the content of other websites.
blood levels before any weight-loss regimen. Vitamin D status should be checked after National Institute for Clinical Excellence Obesity Guidelines:
Dietitians in Obesity Management
http://domuk.org/category/home/
http://domuk.org/wp-content/uploads/2007/11/gastric-by-pass-and-weightloss-patients-october-07.pdf
British Obesity and Metabolic Surgery Association
http://www.british-obesity-surgery.org/index.htm
http://www.british-obesity-surgery.org/bariatric_surgery.htm
Scottish Intercollegiate Guidelines Network – Management of Obesity (115) and Diabetes (116)
http://www.sign.ac.uk/guidelines/fulltext/115/index.html
http://www.sign.ac.uk/guidelines/fulltext/116/index.html
British Obesity Surgery Patient Association
http://www.bospa.org/Default.aspx
http://domuk.org/category/sub-groups/surgery/
Medical Management During Effective Weight-Loss
Medical Management During Effective Weight-Loss
Acknowledgements
We are grateful to colleagues for advice, guidance and criticism, especially from PratikSufi and Dugal Heath at the North London Obesity Surgery Service at the WhittingtonHospital, and Daniel Darko at the Jeffrey Kelson Diabetes Centre, Central MiddlesexHospital. Stephan Rössner at the Obesity unit, Karolinska Institute, Stockholm, Swedenand Henning Bliddal, Frederiksberg Hospital, Copenhagen, Denmark also kindlyreviewed the text. Figures 1-4 are reproduced with the kind permission of Dugal Heath,FRCS.
Biographical Notes
David Haslam is a GP with a special interest in obesity and cardiometabolic disease. He is chair of the National Obesity Forum for which he is also clinical director, and alsoworks in the Centre for Obesity Research at the Luton and Dunstable Hospital. He previously led the formulation of guidelines for adult obesity management in primarycare and guidelines for management of childhood obesity with the Royal College ofPaediatrics and Child Health.
Colin Waine was formerly Chair of the National Obesity Forum and is Visiting Professor in Primary and Community Care at the University of Sunderland. He was chair of the Royal College of General Practitioners from 2000 to 2003 and Director of Primary Care in Sunderland from 1993 to 2003.
Anthony Leeds is Visiting Professor in the Faculty of Life Sciences at the University of Copenhagen, Visiting Senior Fellow at the University of Surrey and Physician within theNorth London Obesity Surgery Service at the Whittington and Central MiddlesexHospitals. He is Medical Director of the Cambridge Weight Plan.
Declaration of Interests:
DH consults for LighterLife and ARL is employed as Medical Director by CambridgeWeight Plan.
Footnote: The US Endocrinology Society is preparing a document ‘Endocrine andNutritional Management of the Post-Bariatric Surgery Patient: An Endocrine SocietyClinical Practice Guideline’. Progress may be checked by visiting www.endo-society.org/towards the end of 2010.
Medical Management During Effective Weight-Loss
Medical Management During Effective Weight-Loss
National Obesity Forum
www.nationalobesityforum.org.uk
Medical Management During Effective Weight-Loss
Medical Management During Effective Weight-Loss
Produced with an educational grant from Cambridge Weight Plan

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Organism list not requested in this search BIOLOGICAL ACTIVITIES ISOLATED FOR XANTHOHUMOL% XANTHOHUMOL (FLAVONOID) PHARMACOLOGY OF COMPOUND - IN VITRO * IC50 31.4 MICROMOLS/ACTIVE * L10219 * VS.CDNA-EXPRESSED HUMAN CYP1A2. PHARMACOLOGY OF COMPOUND - IN VITRO * CONCENTRATION VARIABLE NOT STATED ACTIVE * SEE ARTICLE FOR OTHER TEST RESULTS. * L30201 *PHARMACOLOGY OF COMPOUND - IN VITRO * C

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