Correction to: Adipokines and the insulin resistance syndrome in familial partial lipodystrophy caused by a mutation in lamin A/C.

The authors regret that Alexandra Bargiota's name was spelt incorrectly in the author list. The details given in this correction are correct.

The adipokine zinc-alpha2-glycoprotein (ZAG) is downregulated with fat mass expansion in obesity.

INTRODUCTION: Zinc-alpha2-glycoprotein (ZAG) is a novel adipokine, which may act locally to influence adipocyte metabolism. This study assessed the effect of increased adiposity on ZAG expression in adipose tissue in human subjects. The study also examined the association between ZAG and adiponectin expression in human adipose tissue, and whether ZAG modulates adiponectin secretion by human adipocytes. METHODS: Adipose tissue (visceral and subcutaneous) was collected from human subjects with a wide range of BMIs. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were used for in vitro studies. ZAG mRNA levels were quantified by real-time PCR and protein by Western blotting. RESULTS: In human subjects, ZAG mRNA level was negatively correlated with BMI (r = -0.61, P < 0.001, n = 23, visceral; r = -0.6, P < 0.05, n = 14, subcutaneous) and fat mass (r = -0.62, P < 0.01, visceral; r = -0.6, P < 0.05, subcutaneous). Negative associations were also found between ZAG mRNA and insulin resistance parameters including plasma insulin (r = -0.65, P < 0.001, visceral; r = -0.55, P < 0.05, subcutaneous) and homeostasis model of insulin resistance (HOMA-IR) (r = -0.65, P < 0.001, visceral; r = -0.52, P = 0.055, subcutaneous), and C reactive protein (CRP) (r = -0.46, P < 0.05, visceral; r = -0.53, P < 0.05, subcutaneous). However, ZAG mRNA was positively correlated with adiponectin (r = 0.5, P < 0.05, visceral; r = 0.82, P < 0.001, subcutaneous) but negatively associated with leptin mRNA (r = -0.42, P < 0.05, visceral; r = -0.54, P < 0.05, subcutaneous). ZAG secretion by differentiated human adipocytes was abundant. Addition of recombinant ZAG stimulated adiponectin release from human adipocytes. CONCLUSION: ZAG gene expression in adipose tissue is downregulated with increased adiposity and circulating insulin. ZAG mRNA is positively correlated with adiponectin mRNA, and ZAG enhances adiponectin production by human adipocytes. We suggest that ZAG is linked to obesity and obesity-related insulin resistance.

Ghrelin inhibits autonomic function in healthy controls, but has no effect on obese and vagotomized subjects.

OBJECTIVE: Ghrelin inhibits sympathetic nervous system (SNS) activity in rodents. We studied the effect of ghrelin on healthy humans, in obesity and in vagotomized subjects. DESIGN: Randomized, double-blinded, placebo-controlled crossover. SUBJECTS: Seven lean [mean body mass index (BMI) 23·6 ± 0·9 kg/m(2) ], seven morbidly obese (mean BMI 50·9 ± 4·4 kg/m(2) ) and seven post-gastrectomy subjects (mean BMI 22·0 ± 1·1 kg/m(2) ). MEASUREMENTS: Subjects were randomized to intravenous ghrelin (5 pmol/kg/min) or saline over 270 min. Subjects had a fixed calorie meal and a free choice buffet during the infusion. Heart rate variability (HRV) was measured. Total power (TP) represents overall autonomic function, low-frequency (LF) power represents sympathetic and parasympathetic activity, and high-frequency (HF) power represents parasympathetic activity. Very low (VLO) frequency represents the frequency band associated with thermogenesis. RESULTS: Preliminary anova analysis, looking at all three subject groups together, showed that ghrelin had an overall highly significant inhibitory effect on TP (P = 0·001), HF power (P = 0·04), VLO power (P = 0·03) and no effect on LF (P = 0·07). Further subset analysis revealed that ghrelin had a significant effect on TP (P = 0·03), borderline effect on LF power (P = 0·06) and no effect on HF power (P = 0·1) in healthy controls. By contrast in obese subjects, ghrelin had no effect on TP (P = 0·3), LF (P = 0·5) and HF (P = 0·06) and also no effect in the vagotomized subjects on TP (P = 0·7), LF (P = 0·7) and HF (P = 0·9). Ghrelin had no effect on the LF/HF ratio. CONCLUSIONS: Ghrelin inhibits SNS activity in healthy controls with a moderate effect on parasympathetic nervous system activity but had no effect on obese subjects. Vagotomized subjects also did not respond to ghrelin, suggesting the vagus nerve is important for the effects of peripheral ghrelin on the SNS.

Type 2 diabetes and cardiovascular disease in polycystic ovary syndrome: what are the risks and can they be reduced?

Polycystic ovary syndrome (PCOS) is a risk factor for Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), but these risks are poorly defined. This study aimed to evaluate the evidence for these risks and whether screening and risk reduction are feasible. Medline reviews and data quality analysis were used using standard tools. Results showed that (i) polycystic ovary syndrome is a risk factor forT2DM but the magnitude of risk is uncertain, (ii) fasting plasma glucose is an inadequate screening test forT2DM in this population and the oral glucose tolerance test is superior, (iii) the identification of women with PCOS for diabetes screening is constrained by current diagnostic criteria for PCOS; however, women with oligomenorrhoea and those with diagnosed PCOS and obesity or a family history of T2DM are at highest risk, (iv) risk factors for T2DM are improved by weight loss interventions and by metformin. However, no studies have determined whether T2DM incidence is reduced, (v) polycystic ovary syndrome is associated with cardiovascular disease (CVD) risk factors but data on CVD incidence are weak, (vi) risk factors for CVD are improved by the same interventions and statins and (vi) no studies have evaluated whether CVD incidence is reduced. While PCOS has important metabolic associations, and short-term interventions reduce risk factors for T2DM and CVD, data on prevalence and incidence of T2DM and particularly CVD are poor. There is a need for a clear definition of PCOS, for diabetes screening protocols and for long-term studies to determine whether risks can be reduced.

In humans the adiponectin receptor R2 is expressed predominantly in adipose tissue and linked to the adipose tissue expression of MMIF-1.

In this study, the regional adipose tissue-adiponectin (AT-ADN) and adiponectin receptor (R1 and R2) expression and their relation with metabolic parameters, circulating and AT-derived cytokine expressions were compared. Paired subcutaneous adipose tissue (SCAT) and visceral adipose tissue (VAT) were taken from 18 lean and 39 obese humans, AT-mRNA expression of adipokines analysed by RT-PCR and corresponding serum levels by enzyme-linked immunosorbent assay (ELISA). R1 and R2 adipocyte expression was compared with 17 other human tissues. ADN-gene expression was lower in VAT than SCAT [mean (SD) 1.54 (1.1) vs. 2.84 (0.87); p < 0.001], and lower in obese subjects (VAT : p = 0.01;SCAT : p < 0.001). SCAT-ADN correlated positively with serum ADN (r = 0.33;p = 0.036) but not VAT-ADN. AT expressions of ADN and macrophage migration inhibiting factor (MMIF), IL18 and cluster of differentiation factor 14 (CD14) in both depots showed inverse correlations. R1 and R2 were expressed ubiquitously and R2 highest in SCAT, and this is much higher (x100) than R1 (x100). R expression was similar in lean and obese subjects and unrelated to the metabolic syndrome, however, receptors correlated with VAT-MMIF (R 1: r = 0.4;p = 0.008;R 2: r = 0.35,p = 0.02) and SCAT-MMIF expression (R 2: r = 0.43;p = 0.004). Unlike ADN, its receptors are expressed in many human tissues. Human R2 expression is not highest in the liver but in AT where it is associated with MMIF expression. The adiponectin-dependent insulin-sensitizing action of thiazolidinediones is thus probably to differ amongst species with weaker effects on the human liver.

Ghrelin restores 'lean-type' hunger and energy expenditure profiles in morbidly obese subjects but has no effect on postgastrectomy subjects.

OBJECTIVE: To examine the effects of ghrelin on appetite and energy expenditure in lean, obese and postgastrectomy subjects. DESIGN: A randomized, double-blind, placebo-controlled study. PATIENTS: Nine lean subjects (mean body mass index (BMI) 23.5+/-3 kg/m(2)) and nine morbidly obese subjects (mean BMI 51.4+/-10 kg/m(2)) and eight postgastrectomy subjects (mean BMI 22.4+/-1.0 kg/m(2)). INTERVENTIONS: Subjects were infused with either intravenous ghrelin (5 pmol kg(-1) min(-1)) or saline over 270 min. They were given a fixed energy breakfast followed by a free buffet lunch towards the end of the infusion. MAIN OUTCOME MEASURES: Visual analogue scales were used to record hunger and energy expenditure was measured by indirect calorimetry. RESULTS: Ghrelin increased energy intake at the buffet lunch in lean subjects (a 41% increase, P<0.01) and obese subjects (35% increase, P=0.04) but not in postgastrectomy subjects. Lean subjects showed a characteristic preprandial rise and postprandial fall in hunger scores, which was exaggerated by ghrelin infusion. Obese subjects showed little variation in hunger scores, but a 'lean-type' pattern was restored when given exogenous ghrelin. Ghrelin had no effect on resting metabolic rate but did increase respiratory quotient (RQ) in obese subjects. Ghrelin also increased RQ variability over time in all three groups (ANOVA, P<0.001). CONCLUSIONS: Hunger scores are abnormal in the obese, perhaps because of impaired ghrelin secretion. The effect of ghrelin in restoring normal hunger profiles in the obese suggests causality, confirming an important role in eating behaviour. Ghrelin also increases RQ in obese humans and increased RQ variability in all groups. This suggests that ghrelin regulates substrate utilization and may promote metabolic flexibility.

Effects of peripheral administration of synthetic human glucose-dependent insulinotropic peptide (GIP) on energy expenditure and subjective appetite sensations in healthy normal weight subjects and obese patients with type 2 diabetes.

BACKGROUND: Apart from their role in insulin secretion and glucose homeostasis, the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) exert a number of extra-pancreatic effects which in the case of GIP remain largely unknown. DESIGN/PATIENTS: Six obese male patients with diet-controlled type 2 diabetes (T2DM) and six healthy lean male subjects were studied. The protocol included four experiments for each participant that were carried out in randomized order and included: GLP-1 infusion at a rate of 1 pmol/kg/min for 4 h, GIP at a rate of 2 pmol/kg/min, GLP-1 (at 1 pmol/kg/min) with GIP (at 2 pmol/kg/min), and placebo infusion for 4 h. Energy expenditure (EE) was measured throughout with indirect calorimetry and subjects were given a series of visual analogue scales to rate hourly their hunger, fullness, urge to eat and prospective consumption of food. Immediately following termination of the infusions all subjects were offered a free choice buffet lunch and total calorie and macronutrient intake was calculated. RESULTS: During GIP infusion there was a trend for healthy subjects to report higher hunger scores and a reduction in EE only when compared with placebo. These parameters remained unchanged in patients with T2DM. Ad libitum energy intake after all four infusions was the same in both groups. CONCLUSION: We report here for the first time that GIP infusion may impact on resting EE and subjective appetite sensations in normal weight healthy subjects and further studies with larger numbers of subjects are required to help define more conclusively the precise role of GIP in energy balance in humans.

Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal.

OBJECTIVE: To investigate a potential role for obestatin in humans by examining response to a fixed energy meal. CONTEXT: A new anorectic peptide hormone, obestatin has recently been isolated from rat stomach. The significance of this peptide in humans is unknown. STUDY DESIGN: Case-control study. SETTING: Hospital-based study. PATIENTS: Nine healthy controls, nine morbidly obese subjects and eight post-gastrectomy subjects. INTERVENTION: Subjects attended after an overnight fast and were given a fixed energy meal (1550 kJ). MAIN OUTCOME MEASURE: The response of obestatin to a meal in the different groups. RESULTS: Fasting obestatin was significantly lower in obese subjects as compared to lean subjects (27.8+/-4 vs 17.2+/-2 pg/ml, P=0.03). Obestatin was also decreased in gastrectomy subjects but this did not reach statistical significance (27.8+/-4 vs 21.9+/-3 pg/ml, P=0.3). Obestatin did not change significantly from baseline in response to the meal. Lean and obese subjects had a similar obestatin/ghrelin ratio (0.04+/-0.003 vs 0.05+/-0.009, P=0.32), but this was higher in the gastrectomy group (0.04+/-0.003 vs 0.1+/-0.01, P<0.001). CONCLUSIONS: Obestatin does not vary significantly with a fixed energy meal, but is significantly lower in morbidly obese subjects as compared to lean subjects supporting a possible role for obestatin in long-term body weight regulation. Obestatin tended to be lower in gastrectomy subjects and their obestatin/ghrelin ratio differed from healthy controls. Hence, the expression of obestatin is altered following gastrectomy, suggesting other sites outside the stomach may also secrete obestatin.

Growth hormone and changes in energy balance in growth hormone deficient adults.

BACKGROUND: Adults with growth hormone deficiency (AGHD) have an adverse body composition with an increased prevalence of obesity. It is not known whether growth hormone replacement (GHR) results in alterations in energy intake (EI) and/or energy expenditure (EE). The aim of the study was to investigate the effects of GHR on EI and EE. MATERIALS AND METHODS: Nineteen hypopituitary adults (14 males, 5 females, mean age 46.2 years) with severe GHD (peak GH response to glucagon

Lack of an acute effect of ghrelin on markers of bone turnover in healthy controls and post-gastrectomy subjects.

BACKGROUND: Ghrelin is a gut-brain peptide that powerfully stimulates appetite and growth hormone secretion and is also known to directly regulate osteoblast cell function in vitro and in animal models. Little is known about the effects of ghrelin on bone turnover in humans. As the stomach is the main site of ghrelin synthesis, gastrectomy patients are deficient in ghrelin; they are also prone to osteopenia and osteomalacia. HYPOTHESIS: Ghrelin may play a role in bone regulation in humans; ghrelin deficiency following gastrectomy is associated with the disrupted regulation of bone turnover seen in these subjects. SUBJECTS AND METHODS: In a randomised, double-blind, placebo-controlled study 8 healthy controls and 8 post-gastrectomy subjects were infused with intravenous ghrelin (5 pmol/kg/min) or saline over 240 min on different days. Subjects were given a fixed energy meal during the infusion. Ghrelin, GH, type-1 collagen beta C-telopeptide (betaCTX), a marker of bone resorption, and procollagen type-1 amino-terminal propeptide (P1NP), a marker of bone formation, were measured. RESULTS: Fasting ghrelin was significantly lower in the gastrectomy group during the saline infusion (226.1+/-62.0 vs. 762+/-71.1 ng/l p<0.001). Growth hormone was significantly higher at 90 min after the ghrelin infusion, compared to saline in both healthy controls (61.1+/-8.8 vs. 1.4+/-0.6 mIU/l p<0.001) and gastrectomy subjects (61.1+/-11.8 vs. 0.9+/-0.2 mIU/l p<0.001) confirming the ghrelin was bioactive. Gastrectomy subjects were significantly older and had significantly higher plasma betaCTX than healthy controls at all time points (ANOVA p=0.009). After adjustment for age and BMI ghrelin was found to be a significant predictor of baseline plasma betaCTX and was inversely correlated with baseline plasma betaCTX (beta=-0.54 p=0.03 R2=26%). However, there was no significant effect of the ghrelin infusion on plasma betaCTX or P1NP in either subject group. CONCLUSIONS: Ghrelin infusion has no acute effect on markers of bone turnover in healthy controls and post-gastrectomy subjects, but is inversely correlated with bone resorption.

Gut peptides and the regulation of appetite.

There is a growing worldwide epidemic of obesity. Obese people have a higher incidence of type 2 diabetes and cardiovascular disease, and hence present increasing social, financial and health burdens. Weight loss is always difficult to achieve through lifestyle changes alone, and currently licensed anti-obesity drug treatments, such as orlistat and sibutramine, if tolerated, only achieve modest weight loss. Therefore, there is a need to identify more potent pharmacological targets. In the last 10 years, discoveries of new hormones such as leptin and ghrelin, together with greater understanding of previously described hormones such as cholecystokinin (CCK), pancreatic polypeptide (PP), peptide YY (PYY) and glucagon-like peptide 1 (GLP-1), have led to a rapid increase in our knowledge of the regulation of energy balance. Among the most important factors, controlling appetite and satiety are peptide hormones released from the gut. In this paper, we provide a full up-to-date overview of the current state of knowledge of this field, together with the potential of these peptides as drugs, or as other therapeutic targets, in the treatment of obesity. Finally, we propose an integrated model to describe the complex interplay of these hormones in the broader physiology of energy balance.

Prevalence of obesity in type 2 diabetes in secondary care: association with cardiovascular risk factors.

AIMS: To determine the prevalence of overweight and obesity among patients with type 1 and type 2 diabetes mellitus attending a secondary care diabetes clinic in the United Kingdom, and to assess the impact of overweight and obesity on glycaemic control and cardiovascular risk factors in patients with type 2 diabetes. METHODS: 3637 patients with diabetes were identified from the hospital electronic diabetes register, 916 with type 1 diabetes (mean (SD) age 40.4 (15.1) years, 496 male) and 2721 with type 2 diabetes (mean (SD) age 62.5 (11.8) years, 1436 male). Data on body mass index (BMI), glycaemic control, lipid profiles, and blood pressure were extracted. RESULTS: Of patients with type 1 diabetes, 55.3% were overweight (BMI >or=25 kg/m(2)), 16.6% were obese (BMI >or=30 kg/m(2)), and 0.4% had morbid obesity (BMI >or=40 kg/m(2)). In contrast, 86% of patients with type 2 diabetes were overweight or obese, 52% were obese, and 8.1% had morbid obesity. Obese patients with type 2 diabetes were younger, had poorer glycaemic control, higher blood pressures, worse lipid profiles, and were more likely to be receiving antihypertensive and lipid lowering drugs compared with patients with BMI <30 kg/m(2). CONCLUSIONS: Obesity is the rule among patients attending this hospital diabetes clinic, with 86% of those with type 2 diabetes overweight or obese. Obesity is associated with significantly worse cardiovascular risk factors in this patient group, suggesting that more active interventions to control weight gain would be appropriate.

Endothelial dysfunction: cause of the insulin resistance syndrome.

Insulin resistance has been proposed as the metabolic basis of atherogenesis. This hypothesis is based on the concept of the "insulin resistance syndrome," according to which insulin resistance is viewed as the primary abnormality that gives rise to dyslipidemia, essential hypertension, impaired glucose tolerance, and NIDDM. However, this hypothesis takes no account of the well-established and central role of vascular endothelium in the atherogenic process. Although endothelial injury is an early and prominent feature of atherogenesis, relatively little attention has been given to its metabolic consequences. In subjects with NIDDM, we have shown that endothelial dysfunction is associated with insulin resistance, raising the question of whether this relationship could be causal. In this article, we review the factors that are considered to be responsible for the development of endothelial dysfunction during atherogenesis, together with the metabolic consequences of endothelial dysfunction. While dysfunction of the endothelium in large and medium-sized arteries plays a central role in atherogenesis, we argue that dysfunction of peripheral vascular endothelium, at arteriolar and capillary level, plays the primary role in the pathogenesis of both insulin resistance and the associated features of the insulin resistance syndrome. We propose that the insulin resistance syndrome, together with many aspects of atherogenesis, can be viewed as the diverse consequences of endothelial dysfunction in different vascular beds. This new and testable hypothesis accounts for both the endothelial and metabolic abnormalities associated with atherogenesis.

Nutritional Support of Patient with Inflammatory Bowel Disease.

Ideally, surgical patients should be nutritionally optimized, as better nutritional status correlates with favorable outcomes during the perioperative period. As inflammatory bowel disease often leads to overall malnutrition, special consideration should be given to this patient population by surgeons. In this article, we review methods for nutritional assessment and provide nutritional recommendations for this special surgical population.

Physiological relationships of uncoupling protein-2 gene expression in human adipose tissue in vivo.

The physiological significance of changes in uncoupling protein-2 (UCP-2) gene expression is controversial. In this study we investigated the biochemical and functional correlates of UCP-2 gene expression in sc abdominal adipose tissue in humans in vivo. UCP-2 messenger ribonucleic acid expression was quantified by nuclease protection in adipose tissue from lean and obese humans in both the fasting and postprandial states. Plasma fatty acids, insulin, and leptin were all determined in paired samples from the superficial epigastric vein and radial artery, and local production rates were calculated from 133Xe washout. In the fasting state UCP-2 expression correlated inversely with body mass index (r = -0.45; P = 0.026), percent body fat (r = -0.41; P = 0.05), plasma insulin (r = -0.47; P = 0.02), epigastric venous fatty acids (r = -0.45; P = 0.04), and leptin (r = -0.50; P = 0.018). UCP-2 expression remained inversely related with plasma leptin after controlling for percent body (r = -0.45; P = 0.038). At 2 or 4 h postprandially, there were no significant relationships between UCP-2 expression and biochemical parameters. In conclusion, 1) UCP-2 messenger ribonucleic acid expression in sc adipose tissue is inversely related to adiposity and independently linked to local plasma leptin levels; and 2) UCP-2 expression is not acutely regulated by food intake, insulin, or fatty acids. Reduced UCP-2 expression may be a maladaptive response to sustained energy surplus and could contribute to the pathogenesis and maintenance of obesity.

Insulin resistance, insulin, proinsulin, and ambulatory blood pressure in type II diabetes.

Both insulin resistance and insulin concentrations correlate with blood pressure in nondiabetic subjects, but there is no consensus on these relations in subjects with non-insulin-dependent diabetes, perhaps because of the use of nonspecific insulin assays and clinic blood pressure measurement. Therefore, we have investigated the relation between ambulatory blood pressure, insulin sensitivity (measured by an insulin sensitivity test), and levels of insulin and its principal precursors, measured by specific assays, in 24 subjects with non-insulin-dependent diabetes. Insulin sensitivity (glucose metabolic clearance rate) correlated strongly with mean 24-hour ambulatory systolic blood pressure (r = -.650, P < .001). In contrast, there was no relation between this blood pressure index and fasting levels of insulin (r = .096, P = NS) or all insulin-like molecules (r = .077, P = NS). Dichotomized on 24-hour ambulatory systolic blood pressure levels, the hypertensive group was more insulin resistant than the normotensive group (metabolic clearance rate, 3.6 [0.7] versus 6.5 [3.0] mL.kg-1.min-1, P = .006), whereas there was no difference in insulin or proinsulin concentrations among the groups. In multiple regression analysis, insulin sensitivity was the major determinant of blood pressure. We conclude that in subjects with non-insulin-dependent diabetes mellitus, blood pressure is related to insulin sensitivity but not to fasting levels of insulin, suggesting that hyperinsulinemia is probably not the mediator of this relation.

beta-Adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies.

UNLABELLED: Circulating IL-6 levels are elevated in obesity. Although IL-6 is expressed in adipose tissue, neither its regulation nor cell of origin is well characterized. Here we investigated the beta-adrenergic regulation of IL-6 release in a combination of studies on humans and animals in vivo and cultured adipocytes in vitro. Human in vivo study: Human volunteers were infused with isoproterenol, norepinephrine, or saline [4 M:4F; mean (SD) age 35.5 (5.8) yr; body mass index 24.6 (4.2) kg/m(-2)]. Plasma IL-6 levels increased during a 3-h infusion of isoproterenol (P = 0.01) and fell 2 h post infusion (P = 0.05). IL-6 levels did not change significantly with either norepinephrine or saline. Murine in vivo study: C57BL6/J male mice were injected ip with dobutamine (beta(1) agonist), clenbuterol (beta(2)), CL316243 (beta(3)), or saline placebo. Plasma IL-6 levels at 3 h were increased by clenbuterol (P = 0.02) and CL316243 (P = 0.02) but not dobutamine (P = 0.51), compared with placebo. IN VITRO STUDIES: In human peripheral blood cells, lipopolysaccharide treatment enhanced secretion of IL-6 (vs. controls; P < 0.001), whereas isoproterenol inhibited IL-6 secretion (P = 0.012) and norepinephrine had no significant effect. In contrast, isolated human adipocytes and differentiated 3T3F442A adipocytes all rapidly secreted IL-6 in response to adrenergic agonists (P < 0.01, compared with untreated cells). We conclude that beta 2/beta 3 adrenoceptor stimulation on adipocytes, rather than macrophages, may be responsible for the increases in plasma IL-6 concentrations observed during sympathetic activation and in obesity.

Current status of bariatric surgery in the treatment of type 2 diabetes.

Bariatric surgery (from the Greek words baros meaning 'weight' and iatrikos 'the art of healing') is a rapidly evolving branch of surgical science. The aim is to induce major weight loss in those whose obesity places them at high risk of serious health problems. In an attempt to balance the risks of surgery against the benefits of weight loss, bariatric operations are currently performed only in the morbidly obese, or those with a body mass index (BMI) > 35 kgm(-2) who already have developed comorbidity such as type 2 diabetes. Although weight loss is beneficial for obese patients with diabetes, current medical treatment for obesity is difficult. In contrast, observational studies show a major impact of bariatric surgery on diabetes, raising the question whether this approach should be used more widely to treat diabetes in obese patients? If bariatric surgery were shown to be the best way to treat diabetes in obese subjects the implications for health services would be wide-ranging. Bariatric surgery leads to withdrawal of diabetic treatment in about 60% or more of patients, and reductions of therapy for many others. Although data on bariatric surgery in subjects with diabetes are provocative, most studies have been uncontrolled or flawed in other ways. Most importantly, bariatric surgery has not yet been compared against standard medical treatment for diabetes in randomized controlled trials with diabetes-specific endpoints in all relevant patient groups. Potential indications for bariatric surgery are discussed, and the unanswered questions that need to be addressed by clinical trials are summarized. Although small numbers of patients may be interested in bariatric surgery for type 2 diabetes, current data are insufficient to endorse its wide scale use for this indication. Until essential studies are undertaken the role and economics of bariatric surgery in the diabetic clinic will remain uncertain.