Gastric bypass in morbidly obese kidney transplant recipients

Severe post-transplant obesity has previously been shown to have a negative impact on graft survival following kidney transplantation. It also contributes to late patient mortality and is associated with hypertension, diabetes and hyperlipidemia. We undertook Roux-en-Y gastric bypass (GBP) in three morbidly obese (200-260% ideal body weight) (IBW) patients 6-8 yr following kidney transplantation. Roux-en-Y gastrojejunostomy to a 30 ml stapled gastric pouch was created with the jejunojejunostomy (both loops) 80-120 cm from the ligament of Treitz. By 12 months post-GBP, weight loss plateaued at 100-150% IBW. Both patients that had developed post-transplant diabetes mellitus (PTDM) had complete resolution within 9 months following GBP. On average the patients required 3 less hypertension (HTN) medications after GBP; 2 of the 3 patients are now normotensive off medication. Improvements in hyperlipidemia were also shown. The absolute cyclosporine (CsA) requirement (mg/d) increased by approximately 33% (p = NS), and there was also a significant increase in the weight adjusted CsA requirement from 1.8 to 3.5 mg/kg/d (p = 0.02, ANOVA) following GBP in order to maintain similar TDX trough CsA levels. GBP offers significant reduction in weight, HTN, PTDM and hyperlipidemia in morbidly obese kidney transplant recipients. However, CsA dose requirements may increase after GBP as a consequence of the defunctionalized intestine.     

Interactions between the nematode parasite of pigs, Ascaris suum, and the earthworm Aporrectodea longa

BACKGROUND: Hypothermia during and after major abdominal surgery decreases host defenses, increases the incidence of coagulopathy and may alter blood pressure, cardiac contractility and myocardial stability. METHODS: We designed a prospective randomized study to compare the benefits of a forced air warming system with warm blanket treatments in minimizing the effects of hypothermia on 64 morbidly obese patients undergoing Roux-en-Y gastric bypass. RESULTS: Patients in the forced air warming group (n = 32) had significantly higher perioperative body core temperature, lower central venous pressure and blood pressure readings, lower incidence of shivering, less blood loss intraoperatively and achieved a higher post anesthesia Aldrete Score than those patients in the warmed blanket group (n = 32). CONCLUSION: The forced air warming system is safe, cost effective and beneficial in minimizing the undesirable consequences of hypothermia in morbidly obese patients undergoing Roux-en-Y gastric bypass.     

Anaesthetic management of a morbidly obese patient

Morbid Obesity (MO) is associated with various pathophysiological changes which affect the outcome of anaesthesia and surgery. We report here anaesthetic management of a fit morbidly obese patient for transcervical resection of endometrium (TCRE) under spinal subarachnoid block. The preoperative preparation, intraoperative and postoperative management is described and the various problems in morbidly obese patients are discussed.     

Mortality mapping in Hong Kong, 1979-83 and 1984-88: the patterns of major non-malignant diseases

In this study, human platelets were used as a cellular model for exploring cytosolic free Ca (Cai) regulation in non-insulin-dependent diabetes mellitus (NIDDM). Cai levels were monitored in resting and thrombin-stimulated platelets from obese females with NIDDM; obese, nondiabetic women, and nonobese, nondiabetic women. All subjects were black. Significant and marked elevation of basal Cai levels was observed in platelets from the diabetic subjects when no aspirin was used during platelet isolation. However, no significant differences were observed in Cai between aspirin-treated platelets from women with NIDDM and platelets from nondiabetic women. The rate of the Cai return to basal level after thrombin stimulation was significantly lower in platelets from the diabetic subjects, suggesting an abnormality in platelet Ca extrusion or sequestration in NIDDM. Platelet Cai levels positively correlated with low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL/HDL) and fasting blood glucose. These findings suggest abnormalities in platelet Cai homeostasis in NIDDM that are influenced by the serum lipid profile and perhaps glucose.     

Insulin sensitivity in familial hypercholesterolemia

Insulin resistance is found in association with obesity, non-insulin-dependent diabetes mellitus, and essential hypertension, which are all risk factors for atherosclerotic cardiovascular disease. Furthermore, hyperinsulinemia has been reported in familial combined hyperlipoproteinemia and endogenous hypertriglyceridemia. Finally, relatively high serum triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations invariably accompany hyperinsulinemia. Whether insulin sensitivity is affected by the isolated presence of high levels of serum low-density lipoprotein (LDL) cholesterol has not been clearly established. We studied 13 subjects with heterozygous familial hypercholesterolemia (FHC) and 15 normocholesterolemic subjects selected to be free of any other known cause of insulin resistance. Thus FHC patients and controls had normal body weight and fat distribution, glucose tolerance, blood pressure, and serum triglyceride and HDL cholesterol concentrations, but were completely separated on plasma LDL cholesterol concentrations (6.05 +/- 0.38 v 3.27 +/- 0.15 mmol/L, P < .0001). Fasting plasma levels of glucose, insulin, free fatty acids (FFA), and potassium and fasting rates of net carbohydrate and lipid oxidation were superimposable in the two study groups. During a 2-hour euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 340 pmol/L) clamp, whole-body glucose disposal rates averaged 30.4 +/- 2.3 and 31.1 +/- 3.0 mumol.kg-1 x min-1 in FHC and control subjects, respectively (P = 0.88). The ability of exogenous hyperinsulinemia to stimulate carbohydrate oxidation and energy expenditure and suppress lipid oxidation and plasma FFA and potassium levels was equivalent in FHC and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

The insulin resistance syndrome in native Hawaiians. Native Hawaiian Health Research (NHHR) Project

OBJECTIVE: To investigate whether fasting hyperinsulinemia is associated with a clustering of cardiovascular disease (CVD) risk factors, manifesting as the insulin resistance syndrome (IRS), in a population of native Hawaiians. RESEARCH DESIGN AND METHODS: A total of 574 native Hawaiians > or = 30 years of age were examined for blood pressure, waist-to-hip ratio (WHR), BMI, oral glucose tolerance, and fasting lipid, insulin, and C-peptide concentrations. All statistical analyses (n = 384) excluded 190 individuals who had NIDDM or who were taking hypertension medication. Using logistic regression analysis, fasting insulin and C-peptide levels were compared with CVD risk factors (glucose intolerance, hypertension, central adiposity, elevated triglyceride levels, and low HDL cholesterol levels) after adjusting for age and obesity. RESULTS: Sixty-six percent of native Hawaiians were overweight or obese, and 70% were found to have central adiposity. Fasting insulin concentrations were correlated with BMI, WHR, blood pressure, and triglyceride, HDL cholesterol, and glucose concentrations. Fasting insulin was also significantly associated with an increasing number of CVD risk factors in each participant (P < 0.001). Fasting insulin and C-peptide concentrations were independently associated with glucose intolerance, high triglyceride levels, and low HDL cholesterol levels. However, only fasting C-peptide concentrations were independently associated with hypertension and central adiposity. Apparent differences in the correlates of fasting insulin and C-peptide may be related to multiple factors and warrant further evaluation. CONCLUSIONS: This study provides cross-sectional data confirming the existence of the IRS in native Hawaiians. However, further longitudinal studies are needed to examine the relationship of insulin resistance and/or surrogate markers to increased rates of NIDDM and CVD mortality in native Hawaiians.     

Medical and health impact of complex emergencies: implications for the International Society of Nephrology Disaster Relief Task Force

The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m2) at three time points: before bilio-pancreatic diversion (BPD) surgery (Ob); 3 months after surgery POI; and after reaching stable body weight, at least 2 years after surgery POII. A group of 7 control subjects (C), matched groupwise for sex, age and BMI with POII patients, was also studied. The M value at POI was significantly higher than at Ob (49.12 +/- 8.57 vs 18.14 +/- 8.57 mumol.kg-1.min-1). No statistical difference was observed between the POII and C groups. Similarly, glucose oxidation rate was significantly increased at POI with respect to Ob (24.2 +/- 7.23 vs 9.42 +/- 3.91 mumol.kg-1.min-1) and was not significantly different between POII and C. Basal levels of non-esterified fatty acids (NEFA) decreased significantly both from Ob to POI and from POI to POII (1517.1 +/- 223.9 vs 1039.6 +/- 283.4 vs 616.0 +/- 77.6 mumol.1(-1). The same applied to basal plasma triglycerides (2.07 +/- 0.77 vs 1.36 +/- 0.49 vs 0.80 +/- 0.19 g.1(-1). Weight decreased mainly in the late postoperative period (POI to POII 124.28 +/- 11.22 to 69.71 +/- 11.78, 83% of total decrement), rather than in the early postoperative period (Ob to POI 135.25 +/- 14.99 to 124.28 +/- 11.22 kg, 17% of total decrement). We also report the clinical case of a young woman of normal weight, who underwent BPD for chylomicronaemia (secondary to familial lipoprotein lipase deficiency), whose M value, plasma insulin and blood glucose levels were normalized upon normalization of serum NEFA and triglyceride levels as determined by the therapeutic lipid malabsorption. In conclusion, in obese diabetic patients lipid malabsorption induced by BPD causes a definite enhancement of insulin sensitivity and glucose tolerance. This improvement in metabolism is noticeable before the surgery has major effects on body weight. These observations suggest that lowered plasma lipids, rather than weight loss per se, are the cause of the reversibility of insulin resistance.     

Effective obesity treatments.

To curb the epidemic of obesity in the United States, revised Medicare policy allows support for efficacious obesity treatments. This review summarizes the evidence from rigorous randomized trials (9 lifestyle trials, 5 drug trials, and 2 surgical trials) on the efficacy and risk- benefit profile of lifestyle, drug, and surgical interventions aimed at promoting sustained (= 2 years) reductions in weight. Both lifestyle and drug interventions consistently produced an approximate 7-lb (3.2-kg) weight loss that was sustained for 2 years and was associated with improvements in diabetes, blood pressure, and/or cardiovascular risk factors. Surgical interventions have a less solid empirical base but offer promise for the promotion of significant and sustained weight reduction posttreatment in the morbidly obese but with possible significant short-term side effects. In summary, there is strong and consistent support from rigorous randomized trials that lifestyle or drug interventions result in modest weight loss with minimal risks but disproportionate clinical benefit. Combinations of lifestyle, drug, and, where appropriate, surgical interventions may be the most efficacious approach to achieving sustained weight loss for the widest diversity of patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pulsed-field gel electrophoresis genomic fingerprinting of hospital Escherichia coli bacteraemia isolates

To study the effects of massive weight loss on insulin secretion, we analysed the oscillations of fasting peripheral insulin levels in obese patients who underwent vertical banded gastroplasty as treatment for morbid obesity. Patients were studied before and 6 months after surgery. Serial measurements of plasma free insulin levels were obtained in duplicates from 0 to 60 min at one-minute intervals. Insulin levels were then analysed by autocorrelation and Fourier transformation. In normal controls and obese patients, the first oscillatory insulin component was detected between 10 and 14 min. Compared to obese controls (n = 4), overt Type 2 diabetic patients (n = 4) had reduced amplitudes of insulin pulses and no oscillatory component. These defects were not as pronounced in patients with impaired glucose tolerance (IGT) after an oral glucose tolerance test (OGTT) (n = 5). When detected, the periodicity of the oscillations occurred at different periods. In 3/5 IGT patients, the first positive peak of correlation was found at 13.3 +/- 2.3 min. Weight loss (mean +/- SD) after 6 months was 24.3 +/- 3.7 for subjects with normal glucose tolerance (NGT), 37.9 +/- 9 for those with IGT and 29.8 +/- 5 kgs for Type 2 diabetic subjects. After weight loss, insulin oscillatory activity was detected in 4/5 IGT patients, with a period of 13 +/- 3 min. Weight loss did not reverse the defects observed in obese diabetic patients despite a significant reduction in peripheral insulin levels from 28.6 +/- 6 to 15.6 +/- 6 mU/l (p < 0.05). Insulin values remained higher than in obese controls (7.82 +/- 2, p < 0.05), and Type 2 patients remained mildly hyperglycaemic. These findings indicate that beta-cell activity is abnormal in Type 2 diabetic patients. The absence of modification after weight loss suggests that inherent beta-cell defects may contribute to hyperglycaemia.     

Jejunoileal bypass for the treatment of morbid obesity

With a reported mortality rate of less than 0.5%, and an immediate morbidity of 2% to 4%, jejunoileal bypass may result in a more significant weight loss than can be achieved with gastric bypass. Jejunoileal bypass cannot be outeaten, whereas gastric bypass can. Careful attention to preoperative, intraoperative and postoperative procedures will protect most jejunoileal bypass patients from both the side effects and complications of this surgical technique, allowing the morbidly obese to achieve the maximum benefit from intestinal bypass with fewer adverse results.     

Continuous assay for acid phosphatase using 1-naphthyl phosphate as a substrate

The sequential effects of an American Heart Association (AHA) Step 1 diet and subsequent weight loss on lipoprotein lipids in obese [body mass index (in kg/m2) > 27], postmenopausal women (n = 48) were determined. Subjects followed a euenergetic AHA Step 1 diet for 2 mo, followed by a weight-loss diet (deficit of 1.0-1.5 MJ/d) for 6 mo. The AHA diet lowered concentrations of total (7%), low-density-lipoprotein (LDL) (6%), and high-density-lipoprotein (HDL) (14%) cholesterol (P < 0.01). Weight loss (-5.6 +/- 0.7 kg; P < 0.01) increased plasma triacylglycerol concentrations (9%; P < 0.01) and increased HDL-cholesterol concentrations (8%; P < 0.01) compared with changes after the AHA diet, but there were no changes in total or LDL cholesterol. The combined AHA diet and weight-loss interventions lowered triacylglycerol (10%) and total (6%), LDL (6%), and HDL (7%) cholesterol. These changes correlated indirectly with the baseline concentration for each lipid. When the women were divided on the basis of initial LDL-cholesterol concentration, the AHA diet and weight-loss interventions reduced (P < 0.01) triacylglycerol (19%), total cholesterol (13%), and LDL cholesterol (14%) in the women with hypercholesterolemia but not in normocholesterolemic or midly hypercholesterolemic women. Thus, an AHA Step 1 diet and subsequent weight loss improve lipoprotein lipid profiles of obese, postmenopausal women with hypercholesterolemia. However, because it lowers HDL cholesterol, a low-fat diet without substantial weight loss may not be beneficial for improving lipoprotein lipid risk factors for coronary artery disease in obese, postmenopausal women with normal lipid profiles.     

The treatment and prevention of obesity: a systematic review of the literature

OBJECTIVE: To determine the effectiveness of interventions designed to prevent and treat obesity, and maintain weight loss. DESIGN: A systematic review of randomised controlled trials. SUBJECTS: Overweight and obese adults and children. MEASUREMENTS: Post-intervention changes in weight, fat content and fat distribution, measured relative to baseline. RESULTS: For obese children, family therapy and lifestyle modification appear to be effective in prevention and treatment, respectively. The effectiveness of interventions to prevent and treat obesity in adults remains unclear, although behavioural therapy and multicomponent strategies may be useful. Continued therapist contact appears to be useful for maintaining weight loss. Pharmacological interventions appear to be effective for up to 9 months, after which regain occurs. Surgery appears to be effective for the morbidly obese and gastric bypass is more effective than gastroplasty. In general, the methodological quality of studies was poor. CONCLUSION: Due to problems with methodological quality, it is recommended that research findings indicative of promising interventions are replicated.     

Effects of a quick-release form of bromocriptine (Ergoset) on fasting and postprandial plasma glucose, insulin, lipid, and lipoprotein concentrations in obese nondiabetic hyperinsulinemic women

OBJECTIVE: To assess the effect on various aspects of carbohydrate and lipid metabolism of administering a quick-release formulation of bromocriptine (Ergoset) to obese, nondiabetic, hyperinsulinemic women. RESEARCH DESIGN AND METHODS: Hourly concentrations of prolactin, glucose, insulin, free fatty acid (FFA), and triglyceride were measured for 24 h before and after approximately 8 weeks of treatment with Ergoset. In addition, fasting lipid and lipoprotein concentrations and the steady-state plasma glucose (SSPG) concentration in response to a continuous infusion of somatostatin, insulin, and glucose were determined before and after Ergoset administration. RESULTS: Circulating prolactin concentrations were dramatically decreased (P < 0.001) following treatment, associated with a significant fall (P < 0.05) in 24-h-long plasma glucose, FFA, and triglyceride concentrations. Neither circulating plasma insulin concentrations nor the ability of insulin to mediate glucose disposal changed with treatment. Finally, fasting total cholesterol fell (P < 0.05) and the ratio of total to HDL cholesterol decreased (P = 0.06) in association with Ergoset treatment. CONCLUSIONS: The fact that significant metabolic improvement was seen in the obese nondiabetic hyperinsulinemic women studied suggests that Ergoset could be of therapeutic benefit in clinical conditions of hyperglycemia and/or dyslipidemia.     

Reference range and repeatability of a combined intestinal permeability and function test in clinically healthy Irish setter dogs

We investigated the influence of nutrition and exercise interventions within cognitive/behavioral and public health formats on weight and blood lipid profiles in obese children. Compliance was also examined as well as the relationship of the compliance measures with clinical outcome variables. Three conditions were compared over 16 sessions: nutrition and eating-habit change followed by exercise (NE), exercise followed by nutrition and eating-habit change (EN), and an information control (INFO). NE and EN were presented in a cognitive/ behavioral framework which focused on the development of self-regulation whereas the INFO condition received the same material in a public health/educational model. NE and EN participants evidenced modest, yet significant, reductions in weight and blood lipids, and the impact of these two interventions endured at a five-year follow-up. In contrast, INFO participants displayed stable weight and blood lipids during the course of the program, and most remained morbidly obese at follow-up. Improved nutrition, increased physical activity and fitness were significantly correlated with weight and lipid reductions.     

Other laparoscopic bariatric procedures

Laparoscopic surgery is regarded as a major improvement reflected by a rapid recovery and low perioperative and postoperative morbidity. In obese patients the gains of this new technique may be affected by obesity-related problems, such as impaired respiratory function, high intraabdominal pressure, thick abdominal wall, and liver steatosis. This review describes the development of laparoscopic vertical banded gastroplasty (VBG) and gastric bypass procedures; and it addresses questions such as feasibility, comparability to open procedures, procedure-related problems, and recovery. The clinical outcome after laparoscopic VBG and gastric bypass is also updated. Up to May 1997 we have operated on 105 patients with laparoscopic VBG and another 26 completed laparoscopic gastric bypass procedures. The weight loss after both procedures are in accordance with the weight loss seen with open surgery. Procedure-related complications are described in detail in this paper. It is concluded that laparoscopic bariatric surgery will remain an area of importance for clinical practice, research, and development.     

Capillarovenous angioma of the maxillary sinus. Apropos of a case with review of the literature

Metabolic side-effects of antihypertensive drugs may increase the risk of coronary heart disease despite an adequate blood pressure reduction. Since combinations of different antihypertensive drugs are often necessary and frequently used, we performed a randomized study comparing the effects of a fixed combination of hydrochlorothiazide and sotalol (group A), or hydrochlorothiazide and captopril (group B) on blood pressure and on lipid and glucose metabolism in 40 men with essential hypertension over 1 year. Significant blood pressure reductions (p < 0.001) were achieved in both treatment groups: from 160/105 to 128/88 mmHg in group A (mean doses: hydrochlorothiazide 33 and sotalol 197 mg) and from 162/106 to 135/89 mmHg in group B (hydrochlorothiazide 33 and captopril 64 mg) after 12 months, respectively. No significant changes in body weight were observed in either treatment group. Triglycerides increased (p < 0.05) in both treatment groups (from 183 to 262 mg/dl in A, and from 160 to 196 mg/dl in B) and HDL cholesterol decreased (p < 0.001 and < 0.05) in both groups (from 45.1 to 35.7 mg/dl in A, and from 49.3 to 46.3 mg/dl in B), whereas LDL cholesterol increased significantly (p < 0.05) only in group A from 153 to 164 mg/dl. No significant changes were observed in total cholesterol nor in lipoprotein(a) concentrations in either treatment group. Fasting plasma glucose and hemoglobin A1 increased significantly (p < 0.05) only in group A after 1 year of treatment (from 91.6 to 98.0 mg/dl, and from 6.3 to 6.9%, respectively). Serum levels of creatinine and potassium decreased, and uric acid increased significantly under either combination. Our data show that the diuretic/beta-blocker combination has adverse effects on lipid and glucose metabolism after long-term therapy. The effects of the diuretic/ACE inhibitor combination on lipid metabolism are less pronounced and there are no adverse effects on glucose metabolism. However, the ACE inhibitor component could not completely counteract the metabolic effects of the diuretic. Both combinations have no effects on Lp(a). We conclude that the combination of hydrochlorothiazide with an ACE inhibitor has a better metabolic profile for the treatment of essential hypertension than the combination with a beta-blocker.     

Gastrointestinal surgery for obesity

Surgery is becoming an increasingly common method for treatment of morbid obesity in the United States. This text includes the presentation of a typical morbidly obese man with a number of obesity related comorbidities who was treated with a modification of Roux-en-Y gastric bypass. Subsequently, the gastrointestinal operations currently in use as treatment for morbid obesity are discussed. Preoperative and postoperative care for this patient population is discussed briefly. The results of the various procedures are also discussed in terms of both complications and improvement of medical comorbidities.     

Formulation and in vitro and in vivo availability of diclofenac sodium enteric-coated beads

OBJECTIVE: The beneficial effects of weight loss with a very-low-calorie diet (VLCD) on cardiovascular risk factors have been reported at the end of energy restriction. As the effects, especially on blood pressure, may not remain constant during weight maintenance, we studied the longer-term effects of weight loss on 24h ambulatory blood pressure (ABP), lipids, glucose and insulin. DESIGN: Prospective study of a 17-week weight loss programme containing an eight-week VLCD period and follow-up visit at one-year. SUBJECTS: Twenty-nine moderately obese, normotensive or mildly hypertensive women. The mean +/- s.d. body mass index (BMI) was 36.0 +/- 2.6 kg/m2 and mean age 40.3 +/- 8.3 y. RESULTS: In the last week of the VLCD, the mean (s.d.) weight loss was 12.4 +/- 3.3 kg (P < 0.001), at the end of the programme 15.1 +/- 4.4 kg (P < 0.001 vs baseline), and at one-year follow-up 10.7 +/- 7.6 kg (P < 0.001 vs baseline). Mean 24 h ABP decreased 8.0/4.6 mmHg (P < 0.001 for both) on the last week of the VLCD, at the end of the programme, the systolic ABP decrease was 4.7 mmHg (P < 0.01 vs baseline) and diastolic 2.1 mmHg (not statistically significant (NS) vs baseline). At one-year follow-up, the mean systolic ABP decrease was 4.1 mmHg (P < 0.01 vs baseline) and mean diastolic 3.0 mmHg (P < 0.05 vs baseline). Sodium excretion decreased 55 mmol/24 h in the last VLCD week (P < 0.01) and returned to baseline after that. At the one-year follow-up, beneficial changes, compared with baseline, were observed in mean serum glucose (-0.28 mmol/l, P < 0.05), triglyceride (-0.35 mmol/l, P < 0.01) and HDL cholesterol (+0.16 mmol/l, P < 0.001). CONCLUSIONS: This weight loss programme with a VLCD enabled obese subjects to lose weight and decrease cardiovascular risks. Despite some regain in weight during follow-up, the beneficial effects were overall maintained over the year. Sodium intake tended to increase during follow-up. Information on sodium restriction should be included in weight loss programmes.     

Obesity in Austria: epidemiologic and social medicine aspects

The importance of overweight not only for individual health and life expectancy but also for resulting health economics is stressed considering data from Austria. Epidemiology of overweight in Austria shows 8.5% of the population to be morbidly obese (Body Mass Index [BMI] higher than 30) and 14.5% overweight (BMI between 27 and 29.9). Prevalence of overweight in Austria shows a very masked decrease from eastern to the western districts of the country. As in other countries correlation of overweight with cardiovascular risk factors (cholesterol, triglycerides, glucose and systolic blood pressure) was found to be highly significant also in Austrian health screening programs. As far as treatment of overweight and its prevention is concerned not only short term weight loss, but it maintenance is important. Not only a realistic change in feeding behaviour and dieting but also a change in life style including regular physical activity is recommended requiring repeated and long-term controlling by qualified persons of the health profession.     

Carbohydrate and lipid metabolism in endogenous hypercortisolism: shared features with metabolic syndrome X and NIDDM

Carbohydrate and lipid metabolism was cross-sectionally assessed in 16 patients with endogenous hypercortisolism (endogenous Cushing syndrome). Five patients (31%) had fasting glucose levels over 6.6 mmol/l and a HbA1C over 7.5%. Six patients (38%) had diabetes mellitus based on an abnormal 75 g oral glucose tolerance test (OGTT) and two additional patients (13%) had impaired glucose tolerance based on an OGTT. Compared to obese individuals, patients with Cushing syndrome had an elevated glucose but no elevated insulin response to the OGTT. Regression analysis showed positive correlations between 24-h urinary free cortisol (UFC) and fasting blood glucose (P < 0.0005), UFC and OGTT glucose area under the curve (AUC) (P < 0.01), and UFC and HbA1C (P < 0.005). UFC levels were negatively correlated (P < 0.05) with OGTT insulin AUC and insulin/glucose ratios. Eleven (69%) patients required anti-hypertensive therapy for blood pressure control. Total cholesterol and triglycerides were elevated in patients with Cushing syndrome compared to obese controls, while LDL and HDL cholesterol, and Lp(a) were similar in the two groups. We conclude that impaired glucose tolerance and/or diabetes in patients with endogenous Cushing syndrome is due to the hyperglycemic effects of cortisol with relative insulinopenia. Thus, Cushing syndrome shares features with both the Metabolic Syndrome X and NIDDM, including impaired glucose uptake, hyperlipidemia and hypertension. However, in Cushing syndrome, a relative insulinopenia occurs, while in Metabolic Syndrome X and NIDDM, insulin excess is observed. In Cushing syndrome, as the hypercortisolemia exacerbates, insulinopenia becomes more paramount, suggesting that cortisol exerts a direct or indirect "toxic" effect on the beta-cell.