Reversal of jejunoileal bypass in patients with morbid obesity.

Jejunoileal bypass for morbid obesity was performed on 182 patients between 1971 and 1982. At 19 years' follow-up 60 (33 per cent) have had to undergo reversal. The compelling reasons for reversal were life-threatening malnutrition, immune complex disease, renal oxalate stones, osteomalacia and severe electrolyte disturbance. All patients gained weight after reversal of the jejunoileal bypass; most gained all the weight they had lost. Thirty-one patients returned to grade III obesity and 14 to grade II. Twelve patients had an associated vertical gastroplasty: ten regained their previous weight and only two stayed within normal weight. Patients were generally free from bypass-associated symptoms and complications apart from arthralgia and arthritis. This report concludes a series of articles published by the authors on jejunoileal bypass over the past 20 years describing the rise and fall of this surgical procedure.

The dynamics of weight loss after gastric partition for gross obesity.

Energy intake and expenditure have been assessed in patients before gastric partition for gross obesity, 3 months after operation when they were still losing weight and at 12 months when weight loss was complete and stable. Food intake was drastically reduced after surgery and the energy deficit so produced was sufficient to account completely for the weight loss, even when allowance was made for an adaptive reduction in energy expenditure. In a majority of patients, the eventual reduction in expenditure parallels the regression of metabolic rate against body mass index for a population of stable obese patients. However, the reduction in resting metabolic rate was maximal soon after the operation, when weight loss was far from complete. Weight loss stabilized at about 6 months, not due to a further reduction in energy expenditure but because energy intake recovered until the patient was again in energy balance.

The intragastric balloon: a novel idea proved ineffective.

Twelve grossly obese patients who weighed 121 +/- 22 kg (mean +/- s.d.) had a free-floating 600 ml spherical intragastric balloon inserted per oesophagus and have been followed for 12-24 months. Nine patients lost up to 21 kg (11 +/- 6.4 kg) over 3 months after which they reached a plateau and then regained weight so that by 1 year only one patient had maintained her weight loss. Three patients could not tolerate the balloon owing to complete reflex inhibition of gastric emptying. Such marginal and temporary weight loss is of no value in the treatment of gross obesity.

Radiological appearances following vertical banded gastroplasty.

Vertical banded gastroplasty was performed on 19 grossly obese patients. Upper gastrointestinal contrast studies were performed on all patients in the immediate post-operative period and at 3 months and 1 year in 16 and 12 patients, respectively. The immediate and long-term appearances are presented and discussed. The surgical outcome depends on pouch size, outlet diameter and staple line integrity, which are reliably demonstrated by double-contrast barium studies.

A 13-year review of jejunoileal bypass.

One hundred and eighty patients had a jejunoileal bypass performed during the years 1971-1982. By leaving only 14 in. (35 cm) of intestine in continuity a mean weight loss of 34.4 per cent (s.d. = 8.5) was achieved over 2 years and, unless the operation had to be reversed for complications, this weight loss was maintained. The improvement in quality of life for a majority of patients should not be undervalued. Two-thirds of patients required admission for complications and eight patients died (4 per cent). Many of these problems were provoked by an inability to control eating. There have been no hospital deaths since 1976 which we attribute to better management of complications and a policy of early reversal for patients with excessive weight loss and signs of metabolic failure. Despite performing jejunoileal bypass less often in recent years we are still frequently reversing patients with electrolyte disturbances, metabolic failure, urinary calculi or arthritis. Thirty patients (16.7 per cent) have been reversed, half more than 5 years after bypass. Metabolic failure may occur even after many years of stable weight reduction. Because this is not well known the insidious onset of new weight loss and malaise may not be recognized, or not associated with the bypass many years before. Indefinite outpatient surveillance is mandatory. Changes in the operation have not significantly affected results. There has been no serious liver dysfunction in the 7:7:CJ group but this may reflect better management of lesser metabolic disturbances. Jejunoileal bypass remains the most effective operation for gross obesity and, with experience, can be performed safely. However, the complication rate and difficulty maintaining satisfactory follow-up on large numbers of young patients makes it an unacceptable procedure on any major scale.

Peripheral glucose uptake in young men with myocardial infarction.

Forearm glucose uptake (FGU) was studied during 100 g oral glucose tolerance tests (GTT) in nonobese, nondiabetic men who had suffered a myocardial infarction (MI) at or before the age of 40, and the results compared with the response in age-matched normal men. In the MI group the rise in both glucose and insulin concentrations after glucose loading was similar to that in normal subjects, although in the former, peak levels tended to be slightly higher. Concomitant FGU, however, was significantly greater in the MI group than in control subjects in the period 0-90 min and in the test as a whole (0-180 min). The results show that at least in some nondiabetics suffering MI at an early age hyperinsulinism is not a feature and peripheral tissue sensitivity is increased.

Disparity between glucose-dependent insulinotropic polypeptide and insulin responses in obese man.

Studies were carried out in 32 obese patients and 30 normal-weight control subjects to ascertain the response of glucose-dependent insulinotropic polypeptide (GIP) and insulin to (1) oral and intravenous glucose (10 obese and 10 control subjects), (2) oral fat and intravenous glucose (eight obese and six control subjects) and (3) mixed test meal (14 obese and 14 control subjects). Basal mean insulin was higher in the obese (99 pmol/l) than in the control group (40 pmol/l), but fasting blood glucose and GIP were not significantly different from normal. The total integrated response of insulin in obese subjects after oral glucose was 54.1 versus 33.3 nmol . l-1 . h-1 in control subjects; glucose and GIP responses were similar in both groups. After intravenous glucose the integrated insulin response was 8.8 in the obese versus 5.0 nmol . l-1 . h-1 in control subjects; GIP was unaffected by intravenous glucose and glucose levels were similar. Following oral fat and intravenous glucose, insulin secretion was again abnormal in the obese, 24.5 versus 7.3 nmol . l-1 . h-1 in controls, but GIP responses were normal. However, the control subjects became hypoglycaemic after this test: blood glucose 2.8 mmol/l at 150 min compared with 4.6 mmol/l in the obese group. The insulin response to a mixed meal was also abnormal in obesity.

Diurnal profiles of plasma magnesium and blood glucose in diabetes.

In order to study the relation between plasma magnesium and blood glucose concentrations in diabetes, diurnal profiles were obtained in nine diabetic patients and five healthy subjects. A significant inverse relationship between the two variables was found in seven of the nine diabetic patients and in one healthy subject. This could not be attributed solely to changes in plasma albumin, and its mechanism is unclear. Plasma magnesium levels in diabetes are closely dependent on blood glucose concentration.

Vitamin D status and bone histomorphometry in gross obesity.

Plasma 25-hydroxyvitamin D concentrations and bone histomorphometry were investigated in 24 grossly obese subjects. The mean plasma 25OHD concentration was significantly lower in the obese group than in age-matched, healthy controls. Subnormal values were found in four obese subjects and in a further two subjects, who were investigated at the end of the summer, plasma 25-hydroxyvitamin D levels were at the lower end of the normal winter range. Bone histology was abnormal in two patients. In one, mild osteomalacia and secondary hyperparathyroidism were present while in the other patient the appearance suggested increased bone turnover, possibly as a result of healing osteomalacia. We conclude that gross obesity is associated with an increased risk of vitamin D deficiency, probably because of reduced exposure to uv radiation. Histological evidence of metabolic bone disease may also occur. Preoperative vitamin D deficiency may contribute in some patients to the development of metabolic bone disease after intestinal bypass.

Tissue magnesium status in diabetes mellitus.

Leucocyte and erythrocyte magnesium was assayed in 17 healthy subjects and 17 insulin dependent diabetic patients. Plasma magnesium concentration (mean +/- standard error of mean) was significantly lower in the diabetic patients (0.80 +/- 0.02 mmol/l), compared with the healthy subjects (0.90 +/- 0.02 mmol/l, p less than 0.001), but the leucocyte and erythrocyte magnesium content was not significantly different in the diabetic patients (34.5 +/- 0.8 and 6.2 +/- 0.2 mmol/kg dry solids) compared with the healthy subjects (35.5 +/- 0.8 and 6.5 +/- 0.11 mmol/kg dry solids). In a separate study skeletal muscle obtained by needle biopsy was also assayed. Plasma magnesium in 10 diabetic patients (0.74 +/- 0.01 mmol/l) was significantly lower than in 16 healthy subjects (0.85 +/- 0.02 mmol/l, p less than 0.001), but there was no significant difference in the mean muscle magnesium content (43.0 +/- 0.7 compared with 40.7 +/- 0.9 mmol/kg dry solids in the diabetic patients).

The effect of weight loss on sex steroid secretion and binding in massively obese women.

We have previously reported increased testosterone and androstenedione concentrations and decreased sex hormone binding globulin (SHBG) concentrations in the plasma of massively obese women. We now report that these plasma hormone concentrations return to normal in twelve of the same women after substantial weight reduction and these changes are associated with more normal menstrual cycles. We conclude that body weight and fat are important determinants of sex steroid secretion and binding and thus influence menstrual function.

Changes in thyroid hormones in obese women following jejuno-ileal bypass surgery.

The serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3) and 3,3'5'-triiodothyronine (reverse T3) in 10 massively obese women were studied before and at intervals for one year after jejuno-ileal bypass operation. A significant rise in T3 (P less than 0.01) over the immediately preoperative value, a significant fall in rT3 (P less than 0.01) but no significant change in T4 was found during the post-recovery follow-up period. It is concluded that maintaining a relatively high T3 level following jejuno-ileal bypass surgery may contribute to the substantial weight reduction achieved by patients after this operation.

Musculo-skeletal abnormalities after jejunoileal bypass.

A mixture of osteomalacia and hyperparathyroidism is common after jejunoileal bypass (54 per cent). Bone biopsy is essential for diagnosis. Oral l alpha hydroxyvitamin D3 can rapidly reverse the abnormality. Some patients, however, fail to respond and this may be related to bacterial contamination of the excluded loop. Polyarthralgia is also a common side effect (13 per cent). It occurs in bouts lasting a few days and normally subsides spontaneously. It is often associated with skin lesions of vasculitic type. The attacks can be cut short by metronidazole. In some patients relapses are so frequent and severe that reversal of the bypass is indicated since it brings immediate and lasting relief. The possible immune mechanisms involved are complex.

Treatment of bone disease after jejunoileal bypass for obesity with oral 1 alpha-hydroxyvitamin D3.

The effects of oral 1 alpha-hydroxyvitamin D3 have been investigated in 12 patients with bone disease after jejunoileal bypass for obesity. Bone histology became normal or improved greatly after four to 12 months' treatment in eight patients but showed little change or worsened in four. There was a significant rise in plasma calcium and fall in plasma alkaline phosphatase concentration with 1 alpha-hydroxyvitamin D3 therapy in the patients with a good histological response. Administration of metronidazole and cotrimoxazole to two patients who had failed to respond to 1 alpha-hydroxyvitamin D3 resulted in clinical and biochemical improvement; in one of these patients histological improvement was also documented. It is concluded that oral 1 alpha-hydroxyvitamin D3 can be effective in healing post-bypass bone disease; the failure of some patients to respond may be related to bacterial contamination of the small intestine and in those patients antibiotics may also be indicated.

Abnormal sex steroid secretion and binding in massively obese women.

We have measured the plasma concentrations of sex steroids and sex hormone-binding globulin (SHBG) in twenty-three massively obese women and ten age-matched lean female volunteers. In the obese women increased plasma testosterone (obese 3.2 +/- 0.5 nmol/l controls 1.7 +/- 0.5 nmol/l, P less than 0.3) and androstenedione concentrations (obese 9.7 +/- 1.2 nmol/l, controls 4.4 +/- 0.6 nmol/l, P = less than 0.01) an increased ratio of oestrone:oestradiol (obese 2.4 +/- 0.4, controls 1.0 +/- 0.1, P = less than 0.1) and decreased SHBG levels (obese 30 +/- 4 nmol/l, controls 60 +/- 8 nmol/l, P = less than 0.001) were found. Obesity differed from the polycystic ovary syndrome (in which a similar pattern of changes of sex steroid concentrations and binding are seen) in that it was associated with normal increases in serum luteinizing hormone (LH) follicle stimulating hormone (FSH) levels in response to the administration of LHRH. We conclude that the common occurrence of menstrual abnormalities in obesity results from abnormal secretion and binding of sex steroids. In addition, the unaltered secretion of LH and FSH in the presence of such changes is evidence for a disorder of hypothalamic function.

Evidence for existence of two types of massive obesity.

The responses of growth hormone, cortisol, and prolactin to symptomatic hypoglycaemia during an intravenous insulin tolerance test were measured in 20 massively obese subjects and six lean volunteers. In 11 subjects, who had been obese since early childhood, an impaired growth-hormone response and an absent prolactin response were found. In the nine other obese subjects, however, the growth-hormone and prolactin responses were not significantly impaired. Seven of these subjects had become obese either as a teenager or during adult life. These findings suggest the existence of two types of human obesity similar to those found in rodent models. In one the disorder of hypothalamic function may be due to a basic, possibly genetic abnormality, while in the other it is acquired.

Hypomagnesaemia in diabetes.

The plasma magnesium (Mg) concentrations of 582 unselected diabetic outpatients and 140 control subjects were measured by atomic absorption spectrophotometry. Mean plasma Mg (+/-S.D.) was significantly lower in the diabetic patients (0.737 +/- 0.071 mmol/l) than in the control subjects (0.810 +/- 0.057 mmol/l), and 146 (25%) diabetics had values below those of all control subjects except one. Plasma Mg correlated best with clinic blood glucose concentration (r = -0.32, p less than 0.001) and other significant associations were observed with glycosuria, age, sex, insulin therapy and biguanide therapy. Although its significance is unclear, hypomagnesaemia could conceivably predispose to ischaemic heart disease in diabetes.