Dietary restriction on serum thyroid hormone levels.

To determine the long term effects of a protein sparing fast on serum thyroid hormone levels, the authors studied 38 obese patients ingesting a diet of 320 kcal for up to 13 weeks. The high baseline serum triiodothyronine (T3) levels decreased significantly by the first week, further decreased by the third week, and this lower level persisted for the duration of the fast until realimentation. Serum free T3 index followed the same general pattern as did serum T3 levels. Serum reverse T3 increased significantly by the first week, but by week three, the reverse T3 level had begun to fall, although still significantly increased above baseline. By week seven, reverse T3 had decreased to almost baseline and remained not significantly changed from the baseline to 13 weeks. Serum thyroxine (T4) increased significantly by the first week in all patients, but by the third week had returned to baseline levels which persisted to 13 weeks. The free T4 index and free T4 concentrations showed the same increment at week one and then returned to baseline levels. There were no significant changes in serum thyroxine-binding globulin (TBG) or thyroid-stimulating hormone (TSH) concentrations. The changes in serum T3 and reverse T3 levels are attributable to alterations in peripheral 5'-monodeiodination of T4 and reverse T3 induced by the protein sparing fast.

Mechanisms of hypertension in obesity.

We conclude that the following may explain the rise in blood pressure with obesity and the subsequent fall in blood pressure (Fig. 2): (1) An increase in calories, protein, or carbohydrate leads to an increase in plasma catecholamines, sympathetic nervous system activity, and insulin secretion. (2) These factors, in turn, lead to increased renal sodium retention and stimulation of the renin-aldosterone system which, in turn, leads to: (3) An increased cardiac output with an inability to appropriately adjust the peripheral resistance to maintain normotension with resultant hypertension. Conversely, the fall in blood pressure with weight reduction can be explained by (Fig. 3): (1) A decrease in calorie, carbohydrate, or protein intake which leads to: (2) A decrease in circulating plasma catecholamines, sympathetic nervous system activity, and insulin secretion which results in: (3) A natriuresis and decrease in the renin-aldosterone system, which causes a decrease in circulating blood volume and in cardiac output. This, in turn, lowers blood pressure towards normal. The unanswered question still remains: why do some obese patients become hypertensive and others remain normotensive? Perhaps there are weight-sensitive individuals and weight-resistant individuals just as there appear to be salt-sensitive and salt-resistant hypertensive patients. Perhaps the answer is genetic. These questions also remain to be answered.

Obesity and hypertension: long-term effects of weight reduction on blood pressure.

Long-term follow-up studies were conducted on massively obese hypertensive subjects during and after a successful protein supplemented fast (PSMF) in order to correlate blood pressure changes with caloric intake and body weight. The blood pressures in 43 subjects were compared during rapid weight loss and at identical weights during post-fast weight gain (Study A). Blood pressures and body weights in 50 subjects were compared prior to starting PSMF and prior to restarting the program 21 months later (Study B). One hundred twenty-five compliant subjects were observed after one month of weight maintenance (Study C-1), and 39 subjects were followed during six months of weight maintenance (Study C-2). In Study A, during subsequent weight gain on an unrestricted diet blood pressure was significantly higher than at identical weight during continuous weight loss on PSMF. However, this increase in blood pressure was only approximately 30 percent of the original decrease. In Study B, weight loss and blood pressure reduction were significantly correlated. After one month of weight maintenance following continuous weight loss of 73 lb, there was no increase in blood pressure (Study C-1). A small but significant increase in blood pressure after six months (Study C-2) was associated with similar small weight increment. However, all blood pressures remained well within the normotensive range and significantly lower than control values. In this study, long-term changes in blood pressure correlated with changes in body weight.

BP changes in obese hypertensive subjects during rapid weight loss. Comparison of restricted v unchanged salt intake.

A controlled prospective study compared two groups of obese hypertensive subjects during 12 weeks of a hypocaloric protein-supplemented fast containing 40 mEq of sodium daily. One group received additional sodium chloride sufficient to maintain baseline sodium intake measured prior to the fast (210 m/Eq/day). Sodium restriction resulted in greater weight loss and slightly greater BP reduction only during the initial week of fasting. Thereafter, despite sodium equilibrium, further substantial weight loss and BP reduction were identical in both groups, the decrement in weight being linear (1.89 kg/wk) and the BP reduction asymptotic. Although the initial reduction in BP during the first week of supplemented fast may be attributable to negative salt and water balance, the further reduction in BP during a period of constant sodium balance must be caused by weight loss per se or by the triggering of other antihypertensive mechanisms associated with weight reduction.

Error in blood-pressure measurement due to incorrect cuff size in obese patients.

Trained nurse-specialists obtained 84 000 blood-pressure measurements in 1240 obese subjects using cuffs of the three standard adult sizes in a randomised order. The differences in readings between the three cuffs were smallest in non-obese subjects and became progressively greater with increasing arm circumference (AC) in the obese population. The regular cuff (12 X 23 cm) showed the greatest bias in relation to AC. Formulae and a table have been derived to correct the measurement error caused by cuffs of inappropriate size at various ACs. The reported high prevalence of hypertension in obese subjects may be greatly overestimated.

The effect of weight loss on reproductive hormones in obese men.

The effects of weight reduction on reproductive hormones were investigated in 24 moderately obese men, 18-108% above ideal body weight. Serum estrone (E1), estradiol (E2), testosterone (T), percent free T (%FT), sex hormone binding globulin (SHBG) capacity, and, in 9 subjects, androstenedione (A) were measured serially before and during an outpatient supplemented fasting program (320 kcal/day) for 8-20 weeks. In the baseline state mean E1 was elevated to 100 +/- 7 pg/ml (normal, 30-60 pg/ml). The E2 was slightly elevated to 36 +/- 3 pg/ml (normal, 8-35 pg/ml). The mean T of 400 +/- 20 ng/dl was at the lower end of normal (400-1000 ng/dl). The mean %FT was elevated to 4.1 +/- 0.2% (normal 1.6-3%). The calculated free T was normal. The mean SHBG binding capacity was 0.99 +/- 0.05 micrograms dihydrotestosterone bound/dl (normal, 1.0-1.8 micrograms/dl). The mean A of 52 +/- 5.8 ng/dl was normal. These data were in accord with previous findings in much heavier men. Eight weeks of weight loss (mean, 19.5 kg) were associated with normalization of all the measured parameters. The mean E1 decreased to 48 +/- 23 pg/ml, E2 to 28 +/- 2.1 pg/ml. T increased to 536 +/- 35 pg/dl and %FT fell to 3.2 +/- 0.2%. Data on men remaining on the program for 16 or 20 weeks showed a continued fall of estrogens and stabilization of T and %FT. SHBG and A did not change significantly over the entire time period. In conclusion, increased circulating estrogens and reduced androgen binding were found in moderately obese men, which were completely corrected with weight loss.

Renal damage with intestinal bypass.

Renal function and biopsies were studied in 18 patients, 7 to 108 months after intestinal bypass. Enteropathy was found in 12 and hyperoxaluria in 16. Every biopsy showed a type of focal interstitial nephritis, tubular atrophy, fibrosis, and glomerular hyalinization. Damage ranged from minimal to extensive and renal function from normal to end-stage failure. Tubular injury had resulted partly from oxalate deposits. However, in 10 patients no oxalate crystals were seen. In eight others, most of the damaged areas were remote from crystal deposits. Immunoglobulin M and C3 deposits, found in glomerular capillaries and the messangium in six of 11 specimens, and the presence of circulating immune complexes in five of 10 patients, in addition to the extraintestinal organ involvement, suggested immune complex mesangial injury as one factor in bypass nephropathy. With progressive impairment of renal function, a biopsy appears justified. If damage is significant, the bypass should be dismantled.