John J. Canary

Effects of supplemental chromium on patients with symptoms of reactive hypoglycemia

To determine if chromium (Cr) is involved in hypoglycemia, eight female patients with symptoms of hypoglycemia were supplemented with 200 micrograms of Cr as chromic chloride for three months in a double-blind crossover experimental design study. Chromium supplementation alleviated the hypoglycemic symptoms and significantly raised the minimum serum glucose values observed two to four hours following a glucose load. Insulin binding to red blood cells and insulin receptor number also improved significantly during Cr supplementation. These data suggest that impaired Cr nutrition and/or metabolism may be a factor in the etiology of hypoglycemia.

Insulin secretion and body composition in obesity

Abstract Plasma immunoreactive insulin levels were measured before and for 6 hr following a 100 g oral glucose load in ten normal volunteers and 17 grossly obese subjects. Eleven of the obese had an abnormal glucose tolerance, five of whom were overt diabetics. Twelve of the obese were restudied after significant weight reduction (thinned obese). Eight thinned obese subjects were also restudied 6–12 mo after completion of the weight reduction protocol. Body composition was measured in each subject prior to testing. Obesity was associated with hyperinsulinemia in the fasting state and in response to oral glucose. The obese diabetics demonstrated a delay and an impairment of insulin secretion in response to glucose. After weight reduction, elevated fasting plasma insulin levels fell in all. Insulin response to oral glucose was not different in the thinned obese with normal glucose tolerance from that observed in the normal volunteers. There was significant correlation between both fasting plasma insulin and total measurable insulin following the glucose load, and total body fat in the obese and thinned obese nondiabetics, but not in the obese overt diabetics. There was, however, significant correlation between fasting plasma insulin levels and total body fat in the diabetics who had a normal fasting blood sugar. These data indicate that the hyperinsulinemia of obesity is clearly related to the increase in total body fat. Carbohydrate intolerance occurs in those obese individuals with a limited pancreatic insulin secretory reserve, which fails to compensate for the increase in total body fat.

Osteomalacia in thyrotoxicosis

Abstract In order to evaluate the skeletal changes in thyrotoxicosis, alterations in calcium and phosphorus metabolism were studied in 15 patients with established thyrotoxicosis who were free from renal or cardiac disease. The percentage retention after intravenous administration of a standard calcium infusion was determined, and a roentgenologic study of the skeleton was made in each case. Hypercalcemia was noted in 6 instances and hyperphosphatemia in 8. The 24 hour urinary calcium concentration exceeded 200 mg. in 2 patients, whereas in 5 instances the 24 hour urinary calcium was 50 mg. or less. The percentage retention of infused calcium was increased in 12 of the 15 patients. Skeletal radiolucency was noted in 6 patients, 3 of whom were postmenopausal. The avidity for infused calcium and decrease in urinary calcium concentration were most marked in those with x-ray changes. Elevated serum alkaline phosphatase, although influenced by liver dysfunction in 4 patients, was noted in all but 1 of the patients studied, and was highest in those with x-ray changes. The findings of increased retention of infused calcium, decreased urinary calcium and increased serum alkaline phosphatase concentrations are consistent with a malacic component in the skeletal lesions of thyrotoxicosis.

The renal clearance of citrate in man

Because of the paucity of data in man concerning the renal clearance of citrate, citrate and creatinine chromogen clearances were simultaneously determined in 10 normal subjects and in 8 patients with proved hyperparathyroidism prior to and after surgical correction. The hyperparathyroid patients were hypercalciuric and had recurrent renal stones but were free of infection at the time of this study. Similar determinations were performed repeatedly in 9 patients with idiopathic renal stones without urinary tract infection and in 10 hypoparathyroid patients before specific therapy, to further evaluate the relationship between renal stones, parathyroid hormone and the clearance of citrate in man. No differences in plasma citrate levels were found between these 4 groups of patients. Citrate clearances expressed per 100 ml. of GFR were similar in the normal and idiopathic stone forming group. The mean citrate clearance was slightly lower in the hyperparathyroid patient group preoperatively. Citrate clearances were low in the hypoparathyroid patients and fell to similar significantly low levels postoperatively in the cured hyperparathyroid group. In 5 normal patients parathyroid extract administration did not alter plasma levels or citrate clearances, despite exhibition of its other typical biochemical effects. These data indicate that citrate clearance can vary independently of the plasma levels of citrate in man and suggest that endogenous parathyroid hormone exerts an effect on citrate excretion at the renal level. In addition the data suggest that stone fromation in the hypercalciuric state of hyperparathyroidism and in the idiopathic stone forming group is not due to any absolute decrease in citrate excretion.

Modification of the United States' diet to effect changes in blood lipids and lipoprotein distribution

Twenty men, 19 premenopausal and 14 postmenopausal women consumed a diet for 13 weeks that supplied 35% of the calories from fat, 50% from carbohydrate, and 15% from protein. The diet was low in cholesterol, saturated fat, and salt, and high in complex carbohydrate and fiber. The 7-day menu was composed of common well-accepted foods prepared in a simple attractive manner. Plasma total cholesterol, LDL cholesterol, and VLDL cholesterol were reduced, but triglyceride levels were not different than after self-selected diets. When 20% of the complex carbohydrate was replaced by simple carbohydrate and other diet components remained optimal, triglyceride and VLDL cholesterol levels increased in men and premenopausal women and total cholesterol increased in premenopausal women. These results suggest that beneficial effects on the blood lipids and lipoprotein distribution of men and women may be obtained by minimal modification of a typical U.S. diet.

BODY COMPOSITION BEFORE AND AFTER SURGICAL CORRECTION OF CUSHING'S SYNDROME*

The influence of gluconeogenic hormones of the adrenal cortex on body composition-and particularly on body fat-has received more speculation than experimental scrutiny because of the di5culties inherit in studying this aspect of human biology. Previous reports from this laboratory indicated a substantial increase in adipose tissue during the administration of This study involves the utilization of densitometric, volume distribution, and balance techniques before and after the surgical correction of Cushing’s syndrome to assess the compartmental changes resulting from normalization of adrenal function.

Nitrogen measurement in biological fluids and bone by an automatic Dumas technique

Abstract The micro-Dumas pyrolysis technique for measurement of nitrogen has been applied to biological materials. Measurement of nitrogen in biological materials with this technique is comparable to the standard macro-Kjeldahl procedure. This technique permits one technician to accurately measure the nitrogen content of more than 20 samples per day. The technique has been applied to the measurement of nitrogen in bone samples and the results obtained are in close agreement with studies previously reported with more tedious analytical methods.

NITROGEN BALANCE AND TOTAL BODY WATER IN THE MEASUREMENT OF CHANGE IN BODY FAT

Estimation of change in total body fat can be approached by several methods. One utilizes successive measurements of body density, preferentially combined with measurement of total body water to circumvent abnormality of Another depends upon serial changes in body weight, total body water and nitrogen balance? Previous studies reported from this laboratory concerned evaluation and comparison of these two techniques-termed “densitometric” and “compartmental.”5 While the densitometric approach to estimation of body fat appears reasonable, difficulties in its application to sick individuals and concern regarding constancy of density of the fat-free bodys render application of “compartmental” techniques increasingly important. This study concerns further exploration of the utility of volume distribution and balance methods to assess change in fat and this report illustrates the strengths and weaknesses of such an approach, but particularly its dependency on frequent and very accurate measurements of total body water.

THE PATIENT WITH HYPERPARATHYROIDISM.

Hyperparathyroidism, may be difficult to diagnose. Demonstration of hypercalcemia is the most reliable evidence of its presence. Special preoperative measures are usually unnecessary in most patients. For those with marked hypercalcemia without severe renal insufficiency, a calcium-free diet, 4 to 6 L. water daily, and a high phosphorus intake are indicated.Hemodialysis and ultrafiltration technics against a calcium-free dialysate bath, plus phosphorus supplementation, may permit the performance of safer surgical procedures in patients with severe hypercalcemia and renal insufficiency.The major postoperative clinical problems lie in differential diagnosis of the tetanic syndromes.

Changes in lactate dehydrogenase, LDH isoenzymes, lactate, and pyruvate as a result of feeding low fat diets to healthy men and women

A study was conducted to evaluate the effects on blood lipids and lipoproteins of feeding 21 healthy volunteers, 40-60 yr old, foods commonly eaten in the United States for two 40-day periods. Activities of lactate dehydrogenase (LDH) and LDH isoenzymes, lactate, and pyruvate were monitored. Results showed that LDH activity was significantly lower in all subjects at the end of the 25% fat-calorie period (period I) than at the beginning of the study, but rose above initial levels at the end of the 35% fat-calorie period (period II). While total LDH fell during period I, relative activity of M type subunits of LDH rose significantly in relation to H type in both sexes. This rise is probably indicative of an increase in glycolytic activity as a consequence of the increased intake of dietary carbohydrate. In period I, lactate and pyruvate decreased significantly in males (pyruvate greater than lactate) but not in females. Values for males returned to near initial levels in period II. The ratio of lactate/pyruvate was elevated in both sexes after period I. The greater change in pyruvate relative to lactate with increased dietary carbohydrate suggests increased Krebs Cycle activity. There was a statistically significant positive correlation between lactate, pyruvate, and serum triglyceride for males after they ate the 25% and 35% fat-calorie diets and for females after they ate the 35% fat-calorie diet, but not between lactate, pyruvate, and serum cholesterol for either sex.