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Biomedical subjects

T J Merimee

Publications and source records attributed to T J Merimee.

At least 55 records · Page 3Linked to original sources

Familial combined hyperlipoproteinemia. Evidence for a role of growth hormone deficiency in effecting its manifestation.

Hyperlipidemia associated with an isolated deficiency of growth hormone was investigated in 10 subjects with hypercholesterolemia consistently present over a 10-yr period. 8 of these 10 had serum triglyceride concentrations greater than 185 mg/dl. 13 growth hormone-deficient patients with normal serum lipids, 28 age-matched controls, and 6 families possessing both growth hormone-deficient and hormonally normal members were also studied. Hyperlipidemia occurred with growth hormone deficiency only in families in which hormonally normal subjects likewise exhibited hyperlipidemia. However the elevation of serum lipids, particularly cholesterol, was invariably greater in the growth hormone-deficient members of these families. Studies were most consistent with the classification of this trait as familial combined hyperlipoproteinemia. Basal serum concentrations of insulin, glucose, and free fatty acids were similar in all groups. After oral glucose (1.5 g/kg of body wt) both hyperlipidemic and normolipidemic dwarfs exhibited a similar degree of glucose intolerance associated with insulinopenia. Sensitivity to insulin, assessed after the intravenous injection of insulin (0.05 U/kg of body wt), increased and was virtually identical in the two dwarf groups. Administration of 5 mg of human growth hormone twice a day for 1 wk to five subjects did not alter serum lipid patterns. The data provide no conclusive evidence concerning a direct effect of growth hormone deficiency on hyperlipoproteinemia. We postulate that in some individuals growth hormone deficiency may unmask an underlying defect in lipoprotein metabolism.

Adult↗

Nonenzymatically glycosylated serum protein: spurious elevation due to free glucose in serum.

The presence of free glucose in serum was found to interfere with accurate measurement, by a colorimetric method, of nonenzymatically glycosylated serum proteins. A mean elevation to 241% of basal levels was observed in the serum of 11 nondiabetic subjects to which glucose, in a concentration of 300 mg/dl, had been added immediately before assay. After dialysis of serum samples to remove glucose, levels of nonenzymatically glycosylated serum proteins were 0.27 +/- 0.11 and 0.79 +/- 0.24 nmol 5-hydroxymethylfurfural/mg protein (mean +/- SD), respectively, in 57 nondiabetic and 62 type I diabetic subjects. Levels observed before dialysis of serum were approximately two to three times higher. These studies indicate that removal of free sugar from serum is necessary for accurate measurement of glycosylated protein by the colorimetric method, and this can be achieved by overnight dialysis of serum against normal saline.

Blood Glucose↗

Transient-like function and associated retinal capillary anomalies. Analysis of a patient with early retinopathy secondary to juvenile-onset diabetes mellitus.

A juvenile diabetes patient exhibiting limited early microvascular changes in the retina has been studied intensively. Like some others showing early signs of diabetic retinopathy, he manifests anomalies in a retinally based transient-like function. At all points tested in this case the sustained-like function was found to be normal. Because his functional and anatomic anomalies are stable and cover a reasonably extensive area of visual field and retina, it is possible to attempt correlative studies with other visual response functions. The transient-like function proves to be a more sensitive indicator of anomaly in this patient than static perimetry or critical flicker frequency.

Adolescent↗

Serum protein-bound hexose in diabetes: the effect of glycemic control.

To determine whether the carbohydrate content of serum proteins is related to overall glycemic control, we studied serum protein-bound hexose and glycosylated hemoglobin [HbA1(a+b+c)] in 37 ambulant diabetic patients and 32 nondiabetic controls. Protein-bound hexose was correlated with HbA1(a+b+c) in the diabetic patients (r = 0.36, P less than 0.025). The mean protein-bound hexose level of the diabetic patients was greater than that of the controls (190.8 versus 174.7 mg/dl, P less than 0.01), but diabetic patients with HbA1(a+b+c) less than 12% had a mean protein-bound hexose similar to the controls. In nine of the diabetic patients, mean protein-bound hexose and HbA1(a+b+c) were significantly reduced during a period of intensive outpatient care, while two major serum glycoproteins, haptoglobins and alpha-1-antitrypsin, were unchanged. Our findings support the hypothesis that increased glycosylation of serum proteins may occur in diabetes mellitus; this abnormality in serum protein-bound hexose may be corrected by close attention to overall glycemic control.

Blood Proteins↗

A follow-up study of vascular disease in growth-hormone-deficient dwarfs with diabetes.

Thirty-one growth-hormone-deficient dwarfs were re-examined after a period of 10 to 12 years. These subjects had initially shown glucose intolerance, insulinopenia and hyperlipidemia comparable to those of diabetic patients matched for age and sex, but vascular complications were not present in dwarfs. After 10 years glucose tolerance became progessively more abnormal in dwarfs than could be accounted for by expected deterioration with age, and hyperglycemia after mixed meals remained greater than in control subjects. Serum lipid and serum lipoprotein concentrations were abnormal in over one third of the dwarfs. Despite the metabolic similarity to the diabetic patients, clinical complications of diabetes were absent in dwarfs: retinopathy did not occur, and the prevalence of hypertension and arteriosclerosis was considerably lower in dwarfs than in the diabetic subjects in both study periods. The follow-up data support the hypothesis that growth hormone has at least a supportive role in the pathogenesis of vascular disease in the diabetic state.

Adult↗

Sex variations in free fatty acids and ketones during fasting: evidence for a role of glucagon.

Women differ markedly from men in their metabolic response to caloric deprivation. To determine if these differences could be attributed solely to changes in insulin concentration, a group of 8 women was matched with a group of 7 men so that the mean fall in serum insulin during a 72-h fast did not differ between the groups. Glucose levels fell to a greater degree in the women than in the men. The serum concentrations of free fatty acids and ketone bodies rose more rapidly in the women and closely paralleled the earlier rise in glucagon concentrations. Over the first 36 h of fasting the change in free fatty acids was positively correlated to the change in glucagon and negatively correlated to the change in insulin. For the second 36 h of fasting, only changes in glucagon correlated with changes in free fatty acids. These correlations were true for both sexes and support the hypothesis that glucagon plays a physiologically significant role the regulation of lipolysis during starvation.

Body Weight↗

Ketoacids and the insulin receptor.

The binding of insulin to a specific receptor on IM-9-cultured human lymphocytes was studied in vitro under conditions simulating diabetic ketoacidosis. Compared with control incubations at pH 7.4, binding was reduced by 19 per cent at pH 7.1 and by 48 per cent at pH 6.8. Addition of beta-hydroxybutyrate, at concentrations similar to those seen clinically, "restored" insulin binding toward normal. We suggest that, by counteracting the effects of acidosis, ketoacids themselves maintain normal insulin-receptor binding in diabetic ketoacidosis. These data also illustrate that small molecules, present in vivo, can significantly alter the interactions between a hormone and its receptor in vitro.

Acetoacetates↗

Hypoglycemia in man pathologic and physiologic variants.

To determine if an effective method existed for distinguishing the physiologic hypoglycemia of fasting from pathologic hypoglycemia, 72-hour fasts were conducted in 60 women and 20 men of normal weight, in 16 obese subjects, and in six of 11 patient with insulinomas. Only the pattern of change of the immunoreactive-insulin-to-glucose ratio (the I/G ratio), calculated at major time intervals of the fast, provided a clear-cut distinction between these groups; plasma glucose values alone could not make this distinction. The mean fasting I/G ratio was calculated for each subject from that subject's I/G ratios at 12-hour intervals during the fasting period. In no single case did the mean I/G ratio during fasting for an individual of normal weight equal or exceed the control I/G. I/G ratios increased dramatically during fasting in each patient with an insulinomas. Normal obese patients (15% greater than ideal body weight) did not provide a diagnostic problem, since, regardless of sex, glucose values of less than 55 mg/dl. did not occur. Although the pattern of change of the I/G ratio was extremely useful, the basal I/G ratio alone was potentially misleading; this was due to overlap of basal I/G ratios between subjects with simple obesity and patients with insulinomas. In addition, absolute values for the I/G ratio varied with the technique employed for measuring glucose and insulin. Change of the I/G ratio, however, was independent of the techniques used for measuring glucose and insulin. DIABETES 26:161-65, March, 1977.

Adenoma, Islet Cell↗

Starvation-induced alterations of circulating thyroid hormone concentrations in man.

Serum concentrations of triiodothyronine (T3), thyroxine (T4), and TSH were examined in seven men and seven women of normal weight during a 60-hr fast. Similar studies were conducted in two women who received daily for 1 mo before and during a similar fast, 0.4 mg and 0.5 mg of 1-thyroxine. The serum concentrations of T3 decreased in each of the untreated normal subjects (sign test of significance, P less than 0.001). The mean control concentration of T3 in women was 152 +/- 9 ng/100 ml (X +/- SEM); after 24 hr of fasting, 131 +/- 31 ng/100 ml; and at the termination of the fast, 90 +/- 15 ng/100 ml. The latter value differed from the control value with a p value of less than 0.01. Similar changes of T3 concentration occurred in men (mean basal T = 160 +/- 11 ng/100 ml; mean at termination of fast = 87 +/- 16 ng/100 ml). The range of decrease for T3 in all subjects varied from 24% to 55%. The mean T4 concentration at the beginning of the fast was 6.9 +/- 0.9, and at the termination of the fast, 7.5 +/- 0.6 (p = NS). TSH concentrations remained unchanged (Control, 3.8 +/- 0.45 muU/ml; at 60 hr, 4.0 +/- 0.26 muU/ml, p = NS). Studies in two women who received, before and during a fast, T4, indicate that a decreased peripheral conversion of T4 to T3 is the most likely mechanism responsible for this change.

Adult↗

Insulin removal by isolated perfused rat liver.

Removal of unlabeled insulin was studied in the perfused rat liver. Insulin removal followed first-order kinetics over the range of concentrations found in the portal vein of postabsorptive rats, but deviated from first-order kinetics in experiments with a wider concentration range. Clearance was more than twice as great at concentrations normally found in the portal vein in the postabsorptive state (0.40-1.1nM or about 60-100 muU/ml) than at concentrations expected after pancreatic stimulation (4.5-7.0 nM). Saturation of the liver's capacity to remove insulin, however, was not observed even at higher levels. Insulin clearance diminished when the flow rate was reduced. It was not significantly altered by prolonged starvation. Our results suggest that when the insulin concentration is high a greater percentage escapes hepatic degradation then when it is low. Hepatic insulin clearance is in part dependent on the portal flow rate. The kinetics of insulin removal by the perfused liver cannot be accounted for by the properties of insulin-degrading enzymes described by others.

Animals↗

Diet-induced alterations of hGH secretion in man.

Studies were designed to determine whether variations in diet composition could modify the secretion of human growth hormone. Eight men and seven women ingested experimental diets for 10-12 days. Each experimental diet was preceded by a control diet for five days. Experimental diets studied in men were a) 2300 calorie, 80% carbohydrate (8 men); b) 2300 calorie, 75% high-fat (7 men); c) 2300 calorie, 70% high-protein (5 men); d) 3600 calorie, "control" (40% carbohydrate, 40% fat, 20% protein) (5 men); and e) 3600 calorie, 80% high-carbohydrate (5 men). A control diet and a high-carbohydrate (5 men). A control diet and a high-carbohydrate diet at the 2300 calorie level were studied in women. Each diet study was terminated by a 72 hour fast. Serum samples were collected hourly for 24 hours after each control period, on the eigth, ninth, or tenth day of each study, and during the final day of each fast. High-carbohydrate diets at the 2300 calorie level caused a significant decrease of growth hormone values in serum in each of eight men (sign test of significance, P less than .01). The mean figures were likewise significantly decreased. Isocaloric diets of high fat and high protein did not alter growth hormone concentrations in serum. A high-caloric diet similar to the control diet in composition was without effect on growth hormone secretion in men; however, a high-carbohydrate diet at the higher caloric level again depressed growth hormone values in plasma. On the third day of a 72 hour fast, growth hormone values in serum increased 287% in men, from a mean control serum concentration of 4.4 +/- 0.8 ng/ml to 11.9 +/- 5.0 ng/ml (P less than .01). Women, unlike men, had no significant decrease in growth hormone concentrations in serum over a 24 hour period after the high-carbohydrate diet, and the increase after starvation was significantly less than that in men, achieving significance only when evaluated by paired analysis. Growth hormone values in serum after the infusion of arginine followed a similar pattern, i.e., decreased after high carbohydrate but unaffected by other diets in men; high carbohydrate diets did not alter the growth hormone response of women to arginine.

Adult↗