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Biomedical subjects

S M Genuth

Publications and source records attributed to S M Genuth.

At least 19 recordsLinked to original sources
PubMed1994

The role of the National Diabetes Advisory Board in diabetes management.

The history of the National Diabetes Advisory Board is reviewed, particularly from the perspective of the role of the board in advancing diabetes care. In addition, its potential future activities in the arena of translating research advances, for example, the results of the Diabetes Control and Complications Trial (DCCT), are delineated.

Centers for Disease Control and Prevention, U.S.↗
PubMed1989

Urinary 3-hydroxyadipic acid 3,6-lactone: structural identification and effect of fasting in adults and children.

Increased urinary excretion of medium-chain dicarboxylic acids is a general feature of disordered fatty acid metabolism. The physiological role of the metabolic pathways involved in dicarboxylic acid production has been a subject of controversy. In the present investigation, the existence of 3-hydroxyadipic acid 3,6-lactone, possibly representing a metabolic intermediate in the beta-oxidation of adipic acid to succinic acid, has been demonstrated. The identity of this compound was established by electron-impact mass spectrometry of its trimethylsilyl derivative and by comparison with synthetic authentic samples. 3-Hydroxyadipic acid 3,6-lactone is present in almost every urine sample we have examined. In the nonfasting state, urinary concentrations of 0.9 +/- 0.5 micrograms/mg creatinine were observed in the adults. During fasting, the urinary excretion of this compound increased with time. It reached 19.1 +/- 8.5 micrograms/mg creatinine by the end of the third day. The responses in children were even higher; urinary concentrations of 82 +/- 50 micrograms/mg creatinine were observed by the end of 36 hours. The urinary excretion of the lactone is closely correlated (r2 = 0.8) with that of adipic acid, an indicator of fatty acid omega-oxidation activity. Non-ketotic dicarboxylic aciduria appears to vary in different defects based on the ratio of urinary lactone to adipic acid.

Adipates↗
PubMed1983

Binding of insulin by monkey and pig hypothalamus.

Membrane preparations from monkey and pig hypothalami bound [125I]insulin specifically. The binding appeared to be greater by preparations from anterior than posterior portions of the pig hypothalamus. Binding was time dependent, and its dissociation was first order with a half-time at 22 degrees C of 14 min. Desalanine insulin was as effective as native insulin in inhibiting the binding of [125I]insulin, while proinsulin was less effective and desoctapeptide insulin still less effective in accord with their biologic activities. Binding by membranes from cortex and thalamus appeared to be less than from hypothalamus. [125I]insulin was infused into an arterial split monkey brain preparation to determine if insulin that was blood borne bound specifically to the primate hypothalamus. Half the brain was perfused with [125I]insulin alone and the other half with [125I]insulin plus an excess of unlabeled insulin. Radioautography showed specific binding of insulin localized to the median eminence, infundibular nucleus, and microvessels. Thus, the monkey and pig hypothalami bind insulin with characteristics similar to those reported for known target tissues for insulin. Furthermore, insulin from the blood stream binds to specific anatomical structures in the hypothalamus of the monkey.

Animals↗
PubMed1982

Urinary excretion of acetylcarnitine during human diabetic and fasting ketosis.

The urinary excretion of acetylcarnitine was studied in patients with diabetic ketosis before and during insulin therapy and in normal-weight and obese subjects during fasting. In the diabetic ketotic patients, acetylcarnitine represented 61% of the total acylcarnitine excretion. During the first 24 h of insulin treatment, acetylcarnitine excretion decreased and on the 5th day of treatment was 18% of the acylcarnitines excreted. The urinary excretion of the other acylcarnitines fell slowly. In normal-weight subjects fasted for 3 days, the urinary excretion of acetylcarnitine increased on the 2nd day of fasting, and on the 3rd day acetylcarnitine accounted for 78% of the excreted acylcarnitine. In obese subjects there was a progressive increase in urinary acetylcarnitine excretion, but on day 6 it represented only 55% of the total acylcarnitine excreted. The urinary excretion of acetylcarnitine correlated with blood beta-hydroxybutyrate concentration in the normal-weight subjects during fasting and in the diabetic ketotic patients. Acetylcarnitine accounts for a major fraction of the acylcarnitines excreted in the three ketotic conditions studied. The contribution of acetylcarnitine to the change in acylcarnitines as ketosis appears or disappears is significantly less in the obese subjects than in the normal-weight subjects or in the diabetic patients. This difference may reflect an alteration in the production or disposition of acetyl-CoA and acetylcarnitine in obesity.

Acetylcarnitine↗
PubMed1981

Acute hormonal effects on carnitine metabolism in thin and obese subjects: responses to somatostatin, glucagon, and insulin.

Plasma free carnitine and acylcarnitines were determined in man during acutely induced insulin deficiency. A 5-hr infusion of somatostatin at 6 microgram/min in 10 thin subjects produced profound, sustained hypoinsulinemia and led to rapid increases in plasma free fatty acids and ketoacids (peak increments of 0.67 mM each). Simultaneously, plasma free carnitine decreased, while plasma long-chain and short-chain acylcarnitines increased significantly. When hyperglucagonemia was created by inclusion of glucagon with the somatostatin, the hyperketonemia was reversed after 2 hr and the increase in acylcarnitine abolished. However, the decrease in free carnitine was accentuated. The antiketogenic effect of adding glucagon was due to an eventual breakthrough of the somatostatin blockade on insulin secretion, the latter gradually returning toward preinfusion levels. Inclusion of exogenous insulin with the somatostatin-glucagon infusion immediately lowered free fatty acids and ketoacids. Acylcarnitines also declined promptly, while the accelerated fall in free carnitine produced by glucagon was blunted by the addition of insulin. Qualitatively and quantitatively comparable results were seen in seven obese subjects. This study suggests: (1) the increase in plasma acylcarnitines previously described in fasting and diabetic ketosis is largely due to insulin deficiency; (2) the corresponding decrease in plasma free carnitine is attributable both to insulin deficiency and glucagon excess; and (3) the resistance of obese subjects to ketosis is unlikely to be due to deficits in carnitine or carnitine acyltransferases.

Adult↗
PubMed1980

Carnitine metabolism in normal-weight and obese human subjects during fasting.

Carnitine metabolism was studied in normal-weight and obese subjects by measurement of carnitine and its acyl derivatives in plasma and urine. When first fed an isocaloric, low-carnitine diet, both groups showed a decrease in plasma total carnitine, primarily due to a decrease in the free carnitine fraction. Urinary free carnitine excretion also fell significantly. When fasting was instituted, plasma total carnitine concentration increased. This was the net result of a rapid increase in short-chain and long-chain acylcarnitine and a delayed decrease in free carnitine. Urinary excretion of short-chain acylcarnitines increased parallel to rising plasma concentrations, whereas free carnitine excretion first decreased and then tended to increase slightly. Both plasma and urinary short-chain acylcarnitine correlated with beta-hydroxybutyrate. All of these changes were reversed by refeeding, in the obese even with a low-carnitine hypocaloric intake. Obese subjects also developed hyperketonemia significantly more slowly than did normal-weight subjects, yet demonstrated substantially the same changes in magnitude and direction in carnitine and its metabolites.

Adult↗
PubMed1979

Effect of dietery weight loss on sex steroid binding sex steroids, and gonadotropins in obese postmenopausal women.

Measurements of SSBG, E2, T, and gonadotropins were performed in 12 obese postmenopausal women before, during, and after a supplemented fast. Weight loss (mean 18 kg) was associated with an increase in SSBG to levels above those seen in nonobese postmenopausal women, a decrease in serum E2 levels, unchanged T levels, and an increase in both gonadotropins. Thus we conclude that weight change or the circumstances associated with it lead to alterations in circulating levels of SSBG. These observations are consistent with the presence of elevated free T and possibly higher free E2 levels in obese postmenopausal women.

Body Weight↗
PubMed1978

Experience with low-dose insulin infusion in diabetic ketoacidosis and diabetic hyperosmolarity.

Forty patients with diabetic ketoacidosis and eight patients with the diabetic hyperosmolar state were treated with low-dose insulin infusion in four teaching hospitals in the Cleveland area. The clinical and biochemical responses observed support previous favorable reports on this treatment modality. Two elderly patients with the hyperosmolar syndrome died. The advantages of this form of treatment over intermittent insulin schedules are emphasized. Early potassium administration, unless otherwise contraindicated, is recommended. Rarely, increasing doses of insulin may be required if insulin resistance is encountered.

Adolescent↗
PubMed1977

Supplemented fasting as a large-scale outpatient program.

Although supplemented fasting is now established as an efficient means of achieving substantial weight reduction in massively obese persons, widespread application of this treatment is contingent on its successful adaptation to a large-scale outpatient regimen. Of 519 patients treated as outpatients, 78% lost a minimum of 18.2 kg during the course of treatment. The overall rate of weight loss was 1.5 kg/wk, with females averaging 1.3 kg/wk and males, 2.1 kg/wk. The majority of patients tolerated the regimen well and were able to continue normal daily activities without experiencing any serious side effects.

Body Weight↗