Methods for the quantification of beta-cell sensitivity to glucose (hyperglycemic clamp technique) and of tissue sensitivity to insulin (euglycemic insulin clamp technique) are described. Hyperglycemic clamp technique. The plasma glucose concentration is acutely raised to 125 mg/dl above basal levels by a priming infusion of glucose. The desired hyperglycemic plateau is subsequently maintained by adjustment of a variable glucose infusion, based on the negative feedback principle. Because the plasma glucose concentration is held constant, the glucose infusion rate is an index of glucose metabolism. Under these conditions of constant hyperglycemia, the plasma insulin response is biphasic with an early burst of insulin release during the first 6 min followed by a gradually progressive increase in plasma insulin concentration. Euglycemic insulin clamp technique. The plasma insulin concentration is acutely raised and maintained at approximately 100 muU/ml by a prime-continuous infusion of insulin. The plasma glucose concentration is held constant at basal levels by a variable glucose infusion using the negative feedback principle. Under these steady-state conditions of euglycemia, the glucose infusion rate equals glucose uptake by all the tissues in the body and is therefore a measure of tissue sensitivity to exogenous insulin.

A B S T R A C T The effects of insulin on the renal handling of sodium, potassium, calcium, and phosphate were studied in man while maintaining the blood glucose concentration at the fasting level by negative feedback servocontrol of a variable glucose infusion. In studies on six water-loaded normal subjects in a steady state of water diuresis, insulin was administered i.v. to raise the plasma insulin concentration to between 98 and 193 PU/ml and infused at a constant rate of 2 mU/kg body weight per min over a total period of 120 min. The blood glucose concentration was not significantly altered, and there was no change in the filtered load of glucose; glomerular filtration rate (CIN) and renal plasma flow (CPAH) were unchanged. Urinary sodium excretion (UNaV) decreased from 401±46 (SEM) to 213+18 iteq/min during insulin administration, the change becoming significant (P < 0.02) within the 30-60-min collection period. Free water clearance (CH2o) increased from 10.6±0.6 to 13±0.5 ml/min (P <0.025); osmolar clearance decreased and urine flow was unchanged. There was no change in plasma aldosterone concentration, which was low throughout the studies, and a slight reduction was observed in plasma glucagon concentration. Urinary potassium (UKV) and phosphate (Ui.V) excretion were also both decreased during insulin administration; UKV decreased from 66±9 to 21±1 Meq/min (P < 0.005), and UrV decreased from 504±93 to 230 ±43 Ag/min (P <0.01). The change in UKV was associated with a significant reduction in plasma potassium concentration. There was also a statistically significant but small reduction in plasma phosphate concentration which was not considered sufficient alone to account for the large reduction in UPV. Urinary calcium excretion (UCaV) increased from 126±24 to 200±17 ug/min (P < 0.01).These studies demonstrate a reduction in UNaV associated with insulin administration that occurs in the absence of changes in the filtered load of glucose, glomerular filtration rate, renal blood flow, and plasma aldosterone concentration. The effect of insulin on CH2o suggests that insulin's effect on sodium excretion is due to enhancement of sodium reabsorption in the diluting segment of the distal nephron.

Standard true 24-hour creatinine clearance determinations were performed on 884 subjects of the Baltimore Longitudinal Study. On the basis of clinical data, subjects were placed in categories indicating the presence of specific diseases or medications which might alter glomerular filtration rate. Subjects not included in these categories were considered normal (N=548). In the normals, cross-sectional analysis by 10-year age groups showed a progressive linear decline in clearance from 140 ml/min/1.73m2 at age 30 to 97 at age 80. Three or more serial clearances were obtained at 12- to 18-mo. intervals on 293 normal subjects. These longitudinal data showed an acceleration of the rate of decline in creatinine clearance with advancing age. The decrease in creatinine clearance with age seen in this study represents true renal aging and is not secondary to diseases which become increasingly prevalent in the elderly. A nomogram constructed from these data provides normative age-corrected standards for creatinine clearance.

Consuming a diet high in fruit, vegetables, reduced-fat dairy, and whole grains and low in red and processed meat, fast food, and soda was associated with smaller gains in BMI and waist circumference. Because foods are not consumed in isolation, dietary pattern research based on natural eating behavior may be useful in understanding dietary causes of obesity and in helping individuals trying to control their weight.