Plasma glucose, insulin, and FFA concentrations were determined in 15 normal subjects and 15 patients with noninsulin-dependent diabetes mellitus (NIDDM) from 0800 to 1600 h. Breakfast and lunch were consumed at 0800 and 1200 h, respectively, and plasma concentrations were measured at hourly intervals from 0800-1600 h. Plasma glucose concentrations between 0800 and 1600 h were significantly elevated in patients with NIDDM, and the higher the fasting glucose level, the greater the postprandial hyperglycemia. Hyperglycemia in patients with NIDDM was associated with plasma insulin levels that were significantly higher (P less than 0.001) than those in normal subjects, and substantial hyperinsulinemia occurred between 0800 and 1600 h in patients with mild NIDDM (fasting plasma glucose concentrations, less than 140 mg/dl). Both fasting and postprandial FFA levels were also increased in patients with NIDDM (P less than 0.001), and the greater the plasma glucose response, the higher the FFA response (r = 0.70; P less than 0.001). However, there was no significant correlation between plasma insulin and FFA concentrations. More specifically, hyperinsulinemic patients with mild diabetes (fasting plasma glucose, less than 140 mg/dl) maintained normal ambient FFA levels, while FFA concentrations were significantly elevated in patients with severe NIDDM (fasting plasma glucose, greater than 250 mg/dl), with insulin concentrations comparable to those in normal subjects. These results demonstrate that patients with NIDDM are not capable of maintaining normal plasma FFA concentrations. This defect in FFA metabolism is proportionate to the magnitude of hyperglycemia and occurs despite the presence of elevated levels of plasma insulin. These results are consistent with the view that insulin resistance in NIDDM also involves the ability of insulin to regulate FFA metabolism.

In the first trimester of pregnancy, inactive renin in plasma rapidly increases (to 5 times the average concentration in plasma of nonpregnant controls), then declines slowly until midpregnancy, and falls quickly to the normal range after delivery. Inactive renin has the same large apparent molecular weight in pregnancy as in control plasma. Amniotic fluid contains very high levels of inactive renin; its mobility on Sephadex G-100 is the same as that of inactive plasma renin, but a lower molecular weight is indicated by the delayed elution of inactive renin of amniotic fluid from Sephacryl S-200. This anomalous behavior is probably responsible for the different estimates of molecular is probably responsible for the different estimates of molecular weight previously reported. The plasma concentration of active renin in pregnancy is modestly increased in the first trimester, declining gradually until term, and falling quickly after delivery. Although the increased PRA in early pregnancy involves an increase in active renin, increased angiotensinogen appears to play a more important part in sustaining the increased PRA of late pregnancy. The apparent molecular weight of te active renin in pregnancy plasma is larger than that in normal plasma. Gross changes in sodium intake during pregnancy result in changes in active and inactive renin concentrations parallel to those observed in nonpregnant controls. These responses suggest that the kidneys are an important source of the altered plasma renin in pregnancy, but do not exclude a contribution from other sources.

Plasma glucose, insulin, and free fatty acid (FFA) concentrations were measured from 0800 to 1600 hours in 40 nondiabetic individuals, separated into younger (38 +/- 1.4 years) and older (64 +/- 1.5 years) age groups. Meals were served at 0800 (20% total daily calories) and 1200 h (40% of total daily calories), and blood drawn just before the 0800 hours meal and at hourly intervals thereafter until 1600 hours. Statistical evaluation of the results of these measurements indicated that day-long plasma glucose and insulin levels were higher in the older individuals. In contrast, the day-long FFA response was reduced in this age group. These data suggest that the ability of insulin to maintain normal plasma glucose levels deteriorates with age, whereas regulation of FFA levels does not.