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OBJECTIVE—Insulin stimulates albumin synthesis but inhibits that of fibrinogen in both type 1 diabetic and healthy subjects. In type 2 diabetes, fibrinogen production is increased both in the postabsorptive state and in response to hyperinsulinemia. No data exist on the rate of albumin synthesis and its response to insulin in type 2 diabetes. RESEARCH DESIGN AND METHODS—We measured fractional synthesis rates (FSRs) and absolute synthesis rates (ASRs) of both albumin and fibrinogen in postabsorptive normoalbuminuric type 2 diabetic patients at their spontaneous glucose levels (study A), as well as albumin FSR and ASR before and after a hyperinsulinemic-euglycemic euaminoacidemic clamp (study B), using leucine isotope methods. RESULTS—In postabsorptive type 2 diabetes (study A), albumin FSR (11.2 ± 0.9%/day) and albumin ASR (15.4 ± 1.2 g/day) were not different from control values (albumin FSR: 9.4 ± 0.7%/day; albumin ASR: 13.8 ± 1.2 g/day, P > 0.1 for both). In contrast, in the type 2 diabetic subjects, both fibrinogen FSR (24.9 ± 2.1%/day) and ASR (2.4 ± 0.2 g/day) were greater (P < 0.025 and P < 0.007, respectively) compared with the control subjects (FSR: 18.6 ± 1.51%/day; ASR: 1.6 ± 0.2 g/day). Worse metabolic control in the type 2 diabetic patients was associated with hyperfibrinogenemia and increased leucine rate of appearance, whereas neither the (increased) fibrinogen ASR nor the (normal) albumin production was affected. In study B, after hyperinsulinemia (raised to ∼860 nmol/l), albumin FSR and ASR increased by ∼25% versus basal (P < 0.04) and to the same extent in both type 2 diabetic and control subjects. CONCLUSIONS—In normoalbuminuric type 2 diabetic patients, postabsorptive albumin synthesis and its response to insulin were normal, whereas fibrinogen synthesis was increased, irrespective of metabolic control. Furthermore, in normoalbuminuric type 2 diabetic patients, a normal insulin sensitivity with respect to albumin production but a selective hepatic dysregulation of fibrinogen metabolism were present.

The aim of the study was to measure for the first time in humans surfactant disaturated-phosphatidylcholine (DSPC) net synthesis and kinetics by using a novel, dual stable isotope tracer approach. Ten infants with congenital diaphragmatic hernia [CDH; birth weight, 3.4 +/- 0.2; gestational age, 39.8 +/- 0.4 wk] and 6 age-matched control subjects with no lung disease (birth weight, 3.2 +/- 0.3 kg; gestational age, 39.1 +/- 1.1 wk), all of whom were admitted to the neonatal intensive care unit (Padua, Italy), were studied. All infants received simultaneously an intratracheal (carbon-13 di-palmitoyl-phosphatidylcholine) and an i.v. (deuterated palmitic acid) stable isotope tracer. Isotopic enrichment curves of DSPC from sequential tracheal aspirates were analyzed by mass spectrometry. DSPC kinetic data were expressed as mean +/- SEM and compared by the Mann-Whitney test. DSPC net synthesis from plasma palmitate was nearly identical in infants with CDH and control subjects (8.6 +/- 2.2 and 8.1 +/- 1.5 mg. kg(-1). d(-1); P = 0.7). DSPC apparent pool size was 36.7 +/- 7.5 and 58.5 +/- 9.1 mg/kg (P = 0.07) and half-life was 26.7 +/- 4.5 and 50.3 +/- 9.7 h (P = 0.03) in infants with CDH and control subjects, respectively. Both DSPC turnover and percentage of catabolism/recycling significantly correlated with duration of mechanical ventilation. In conclusion, the measurements of net DSPC synthesis and catabolism/recycling were reported for the first time in humans. Mean net DSPC synthesis was approximately 8 mg. kg(-1). d(-1). No significant differences were found between control subjects and infants with CDH. DSPC turnover was faster in infants with CDH, presumably reflecting an increased DSPC catabolism/recycling. Whether this may ultimately lead to a secondary surfactant deficiency in infants with CDH is still to be ascertained.