Purpose: To prospectively determine the distribution, extent, and age of venous thrombosis in patients presenting with acute signs and symptoms of venous thromboembolism and identify candidates for thrombolysis.Materials and Methods: Five hundred seventy-six consecutive patients (281 male, 295 female; mean age 58) referred for lower extremity deep vein thrombosis (DVT) assessment between November 2007 and April 2008 were included in the study. Documented cases of DVT were categorized by age (acute, chronic, and acute on chronic), anatomic location, and extent. Patients with iliofemoral and femoropopliteal DVT were evaluated for thrombolysis using standard criteria.Results: DVT was found in 19% of patients (112/576). Of these, 31 patients (27.7%, 31/112) had isolated calf DVT, 61 patients (54.5%, 61/112) had proximal vein thrombosis extending into the femoropopliteal venous segments, and 20 patients (17.9%, 20/112) presented with iliofemoral DVT. Using standard criteria, 12 patients were selected as potential candidates for pharmacomechanical thrombolysis (PhMT). This equated to an incidence of 2% (12/576) in the population studied, 11% of patients (12/112) with DVT, 26.1% of patients (12/46) presenting with acute proximal DVT, and 20% of patients (4/20) with iliofemoral DVT.Conclusion: The incidence of potential candidates for thrombolysis is low. These data should be considered when recruiting centers to participate in ongoing clinical trials assessing the efficacy of these techniques. (J Vase Surg 2010;51:908-12.)

The frequent occurrence of hypoglycemia in people with type 1 diabetes is attributed to abnormalities in the blood glucose counterregulatory response. In view of recent findings indicating that the kidney contributes to prevent and correct hypoglycemia in healthy subjects, we decided to investigate the role of renal glucose handling in hypoglycemia in type 1 diabetes. Twelve type 1 diabetic patients and 14 age-matched normal individuals were randomized to hyperinsulinemic-euglycemic (n = 6 diabetic subjects and n = 8 control subjects) or hypoglycemic (n = 6 each) clamps with blood glucose maintained either stable near 100 mg/dl (5.6 mmol/l) or reduced to 54 mg/dl (3.0 mmol/l). All study subjects had their renal vein catheterized under fluoroscopy, and net renal glucose balance and renal glucose production and utilization rates were measured using a combination of arteriovenous concentration difference with stable isotope dilution technique. Blood glucose and insulin were comparable in both groups in all studies. In patients with diabetes, elevations in plasma glucagon, epinephrine, and norepinephrine were blunted, and both the compensatory rise in endogenous glucose production and in the net glucose output by the kidney seen in normal subjects with equivalent hypoglycemia were absent. Renal glucose balance switched from a mean +/- SE baseline net uptake of 0.6 +/- 0.4 to a net output of 4.5 +/- 1.3 micromol x kg(-1) x min(-1) in normal subjects, but in patients with diabetes there was no net renal contribution to blood glucose during similar hypoglycemia (mean +/- SE net glucose uptake [baseline 0.7 +/- 0.4] remained at 0.4 +/- 0.3 micromol x kg(-1) x min(-1) in the final 40 min of hypoglycemia; P < 0.01 between groups). We conclude that adrenergic stimulation of glucose output by the kidney, which represents an additional defense mechanism against hypoglycemia in normal subjects, is impaired in patients with type 1 diabetes and contributes to defective glucose counterregulation.

To examine the potential contribution of precursor substrates to renal gluconeogenesis during hypoglycemia, 14 healthy subjects had arterialized hand vein and renal vein (under fluoroscopy) catheterized after an overnight fast. Net renal balance of lactate, glycerol, alanine, and glutamine was determined simultaneously with systemic and renal glucose kinetics using arteriovenous concentration differences and 6-[2H2]glucose tracer dilution. Renal plasma flow was measured by para-aminohippurate clearance and was converted to blood flow using the mathematical value (1-hematocrit). Arterial and renal vein samples were obtained in the postabsorptive state and during a 180-min hyperinsulinemic period during either euglycemia or hypoglycemia. Insulin increased from 49 +/- 14 to 130 +/- 25 pmol/l (hypoglycemia) and to 102 +/- 10 pmol/l (euglycemia). Arterial blood glucose decreased from 4.5 +/-0.2 to 3.0 +/- 0.1 mmol/l during hypoglycemia but did not change during euglycemia (4.3 +/- 0.2 mmol/l). After 150 min, endogenous glucose production reached a plateau value that was higher during hypoglycemia (10.3 +/0.6 micromol x kg(-1) x min(-1)) than during euglycemia (5.73 +/-0.6 micromol x kg(-1) x min(-1), P < 0.001). Hypoglycemia was associated with a rise in renal glucose production (RGP) from 3.0 +/- 0.7 to 5.4 +/- 0.6 micromol x kg(-1) x min(-1) (P < 0.05), although glucose utilization remained the same (2.0 +/- 0.8 vs. 2.1 +/-0.6 micromol x kg(-1) x min(-1)). As a result, net renal glucose output increased from 1.0 +/- 0.3 to 3.3 +/- 0.40 micromol x kg(-1) x min(-1). Elevations in net renal uptake of lactate (2.4 +/- 0.5 to 3.5 +/- 0.7 vs. 2.8 +/- 0.4 micromol x kg(-1) x min(-1)), glycerol (0.6 +/- 0.3 to 1.3 +/- 0.5 vs. 0.4 +/- 0.2 micromol x kg(-1) x min(-1)), and glutamine (0.7 +/- 0.2 to 1.1 +/- 0.3 vs. 0.1 +/- 0.3 micromol x kg(-1) x min(-1)) during hypoglycemia versus euglycemia (P < 0.05) could account for nearly 60% of all glucose carbons released in the renal vein during hypoglycemia. Our data indicate that extraction of circulating gluconeogenic precursors by the kidney is enhanced and responsible for a substantial fraction of the compensatory rise in RGP during sustained hypoglycemia. Increased renal gluconeogenesis from circulating substrates represents an additional physiological mechanism by which the decrease in blood glucose concentration is attenuated in humans.

To determine the effects of peripheral insulin infusion on total, hepatic, and renal glucose production and on the percent contribution to glucose production of gluconeogenesis versus glycogenolysis, 10 healthy subjects had arterialized hand and hepatic vein catheterization after an overnight fast and the results were compared with data from 12 age- and weight-matched subjects with renal vein catheterization during a 180-minute infusion of either insulin (0.25 mU/kg min) with dextrose, or saline. Endogenous, hepatic, and renal glucose production was measured with [6,6-H-2(2)]glucose, regional lactate, alanine, and glycerol balance by arteriovenous difference; hepatic blood flow by indocyanine green clearance; and renal blood flow by p-aminohippurate clearance, before and every 30 minutes during each infusion period. Insulin increased from about 42 to 98 pmol/L and blood glucose remained constant in all studies (3.8 +/- 0.2 v 4.4 +/- 0.1 mu mol/ml, hepatic v renal vein). In response to insulin infusion, endogenous, hepatic, and renal glucose production decreased immediately (30 minutes) and reached a lower plateau value (10.8 +/- 0.8 v 6.4 +/- 0.7, 10.4 +/- 1.1 v 7.8 +/- 1.0, and 2.8 +/- 0.6 v 1.5 +/- 0.6 mu mol/kg min, respectively) between 120 and 180 minutes (all P < .05). Net renal uptake of lactate (2.4 +/- 0.4 v 0.9 +/- 0.6) decreased earlier (30 minutes) and returned to baseline between 120 and 180 minutes (2.4 +/- 0.5 mu mol/kg min), whereas net splanchnic uptake of lactate (5.7 +/- 0.7 v 0.7 +/- 0.6) and alanine (1.8 +/- 0.1 v 1.0 +/- 0.5 mu mol/kg min) decreased later (120 to 180 minutes). Net renal (0.3 +/- 0.1 v 0.1 +/- 0.1) and splanchnic (0.7 +/- 0.3 v 0.4 +/- 0.2 mu mol/kg min) glycerol uptake decreased 90 to 180 minutes after insulin and increased (P < .05) with saline infusion (0.4 +/- 0.1 v 0.6 +/- 0.3 and 1.0 +/- 0.5 v 1.8 +/- 0.4 mu mol/kg min, respectively). These data indicate that the rapid suppression of endogenous glucose production by insulin reflects primarily a decrease in hepatic glucose release, most likely due to inhibition of net glycogenolysis, combined with suppression of renal gluconeogenesis. Inhibition of hepatic gluconeogenesis presumably occurs later during hyperinsulinemia. We conclude that peripheral insulin, in addition to its inhibition of glycogen degradation, regulates endogenous glucose production, in part, by modifying the splanchnic and renal substrate supply. Copyright (C) 2000 by W.B. Saunders Company.

Eighteen healthy subjects had arterialized hand and renal veins catheterized after an overnight fast. Systemic and renal glucose and glycerol kinetics were measured with [6,6-2H2]glucose and [2-13C]glycerol before and after 180-min peripheral infusions of insulin at 0.125 (LO) or 0.25 (HI) mU. kg-1. min-1 with variable [6, 6-2H2]dextrose or saline (control). Renal plasma flow was determined by plasma p-aminohippurate clearance. Arterial insulin increased from 37 +/- 8 to 53 +/- 5 (LO) and to 102 +/- 10 pM (HI, P < 0.01) but not in control (35 +/- 8 pM). Arterial glucose did not change and averaged 5.2 +/- 0.1 (control), 4.7 +/- 0.2 (LO), and 5.1 +/- 0. 2 (HI) micromol/ml; renal vein glucose decreased from 4.8 +/- 0.2 to 4.5 +/- 0.2 micromol/ml (LO) and from 5.3 +/- 0.2 to 4.9 +/- 0.1 micromol/ml (HI) with insulin but not saline infusion (5.3 +/- 0.1 micromol/ml). Endogenous glucose production decreased from 9.9 +/- 0. 7 to 6.9 +/- 0.5 (LO) and to 5.7 +/- 0.5 (HI) micromol. kg-1. min-1; renal glucose production decreased from 2.5 +/- 0.6 to 1.5 +/- 0.5 (LO) and to 1.2 +/- 0.6 (HI) micromol. kg-1. min-1, whereas renal glucose utilization increased from 1.5 +/- 0.6 to 2.6 +/- 0.7 (LO) and to 2.9 +/- 0.7 (HI) micromol. kg-1. min-1 after insulin infusion (all P < 0.05 vs. baseline). Neither endogenous glucose production (10.0 +/- 0.4), renal glucose production (1.1 +/- 0.4), nor renal glucose utilization (0.8 +/- 0.4) changed in the control group. During insulin infusion, systemic gluconeogenesis from glycerol decreased from 0.67 +/- 0.05 to 0.18 +/- 0.02 (LO) and from 0.60 +/- 0.04 to 0.20 +/- 0.02 (HI) micromol. kg-1. min-1 (P < 0.01), and renal gluconeogenesis from glycerol decreased from 0.10 +/- 0.02 to 0.02 +/- 0.02 (LO) and from 0.15 +/- 0.03 to 0.09 +/- 0.03 (HI) micromol. kg-1. min-1 (P < 0.05). In contrast, during saline infusion, systemic (0.66 +/- 0.03 vs. 0.82 +/- 0.05 micromol. kg-1. min-1) and renal gluconeogenesis from glycerol (0.11 +/- 0.02 vs. 0. 41 +/- 0.04 micromol. kg-1. min-1) increased (P < 0.05 vs. baseline). We conclude that glucose production and utilization by the kidney are important insulin-responsive components of glucose metabolism in humans.

We investigated the effects of hypoglycemia on renal glucose production (RGP) and renal glucose uptake (RGU) using arteriovenous balance combined with tracer technique in humans. Our 14 healthy subjects had arterialized hand veins (artery) and renal veins (under fluoroscopy) catheterized after an overnight fast. Systemic and renal glucose kinetics were measured with infusion of [6-(2)H2]glucose, and renal plasma flow was measured by para-aminohippurate clearance. After a 150-min equilibration period, artery and renal vein samples were obtained between -30 and 0 min, and subjects received a 180-min peripheral insulin infusion (0.250 mU kg(-1) x min(-1)) with a variable infusion of [6-(2)H2]dextrose adjusted to maintain plasma glucose at either approximately 60 mg/dl (hypoglycemic clamp) or approximately 90 mg/dl (euglycemic clamp). Blood samples were obtained between 150 and 180 min during the study period. Insulin increased from 49 +/- 14 to 130 +/- 25 (hypoglycemia) and to 102 +/- 10 (euglycemia) pmol/l. Glucose decreased from 5.32 +/- 0.11 to 3.58 +/- 0.07 micromol/ml during hypoglycemia, but it did not change during euglycemia (5.20 +/- 0.19 vs. 5.05 +/- 0.15 micromol/ml). Endogenous glucose production decreased (9.30 +/- 0.70 vs. 5.65 +/- 0.50) during euglycemia but not during hypoglycemia (9.80 +/- 0.50 vs. 10.25 +/- 0.60 micromol x kg(-1) x min(-1)). During hypoglycemia, net renal glucose output increased from 0.54 +/- 0.30 to 2.31 +/- 0.40, RGP increased from 1.88 +/- 0.70 to 3.65 +/- 0.50 (P < 0.05), and RGU did not change (1.34 +/- 0.50 vs. 1.34 +/- 0.60 micromol x kg(-1) x min(-1)). During euglycemia, renal glucose balance switched from a net output of 0.72 +/- 0.20 to a net uptake of 1.70 +/- 0.92, RGP decreased from 2.31 +/- 0.50 to 1.20 +/- 0.58, and RGU increased from 1.59 +/- 0.50 to 2.90 +/- 0.70 micromol x kg(-1) x min(-1) (P < 0.05). During hypoglycemia, arterial glucagon increased from 105 +/- 6 to 129 +/- 8, epinephrine increased from 116 +/- 28 to 331 +/- 33, norepinephrine increased from 171 +/- 9 to 272 +/- 9 (all P < 0.05), and renal vein norepinephrine increased from 236 +/- 13 to 426 +/- 50 (P < 0.001). These data indicate that, in addition to counterregulatory hormones, activation of the autonomic nervous system during hypoglycemia stimulates glucose production by the kidney, which may represent an important additional component of the body's defense against hypoglycemia in humans.