Biomedical subjects

G Boden

Publications and source records attributed to G Boden.

At least 37 records · Page 2Linked to original sources

PubMed1999

The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects.

We have quantitatively determined gluconeogenesis (GNG) from all precursors, using a novel method employing 2H20 to address the question of whether changes in plasma free fatty acids (FFA) affect GNG in healthy, nonobese subjects. In the first study (n = 6), plasma FFA were lowered at 16 to 20 hours with nicotinic acid (NA) and were then allowed to rise at 20 to 24 hours (FFA rebound after administration of NA). FFA decreased from 387 microM at 16 hours to 43 microM at 20 hours, and then rebounded to 1,823 microM at 24 hours. GNG decreased from 58.1% at 16 hours to 38.6% of endogenous glucose production at 20 hours (P < 0.005) and then rebounded to 78. 9% at 24 hours (P < 0.05). Conversely, glycogenolysis (GL) increased from 41.9% at 16 hours to 61.4% at 20 hours (P < 0.05), and then decreased to 21.1% at 24 hours (P < 0.05). In the second study (controls; n = 6), volunteers were analyzed between 16 and 24 hours after the last meal. FFA rose from 423 to 681 microM (P < 0.05), and GNG from 50.3% to 61.7% (P < 0.02), whereas GL decreased from 49.7% to 38.3% (P < 0.05). Endogenous glucose production decreased at the same rate in both studies, from 10.7 to 8.6 micromol/kg/min (P < 0. 05). In study 3 (n = 6), in which the NA-mediated decrease of plasma FFA was prevented by infusion of lipid and heparin, neither FFA nor GNG changed significantly. In summary, our data suggest that (a) acute changes in plasma FFA produce acute changes in GNG and reciprocal changes in GL; (b) the decrease in EGP between 16 and 24 hours of fasting is due to a fall in GL; and (c) NA has no direct effect on GNG.

Adult↗

PubMed1999

Disruption of circadian insulin secretion is associated with reduced glucose uptake in first-degree relatives of patients with type 2 diabetes.

The objective of this study was to evaluate whether first-degree relatives (FDRs) of patients with type 2 diabetes had abnormal circadian insulin secretion and, if so, whether this abnormality affected their glucose metabolism. Six African-American FDRs with normal glucose tolerance and 12 matched normal control subjects (who had no family history of diabetes) were exposed to 48 h of hyperglycemic clamping (approximately 12 mmol/l). Insulin secretion rates (ISRs) were determined by deconvolution of plasma C-peptide levels using individual C-peptide kinetic parameters. Detrending and smoothing of data (z-scores) and computation of autocorrelation functions were used to identify ISR cycles. During the initial hours after start of glucose infusions, ISRs were approximately 60% higher in FDRs than in control subjects (585 vs. 366 nmol/16 h, P < 0.05), while rates of glucose uptake were the same (5.6 mmol x kg(-1) x h(-1)), indicating that the FDRs were insulin resistant. Control subjects had well-defined circadian (24 h) cycles of ISR and plasma insulin that rose in the early morning, peaked in the afternoon, and declined during the night. In contrast, FDRs had several shorter ISR cycles of smaller amplitude that lacked true periodicity. This suggested that the lack of a normal circadian ISR increase had made it impossible for the FDRs to maintain their compensatory insulin hypersecretion beyond 18 h of hyperglycemia. As a result, ISR decreased to the level found in control subjects, and glucose uptake fell below the level of control subjects (61 vs. 117 micromol x kg(-1) x min(-1), P < 0.05). In summary, we found that FDRs with normal glucose tolerance had defects in insulin action and secretion. The newly recognized insulin secretory defect consisted of disruption of the normal circadian ISR cycle, which resulted in reduced insulin secretion (and glucose uptake) during the ascending part of the 24 h ISR cycle.

Adult↗

PubMed1999

Effects of fatty acids and ketone bodies on basal insulin secretion in type 2 diabetes.

The objective of this study was to assess the role of free fatty acids (FFAs) as insulin secretagogues in patients with type 2 diabetes. To this end, basal insulin secretion rates (ISR) in response to acute increases in plasma FFAs were evaluated in patients with type 2 diabetes and in age- and weight-matched nondiabetic control subjects during 1) intravenous infusion of lipid plus heparin (L/H), which stimulated intravascular lipolysis, and 2) the FFA rebound, which followed lowering of plasma FFAs with nicotinic acid (NA) and was a consequence of increased lipolysis from the subject's own adipose tissue. At comparable euglycemia, diabetic patients had similar ISR but higher plasma beta-hydroxybutyrate (beta-OHB) levels during L/H infusion and higher plasma FFA and beta-OHB levels during the FFA rebound than nondiabetic control subjects. Correlating ISR with plasma FFA plus beta-OHB levels showed that in response to the same changes in FFA plus beta-OHB levels, diabetic patients secreted approximately 30% less insulin than nondiabetic control subjects. In addition, twice as much insulin was secreted during L/H infusion as during the FFA rebound in response to the same FFA/beta-OHB stimulation by both diabetic patients and control subjects. Glycerol, which was present in the infused lipid (272 mmol/l) did not affect ISR. We concluded that 1) assessment of FFA effects on ISR requires consideration of effects on ISR by ketone bodies; 2) ISR responses to FFA/beta-OHB were defective in patients with type 2 diabetes (partial beta-cell lipid blindness), but this defect was compensated by elevated plasma levels of FFAs and ketone bodies; and 3) approximately two times more insulin was released per unit change in plasma FFA plus beta-OHB during L/H infusion than during the FFA rebound after NA. The reason for this remains to be explored.

3-Hydroxybutyric Acid↗

PubMed1999

Effect of insulin on fat metabolism during and after normal pregnancy.

Whereas development of resistance to the action of insulin on glucose metabolism during gestation has been recognized, it is presently not known whether there is also resistance to the action of insulin on lipid metabolism. We have, therefore, examined the effect of physiological hyperinsulinemia (during euglycemic-hyperinsulinemic clamping) on free fatty acid (FFA) turnover in seven nondiabetic overweight or obese women during and after pregnancy. Basal rates of FFA release, oxidation, and reesterification and basal plasma FFA concentrations were not significantly different from each other during the 2nd and 3rd trimester of pregnancy and postpartum. During euglycemic-hyperinsulinemic (approximately 500 pmol/l) clamping, however, lipolysis was significantly less inhibited during the 3rd trimester (from 7.0 +/- 0.9 to 4.9 +/- 0.9 micromol x kg(-1) x min(-1), -30%) than during the 2nd trimester (from 8.4 +/- 0.6 to 4.1 +/- 0.9 micromol x kg(-1) x min(-1), -51%) and postpartum (from 8.5 +/- 1.1 to 4.2 +/- 0.6 micromol x kg(-1) x min(-1), -51%). Similarly, fat oxidation was not inhibited at all (from 3.5 +/- 0.3 to 3.8 +/- 0.5 micromol x kg(-1) x min(-1)) during the 3rd trimester but was suppressed by 51% (from 3.9 +/- 0.2 to 1.9 +/- 0.3 micromol x kg(-1) x min(-1)) during the 2nd trimester and by 38% (from 2.6 +/- 0.7 to 1.6 +/- 0.5 micromol x kg(-1) x min(-1) postpartum. These data demonstrated that resistance to the action of insulin on lipolysis and on fat oxidation developed during late gestation and disappeared postpartum.

Adult↗

PubMed1999

Activation of the tissue factor pathway of blood coagulation during prolonged hyperglycemia in young healthy men.

Patients with diabetes have an increased prevalence of premature atherosclerotic vascular disease, and alterations in plasma coagulation proteins have been incriminated as a possible cause. The roles of hyperglycemia and hyperinsulinemia in the pathogenesis of these changes are unknown. To examine the effects of prolonged hyperglycemia and of selective hyperinsulinemia on the tissue factor pathway of blood coagulation, nine healthy young men were infused with glucose to maintain levels at 11.1 mmol/l (approximately 200 mg/dl) for 18-72 h (hyperglycemia-hyperinsulinemia group). Five normal men were infused with regular insulin to maintain levels comparable to that in the previous group (900 pmol/l, approximately 150 microU/ml) and with glucose to maintain levels at 5.6 mmol/l (approximately 100 mg/dl) (euglycemia-hyperinsulinemia group). Measured were plasma activated factor VII activity (FVIIa), FVII coagulant (FVIIC) activity, FVIII coagulant (FVIIIC) activity, tissue factor pathway inhibitor (TFPI) antigen, and thrombin markers; and serum glucose, insulin, and electrolytes. Plasma FVIIa, FVIIC, FVIIIC, and TFPI rose during hyperglycemic-hyperinsulinemia but not during euglycemic-hyperinsulinemia. Markers of thrombin generation rose transiently and inconsistently during hyperglycemia-hyperinsulinemia. We concluded that in normal subjects, hyperglycemia-hyperinsulinemia induced activation of the tissue factor pathway, reflected by increases in plasma FVIIa, FVIIC, and TFPI. This activation was independent of hyperinsulinemia, hypertriglyceridemia, and hyperosmolality. The elevations in plasma coagulation factors during hyperglycemia-hyperinsulinemia, characteristic of type 2 diabetes, may constitute a potential for enhanced thrombin generation and thrombosis when triggered by exposure of tissue factor, such as during arterial plaque rupture.

Adult↗

PubMed1999

Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects.

Obesity is commonly associated with elevated plasma free fatty acid (FFA) levels, as well as with insulin resistance and hyperinsulinemia, two important cardiovascular risk factors. What causes insulin resistance and hyperinsulinemia in obesity remains uncertain. Here, we have tested the hypothesis that FFAs are the link between obesity and insulin resistance/hyperinsulinemia and that, therefore, lowering of chronically elevated plasma FFA levels would improve insulin resistance/hyperinsulinemia and glucose tolerance in obese nondiabetic and diabetic subjects. Acipimox (250 mg), a long-acting antilipolytic drug, or placebo was given overnight (at 7:00 P.M., 1:00 A.M., 7:00 A.M.) to 9 lean control subjects, 13 obese nondiabetic subjects, 10 obese subjects with impaired glucose tolerance, and 11 patients with type 2 diabetes. Euglycemic-hyperinsulinemic clamps and oral glucose tolerance tests (75 g) were performed on separate mornings after overnight Acipimox or placebo treatment. In the three obese study groups, Acipimox lowered fasting levels of plasma FFAs (by 60-70%) and plasma insulin (by approximately 50%). Insulin-stimulated glucose uptake during euglycemic-hyperinsulinemic clamping was more than twofold higher after Acipimox than after placebo. Areas under the glucose and insulin curves during oral glucose tolerance testing were both approximately 30% lower after Acipimox administration than after placebo. We conclude that lowering of elevated plasma FFA levels can reduce insulin resistance/hyperinsulinemia and improve oral glucose tolerance in lean and obese nondiabetic subjects and in obese patients with type 2 diabetes.

Adult↗

PubMed1998

Free fatty acids (FFA), a link between obesity and insulin resistance.

Evidence, gained from human studies, is reviewed showing that elevation of plasma FFA levels produce peripheral and probably also hepatic insulin resistance in obese healthy and diabetic subjects. First, plasma FFA levels are elevated in most obese subjects. Second, physiological elevations of plasma FFA inhibit acutely as well as chronically insulin stimulated glucose uptake in a dose dependent fashion. Responsible for this inhibition is a FFA induced defect in insulin stimulated glucose transport and/or phosphorylation which develops after 3-4 hours of raising plasma FFA and a second defect, consisting of inhibition of glycogen synthase, the rate limiting enzyme of glycogen synthesis, which develops after 4-6 hours. FFA induced inhibition of fatty acid oxidation (Randle effect) does not affect insulin stimulated glucose uptake or glycogen synthesis and thus does not cause insulin resistance. Elevated plasma FFA levels also modestly increase insulin suppressed endogenous glucose production (EGP) although this effect has not been found by all investigators. The reasons why it has been difficult to demonstrate unequivocal effects of FFA on EGP include 1) the fact that FFA promote insulin secretion which counteracts its effect on EGP (FFA increase, while insulin decreases EGP); 2) the recognition that FFA induced increase in gluconeogenesis may be compensated by intrahepatic downregulation of EGP (i.e., by a decrease in glycogenolysis). The FFA induced insulin resistance is physiologically important during starvation by preserving carbohydrate for oxidation in the central nervous system and during pregnancy, where the well recognized accelerated starvation pattern provides carbohydrate for the growing fetus. In obesity, however, there is no need to spare carbohydrate and the FFA induced insulin resistance may result in type 2 diabetes and other cardiovascular risk factors.

Animals↗

PubMed1998

Leptin in human pregnancy: the relationship with gestational hormones.

OBJECTIVES: The aims of the study were (1) to examine the relationship between leptin and placental hormones by measuring serial changes in serum levels of leptin during and after pregnancy and (2) to study the effects of several gestational hormones on leptin release from fully differentiated 3T3-L1 adipocyte cell cultures. STUDY DESIGN: Serum levels of leptin were measured throughout pregnancy and at 3 months post partum in 29 healthy women and were also measured in 18 healthy women at delivery by cesarean section and on postpartum day 3. In addition, 3T3-L1 mouse adipocytes were incubated for 24 hours in media containing various reproductive hormones and leptin production was measured. RESULTS: Serum leptin levels increased significantly (8.4 +/- 0.9 vs 13.5 +/- 1.5 ng/mL; P <.001) between the first 2 trimesters of pregnancy but not between the second and third trimesters. These changes in leptin did not correlate significantly with changes in body mass index. Leptin levels dropped significantly during the immediate postpartum period, from 34.1 +/- 4.9 at cesarean delivery to 7.3 +/- 1.4 ng/mL on postpartum day 3 (P <.001). Fasting insulin level did not correlate significantly with leptin level during pregnancy but did so during the postpartum period (r = 0.60; P <.05). Leptin secretion from 3T3-L1 adipocytes was increased significantly when cells were cultured with human chorionic gonadotropin (150%, P <.01) and also when they were cultured with estrogen (120%, P <.03). CONCLUSION: The data suggest that leptin production by adipose tissue is stimulated by several hormones of pregnancy, which may contribute to the increased leptin levels observed during gestation.

3T3 Cells↗

PubMed1998

[Mucinous cystadenoma of the appendix].

A 63-year old female patient was admitted with a unclear abdominal ultrasound scan. Despite all our diagnostic examinations, the diagnosis--mucinous cystadenoma--was first established during surgery by intraoperative histological evaluation. We discuss the diagnostic possibilities and therapeutic approach.

Appendectomy↗

PubMed1998

Free fatty acids and insulin resistance during pregnancy.

The purpose of this study was to determine whether elevation of plasma free fatty acids (FFA) in early pregnancy would cause alterations in insulin-stimulated glucose disposal similar to those occurring in late gestation. Seven glucose-tolerant women underwent 4-h euglycemic hyperinsulinemic (1 mU/kg.min) clamping during the early second trimester of pregnancy (14-17 weeks) on 2 consecutive days, receiving either lipid (Liposyn II; 1.5 mL/min) and heparin (0.4 U/kg.min; L/H) or saline/glycerol (2.25 g/h; S/G) infusions. Rates of total body glucose disposal (6,6-2H2 glucose) and of carbohydrate and fat oxidation (indirect calorimetry) were determined at hourly intervals. Blood glucose was clamped at about 85 mg/dL. Plasma FFA increased from 290 +/- 50 to 1000 +/- 139 mumol/L during L/H infusion and decreased from 351 +/- 60 to 35 +/- 11 mumol/L during S/G infusion. L/H infusion inhibited insulin stimulation of total body glucose disposal by 28% compared with S/G infusion (from 6.7 +/- 0.7 to 4.9 +/- 0.6 mg/kg.min; P < 0.01). L/H infusion increased fat oxidation from 0.73 +/- 0.04 to 1.26 +/- 0.2 mg/kg.min (P < 0.05) and decreased carbohydrate oxidation from 2.0 +/- 0.2 to 1.6 +/- 0.2 mg/kg.min (P < 0.05). Endogenous glucose production decreased equally by approximately 70% during L/H and S/G infusions. These data showed that elevating plasma FFA levels during early pregnancy inhibits total body glucose uptake and oxidation. We conclude that elevation of plasma FFA can contribute to the peripheral insulin resistance commonly observed during late pregnancy.

Adult↗

PubMed1998

Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetic and nondiabetic subjects.

The objective of this study was to determine whether basal plasma free fatty acid (FFA) concentrations affect basal insulin secretion rates (ISRs). Effects of FFA levels on basal ISRs were evaluated by lowering basal plasma FFA levels with nicotinic acid (NA) (100-150 mg p.o., q 30 min x 4 h) in type 2 diabetic patients and in normal volunteers. Lowering of FFAs (from approximately 600 to approximately 100 micromol/l) lowered ISRs in type 2 diabetic patients during isoglycemic clamping (from 139 to 101 pmol/min; -23%; P < 0.02) and euglycemic clamping (from 99 to 63 pmol/min; -36%; P < 0.03) and in normal subjects during euglycemic clamping (from 127 to 96 pmol/min; -25%; P < 0.03). In addition, peripheral insulin concentrations decreased by approximately 30% in diabetic and nondiabetic subjects. NA had no direct effect on ISRs; that is, NA did not change ISRs when plasma FFAs were prevented from decreasing with a lipid/heparin infusion. We concluded that 1) basal plasma FFAs exerted physiologically important, long-lasting effects supporting 25-33% of basal insulin secretion in nondiabetic and diabetic subjects; 2) basal plasma FFAs were responsible for some of the hyperinsulinemia in normoglycemic obese subjects; and 3) NA had no direct effect on insulin secretion.

3-Hydroxybutyric Acid↗

PubMed1997

Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects.

We have studied the effect of prolonged hyperinsulinemia and hyperglycemia on serum leptin levels in young nonobese males during 72-h euglycemic-hyperinsulinemic and hyperglycemic ( approximately 8.5 and 12.6 mM) clamps. Hyperinsulinemia increased serum leptin concentrations (by RIA) dose-dependently. An increase in serum insulin concentration of > 200 pM for > 24 h was needed to significantly increase serum leptin. An increase of approximately 800 pM increased serum leptin by approximately 70% over 72 h. Changes in plasma glucose concentrations (from approximately 5.0 to approximately 12.6 mM) or changes in plasma FFA concentrations (from < 100 to > 1,000 microM) had no effect on serum leptin. Serum leptin concentrations changed with circadian rhythmicity. The cycle length was approximately 24 h, and the cycle amplitude (peak to trough) was approximately 50%. The circadian leptin cycles and the circadian cycles of total body insulin sensitivity (i.e., GIR, the glucose infusion rates needed to maintain euglycemia during hyperinsulinemic clamping) changed in a mirror image fashion. Moreover, GIR decreased between Days 2 and 3 (from 11.4+/-0.2 to 9. 8+/-0.2 mg/kg min, P< 0.05) when mean 24-h leptin levels reached a peak. In summary, we found (a) that 72 h of hyperinsulinemia increased serum leptin levels dose-dependently; (b) that hyperglycemia or high plasma FFA levels did not affect leptin release; (c) that leptin was released with circadian rhythmicity, and (d) that 24-h leptin cycles correlated inversely with 24-h cycles of insulin sensitivity. We speculate that the close positive correlation between body fat and leptin is mediated, at least in part, by insulin.

Adult↗

PubMed1997

Leptin is present in human cord blood.

It has recently been reported that the ob gene receptor was expressed on human and murine hematopoietic stem cells and that the ob gene product leptin stimulated hemato- and lymphopoiesis at the stem cell level. These findings suggest a role for leptin in hemato- and lymphopoiesis during fetal development. There is at present no evidence, however, that leptin is synthesized and released by the fetus. To investigate this possibility, we have measured plasma leptin concentrations in the cord blood of 78 newborn infants. We found that leptin was present in all 78 infants in concentrations comparable with those found in adults (0.6-55.7 ng/ml). Overall, plasma leptin concentrations in the cord blood of infants correlated with birth weight (r = 0.74, P < 0.001). These observations show that leptin is synthesized and released by fetal fat cells. In addition, they are compatible with the concept that leptin may play a role in human fetal hematopoiesis.

Birth Weight↗

PubMed1997

Longitudinal study of carbohydrate metabolism in healthy obese pregnant women.

OBJECTIVE: To longitudinally characterize changes in insulin sensitivity in obese women during and after pregnancy. RESEARCH DESIGN AND METHODS: Six glucose-tolerant obese women underwent a 4-h euglycemic-hyperinsulinemic (500-600 pmol/l) clamping during the second (22.5 +/- 2 weeks [mean +/- SD]) and third trimester (36.8 +/- 0.9) of pregnancy and again 15.6 +/- 1.4 weeks after delivery. Rates of total body glucose turnover (with [6.6-2H2]glucose) and oxidation (with indirect calorimetry) were measured. RESULTS: There were no significant changes with respect to the action of insulin on rates of glucose disappearance (GRd), carbohydrate oxidation, or endogenous glucose production (EGP), comparing the second trimester of pregnancy with the nonpregnant (postpartum) state. The third trimester, however, was characterized 1) by reductions in insulin-stimulated GRd (-28%, P < 0.05, compared with the second trimester and -40%, P < 0.05, compared with postpartum); 2) by even larger reductions in insulin-stimulated carbohydrate oxidation (-46%, P < 0.05, compared with the second trimester and -54%, P < 0.02, compared with postpartum); and 3) by reduction of insulin suppression of EGP (-39% compared with -79% at the second trimester and -77% postpartum, P < 0.01). CONCLUSIONS: Glucose-tolerant obese women developed peripheral was well as hepatic insulin resistance during the third trimester of pregnancy. These alterations were reversed after delivery and appeared to be adaptive mechanisms to cope with the increased demand for glucose of the growing fetus.

Adaptation, Physiological↗

PubMed1997

Role of fatty acids in the pathogenesis of insulin resistance and NIDDM.

Evidence is reviewed that free fatty acids (FFAs) are one important link between obesity and insulin resistance and NIDDM. First, plasma FFA levels are elevated in most obese subjects. Second, physiological elevations in plasma FFA concentrations inhibit insulin stimulated peripheral glucose uptake in a dose-dependent manner in normal controls and in patients with NIDDM. Two possible mechanisms are identified: 1) a fat-related inhibition of glucose transport or phosphorylation, which appears after 3-4 h of fat infusion, and 2) a decrease in muscle glycogen synthase activity, which appears after 4-6 h of fat infusion. Third, FFAs stimulate insulin secretion in nondiabetic individuals. Some of this insulin is transmitted in the peripheral circulation and is able to compensate for FFA-mediated peripheral insulin resistance. FFA-mediated portal hyperinsulinemia counteracts the stimulation of FFAs on hepatic glucose production (HGP) and thus prevents hepatic glucose overproduction. We speculate that, in obese individuals who are genetically predisposed to develop NIDDM, FFAs will eventually fail to promote insulin secretion. The stimulatory effect of FFAs on HGP would then become unchecked, resulting in hyperglycemia. Hence, continuously elevated levels of plasma FFAs may play a key role in the pathogenesis of NIDDM in predisposed individuals by impairing peripheral glucose utilization and by promoting hepatic glucose overproduction.

Animals↗

PubMed1996

Kininogen changes in human plasma following a test meal or insulin administration.

In healthy, fasted volunteers, the ingestion of a test meal produced within 30 min, a decrease of ca. 40% of high molecular weight kininogen (HK) in plasma. Return to control (fasting) levels occurred after 90-120 min. Low molecular weight kininogen (LK) remained unchanged or was slightly elevated. On another occasion, the same group of fasted volunteers received an intravenous, euglycemic-clamped infusion of insulin. This treatment reproduced the effects of the test meal on HK. Insulin had no effect on kininogen following incubation with plasma or whole blood. Slight systemic hypotension and increased leg muscle blood flow accompanied postprandial plasma kininogen change. It is suggested that such vascular changes may in part, be due to bradykinin (BK) released from HK cleaved at vascular, possibly endothelial sites activated by insulin following its release by alimentary stimulation. A decreased capacity to release BK due to absence of, or lowered sensitivity to, insulin may play a role in the origin of hypertension in diabetes.

Blood Pressure↗

PubMed1996

Effects of vanadyl sulfate on carbohydrate and lipid metabolism in patients with non-insulin-dependent diabetes mellitus.

The safety and efficacy of vanadyl sulfate (VS) was tested in a single-blind, placebo-controlled study. Eight patients (four men and four women) with non-insulin-dependent diabetes mellitus (NIDDM) received VS (50 mg twice daily orally) for 4 weeks. Six of these patients (four men and two women) continued in the study and were given a placebo for an additional 4 weeks. Euglycemic-hyperinsulinemic clamps were performed before and after the VS and placebo phases. VS was associated with gastrointestinal side effects in six of eight patients during the first week, but was well tolerated after that. VS administration was associated with a 20% decrease in fasting glucose concentration (from 9.3 +/- 1.8 to 7.4 +/- 1.4 mmol/L, P < .05) and a decrease in hepatic glucose output (HGO) during hyperinsulinemia (from 5.0 +/- 1.0 pre-VS to 3.1 +/- 0.9 micromol/kg x min post-VS, P < .02). The improvement in fasting plasma glucose and HGO that occurred during VS treatment was maintained during the placebo phase. VS had no significant effects on rates of total-body glucose uptake, glycogen synthesis, glycolysis, carbohydrate (CHO) oxidation, or lipolysis during euglycemic-hyperinsulinemic clamps. We conclude that VS at the dose used was well tolerated and resulted in modest reductions of fasting plasma glucose and hepatic insulin resistance. However, the safety of larger doses and use of vanadium salts for longer periods remains uncertain.

Blood Glucose↗

PubMed1996

Fuel metabolism in pregnancy and in gestational diabetes mellitus.

Fuel metabolism during pregnancy and in gestational diabetes mellitus (GDM) is reviewed with emphasis on carbohydrate and fat metabolism. In early pregnancy, insulin secretion in response to glucose is increased, peripheral insulin sensitivity is normal or increased, glucose tolerance is normal or slightly enhanced. In addition, there is maternal fat accumulation. During late pregnancy, there is increased fetal growth and increased fetal demand for nutrients. Maternal responses to these demands consist of an accelerated switch from carbohydrate to fat utilization that is facilitated by peripheral insulin resistance and by high blood levels of lipolytic hormones. In patients with GDM, insulin resistance is either comparable or greater than in nondiabetic pregnancy whereas insulin secretion appears to be compromised. Important short term consequences of GDM are perinatal complications, whereas long term complications include an increased rate of development of maternal non-insulin-dependent diabetes mellitus.

Carbohydrate Metabolism↗