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Biomedical subjects

G F Lewis

Publications and source records attributed to G F Lewis.

At least 55 records · Page 3Linked to original sources
PubMed1997

Glucagon enhances the direct suppressive effect of insulin on hepatic glucose production in humans.

The present study examines the role of glucagon in modulating the hepatic and extrahepatic effects of insulin on hepatic glucose production (HGP). We infused glucagon at a constant rate (0.65 ng x kg(-1) x min(-1)) during equimolar portal and peripheral insulin delivery in seven healthy males by our previously published tolbutamide infusion method. In contrast to our previous study, in which glucagon fell by approximately 30% during hyperinsulinemia and suppression of HGP was significantly greater with equimolar peripheral than with portal insulin delivery, HGP was actually suppressed to a lesser extent with peripheral insulin delivery (69 +/- 10%) than when insulin was delivered portally (76 +/- 5%, P < 0.05). To further examine whether glucagon was enhancing the effect of portal insulin, in four additional individuals HGP was suppressed to a greater extent during a tolbutamide infusion when glucagon was administered continuously throughout the basal and hyperinsulinemic periods than when glucagon was infused during the basal period only; HGP suppressed by 63 +/- 3 vs. 52 +/- 3%, respectively, P = 0.02). Tolbutamide had no effect on HGP when infused into three C-peptide-negative individuals with type I diabetes during a low-dose insulin and glucagon infusion. These data suggest that glucagon levels are an important determinant of the balance between insulin's direct and indirect effects on HGP, with glucagon likely potentiating the direct hepatic effect of insulin.

Adult↗
PubMed1997

Fatty acids mediate the acute extrahepatic effects of insulin on hepatic glucose production in humans.

We have shown previously in humans that insulin partly suppresses hepatic glucose production (HGP) by an extrahepatic (indirect) mechanism. In the present study, we investigated the role of free fatty acids (FFAs) in mediating the extrahepatic effects of insulin in humans and determined the extent to which insulin can regulate HGP by a non-FFA-mediated effect. Sixteen healthy men received an intravenous tolbutamide infusion for 3 h, and pancreatic insulin secretion was calculated by deconvolution of peripheral C-peptide levels. On a subsequent occasion, equimolar exogenous insulin was infused by peripheral vein. In both studies, glucose was clamped at euglycemia. We have previously validated this method and shown no independent insulin-like activity of tolbutamide. During the clamp, 9 of the 16 subjects received a low dose of heparin and Intralipid to prevent the insulin-induced suppression of FFAs, while 7 subjects received a high dose of heparin and Intralipid to raise FFAs approximately 2.5-fold. In both the high- and low-dose groups, peripheral insulin was higher and calculated portal insulin lower with peripheral versus portal insulin delivery. In the low-dose group, HGP decreased by 68.3 +/- 2.1% with portal insulin delivery and 64.7 +/- 3.7% with peripheral insulin delivery (NS). In the high-dose group, HGP decreased by 58.0 +/- 4.5% with portal insulin and 48.3 +/- 5.0% with peripheral insulin (P < 0.05). Four individuals who participated in the high-dose group underwent an additional peripheral insulin study in which the same dose of exogenous insulin was infused as in the high-dose group but in the absence of heparin and Intralipid. During this latter study, FFA levels declined by approximately 90% during hyperinsulinemia, and HGP was suppressed by 71.8 +/- 5.6%, which was a much greater suppression (P < 0.01) than when FFA levels were raised in these subjects during the equivalent rate insulin infusion. In summary, the previously observed greater suppression of HGP with equimolar peripheral versus portal insulin is eliminated or reversed, depending on plasma FFA levels, if FFAs are prevented from decreasing, suggesting an important role of FFAs in mediating the extrahepatic effects of insulin on HGP. However, the effect of FFA clamping is relatively small with a significant degree of suppression of HGP (by approximately 50%), which remains even when FFAs are elevated above basal levels, suggesting that in the physiological range FFAs only partially influence the suppression of HGP in humans. This suggests that other mechanisms, most likely hepatic, dominate the acute insulin-induced suppression of glucose production.

Adult↗
PubMed1997

Clearance of postprandial and lipolytically modified human HDL in rabbits and rats.

Triglyceride (TG) enrichment of high density lipoproteins (HDL) in hypertriglyceridemic states renders the particles vulnerable to lipolysis, which reduces their size. In the present study we modified the size and composition of HDL in vivo in hypertriglyceridemic humans by administering a bolus of intravenous heparin, and tested the subsequent clearance of the isolated HDL particles in rabbits and rats. HDL was isolated by ultracentrifugation from 21 moderately hypertriglyceridemic humans, 5 h after ingestion of a high fat meal and then 15 min after an intravenous heparin bolus (60 U/kg). Postprandial large TG-rich preheparin HDL and small, TG-poor postheparin HDL were labeled with either 125I or 131I. The clearance of apoA-I associated with each HDL tracer was determined by injecting the tracers 1) simultaneously (n = 13) and 2) sequentially (n = 8) into male New Zealand White rabbits, an hepatic lipase-deficient animal, and 3) by injecting the tracers simultaneously into male Sprague-Dawley rats (n = 8), an animal that has hepatic lipase. Die-away curves of each radiolabeled tracer were analyzed using a two-pool model that assumes the existence of an intravascular pool in dynamic equilibrium with an extravascular pool. In the rabbit studies, the fractional catabolic rate (FCR) of small, postheparin TG-poor HDL was greater than the FCR of the larger TG-rich HDL (11% greater in the simultaneous study, P < 0.001, and 45% greater in the sequential study, P < 0.001). Opposite results were observed in rats as large TG-rich preheparin particles showed a greater FCR (1.8-fold) than smaller TG-poor postheparin HDL (P < 0.05). These data suggest that although size and composition of HDL can influence its catabolism, the effect is not always in the same direction and depends on other factors present in vivo.

Animals↗
PubMed1997

Chronic exogenous insulin and chronic carbohydrate supplementation increase de novo VLDL triglyceride fatty acid production in rats.

We have investigated hepatic de novo lipogenesis and the ratio of apoB-48/apoB-100 during chronic carbohydrate supplementation with or without administration of exogenous insulin in rats. Two groups received chronic (2 weeks) carbohydrate supplementation either as 10% glucose or 10% fructose (wt/v) in their drinking water. Two other groups received exogenous insulin chronically, in addition to the monosaccharides above. The insulin was given for 2 weeks as daily human ultralente insulin injections in increasing doses up to 6 units per day. A fifth group of rats (normal control) received only chow and water. The fractional synthetic rate (FSR), the fraction of very low density lipoprotein triglyceride (VLDL-TG) palmitate that was newly made during an 8-h infusion with sodium [1-13C]acetate, was evaluated. The glucose and fructose groups had a 4-fold (0.60%/h) and 7.5-fold (1.13%/h) increase in FSR from baseline, respectively, compared to chow-fed controls (0.15%/h). Chronic exogenous insulin administration resulted in a 11.5 (1.73%/h) and 11.0 (1.65%/h)-fold increase over baseline in the synthesis of newly made VLDL-TG palmitate in the glucose and fructose groups, respectively. The ratio of apoB-48/apoB-100, i.e. apoB-48 enrichment, in VLDL was positively correlated with insulin levels (r = 0.41, P < 0.01) and with FSR (r = 0.39, P < 0.01). The present study shows that carbohydrate supplementation significantly increases the FSR of newly made VLDL-TG palmitate and that this increase is further augmented by chronic hyperinsulinemia.

Acetates↗
PubMed1996

Postprandial changes in high-density lipoprotein composition and subfraction distribution are not altered in patients with insulin-dependent diabetes mellitus.

A detailed analysis of postprandial changes in the size, density, composition, and relative proportion of the major high-density lipoprotein (HDL) subfractions, HDL2 and HDL3, was performed in seven normolipidemic patients with insulin-dependent diabetes mellitus (IDDM) in moderate glycemic control and seven age-, sex-, and weight-matched healthy nondiabetic controls. IDDM subjects received an overnight insulin infusion to maintain euglycemia, with an incremental increase in the insulin infusion rate at the time of the test meal (containing 60 g fat/m2). Samples for detailed analysis of HDL by gradient density ultracentrifugation and nondenaturing gradient gel electrophoresis (GGE) were collected at 0, 4, Br, and 12 hours after the test meal. The composition of HDL, HDL2, and HDL3 was significantly altered in the postprandial state in IDDM subjects and controls with an increase in triglyceride content at 4 to 8 hours and a reciprocal decrease in cholesteryl ester, reflecting exchange of lipid constituents of HDL with triglyceride (TG)-rich lipoproteins. In addition, the phospholipid content of the particles increased at 8 hours after the meal. Peak density of HDL2 and HDL3 decreased slightly at 4 to 8 hours, reaching significance only in controls at 8 hours (P < .05), whereas the mean radius size of these subfractions did not change significantly. In controls and IDDM subjects, the ratio of HDL3 to HDL2 at 8 to 12 hours increased significantly (P < .005). Significant differences in the composition, size, density, or subfraction distribution of HDL between subjects with IDDM and controls were not observed following ingestion of the lipid-rich meal. We conclude from these data that in patients with IDDM in moderate glycemic control, there do not appear to be any significant gross abnormalities in postprandial HDL metabolism with respect to the size, density, or compositional changes of HDL particles.

Adult↗
PubMed1996

Hyperinsulinemia and triglyceride-rich lipoproteins.

Hypertriglyceridemia is the most frequent form of hyperlipidemia seen in diabetes. Because hypertriglyceridemia and hyperinsulinemia often coexist in the general population and because patients with NIDDM generally are hyperinsulinemic, we have undertaken a series of in vivo studies to examine the effects of hyperinsulinemia on VLDL production. These studies showed that chronic hyperinsulinemia is accompanied by increased VLDL production and that this occurs even when plasma free fatty acid (FFA) levels have fallen. By contrast, acute hyperinsulinemia is accompanied by a reduction in VLDL production, and this reduction is, at least in part, mediated by an associated reduction in the availability of plasma FFAs as a substrate for VLDL-triglyceride (TG). The studies also raise the possibility that the difference in the dependence of VLDL production on plasma FFAs in acute versus chronic hyperinsulinemia results from an increase in hepatic lipogenic enzymes and from the availability of an alternate substrate such as fructose. The overall effect of hyperinsulinemia on VLDL production is postulated to reflect both the effect of insulin on apolipoprotein B production and the hepatic synthesis of TG from either plasma FFAs or newly made fatty acids.

Animals↗
PubMed1996

Hepatic glucose production is regulated both by direct hepatic and extrahepatic effects of insulin in humans.

The present study examines the effect of the route of insulin delivery on glucose turnover in humans. By using a new noninvasive in vivo method, the acute effect of insulin secreted by the pancreas can be compared with that of insulin delivered by a peripheral vein. Three euglycemic-hyperinsulinemic studies were performed in lean healthy men. In the first study (n = 10), constant portal hyperinsulinemia was produced using a programmed intravenous tolbutamide infusion algorithm, and the insulin secretion rate was mathematically derived by deconvolution from peripheral plasma C-peptide levels. In the second study (n = 10), exogenous insulin was infused by peripheral vein at the same rate as that determined in the first study. In the third study (n = 7), the peripheral insulin levels in the first study were matched by infusing exogenous insulin into a peripheral vein at half that rate. Peripheral insulin levels were higher (P < 0.001) with the full-rate peripheral insulin infusion (266.3 +/- 28.1 pmol/l) than with the portal delivery of insulin (171.1 +/- 30.4 pmol/l) or the half-rate peripheral insulin infusion (158.6 +/- 7.4 pmol/l) (portal versus half-rate peripheral insulin infusion, NS). Calculated hepatic insulin levels were higher (P < 0.001) in the portal insulin study (443.1 +/- 52.6 pmol/l) than in the full-rate peripheral insulin study (303.6 +/- 30.9 pmol/l) or in the half-rate peripheral insulin study (204.5 +/- 9.8 pmol/l). Hepatic glucose production (HGP) was suppressed to a greater extent with the full-rate peripheral insulin infusion (69.3 +/- 7.8%, P < 0.001 vs. portal or half-rate peripheral insulin) than portal (50.3 +/- 9.8%) or half-rate peripheral insulin infusion (36.8 +/- 3.8%). In the portal insulin study, however, suppression was greater than in the half-rate peripheral insulin study (P < 0.01), in spite of equal peripheral insulin levels. The assumption that tolbutamide, when used in this fashion, has no independent effect on glucose turnover, glucagon, or gluconeogenic precursor and energy substrates for gluconeogenesis was validated in five C-peptide-negative patients with IDDM. We conclude that in nondiabetic humans, 1) peripheral effects of insulin are important in suppressing HGP, as evidenced by the greater suppression of HGP with equivalent rate peripheral versus portal insulin delivery, and 2) because HGP was suppressed to a greater extent with portal verus peripheral insulin delivery at half the rate when peripheral insulin levels were matched, insulin-induced suppression of HGP is also partly mediated by a direct hepatic effect.

Adult↗
PubMed1996

Acute effects of insulin in the control of VLDL production in humans. Implications for the insulin-resistant state.

The role of hyperinsulinemia in the pathogenesis of triglyceride (TG) and VLDL over-production in insulin-resistant states remains controversial. While studies in humans and animals have generally suggested that chronic hyperinsulinemia facilitates VLDL production, particularly in the presence of an abundant supply of substrate for VLDL synthesis, the majority of in vitro studies using cultured hepatocytes and hepatoma cell lines have demonstrated an acute inhibitory effect of insulin. Using radiolabeled VLDL tracers we have examined the acute effect of hyperinsulinemia on VLDL production in humans. We found a rapid suppression of plasma free fatty acid (FFA) levels in response to insulin and a consistent 50-60% insulin-induced suppression of both VLDL TG and VLDL apolipoprotein (apo) B in lean insulin-sensitive individuals. Elevation of plasma FFA levels by infusing heparin and Intralipid without hyperinsulinemia resulted in a marked increase in VLDL TG and VLDL apoB production. When the insulin-induced suppression of plasma FFA levels was prevented during hyperinsulinemia, VLDL TG production was still inhibited, although to a lesser extent than with insulin alone. We concluded from these findings that insulin suppresses VLDL production in insulin-sensitive humans partly by suppressing plasma FFA levels and partly by a non-FFA-mediated (perhaps direct hepatic) mechanism. In addition, we found that chronically insulin-resistant hyperinsulinemic obese individuals were resistant to this suppressive effect of insulin on VLDL apoB production, in keeping with similar findings by others performing in vitro experiments using cultured hepatocytes isolated from insulin-resistant or hyperinsulinemic rats. The relevance of these findings to the mechanism of hypertriglyceridemia associated with chronic insulin-resistant states in humans remains a matter of speculation. One hypothesis is that resistance to the normal suppressive effect of insulin, in association with other metabolic abnormalities associated with insulin resistance, may contribute to postprandial and postabsorptive hypertriglyceridemia.

Animals↗
PubMed1995

Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans.

Changes in VLDL triglyceride and VLDL apo B production were determined semiquantitatively in healthy young men by examining the effect of altering plasma insulin and/or FFA levels on the change in the slopes of the specific activity of VLDL [3H]triglyceride glycerol or the 131I-VLDL apo B versus time curves. In one study (n = 8) insulin was infused for 5 h using the euglycemic hyperinsulinemic clamp technique. Plasma FFA levels declined by approximately 80% (0.52 +/- 0.01 to 0.11 +/- 0.02 mmol/liter), VLDL triglyceride production decreased by 66.7 +/- 4.2% (P = 0.0001) and VLDL apo B production decreased by 51.7 +/- 10.6% (P = 0.003). In a second study (n = 8) heparin and Intralipid (Baxter Corp., Toronto, Canada) were infused with insulin to prevent the insulin-mediated fall in plasma FFA levels. Plasma FFA increased approximately twofold (0.43 +/- 0.05 to 0.82 + 0.13 mmol/liter), VLDL triglyceride production decreased to a lesser extent than with insulin alone (P = 0.006) (-31.8 +/- 9.5%, decrease from baseline P = 0.03) and VLDL apo B production did not decrease significantly (-6.3 +/- 13.6%, P = NS). In a third study (n = 8) when heparin and Intralipid were infused without insulin, FFA levels rose approximately twofold (0.53 +/- 0.04 to 0.85 +/- 0.1 mmol/liter), VLDL triglyceride production increased by 180.1 +/- 45.7% (P = 0.008) and VLDL apo B production increased by 94.2 +/- 28.7% (P = 0.05). We confirm our previous observation that acute hyperinsulinemia suppresses VLDL triglyceride and VLDL apo B production in healthy humans. In addition, we have demonstrated that elevation of plasma FFA levels acutely stimulates VLDL production in vivo in healthy young males. Elevating plasma FFA during hyperinsulinemia attenuates but does not completely abolish the suppressive effect of insulin on VLDL production, at least with respect to VLDL triglycerides. Therefore, in normal individuals the acute inhibition of VLDL production by insulin in vivo is only partly due to the suppression of plasma FFA, and may also be due to an FFA-independent process.

Adult↗
PubMed1995

Diabetic dyslipidemia: a case for aggressive intervention in the absence of clinical trial and cost effectiveness data.

Patients with diabetes mellitus have a two- to fourfold increase in clinical manifestations of atherosclerotic cardiovascular disease (ASCVD). Traditional risk factors such as age, hypertension, left ventricular hypertrophy, hyperlipidemia and smoking are still operative in diabetes but do not account for the total increase in ASCVD risk associated with diabetes. The most common lipid abnormalities in noninsulin-dependent diabetes mellitus and poorly controlled insulin-dependent diabetes mellitus are hypertriglyceridemia and low high density lipoprotein cholesterol. Evidence is presented to support the hypothesis that these lipid abnormalities are atherogenic in diabetes. Treatment of diabetic dyslipidemia with conservative measures (diet, weight loss, aerobic exercise, improved glycemic control) and pharmacological management have been shown to be highly effective in normalizing the lipid abnormalities. However, few trials of lipid lowering therapy have included patients with known diabetes mellitus and, to date, there have been no well-controlled prospective trials of lipid lowering therapy in diabetes. There is therefore no definitive proof regarding the benefit of lipid lowering therapy in diabetes mellitus. There are also no data regarding the cost effectiveness of lipid lowering therapy in reducing ASCVD complications in diabetes. There are data, however, showing that complications of ASCVD in patients with diabetes account for a large percentage of total health care expenditures. The overwhelming evidence that patients with diabetes have a high rate of ASCVD, that traditional risk factors for ASCVD are operative in diabetes and that the dyslipidemia of diabetes is highly prevalent and proatherogenic, predicts that the treatment of ASVD risk factors, including dyslipidemia, will be associated with a substantial reduction in ASCVD complications.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗
PubMed1994

VLDL production is decreased to a similar extent by acute portal vs. peripheral venous insulin.

Acute changes in very low-density lipoprotein (VLDL) triglyceride (TG) and VLDL apolipoprotein (apo) B production were examined in 11 healthy young males in response to insulin delivered either by the peripheral venous route or secreted directly by the pancreas. Steady rates of pancreatic insulin secretion were achieved for 5 h by a programmed intravenous tolbutamide infusion, while euglycemia was maintained with a dextrose infusion. Insulin secretory rate was calculated from peripheral C-peptide levels by deconvolution, and, in a subsequent study, exogenous insulin was infused peripherally to match this pancreatic insulin secretory rate in each subject. Changes in VLDL TG and VLDL apo B production were determined semiquantitatively on each occasion by examining the change in slope of the specific activity (SA) of 3H-labeled triglyceride glycerol ([3H]TGG) and 131I-VLDL apo B vs. time curves, respectively, occurring with acute hyperinsulinemia. Plasma-free fatty acids (FFA), TG, apo B, and VLDL TG/VLDL apo B ratio decreased to a similar extent in both studies after the onset of hyperinsulinemia. VLDL TG production decreased significantly in both the tolbutamide (-47.1 +/- 7.3%, P < 0.002) and the exogenous insulin infusion study (-52.8 +/- 12.4%, P < 0.005). VLDL apo B production also decreased significantly in both studies (-58.9 +/- 7.5%, P = 0.0007 and -52.1 +/- 6.8%, P < 0.006, respectively), and there were no significant differences between studies. Tolbutamide was shown to have no independent effect on VLDL TG or VLDL apo B production in four insulin-deficient diabetic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

A new method for comparing portal and peripheral venous insulin delivery in humans: tolbutamide versus insulin infusion.

We describe a new noninvasive method for comparing insulin secreted acutely by the pancreas vs. a matched peripheral venous insulin infusion in humans. An intravenous tolbutamide infusion algorithm was developed that produced sustained steady rates of portal insulin secretion over 5 h in 11 healthy young men. Plasma glucose levels were maintained in the euglycemic range by adjusting the rate of an iv dextrose (20%) infusion. The pancreatic insulin secretory rate was calculated from peripheral C-peptide levels by deconvolution using standard parameters for a two-compartment mathematical model for C-peptide distribution and metabolism. On a subsequent occasion in the same subject, exogenous insulin was infused peripherally at a rate that matched the earlier tolbutamide-induced pancreatic insulin secretory rate, and euglycemia was maintained with a variable 20% dextrose infusion. The assumption that tolbutamide, when used in this fashion, has no independent insulin-like or insulin-potentiating effect at either low or high levels of peripheral insulinemia, does not affect insulin clearance, and does not suppress peripheral glucagon levels was validated in four patients with insulin-dependent diabetes mellitus. Mean peripheral immunoreactive insulin was significantly higher in the insulin infusion study than in the tolbutamide study (286 +/- 31 vs. 156 +/- 21 pmol/L; P = 0.0001). The dextrose infusion rates required to maintain euglycemia were also higher in the insulin infusion study (0.44 +/- 0.03 vs. 0.32 +/- 0.03 mmol/kg.min; P = 0.003). The MCR of insulin was greater in the tolbutamide infusion vs. the exogenous insulin infusion study (32.6 +/- 2.9 vs. 19.8 +/- 2.2 mL/kg.min; P = 0.0003), probably due to the hepatic first pass effect on insulin clearance when insulin is delivered by the portal route. This noninvasive method can be used in future studies to examine the relative importance of direct hepatic vs. peripheral effects of insulin in controlling hepatic glucose and lipid production.

Adult↗
PubMed1993

Effects of acute hyperinsulinemia on VLDL triglyceride and VLDL apoB production in normal weight and obese individuals.

The effects of short-term hyperinsulinemia on the production of both VLDL triglyceride and VLDL apoB were determined semiquantitatively before and during a 6-h euglycemic hyperinsulinemic clamp (40 mU.m-2 x min-1) in 17 women (8 chronically hyperinsulinemic obese, BMI = 35.7 kg/m2; 9 normal weight, BMI = 22.5 kg/m2). During acute hyperinsulinemia, plasma FFA decreased by approximately 95% within 1 h in both groups. VLDL triglyceride production decreased 66% in the control subjects (P = 0.0003) and 67% in obese subjects (P = 0.0003). ApoB production decreased 53% in control subjects (P = 0.03) but only 8% in obese (NS). Plasma triglycerides decreased by 40% from baseline in control subjects (P < 0.0001) but only by 10% in obese subjects (P = NS). Despite the similar decrease in triglyceride and apoB production in control subjects, VLDL particle size (triglyceride-to-apoB ratio) decreased with hyperinsulinemia (P = 0.003). In obese subjects, despite a decrease in triglyceride production similar to that in control subjects but no change in apoB production, VLDL size did not change appreciably. Acute hyperinsulinemia in humans: 1) suppresses plasma FFA equally in control and obese subjects at this high dose of insulin; 2) inhibits VLDL triglyceride production equally in control and obese subjects, perhaps secondary to the decrease in FFA; 3) inhibits VLDL apoB production in control but less so in obese subjects, suggesting that obese subjects may be resistant to this effect of insulin; 4) decreases plasma triglyceride and VLDL particle size in control subjects, reflecting either stimulation of LPL activity or a greater relative decrease in triglyceride to apoB production; and 5) does not decrease plasma triglyceride or VLDL size in obese subjects to the same extent as it does in control subjects. Thus, the insulin resistance of obesity affects some but not all aspects of VLDL metabolism.

Acute Disease↗
PubMed1993

Prior feeding alters the response to the 50-g glucose challenge test in pregnancy. The Staub-Traugott effect revisited.

OBJECTIVE: To examine the effect of prior meal ingestion on the glucose, insulin, and C-peptide response to a 50-g glucose challenge test in the third trimester of pregnancy. RESEARCH DESIGN AND METHODS: Ten pregnant women with gestational diabetes mellitus and 12 nondiabetic pregnant control subjects matched for age and weight underwent a 50-g glucose challenge test on three occasions within a 2-wk period, in random order. On one occasion the test was administered in the fasting state (fasting glucose challenge test), on a second occasion the test was administered 1 h after ingestion of a standard mixed meal (1-h postprandial study), and on a third occasion the test was administered 2 h after ingestion of a standard mixed meal (2-h postprandial study). RESULTS: In the control subjects, the plasma glucose level 1 h after ingestion of 50 g of glucose was higher in the fasting study (7.8 +/- 0.4 mM, 7 of 12 subjects with glucose > or = 7.8 mM) than in the 1-h postprandial study (6.7 +/- 0.3 mM, 3 of 12 subjects with glucose > or = 7.8 mM) and the 2-h postprandial study of (6.3 +/- 0.4 mM, 3 of 12 with glucose > or = 7.8 mM) (P < 0.01). In the postprandial studies of control subjects, insulin and C-peptide levels were higher at the time of ingestion of the 50 g of glucose, but the early (1 h) insulin secretory response was less than in the fasting study. In the diabetic patients, glucose levels 1 h after 50-g glucose ingestion were similar in the fasting study (10.5 +/- 0.4 mM, no subjects with glucose value < 7.8 mM) and the 1-h postprandial study (11.0 +/- 0.6 mM, 1 subject with glucose < 7.8 mM), but was lower in the 2-h postprandial study (9.3 +/- 0.3 mM, 1 subject with glucose < 7.8 mM) (P < 0.03). In contrast to the control subjects, the insulin secretory response to 50 g of oral glucose was greater in the two postprandial studies than in the fasting study. CONCLUSIONS: We have reached the following conclusions. 1) In nondiabetic gravidas, plasma glucose concentrations 1 h after ingestion of a 50-g oral glucose load are higher if administered in the fasting state compared with the postprandial state. 2) During normal pregnancy the Staub-Traugott Effect, i.e., improved glucose disposal after successive glucose load administrations, occurs and appears to be caused by mechanisms other than enhanced insulin secretion with successive glucose loads. 3) The effect of the prandial state on plasma glucose response to the 50-g glucose challenge test used to screen for gestational diabetes mellitus may be of sufficient magnitude to significantly alter the operating characteristics, i.e., sensitivity and specificity, of this test.

Adult↗
PubMed1992

Role of basal triglyceride and high density lipoprotein in determination of postprandial lipid and lipoprotein responses.

The present study reports on the interaction between basal triglyceride and high density lipoprotein (HDL) cholesterol in determining the magnitude of postprandial triglyceridemia. The vitamin A fat-loading test was used to label intestinally derived triglyceride-rich particles after a high fat meal in 18 subjects with low HDL cholesterol and 6 control subjects who had normal fasting triglyceride and HDL cholesterol levels. The patients with low HDL cholesterol were divided into 2 groups on the basis of their basal triglyceride concentrations; 11 had normal triglyceride levels, and 7 had elevated serum triglycerides (HTG). In the HTG-low HDL group, the incremental area under the triglyceride curve was significantly greater (P less than 0.0003) than that in the other 2 groups, between whom no significant differences in triglyceride response were observed. Retinyl palmitate levels measured in whole plasma, an Sf greater than 1000 chylomicron fraction, and an Sf less than 1000 nonchylomicron fraction were also significantly greater in low HDL subjects with HTG, while the concentrations in low HDL subjects with normal triglyceride levels and control subjects were similar. Although basal HDL cholesterol levels in all study subjects were negatively correlated with the area under the incremental triglyceride curve (r = -0.42; P less than 0.05), this correlation was weak, in contrast to the correlation between fasting triglyceride levels and incremental triglyceride area (r = 0.56; P less than 0.005). Furthermore, basal HDL cholesterol levels did not correlate with the area under the chylomicron or nonchylomicron curves, whereas basal triglyceride levels were significantly correlated (P = 0.0001) with both of these variables. The HDL particles of both low HDL groups had a significantly higher proportion of triglyceride compared to the HDL particles in the control subjects. In conclusion, 1) fasting triglyceride levels are a more powerful indicator of the postprandial lipid response than basal HDL cholesterol in subjects with low HDL cholesterol levels; 2) patients with low HDL cholesterol levels do not preferentially accumulate chylomicron remnants after a meal unless they have coexisting hypertriglyceridemia; and 3) abnormalities in the levels of triglyceride-rich particles post-prandially are unlikely to be responsible for the increased incidence of atherosclerosis in low HDL patients who are normotriglyceridemic.

Blood Glucose↗
PubMed1992

Hypoglycemic thresholds for cognitive dysfunction in IDDM.

Fourteen poorly controlled insulin-dependent diabetes mellitus (IDDM) patients (HbA1c 11 +/- 0.5%) with a mean +/- SE duration of disease of 15 +/- 2 yr were studied to evaluate the hypoglycemic threshold for cognitive dysfunction under insulin-induced hypoglycemia. The P300 event-related potential, a measure of cognitive function, and reaction time (RT) in response to visual stimuli under euglycemic conditions and at plasma glucose concentrations of 3.5 and 2.5 mM (63 and 45 mg/dl, respectively) during a constant insulin infusion were recorded. Baseline P300 latency was similar to that of a nondiabetic control group, but baseline RT was greater in the IDDM group. There was no increase in P300 latency or RT under euglycemic clamp conditions or at a plasma glucose level of 3.5 mM (63 mg/dl). However, when plasma glucose was lowered to 2.5 mM (45 mg/dl), there was an increase in P300 latency and a prolongation of RT. As plasma glucose returned to baseline, P300 latency and RT remained prolonged. After administration of intravenous glucose and a meal, P300 latency and RT returned to baseline. P140, an event-related potential reflecting sensory processes, was not altered. Because P300 latency changes paralleled RT changes, hypoglycemia appears to slow decision-making processes in IDDM. This study revealed that 1) baseline P300 latency is not elevated in poorly controlled IDDM patients, suggesting no cumulative cognitive dysfunction.

Blood Glucose↗