The disposal of an oral glucose load in patients with non-insulin-dependent diabetes

Ferrannini, Eleuterio; Simonson, Donald C.; Katz, Lee D.; Reichard, George A.; Bevilacqua, Stefano; Barrett, Eugene J.; Olsson, Maggie; DeFronzo, Ralph A.

doi:10.1016/0026-0495(88)90033-9

Cited by 265 publications

(209 citation statements)

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“…Because the splanchnic area takes up ϳ30 -40% of an ingested glucose load (1)(2)(3)(4)(5)(6)23,24), inhibition of SGU by elevated plasma FFA levels represents an important potential site of impaired glucose homeostasis in type 2 diabetic individuals, especially in those who are in poor glycemic control. As a corollary, our observations also suggest that drugs, which enhance SGU and/or lower plasma FFA levels (45), may be beneficial in improving glycemic control in type 2 diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

“…It has been shown that elevated plasma FFA concentrations inhibit glucokinase in the liver in vitro (21) and that glucokinase activity is decreased in the liver of type 2 diabetic subjects (22). Some (23-25), but not all (4,26), studies have demonstrated an impairment in SGU in type 2 diabetic subjects. Thus, it is possible that elevated plasma FFA levels are responsible for or contribute to the defect in SGU that has been observed in some type 2 diabetic individuals.…”

Section: Studies By Defronzo Et Al (3) and Adkins Et Al (5) Havementioning

confidence: 99%

“…In conclusion, an elevation in plasma FFA concentration impairs both peripheral and SGU in patients with type 2 diabetes. Diabetes 51:3043-3048, 2002 S planchnic glucose uptake (SGU) plays a major role in the disposal of an oral glucose load (OGL) (1)(2)(3)(4)(5)(6). Hyperglycemia per se enhances SGU in proportion to the increase in plasma glucose concentration, such that the splanchnic glucose clearance remains unchanged (2).…”

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Free Fatty Acids Reduce Splanchnic and Peripheral Glucose Uptake in Patients With Type 2 Diabetes

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Splanchnic glucose uptake (SGU) plays a major role in the disposal of an oral glucose load (OGL). To investigate the effect of an elevated plasma free fatty acid (FFA) concentration on SGU in patients with type 2 diabetes, we measured SGU in eight diabetic patients (mean age 51 ؎ 4 years, BMI 29.3 ؎ 1.4 kg/m 2 , fasting plasma glucose 9.3 ؎ 0.7 mmol/l) during an intravenous Intralipid/heparin infusion and 7-10 days later during a saline infusion. SGU was estimated by the OGL insulin clamp method: subjects received a 7-h euglycemichyperinsulinemic clamp (insulin infusion rate ‫؍‬ 100 mU ⅐ m ؊2 ⅐ min ؊1 ), and a 75-g OGL was ingested 3 h after starting the insulin clamp. After glucose ingestion, the steady-state glucose infusion rate during the insulin clamp was decreased appropriately to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in glucose infusion rate during the 4-h period after glucose ingestion from the ingested glucose load (75 g). 3-[ 3 H]glucose was infused during the 3-h insulin clamp before glucose ingestion to determine the rates of endogenous glucose production and glucose disappearance (R d ). Intralipid/heparin or saline infusion was initiated 2 h before the start of the OGL clamp. Plasma FFA concentrations were significantly higher during the OGL clamp with the intralipid/heparin infusion than with the saline infusion (2.5 ؎ 0.3 vs. 0.11 ؎ 0.02 mmol/l, P < 0.001). During the 3-h insulin clamp period before glucose ingestion, Intralipid/heparin infusion reduced R d (4.4 ؎ 0.3 vs. 5.3 ؎ 0.3 mg ⅐ kg ؊1 ⅐ min ؊1 , P < 0.01). During the 4-h period after glucose ingestion, SGU was significantly decreased during the intralipid/heparin versus saline infusion (30 ؎ 2 vs. 37 ؎ 2%, P < 0.01). In conclusion, an elevation in plasma FFA concentration impairs both peripheral and SGU in patients with type 2 diabetes. Diabetes 51:3043-3048, 2002 S planchnic glucose uptake (SGU) plays a major role in the disposal of an oral glucose load (OGL) (1-6). Hyperglycemia per se enhances SGU in proportion to the increase in plasma glucose concentration, such that the splanchnic glucose clearance remains unchanged (2). This mass action effect of hyperglycemia to augment SGU depends on maintained portal insulin levels (2). Insulin per se, in the absence of hyperglycemia, does not increase SGU (2,7). Studies by DeFronzo et al. (3) and Adkins et al. (5) haveshown that the gastrointestinal route of glucose administration has a specific enhancing effect on SGU (3) and that after glucose ingestion, the fractional, as well as absolute uptake of glucose by the splanchnic tissues is significantly greater than the combined effects of hyperinsulinemia plus hyperglycemia created by intravenous glucose/insulin administration (2,5).Disturbances in free fatty acid (FFA) metabolism are characteristic in type 2 diabetic individuals (8 -11), who manifest day-long increased plasma FFA levels (11) and increased rates of lipolysis (8 -11). Elevated plasma FFA concentrations have been shown to impair glucose met...

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Section: Discussionmentioning

confidence: 99%

Section: Studies By Defronzo Et Al (3) and Adkins Et Al (5) Havementioning

confidence: 99%

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Free Fatty Acids Reduce Splanchnic and Peripheral Glucose Uptake in Patients With Type 2 Diabetes

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“…Only a few studies have examined the effect of type 2 diabetes on splanchnic glucose uptake, and the results from these data are not concordant. Several studies (12,13,15,16) have demonstrated that the greater net splanchnic glucose release observed in diabetic compared with nondiabetic subjects after glucose injection was attributable to excessive endogenous glucose production rather than to lower initial splanchnic extraction of the …”

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Inclusion of Low Amounts of Fructose With an Intraduodenal Glucose Load Markedly Reduces Postprandial Hyperglycemia and Hyperinsulinemia in the Conscious Dog

et al. 2002

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Intraportal infusion of small amounts of fructose markedly augmented net hepatic glucose uptake (NHGU) during hyperglycemic hyperinsulinemia in conscious dogs. In this study, we examined whether the inclusion of catalytic amounts of fructose with a glucose load reduces postprandial hyperglycemia and the pancreatic ␤-cell response to a glucose load in conscious 42-hfasted dogs. Each study consisted of an equilibration (؊140 to ؊40 min), control (؊40 to 0 min), and test period (0 -240 min). During the latter period, glucose (44.4 mol ⅐ kg ؊1 ⅐ min ؊1 ) was continuously given intraduodenally with (2.22 mol ⅐ kg ؊1 ⅐ min ؊1 ) or without fructose. The glucose appearance rate in portal vein blood was not significantly different with or without the inclusion of fructose (41.3 ؎ 2.7 vs. 37.3 ؎ 8.3 mol ⅐ kg ؊1 ⅐ min ؊1 , respectively). In response to glucose infusion without the inclusion of fructose, the net hepatic glucose balance switched from output to uptake (from 10 ؎ 2 to 11 ؎ 4 mol ⅐ kg ؊1 ⅐ min ؊1 ) by 30 min and averaged 17 ؎ 6 mol ⅐ kg ؊1 ⅐ min ؊1 . The fractional extraction of glucose by the liver during the infusion period was 7 ؎ 2%. Net glycogen deposition was 2.44 mmol glucose equivalent/kg body wt; 49% of deposited glycogen was synthesized via the direct pathway. Net hepatic lactate production was 1.4 mmol/kg body wt. Arterial blood glucose rose from 4.1 ؎ 0.2 to 7.3 ؎ 0.4 mmol/l, and arterial plasma insulin rose from 42 ؎ 6 to 258 ؎ 66 pmol/l at 30 min, after which they decreased to 7.0 ؎ 0.5 mmol/l and 198 ؎ 66 pmol/l, respectively. Arterial plasma glucagon decreased from 54 ؎ 7 to 32 ؎ 3 ng/l. In response to intraduodenal glucose infusion in the presence of fructose, net hepatic glucose balance switched from 9 ؎ 1 mol ⅐ kg G lucose uptake by the liver contributes in a major way to the disposal of alimentary glucose (1). In healthy humans, 20 -30% of absorbed glucose is taken up by the liver, and hepatic glycogen synthesis accounts for the disposal of about 70% of that amount. Liver glycogen is synthesized by both direct (glucose 3 glucose-6-phosphate [G6P] 3 glucose-1-phosphate 3 uridine 5Ј-diphosphate [UDP] glucose 3 glycogen) and indirect (three carbon unit 3 phosphoenolpyruvate 3 G6P 3 glucose-1-phosphate 3 UDP glucose 3 glycogen) pathways (2). After oral glucose ingestion in the healthy human, 50 -77% of the liver glycogen synthesized is derived via the direct pathway (3-6). The response of the conscious dog is similar to that of humans, with 25-40% of a gastrointestinal glucose load being taken up by the liver and 50 -62% of accumulated hepatic glycogen being synthesized via the direct pathway (7-9).Individuals with diabetes exhibit excessive postprandial hyperglycemia, with a defect in meal-or glucose-induced suppression of endogenous glucose production (10 -15). Only a few studies have examined the effect of type 2 diabetes on splanchnic glucose uptake, and the results from these data are not concordant. Several studies (12,13,15,16) have demonstrated that the greater net splanchnic glucose rel...

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Deriving whole body skeletal muscle mass from magnetic resonance imaging in type 2 diabetic men of White and Black ethnicity

Hakim

Goff

2017

Proc. Nutr. Soc.

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Accurate measurement of skeletal muscle mass (SMM) is important in type 2 diabetes (T2D) research as it is responsible for 80-90 % of insulin stimulated glucose disposal (1) . Direct measures, such as whole body magnetic resonance imaging (MRI), offer the greatest accuracy but are expensive and time-consuming. To overcome these limitations a number of methods that derive whole body SMM from regional or single slice MRI have been developed and validated, but only in Caucasian populations. Ethnic minority populations suffer disproportionately high rates of T2D and are therefore a focus of current research (2) . The aim of this analysis was to compare methods of estimating whole body SMM from MRI between men of Black West African (BWA) and White European (WE) ethnicity with T2D.Seventeen WE and 20 BWA men underwent MRI scanning (Siemens 1·5-Tesla) from neck to knee. Whole body SMM was derived by extrapolation of thigh muscle data using two methods by Lee et al. (3) : using a single MRI image in the mid-thigh region (20 cm below femoral head) to determine muscle area; and by assessing 7 equally spaced thigh images to determine the volume of 30 cm of thigh muscle. The extracted area and volume measurements were used in regression equations to determine whole-body SMM.The ethnic groups were well matched for age, weight and BMI (all p > 0·05). Whole body SMM was significantly higher amongst BWA men when derived from a single slice image (20 cm below femoral head) (p = 0·008). However there were no differences between ethnic groups when whole body SMM was derived from the 7 slice method (p = 0·12) ( Table 1). Further investigation of the discrepancy in the two methods showed the BWA men had higher muscle area in the mid to lower-thigh region compared to WE men.Methods of deriving whole body SMM, which have been validated against direct measurements in Caucasian populations, provide inconsistent estimations of whole body SMM in BWA men. Further validation of these methods against direct assessments in BWA populations is required; until such data is available these methods should be used with caution in BWA populations. *Data presented as median and interquartile range for non-parametric data. Ethnic differences were determined using independent t-tests for parametric data or a

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The disposal of an oral glucose load in patients with non-insulin-dependent diabetes

Cited by 265 publications

References 19 publications

Free Fatty Acids Reduce Splanchnic and Peripheral Glucose Uptake in Patients With Type 2 Diabetes

Free Fatty Acids Reduce Splanchnic and Peripheral Glucose Uptake in Patients With Type 2 Diabetes

Inclusion of Low Amounts of Fructose With an Intraduodenal Glucose Load Markedly Reduces Postprandial Hyperglycemia and Hyperinsulinemia in the Conscious Dog

Deriving whole body skeletal muscle mass from magnetic resonance imaging in type 2 diabetic men of White and Black ethnicity

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