23-OR: The Effect of 14-Day Atorvastatin Treatment on Postprandial Glucose Metabolism in Healthy Males—A Link to Why Statin Therapy Increases the Risk of Type 2 Diabetes?

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 23-OR
Author(s):  
MARTIN L. THOMASEN ◽  
DAVID P. SONNE ◽  
MARTIN L. KÅRHUS ◽  
ANDREAS BRØNDEN ◽  
BART STAELS ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Statin Therapy ◽  
Postprandial Glucose ◽  
Atorvastatin Treatment ◽  
Healthy Males

scholarly journals Atorvastatin administration is associated with dose-related changes in IGF bioavailability

2013 ◽  
Vol 168 (4) ◽  
pp. 543-548 ◽  
Author(s):  
Ram P Narayanan ◽  
Matthew Gittins ◽  
Kirk W Siddals ◽  
Robert L Oliver ◽  
Julie E Hudson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Statin Therapy ◽  
Group Differences ◽  
High Dose ◽  
Differential Impact ◽  
Atorvastatin Treatment ◽  
Atorvastatin Therapy ◽  
Design And Methods ◽  
Trial Participants

ObjectiveIGF levels, their binding proteins (IGFBPs) and high-dose statin therapy have been linked to the development of diabetes. We aimed to identify whether atorvastatin caused dose-related changes in IGF proteins.Design and methodsWe measured IGF1, IGF2, IGFBP1 and IGFBP3 concentrations at baseline, 6 and 12 months in Protection Against Nephropathy in Diabetes with Atorvastatin trial participants with type 2 diabetes randomised to 10 mg (n=59) vs 80 mg (n=60) of atorvastatin (n=119; mean (s.d.): age 64 (10) years; 83% male; HbA1c 61 (10) mmol/mol; blood pressure 131/73 mmHg).ResultsAtorvastatin was associated with overall reductions in circulating IGF1, IGF2 and IGFBP3 concentrations (P<0.05 for all changes). The adjusted mean (95% CI) between-group differences that indicate dose-related changes in IGF proteins were not significant for IGF1: −3 (−21 to 14) ng/ml; IGF2: −23 (−65 to 18) ng/ml and IGFBP3: −0.34 (−0.71 to 0.03) μg/ml, negative values indicating numerically greater lowering with high dose. The IGFBP1 concentration did not change with atorvastatin therapy overall but the adjusted mean (95% CI) between-group difference indicating a dose-related change in log IGFBP1 was highly significant −0.41 (−0.69 to 0.13, P=0.004).ConclusionIGF1, IGF2 and IGFBP3 concentrations decreased following atorvastatin therapy. A differential effect of low- vs high-dose atorvastatin on IGFBP1 concentrations was observed with likely implications for IGF bioavailability. The dose-related differential impact of atorvastatin treatment on concentration of IGF proteins merits investigation as a mechanism to explain the worsening of glucose tolerance with statin therapy.

scholarly journals Effects of Sustained Treatment With Lixisenatide on Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: A Randomized Controlled Trial

Diabetes Care ◽  
2020 ◽  
Vol 43 (8) ◽  
pp. 1813-1821 ◽  
Author(s):  
Christopher K. Rayner ◽  
Linda E. Watson ◽  
Liza K. Phillips ◽  
Kylie Lange ◽  
Michelle J. Bound ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Randomized Controlled Trial ◽  
Gastric Emptying ◽  
Glucose Metabolism ◽  
Controlled Trial ◽  
Postprandial Glucose ◽  
Randomized Controlled

scholarly journals Effects of Ipragliflozin on Postprandial Glucose Metabolism and Gut Peptides in Type 2 Diabetes: A Pilot Study

2018 ◽  
Vol 9 (1) ◽  
pp. 403-411 ◽  
Author(s):  
Hiroaki Ueno ◽  
Hiroko Nakazato ◽  
Emi Ebihara ◽  
Kenji Noma ◽  
Takahisa Kawano ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Pilot Study ◽  
Glucose Metabolism ◽  
Postprandial Glucose ◽  
Gut Peptides

Abnormal renal, hepatic, and muscle glucose metabolism following glucose ingestion in type 2 diabetes

2004 ◽  
Vol 287 (6) ◽  
pp. E1049-E1056 ◽  
Author(s):  
Christian Meyer ◽  
Hans J. Woerle ◽  
Jean M. Dostou ◽  
Stephen L. Welle ◽  
John E. Gerich
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Postprandial Glucose ◽  
Glucose Disposal ◽  
Glucose Release ◽  
Glucose Ingestion ◽  
Endogenous Glucose

Recent studies indicate an important role of the kidney in postprandial glucose homeostasis in normal humans. To determine its role in the abnormal postprandial glucose metabolism in type 2 diabetes mellitus (T2DM), we used a combination of the dual-isotope technique and net balance measurements across kidney and skeletal muscle in 10 subjects with T2DM and 10 age-, weight-, and sex-matched nondiabetic volunteers after ingestion of 75 g of glucose. Over the 4.5-h postprandial period, diabetic subjects had increased mean blood glucose levels (14.1 ± 1.1 vs. 6.2 ± 0.2 mM, P < 0.001) and increased systemic glucose appearance (100.0 ± 6.3 vs. 70.0 ± 3.3 g, P < 0.001). The latter was mainly due to ∼23 g greater endogenous glucose release (39.8 ± 5.9 vs. 17.0 ± 1.8 g, P < 0.002), since systemic appearance of the ingested glucose was increased by only ∼7 g (60.2 ± 1.4 vs. 53.0 ± 2.2 g, P < 0.02). Approximately 40% of the diabetic subjects’ increased endogenous glucose release was due to increased renal glucose release (19.6 ± 3.1 vs. 10.6 ± 2.4 g, P < 0.05). Postprandial systemic tissue glucose uptake was also increased in the diabetic subjects (82.3 ± 4.7 vs. 69.8 ± 3.5 g, P < 0.05), and its distribution was altered; renal glucose uptake was increased (21.0 ± 3.5 vs. 9.8 ± 2.3 g, P < 0.03), whereas muscle glucose uptake was normal (18.5 ± 1.8 vs. 25.9 ± 3.3 g, P = 0.16). We conclude that, in T2DM, 1) both liver and kidney contribute to postprandial overproduction of glucose, and 2) postprandial renal glucose uptake is increased, resulting in a shift in the relative importance of muscle and kidney for glucose disposal. The latter may provide an explanation for the renal glycogen accumulation characteristic of diabetes mellitus as well as a mechanism by which hyperglycemia may lead to diabetic nephropathy.

Mechanisms for abnormal postprandial glucose metabolism in type 2 diabetes

2006 ◽  
Vol 290 (1) ◽  
pp. E67-E77 ◽  
Author(s):  
Hans J. Woerle ◽  
Ervin Szoke ◽  
Christian Meyer ◽  
Jean M. Dostou ◽  
Steven D. Wittlin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Postprandial Glucose ◽  
Postprandial Hyperglycemia ◽  
Glucose Disposal ◽  
Glucose Release ◽  
Isotope Technique ◽  
Glucose Storage ◽  
And Storage

To assess mechanisms for postprandial hyperglycemia, we used a triple-isotope technique ([\3-3H]glucose and [14C]bicarbonate and oral [6,6-dideutero]glucose iv) and indirect calorimetry to compare components of glucose release and pathways for glucose disposal in 26 subjects with type 2 diabetes and 15 age-, weight-, and sex-matched normal volunteers after a standard meal. The results were as follows: 1) diabetic subjects had greater postprandial glucose release ( P < 0.001) because of both increased endogenous and meal-glucose release; 2) the greater endogenous glucose release ( P < 0.001) was due to increased gluconeogenesis ( P < 0.001) and glycogenolysis ( P = 0.01); 3) overall tissue glucose uptake, glycolysis, and storage were comparable in both groups ( P > 0.3); 4) glucose clearance ( P < 0.001) and oxidation ( P = 0.004) were reduced, whereas nonoxidative glycolysis was increased ( P = 0.04); and 5) net splanchnic glucose storage was reduced by ∼45% ( P = 0.008) because of increased glycogen cycling ( P = 0.03). Thus in type 2 diabetes, postprandial hyperglycemia is primarily due to increased glucose release; hyperglycemia overcomes the effects of impaired insulin secretion and sensitivity on glucose transport, but intracellular defects persist so that pathways of glucose metabolism are abnormal and glucose is shunted away from normal sites of storage (e.g., liver and muscle) into other tissues.

scholarly journals Effects of sustained treatment with lixisenatide on gastric emptying and postprandial glucose metabolism in type 2 diabetes: a randomized controlled trial

2020 ◽  
Author(s):  
Christopher K. Rayner ◽  
Linda E. Watson ◽  
Liza K. Phillips ◽  
Kylie Lange ◽  
Michelle J. Bound ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Glucose Metabolism ◽  
Postprandial Glucose ◽  
Oral Glucose ◽  
Continuous Exposure ◽  
Short Acting ◽  
Postprandial Glycemia ◽  
Gastric Emptying Scintigraphy

<i>Objective</i> <p>Slowing of gastric emptying by GLP-1 exhibits tachyphylaxis with continuous exposure. We therefore aimed to establish whether prolonged use of a “short-acting” GLP-1 receptor agonist (GLP-1RA), lixisenatide, achieves sustained slowing of gastric emptying and reduction in postprandial glycemia. </p> <p> </p> <p><i>Research design and methods</i></p> <p>30 patients with metformin-treated type 2 diabetes underwent assessment of gastric emptying (scintigraphy) and glucose metabolism (dual tracer technique) after a 75g glucose drink, before and after 8 weeks’ treatment with lixisenatide (20µg subcutaneously daily) or placebo, in a double-blind randomized parallel design.</p> <p> </p> <p><i>Results</i></p> <p>Gastric retention of the glucose drink was markedly increased after lixisenatide versus placebo (ratio of adjusted geometric means for area under curve (AUC) over 240 min of 2.19 (95% CI 1.82, 2.64; P<0.001), associated with substantial reductions in the rate of systemic appearance of oral glucose (P<0.001) and incremental AUC for blood glucose (P<0.001). Lixisenatide suppressed both glucagon (P=0.003) and insulin (P=0.032), but not endogenous glucose production, over 120 min after oral glucose. Postprandial glucose-lowering over 240 min was strongly related to the magnitude of slowing of gastric emptying by lixisenatide (r = -0.74, P = 0.002) and to the baseline rate of emptying (r = 0.52, P = 0.048), but unrelated to ß-cell function (assessed by ß-cell glucose sensitivity).</p> <p> </p> <p><i>Conclusions</i></p> <p>8 weeks’ treatment with lixisenatide is associated with sustained slowing of gastric emptying and marked reductions in postprandial glycemia and appearance of ingested glucose. Short-acting GLP-1RAs therefore potentially represent an effective long-term therapy for specifically targeting postprandial glucose excursions.</p>

scholarly journals Effects of sustained treatment with lixisenatide on gastric emptying and postprandial glucose metabolism in type 2 diabetes: a randomized controlled trial

2020 ◽  
Author(s):  
Christopher K. Rayner ◽  
Linda E. Watson ◽  
Liza K. Phillips ◽  
Kylie Lange ◽  
Michelle J. Bound ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gastric Emptying ◽  
Glucose Metabolism ◽  
Postprandial Glucose ◽  
Oral Glucose ◽  
Continuous Exposure ◽  
Short Acting ◽  
Postprandial Glycemia ◽  
Gastric Emptying Scintigraphy

<i>Objective</i> <p>Slowing of gastric emptying by GLP-1 exhibits tachyphylaxis with continuous exposure. We therefore aimed to establish whether prolonged use of a “short-acting” GLP-1 receptor agonist (GLP-1RA), lixisenatide, achieves sustained slowing of gastric emptying and reduction in postprandial glycemia. </p> <p> </p> <p><i>Research design and methods</i></p> <p>30 patients with metformin-treated type 2 diabetes underwent assessment of gastric emptying (scintigraphy) and glucose metabolism (dual tracer technique) after a 75g glucose drink, before and after 8 weeks’ treatment with lixisenatide (20µg subcutaneously daily) or placebo, in a double-blind randomized parallel design.</p> <p> </p> <p><i>Results</i></p> <p>Gastric retention of the glucose drink was markedly increased after lixisenatide versus placebo (ratio of adjusted geometric means for area under curve (AUC) over 240 min of 2.19 (95% CI 1.82, 2.64; P<0.001), associated with substantial reductions in the rate of systemic appearance of oral glucose (P<0.001) and incremental AUC for blood glucose (P<0.001). Lixisenatide suppressed both glucagon (P=0.003) and insulin (P=0.032), but not endogenous glucose production, over 120 min after oral glucose. Postprandial glucose-lowering over 240 min was strongly related to the magnitude of slowing of gastric emptying by lixisenatide (r = -0.74, P = 0.002) and to the baseline rate of emptying (r = 0.52, P = 0.048), but unrelated to ß-cell function (assessed by ß-cell glucose sensitivity).</p> <p> </p> <p><i>Conclusions</i></p> <p>8 weeks’ treatment with lixisenatide is associated with sustained slowing of gastric emptying and marked reductions in postprandial glycemia and appearance of ingested glucose. Short-acting GLP-1RAs therefore potentially represent an effective long-term therapy for specifically targeting postprandial glucose excursions.</p>

scholarly journals Effects of Type 2 Diabetes on Insulin Secretion, Insulin Action, Glucose Effectiveness, and Postprandial Glucose Metabolism

Diabetes Care ◽  
2009 ◽  
Vol 32 (5) ◽  
pp. 866-872 ◽  
Author(s):  
A. Basu ◽  
C. Dalla Man ◽  
R. Basu ◽  
G. Toffolo ◽  
C. Cobelli ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Insulin Action ◽  
Postprandial Glucose ◽  
Glucose Effectiveness
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