Tetrahydrobiopterin increases insulin sensitivity in patients with type 2 diabetes and coronary heart disease

2004 ◽  
Vol 287 (5) ◽  
pp. E919-E925 ◽  
Author(s):  
Thomas Nyström ◽  
Arne Nygren ◽  
Åke Sjöholm
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Endothelial Function ◽  
Healthy Subjects ◽  
Diabetic Patients ◽  
Sensitivity Index ◽  
Type 2 Diabetic Patients ◽  
Brachial Artery Diameter ◽  
Type 2 Diabetic

Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase that improves endothelial function in diabetics, smokers, and patients with hypercholesterolemia. Insulin resistance has been suggested as a contributing factor in the development of endothelial dysfunction via an abnormal pteridine metabolism. We hypothesized that BH4 would restore flow-mediated vasodilation (FMD, endothelial-dependent vasodilation), which may affect insulin resistance in type 2 diabetic patients. Thirty-two subjects (12 type 2 diabetic subjects, 10 matched nondiabetic subjects, and 10 healthy unmatched subjects) underwent infusion of BH4 or saline in a random crossover study. Insulin sensitivity index (SI) was measured by hyperinsulinemic isoglycemic clamp. FMD was measured using ultrasonography. BH4 significantly increased SI in the type 2 diabetics [3.6 ± 0.6 vs. 4.9 ± 0.7 × 10−4 dl·kg−1·min−1/(μU/ml), P < 0.05], while having no effects in nondiabetics [8.9 ± 1.1 vs. 9.0 ± 0.9 × 10−4 dl·kg−1·min−1/(μU/ml), P = 0.92] or in healthy subjects [17.5 ± 1.6 vs. 18 ± 1.8 × 10−4 dl·kg−1·min−1/(μU/ml), P = 0.87]. BH4 did not affect the relative changes in brachial artery diameter from baseline FMD (%) in type 2 diabetic subjects (2.3 ± 0.8 vs. 1.8 ± 1.0%, P = 0.42), nondiabetic subjects (5.3 ± 1.1 vs. 6.6 ± 0.9%, P = 0.32), or healthy subjects (11.9 ± 0.6 vs. 11.0 ± 1.0%, P = 0.48). In conclusion, BH4 significantly increases insulin sensitivity in type 2 diabetic patients without any discernible improvement in endothelial function.

scholarly journals Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients

2011 ◽  
Vol 106 (3) ◽  
pp. 383-389 ◽  
Author(s):  
Pál Brasnyó ◽  
Gergő A. Molnár ◽  
Márton Mohás ◽  
Lajos Markó ◽  
Boglárka Laczy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Cell Function ◽  
Diabetic Patients ◽  
Β Cell ◽  
Type 2 Diabetic Patients ◽  
Β Cell Function ◽  
Type 2 Diabetic

Although resveratrol has widely been studied for its potential health benefits, little is known about its metabolic effects in humans. Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action. After an initial general examination (including blood chemistry), nineteen patients enrolled in the 4-week-long double-blind study were randomly assigned into two groups: a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo. Before and after the second and fourth weeks of the trial, insulin resistance/sensitivity, creatinine-normalised ortho-tyrosine level in urine samples (as a measure of oxidative stress), incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B (Akt) ratio in platelets were assessed and statistically analysed. After the fourth week, resveratrol significantly decreased insulin resistance (homeostasis model of assessment for insulin resistance) and urinary ortho-tyrosine excretion, while it increased the pAkt:Akt ratio in platelets. On the other hand, it had no effect on parameters that relate to β-cell function (i.e. homeostasis model of assessment of β-cell function). The present study shows for the first time that resveratrol improves insulin sensitivity in humans, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway.

Beneficial effects of a long-term oral l-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients

2006 ◽  
Vol 291 (5) ◽  
pp. E906-E912 ◽  
Author(s):  
Pietro Lucotti ◽  
Emanuela Setola ◽  
Lucilla D. Monti ◽  
Elena Galluccio ◽  
Sabrina Costa ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Exercise Training ◽  
Endothelial Function ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Exercise Training Program ◽  
Diet And Exercise ◽  
Type 2 Diabetic

Because chronic l-arginine supplementation improves insulin sensitivity and endothelial function in nonobese type 2 diabetic patients, the aim of this study was to evaluate the effects of a long-term oral l-arginine therapy on adipose fat mass (FM) and muscle free-fat mass (FFM) distribution, daily glucose levels, insulin sensitivity, endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance who were treated with a combined period of hypocaloric diet and exercise training. Thirty-three type 2 diabetic patients participated in a hypocaloric diet plus an exercise training program for 21 days. Furthermore, they were divided into two groups in randomized order: the first group was also treated with l-arginine (8.3 g/day), and the second group was treated with placebo. Although in the placebo group body weight, waist circumference, daily glucose profiles, fructosamine, insulin, and homeostasis model assessment index significantly decreased, l-arginine supplementation further decreased FM ( P < 0.05) and waist circumference ( P < 0.0001), preserving FFM ( P < 0.03), and improved mean daily glucose profiles ( P < 0.0001) and fructosamine ( P < 0.03). Moreover, change in area under the curve of cGMP (second messenger of nitric oxide; P < 0.001), superoxide dismutase (index of antioxidant capacity; P < 0.01), and adiponectin levels ( P < 0.02) increased, whereas basal endothelin-1 levels ( P < 0.01) and leptin-to-adiponectin ratio ( P < 0.05) decreased in the l-arginine group. Long-term oral l-arginine treatment resulted in an additive effect compared with a diet and exercise training program alone on glucose metabolism and insulin sensitivity. Furthermore, it improved endothelial function, oxidative stress, and adipokine release in obese type 2 diabetic patients with insulin resistance.

Red wine consumption improves insulin resistance but not endothelial function in type 2 diabetic patients

Metabolism ◽  
2005 ◽  
Vol 54 (3) ◽  
pp. 306-313 ◽  
Author(s):  
Raffaele Napoli ◽  
Domenico Cozzolino ◽  
Vincenzo Guardasole ◽  
Valentina Angelini ◽  
Emanuela Zarra ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Function ◽  
Red Wine ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Wine Consumption ◽  
Type 2 Diabetic

scholarly journals Plasma adiponectin concentration and tumor necrosis factor-α system activity in lean non-diabetic offspring of type 2 diabetic subjects

2006 ◽  
Vol 154 (2) ◽  
pp. 319-324 ◽  
Author(s):  
Irina Kowalska ◽  
Marek Strączkowski ◽  
Agnieszka Nikolajuk ◽  
Agnieszka Krukowska ◽  
Ida Kinalska ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Diabetic Patients ◽  
Sensitivity Index ◽  
Type 2 Diabetic Patients ◽  
Tnf Α ◽  
Type 2 Diabetic ◽  
Necrosis Factor

Objective: There is growing evidence that adiponectin function is related to the pathogenesis of insulin resistance. Insulin resistance might be present even in lean subjects with a strong family history of type 2 diabetes. The aim of the study was to look for adiponectin’s role in the pathogenesis of insulin resistance in offspring of type 2 diabetic patients, and its relation to the activity of the tumor necrosis factor (TNF)-α system. Research design and methods: The study was carried out in 23 lean offspring of type 2 diabetic subjects and in 23 controls matched for age, sex and body mass index. The oral glucose tolerance test for glucose and insulin estimations and hyperinsulinemic, euglycemic clamp studies were performed in all patients. The plasma concentration of adiponectin, TNF-α, soluble TNF receptors 1 and 2 (sTNFR1, sTNFR2), HbA1c, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein-cholesterol and triglycerides were estimated. Results: The insulin sensitivity index, normalized for fat-free mass (Mffm) and adiponectin concentrations were markedly decreased in offspring of type 2 diabetic subjects compared with the control group (P = 0.0046 and P = 0.00 058 respectively). TNF-α and sTNFR1 concentrations did not differ between the studied groups; however the concentration of sTNFR2 was markedly increased in the offspring of type 2 diabetic patients (P = 0.0002). Adiponectin concentration was positively correlated to the insulin sensitivity index (r = 0.34; P = 0.020) and to HDL-cholesterol (r = 0.29, P = 0.047) and was inversely related to sTNFR2 (r = −0.33, P = 0.027). Conclusions: The obtained results suggest that adiponectin could play a role in the pathogenesis of insulin resistance in lean offspring of type 2 diabetic subjects.

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