Plasma lipids and oxidized LDL levels by Apo-E polymorphism in subjects with type 2 diabetes

2004 ◽  
Vol 14 (5) ◽  
pp. 283
2010 ◽  
Vol 18 (2) ◽  
pp. 49-54
Author(s):  
Douglas E. Barre D.E. ◽  
Kazimiera A. Mizier-Barre K.A. ◽  
Odette Griscti O. ◽  
Kevin Hafez K.

Lipids ◽  
2014 ◽  
Vol 49 (7) ◽  
pp. 677-684 ◽  
Author(s):  
Vanessa M. Silva ◽  
Carmen G. C. Vinagre ◽  
Luis A. O. Dallan ◽  
Ana P. M. Chacra ◽  
Raul C. Maranhão

2019 ◽  
Vol 11 (475) ◽  
pp. eaau3441 ◽  
Author(s):  
Adrian Vella ◽  
Jennifer L. R. Freeman ◽  
Imogene Dunn ◽  
Kit Keller ◽  
John B. Buse ◽  
...  

The therapeutic success of interventions targeting glucokinase (GK) activation for the treatment of type 2 diabetes has been limited by hypoglycemia, steatohepatitis, and loss of efficacy over time. The clinical characteristics of patients with GK-activating mutations or GK regulatory protein (GKRP) loss-of-function mutations suggest that a hepatoselective GK activator (GKA) that does not activate GK in β cells or affect the GK-GKRP interaction may reduce hyperglycemia in patients with type 2 diabetes while limiting hypoglycemia and liver-associated adverse effects. Here, we review the rationale for TTP399, an oral hepatoselective GKA, and its progression from preclinical to clinical development, with an emphasis on the results of a randomized, double-blind, placebo- and active-controlled phase 2 study of TTP399 in patients with type 2 diabetes. In this 6-month study, TTP399 (800 mg/day) was associated with a clinically significant and sustained reduction in glycated hemoglobin, with a placebo-subtracted least squares mean HbA1c change from baseline of −0.9% (P < 0.01). Compared to placebo, TTP399 (800 mg/day) also increased high-density lipoprotein cholesterol (3.2 mg/dl; P < 0.05), decreased fasting plasma glucagon (−20 pg/ml; P < 0.05), and decreased weight in patients weighing ≥100 kg (−3.4 kg; P < 0.05). TTP399 did not cause hypoglycemia, had no detrimental effect on plasma lipids or liver enzymes, and did not increase blood pressure, highlighting the importance of tissue selectivity and preservation of physiological regulation when targeting key metabolic regulators such as GK.


2005 ◽  
Vol 62 (7-8) ◽  
pp. 529-536 ◽  
Author(s):  
Miroslava Zamaklar ◽  
Katarina Lalic ◽  
Natasa Rajkovic ◽  
Danijela Trifunovic ◽  
Mirjana Dragasevic ◽  
...  

Background. Abnormal lipid profile is an important risk factor in the development of macrovascular atherosclerotic complications in patients with type 2 diabetes mellitus (T2D). Factors that contribute to endothelial cell dysfunction associated with the initiation of atherosclerosis include oxidative stress. The aim of this study was to investigate the relationship between lipid profile and oxidative stress in type 2 diabetics with and without ischemic heart disease (IHD). Methods. We studied 80 patients with T2D, 40 with IHD (group A1) and 40 without IHD (group A2). We also studied 51 non-diabetics, 31 with IHD (group B1), and 20 without IHD (group B2 - control group). Lipid profile was estimated by the total cholesterol, HDL cholesterol, LDL cholesterol, the level of triglyceride (Tg), lipoproteina a (Lp a), Apo A I, A II, B 100 and E. To evaluate the oxidative status we measured circulating oxidized LDL (ox LDL), erythrocyte antioxidative enzyme activity: superoxide dismutase (E-SOD), glutathione peroxidase (E-GPX), as well as the total antioxidative serum activity (TAS). Inflammatory reaction was estimated by C-reactive protein (CRP) and fibrinogen. Results. No significant difference was found in the lipid profile in groups A1, A2 and B1, but the group B2 had the lowest one. Lp a level was significantly higher in group B1 comparing to other groups (p < 0.05). There was no significant difference in the level of ox LDL between the groups. In diabetics, ox LDL positively correlated with the total cholesterol, LDL cholesterol, non HDL cholesterol, Apo B 100 and the relations between LDL/HDL and Tg/HDL (p < 0.001), as well as with Tg and fibrinogen (p < 0.05). In group B1, ox LDL positively correlated with total cholesterol, Tg (p < 0.01), LDL, and non HDL cholesterol (p < 0.05) and significantly with Apo B 100 (p < 0.001). There was no significant difference in the antioxidant enzyme activities between the groups of diabetics (A1 and A2), but fibrinogen was higher in the group with IHD (group A1, p < 0.05). Group B1 had lower ESOD activity than the groups A1 and A2 (p < 0.05), but CRP was higher (p < 0.05). There were no significant correlations between oxLDL and CRP in groups A1 and A2, but it was statistically significant in the group B1 (p < 0.05). Conclusion. In this study we demonstrated the increased oxidative stress in diabetics compared to non-diabetics regardless of the presence of IHD. Fibrinogen, but not CRP, was higher in diabetics with IHD, compared to diabetics without IHD. The increased oxidative stress, the reduced antioxidative activity E-SOD, and the higher level of CRP were found in non-diabetics with IHD compared to non-diabetics without IHD.


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