Tag Archives: type 2 diabetes

Activation of the PI3K/AKT/MTOR/P70S6K1 signaling cascade in peripheral blood mononuclear cells in patients with type 2 diabetes

T. S. Vatseba1*, L. K. Sokolova2, V. M. Pushkarev2,
O. I. Kovzun2, B. B. Guda2, V. V. Pushkarev2,
M. D. Tronko2, N. V. Skrypnyk1, L. M. Zaiats1

1Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine;
2SI “V.P. Komisarenko Institute of Endocrinology and Metabolism of NAMS of Ukraine”, Kyiv;
*e-mail: tamara.vatseba@gmail.com

Received: 17 April 2020; Accepted: 13 November 2020

Modern research shows that patients with diabetes mellitus have an increased risk of cancer. PI3K/Akt/mTOR/p70S6K1 signaling pathway plays an important role in the pathogenesis of cancer and diabetes. The aim of this study was to determine the state of РІ3K/Akt/mTORC1/p70S6K signaling cascade activity in peripheral mononuclear blood cells (PBMC) of patients with type 2 diabetes (T2D) relatively to the insulin and insulin-like growth factor (IGF-1) concentrations in blood plasma. Enzyme-linked immunosorbent assay was used to examine the levels of insulin and IGF-1 in blood plasma as well as the content of phosphorylated forms of Akt (Ser473), PRAS40 (Thr246), and p70S6K (Thr389) in PMBC. It was shown that in the blood plasma of patients with T2D the levels of insulin and IGF-1 were increased. Phosphorylation and activation of Akt by the mTORC2 protein kinase complex was not observed. At the same time, the relative degree of phosphorylation of mTORC1 inhibitor, PRAS40, and its substrate, p70S6K, was higher in PMBC of T2D patients in comparison with control values. These data suggest that phosphoinositide-dependent protein kinase 1 (PDK1) and, possibly, mitogen-activated protein kinase (MAPK) could mediate the effects of IGF-1 on Akt activation under type 2 diabetes.

Hypertriglyceridemia is associated with long-term risk of cardiovascular events and specific comorbidity in very high-risk hypertensive patients

O. Ya. Korolyuk, O. M. Radchenko

Danylo Halytskyi Lviv National Medical University, Department of Internal Medicine No 2, Lviv, Ukraine;
e-mail: korolyukolga7619@gmail.com

Received: 19 December 2019; Accepted: 27 March 2020

Although hypertriglyceridemia (HTG) frequently occurs in hypertensive patients and may increase cardiovascular risk, the need for and manner of its reduction remain controversial. The objectives of this study were to compare lipid profiles, parameters of glucose homeostasis, comorbidity, and 5-year survival without cardiovascular events in very high-risk hypertensive (VHRH) patients with and without HTG, who received moderate intensity atorvastatin therapy. After initial assessment, 107 VHRH subjects were divided into two groups, i.e., without (n = 49) and with HTG (n = 58). During observation once annually patients were interviewed about prior hospitalizations with further screening for diabetes. Combined endpoint included­ hospitalization due acute myocardial infarction, decompensated heart failure, stroke or death. Survival was analyzed by Kaplan-Meier’s method. Nonparametric methods were used for statistical analysis. Higher median­ values of logarithmic value of triglycerides-to-HDL-cholesterol ratio, lipid accumulation product, fasting insulin, and HOMA index were observed in group 2 (< 0.002) that reflect predominance of small dense LDL particles, ectopic lipid deposition and insulin resistance. Patients with HTG more commonly had type 2 diabetes (58.6% vs 34.5%, including first-detected cases during initial assessments and observation, P = 0.02), liver steatosis (81.0% vs 55.1%, P = 0.006), and lithogenic gallbladder disorders (55.2% vs 34.7%, P=0.05). Women with HTG frequently had a history of hysterovariectomy (55.2% vs 19.0%, Р = 0.018). Despite long-term statin therapy, they often failed to reach recommended LDL-C targets and had worse survival due to significantly higher incidence of combined endpoint (39.6% vs 22.4%, P = 0.027). Further studies are necessary to find safe and effective strategy for secondary prevention in this population.

Cardiovascular disease among patients with type 2 diabetes: role of homocysteine as an inflammatory marker

Ashok Sahu1,2, Trapti Gupta2, Arvind Kavishwar3, R. K. Singh4

1MGM Medical College Indore, Jabalpur, India;
e-mail: asahu888@gmail.com; asahu888@yahoo.co.in;
2NSCB Medical College, Jabalpur, India;
3Regional Malaria Research Centre of Tribal (ICMR), Jabalpur, India;
4Chirayu Hospital, Bhopal, India

It is known that inflammation has a role in the pathogenesis of cardiovascular diseases; measurement of inflammatory markers improves the risk prediction of cardiovascular diseases. Hyperhomocysteinemia has been correlated with the occurrence of blood clots, heart attacks and strokes; though it is unclear whether hyperhomocysteinemia is an independent risk factor for these conditions. In the present study, we aimed to evaluate the role of homocysteine in type 2 diabetes patients with cardiovascular disease in a population of Madhya Pradesh India. Total 100 type 2 diabetes patients were included in the study, of these 50 had angiographically proven cardiovascular disease and 50 had no evidence of it. High sensitivity C-reactive protein, fibrinogen, and lipoprotein (a) were measured in serum. Homocysteine, blood glucose in plasma, erythrocyte sedimentation rate, glycated haemoglobin were measured in whole blood. A albumin excretion rate, creatinine clearance rate were measured in the urine sample for renal function. It was shown that, levels of homocysteine and other inflammatory markers were elevated significantly in the group II (n = 50). A correlation between hyperhomocysteinemia and inflammatory markers in patients with impaired renal function was observed. It was concluded that impairment of renal function is a key factor that affects homocysteine level.